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Donglin Jiang,1 Yangxue Wu,1 Ling Liu,1 Yajing Shen,1 Tiandong Li,1 Yin Lu,1 Peng Wang,2 Changqing Sun,2 Kaijuan Wang,2 Keyan Wang,3 Hua Ye1 1College of Public Health, Zhengzhou University, Gaoxin District, Zhengzhou, Henan, 450001, People’s Republic of China; 2Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 3Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Hua Ye, College of Public Health, Zhengzhou University, Gaoxin District, Zhengzhou, Henan, 450001, People’s Republic of China, Tel +86 186-3853-6001, Fax +86 371-67781018, Email yehua@zzu.edu.cnBackground: Gastrointestinal tumors represent a significant component of the cancer burden in Asia. This study aims to evaluate the burden of gastrointestinal tumors in Asia from 1990 to 2021 using data from the Global Burden of Disease Study 2021 (GBD 2021).Methods: The absolute incidence, mortality, and disability adjusted life years (DALYs) number and rate of six gastrointestinal tumors(colon and rectum cancer (CRC), stomach cancer (SC), pancreatic cancer (PC), esophageal cancer (EC), liver cancer (LC) and gallbladder and biliary tract cancer (GBTC)) in 48 Asian countries were extracted from GBD 2021. Differences were analyzed based on gender, age, year, location and socio-demographic index (SDI).Results: In 2021, SC accounted for the highest disease burden in Asia (DALYs=16.41million [95% UI: 13.70, 19.62]). From 1990 to 2021, the age-standardized incidence rates of EC, LC, and SC in Asia declined, while the incidence rates of CRC and PC increased significantly, with CRC showing the largest rise (AAPC=1.08 [95% CI: 1.02 to 1.12]). Gastrointestinal tumors DALY rates peaked at age 70 and above, with males generally exhibiting higher rates than females. Furthermore, East Asia bears a higher burden compared to other Asian subregions. A higher SDI correlates with increased DALY rates for PC, but no linear relationship was observed for other gastrointestinal tumors.Conclusion: The burden of gastrointestinal tumors in Asia remains high and may continue to increase. Therefore, effective prevention and treatment measures are essential to address the challenge posed by gastrointestinal tumors.Keywords: Asia, gastrointestinal tumors, burden, trends

Xiawan Yang,1– 3,* Yingying Shen,1– 3,* Tonglin Hu,1– 3 Hangchao Li,1– 3 Yun Zhang,1– 3 Yiping Shen,1– 3 Dijiong Wu1– 4 1Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3National Traditional Chinese Medicine Clinical Research Base (Hematology), Hangzhou, Zhejiang, People’s Republic of China; 4Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dijiong Wu; Yiping Shen, Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Youdian Road No. 54, Hangzhou, 310006, Zhejiang, People’s Republic of China, Tel +86-0571-86620325, Email wudijiong@zcmu.edu.cn; shenyp_@126.comBackground: Perianal infection has a high incidence and mortality rate in patients with acute myeloid leukemia (AML). Sometimes there is a lack of effective anti-infective treatment regimens.Case Presentation: A 58-year-old male diagnosed with AML presented with secondary perianal infection and septic shock upon admission. Although multiple pathogen cultivation and antibiotic sensitivity tests indicated the presence of sensitive strains, the corresponding antibiotics were ineffective. As a last resort, carrimycin was introduced, ultimately controlling the infection and leading to disease remission.Conclusion: Carrimycin is a complementary treatment option when conventional antibiotic therapy fails. It operates through multiple mechanisms beyond its antibiotic properties and warrants further investigation.Keywords: carrimycin, perianal infection, acute myeloid leukemia, immunomodulatory

Ya Shen,1,2,* Shun-Shun Cui,3,* Xiao-Bao Teng,2,* Ming-Feng Han,2 Yan-Bei Zhang1 1Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Fuyang Infectious Disease Clinical College of Anhui Medical University, Fuyang, 236000, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Fuyang People’s Hospital, Fuyang, 236000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan-Bei Zhang, Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, No. 218 of Jixi Road, Shushan District, Hefei, 230000, People’s Republic of China, Tel +86-13093340370, Email zhangyanbeizyb@126.com Ming-Feng Han, Department of Respiratory and Critical Care Medicine, Fuyang Infectious Disease Clinical College of Anhui Medical University, No.1088 of Yinghexi Road, Yingzhou District, Fuyang, 236000, People’s Republic of China, Tel +86-16655800262, Email mingfeng_han@126.comObjective: The aim of this study was to assess the prevalence of Tropheryma whipplei (TW) infection in the population and to investigate the clinical symptoms, as well as the laboratory and imaging characteristics of patients testing positive for TW using next-generation sequencing (NGS).Methods: A retrospective review was conducted on 1346 bronchoalveolar lavage fluid (BALF) samples collected between January 2021 and September 2023. The case group comprised patients with TW detected using NGS while the control group included 65 randomly chosen Gram-positive bacterial infection patients without TW. Comparative analyses were carried out on the basic demographics, laboratory parameters, and imaging findings between the two groups. Additionally, the case group underwent an in-depth examination of underlying diseases, pathogens, final diagnoses, treatment strategies.Results: The case group comprised of 51 patients with TW, constituting 3.8% of the total. There was no significant difference in gender and age between the case and control groups (P = 0.84, P = 0.07). Symptoms such as coughing, expectoration, wheezing, fever, and hemoptysis are less commonly detected in the case group with a higher incidence of chest pain when compared to the control group (P > 0.05). The case group exhibited decreased albumin levels and increased C-reactive protein and D-dimer levels compared to normal levels. Imaging findings in the case group commonly included nodules, patchy images, and interstitial changes, the most common underlying disease is cardiovascular disease, and the most frequently co-occurring pathogen is the human herpesvirus. Among the case group, 27 patients received a final diagnosis of pneumonia, and 3 patients clinically diagnosed with Whipple’s disease demonstrated improvement in both symptoms and imaging after treatment.Conclusion: NGS revealed a relatively low overall detection rate of TW-positive patients using BALF. TW was more prevalent in middle-aged and elderly male patients characterized by symptoms such as cough, expectoration, shortness of breath, and fever. Chest imaging in these cases typically showed nodules and interstitial changes.Keywords: bronchoalveolar lavage fluid, feature, image, NGS, Tropheryma whipplei

Haotian Zhou,1,2,* Yaji Yang,1,2,* Yanhao Zhang,3 Feilong Li,1,2 Yidong Shen,4 Leilei Qin,1,2 Wei Huang1,2 1Department of Orthopaedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3College of Pharmacy, Army Military Medical University, Chongqing, 400038, People’s Republic of China; 4Department of Orthopaedics, The First People’s Hospital of Yancheng, Yancheng, 224000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Leilei Qin; Wei Huang, Email 253505921@qq.com; huangwei68@263.netAbstract: Periprosthetic joint infection (PJI) is a catastrophic complication following joint replacement surgery, posing significant challenges to orthopedic surgeons. Due to the lack of a definitive diagnostic gold standard, timely treatment initiation is problematic, resulting in substantial economic burdens on patients and society. In this review, we thoroughly analyze the complexities of PJI and emphasize the importance of accurate diagnosis and effective treatment. The article specifically focuses on the advancements in diagnostic techniques, ranging from traditional pathogen culture to advanced molecular diagnostics, and discusses their role in enhancing diagnostic accuracy. Additionally, we review the latest surgical management strategies, including everything from debridement to revision surgeries. Our summary aims to provide practical information for the diagnosis and treatment of PJI and encourages further research to improve diagnostic accuracy and treatment outcomes.Keywords: arthroplasty, periprosthetic joint infection, PJI, molecular diagnosis, pathogenesis diagnosis, antibiotic application, recurrence of infection

Yingying Shen,1,2,* Junmin Cao,3,* Tonglin Hu,1,2 Xiawan Yang,1,2 Yuechao Zhao,1,2 Yiping Shen,1,2 Baodong Ye,1,2 Yunsong Yu,4 Dijiong Wu1,2 1Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2National Traditional Chinese Medicine Clinical Research Base (Hematology), Hangzhou, Zhejiang, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 4Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dijiong Wu, Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China, Tel +86-0571-86620325, Email wudijiong@zcmu.edu.cn Yunsong Yu, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, 310024, People’s Republic of China, Tel +8613805790432, Email yvys119@zju.edu.cnBackground: Carbapenem-resistant P. aeruginosa (CRPA) is a common hospital-acquired bacterium. It exhibits high resistance to many antibiotics, including ceftazidime/avibactam and cefteolozane/tazobactam. The presence of carbapenem-resistant genes and co-existence Klebsiella pneumoniae carbapenemase (KPC) and metallo-β-lactamases (MBLs) further inactivated all β-lactams. Understanding the resistance genes of CRPA can help in uncovering the resistance mechanism and guiding anti-infective treatment. Herein, we reported a case of perianal infection with hypervirulent ST463 Pseudomonas aeruginosa.Case Presentation: The case is a 32-year-old acute myeloid leukemia (AML) patient with fever and septic shock during hematopoietic stem cell transplantation (HSCT), and the pathogen was finally identified as a highly virulent sequence type 463 (ST463) P. aeruginosa harboring carbapenem-resistant genes blaAFM-1 and blaKPC-2, which was detected in the bloodstream and originated from a perianal infection. The strain was resistant to ceftazidime/avibactam but successfully treated with polymyxin B, surgical debridement, and granulocyte engraftment after HSCT. The AML was cured during the 19-month follow-up.Conclusion: This case emphasizes the importance of metagenomic next-generation sequencing (mNGS) and whole-genome sequencing (WGS) in identifying microbes with rare resistant genes, and managing CRPA, especially in immunocompromised patients. Polymyxin B may be the least resistant option.Keywords: carbapenem-resistant pseudomonas aeruginosa, blaAFM, blaKPC, ST463

Guocan Yu,1 Yanqin Shen,2 Liwei Yao,2 Xudong Xu1 1Zhejiang Tuberculosis Diagnosis and Treatment Center, Hangzhou Red Cross Hospital, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Nursing, Hangzhou Red Cross Hospital, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Liwei Yao; Xudong Xu, Email ylwmed@163.com; xuxudong234@163.comPurpose: This study aimed to evaluate the efficacy of nanopore sequencing for diagnosing pulmonary tuberculosis (PTB) using smear-negative clinical specimens.Methods: We conducted a retrospective study based on a review of patient medical records to assess the accuracy of nanopore sequencing as a diagnostic tool for smear-negative PTB. Compared with clinical diagnosis, we determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of nanopore sequencing.Results: A total of 647 patients were evaluated. Nanopore sequencing demonstrated an overall sensitivity of 91.7%, specificity of 85.3%, PPV of 95.1%, NPV of 76.4%, and AUC of 0.88. Notably, the overall diagnostic accuracy of nanopore sequencing was significantly higher than that of Mycobacterium tuberculosis (MTB) culture technique.Conclusion: Nanopore sequencing exhibited satisfactory overall diagnostic accuracy for smear-negative PTB, regardless of MTB culture status. Therefore, if conditions permit, nanopore sequencing is recommended as a diagnostic method for smear-negative PTB.Keywords: nanopore sequencing, smear-negative specimens, pulmonary tuberculosis, diagnostic accuracy

Weiqiang Xiao,1,* Xiaokun Wang,1,* Yuanye Qu,1 Mingyue Sun,1 Yanmin Chang,1 Wenjiao Li,1 Yong Shen,1,2 Xiufang Shi,3 Min Jing,1 Qingxia Xu1,4 1Department of Clinical Laboratory, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Institute of Biophysics, Chinese Academy of Sciences, Foshan, People’s Republic of China; 3School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 4Zhengzhou Key Laboratory for Diagnosis of Digestive System Tumor Markers, Zhengzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingxia Xu; Xiufang Shi, Email zlyyxuqingxia0575@zzu.edu.cn; xfshi@zzu.edu.cnBackground: Emergence of blaKPC and blaNDM co-harboring Klebsiella pneumoniae has escalated the threat of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to healthcare. It remains unknown the prevalence and molecular characteristics of CRKP co-producing KPC and NDMs carbapenemases in Henan.Methods and Results: Twenty-seven CRKP strains isolated from different times were selected randomly in affiliated cancer hospital of Zhengzhou University from January 2019 to January 2021, among which one KPC-2 and NDM-5 positive CRKP named K9 was isolated from an abdominal pus sample of a 63-year-old male patient with leukemia. Sequencing of K9 determined that K9 belonged to ST11-KL47, which is resistant to antibiotics such as meropenem, ceftazidime-avibactam and tetracycline. K9 carried two different plasmids that contained blaNDM− 5 and blaKPC− 2. Both plasmids were shown to be novel hybrid plasmids and IS 26 played an important role in generation of two plasmids. Gene blaKPC-2 was flanked by the NTEKPC-Ib-like genetic structure (IS 26-ΔTn 3-ISKpn8-blaKPC-2-ISKpn6-IS 26) and was located on a conjugative IncFII/R/N type hybrid plasmid.Conclusion: The resistance gene blaNDM− 5 located on a region organized as IS 26-blaNDM– 5-ble-trpF-dsbD-ISCR1-sul1-aadA2-dfrA12-IntI1-IS 26 was carried by a phage-plasmid. We described a clinical CRKP co-producing KPC-2 and NDM-5 and emphasized an urgent need to control their further spread.Keywords: carbapenem-resistant Klebsiella pneumoniae, KPC-2, NDM-5, beta-lactamases, hybrid plasmid, IS 26

Yani Zhou,1 Qi Wang,1 Yujuan Shen,1 Bin Shen,1 Yan Zhang,2 Weihong Wang,1 Xiaofeng Li1,3 1Department of Infectious Diseases, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, Zhejiang Province, People’s Republic of China; 2Department of Nursing, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, Zhejiang Province, People’s Republic of China; 3Huzhou Key Laboratory of Precision Medicine Research and Translation for Infectious Diseases, Huzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xiaofeng Li, Email xf_li0728@163.comBackground: Japanese spotted fever (JSF) is a rare disease, caused by Rickettsia japonica; no case has been reported in Zhejiang Province, China.Case Presentation: An elderly woman presented to the hospital with abdominal pain and fever. Her condition rapidly worsened with severe complications, such as multiple organ failure and central nervous system damage. The presence of R. japonica was quickly detected by metagenomic next-generation sequencing. On the basis of combined clinical manifestations and laboratory results, critical JSF was diagnosed and treated with doxycycline. The patient showed good prognosis. Typical symptoms (eschar and rash) were not observed in the early stage, consequently increasing the difficulty of clinical diagnosis.Conclusion: The delay of treatment caused by non-specific symptoms is an important factor affecting the progression of JSF. As an emerging pathogen detection method, mNGS has been successfully applied for disease diagnosis and treatment, and can be an important complement for the diagnosis of this disease.Keywords: Japanese spotted fever, Rickettsia japonica, spotted fever group Rickettsia, mNGS, fever, multiple organ failure, central nervous system damage

Bo Liu,1,2 Junjie You,1 Lingyi Huang,1 Mengling Chen,1 Yushan Shen,1 Longyu Xiong,1 Silin Zheng,3 Min Huang2 1School of Nursing, Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China; 3Nursing Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of ChinaCorrespondence: Silin Zheng, Nursing Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China, Tel +86 13002866667, Email 1400223549@qq.com Min Huang, Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China, Tel +86 18982482624, Email hm20140313@163.comPurpose: To perform a bibliometric analysis of the 100 most-cited articles (T100 articles) on COVID-19 vaccine hesitancy to characterize current trends.Methods: The data of the bibliometric analysis were retrieved from the Web of Science Core Collection (WoSCC) database on January 29, 2023, and the results were sorted in descending order by citations. Two researchers independently extracted the characteristics of the top 100 cited articles, including title, author, citations, publication year, institution, country, author keywords, Journal Cited Rank, and impact factor. Excel and VOSviewer were used to analyze the data.Results: The T100 articles ranged from 79 to 1125 citations, with a mean of 208.75. The T100 articles were contributed by 29 countries worldwide, of which the USA ranked first with 28 articles and 5417 citations. The T100 articles were published in 61 journals; the top three citations were VACCINES, NATURE MEDICINE, and EUROPEAN JOURNAL OF EPIDEMIOLOGY, and the number of citations was 2690, 1712, and 1644, respectively. Professor Sallam, M(n=4) from Jordan, is the author who participated in the most published articles. Catholic University of the Sacred Heart (n=8) had the most T100 articles.Conclusion: It is the first bibliometric analysis of the T100 articles in the field of COVID-19 vaccine hesitancy. We carefully analyzed and described the characteristics of these T100 articles, which provide ideas for further strengthening COVID-19 vaccination and fighting against the epidemic in the future.Keywords: COVID-19, vaccine hesitancy, bibliometric analysis, citation

Ling-Zhi Jiang, Ye Shen, Feng Liang, Xiang-Ming Ye, Jing Chen, Yan-Mei Yu Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Xiang-Ming Ye, Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Tel +86-13750814756, Email yexmdr@hotmail.comAbstract: Intracranial infections are the most serious and common postoperative complications with significant mortality and morbidity. Myroides odoratimimus (M. odoratimimus), a Gram-negative environmental species and an opportunistic microorganism, predominantly infects immunocompromised individuals. Limited clinical experiences and documented multidrug resistance have resulted in a scarcity of data on the treatment of M. odoratimimus infections. As far as we know, this is the first reported case of an intracranial M. odoratimimus infection with external ventricular drains (EVD) that was effectively treated with a combination of intravenous and intraventricular tigecycline in an immunocompetent adult host.Keywords: Myroides odoratimimus, M. odoratimimus, intracranial infection, immunocompetent host, tigecycline

Chenglin Wang,1 Shilin Li,1 Yuzhou Shen,1 Yang Li,1 Muhu Chen,1 Youqiang Wang,2 Youyu Lan,3 Yingchun Hu1 1Department of Emergency Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Laboratory Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Rheumatology and Immunology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Yingchun Hu, Department of Emergency Medicine, The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou, Sichuan, People’s Republic of China, Tel +86-15228232720, Fax +86-0830-3165120, Email huyingchun913@swmu.edu.cn Youyu Lan, Department of Rheumatology and Immunology, The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou, Sichuan, People’s Republic of China, Tel +86-18090861701, Fax +86-0830-3165120, Email 494077025@qq.comPurpose: To explore the potential active targets and mechanisms of Panax Ginseng in the treatment of sepsis using network pharmacology and RNA-seq technology.Patients and Methods: Patients with sepsis and healthy volunteers were collected according to SEPSIS 3.0, and their peripheral blood was used for RNA-seq analysis. The active ingredients and targets of Panax Ginseng were obtained using the TCMSP database, PPI and GO analysis were performed for disease-drug intersection targets. Then, we used Meta-analysis to screen core genes. Finally, single-cell RNA-seq was used to perform cell localization analysis on core genes.Results: RNA-seq analysis collected 4521 sepsis-related genes, TCMSP database obtained 86 Panax Ginseng active ingredients and their 294 active targets. PPI and GO analysis showed intersection targets were closely linked, and mainly involved in cellular response to chemical stress, response to drug and molecule of bacterial origin, etc. Then, core targets, IL1B, ALOX5, BCL2 and IL4R, were sorted by Meta-analysis, and all four genes have high expression in the sepsis survivor group compared to the sepsis non-survivor group; single-cell RNA-seq revealed that IL1B was mainly localized in macrophages, ALOX5 was mainly localized in macrophages and B cells, BCL2 was mainly localized in natural killer cells, T cells and B cells, IL4R was widely distributed in immune cells. Finally, according to the correspondence between the active ingredients and targets of Panax Ginseng in TCMSP database, we found that Ginsenoside rh2 regulates the expression of IL1B, Ginsenoside rf regulates the expression of IL1B and IL4R, Kaempferol regulates the expression of ALOX5 and BCL2, and β-sitosterol regulates the expression of BCL2.Conclusion: Ginsenoside rh2, Ginsenoside rf, Kaempferol and β-sitosterol may produce anti-sepsis effects by regulating the expression of IL1B, ALOX5, BCL2 and IL4R, thus improving the survival rate of sepsis patients.Keywords: Panax Ginseng, sepsis, RNA-seq, single-cell RNA-seq, network pharmacology

Ying Shi1– 3*, Wenming Kong1 *, Haiqin Jiang,2,3 Wenyue Zhang,2,3 Chen Wang,2– 4 Limei Wu,1 Yunliang Shen,1 Qiang Yao,1 Hongsheng Wang1– 3,5 1Department of Leprosy Control, Zhejiang Provincial Institute of Dermatology, Huzhou, People’s Republic of China; 2Hospital of Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, People’s Republic of China; 3National Centre for STD and Leprosy Control, China CDC, Nanjing, People’s Republic of China; 4Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 5Centre for Global health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China* These authors contributed equally to this workCorrespondence: Qiang Yao, Department of Leprosy Control, Zhejiang Provincial Institute of Dermatology, St 61, Zhejiang, People’s Republic of China, Email 7793908@qq.com Hongsheng Wang, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 12 Jiangwangmiao Street, Nanjing, People’s Republic of China, Tel: +86 025 8547 8953, Email whs33@vip.sina.comPurpose: Reports on antimicrobial resistance (AMR) of Mycobacterium leprae (M. leprae) in Zhejiang Province are limited. Thus, this study aimed to investigate the drug resistance of new leprosy cases within several years and analyse the emergence of AMR mutations from Zhejiang Province.Methods: This study enrolled 34 leprosy cases in Zhejiang Province, China, from 2018 to 2021. Gene mutation of WHO-recommended DRDRs (folP1, rpoB and gyrA) and genes of compensatory AMR-associated DRDRs, including nth, rpoA, rpoC, gyrB and 23S rRNA, were detected by amplification. Clinical data analysis was performed to investigate the epidemiological association of leprosy.Results: Of the 34 samples, 2 (5.9%) strains showed drug resistance, which were mutated to dapsone and ofloxacin, separately. Two single mutations in gyrB were detected in different strains (5.9%), whereas one of the rpoC mutation was also detected in one strain each (2.9%), which were proved to be polymorphs. No correlation of drug resistance proportion was identified in male vs female, nerve vs no nerve involvement, deformity vs no deformity and reaction vs non-reaction cases.Conclusion: Results showed well control of leprosy patients in Zhejiang Province. Gene mutations of WHO-recommended DRDRs folP1 and gyrA confirmed the resistance to dapsone and ofloxacin. Compensatory AMR-associated mutations confirmed to be polymorphs still require further study to determine their phenotypic outcomes in M. leprae. The results demonstrated that drug-resistant strains are not epidemic in this area. Given the few cases of leprosy, analysing the AMR of M. leprae in Zhejiang Province more comprehensively is difficult. However, regular MDT treatment and population management in the early stage may contribute to the low prevalence of leprosy.Keywords: M. leprae, antimicrobial resistance, gene mutation

Yuhuan Shen,1,&ast; Xiaoyan Dong,2,&ast; Jinlin Liu,1 Huoyang Lv,1 Yumei Ge1,3 1Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 2Department of Clinical Laboratory, Ningbo Blood Centers, Ningbo, Zhejiang, People’s Republic of China; 3Key Laboratory of Biomarkers and in vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumei Ge, Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158, Shang-Tang Road, Gong-Shu District, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-0571-85893264, Email 11218070@zju.edu.cnBackground: Interleukin-26 (IL-26) is an atypical proinflammatory cytokine due to its binding to circulating double-stranded DNA and direct antibacterial activity. Although IL-26 has been confirmed to be involved in the pathophysiology of cancer, chronic inflammatory diseases and infections, the diagnostic and prognostic values of IL-26 levels in syphilis patients are not clear. This study aimed to investigate IL-26 levels in different stages of syphilis progression.Methods: A total of 30 healthy controls and 166 patients with syphilis at different stages of disease progression were enrolled. Serum IL-26 levels were quantified in accordance with the protocols of RayBio® Human Interleukin-26 Enzyme Linked Immunosorbent Assay (ELISA) kits. Clinical laboratory diagnostic parameters and blood analysis data were detected and collected according to clinical medical laboratory standards.Results: The levels of serum IL-26 were significantly higher in neurosyphilis patients than in healthy subjects (6.87 (4.36, 12.14) and 1.67 (0.09, 4.89) pg/μL, respectively; &ast;&ast;&ast;&ast;p < 0.0001), latent syphilis (1.48 (0.40, 2.05) pg/μL, &ast;&ast;&ast;&ast;p < 0.0001), seroresistant syphilis (0.81 (0.20, 2.91) pg/μL, &ast;&ast;&ast;&ast;p < 0.0001) and secondary syphilis (1.66 (0.41, 4.25) pg/μL, &ast;&ast;&ast;&ast;p < 0.0001) with data presented as the median with interquartile range. The concentration of serum IL-26 was most sensitive to serum low-density lipoprotein concentration (r = − 0.438, &ast;&ast;p = 0.004) in latent syphilis, urine epithelial cells (r = 0.459, &ast;&ast;p = 0.003) in seroresistant syphilis, and serum creatinine levels (r = 0.463, &ast;&ast;p = 0.004) and urea creatinine ratio levels (r = 0.500, &ast;&ast;p = 0.008) in secondary syphilis patients. There was no significant correlation with the concentration of IL-26 and toluidine red unheated serum test (TRUST) titers in each type of syphilis patient.Conclusion: Circulating IL-26 in serum displays diagnostic potential in the progression of neurosyphilis and warrants further evaluation in clinical trials.Keywords: neurosyphilis, interleukin-26, IL-26, disease progression, biomarker, diagnosis

Guocan Yu,1,&ast; Linhua Wang,2 Yanqin Shen,1 Likui Fang,1 Jun Yang,1 Bo Ye,1 Kan Xu,1 Fangming Zhong1,&ast; 1Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Hospital Infection, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guocan Yu; Fangming Zhong, Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China, Email dabaitwo@163.com; zhongfangm@126.comPurpose: We evaluated CapitalBio Mycobacterium RT-PCR assay diagnosing tuberculous pericarditis (TBP), performed a head-to-head comparison with Xpert MTB/RIF, and assessed the impact of a parallel test (positive result for either of these two tests).Methods: We reviewed suspected TBP patients with Xpert MTB/RIF, CapitalBio Mycobacterium RT-PCR assay, and Mycobacterium tuberculosis (MTB) culture. We analyzed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC).Results: Seventy-four patients were included. Overall sensitivity, specificity, PPV, NPV, and AUC of CapitalBio Mycobacterium RT-PCR assay compared with culture were 50%, 91.1%, 64.3%, 85%, and 0.71, respectively. Overall sensitivity, specificity, PPV, NPV, and AUC of Xpert MTB/RIF for TBP were 61.1%, 91.1%, 68.8%, 87.9%, and 0.76. Parallel test values were 72.2%, 91.1%, 72.2%, 91.1%, and 0.82. The diagnostic accuracy of Xpert MTB/RIF was higher than CapitalBio Mycobacterium RT-PCR assay but was not significant (P > 0.05). The parallel test could improve diagnostic accuracy, but it was not significant compared to single tests (P > 0.05).Conclusion: CapitalBio Mycobacterium RT-PCR assay had a moderate diagnostic accuracy, similar to Xpert MTB/RIF. The parallel test maximized diagnostic efficacy, but differences were not significant. CapitalBio Mycobacterium RT-PCR assay and Xpert MTB/RIF for TBP could be an initial option for early diagnosis.Keywords: tuberculosis pericarditis, polymerase chain reaction, Xpert MTB/RIF, CapitalBio, accuracy

Yanqin Shen, Likui Fang, Bo Ye, Xudong Xu, Guocan Yu,&ast; Lihong Zhou&ast; Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Zhejiang Chinese Medicine and Western Medicine Integrated Hospital, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guocan Yu; Lihong Zhou, Email dabaitwo@163.com; zhoulh198508@163.comBackground: Early lymph node tuberculosis (LNTB) diagnosis is still difficult. The majority of LN specimens require the undertaking of invasive and unpleasant procedures.Purpose: To evaluate the diagnostic efficacy of pathology when combined with molecular tests for the diagnosis of LNTB in core needle biopsy (CNB) specimens and to compare that diagnostic efficacy with that deriving from tissue specimens’ examination alone.Methods: We retrospectively analyzed the medical records of LNTB patients who met the inclusion criteria. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of pathology, molecular tests, and parallel test (positive result for either of these two assays) were calculated to evaluate their diagnostic efficacy compared with a composite reference standard.Results: A total of 289 patients were included in the study. The overall sensitivity, specificity, PPV, NPV, and AUC of pathology, molecular tests, and parallel test were 94.5%, 97.2%, 99.6%, 71.4%, 0.96; 73.1%, 100.0%, 100.0%, 34.6%, 0.87; and 98.4%, 97.2%, 99.6%, 89.7%, 0.98, respectively. For CNB specimens, these values for pathology, molecular tests, and parallel test were 93.3%, 96.2%, 99.4%, 69.4%, 0.95; 76.4%, 100.0%, 100.0%, 40.0%, 0.88; and 99.4%, 96.2%, 99.4%,96.2%,0.98, while those same values for the tissue were 96.6%, 100.0%, 100.0%, 76.9%, 0.98; 67.1%, 100.0%, 100.0%, 25.6%, 0.84; and 96.6%, 100.0%, 100.0%, 76.9%,0.98, respectively.Conclusion: The validity of pathology and molecular testing when using CNB specimens was similar to that of tissue specimens for relevant assessment approaches. For the LNTB diagnosis, CNB specimens were preferred for the simultaneous undertaking of pathological examination and molecular testing.Keywords: pathology, molecular tests, CapitalBio assay, Xpert, lymph node tuberculosis, CNB, tissue, accuracy

Hua Zou,&ast; Yan Shen,&ast; Chunli Li, Qiuhong Li Department of Laboratory Medicine, Chongqing Health Center for Women and Children, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunli Li; Qiuhong Li Tel +8615823827032; +8613212377189Email lcl518023@126.com; 1963163263@qq.comPurpose: Severe infection has been the leading causes of neonatal death, especially the emergency of multidrug-resistant bacteria such as carbapenem-resistant Enterobacteriaceae. This study aimed to investigate the outbreak of carbapenem-resistant Klebsiella pneumoniae (CR-KP) in neonatal wards and to explore the possible pathogenesis of Klebsiella pneumoniae.Materials and Methods: CR-KP were collected from neonatal ward of Chongqing Health Center for Women and Children between 2017 and 2019. Broth microdilution method was used to evaluate the antimicrobial activities in vitro, at the same time, the virulence of the strain was evaluated by in vitro and in vivo experiments. At last, prokaryotic chain specific transcriptome sequencing was conducted to explore the possible pathogenesis of CR-KP.Results: In this study, a total of 14 carbapenem-resistant-Klebsiella pneumoniae (CR-KP) strains were isolated from Chongqing Health Center for Women and Children, among which all CR-KP isolates were identified as NDM-1-producers. Molecular epidemiological studies revealed ST147 being the most common sequence type (ST). Moreover, we first found two phenotypes of K. pneumoniae with different virulence from the same specimen. Type I, which was a white and sticky colony had a slight increase in virulence with higher biofilm formation, serum resistance and virulence than Type II with gray colony. Compared with the Type II, 10 pathways were obviously changed in Type I especially amino acid metabolism, such as arginine and proline metabolism.Conclusion: Our findings revealed a new potential threat of NDM-1-positive CR-KP with higher virulence in neonatal ICU ward. We found two phenotypes of K. pneumoniae with different virulent, which may be due to the difference expression of arginine and proline metabolism.Keywords: neonates, carbapenem-resistant-Klebsiella pneumoniae, NDM-1, virulence

Ganfeng Liang,1,&ast; Yuting Rao,2,3,&ast; Shuang Wang,4 Xiaohui Chi,2 Hao Xu,2 Yang Shen1 1Department of Infectious Diseases, The First Hospital of Taizhou, Taizhou, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Laboratory Medicine, Puyang Oil Field General Hospital, Puyang, People’s Republic of China; 4Institute of Bacterial Infection Disease Control, Shandong Centre for Disease Control and Prevention, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Shen; Hao Xu Email Shenyanghtt@163.com; xuhao0523@zju.edu.cnBackground: The emergence of the plasmid-borne colistin-resistant gene (mcr-1) poses a great threat to human health. What is worse, the recent observations of the coexistence of mcr-1 with carbapenemase encoding genes in some bacteria caused even more concern. Yet, there is a lack of observations of such strains in the human gut.Methods: The isolation of E. coli L889 was performed on selective medium plates. Antibiotic susceptibilities were determined by an agar dilution and a broth microdilution method. Multi-locus sequence typing (MLST) and acquired resistance genes were also characterized. Transferability of blaNDM-9/mcr-1-carrying plasmids was determined by conjugation, replicon typing and S1-Pulsed-field gel electrophoresis (S1-PFGE), and Southern blotting. The sequences of these plasmids were analyzed by using whole-genome sequencing with Illumina Novaseq and Nanopore platforms.Results: E. coli L889 was identified as ST1101 concomitantly carrying blaNDM-9 and mcr-1 from a stool sample. Antimicrobial susceptibility tests showed that it was resistant to various antimicrobial agents and only susceptible to tigecycline. Notably, blaNDM-9 was located on a ∼ 114-kb untypable plasmid, while mcr-1 was located on a ∼ 63-kb IncI2 plasmid.Conclusion: Our research, to our knowledge, first reported an ST1101 E. coli strain with an untypeable blaNDM-9-harbouring plasmid and an IncI2 mcr-1-carrying plasmid. The colonized E. coli strains potentially contribute to the dissemination and transfer of blaNDM-9 and mcr-1 to clinical isolates, which is a considerable threat to public health and should be closely monitored.Keywords: blaNDM-9, mcr-1, gut, Escherichia coli, ST1101

Qin Zou,1 Hua Zou,1 Yan Shen,1 Lang Yu,1 Wei Zhou,2 Chenglin Sheng,3 Ang Liao,4 Chunli Li1 1Department of Laboratory Medicine, Chongqing Health Center for Women and Children, Chongqing, People’s Republic of China; 2Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children, Chongqing, People’s Republic of China; 3Department of Laboratory Medicine, Wanzhou Health Center for Women and Children, Chongqing, People’s Republic of China; 4Department of Laboratory Medicine, Yongchuan Health Center for Women and Children, Chongqing, People’s Republic of ChinaCorrespondence: Chunli LiDepartment of Laboratory Medicine, Chongqing Health Center for Women and Children, Chongqing, 401147, People’s Republic of ChinaTel +86 23-60354459Fax +86 23-63840868Email lcl518023@126.comPurpose: Bloodstream infections (BSIs) cause morbidity and mortality in postpartum patients, resulting in poor prognosis for both mother and neonate. Gram-negative bacteremia is a public health threat, with high mortality among vulnerable populations and significant global economic costs. Gram-negative bacteremia and antimicrobial resistance are increasing. This study retrospectively analyzed the pathogen distribution and drug sensitivity among postpartum patients with BSIs to identify appropriate antibacterial agents for perioperative therapy.Material and Methods: All bacteremia cases between January 2015 and December 2020 from three Health Centers for Women and Children in Chongqing, China, were retrospectively reviewed. Clinical data were collected from medical records and charts. Blood samples were cultured by BD BACTEC FX200. Bacterial and fungal species and bacterial susceptibility were identified by a BD PhoenixTM M50 automatic detection machine.Results: In total, 274 pathogenic strains were isolated from 272 blood samples. Excluding 25 suspected contamination strains, 248 blood samples yielded 249 microorganisms, including 214 gram-negative bacteria (85.9%), 34 gram-positive bacteria (13.6%), and 1 fungus (0.5%). Escherichia coli (E. coli) was the most frequently isolated pathogen, both overall and among gram-negative bacilli (73.5%). Streptococcus agalactiae represented 3.6% of gram-positive cocci (n = 9). Laboratory-confirmed anaerobic infections comprised 9.2% of cases (n = 23). Additionally, 47.4% of postpartum patients with BSIs suffered premature rupture of membranes (PROM), a suspected infection risk factor. Drug sensitivity levels remained unchanged for less commonly used drugs, but resistance increased against commonly used drugs. Specifically, E. coli resistance against fourth-generation cephalosporins increased during this study period.Conclusion: E. coli is the most common gram-negative bacillus in postpartum patients with BSIs, and increased anaerobic bacterial detections suggest genital tract inflammation control before delivery is necessary. Effective drug resistance monitoring remains necessary to alleviate bacterial resistance, such as preventing inappropriate antibiotic applications.Keywords: bacteremia, Escherichia coli, anaerobic bacterial, perioperative therapy

Yingying Shen,1 Yuzhu Li,2 Hangchao Li,2 Qi Liu,2 Huijie Dong,2 Bo Wang,1 Baodong Ye,1 Shenyun Lin,1 Yiping Shen,1 Dijiong Wu1 1Department of Hematology, First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of TCM, Hangzhou, Zhejiang Province, People’s Republic of China; 2First Clinical Medical College, Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of TCM, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Dijiong Wu; Yiping ShenDepartment of Hematology, First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54 Youdian Road, Hangzhou, Zhejiang Province, People’s Republic of ChinaEmail wudijiong@zcmu.edu.cn; shenyp_@126.comAbstract: Monocytopenia and mycobacterial infection (MonoMAC) syndrome is a rare disease. Herein, we reported a 65-year-old Asian woman, previously diagnosed with myelodysplastic syndrome (MDS), suffering from recurrent pneumonia, intermittent fever, fatigue, and chest tightness lasting for five months. She was ultimately diagnosed with MonoMAC syndrome with Mycobacterium kansasii (M. kansasii) infection and GATA2 mutation through metagenomic generation sequencing (mNGS) of peripheral blood specimen, for which she was given anti-NTM therapy. Her situation significantly improved within 2 weeks of therapy. We discussed the clinical features, genetic characteristic, and prognosis of this disorder, aiming to further elucidate this rare syndrome. For MDS/AML patient with recurrent mixed infection and pancytopenia (especially with monocyte absence), MonoMAC syndrome should be highly suspected, and germline mutation and pathogen sequencing should be performed.Keywords: monocytopenia and mycobacterial infection syndrome, MonoMAC, M. kansasii, GATA-2 germline mutation, nontuberculous mycobacteria, next-generation sequencing

Fuchu Qian,1,2 Weihua Zou,3 Fang Jin,1,2 Dongli Li,1,2 Yujuan Shen4 1Department of Precision Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People’s Republic of China; 2Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People’s Republic of China; 3Department of Laboratory Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People’s Republic of China; 4Department of Infectious Diseases, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People’s Republic of ChinaCorrespondence: Fuchu Qian Tel +86 572-2555801Email qfc313009@126.comBackground and Aims: Potential drug resistance (DR) related variants in the hepatitis B virus (HBV) reverse transcriptase (RT) region may be associated with the effectiveness of antiviral drugs and disease progression. The aim of this study was to investigate the prevalence and clinical characteristics of potential DR-related variants in Chinese CHB patients not receiving nucleos(t)ide analogues (NAs).Patients and Methods: Two hundred and six untreated CHB patients from Huzhou Central Hospital in eastern China were recruited for this study. The serum DNA was extracted and the HBV RT region was amplified using nest polymerase chain reaction (nest-PCR). The 42 potential DR-related variants were analyzed by direct sequencing.Results: Among these CHB patients, HBV genotype B and genotype C were identified in 121 (58.7%) and 85 (41.3%) patients, respectively. Potential DR-related variants were detected in 42.7% (88/206) of patients. Primary and secondary DR variants were found in 7.3% (15/206) of patients, including rtL80I/V, rtI169T, rtV173L rtL180M, rtA181T/V, rtM204I/V, and rtN236T. The variants at rt53, rt82, rt221, rt233, rt237, and rt256 were specific for genotype B, and those at rt38, rt84, rt126, rt139, rt153, rt191, rt214, rt238, and rt242 were specific for genotype C. Moreover, the variation frequency in the A-B interdomain (3.96%) was significantly higher than that in the functional domains (1.17%) and non-A-B interdomains (1.11%). Multivariate logistic regression analysis showed that lower HBV-DNA load (< 106 IU/mL) was an independent factor associated with potential DR-related variants in untreated CHB patients (P < 0.05).Conclusion: Potential DR-related variants were frequent and complex in untreated Chinese CHB patients. Furthermore, the variants may contribute to decreased serum HBV-DNA loads. However, the effects of potential DR-related variants on the antiviral therapy and liver disease progression require further study.Keywords: Hepatitis B virus, potential, resistance, reverse transcriptase, variants

Yinzhong Shen, Jingna Xun, Wei Song, Zhenyan Wang, Jiangrong Wang, Li Liu, Renfang Zhang, Tangkai Qi, Yang Tang, Jun Chen, Jianjun Sun, Hongzhou Lu Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, People’s Republic of ChinaCorrespondence: Hongzhou Lu Email luhongzhou@fudan.edu.cnPurpose: Tuberculosis (TB) is the leading cause of mortality in individuals infected with human immunodeficiency virus (HIV), yet the methods for detecting Mycobacterium tuberculosis at an early stage remain insensitive or ineffective. This study aimed to discover plasma biomarkers for distinguishing HIV-TB coinfected individuals from HIV individuals without TB (HIV-nonTB).Patients and Methods: A total of 200 Chinese HIV-positive patients were recruited, 100 each for HIV-nonTB group and HIV-TB group. Plasma proteomic profiles were analyzed for 50 patients each in both groups, using data-independent acquisition (DIA)-mass spectrometry-based proteomics. Differently expressed proteins were revealed with ridge regression analysis. Enzyme-linked immunosorbent assay (ELISA) analyses were performed for further validation in other 100 patients.Results: DIA-mass spectrometry revealed 13 upregulated and 33 downregulated proteins in the HIV-TB group. AMACR (α-methylacyl-CoA racemase), LDHB (L-lactate dehydrogenase B chain), and RAP1B (Ras-related protein Rap-1b) were selected for building a diagnostic model, for which the receiver operation characteristic curve had under areas of 0.99 and 0.89 testing with proteomics data (sensitivity = 92%, specificity = 100%) and ELISA data (sensitivity = 76%, specificity = 92%), respectively.Conclusion: The combination of AMACR, LDHB, and RAP1B proteins may serve as a potential marker of TB in HIV-infected patients.Keywords: diagnosis, coinfection, AIDS-related opportunistic infections, Mycobacterium tuberculosis, ROC curve, proteome

Daofeng Qu,1,2 Yang Shen,2 Lingfei Hu,1 Xiaoyuan Jiang,1 Zhe Yin,1 Bo Gao,1 Yuee Zhao,1 Wenhui Yang,1 Huiying Yang,1 Jianzhong Han,2 Dongsheng Zhou1 1State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; 2School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, China Background: IncR, IncFII, IncpA1763-KPC, and IncN1 plasmids have been increasingly found among Enterobacteriaceae species, but plasmids with hybrid structures derived from the above-mentioned incompatibility groups have not yet been described.Methods: Plasmids p721005-KPC, p504051-KPC, and pA3295-KPC were fully sequenced and compared with previously sequenced related plasmids pHN84KPC (IncR), pKPHS2 (IncFIIK), pKOX_NDM1 (IncFIIY), pHN7A8 (IncFIIpHN7A8), and R46 (IncN1).Results: The backbone of p721005-KPC/p504051-KPC was a hybrid of the entire 10-kb IncR-type backbone from pHN84KPC, the entire 64.3-kb IncFIIK-type maintenance, and conjugal transfer regions from pKPHS2, a 15.5-kb IncFIIY-type maintenance region from pKOX_NDM1 and a 5.6-kb IncpA1763-KPC-type backbone region from pA1763-KPC, and it contained a primary IncR replicon and two auxiliary IncpA1763-KPC and IncN1 replicons. The backbone of pA3295-KPC was a hybrid of a 7.2-kb IncFIIpHN7A8-type backbone region from pHN7A8, the almost entire 33.3-kb IncN1-type maintenance and conjugal transfer regions highly similar to R46, a 26.2-kb IncFIIK-type maintenance regions from pKPHS2, the above 15.5-kb IncFIIY-type maintenance region, and the above 5.6-kb IncpA1763-KPC-type backbone region, and it contained a primary IncFIIpHN7A8 replicon and two auxiliary IncpA1763-KPC and IncN1 replicons. Each of p721005-KPC, p504051-KPC, and pA3295-KPC acquired a wealth of accessory modules, carrying a range of intact and residue mobile elements (such as insertion sequences, unit transposons, and integrons) and resistance markers (such as blaKPC, tetA, dfrA, and qnr).Conclusion: In each of p721005-KPC, p504051-KPC, and pA3295-KPC, multiple replicons in coordination with maintenance and conjugation regions of various origins would maintain a broad host range and a stable replication at a steady-state plasmid copy number. Keywords: multi-replicon plasmids, multi-drug resistance, blaKPC-2, mobile elements

Hao Wang,1,* Caishuang Pang,2,* Ni Zeng,1 Chun Wan,1 Yongchun Shen,1 Fuqiang Wen1 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, and Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Chengdu, China; 2Chongqing Cancer Institute & Hospital & Cancer Center, Chongqing, China *These authors contributed equally to this work Background: The gene polymorphism of interleukin-6 (IL-6) has been shown to be implicated in tuberculosis susceptibility in many studies, but with conflicting results. This study aimed to provide more accurate estimation of the relationship between IL-6 gene polymorphism and tuberculosis risk through a meta-analysis Method: A literature search was performed in PubMed, EMBASE, and other databases. Data were retrieved, and pooled odds ratio (OR) with 95% CI were calculated. Statistical analyses were performed by using STATA 12.0. Results: Twelve publications with 2635 cases and 3049 controls were included. The pooled analysis demonstrated significant evidence of association between IL-6 (-174G/C) and low risk of tuberculosis in dominant model (CC+GC vs GG: OR =0.693, 95% CI 0.581–0.826, p