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Yanwan Shangguan,* Zhongkang Ji,* Wanru Guo, Wenjuan Hu, Xiaomeng Li, Kaijin Xu State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kaijin Xu, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Tel/Fax +86-0571-87236440, Email zdyxyxkj@zju.edu.cnAbstract: Linezolid-induced black hairy tongue is a self-limiting benign disease that is rare. Here, we report three patients who developed black hairy tongue after linezolid treatment. The severe dysbiosis of oral bacterial communities was observed in all these patients. Proteobacteria was the most prevalent phylum (over 90%) at the black tongue stage. Furthermore, the dramatic oral bacterial alteration took a long time to reverse after the BHT resolved.Keywords: tuberculosis infection, linezolid, treatment, side-effect, black-hairy tongue, microorganism metabolism

Despite the achievements obtained worldwide in the control of tuberculosis in recent years, many countries and regions including China still face challenges such as low diagnosis rate, high missed diagnosis rate, and delayed diagnosis of the disease. The discovery strategy of tuberculosis in China has changed from “active discovery by X-ray examination” to “passive discovery by self-referral due to symptoms”, and currently the approach is integrated involving self-referral due to symptoms, active screening, and physical examination. Active screening could help to identify early asymptomatic and untreated cases. With the development of molecular biology and artificial intelligence-assisted diagnosis technology, there are more options for active screening among the large-scale populations. Although the implementation cost of a population-based active screening strategy is high, it has great value in social benefits, and active screening in special populations can obtain better benefits. Active screening of tuberculosis is an important component of the disease control. It is suggested that active screening strategies should be optimized according to the specific conditions of the regions to ultimately ensure the benefit of the tuberculosis control.

Dan Cao,* Ju Wang,* Zhongkang Ji, Yanwan Shangguan, Wanru Guo, Xuewen Feng, Kaijin Xu, Jiezuan Yang State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiezuan YangState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou 310003 Zhejiang, People’s Republic of ChinaTel +86 571 87236756Fax +86 571 87236423Email yangyan@zju.edu.cnPurpose: To identify candidate hub genes and miRNAs associated with active tuberculosis (ATB) and reveal the potential molecular mechanisms of disease progression.Patients and Methods: The expression of mRNA and miRNA was evaluated in peripheral blood mononuclear cells (PBMC) from 4 ATB patients and 4 healthy donors (HD) using high throughput sequencing (HTS) and bioinformatics analysis. Moreover, differentially expressed miRNAswere validated with 35 ATB patients and 35 HDs using reverse transcription quantitative real-time PCR (RT-qPCR).Results: A total of 2658 significantly differentially expressed genes (DEG) including 1415 up-regulated genes and 1243 down-regulated genes were identified in the ATB group compared with HDs, and the DEGs enriched in immune-related pathways, especially in TNF signaling pathway, cytokine–cytokine receptor interaction, mitogen-activated protein kinase (MAPK) signaling pathways and tuberculosis. Additionally, 10 hub genes were acquired according to protein–protein interaction (PPI) analysis of DEGs. Moreover, 26 differentially expressed miRNAs were found in ATB group compared with HDs. Furthermore, RT-qPCR results showed that hsa-miR-23a-5p (P=0.0106), hsa-miR-183-5p (P=0.0027), hsa-miR-193a-5p (P=0.0021) and hsa-miR-941(P=0.0001) were significantly increased in the ATB patients compared with HD group, and the hsa-miR-16-1-3p was significantly decreased (P=0.0032).Conclusion: Our research provided a characteristic profile of mRNAs and miRNAs expressed in ATB subjects, and 10 hub genes related with ATB were found, which will contribute to explore the role of miRNAs and hub genes in the pathogenesis of ATB, and improve the ability of differential diagnosis and treatment for the disease.Keywords: mRNA, miRNA, active tuberculosis, high throughput sequencing, RT-qPCR

Cheng Ding, Shuting Wang, Yanwan Shangguan, Xuewen Feng, Wanru Guo, Pei Shi, Zhongkang Ji, Kaijin Xu State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People’s Republic of ChinaCorrespondence: Kaijin Xu Email zdyxyxkj@zju.edu.cnPurpose: Tuberculosis remains a major public health problem globally, especially in undeveloped countries. This study aimed to evaluate and review the long-term epidemic trends of tuberculosis in China.Methods: Data were extracted from the Global Health Data Exchange. Metrics (prevalence, incidence and mortality) and Joinpoint regression were used to identify the epidemic trends.Results: From 1990 to 2017, decreasing trends in prevalence (average annual percent change, AAPC: − 0.5%, 95% CI: − 0.6% to − 0.5%), incidence (− 3.2%, 95% CI: − 3.5% to − 2.9%), and mortality (− 5.7%, 95% CI: − 6.2% to − 5.3%) of tuberculosis were observed. The incidence and mortality of multidrug-resistant tuberculosis (MDR-TB) decreased with AAPC of − 2.3% (− 3.1% to − 1.4%) and − 4.9% (− 5.4% to − 4.5%), respectively, while the prevalence increased with an AAPC of 1.2% (0.3% to 2.0%). The burden of extensively drug-resistant tuberculosis (XDR-TB) increased with an AAPC of 12.5% (11.9% to 13.2%) in prevalence, 7.6% (6.5% to 8.7%) in incidence, and 4.5% (3.6% to 5.4%) in mortality. The disease burden of tuberculosis increased with age and peaked among those aged over 70.Conclusion: The epidemic of tuberculosis decreased in China, while the disease burden was still challenging to control. MDR-TB and XDR-TB should be emphasized along with the epidemic. It will certainly be a difficult task to achieve the post-2015 global targets by 2025 and 2035.Keywords: tuberculosis, drug-resistant, epidemic, China