A high proportion of all patients with tuberculosis (TB) present with extrapulmonary TB (EPTB), including concurrent EPTB involving more than one extrapulmonary lesion site. However, previous reports only characterized lesions of single-site EPTB cases. This study aimed to investigate epidemiological characteristics and association rules of concurrent EPTB cases in China. An observational multi-centre study of 208,214 patients with EPTB lesions was undertaken in China from January 2011 to December 2017. Multi-variable logistic regression analysis was used to identify associations between gender and concurrent EPTB, and age and concurrent EPTB. Association rules were analysed for significance using the Apriori algorithm. The most common EPTB lesion was tuberculous pleurisy (49.8%), followed by bronchial TB (14.8%) and tuberculous meningitis (7.6%). The most common type of concurrent EPTB was tuberculous pleurisy concurrent with tuberculous peritonitis (1.80%). In total, 22 association rules, including 20 strong association rules, were identified; among these, the highest confidence rates were found for tuberculous myelitis concurrent with tuberculous meningitis, and sacral TB concurrent with lumbar vertebral TB. The association rules of EPTB concurrent with other EPTB types were found to vary with gender and age. The confidence rate of tuberculous myelitis concurrent with tuberculous meningitis was higher in females (83.67%) than males, and was highest in patients aged 25-34 years (87.50%). Many types of concurrent EPTB were found. Greater awareness of concurrent EPTB disease characteristics is needed to ensure timely clinical diagnosis and treatment of this disease.

Objectives: Subclinical tuberculosis (TB) represents a substantial proportion of individuals with TB disease, although limited evidence is available to understand the epidemiological characteristics of these cases. We aimed to explore the prevalence of subclinical patients with TB and identify the underlying association between the subclinical TB cases in the study setting and the Beijing genotype.Methods: A retrospective study was conducted among patients with incident TB at the Fifth People’s Hospital of Suzhou between January and December 2018. A total of 380 patients with TB were included in our analysis.Results: Of the 380 patients, 81.8% were active TB cases, whereas the other 18.2% were subclinical TB cases. Compared with patients aged 65 years and older, the risk of having subclinical TB is higher among younger patients. The use of smear, culture, and Xpert identified 3, 16, and 13 subclinical TB cases, respectively. When using a combination of positive culture and Xpert results, the sensitivity improved to 33.3%. In addition, the neutrophil-to-lymphocyte ratio was significantly elevated in the active TB group compared with that in the subclinical TB group. We also observed that the proportion of the Beijing genotype in the subclinical TB group was significantly lower than that in the active TB group.Conclusion: To conclude, our data demonstrate that approximately one-fifth of patients with TB were subclinical in Suzhou. Mycobacterium tuberculosis could be detected by the existing microbiologic diagnostics in one-third of patients with subclinical TB. The patients with subclinical TB are more prone to having low neutrophil-to-lymphocyte ratio values than those with active TB. Additionally, non-Beijing genotype strains are associated with subclinical TB.

Programmed death-1 (PD-1) expression has been revealed to be upregulated on T cells and contributes to T cell exhaustion in patients with hepatitis B virus (HBV) infection. In this study, we investigated the dynamic expression of programmed death ligand-1 (PD-L1), the ligand of PD-1, on circulating CD14⁺ monocytes and CD19⁺ B cells of HBV-infected patients at the stages of chronic HBV (CHB) infection, liver cirrhosis (LC), and hepatocellular carcinoma (HCC), respectively. The results showed that compared with healthy controls, the levels of PD-L1 expression on CD14⁺ and CD19⁺ populations were both upregulated in CHB, LC, and HCC groups. Although there was no significant difference of PD-L1 expression on CD14⁺ population among three disease groups, further analysis demonstrated that the frequency of CD14⁺PD-L1⁺ population was negatively correlated with HBV DNA load, the levels of alanine aminotransaminase (ALT), and the levels of aspartate aminotransferase (AST), respectively, at CHB stage, while it did not present significant correlation with such parameters at LC stage and was only positively correlated with HBV DNA load at HCC stage. Similarly, the levels of PD-L1 expression on CD19⁺ population also did not present much difference among three disease groups. Intriguingly, the frequencies of CD19⁺PD-L1⁺ population at CHB and LCC stages were both positively correlated with the levels of ALT and AST, but they were not significantly correlated with HBV DNA load. Thereby, the current study elucidated the dynamics of PD-L1 expression on monocytes and B cells, along with the dynamic regulation of PD-1 on T cells, which had a close relationship during the progression of HBV infection. Collectively, our findings demonstrated that in the course of HBV infection development, PD-L1 expression on CD14⁺ monocytes and CD19⁺ B cells varied and significantly correlated with clinical parameters, which could be utilized as a potential clinical indicator.

Background: As an immune checkpoint, upregulation of B and T lymphocyte attenuator (BTLA) contributes to T-cell exhaustion in chronic infection. However, the characteristics of BTLA on T cells of patients with pulmonary tuberculosis (PTB) are still uncovered. Aims: The aim of the study was to elucidate the dynamics and clinical significance of BTLA expression on circulating CD4⁺ and CD8⁺ T cells of PTB patients. Materials and Methods: BTLA expression on T cells from PTB patients with smear positivity (n = 86) and healthy controls (HCs) (n = 40) were determined using flow cytometry. Results: The levels of BTLA expression on circulating CD4⁺ and CD8⁺ T cells of PTB patients with smear positivity were both upregulated, compared with HC. At the same time, the levels of BTLA expression on CD4⁺ and CD8⁺ T cells of patients with retreatment were both higher than that of those with initial treatment and gradually upregulated along with the increase of the bacillary load in sputum. In addition, the patients with lung cavity were discovered to present higher levels of BTLA expression on CD4⁺ and CD8⁺ T cells than those without lung cavity. Whereas we noted that there was no correlation between the levels of BTLA expression and the positivity or negativity of anti-Mycobacterium tuberculosis antibody. Conclusions: The levels of BTLA expression were upregulated on CD4⁺ and CD8⁺ T cells of PTB patients and associated with disease progression. Thereby, BTLA expression on T cells may be considered as a potential clinical indicator and utilized as a therapeutic target for PTB.

Vitamin D receptor (VDR) gene FokI polymorphism have been studied in relation to tuberculosis (TB) in many populations and provided inconsistent results. In this study, we carried out a meta-analysis to derive a more reliable assessment on FokI polymorphism and the risk of HIV-negative TB. The Embase, PubMed, and Cochrane Library databases were used to undertake a comprehensive systematic literature review of all current published VDR gene FOKI association studies aimed at the risk of TB up to June 30, 2015. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were used to measure the strength of the models. A total of 14 studies (1,668 cases and 1,893 controls) were retrieved in the meta-analysis. The pooled OR was 1.60 (95% = 1.28–1.97, P<0.001; I² = 29.5%, and P = 0.141 for heterogeneity) in the best genetic model (recessive model: ff vs. fF+FF). In the subgroup analysis by ethnicities, a significantly increased risk was found in the Asian group (OR = 1.82, 95% CI = 1.42–2.33, P<0.001; I² = 31.0%, and P = 0.150 for heterogeneity) in the recessive model. Similarly, significant associations were also found in the polymerase chain reaction-restriction fragment length polymorphism group, high-quality studies, and the population based or hospital based groups. Moderate heterogeneity was found in this study. Our results suggested that VDR FokI polymorphism contributes to increasing the risk of TB in HIV-negative individuals, especially in the Asian region. Further studies on this topic in other races are expected to be conducted in future.