Development and Evaluation of a Promising Biomarker for Diagnosis of Latent and Active Tuberculosis Infection

Background:Diagnosing latent tuberculosis(TB)infection(LTBI)and active TB(ATB)is crucial for preventing disease progression and transmission.However,current diagnostic tests have limitations in terms of accuracy and sensitivity,making it challenging to diagnose these different infection states.Therefore,this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic tests.Methods:We developed a novelmultiepitope-based diagnostic biomarker(MEBDB)fromLTBI region of differentiation antigens using bioinformatics and immunoinformatics.Immune responses induced byMEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead assays.This study was conducted from April 2022 to December 2022 in the SeniorDepartment of Tuberculosis at the 8thMedical Center of PLA General Hospital,China.Blood samples were collected from participants with ATB,individuals with LTBI,and healthy controls(HCs).The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic curves.Results:A novel MEBDB,designated as CP19128P,was generated.CP19128P comprises 19 helper T lymphocyte epitopes,12 cytotoxic T lymphocyte epitopes,and 8 B-cell epitopes.In silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune responses.CP19128P generated significantly higher levels of tumor necrosis factor(TNF-α),interleukin 4(IL-4),and IL-10 in ATB patients(n=7)and LTBI(n=8)individuals compared with HCs(n=62)(P<0.001).Moreover,CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and specificity.Combining IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs(the area under the receiver operating characteristic curve[AUC],0.976[95% confidence interval[CI],0.934-1.000]or 0.986[0.956-1.000]),whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from HCs(AUC,0.887[0.782-0.993]or 0.984[0.958-1.000]).Conclusions:Our study revealed that CP19128P is a potential MEBDBfor the diagnosis of LTBI andATB.Our findings suggest a promising strategy for developing novel,accurate,and sensitive diagnostic biomarkers and identifying new targets for TB diagnosis and management.

Application of artificial intelligence in diagnosis of pulmonary tuberculosis

Tuberculosis(TB)is an infectious disease caused by Mycobacterium tuberculosis.Although the diagnostic technology of pulmonary tuberculosis(PTB)has advanced,accurate and differential diagnoses of PTB are still challenging.In recent years,the rapid development of artificial intelligence(AI)and its wide application in the medical field have provided new opportunities for diagnosing and treating TB and PTB.The machine learning model of AI has not only helped physicians improve diagnostic accuracy,but also enabled them to make early preventive diagnoses for individuals at increased risk of infection.Furthermore,AI can guide physicians to formulate targeted treatment strategies for PTB patients with different conditions.

The effect of wind on the dispersal of a tropical small river plume

Wanquan River is a small river located in Hainan, a tropical island in China. As the third largest river in Hainan, the river plume plays an important role in the regional terrigenous mass transport, coastal circulation, and the coral reef＇s ecosystem. Studies have shown that wind forcings significantly influence river plume dynamics. In this study, wind effects on the dispersal of the river plume and freshwater transport were examined numerically using a calibrated, unstructured, finite volume numerical model （FVCOM）. Both wind direction and magnitude were determined to influence plume dispersal. Northeasterly （downwelling-favorable） winds drove fresh- water down-shelf while southeasterly （onshore） winds drove water up-shelf （in the sense of Kelvin wave propagation） , and were confined near the coast. Southwesterly （upwelling-favorable） and northwesterly （off： shore） winds transport more freshwater offshore. The transport flux is decomposed into an advection, a vertical shear, and an oscillatory component. The advection flux dominates the freshwater transport in the coastal area and the vertical shear flux is dominant in the offshore area. For the upwelling-favorable wind, the freshwater transport becomes more controlled by the advection transport with an increase in wind stress, due to enhanced vertical mixing. The relative importance of wind forcing and buoyancy force was investigated. It was found that, when the Wedderburn number is larger than one, the plume was dominated by wind forcing, although the importance of wind varies in different parts of the plume. The water column stratification decreased as a whole under the prevailing southwesterly wind, with the exception of the up-shelf and offshore areas.

A case of ischemic-hypoxic encephalopathy due to oral succinylcholine ingestion

Dear Editor,Cases of succinylcholine poisoning are rarely seen in clinic,and severe brain damage due to ingestion of succinylcholine is even rarer.Here,we report on a patient who poisoned herself via oral ingestion of succinylcholine,discuss the clinical characteristics,pathogenesis,and treatment of the succinylcholine-related ischemic-hypoxic encephalopathy that this patient suffered,and review the relevant literature.This study aimed to improve clinicians'understanding of ischemic-hypoxic encephalopathy due to succinylcholine chloride toxicity.