Contezolid-Containing Regimen Successfully Treated Multiple Drug Resistance Mycobacterium Abscessus Complex Infection of Skin: A Case Report and Literature Review.

Background: In recent decades, there has been a substantial surge in the incidence of non-tuberculous Mycobacteria (NTM) infections. However, the diagnosis and management of NTM globally present significant challenges, particularly in cases involving Mycobacterium abscessus complex (MABC) infection where effective therapeutic options are limited. Case Presentation: We reported a 38-year-old female patient who was infected with MABC of skin due to "beauty needle" at a beauty salon, with mass on both cheeks, accompanied by redness, and pain, and some of them was ulcered and effused. Puncture pumping pus from bilateral cheek mass for many times, rinsed with "metronidazole", and oral "cephalosporin" treatment did not work. Therefore, she came to our hospital. MABC was detected in abscess paracentesis pus by nucleic acid mass spectrometry, and was proved by the cultured result of the pus. Thus, the patient was diagnosed as skin MABC infection, and anti-NTM treatment was taken. However, adverse reactions such as tinnitus, hepatotoxicity and neurovirulence occurred during the initial treatment. After adjusting to the contezolid-containing regimen, these adverse reactions improved. After nearly 6 months of treatment, the cheek mass was gradually reduced and the skin ruptures were gradually healed. Follow-up for 10 months showed that the patient's facial symptoms were significantly improved, and no drug-related adverse reactions happened. Conclusion: This was the first successful case of multiple drug resistance MABC infection of skin treated with contezolid-containing antibiotic management strategies, which exhibited remarkable efficacy and good safety in this intractable disease.

The positivity rates and drug resistance patterns of Mycobacterium tuberculosis using nucleotide MALDI-TOF MS assay among suspected tuberculosis patients in Shandong, China: a multi-center prospective study.

Objective: To investigate the positivity rates and drug resistance characteristics of Mycobacterium tuberculosis (MTB) among suspected tuberculosis (TB) patients in Shandong Province, the second-largest population province in China. Methods: A prospective, multi-center study was conducted from April 2022 to June 2023. Pathogen and drug resistance were identified using nucleotide matrix-assisted laser desorption ionization time-of-flight mass spectrometry (nucleotide MALDI-TOF MS). Results: Of 940 suspected TB patients included in this study, 552 cases were found to be infected with MTB giving an overall positivity rate of 58.72%. Total of 346 cases were resistant to arbitrary anti-TB drug (62.68%), with Zibo (76.47%), Liaocheng and Weihai (both 69.23%) ranking top three and TB treatment history might be a related factor. Monoresistance was the most common pattern (33.53%), with isoniazid the highest at 12.43%, followed by rifampicin at 9.54%. Further analysis of gene mutations conferring resistance revealed diverse types with high heteroresistance rate found in multiple anti-TB drugs. Conclusion: A relatively high rate of MTB positivity and drug resistance was found in Shandong Province during and after the COVID-19 pandemic, indicating the need for strengthening rapid identification of species and drug resistance among suspected TB patients to guide better medication and minimize the occurrence of drug resistance.

Accuracy of Xpert® MTB/RIF Ultra test for posterior oropharyngeal saliva for the diagnosis of paucibacillary pulmonary tuberculosis: a prospective multicenter study.

BACKGROUND: Posterior oropharyngeal saliva (POS) is increasingly recognized as an alternative specimen for detecting respiratory pathogens. The accuracy of Xpert® MTB/RIF Ultra (X-Ultra), when performed on POS obtained from patients with paucibacillary pulmonary tuberculosis (TB) is unclear. METHODS: We consecutively recruited adults with symptoms suggestive of pulmonary TB who were negative by both smear microscopy and Xpert MTB/RIF (X-Classic). Each participant was required to provide one bronchoalveolar lavage fluid (BALF) and one POS specimen, respectively. Diagnostic performances of X-Ultra and X-Classic on POS were compared against clinical and mycobacterial reference standards. FINDINGS: 686 participants meeting inclusion criteria were consecutively enrolled into the study. The overall diagnostic sensitivities of X-Ultra and X-Classic on POS samples were 78.9% [95% confidence interval (CI): 72.8-83.8] and 56.4% (95% CI: 49.7-62.9), respectively; the specificities were 96.6% (95% CI: 94.3-98.1) for X-Ultra and 97.6 (95CI: 95.5-98.8) for X-Classic in POS specimens. Notably, the sensitivity of X-Ultra on POS was as sensitive as X-Classic on BALF against microbiological reference standard (78.9% VS 73.1%). Against clinical diagnosis as a reference standard, the sensitivities of X-Ultra and X-Classic on POS were 55.9% (95% CI: 50.5-61.2; 193/345) and 40.0% (95% CI: 34.8-45.4; 138/345), respectively. The risk of negative results with POS was dramatically increased with decreasing bacterial loads. CONCLUSIONS: The testing of POS using X-Ultra shows promise as a tool to identify patients with paucibacillary TB. Considering that bronchoscopy is a semi-invasive procedure, POS testing ahead of bronchoscopy, may decrease the need for bronchoscopic procedures, and the cost of care.

LncRNA MIR9-3HG enhances LIMK1 mRNA and protein levels to contribute to the carcinogenesis of lung squamous cell carcinoma via sponging miR-138-5p and recruiting TAF15.

The aberrantly expressed long non-coding RNAs (lncRNAs) are closely correlated with the malignant progression of cancer cells. In our study, we identified lncRNA MIR9-3 host gene (MIR9-3HG) as the research target and explored its roles in lung squamous cell carcinoma (LUSC). RT-qPCR was conducted to reveal that MIR9-3HG was observably overexpressed in LUSC cells. Functional assays encompassing colony formation, 5-ethynyl-2'-deoxyuridine (EdU) staining, transwell and flow cytometry assays and western blot detecting related proteins demonstrated that MIR9-3HG depletion hampered cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) while accelerating cell apoptosis in LUSC. Subcellular fractionation assay were performed to demonstrate that MIR9-3HG was prominently distributed in the cytoplasm of LUSC cells. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), immunofluorescence (IF), fluorescent in situ hybridization (FISH) and RNA pull down assays were implemented to confirm that MIR9-3HG modulates LIM domain kinase 1 (LIMK1) mRNA and protein levels by sequestering microRNA-138-5p (miR-138-5p) and recruiting TATA-box binding protein associated factor 15 (TAF15) protein. Taken together, our research determined that MIR9-3HG up-regulated LIMK1 mRNA and protein levels to promote LUSC carcinogenesis, which offers a novel insight into mechanisms of LUSC.

LncRNA LINC00649 recruits TAF15 and enhances MAPK6 expression to promote the development of lung squamous cell carcinoma via activating MAPK signaling pathway.

Lung squamous cell carcinoma (LUSC) represents one of the commonest types of lung cancer featured with high morbidity and poor prognosis. Many types of research have documented that long noncoding RNAs (lncRNAs) exert crucial functions in the development of cancers, and LUSC is included. In our study, we aimed at unveiling the mechanism underlying long intergenic nonprotein coding RNA 0649 (LINC00649) in LUSC cells. As a result, LINC00649 was discovered to be with high expression in LUSC cells. Moreover, it was confirmed through functional assays that the knockdown of LINC00649 hindered the occurrence and progression of LUSC. Results of mechanism assays validated that E2F transcription factor 7 (E2F7) was a transcription activator of LINC00649 and induced its up-regulation in LUSC cells. Furthermore, LINC00649 recruited TAF15, which is TATA-box binding protein associated factor 15 to stabilize mitogen-activated protein kinase 6 (MAPK6) expression and activate the transcription of MAPK6, thereby enhancing MAPK6 expression to activate the MAPK signaling pathway. Eventually, results of rescue assays suggested that overexpression of MAPK6 offset the influence of LINC00649 silencing on LUSC progression. In summary, our research determined the E2F7/LINC00649/TAF15/MAPK6/MAPK signaling pathway in regulating LUSC development, which made LINC00649 a potential biomarker for LUSC treatment.

Long non-coding RNA LALTOP promotes non-small cell lung cancer progression by stabilizing topoisomerase IIα mRNA.

The long noncoding RNAs (lncRNAs) have been shown to actively participate in various biological processes including cancer progression. However, most lncRNAs still have undefined functions. In current work, we identified a novel lncRNA named LALTOP which displayed an oncogenic function in non-small cell lung cancer (NSCLC). LALTOP expression is increased in NSCLC tissues and cell lines. Moreover, LALTOP strongly promoted proliferation and migration of A549 and H1793 cells. RNA-RNA interaction assay showed that LALTOP bound and stabilized topoisomerase II alpha (Top2α) mRNA. Positive correlation can be found between LALTOP and Top2α mRNA expressions in clinical specimens. ASOs targeting LALTOP could markedly inhibit malignant phenotypes of NSCLC. Collectively, LALTOP may serve as an oncogenic lncRNA and enhances NSCLC progression. Targeting LALTOP has therapeutic potential for eradicating lung cancer cells.

Role of medical thoracoscopy in the treatment of tuberculous pleural effusion.

BACKGROUND: Fibrous tuberculous pleural effusion (TPE) represents common disease in tuberculous clinic. Medical thoracoscopy has been used to treat pleural empyema and shown promising outcomes, but data of its use in multiloculated and organized TPE remains limited to know. METHODS: The study was performed on 430 cases with TPE. The cases were divided into free-flowing, multiloculated effusion and organized effusion group. Each group was subdivided into two or three types of therapeutic approaches: ultrasound guided pigtail catheter, large-bore tube chest drainage and medical thoracoscopy. Patients with multiloculated or organized effusions received streptokinase, introduced into the pleural cavity via chest tubes. The successful effectiveness of the study was defined as duration of chest drainage, time from treatment to discharge days and no further managements. RESULTS: Patients with organized effusion were older than those with free-flowing effusion and incidence of organized effusion combined with pulmonary tuberculosis (PTB) was higher than those of multiloculated effusion and free-flowing effusion respectively. Positive tuberculosis of pleural fluid culture was higher in organized effusion than that in free-flowing effusion. Sputum positive for acid-fast bacillus (AFB) in organized effusion was higher than that in multiloculated effusion and free-flowing effusion. Medical thoracoscopy showed significant efficacy in the group of multiloculated effusion and organized effusion but free-flowing effusion. No chronic morbidity and mortality related to complications was observed. CONCLUSIONS: Medical thoracoscopy was a safe and successful method in treating multiloculated and organized TPE.