Rapid diagnosis of alveolar echinococcosis from lung puncture sample using metagenomic next-generation sequencing: a case report.

INTRODUCTION: Alveolar echinococcosis (AE), caused by the larval forms of Echinococcus multilocularis, is a zoonotic disease affecting the liver, lungs, lymph nodes, kidneys, brain, bones, thyroid, and other organs. Diagnosing AE in a non-endemic area is usually challenging. With the rapid development and increasing application of sequencing techniques in recent years, metagenomic next-generation sequencing (mNGS) has become a powerful tool for diagnosing rare infectious diseases. CASE PRESENTATION: A 45-year-old woman was admitted to the hospital for the presence of pulmonary shadows for more than 3 months. The lung computed tomography (CT) at a local hospital revealed scattered solid and quasi-circular nodules in the left upper lobe, left lower lobe, right middle lobe, and right lower lobe. The largest nodule was located in the dorsal part of the right lung, measuring 2.0 × 1.7 × 1.5 cm. Moreover, abdominal CT revealed one space-occupying lesion each in the left and right lobes. The pathological analysis of the lung biopsy specimen revealed infiltration of lymphocytes, plasma cells, and eosinophils in the alveolar wall and interstitial area. No pathogenic bacteria were observed in the sputum smear and culture tests. There were no parasite eggs in the stool. The mNGS of the lung puncture tissue revealed 6156 sequence reads matching E. multilocularis; thus, the condition was diagnosed as AE. Albendazole 400 mg was administered twice daily, and the patient was stable during follow-up. CONCLUSION: This case emphasizes the role of mNGS in diagnosing AE. As a novel, sensitive, and accurate diagnostic method, mNGS could be an attractive approach for facilitating early diagnosis and prompt treatment of infectious diseases, especially when the infection was caused by rare pathogens.

Analysis of pulmonary microecology and clinical characteristics of patients carrying human herpesvirus.

Aim: To investigate the impact of human herpes virus (HHV) carriage on lung microbiota, and its correlation with clinical features and laboratory indicators in patients. Methods: Retrospective analysis was conducted on 30 outpatient lung infection cases, which were divided into HHV (n = 15) and non-HHV (n = 15) groups. mNGS detected microbial composition. Microbial diversity and abundance were tested using Shannon and Chao1 indices. Their relationship with laboratory indicators were explored. Results: Significant differences in microbial abundance and distribution were found between two groups (p < 0.05). Moreover, HHV group showed negative correlations (p < 0.05) between Prevotella, Porphyromonas, Streptococcus and basophil/eosinophil percentages. Conclusion: HHV carriage impacts lung microbiota, emphasizing the need for clinicians to pay attention to HHV reactivation in outpatient lung infection patients.

This study looked at how a common virus called human herpesvirus (HHV) affects the bacteria in our lungs. We wanted to see if HHV is linked to how sick we feel and what tests show. We split 30 people who had lung infections into two groups ­ 15 with HHV and 15 without ­ and checked how sick they felt, did some tests, and looked at the types of bacteria in their lungs. Both groups felt similarly sick and got better with medicine, but people with HHV had fewer of a certain type of blood cell. People with and without HHV also had different types of bacteria in their lungs. This study helps us understand why people get sick with lung infections and how to make them better. It might also help doctors decide how to treat people with lung infections.

High TLX1 expression correlates with poor prognosis and immune infiltrates in patients with lung adenocarcinoma.

BACKGROUND: To develop optimal personalized therapy for lung adenocarcinoma (LUAD), potential biomarkers associated with the prognosis are urgently needed. It is unclear what role T Cell Leukemia Homeobox 1 (TLX1) plays in LUAD. OBJECTIVE: In this study, TLX1's relationship with LUAD was investigated using TCGA database analysis, bioinformatics analysis, and experimental validation. METHODS: We examined the expression of TLX1 in pan cancer and LUAD, the relationship between TLX1 expression and clinical features, immune infiltration, its diagnostic and prognostic value, as well as TLX1 related pathways. The analysis included various statistical methods, including the Kaplan-Meier method, Cox regression analysis, GSEA, and immune infiltration analysis. TLX1 expression in LUAD cell lines was validated using qRT-PCR. RESULT: In LUAD patients, high expression of TLX1 was associated with T stage (P<0.001). High TLX1 expression was associated with worse overall survival (OS) (HR: 1.57; 95% CI: 1.18-2.1; P=0.002). And TLX1 [removed]HR: 1.619; 95% CI: 1.012-2.590; P=0.044) was independently correlated with OS in LUAD patients. TLX1 expression was associated with the pathways, including Rho GTPase effectors, DNA repair, TCF dependent signaling in response to WNT, signaling by Nuclear Receptors, signaling by Notch, chromatin-modifying enzymes, ESR-mediated signaling, cellular senescence, and transcriptional regulation by Runx1. TLX1 expression was correlated with aDC, Tcm, and TReg cells. The expression of TLX1 was significantly increased in LUAD cells compared to BEAS-2B cells. CONCLUSION: An association between high TLX1 expression and poor survival and immune infiltration was found in LUAD patients. There may be a potential role for TLX1 in diagnosis, prognosis, and immunotherapy for LUAD.

Identification of a TGF-ß signaling-related gene signature for prediction of immunotherapy and targeted therapy for lung adenocarcinoma.

BACKGROUND: Transforming growth factor (TGF)-ß signaling functions importantly in regulating tumor microenvironment (TME). This study developed a prognostic gene signature based on TGF-ß signaling-related genes for predicting clinical outcome of patients with lung adenocarcinoma (LUAD). METHODS: TGF-ß signaling-related genes came from The Molecular Signature Database (MSigDB). LUAD prognosis-related genes were screened from all the genes involved in TGF-ß signaling using least absolute shrinkage and selection operator (LASSO) Cox regression analysis and then used to establish a risk score model for LUAD. ESTIMATE and CIBERSORT analyzed infiltration of immune cells in TME. Immunotherapy response was analyzed by the TIDE algorithm. RESULTS: A LUAD prognostic 5-gene signature was developed based on 54 TGF-ß signaling-related genes. Prognosis of high-risk patients was significantly worse than low-risk patients. Both internal validation and external dataset validation confirmed a high precision of the risk model in predicting the clinical outcomes of LUAD patients. Multivariate Cox analysis demonstrated the model independence in OS prediction of LUAD. The risk model was significantly related to the infiltration of 9 kinds of immune cells, matrix, and immune components in TME. Low-risk patients tended to respond more actively to anti-PD-1 treatment, while high-risk patients were more sensitive to chemotherapy and targeted therapy. CONCLUSIONS: The 5-gene signature based on TGF-ß signaling-related genes showed potential for LUAD management.

Hypomethylation-driven overexpression of HJURP promotes progression of hepatocellular carcinoma and is associated with poor prognosis.

Our previous studies have initially identified HJURP, which encodes a Holliday junction recognizing protein, as a hepatocellular carcinoma (HCC) susceptibility gene. In this report, we showed that the HJURP is highly expressed in HCC tissues compared to adjacent normal tissues. Overexpression of HJURP in HCC tissues is mainly due to the hypomethylation of HJURP promoter region. Clinically, high expression of HJURP is significantly associated with poor overall survival and disease-free survival of patients with HCC, as well as in multiple other types of cancer. Gain- and loss-of functional studies demonstrated that HJURP promotes HCC cell proliferation, clone formation, migration and invasion. Additionally, HJURP enhances HCC tumorigenesis via reducing G0/G1 arrest and apoptosis. Mechanistically, by gene set enrichment analysis (GSEA) analysis, HJURP was identified as a modulator involved in CENPA-mediated centromere maintenance. Our results provide evidence of HJURP as an important oncogene that promotes HCC progression, and the HJURP pathway may be a potential target for the treatment of HCC.

Genomic Mutations of Primary and Metastatic Lung Adenocarcinoma in Chinese Patients.

Lung cancer is still the leading cause of cancer-related death worldwide. Of lung cancer, lung adenocarcinoma (LUAD) is the most common subtype. Most patients with LUAD would develop into metastasis, which limits the available treatment. Targeted therapy and immunotherapy provided options for those advanced patients. But they also broached up challenges to identify the appropriate patients. This study aims to reveal the landscapes of genomic mutations in primary and metastatic LUAD and their actionability. This study enrolled 636 patients with LUAD, of whom 85 and 551 were from patients with and without metastasis, respectively. Next-generation sequencing technology was used to retrieve their genomic information. Genomic mutations including short nucleotide variation, long variation, copy number variations, and fusions were called. The corresponding actionability was revealed. A comparison of genomic mutations and actionability between primary and metastatic LUAD was performed. In primary tumors, BRCA2 and FAT3 were significantly mutated in older patients; while in metastases, ALK and NOTCH2 were significantly mutated in younger patients. Primary tumors in male patients were significantly mutated in LRP1B and KRAS. Compared to primary tumors, metastases harbored less short nucleotide variations but more copy number variations and fusions. In metastases, chromosome 1 and chromosome 9 had less short nucleotide variations and more CNV than in primary tumors. Genomic variations of activated dendritic cells were more frequently mutated in metastases. EGFR genomic variations were negatively associated with PD-L1 and TMB. Patients with EGFR inhibitor treatment tend to have lower PD-L1 expression. The revealed discrepancy between primary and metastatic lung cancer could help guide the treatment strategies and the development of novel drugs.

Three-Dimensional Numerical Investigation of Pore Water Pressure and Deformation of Pumped Aquifer Systems.

Excessive groundwater withdrawal has caused severe land subsidence worldwide. The pore water pressure and the deformation of pumped hydrostratigraphic units are complex. A fully coupled three-dimensional numerical simulation was carried out for different pumping plans in this paper. When groundwater is pumped from a confined aquifer, the great compaction occurs in the pumped aquifer and its upper and lower adjacent aquitard units. Land subsidence is smaller and the area affected by land subsidence is greater when groundwater is pumped from the deeper confined aquifer. The pore water pressure in the pumped confined aquifer changes immediately with pumpage. In the adjacent aquitard units, however, the pore water pressure increases in the early pumping time and decreases in the early recharging time. The decrease in the pore water pressure vertically spreads from the interface between aquitard and pumped aquifer to the other surface of the aquitard. The pumped aquifer compacts and rebounds immediately with pumping and non-pumping or recharging actions, while the compaction and rebounding of the aquitard units clearly lag behind. The compaction of the adjacent aquitard unit first occurs near the interface between aquitard and pumped aquifer units, and the compaction zone spreads outward as the pumping goes on. The aquitards may expand vertically within some zones. Due to the inelastic deformation of soil skeleton, different pumping plans result in different land subsidence. For the same net pumpage, maximal land subsidence and horizontal displacement are the smallest for constant discharge and the greatest for recharge-discharge cycle.

Laboratory experiments on HMC coupling mechanisms in innovative clean foundation treatments for Zn-contaminated dredger fills.

Large-scale contaminated dredger fills have comprehensively resulted from human activities and geological deposition processes, and their disposal is a worldwide challenge. Innovative soil remediation coupling foundation treatment methods, namely, clean foundation treatment methods (CFTMs), were proposed and verified using a hydraulic-mechanical-chemical coupling triaxial testing system. The CFTM exploration triaxial tests on undisturbed clayey, silty, and sandy dredger fills showed that the critical injection significantly dilated soil volume even after the soil was vacuum pumped. Critical injection-vacuum soil flushing (CIVF), critical injection soil flushing (CIF), and vacuum soil flushing (VF) were proposed to perform clean foundation treatment for clayey silt, sandy silt, and silty sand of 1900-2300 ppm Zn. EDDS, HCl + CaCl2, and HCl were selected as the three chelating agents. Orthogonal tests on three factors (CFTM, soil type, and eluent) showed that CIF with 5:1 EDDS aq. of pH 3.8 was the best CFTM scheme for the three soil types at a depth of 2.5-10 m. CIF with HCl aq. of pH 3.8 also reached a high comprehensive clean foundation treatment efficiency for silty sand at a depth of 2.5 m. The deep depth and heterogeneous texture resulted in low Zn contamination extraction efficiency.

Distribution and origination of zinc contamination in newly reclaimed heterogeneous dredger fills: Field investigation and numerical simulation.

Heavy metal elements, including Zn, Cd, As, Ni, Cu, Pb and Cr, were detected in soils (no deeper than 75 m) from newly reclaimed zones of Shanghai, China. The Zn concentration exceeded soil quality limits. The Zn contamination was tested in both dredger fills and sedimentary layers (①3-3, ②3, ④ and ⑤1-1). However, it was not detected in layer ⑤1-2-⑨. PCA and HCA analysis show that exogenous Zn probably was the contaminant source of dredger fills before the fills were dredged from the neighboring waters. Stochastic heterogeneity of the dredger fills affects the Zn-depollution remarkably. Numerical simulations show both acid precipitation and widespread drainage channels in the zones contributed to Zn-decrease in the dredger fills no deeper than 1.2 m. Acid rainstorms work better than acid constant precipitation in Zn-remediation for layers below 0.4 m. To remove Zn contamination in deep dredger fills, un-consolidation of the fills should be utilized.

High expression of RBM8A predicts poor patient prognosis and promotes tumor progression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a huge threat for human health worldwide. As a complicated tumor, the molecular basis for HCC development especially metastasis requires exploration. Although RNA binding motif (RBM) proteins are closely related to various cancers, the clinical importance and underlying mechanisms of RBM8A in HCC remain elusive. In this study, we found that RBM8A was highly expressed in HCC tumor tissues compared to normal liver tissues. Overexpression of RBM8A was associated with HbsAg and Edmondson pathological grading. Moreover, Kaplan-Meier survival analysis showed that high expression of RBM8A was related to the poor overall survival and progression-free survival of patients with HCC. Gain- and loss-of-function experiments further demonstrated that RBM8A promoted tumor cell migration and invasion in HCC via activation of epithelial-mesenchymal transition signaling pathway. It is also noteworthy that RBM8A is required for tumor cell proliferation and anti-apoptosis in HCC. Altogether, our results revealed a close relationship between RBM8A and HCC prognosis as well as a critical tumor-promoting function of RBM8A in HCC progression, suggesting that RBM8A might be a potential bio-marker and drug target in HCC therapy.

MicroRNA-148a Acts as a Tumor Suppressor in Osteosarcoma via Targeting Rho-Associated Coiled-Coil Kinase.

MicroRNAs (miRs) have been demonstrated to be involved in the development and progression of osteosarcoma (OS), but the molecular mechanism still remains to be fully investigated. The present study investigated the function of miR-148a in OS, as well as its underlying mechanism. Our data showed that miR-148a was significantly downregulated in OS tissues compared to their matched adjacent normal tissues, and also in OS cell lines compared to normal human osteoblast cells. Low expression of miR-148a was significantly associated with tumor progression and a poor prognosis for OS patients. Rho-associated coiled-coil kinase 1 (ROCK1) was then identified as a target of miR-148a in Saos-2 and U2OS cells, and the expression of ROCK1 was significantly increased in OS tissues and cell lines. Moreover, the protein expression of ROCK1 was markedly reduced in miR-148a-overexpressing Saos-2 and U2OS cells, but significantly increased in miR-148a-downregulated Saos-2 and U2OS cells. Further investigation indicated that miR-148a had a suppressive effect on the proliferative, migratory, and invasive capacities of Saos-2 and U2OS cells. Moreover, overexpression of ROCK1 attenuated the inhibitory effects of miR-148a upregulation on the malignant phenotypes of Saos-2 and U2OS cells. In addition, overexpression of miR-148a significantly inhibited the tumor growth of U2OS cells in nude mice. Taken together, these data demonstrate that miR-148a acts as a tumor suppressor in OS, at least partly, via targeting ROCK1. Therefore, the miR-148a/ROCK1 axis may become a potential therapeutic target for OS.