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Primary central nervous system lymphoma (PCNSL) is a rare extra-nodal non-Hodgkin lymphoma confined to the central nervous system. The cancer biology of PCNSL remains incomplete and is often associated with genetic aberrations with abnormal signaling pathways, cell differentiation, regulation of epigenetic modification, and the tumor microenvironment. Stereotactic brain biopsy remains the gold standard for the diagnosis of PCNSL. For patients ill-suited for biopsy, MYD88 and IL-10 may be important biomarkers to diagnose PCNSL. High-dose methotrexate-based polychemotherapy is currently the standard induction treatment for PCNSL, followed by consolidation treatments including autologous stem cell transplant and whole-brain radiotherapy. Some studies suggest that low-dose lenalidomide is recommended as a maintenance therapy for PCNSL. Currently, relapse rates of PCNSL range from 25 to 50% with poor prognosis. Insight research is necessary to identify novel targeted treatments to improve outcomes in relapsed/refractory disease, such as immunomodulatory drugs, immune checkpoint inhibitors, signaling pathway inhibitors, and chimeric antigen receptor T-cell therapy.

Purpose. To determine the advantages of next-generation metagenomic sequencing (mNGS) technology in the diagnosis and treatment of infectious keratitis (IK). Methods. A total of 287 patients with IK admitted to the Department of Ophthalmology of Nanjing First Hospital between August 2018 and December 2022 were analyzed retrospectively, and the pathogenic causes, etiological characteristics, detection, treatment methods, and efficacy were summarized. Results. Trauma and foreign matter were the most common causes of IK (144 patients, 50.2%). Of the 287 patients, 228 (79.4%) were diagnosed with a specific etiology, including 110 (48.2%) fungal infections, 44 (19.3%) viral infections, 42 (18.4%) mixed infections, and 30 (13.2%) bacterial infections. Filamentous fungi represented by Fusarium and Aspergillus were the most common, followed by bacteria such as Pseudomonas aeruginosa, Streptococcus pneumoniae, viruses (Herpes Simplex Virus/Varicella-Zoster Virus), and parasites. The positivity rates of secretion culture, corneal laser confocal microscopy (CM), mNGS, and pathological sections were 47.3% (133/281), 45.3% (111/245), 83.9% (104/124), and 19.3% (40/207), respectively. The positivity rate of mNGS for bacteria and viruses was higher than that of the other methods, and the positivity rate for fungi was the same as that for CM. As a result, 214 cases (74.6%) were cured, 51 cases (17.8%) improved, 8 cases (2.8%) did not heal, ocular content enucleation was performed in 14 cases (4.9%), and the overall efficacy rate was 92.3%. Conclusion. Trauma and foreign matter are the main causes of IK. The mNGS technology is an efficient and comprehensive detection method for viruses and bacteria, especially for mixed infections.

Cancer, which presents with high incidence and mortality rates, has become a significant health threat worldwide. However, there is currently no effective solution for rapid screening and high-quality treatment of early-stage cancer patients. Metal-based nanoparticles (MNPs), as a new type of compound with stable properties, convenient synthesis, high efficiency, and few adverse reactions, have become highly competitive tools for early cancer diagnosis. Nevertheless, challenges such as the difference between the microenvironment of detected markers and the real-life body fluids remain in achieving widespread clinical application of MNPs. This review provides a comprehensive review of the research progress made in the field of in vitro cancer diagnosis using metal-based nanoparticles. By delving into the characteristics and advantages of these materials, this paper aims to inspire and guide researchers towards fully exploiting the potential of metal-based nanoparticles in the early diagnosis and treatment of cancer.

Renal involvement by non-Hodgkin lymphoma (NHL) is under-recognized and often misdiagnosed as interstitial nephritis. Kidney biopsy remains the gold standard for confirming lymphoma interstitial infiltration. Currently, the histopathological characteristics of lymphoma-related renal interstitial infiltration and their relationship with clinical prognosis remain unclear. We retrospectively analyzed 36 biopsy-proven cases to characterize clinicopathological features, prognostic markers such as tubular basement membrane (TBM) deposits and patient outcomes. Clinicopathological data were collected at the time of kidney biopsy. The cohort included 21 males and 15 females, with a median age of 65 years (range: 19-84). Among them, 26 had indolent B-cell NHL, seven had aggressive B-cell NHL, and three had T-cell NHL. In indolent B-cell NHL, lymphoma infiltration ranged from 10 to 90%. Glomerular lesions were observed in 23 patients (23/26, 88.5%). TBM deposits were found by electron microscopy in four patients. Notably, TBM immune deposits were associated with worse kidney outcomes (  = 0.03). In aggressive B-cell and T-cell NHL, diffuse interstitial infiltration was prominent, resulting in acute kidney injury (AKI) and kidney enlargement. T-cell NHL was linked to poorer kidney outcomes and overall survival (  < 0.001). In conclusion, different lymphoma types exhibited different kidney lesions, with T-cell NHL was associated with worse outcomes. TBM deposits were associated with poor kidney prognosis in indolent B-cell NHL. Our findings highlight that the presence of a diffuse, monomorphic interstitial infiltrate-particularly when accompanied by invasion of sclerotic glomeruli or the renal capsule-should raise strong suspicion for lymphomatous infiltration over interstitial nephritis.

The genus Elizabethkingia has recently emerged as a cause of life-threatening infections in humans, particularly in immunocompromised patients. Several new species in the genus Elizabethkingia have been proposed in the last decade. Numerous studies have indicated that Elizabethkingia anophelis, rather than Elizabethkingia meningoseptica, is the most prevalent pathogen in this genus. Matrix-assisted laser desorption/ionization–time of flight mass spectrometry systems with an extended spectrum database could reliably identify E. anophelis and E. meningoseptica, but they are unable to distinguish the remaining species. Precise species identification relies on molecular techniques, such as housekeeping gene sequencing and whole-genome sequencing. These microorganisms are usually susceptible to minocycline but resistant to most β-lactams, β-lactam/β-lactam inhibitors, carbapenems, and aminoglycosides. They often exhibit variable susceptibility to piperacillin, piperacillin-tazobactam, fluoroquinolones, and trimethoprim-sulfamethoxazole. Accordingly, treatment should be guided by antimicrobial susceptibility testing. Target gene mutations are markedly associated with fluoroquinolone resistance. Knowledge on the genomic characteristics provides valuable insights into in these emerging pathogens.

Elizabethkingia bruuniana is a novel species of the Elizabethkingia genus. There is scant information on this microorganism. Here, we report the whole-genome features and antimicrobial susceptibility patterns of E . bruuniana strain EM798-26. Elizabethkingia strain EM798-26 was initially identified as E . miricola . This isolate contained a circular genome of 4,393,011 bp. The whole-genome sequence-based phylogeny revealed that Elizabethkingia strain EM798-26 was in the same group of the type strain E . bruuniana G0146 T . Both in silico DNA-DNA hybridization and average nucleotide identity analysis clearly demonstrated that Elizabethkingia strain EM798-26 was a species of E . bruuniana . The pan-genome analysis identified 2,875 gene families in the core genome and 5,199 gene families in the pan genome of eight publicly available E . bruuniana genome sequences. The unique genes accounted for 0.2–12.1% of the pan genome in each E . bruuniana . A total of 59 potential virulence factor homologs were predicted in the whole-genome of E . bruuniana strain EM798–26. This isolate was nonsusceptible to multiple antibiotics, but susceptible to aminoglycosides, minocycline, and levofloxacin. The whole-genome sequence analysis of E . bruuniana EM798-26 revealed 29 homologs of antibiotic resistance-related genes. This study presents the genomic features of E . bruuniana . Knowledge of the genomic characteristics provides valuable insights into a novel species.

Anaplastic lymphoma kinase (ALK) rearrangements are drivers of a subset of non‐small cell lung cancer (NSCLC). The rapid progression of ALK inhibitors has significantly prolonged the progression‐free survival of patients with ALK gene‐sensitive mutations. However, the response of patients with rare ALK rearrangements to tyrosine kinase inhibitors remains unknown. Here, we report a rare case of striatin (STRN)‐ALK‐positive NSCLC showing primary resistance to first‐line therapy alectinib and limited clinical activity of crizotinib in the alectinib‐resistant setting. Here, we report a rare case of striatin (STRN)‐ALK‐positive NSCLC responding to crizotinib after the failure of alectinib. Our study highlights the heterogeneity in response of STRN‐ALK fusion to targeted drugs and provides clinical evidence of STRN‐ALK fusion responding to crizotinib.

Fluoroquinolones are potentially active against Elizabethkingia anophelis. Rapidly increased minimum inhibitory concentrations (MICs) and emerging point mutations in the quinolone resistance-determining regions (QRDRs) following exposure to fluoroquinolones have been reported in E. anophelis. We aimed to investigate point mutations in QRDRs through exposure to levofloxacin (1 × MIC) combinations with different concentrations (0.5× and 1 × MIC) of minocycline, rifampin, cefoperazone/sulbactam, or sulfamethoxazole/trimethoprim in comparison with exposure to levofloxacin alone. Of the four E. anophelis isolates that were clinically collected, lower MICs of levofloxacin were disclosed in cycle 2 and 3 of induction and selection in all levofloxacin combination groups other than levofloxacin alone (all p = 0.04). Overall, no mutations were discovered in parC and parE throughout the multicycles inducted by levofloxacin and all its combinations. Regarding the vastly increased MICs, the second point mutations in gyrA and/or gyrB in one isolate (strain no. 1) occurred in cycle 2 following exposure to levofloxacin plus 0.5 × MIC minocycline, but they were delayed appearing in cycle 5 following exposure to levofloxacin plus 1 × MIC minocycline. Similarly, the second point mutation in gyrA and/or gyrB occurred in another isolate (strain no. 3) in cycle 4 following exposure to levofloxacin plus 0.5 × MIC sulfamethoxazole/trimethoprim, but no mutation following exposure to levofloxacin plus 1 × MIC sulfamethoxazole/trimethoprim was disclosed. In conclusion, the rapid selection of E. anophelis mutants with high MICs after levofloxacin exposure could be effectively delayed or postponed by antimicrobial combination with other in vitro active antibiotics.

Background The poor outcome of high-grade B-cell lymphoma, with rearrangements of MYC, BCL2 and/or BCL6, also known as double-hit lymphoma or triple-hit lymphoma (DHL or THL), has been well documented, while the clinical significance of extra copies of MYC, BCL2 or BCL6 are still less well known. Methods In total, 130 cases of diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS) were included in our study. Fluorescence in situ hybridization and immunohistochemistry were performed in all cases to evaluate the genetic status and protein expression levels of MYC, BCL2 and BCL6. Results Among the 130 cases of DLBCL, the prevalence rates of extra copies of MYC, BCL2 and BCL6 were 10.8, 20.0 and 14.6%, respectively, and the corresponding rates of gene rearrangement were 10.0, 14.6 and 16.9%, respectively. In total, 7.7% (10/130) of patients were DHL/THL; 9.2% (12/130) of patients were DLBCL with MYC and BCL2 and/or BCL6 gene abnormalities including rearrangements or extra copies, while excluded DHL/THL. The positive protein expression rates of MYC, BCL2 and BCL6 were 46.9% (61), 75.4% (98) and 70.0% (91), respectively. Among the 51 cases with MYC/BCL2 co-expression, 14 cases showed concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities, and the remaining 37 cases were classified as double-expressor lymphoma (DEL). MYC and BCL2 rearrangement and BCL2 extra copies were all associated with upregulated protein expression. Cases with concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities were both associated with MYC/BCL2 co-expression. Patients with concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities excluded DHL/THL had shorter OS ( P  < 0.001) than patients with DLBCL with no genetic change, and showed no statistical different with patients with DHL/THL ( P  = 0.419). Extra copies of MYC was independent prognostic factors for DLBCL. Conclusions Patients with MYC and BCL2 and/or BCL6 gene extra copies might show a trend towards poor prognosis, and the detection of extra copies of MYC, BCL2 and BCL6 might deserve more attention.

Bacteria in the genus Elizabethkingia have emerged as a cause of life-threatening infections in humans. However, accurate species identification of these pathogens relies on molecular techniques. We aimed to evaluate the accuracy of 16S rRNA and complete RNA polymerase β-subunit (rpoB) gene sequences in identifying Elizabethkingia species. A total of 173 Elizabethkingia strains with whole-genome sequences in GenBank were included. The 16S rRNA gene and rpoB gene sequences from the same Elizabethkingia strains were examined. Of the 41 E. meningoseptica strains, all exhibited >99.5% 16S rRNA similarity to its type strain. Only 83% of the 99 E. anophelis strains shared >99.5% 16S rRNA gene similarity with its type strain. All strains of E. meningoseptica and E. anophelis formed a cluster distinct from the other Elizabethkingia species in the 16S rRNA and rpoB gene phylogenetic trees. The polymorphisms of 16S rRNA gene sequences are not sufficient for constructing a phylogenetic tree to discriminate species in the E. miricola cluster (E. miricola, E. bruuniana, E. occulta, and E. ursingii). The complete rpoB gene phylogenetic tree clearly delineates all strains of Elizabethkingia species. The complete rpoB gene sequencing could be a useful complementary phylogenetic marker for the accurate identification of Elizabethkingia species.