Treating type 2 diabetes (T2D) patients with sodium–glucose cotransporter 2 (SGLT2) inhibitors may be associated with an increased risk of urinary tract infections (UTIs), such as diabetes-induced asymptomatic bacteriuria. Pyuria—a condition wherein leukocytes are detected in the urine—is a predictor of UTIs. The aim of this study was to examine the urinary microbiome of Taiwanese T2D patients, with or without pyuria, undergoing SGLT2 treatment. We recruited seven T2D patients, recorded their clinical and biochemical characteristics, and collected their urine samples for 16S metagenomic sequencing. The primary outcomes were the diversity of urinary microbiota and the relative abundance of different species. We found that the microbiome of the pyuria group was significantly less diverse than the non-pyuria group (0.24 ± 0.04 vs. 2.21 ± 0.28, p = 0.002), while the number of operational taxonomic units did not differ significantly (763.5 ± 78.67 and 747 ± 141.3, p = 0.92). Escherichia-Shigella spp. dominated the microbiome of the pyuria group (97.4%–99.4%), and these patients tended to have more comorbidities. In conclusion, pyuria is associated with urinary microbiota dysbiosis in T2D patients being treated with SGLT2 inhibitors.

Esophageal squamous cell carcinoma (ESCC) remains a leading cause of cancer-related mortality worldwide. Despite neoadjuvant concurrent chemoradiotherapy (nCCRT), approximately half of patients exhibit incomplete pathological response with persistent lymph node (LN) infiltration. The tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs) and natural killer (NK) cells, plays crucial roles in treatment outcomes, yet specific cellular signatures associated with LN infiltration status remain poorly characterized. We performed single-cell RNA sequencing analysis on tumor and adjacent normal tissues from 10 ESCC patients who underwent nCCRT followed by surgical resection. Patients were stratified into presence (n = 5) and absence (n = 5) groups based on histological draining LN infiltration status according to ypTNM staging. Cell-type identification, subclustering analysis, differential expression analysis, pathway enrichment, and pseudotime trajectory analysis were performed to characterize infiltration-associated signatures. Analysis of 47,907 cells revealed nine cell populations with significant compositional differences between group. Patients with LN infiltration were characterized by significant enrichment of CLEC2B^himyCAF subtype (10.64% vs. 0.58%), highly expressing NFKB1 and associated with immunosuppressive pathways. Conversely, patients without infiltration showed markedly increased abundance of CD56dim NK subset (19.14% vs. 1.73%), linked to enhanced cytotoxic function. Pseudotime trajectory analysis revealed that cells from different groups occupied opposite ends of trajectories. Treatment-associated cellular signatures extended beyond tumor regions to adjacent normal tissues within the radiation field, indicating regional tissue reprogramming associated with therapeutic exposure. This single-cell analysis reveals that LN infiltration status in ESCC is characterized by distinct TME signatures involving CLEC2B^himyCAF in patients with infiltration and F11R^hiCD56dim NK in patients without infiltration. These findings provide new insights into cellular mechanisms underlying different pathological outcomes following nCCRT and offer potential biomarkers for patient stratification and therapeutic targets in ESCC management.

Lynch syndrome (LS) is an autosomal dominant disorder characterized by increased risks of colorectal and endometrial cancers. LS is defined by pathogenic variants in mismatch repair (MMR) genes, including MLH1, MSH2, and MSH6. Data on the prevalence and associated cancer risks of LS in the Han Chinese population remain limited. In this study, using a broad biobank approach through the Taiwan Precision Medicine Initiative (TPMI), we identified LS-associated MMR gene variants within a cohort of 42,828 participants from a Taiwanese medical center. A total of 89 individuals were found to carry pathogenic MMR variants: MLH1 (n = 22, 25%), MSH2 (n = 47, 53%), and MSH6 (n = 20, 22%). The overall prevalence of MMR variants was calculated, and cancer incidence rates among carriers were determined. The prevalence of MMR variants in the study population was 1 in 481. The distribution of MLH1, MSH2, and MSH6 variants were 24.7%, 52.8%, and 22.5%, respectively. Cumulative cancer incidence rates of carriers were 40.9% for MLH1 carriers, 29.8% for MSH2, and 40% for MSH6. Among the 19 individuals who underwent colonoscopy screening, the prevalence of polyps was similar to that of the control group (adenoma detection rate: 32% vs 26%, p = 0.585). A meticulous analysis of the detected polyps in seven participants, considering factors such as location, size, morphology, and pathological features, showed no significant differences from controls. A significant cancer risk is associated with LS-related MMR variants in the Taiwanese population. The apparent under diagnosis of LS highlights the urgent need for enhanced surveillance and genetic counseling in this demographic. Our findings suggest that adjustments in the current screening protocols may be warranted to better identify and manage at-risk individuals.

Background/Objectives: Intra-abdominal infections (IAIs) constitute significant clinical challenges that can rapidly progress to life-threatening conditions if not promptly diagnosed and treated. Traditional pathogen identification methodologies, predominantly culture-based, frequently necessitate extended turnaround times (TATs) and exhibit limitations in detecting polymicrobial or anaerobic infections. Methods: We implemented Oxford Nanopore Technology (ONT) sequencing to analyze the microbiota in patients with IAIs at Taichung Veterans General Hospital. The study cohort comprised sixteen patients with IAIs. Following specimen collection, DNA extraction was performed, and then full-length 16S rRNA and ITS region amplification and subsequent ONT sequencing were conducted. Results: Conventional clinical culture-based methodologies detected pathogens in 13 patients. Among the 14 successfully sequenced specimens, ONT sequencing elucidated a diverse spectrum of bacteria and fungi, with read counts ranging from 375 to 19,716. Polymicrobial and anaerobe-enriched communities were predominantly observed in lower gastrointestinal tract infections, specifically colonic or small bowel perforations, whereas upper gastrointestinal perforations, including those of the stomach or duodenum, were frequently dominated by Streptococcus, Granulicatella, or Candida species. The sequencing identified pathogens concordant with culture results, including Escherichia coli, Enterococcus, and Candida albicans. In addition, anaerobic or low-abundance taxa were exclusively identifiable through sequencing methodologies. Conclusions: ONT sequencing facilitated results within up to 24 h and successfully detected pathogens in culture-negative cases. These findings underscore the utility of ONT sequencing as an expeditious and comprehensive diagnostic modality for IAIs.

The specific impacts of LDLR and APOB variants on premature coronary artery disease (CAD) that requires revascularization are less explored in Han Chinese