Background: Tuberculosis (TB) is a global issue that seriously endangers public health. Pathology is one of the most important means for diagnosing TB in clinical practice. To confirm TB as the diagnosis, finding specially stained TB bacilli under a microscope is critical. Because of the very small size and number of bacilli, it is a time-consuming and strenuous work even for experienced pathologists, and this strenuosity often leads to low detection rate and false diagnoses. We investigated the clinical efficacy of an artificial intelligence (AI)-assisted detection method for acid-fast stained TB bacillus. Methods: We built a convolutional neural networks (CNN) model, named tuberculosis AI (TB-AI), specifically to recognize TB bacillus. The training set contains 45 samples, including 30 positive cases and 15 negative cases, where bacilli are labeled by human pathologists. Upon training the neural network model, 201 samples (108 positive cases and 93 negative cases) were collected as test set and used to examine TB-AI. We compared the diagnosis of TB-AI to the ground truth result provided by human pathologists, analyzed inconsistencies between AI and human, and adjusted the protocol accordingly. Trained TB-AI were run on the test data twice. Results: Examined against the double confirmed diagnosis by pathologists both via microscopes and digital slides, TB-AI achieved 97.94% sensitivity and 83.65% specificity. Conclusions: TB-AI can be a promising support system to detect stained TB bacilli and help make clinical decisions. It holds the potential to relieve the heavy workload of pathologists and decrease chances of missed diagnosis. Samples labeled as positive by TB-AI must be confirmed by pathologists, and those labeled as negative should be reviewed to make sure that the digital slides are qualified.

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. 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. 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. 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.

POLE mutation is a prognostic marker associated with excellent outcome in endometrial carcinoma (EC). However, these EC tumors frequently have aggressive histology. The aim of this study was to determine how to integrate the implications of POLE mutations into existing risk assessment strategies and further stratify patients. We detected POLE mutations in a cohort of 426 ECs from Chinese women and observed their prognostic significance in terms of survival and recurrence outcomes in combination with histological and other molecular characteristics, including microcystic, elongated and fragmented (MELF) pattern invasion, histologic subtype, tumor grade, myometrial invasion and p53 protein and mismatch repair protein expression status. POLE mutations were identified in 38 of 426 ECs (8.9%). The most common mutations were P286R (31.6%), V411L (15.8%) and Q453R (15.8%). We confirmed that POLE mutation was associated with improved overall survival (P = .047), although it did not show a statistically significant relationship with progression-free survival (P = .45). Interestingly, further analyses indicated that in POLE-mutant tumors, MELF pattern invasion was associated with a 15.1-fold increase in tumor recurrence or progression risk (HR = 15.1, 95%CI = 1.57-145.3, P = .018), whereas this phenomenon was not present in the POLE-wild-type subgroup (HR = 0.90, 95%CI = 0.39-2.08, P = .80). Furthermore, higher staging and deeper myometrial invasion also showed much higher risk in patients harboring POLE mutations compared with those without POLE mutations. Although POLE mutation was associated with favorable overall survival, the combined consideration of POLE mutation status and established clinicopathologic factors in the risk assessment of endometrial cancer is more accurate than the consideration of clinicopathologic factors alone and might lead to precise and individualized therapeutic strategies.

The mechanism for inactivation of positive regulatory domain containing I (PRDM1), a newly identified tumour suppressor gene in extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT) has not been well defined. The aim of the present study was to investigate the expression of PRDM1 in EN-NK/T-NT and analyse its downregulation by miRNAs. PRDM1 and miRNA expression were evaluated in EN-NK/T-NT samples by immunohistochemical analysis, qRT-PCR, and in situ hybridisation. Luciferase assays were performed to verify the direct binding of miR-223 to the 3′-untranslated region of PRDM1 mRNA. In addition, the effect of miR-223 on PRDM1 expression was assessed in NK/T lymphoma cell lines by transfecting a miR-223 mimic or inhibitor to increase or decrease the effective expression of miR-223. Overall survival and failure-free survival in EN-NK/T-NT patients were analysed using Kaplan-Meier single-factor analysis and the log-rank test. Investigation of the downregulation of PRDM1 in EN-NK/T-NT cases revealed that PRDM1-positive staining might be a favourable predictor of overall survival and failure-free survival in EN-NK/T-NT patients. However, the negative staining of PRDM1 usually presented transcripts, suggesting a possible post-transcriptional regulation. miR-223 and its putative target gene, PRDM1, exhibited opposite patterns of expression in EN-NK/T-NT tissues and cell lines. Moreover, PRDM1 was identified as a direct target gene of miR-223 by luciferase assays. The ectopic expression of miR-223 led to the downregulation of the PRDM1 protein in the NK/T-cell lymphoma cell line, whereas a decrease in miR-223 restored the level of PRDM1 protein. Our findings reveal that the downregulation of the tumour suppressor PRDM1 in EN-NK/T-NT samples is mediated by miR-223 and that PRDM1-positive staining might have prognostic value for evaluating the clinical outcome of EN-NK/T-NT patients.

Maternal sepsis is a life-threatening condition and ranks among the top five causes of maternal death in pregnancy and the postpartum period. Herein, we conducted a retrospective study on sepsis cases to explain the related risk factors by comparing them with bloodstream infection (BSI) and control maternities. In total, 76 sepsis cases were enrolled, and 31 BSI and 57 maternal cases of the same age but with neither sepsis nor BSI were set as controls. Genital tract infection (GTI) and pneumonia were the two most common infection sources in both sepsis (22 cases, 29% and 29 cases, 38%) and BSI cases (18 cases, 58% and 8 cases, 26%). Urinary tract infection (UTI)/pyelonephritis (9 cases, 12%) and digestive infection cases (11 cases, 14%) only existed in the sepsis group. Significantly different infection sources were discovered between the sepsis-death and sepsis-cure groups. A higher proportion of pneumonia and a lower proportion of GTI cases were present in the sepsis-death group (17 cases, 45% pneumonia and 9 cases, 24% GTI) than in the sepsis-cure group (12 cases, 32% pneumonia and 13 cases, 34% GTI). In addition, although gram-negative bacteria were the dominant infectious microorganisms as previously reported, lower proportion of gram-negative bacteria infectious cases in sepsis (30 cases, 50%) and even lower in sepsis-death group (14 cases, 41%) was shown in this study than previous studies. As expected, significantly greater adverse maternal and fetal outcomes, such as higher maternal mortality (26.3% vs. 0% vs. 0%), higher fetal mortality (42.2% vs. 20.8% vs. 0%), earlier gestational age at delivery (26.4 ± 9.5 vs. 32.3 ± 8.1 vs. 37.7 ± 4.0) and lower newborn weight (1,590 ± 1287.8 vs. 2859.2 ± 966.0 vs. 3214.2 ± 506.4), were observed in the sepsis group. This study offered some potential pathogenesis and mortality risk factors for sepsis, which may inspire the treatment of sepsis in the future.