Atypical BCR-ABL1 transcript in mixed phenotype acute leukemia with bone marrow necrosis.

Mixed phenotype acute leukemia (MPAL) is a type of acute leukemia in which encompasses mixed features of myeloid, T-lymphoid, and/or B-lymphoid differentiation. Philadelphia chromosome-positive (Ph+) MPAL is a rare subgroup with a poor prognosis and accounts for ＜1% of adult acute leukemia. Until now, there is still no consensus on how to best treat Ph+ MPAL. Here, we report a 62-year-old male with Ph+ (atypical e13a2 BCR-ABL1 fusion protein) MPAL. This patient presented with recurrent and intense bone pain due to bone marrow necrosis (BMN). Besides, he did not achieve a complete remission for the first two chemotherapies, until he received flumatinib combined with hyper-CVAD (B) (a dose-intensive regimen include methotrexate and cytarabine). To our knowledge, this is the first report to describe the coexistence of BMN and atypical e13a2 BCR-ABL1 transcripts in patients with MPAL. This finding will bring new understandings in the diagnosis and treatment of Ph+ MPAL.

Characteristics of Molecular Genetic Mutations and Their Correlation with Prognosis in Adolescent and Adult Patients with Acute Lymphoblastic Leukemia.

INTRODUCTION: The prognosis of acute lymphoblastic leukemia (ALL) in adolescents and adults is poor, and recurrence is an important cause of their death. Changes of genetic information play a vital role in the pathogenesis and recurrence of ALL; however, the impact of molecular genetic mutations on disease diagnosis and prognosis remains unexplored. This study aimed to explore the frequency spectrum of gene mutations and their prognostic significance, along with the minimal residual disease (MRD) level and hematopoietic stem cell transplantation (HSCT), in adolescent and adult patients aged ≥15 years with ALL. METHODS: The basic characteristics, cytogenetics, molecular genetics, MRD level, treatment regimen, and survival outcome of patients with untreated ALL (≥15 years) were collected, and the correlation and survival analysis were performed using the SPSS 25.0 and R software. RESULTS: This study included 404 patients, of which 147 were selected for next-generation sequencing (NGS). NGS results revealed that 91.2% of the patients had at least one mutation, and 67.35% had multiple (≥2) mutations. NOTCH1, PHF6, RUNX1, PTEN, JAK3, TET2, and JAK1 were the most common mutations in T-ALL, whereas FAT1, TET2, NARS, KMT2D, FLT3, and RELN were the most common mutations in B-ALL. Correlation analysis revealed the mutation patterns, which were significantly different between T-ALL and B-ALL. In the prognostic analysis of 107 patients with B-ALL, multivariate analysis showed that the number of mutations ≥5 was an independent risk factor for overall survival and the RELN mutation was an independent poor prognostic factor for event-free survival. DISCUSSION: The distribution of gene mutations and the co-occurrence and repulsion of mutant genes in patients with ALL were closely related to the immunophenotype of the patients. The number of mutations ≥5 and the RELN mutation were significantly associated with poor prognosis in adolescent and adult patients with ALL.

From Detection to Cure - Emerging Roles for Urinary Tumor DNA (utDNA) in Bladder Cancer.

PURPOSE OF REVIEW: This review sought to define the emerging roles of urinary tumor DNA (utDNA) for diagnosis, monitoring, and treatment of bladder cancer. Building from early landmark studies the focus is on recent studies, highlighting how utDNA could aid personalized care. RECENT FINDINGS: Recent research underscores the potential for utDNA to be the premiere biomarker in bladder cancer due to the constant interface between urine and tumor. Many studies find utDNA to be more informative than other biomarkers in bladder cancer, especially in early stages of disease. Points of emphasis include superior sensitivity over traditional urine cytology, broad genomic and epigenetic insights, and the potential for non-invasive, real-time analysis of tumor biology. utDNA shows promise for improving all phases of bladder cancer care, paving the way for personalized treatment strategies. Building from current research, future comprehensive clinical trials will validate utDNA's clinical utility, potentially revolutionizing bladder cancer management.

Targeting N6-methyladenosine reader YTHDF1 with siRNA boosts antitumor immunity in NASH-HCC by inhibiting EZH2-IL-6 axis.

BACKGROUND & AIMS: RNA N6-methyladenosine (m6A) reader protein YTHDF1 has been implicated in cancer; however, its role in hepatocellular carcinoma (HCC), especially in non-alcoholic steatohepatitis-associated HCC (NASH-HCC), remains unknown. Here, we investigated the functional role of YTHDF1 in NASH-HCC and its interplay with the tumor immune microenvironment. METHODS: Hepatocyte-specific Ythdf1-overexpressing mice were subjected to a NASH-HCC-inducing diet. Tumor-infiltrating immune cells were profiled with single-cell RNA-sequencing, flow cytometry, and immunostaining. The molecular target of YTHDF1 was elucidated with RNA-sequencing, m6A-sequencing, YTHDF1 RNA immunoprecipitation-sequencing, proteomics, and ribosome-profiling. Ythdf1 in NASH-HCC models was targeted by lipid nanoparticle (LNP)-encapsulated small-interfering Ythdf1. RESULTS: YTHDF1 is overexpressed in tumor tissues compared to adjacent peri-tumor tissues from patients with NASH-HCC. Liver-specific Ythdf1 overexpression drives tumorigenesis in dietary models of spontaneous NASH-HCC. Single-cell RNA-sequencing and flow cytometry revealed that Ythdf1 induced accumulation of myeloid-derived suppressor cells (MDSCs) and suppressed cytotoxic CD8+ T-cell function. Mechanistically, Ythdf1 expression in NASH-HCC cells induced the secretion of IL-6, which mediated MDSC recruitment and activation, leading to CD8+ T-cell dysfunction. EZH2 mRNA was identified as a key YTHDF1 target. YTHDF1 binds to m6A-modified EZH2 mRNA and promotes EZH2 translation. EZH2 in turn increased expression and secretion of IL-6. Ythdf1 knockout synergized with anti-PD-1 treatment to suppress tumor growth in NASH-HCC allografts. Furthermore, therapeutic targeting of Ythdf1 using LNP-encapsulated small-interfering RNA significantly increased the efficacy of anti-PD-1 blockade in NASH-HCC allografts. CONCLUSIONS: We identified that YTHDF1 promotes NASH-HCC tumorigenesis via EZH2-IL-6 signaling, which recruits and activates MDSCs to cause cytotoxic CD8+ T-cell dysfunction. YTHDF1 may be a novel therapeutic target to improve responses to anti-PD-1 immunotherapy in NASH-HCC. IMPACT AND IMPLICATIONS: YTHDF1, a N6-methyladenosine reader, is upregulated in patients with non-alcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC); however, its role in modulating the tumor immune microenvironment in NASH-HCC remains unclear. Here, we show that Ythdf1 mediates immunosuppression in NASH-HCC and that targeting YTHDF1 in combination with immune checkpoint blockade elicits robust antitumor immune responses. Our findings suggest novel therapeutic targets for potentiating the efficacy of immune checkpoint blockade in NASH-HCC and provide the rationale for developing YTHDF1 inhibitors for the treatment of NASH-HCC.

METTL3 Inhibits Antitumor Immunity by Targeting m6A-BHLHE41-CXCL1/CXCR2 Axis to Promote Colorectal Cancer.

BACKGROUND & AIMS: N6-Methyladenosine (m6A) is the most prevalent RNA modification and recognized as an important epitranscriptomic mechanism in colorectal cancer (CRC). We aimed to exploit whether and how tumor-intrinsic m6A modification driven by methyltransferase like 3 (METTL3) can dictate the immune landscape of CRC. METHODS: Mettl3 knockout mice, CD34+ humanized mice, and different syngeneic mice models were used. Immune cell composition and cytokine level were analyzed by flow cytometry and Cytokine 23-Plex immunoassay, respectively. M6A sequencing and RNA sequencing were performed to identify downstream targets and pathways of METTL3. Human CRC specimens (n = 176) were used to evaluate correlation between METTL3 expression and myeloid-derived suppressor cell (MDSC) infiltration. RESULTS: We demonstrated that silencing of METTL3 in CRC cells reduced MDSC accumulation to sustain activation and proliferation of CD4+ and CD8+ T cells, and eventually suppressed CRC in ApcMin/+Mettl3+/- mice, CD34+ humanized mice, and syngeneic mice models. Mechanistically, METTL3 activated the m6A-BHLHE41-CXCL1 axis by analysis of m6A sequencing, RNA sequencing, and cytokine arrays. METTL3 promoted BHLHE41 expression in an m6A-dependent manner, which subsequently induced CXCL1 transcription to enhance MDSC migration in vitro. However, the effect was negligible on BHLHE41 depletion, CXCL1 protein or CXCR2 inhibitor SB265610 administration, inferring that METTL3 promotes MDSC migration via BHLHE41-CXCL1/CXCR2. Consistently, depletion of MDSCs by anti-Gr1 antibody or SB265610 blocked the tumor-promoting effect of METTL3 in vivo. Importantly, targeting METTL3 by METTL3-single guide RNA or specific inhibitor potentiated the effect of anti-programmed cell death protein 1 (anti-PD1) treatment. CONCLUSIONS: Our study identifies METTL3 as a potential therapeutic target for CRC immunotherapy whose inhibition reverses immune suppression through the m6A-BHLHE41-CXCL1 axis. METTL3 inhibition plus anti-PD1 treatment shows promising antitumor efficacy against CRC.

Artificial Intelligence-Assisted Colonoscopy for Colorectal Cancer Screening: A Multicenter Randomized Controlled Trial.

BACKGROUND AND AIMS: Artificial intelligence (AI)-assisted colonoscopy improves polyp detection and characterization in colonoscopy. However, data from large-scale multicenter randomized controlled trials (RCT) in an asymptomatic population are lacking. METHODS: This multicenter RCT aimed to compare AI-assisted colonoscopy with conventional colonoscopy for adenoma detection in an asymptomatic population. Asymptomatic subjects 45-75 years of age undergoing colorectal cancer screening by direct colonoscopy or fecal immunochemical test were recruited in 6 referral centers in Hong Kong, Jilin, Inner Mongolia, Xiamen, and Beijing. In the AI-assisted colonoscopy, an AI polyp detection system (Eagle-Eye) with real-time notification on the same monitor of the endoscopy system was used. The primary outcome was overall adenoma detection rate (ADR). Secondary outcomes were mean number of adenomas per colonoscopy, ADR according to endoscopist's experience, and colonoscopy withdrawal time. This study received Institutional Review Board approval (CRE-2019.393). RESULTS: From November 2019 to August 2021, 3059 subjects were randomized to AI-assisted colonoscopy (n = 1519) and conventional colonoscopy (n = 1540). Baseline characteristics and bowel preparation quality between the 2 groups were similar. The overall ADR (39.9% vs 32.4%; P < .001), advanced ADR (6.6% vs 4.9%; P = .041), ADR of expert (42.3% vs 32.8%; P < .001) and nonexpert endoscopists (37.5% vs 32.1%; P = .023), and adenomas per colonoscopy (0.59 ± 0.97 vs 0.45 ± 0.81; P < .001) were all significantly higher in the AI-assisted colonoscopy. The median withdrawal time (8.3 minutes vs 7.8 minutes; P = .004) was slightly longer in the AI-assisted colonoscopy group. CONCLUSIONS: In this multicenter RCT in asymptomatic patients, AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists. (ClinicalTrials.gov, Number: NCT04422548).

Identification of ORM1, vWF, SPARC, and PPBP as immune-related proteins involved in immune thrombocytopenia by quantitative LC-MS/MS.

BACKGROUND: Immune thrombocytopenia (ITP) is a common autoimmune disease characterized by loss of immune tolerance to platelet autoantigens leading to excessive destruction and insufficient production of platelets. METHOD: Quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed to detect the differentially expressed proteins in bone marrow samples from active ITP patients and normal controls. RESULT: Our bioinformatic analysis identified two upregulated proteins (ORM1 and vWF) and two downregulated proteins (PPBP and SPARC) related to immune function. The four proteins were all found to be related to the tumor necrosis factor (TNF) -α signalling pathway and involved in the pathogenesis of ITP in KEGG pathway analysis. CONCLUSION: Bioinformatics analysis identified differentially expressed proteins in bone marrow that are involved in the TNF-α signalling pathway and are related to the activation of immune function in ITP patients. These findings could provide new ideas for research on the loss of immune tolerance in ITP patients.

Novel deep learning-based computer-aided diagnosis system for predicting inflammatory activity in ulcerative colitis.

BACKGROUND AND AIMS: Endoscopy is increasingly performed for evaluating patients with ulcerative colitis (UC). However, its diagnostic accuracy is largely affected by the subjectivity of endoscopists' experience and scoring methods, and scoring of selected endoscopic images cannot reflect the inflammation of the entire intestine. We aimed to develop an automatic scoring system using deep-learning technology for consistent and objective scoring of endoscopic images and full-length endoscopic videos of patients with UC. METHODS: We collected 5875 endoscopic images and 20 full-length videos from 332 patients with UC who underwent colonoscopy between January 2017 and March 2021. We trained the artificial intelligence (AI) scoring system using these images, which was then used for full-length video scoring. To more accurately assess and visualize the full-length intestinal inflammation, we divided the large intestine into a fixed number of "areas" (cecum, 20; transverse colon, 20; descending colon, 20; sigmoid colon, 15; rectum, 10). The scoring system automatically scored inflammatory severity of 85 areas from every video and generated a visualized result of full-length intestinal inflammatory activity. RESULTS: Compared with endoscopist scoring, the trained convolutional neural network achieved 86.54% accuracy in the Mayo-scored task, whereas the kappa coefficient was .813 (95% confidence interval [CI], .782-.844). The metrics of the Ulcerative Colitis Endoscopic Index of Severity-scored task were encouraging, with accuracies of 90.7%, 84.6%, and 77.7% and kappa coefficients of .822 (95% CI, .788-.855), .784 (95% CI, .744-.823), and .702 (95% CI, .612-.793) for vascular pattern, erosions and ulcers, and bleeding, respectively. The AI scoring system predicted each bowel segment's score and displayed distribution of inflammatory activity in the entire large intestine using a 2-dimensional colorized image. CONCLUSIONS: We established a novel deep learning-based scoring system to evaluate endoscopic images from patients with UC, which can also accurately describe the severity and distribution of inflammatory activity through full-length intestinal endoscopic videos.

Comparison of the efficacy and safety of an oral sulfate solution and 3-L polyethylene glycol on bowel preparation before colonoscopy: a phase III multicenter randomized controlled trial.

BACKGROUND AND AIMS: Adequate bowel preparation is crucial for clear mucosal visualization during colonoscopy. We aimed to comprehensively compare oral sulfate solution (OSS) and 3-L split-dose polyethylene glycol (PEG) for bowel preparation before colonoscopy. METHODS: This randomized, active-controlled, noninferiority study was performed in 10 medical centers. Eligible subjects were enrolled to receive OSS or 3-L PEG in a split-dose regimen. The quality of bowel preparation, adverse reactions, and acceptability were evaluated. The quality of bowel preparation was evaluated using the Boston Bowel Preparation Scale. Safety was evaluated by adverse reactions. The study population was divided into the full analysis set (FAS), the safety set, the modified FAS (mFAS), and the per-protocol set (PPS). RESULTS: Three hundred forty-eight potentially eligible subjects were enrolled. Three hundred forty-four subjects were included in the FAS and safety set, 340 subjects were included in the mFAS, and 328 subjects were included in the PPS. Adequate bowel preparation of the OSS was not inferior to 3-L PEG in the mFAS (98.22% vs 97.66%) and the PPS (98.17% vs 98.78%). There was no significant difference in acceptability between the 2 groups (94.74% vs 94.80%, P = .9798). Overall adverse reactions were similar (50.88% vs 44.51%, P = .2370) between the 2 groups. CONCLUSIONS: The split-dose OSS regimen was not inferior to the split-dose 3-L PEG regimen for the quality of bowel preparation in a Chinese adult population. The safety and acceptability of the 2 groups were similar. (Clinical trial registration number: NCT05465889.).

CD4+ T-Cell Subsets in Aplastic Anemia, Myelodysplastic Syndrome, and Acute Myelogenous Leukemia Patients: a Comparative Analysis.

BACKGROUND: Systematic and comparative studies on CD4+ T-lymphocytes in aplastic anemia (AA), myelodysplastic syndrome (MDS), and acute myelogenous leukemia (AML) are scarce. This study aimed to investigate the importance of CD4+ T-cells in bone marrow (BM) failure. METHODS: The proportions of Th1, Th2, Th17, and Treg cells in peripheral blood mononuclear cells (PBMCs) were examined by flow cytometry (FCM). The mRNA expression levels of transcription factors were measured using real-time PCR. RESULTS: The proportions of Th1, Th17 cells, and Th1/Th2 in the AA group were higher, whereas Th2 and Tregs were lower compared to controls. The proportions of Th17 and Treg cells accompanied by RORγt, and Foxp3 expression were significantly higher in the MDS group. The proportions of Th1, Th17, and Th1/Th2 were higher, whereas Th2 cells and GATA3 expression were significantly lower in MDS-multilineage dysplasia group, than in control group. The proportions of Th1, Th17, and Th1/Th2 were lower in MDS-excess blasts, and AML groups, than in controls, whereas that of Th2 and Treg cells accompanied by GATA3, and Foxp3 expression were significantly higher. CONCLUSIONS: Imbalance in CD4+ T-cell subsets may play a critical role in the pathogenesis and BM failure in the investigated diseases.

Nonlinear error reduction for phase-shifting profilometry considering periodicity and symmetry of a phase histogram.

Phase-shifting profilometry is extensively utilized for three-dimensional (3D) measurement. However, because of gamma nonlinearity, the image intensities of the captured fringe patterns are regrettably distorted. An effective nonlinear error reduction method without requiring parameter estimation is presented in this paper. Differing from the traditional whole-period phase histogram equalization (PHE) method, our method takes into account not only the periodicity but also the symmetry of the phase histogram. Taking a three-step phase-shifting algorithm as an example, the phase error frequency triples the fringe frequency; thus, we first propose a 1/3-period PHE method. Moreover, since the phase error distribution is sinusoidal with symmetry, we further propose a 1/6-period PHE method. Simulations and experiments both indicate that the 1/6-period PHE method, compared with the whole-period PHE and 1/3-period PHE methods, can further reduce the nonlinear error.

Microbial Community Heterogeneity Within Colorectal Neoplasia and its Correlation With Colorectal Carcinogenesis.

BACKGROUND & AIMS: Gut microbial dysbiosis has pivotal involvement in colorectal cancer (CRC). However, the intratumoral microbiota and its association with CRC progression remain elusive. We aimed to determine the microbial community architecture within a neoplasia (CRC or adenoma) and its contribution to colorectal carcinogenesis. METHODS: We collected 436 tissue biopsies from patients with CRC (n = 36) or adenoma (n = 32) (2-6 biopsies from a neoplasia plus 2-5 biopsies from adjacent normal tissues per individual). Microbial profiling was performed using 16S ribosomal RNA gene sequencing with subsequent investigation of microbiota diversities and heterogeneity. The correlation between microbial dysbiosis and host genetic alterations (KRAS mutation and microsatellite instability) in all neoplasia biopsies was also analyzed. RESULTS: We discovered that intra-neoplasia microbial communities are heterogeneous. Abundances of some CRC-associated pathobionts (eg, Fusobacterium, Bacteroides, Parvimonas, and Prevotella) were found to be highly varied within a single neoplasia. Correlation of such heterogeneity with CRC development revealed alterations in microbial communities involving microbes with high intra-neoplasia variation in abundance. Moreover, we found that the intra-neoplasia variation in abundance of individual microbes changed along the adenoma-carcinoma sequence. We further determined that there was a significant difference in intra-neoplasia microbiota between biopsies with and without KRAS mutation (P < .001) or microsatellite instability (P < .001), and illustrated the association of intratumoral microbial heterogeneity with genetic alteration. CONCLUSIONS: We demonstrated that intra-neoplasia microbiota is heterogeneous and correlated with colorectal carcinogenesis. Our findings provide new insights on the contribution of gut microbiota heterogeneity to CRC progression.

A Novel Convolutional Neural Network Model as an Alternative Approach to Bowel Preparation Evaluation Before Colonoscopy in the COVID-19 Era: A Multicenter, Single-Blinded, Randomized Study.

INTRODUCTION: Adequate bowel preparation is key to a successful colonoscopy, which is necessary for detecting adenomas and preventing colorectal cancer. We developed an artificial intelligence (AI) platform using a convolutional neural network (CNN) model (AI-CNN model) to evaluate the quality of bowel preparation before colonoscopy. METHODS: This was a colonoscopist-blinded, randomized study. Enrolled patients were randomized into an experimental group, in which our AI-CNN model was used to evaluate the quality of bowel preparation (AI-CNN group), or a control group, which performed self-evaluation per routine practice (control group). The primary outcome was the consistency (homogeneity) between the results of the 2 methods. The secondary outcomes included the quality of bowel preparation according to the Boston Bowel Preparation Scale (BBPS), polyp detection rate, and adenoma detection rate. RESULTS: A total of 1,434 patients were enrolled (AI-CNN, n = 730; control, n = 704). No significant difference was observed between the evaluation results ("pass" or "not pass") of the groups in the adequacy of bowel preparation as represented by BBPS scores. The mean BBPS scores, polyp detection rate, and adenoma detection rate were similar between the groups. These results indicated that the AI-CNN model and routine practice were generally consistent in the evaluation of bowel preparation quality. However, the mean BBPS score of patients with "pass" results were significantly higher in the AI-CNN group than in the control group, indicating that the AI-CNN model may further improve the quality of bowel preparation in patients exhibiting adequate bowel preparation. DISCUSSION: The novel AI-CNN model, which demonstrated comparable outcomes to the routine practice, may serve as an alternative approach for evaluating bowel preparation quality before colonoscopy.

In-suitgrowth of Cu4SnS4nanoplates on reduced graphene oxide (rGO) with ligand exchange exhibiting enhanced photodegradation property.

In the present study, a novel Cu4SnS4/reduced graphene oxide (CTS/rGO) composite was successfully prepared using a simple one-pot heat-up method. Post-synthetic ligand exchange (LE) and annealing process were performed to further increase the dispersibility and the conductivity of the prepared composite. An unexpected phase transformation from CTS to Cu3SnS4with an enhanced absorption in the near-infrared (NIR) region were observed after LE. Furthermore, the photodegradation of Rhodamine B (RhB) by the CTS/rGO composite was investigated. The CTS nanoplates with 10 wt% rGO treated through LE (CTS-10%rGO-LE) exhibited the highest (99.92%) degradation rate of RhB after 90 min of visible-light irradiation, which is approximately 10 and 1.28 times that of the pure CTS and the CTS-10%rGO treated using annealing (CTS-10%rGO-A). The enhancement of the photodegradation activity could be ascribed to the in-suit growth of CTS on rGO and the subsequent LE treatment, which effectively reduced the agglomeration of CTS and increased the electron-transfer ability of the composite materials. The CTS/rGO composite also exhibited high chemical stability of the photodegradation of RhB after four recycles. The electron paramagnetic resonance spectra reveal that ·OH and h+are the main active species in the photocatalytic degradation of RhB with CTS-LE and CTS-10%rGO-LE photocatalysts. The in-suit growth of the CTS/rGO composite with a subsequent LE treatment has the potential to serve as an efficient photocatalysts for the degradation of organic pollutants.

Database of word-level statistics for Mandarin Chinese (DoWLS-MAN).

In this article we present the Database of Word-Level Statistics for Mandarin Chinese (DoWLS-MAN). The database addresses the lack of agreement in phonological syllable segmentation specific to Mandarin by offering phonological features for each lexical item according to 16 schematic representations of the syllable (8 with tone and 8 without tone). Those lexical statistics that differ per phonological word and nonword due to changes in syllable segmentation are of the variant category and include subtitle lexical frequency, phonological neighborhood density measures, homophone density, and network science measures. The invariant characteristics consist of each items' lexical tone, phonological transcription, and syllable structure among others. The goal of DoWLS-MAN is to provide researchers both the ability to choose stimuli that are derived from a segmentation schema that supports an existing model of Mandarin speech processing, and the ability to choose stimuli that allow for the testing of hypotheses on phonological segmentation according to multiple schemas. In an exploratory analysis we illustrate how multiple schematic representations of the phonological mental lexicon can aid in hypothesis generation, specifically in terms of phonological processing when reading Chinese orthography. Users of the database can search among over 92,000 words, over 1600 out-of-vocabulary Chinese characters, and 4300 phonological nonwords according to either Chinese orthography, pinyin, or ASCII phonetic script. Users can also generate a list of phonological words and nonwords according to user-defined ranges and categories of lexical characteristics. DoWLS-MAN is available to the public for search or download at https://dowls.site .

[Value of Blood Urea Nitrogen-to-Creatinine Ratio for Differentiating the Site of Gastrointestinal Bleeding and Assessing the Prognosis of Patients with Acute Nonvariceal Upper Gastrointestinal Bleeding].

Objective: To explore the diagnostic performance of blood urea nitrogen-to-creatinine (BUN/Cr) ratio in differentiating the site of gastrointestinal bleeding, and to assess the predictive value of early elevated BUN/Cr ratio for clinical outcomes in patients with acute nonvariceal upper gastrointestinal bleeding (ANVUGIB). Methods: The adult patients diagnosed with gastrointestinal bleeding who were hospitalized in the Department of Gastroenterology, Zhongshan Hospital, Xiamen University between May 2020 and May 2021 were retrospectively enrolled. According to the site of gastrointestinal bleeding, the patients were divided into the upper gastrointestinal tract group, the proximal small intestinal bleeding group, and the distal small intestinal and colonic bleeding group. According to the early dynamic changes of BUN/Cr ratio within 6-48 hours after admission, patients with ANVUGIB were divided into early dynamic elevated BUN/Cr ratio group and non-early dynamic elevated BUN/Cr ratio group. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of BUN/Cr ratio in differentiating the site of gastrointestinal bleeding and examine the predictive efficacy of early dynamic elevated BUN/Cr ratio after admission, Rockall scoring system, and the combined indicator of the two for estimating the primary clinical outcomes in ANVUGIB patients. Results: A total of 266 patients were enrolled. Among them, 204 cases were in the upper gastrointestinal bleeding group, 15 cases were in the proximal small intestinal bleeding group, and 47 cases were in the distal small intestinal and colonic bleeding group. In the ANVUGIB patients, 16 were in the group with early dynamic elevated BUN/Cr ratio after admission, and 146 were in the group with non-early dynamic elevated BUN/Cr ratio after admission. The area under the ROC curve of the BUN/Cr ratio was 0.831 (95% CI: 0.780-0.874), the optimal cut-off value being 34.59 mg/g for differentiation between upper and lower gastrointestinal bleeding. The area under the ROC curve of the BUN/Cr ratio was 0.901 (95% CI: 0.798-0.963) and the optimal cut-off value was 19.27 mg/g for differentiation between proximal small intestinal bleeding and the distal small intestinal and colonic bleeding. The area under the ROC curve of the early dynamic elevated BUN/Cr ratio after admission was 0.806 (95% CI: 0.737-0.864) for predicting the primary clinical outcome in patients with ANVUGIB. The area under the ROC curve of the combined indicator included the early dynamic elevated BUN/Cr ratio after admission and the Rockall scoring system was 0.909 (95% CI: 0.854-0.949) for predicting the primary clinical outcome in patients with ANVUGIB. Conclusion: The BUN/Cr ratio shows rather reliable diagnostic performance for identifying the site of gastrointestinal bleeding, and the early dynamic elevated BUN/Cr ratio after admission is a reliable indicator for predicting clinical outcomes in patients with ANVUGIB.

Serum pepsinogen levels in different regions of China and its influencing factors: a multicenter cross-sectional study.

BACKGROUND: The aim of this study is to investigate the difference of serum pepsinogen (PG) baseline levels in different regions of China and its influencing factors. METHODS: From October 2016 to October 2018, asymptomatic health checkup people who underwent nasal endoscopy in nine health management centers in different regions of China were collected. Lifestyle questionnaires were conducted, and serum PG and gastroscopy were performed. The differences in PG levels in baseline population (OLGA-0 grade) were studied according to geographical subregions of China. SPSS software was used for statistical analysis. RESULTS: 1922 patients were included in the final analysis. Compared with the non-atrophy (OLGA-0) group, PGR levels in atrophy group (OLGA-I to IV) were significantly decreased with the atrophy degree (p < 0.05). A total of 1590 baseline people (OLGA-0) were included in the study, including 254 from South China, 574 from East China, 210 from Southwest China, 332 from Northeast China, and 220 from Central/Northern China. There were significant differences in baseline PGI levels among the five regions (p < 0.05). The PGII levels were also different among the five regions, except for Central/Northern versus Southern China. PGR (PGI/PGII ratio) levels in Southern China were higher than other four regions. Further studies were conducted on the related factors that might affect the baseline PG level, which was affected by nationality, dietary habits, smoking, Helicobacter pylori infection and other related factors. CONCLUSION: Influenced by many factors, the baseline PG levels are different in different regions of China. In the follow-up studies of PG cut-off value, different PG cut-off value based on region may be more effective in the screening of gastric cancer and precancerous lesions in China.

Monocyte to high-density lipoprotein cholesterol ratio as an independent risk factor for papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is considered to be an inflammatory disease. This study aimed to investigate the association of monocyte to high-density lipoprotein cholesterol ratio (MHR) with PTC. METHODS: Clinical parameters from 300 patients with PTC and 552 patients with benign thyroid nodule were compared. Serum renal function and liver enzymes, fasting plasma glucose, lipid profile, and blood cell count were measured. RESULTS: Patients with PTC had a higher MONO (p < 0.001) and MHR (p < 0.001). There was a step-wise increase in the prevalence of PTC (p = 0.003) with the tertile of MHR. Logistic regression analysis revealed that MHR could be considered an independent risk factor (p < 0.001) in the case-control study and the cohort study. Pearson correlation analysis and simple linear regression analysis indicated that MHR was positively associated with neutrophil (NEU) and lymphocyte (LYM) count as well as neutrophil-to-lymphocyte ratio (NLR). Area under the curve (AUC) was 0.711. The optimal cutoff of MHR was 0.33 × 109 /mmol. CONCLUSION: This study identifies novel evidence that patients with PTC have a higher MHR. MHR is an independent risk factor for PTC. These findings support the application of MHR to predict, diagnose, and evaluate the occurrence of PTC.

Cyberknife radiosurgery on the brainstem metastases of non-small cell lung cancer.

OBJECTIVE: Management of brainstem metastatic tumor is challenging. This study aimed to evaluate overall survival and quality-of-life in patients with non-small cell lung cancer (NSCLC) brainstem metastases who were treated with the Cyberknife stereotactic radiosurgery. METHODS: From August 2007 through August 2016, a total of 32 patients with 34 brainstem metastases of NSCLC were consecutively enrolled and treated with the Cyberknife radiosurgery (CKRS) at The Huashan Hospital. The study was limited to patients with NSCLC, which was confirmed by postoperative pathological examination. Patients were treated by CKRS as an initial treatment or a second treatment after whole-brain radiation therapy (WBRT). Quality of life was assessed by the SF-12 score and neurological examination. RESULTS: Four out of the 32 (12.5%) patients received WBRT before or concurrent with CKRS treatment. The mean survival time after CKRS was 10.0 (95%CI: 6.0-14.0) months. Karnofsky performance score was not the independent predictor of survival after radiosurgery as analyzed by log-rank test (p = 0.392). Age, however, was a significant predictor of improved survival as analyzed by multivariate analysis (p = 0.024). SF-12 physical component scores demonstrated no significant change after treatment. CONCLUSIONS: The CKSR is a non-invasive, safe, and effective modality in the treatment of patients with brainstem metastases of NSCLC. Better therapeutic outcomes of CKSR for brainstem metastasis might be achieved in the patients older than 65 years old.

Expression of deubiquitinases in human gingiva and cultured human gingival fibroblasts.

BACKGROUND: Although deubiquitinating enzymes (DUBs) such as CYLD, A20 and OTULIN are expressed in multiple tissues and thought to be linked with inflammatory diseases, their expression in periodontal tissues remains to be determined. This research was designed to assess the expression of CYLD, A20 and OTULIN in human gingiva, and to evaluate the regulation of these DUBs in human gingival fibroblasts (HGFs) upon different stimuli. METHODS: Immunohistochemistry assay was conducted to determine the expression of CYLD, A20 and OTULIN in human gingiva. Immunofluorescence assay was employed to observe the protein expression of CYLD, A20 and OTULIN in HGFs. RT-PCR and western blots were carried out to assess gene and protein expression changes of these DUBs in HGFs upon LPS or TNF-α. RESULTS: CYLD, A20 and OTULIN were found to be expressed in human gingiva and HGFs. The expression of CYLD, A20 and OTULIN was lower in the inflamed gingival tissue samples compared with the healthy gingival tissue samples. Further, the expression of CYLD, A20 and OTULIN in HGFs exhibited distinct regulation by different stimuli. TNF-α treatment markedly increased NF-κB activation in HGFs CONCLUSIONS: Our findings suggest that CYLD, A20 and OTULIN might play a role in the progression of periodontitis.