RETRACTED: Liu et al. Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer. Nutrients 2016, 8, 360.

The journal retracts the article, "Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer" [...].

Prospective, multicenter, self-controlled clinical trial on the effectiveness and safety of a cable-transmission magnetically controlled capsule endoscopy system for the examination of upper GI diseases.

BACKGROUND AND AIMS: Many GI disorders and precancerous conditions often present asymptomatically, leading to delayed patient diagnoses and treatment interventions. In this study, we developed a novel cable-transmission magnetically controlled capsule endoscopy (CT-MCCE) system for detecting GI diseases and assessed its safety and feasibility through clinical trials. METHODS: This prospective, multicenter trial compared CT-MCCE with conventional gastroscopy in patients aged 18 to 75 years with upper GI tract diseases between October 2022 and July 2023. The primary endpoints were the evaluation of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in the detection of focal lesions within the esophagus, stomach, and duodenal bulb using CT-MCCE. RESULTS: One hundred eighty individuals (mean age, 43.1 years; 52.22% women) were recruited from 3 hospitals in China. CT-MCCE detected lesions in the esophagus with a sensitivity of 97.22%, specificity of 100%, PPV of 100%, NPV of 98.18%, and accuracy of 98.89%; detected gastric focal lesions in the entire stomach with a sensitivity of 96.81%, specificity of 98.84%, PPV of 98.91%, NPV of 96.59%, and accuracy of 97.78%; and detected lesions in the duodenal bulb with a sensitivity of 100%, specificity of 100%, PPV of 100%, NPV of 100%, and accuracy of 100%. There were no significant differences between CT-MCCE and EGD regarding the cleanliness of the upper GI tract and visibility of the upper GI mucosa. However, CT-MCCE was associated with a lower incidence of discomfort than EGD (P < .001). CONCLUSIONS: The diagnostic performance of CT-MCCE is comparable with that of EGD in the completion of upper GI tract examinations and lesion detection. Furthermore, the improved tolerance of CT-MCCE in detecting upper GI diseases was noted without any observed adverse events. (Clinical trial registration number: ChiCTR2200063630.).

Quantum Interference and Coherent Population Trapping in a Double Quantum Dot.

Quantum interference is a natural consequence of wave-particle duality in quantum mechanics, and is widely observed at the atomic scale. One interesting manifestation of quantum interference is coherent population trapping (CPT), first proposed in three-level driven atomic systems and observed in quantum optical experiments. Here, we demonstrate CPT in a gate-defined semiconductor double quantum dot (DQD), with some unique twists as compared to the atomic systems. Specifically, we observe CPT in both driven and nondriven situations. We further show that CPT in a driven DQD could be used to generate adiabatic state transfer. Moreover, our experiment reveals a nontrivial modulation to the CPT caused by the longitudinal driving field, yielding an odd-even effect and a tunable CPT. Our results broaden the field of CPT, and open up the possibility of quantum simulation and quantum computation based on adiabatic passage in quantum dot systems.

A new species of Cincticostella Allen, 1971 (Ephemeroptera, Ephemerellidae) from Yunnan, China and establishment of a new species complex.

Cincticostellajianchuan sp. nov. from Dali Bai Autonomous Prefecture, Yunnan Province, China, is described based on chorionic structure, nymph, and winged stages. The new species is closely related to C.fusca (Kang & Yang, 1995), but it can be distinguished in the male imago stage by its mesonotum and penes morphology, coloration, and the forking point of the stem of MA+Rs on the forewing; in the nymph stage, it can be distinguished by the length of the posterolateral projections of abdominal segment IX and the setation of the abdominal terga. Compared to other congeners, nymphs and male imagoes of the new species and C.fusca share several morphological characteristics, such as a larger body, mesothorax with medially notched anterolateral projections, forefemur without a subapical band of transverse spines of the nymphs, the area between C, Sc and R1 of the forewings distinctly pigmented, and an apical sclerite on the ventral face of the penes of the male imagoes, supporting the proposition of a new species complex, the jianchuan complex. The systematics of Cincticostella and related genera are discussed briefly.

Plasma metabolomics and lipidomics reveal potential novel biomarkers in early gastric cancer: An explorative study.

BACKGROUND: Early identification and therapy can significantly improve the outcome for gastric cancer. However, there is still no perfect biomarker available for the detection of early gastric cancer. This study aimed to investigate the alterations in the plasma metabolites of early gastric cancer using metabolomics and lipidomics based on high-performance liquid chromatography-mass spectrometry (HPLC-MS), which detected potential biomarkers that could be used for clinical diagnosis. METHODS: To investigate the changes in metabolomics and lipidomics, a total of 30 plasma samples were collected, consisting of 15 patients with early gastric cancer and 15 healthy controls. Extensive HPLC-MS-based untargeted metabolomic and lipidomic investigations were conducted. Differential metabolites and metabolic pathways were uncovered through the utilization of statistical analysis and bioinformatics analysis. Candidate biomarker screening was performed using support vector machine-based multivariate receiver operating characteristic analysis. RESULTS: A disturbance was observed in a combined total of 19 metabolites and 67 lipids of the early gastric cancer patients. The analysis of KEGG pathways showed that the early gastric cancer patients experienced disruptions in the arginine biosynthesis pathway, the pathway for alanine, aspartate, and glutamate metabolism, as well as the pathway for glyoxylate and dicarboxylate metabolism. Plasma metabolomics and lipidomics have identified multiple biomarker panels that can effectively differentiate early gastric cancer patients from healthy controls, exhibiting an area under the curve exceeding 0.9. CONCLUSION: These metabolites and lipids could potentially serve as biomarkers for the screening of early gastric cancer, thereby optimizing the strategy for the detection of early gastric cancer. The disrupted pathways implicated in early gastric cancer provide new clues for additional understanding of gastric cancer's pathogenesis. Nonetheless, large-scale clinical data are required to prove our findings.

Proteomics Study of Benzene Metabolite Hydroquinone Induced Hematotoxicity in K562 Cells.

Objective: Hydroquinone (HQ), one of the phenolic metabolites of benzene, is widely recognized as an important participant in benzene-induced hematotoxicity. However, there are few relevant proteomics in HQ-induced hematotoxicity and the mechanism hasn't been fully understood yet. Methods: In this study, we treated K562 cells with 40 µmol/L HQ for 72 h, examined and validated protein expression changes by Label-free proteomic analysis and Parallel reaction monitoring (PRM), and performed bioinformatics analysis to identify interaction networks. Results: One hundred and eighty-seven upregulated differentially expressed proteins (DEPs) and 279 downregulated DEPs were identified in HQ-exposed K562 cells, which were involved in neutrophil-mediated immunity, blood microparticle, and other GO terms, as well as the lysosome, metabolic, cell cycle, and cellular senescence-related pathways. Focusing on the 23 DEGs and 5 DEPs in erythroid differentiation-related pathways, we constructed the network of protein interactions and determined 6 DEPs (STAT1, STAT3, CASP3, KIT, STAT5B, and VEGFA) as main hub proteins with the most interactions, among which STATs made a central impact and may be potential biomarkers of HQ-induced hematotoxicity. Conclusion: Our work reinforced the use of proteomics and bioinformatic approaches to advance knowledge on molecular mechanisms of HQ-induced hematotoxicity at the protein level and provide a valuable basis for further clarification.

A Rapid On-Line Evaluation (ROLE) Protocol in the Diagnostic Performance Improvement in Endoscopic Ultrasound-Guided Tissue Acquisition for Solid Pancreatic Lesions.

We assessed the rapid on-line evaluation (ROLE) protocol as a modification to the conventional rapid on-site evaluation (ROSE) in the diagnostic performance improvement in endoscopic ultrasound-guided tissue acquisition (EUS-TA) for solid pancreatic lesions. This single-center, retrospective study involved consecutive patients with solid pancreatic lesions undergoing EUS-TA at Peking University First Hospital between October 2017 and March 2021. Among 137 patients enrolled, 75 were in the ROLE group and 62 were in the non-ROSE group. The diagnostic yield (97.3% vs. 85.5%, p = 0.023), accuracy (94.7% vs. 82.3%, p = 0.027), and sensitivity (95.7% vs. 81.1%, p = 0.011) were significantly higher in the ROLE group compared to the non-ROSE group. However, specificity, positive predictive value, negative predictive value, and area under the curve (AUC) showed no significant differences (all p-values > 0.05). Additionally, there was a noteworthy reduction in the number of needle passes required in the ROLE group compared to the non-ROSE group (two vs. three, p < 0.001). In a subgroup analysis, fine needle biopsy (FNB) combined with ROLE demonstrated superior diagnostic accuracy compared to FNB with non-ROSE (100% vs. 93.1%, p = 0.025). Compared with the non-ROSE protocol, the ROLE protocol might improve the diagnostic performance of EUS-TA for solid pancreatic lesions, and potentially reduce the number of needle passes requirement.

Exploration of the Catalytic Cycle Dynamics of Vigna Radiata H+-Translocating Pyrophosphatases Through Hydrogen-Deuterium Exchange Mass Spectrometry.

Vigna radiata H+-translocating pyrophosphatases (VrH+-PPases, EC 3.6.1.1) are present in various endomembranes of plants, bacteria, archaea, and certain protozoa. They transport H+ into the lumen by hydrolyzing pyrophosphate, which is a by-product of many essential anabolic reactions. Although the crystal structure of H+-PPases has been elucidated, the H+ translocation mechanism of H+-PPases in the solution state remains unclear. In this study, we used hydrogen-deuterium exchange (HDX) coupled with mass spectrometry (MS) to investigate the dynamics of H+-PPases between the previously proposed R state (resting state, Apo form), I state (intermediate state, bound to a substrate analog), and T state (transient state, bound to inorganic phosphate). When hydrogen was replaced by proteins in deuterium oxide solution, the backbone hydrogen atoms, which were exchanged with deuterium, were identified through MS. Accordingly, we used deuterium uptake to examine the structural dynamics and conformational changes of H+-PPases in solution. In the highly conserved substrate binding and proton exit regions, HDX-MS revealed the existence of a compact conformation with deuterium exchange when H+-PPases were bound with a substrate analog and product. Thus, a novel working model was developed to elucidate the in situ catalytic mechanism of pyrophosphate hydrolysis and proton transport. In this model, a proton is released in the I state, and the TM5 inner wall serves as a proton piston.

The role of GATA switch in benzene metabolite hydroquinone inhibiting erythroid differentiation in K562 cells.

The phenolic metabolite of benzene, hydroquinone (HQ), has potential risks for hematological disorders and hematotoxicity in humans. Previous studies have revealed that reactive oxygen species, DNA methylation, and histone acetylation participate in benzene metabolites inhibiting erythroid differentiation in hemin-induced K562 cells. GATA1 and GATA2 are crucial erythroid-specific transcription factors that exhibit dynamic expression patterns during erythroid differentiation. We investigated the role of GATA factors in HQ-inhibited erythroid differentiation in K562 cells. When K562 cells were induced with 40 µM hemin for 0-120 h, the mRNA and protein levels of GATA1 and GATA2 changed dynamically. After exposure to 40 µM HQ for 72 h, K562 cells were induced with 40 µM hemin for 48 h. HQ considerably reduced the percentage of hemin-induced Hb-positive cells, decreased the GATA1 mRNA, protein, and occupancy levels at α-globin and ß-globin gene clusters, and increased the GATA2 mRNA and protein levels significantly. ChIP-seq analysis revealed that HQ reduced GATA1 occupancy, and increased GATA2 occupancy at most gene loci in hemin-induced K562 cells. And GATA1 and GATA2 might play essential roles in the erythroid differentiation protein interaction network. These results elucidate that HQ decreases GATA1 occupancy and increases GATA2 occupancy at the erythroid gene loci, thereby downregulating GATA1 and upregulating GATA2 expression, which in turn modulates the expression of erythroid genes and inhibits erythroid differentiation. This partially explains the mechanism of benzene hematotoxicity.

Effectiveness of Inner Traction-Facilitated Endoscopic Submucosal Dissection Using Rubber Band and Clips for Colorectal Neoplasms: A Propensity Score-Matched Study.

BACKGROUND: Colorectal endoscopic submucosal dissection is a technically demanding but effective treatment for superficial neoplasms. We conducted a study to compare the effectiveness and safety of inner traction-facilitated endoscopic submucosal dissection using rubber band and clip with conventional endoscopic submucosal dissection. METHODS: We retrospectively evaluated 622 consecutive patients who underwent colorectal endoscopic submucosal dissection between January 2016 and December 2019. To overcome selection bias, we used propensity score matching (1:4) between endoscopic submucosal dissection using rubber band and clip and conventional endoscopic submucosal dissection. The frequency of en bloc resections, R0 resections, curative resections, procedure speed, and complications were evaluated. RESULTS: After propensity score matching, 35 patients were included in the endoscopic submucosal dissection using rubber band and clip group and 140 were included in the conventional endoscopic submucosal dissection group. Endoscopic submucosal dissection using rubber band and clip resulted in a significant increase in resection speed (0.14 vs. 0.09 cm2/min; P = .003). There were no significant differences in en bloc, R0, and curative resection rates between the 2 groups. In subgroup analysis, the resection speed of endoscopic submucosal dissection using rubber band and clip was significantly higher than that of conventional endoscopic submucosal dissection when the lesions were equal to or larger than 2 cm, macroscopically presenting as lateral spreading tumor, and located in transverse colon to ascending colon. CONCLUSIONS: Endoscopic submucosal dissection using rubber band and clip is safe and effective in treating colorectal neoplasms, especially in lesions presenting a particular difficulty.

Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patients.

Background: Numerous studies have shown autophagy affects cellular immune responses. This study aims to explore prognosis and immunotherapeutic biomarkers related to autophagy in colon adenocarcinoma (COAD). Methods: Based on R software, we performed the ssGSEA, differential expression analysis, Kaplan-Meier survival analysis, correlation analysis, and enrichment analysis. For wet experiment, we did qRT-PCR, immunohistochemistry and CCK-8 experiments. Results: Using autophagy-related genes (ARGs) and the ssGSEA, COAD patients were divided into low and high autophagy groups. For immune score, stromal score, tumor purity, tumor infiltrating immune cells, co-signaling molecules, tumor mutational burden, microsatellite instability, mismatch repair, immune-related pathways, immune signatures, somatic mutations and subtype analysis, high autophagy group might benefit more from immunotherapy. Among 232 ARGs, IFNG was generally significantly correlated with tumor immunotherapy biomarkers (PD-L1, CD8A and cytotoxic T lymphocytes (CTL)). The disease-free survival of high IFNG group was significantly longer than that of low group. On above-mentioned immune-related research, the high IFNG group reached the same conclusion. The qRT-PCR and IHC analysis confirmed that IFNG was significantly higher expressed in dMMR samples compared to pMMR samples. For chemotherapy, the autophagy and IFNG were significantly negatively related to the chemosensitivity to cisplatin; IFNG inhibitor glucosamine increased cisplatin chemoresistance while IFNG increased cisplatin chemosensitivity; IFNG could reverse glucosamine induced chemoresistance. The functional enrichment analysis of IFNG, PD-L1, CD8A and 20 similar proteins were related to the activation of the immune system. The GSEA and ceRNA network partly described interaction mechanisms of IFNG with PD-L1 and CD8A. Conclusion: Autophagy score and IFNG expression were novel immunotherapy predictive biomarkers, which might play predictive effects through the JAK-STAT signaling pathway. IFNG might be a potential targeted therapy for cisplatin resistant colon cancer. Besides, IFNG was also a prognostic indicator.

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).

A convolutional neural network-based system for detecting early gastric cancer in white-light endoscopy.

BACKGROUND: White-light endoscopy (WLE) is a main and standard modality for detection of early gastric cancer (EGC). The detection rate of EGC is not satisfactory so far. In this single-center retrospective study we developed a convolutional neural network (CNN)-based system to automatically detect EGC in WLE images. METHODS: An EGC detecting system was constructed based on the CNN architecture EfficientDet. We trained our system with a data set including 4527 images from 130 cases (cancerous images, 1737; noncancerous images, 2790). Then we tested its performance with a data set including 1243 images from 64 cases (cancerous images, 445; noncancerous images, 798). RESULTS: For case-based analysis, our system successfully detected EGC in 63 of 64 cases and the sensitivity was 98.4%. For image-based analysis, the accuracy was 88.3%. The sensitivity, specificity, positive predictive value and negative predictive value were 84.5%, 90.5%, 83.2% and 91.3%, respectively. The most common cause for false positives was gastritis (57.9%). The most common cause for false negatives was that the lesion was too small with a diameter of 10 mm or less (44.9%). CONCLUSION: Our CNN-based EGC detecting system was able to achieve satisfactory sensitivity for detecting EGC in WLE images and shows great potential in assisting endoscopists with the detection of EGC.

Asia-Pacific Colorectal Screening Score Combined With Stool DNA Test Improves the Detection Rate for Colorectal Advanced Neoplasms.

BACKGROUND & AIMS: The Asia-Pacific Colorectal Screening (APCS) scoring system was developed to stratify the risk of colorectal advanced neoplasm (AN). We aimed to evaluate the performance of the APCS score combined with a stool DNA test used for colorectal cancer screening. METHODS: A total of 2842 subjects who visited outpatient clinics or cancer screening centers were enrolled. Age, sex, smoking status, and family history were recorded and APCS scores were calculated in 2439 participants. A stool DNA test (SDC2 and SFRP2 tests) and fecal immunochemical test (FIT) were performed and colonoscopy was used as the gold standard among 2240 subjects who completed all study procedures. We used a threshold of 4.4 µg/g for the FIT, in addition to the manufacturer's recommended threshold of 20 µg/g to match the specificity of a stool DNA test. RESULTS: Based on the APCS score, 38.8% (946 of 2439) of the subjects were categorized as high risk, and they had a 1.8-fold increase in risk for AN (95% CI, 1.4-2.3) compared with low and moderate risk. The APCS combined with the stool DNA test detected 95.2% of invasive cancers (40 of 42) and 73.5% of ANs (253 of 344), while the colonoscopy workload was only 47.1% (1056 of 2240). The sensitivity for AN of APCS combined with stool DNA test was significantly higher than that of APCS combined with FIT (73.5% vs 62.8% with FIT cut-off value of 20 µg/g, and 73.5% vs 68.0% with FIT cut-off value of 4.4 µg/g; both P < .01). CONCLUSIONS: The APCS score combined with a stool DNA test significantly improved the detection of colorectal ANs, while limiting colonoscopy resource utilization (Chictr.org.cn, ChiCTR-DDD-17011169).

Anti-Thymocyte Globulin (ATG)-Free Nonmyeloablative Haploidentical PBSCT Plus Post-Transplantation Cyclophosphamide Is a Safe and Efficient Treatment Approach for Pediatric Acquired Aplastic Anemia.

Most cases of acquired aplastic anemia (AA) arise from autoimmune destruction of hematopoietic stem and progenitor cells. Human leukocyte antigen (HLA)-haploidentical nonmyeloablative hematopoietic stem cell transplantation (HSCT) plus post-transplantation cyclophosphamide (PTCy) is increasingly applied to salvage AA using bone marrow as graft and anti-thymocyte globulin (ATG) in conditioning. Herein, we characterize a cohort of twelve AA patients clinically and molecularly, six who possessed other immunological disorders (including two also carrying germline SAMD9L mutations). Each patient with SAMD9L mutation also carried an AA-related rare BCORL1 variant or CTLA4 p.T17A GG genotype, respectively, and both presented short telomere lengths. Six of the ten patients analyzed harbored AA-risky HLA polymorphisms. All patients recovered upon non-HSCT (n = 4) or HSCT (n = 8) treatments. Six of the eight HSCT-treated patients were subjected to a modified PTCy-based regimen involving freshly prepared peripheral blood stem cells (PBSC) as graft and exclusion of ATG. All patients were engrafted between post-transplantation days +13 and +18 and quickly reverted to normal life, displaying a sustained complete hematologic response and an absence of graft-versus-host disease. These outcomes indicate most AA cases, including of the SAMD9L-inherited subtype, are immune-mediated and the modified PTCy-based regimen we present is efficient and safe for salvage.

Surgical treatment confers prognostic significance in pediatric malignant mediastinal germ cell tumors.

BACKGROUND: Primary malignant mediastinal germ cell tumors (GCTs) are rare pediatric tumors that have a poorer prognosis compared to GCTs occurring elsewhere in the body. The current study aimed to assess the prognostic factors and treatment outcomes of children with primary malignant mediastinal GCT in Taiwan. METHODS: The authors retrospectively reviewed children 0-18 years old who were newly diagnosed with primary malignant mediastinal GCT between January 1, 2005 and December 31, 2019 and were registered in the Taiwan Pediatric Oncology Group patient registry. The impact of presenting characteristics, including sex, age, tumor stage, histology subtype, surgical treatment, and chemotherapy regimens of the patients were analyzed. RESULTS: This study enrolled 52 children with malignant mediastinal GCT who had a median age of 16.0 (range, 6.0-17.9) years at diagnosis. The most common histological subtypes were mixed GCTs (n = 20) and yolk sac tumors (n = 15). Advanced disease stage and choriocarcinoma histology subtype were associated inferior outcomes. Children who received surgical treatment exhibited better outcomes compared to those who did not (5-year overall survival, 78% vs. 7%, p < .001). After comparing patients who received first-line cisplatin- and carboplatin-based chemotherapy, no difference in treatment outcomes was observed. Multivariate analysis showed that surgical management was the only independent predictor for superior OS. CONCLUSIONS: Surgical treatment is recommended for mediastinal GCT. Cisplatin-based chemotherapy was not superior to carboplatin-based chemotherapy as first-line treatment and may be avoided due to toxicity concerns.