Artificial intelligence-assisted system for the assessment of Forrest classification of peptic ulcer bleeding: a multicenter diagnostic study.

BACKGROUND: Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB). METHODS: A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists. RESULTS: The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%-92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%-97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists. CONCLUSION: The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy.

Antennal transcriptome analysis of Psyttalia incisi (silvestri) (Hymenoptera: Braconidae): identification and tissue expression profiling of candidate odorant-binding protein genes.

BACKGROUND: Olfaction plays an important role in host-seeking by parasitoids, as they can sense chemical signals using sensitive chemosensory systems. Psyttalia incisi (Silvestri) (Hymenoptera: Braconidae) is the dominant parasitoid of Bactrocera dorsalis (Hendel) in fruit-producing regions of southern China. The olfactory behavior of P. incisi has been extensively studied; however, the chemosensory mechanisms of this species are not fully understood. RESULTS: Bioinformatics analysis of 64,515 unigenes from the antennal transcriptome of both male and female adults P. incisi identified 87 candidate chemosensory genes. These included 13 odorant-binding proteins (OBPs), seven gustatory receptors (GRs), 55 odorant receptors (ORs), 10 ionotropic receptors (IRs), and two sensory neuron membrane proteins (SNMPs). Phylogenetic trees were constructed to predict evolutionary relationships between these chemosensory genes in hymenopterans. Moreover, the tissue expression profiles of 13 OBPs were analyzed by quantitative real-time PCR, revealing high expression of seven OBPs (1, 3, 6, 7, 8, 12, and 13) in the antennae. CONCLUSION: This study represents the first identification of chemosensory genes and the determination of their expression patterns in different tissues of P. incisi. These results contribute to a better understanding of the function of the chemosensory system of this parasitoid species.

Effect of multidisciplinary cooperative continuous nursing and psychological nursing on multiple myeloma with a peripherally inserted central catheter.

Objective: This study was conducted to analyze the effectiveness of multidisciplinary cooperative continuous nursing combined with psychological nursing intervention in multiple myeloma (MM) patients undergoing peripherally inserted central catheter (PICC). Methods: The Numerical Pain Rating Scale (NPRS), Anxiety Self-Assessment Scale (SAS), Depression Self-Assessment Scale (SDS) and Revised Piper Fatigue Scale (PFS-R), Self-Care Ability Scale (ESCA), Quality of Life Core Questionnaire (QLQ-C30), incidence of unplanned extubation of PICC, total incidence of catheter-related complications and satisfaction with nursing were compared between the two groups of patients in a prospective study. Results: Patients in the observation group had reduced NPRS, SAS, SDS and PFS-R scores, total incidence of unplanned extubation of PICC and the total incidence of catheter-related complications, and a higher nursing satisfaction rate in comparison to those in the control group. Conclusion: Multidisciplinary cooperative continuous nursing combined with psychological nursing interventions can relieve pain in MM patients.

Tunable extraordinary optical transmission spectrum properties of long-wavelength infrared metamaterials.

Metamaterial filters represent an essential method for researching the miniaturization of infrared spectral detectors. To realize an 8-2 µm long-wave infrared tunable transmission spectral structure, an extraordinary optical transmission metamaterial model was designed based on the grating diffraction effect and surface plasmon polariton resonance theory. The model consisted of an Al grating array in the upper layer and a Ge substrate in the lower layer. We numerically simulated the effects of different structural parameters on the transmission spectra, such as grating height (h), grating width (w), grating distance (d), grating constant (p), and grating length (S 1), by utilizing the finite-difference time-domain method. Finally, we obtained the maximum transmittance of 81.52% in the 8-12 µm band range, with the corresponding structural parameters set to h=50n m, w=300n m, d=300n m, and S 1=48µm, respectively. After Lorentz fitting, a full width at half maximum of 0.94±0.01µm was achieved. In addition, the Ge substrate influence was taken into account for analyzing the model's extraordinary optical transmission performance. In particular, we first realized the continuous tuning performance at the transmission center wavelength (8-12 µm) of long-wave infrared within the substrate tuning thickness (D) range of 1.9-2.9 µm. The structure designed in this paper features tunability, broad spectral bandwidth, and miniaturization, which will provide a reference for the development of miniaturized long-wave infrared spectral filter devices.

The male germline-specific protein MAPS is indispensable for pachynema progression and fertility.

Meiosis is a specialized cell division that creates haploid germ cells from diploid progenitors. Through differential RNA expression analyses, we previously identified a number of mouse genes that were dramatically elevated in spermatocytes, relative to their very low expression in spermatogonia and somatic organs. Here, we investigated in detail 1700102P08Rik, one of these genes, and independently conclude that it encodes a male germline-specific protein, in agreement with a recent report. We demonstrated that it is essential for pachynema progression in spermatocytes and named it male pachynema-specific (MAPS) protein. Mice lacking Maps (Maps-/- ) suffered from pachytene arrest and spermatocyte death, leading to male infertility, whereas female fertility was not affected. Interestingly, pubertal Maps-/- spermatocytes were arrested at early pachytene stage, accompanied by defects in DNA double-strand break (DSB) repair, crossover formation, and XY body formation. In contrast, adult Maps-/- spermatocytes only exhibited partially defective crossover but nonetheless were delayed or failed in progression from early to mid- and late pachytene stage, resulting in cell death. Furthermore, we report a significant transcriptional dysregulation in autosomes and XY chromosomes in both pubertal and adult Maps-/- pachytene spermatocytes, including failed meiotic sex chromosome inactivation (MSCI). Further experiments revealed that MAPS overexpression in vitro dramatically decreased the ubiquitination levels of cellular proteins. Conversely, in Maps-/- pachytene cells, protein ubiquitination was dramatically increased, likely contributing to the large-scale disruption in gene expression in pachytene cells. Thus, MAPS is a protein essential for pachynema progression in male mice, possibly in mammals in general.

Bi2WO6/TiO2-based visible light-driven photoelectrochemical enzyme biosensor for glucose measurement.

Nowadays, the frequent occurrence of food adulteration makes glucose detection particularly important in food safety and quality management. The quality and taste of honey are closely related to the glucose content. However, due to the drawbacks of expensive equipment, complex operating procedures, and time-consuming processes, the application scope of traditional glucose detection methods is limited. Hence, this study developed a photoelectric chemical (PEC) sensor, which is composed of a photoactive material of bismuth tungstate (Bi2WO6) with titanium dioxide (TiO2) and glucose oxidase (GOD), for simple and rapid detection of glucose. Notably, the composites' absorption prominently increased in the visible light region, and the photo-generated electron-hole pairs were efficiently separated by virtue of the unique nanostructure system, thus playing a crucial role in facilitating PEC activity. In the presence of dissolved oxygen, the photocurrent intensity was enhanced by H2O2 generated from glucose under electro-oxidation specifically catalyzed by GOD fixed on the modified electrode. When the working potential was 0.3 V, the changes of photocurrent response indicated that the PEC enzyme biosensor provides a low detection limit (3.8 µM), and a wide linear range (0.008-8 mM). This method has better selectivity in honey samples and broad application prospects in clinical diagnosis for future.

Leveraging the ATP-P2X7 receptor signalling axis to alleviate traumatic CNS damage and related complications.

The P2X7 receptor is an exceptional member of the P2X purinergic receptor family, with its activation requiring high concentrations of extracellular adenosine 5'-triphosphate (ATP) that are often associated with tissue damage and inflammation. In the central nervous system (CNS), it is highly expressed in glial cells, particularly in microglia. In this review, we discuss the role and mechanisms of the P2X7 receptor in mediating neuroinflammation and other pathogenic events in a variety of traumatic CNS damage conditions, which lead to loss of neurological and cognitive functions. We raise the perspective on the steady progress in developing CNS-penetrant P2X7 receptor-specific antagonists that leverage the ATP-P2X7 receptor signaling axis as a potential therapeutic strategy to alleviate traumatic CNS damage and related complications.

Light-Controlled Particle Enrichment Patterns in Droplets.

Precision manipulation of particle-enrichment patterns in droplets is challenging but important in biochemical analysis and clinical diagnosis. Herein, a light strategy for precisely manipulating particle enrichment patterns is reported. Focused laser irradiation to the droplet induces a Marangoni flow owing to a localized photothermal effect, which carries in-droplet particles and concentrates them at the laser-spot-acted region. Owing to high flexibility of light, multiple particle-enriched sites are formed in a droplet, and the concentrated particles can be transported and reconstructed on demand. In addition to the island-like enrichment pattern, this optical particle manipulation strategy enables the formation of various particle-enriched patterns, such as the line-shape and circle-shape patterns. Further, light directly acts on the working fluid instead of target particles, considerably weakening dependence on particle properties. For particles whose density is similar to that of the working fluid, a portion of particles can still be concentrated. It is also found that only a small portion of submicron particles can be concentrated, while nanoparticles are hardly concentrated by this light strategy. Moreover, high reconfigurability of light enables in-parallel high-throughput operations, which is demonstrated using two laser beams to form two particle enrichment sites in a droplet simultaneously. Finally, this light strategy is also demonstrated by concentrating cells and nucleic acid molecules. This work paves the way for the applications of optofluidics in cell sorting, point-of-care analysis, and drug screening.

Mosaic Patterned Surfaces toward Generating Hardly-Volatile Capsular Droplet Arrays for High-Precision Droplet-Based Storage and Detection.

Precise detection involving droplets based on functional surfaces is promising for the parallelization and miniaturization of platforms and is significant in epidemic investigation, analyte recognition, environmental simulation, combinatorial chemistry, etc. However, a challenging and considerable task is obtaining mutually independent droplet arrays without cross-contamination and simultaneously avoiding droplet evaporation-caused quick reagent loss, inaccuracy, and failure. Herein, a strategy to generate mutually independent and hardly-volatile capsular droplet arrays using innovative mosaic patterned surfaces is developed. The evaporation suppression of the capsular droplet arrays is 1712 times higher than the naked droplet. The high evaporation suppression of the capsular droplet arrays on the surfaces is attributed to synergistic blocking of the upper oil and bottom mosaic gasproof layer. The scale-up of the capsular droplet arrays, the flexibility in shape, size, component (including aqueous, colloidal, acid, and alkali solutions), liquid volume, and the high-precision hazardous substance testing proves the concept's high compatibility and practicability. The mutually independent capsular droplet arrays with amazingly high evaporation suppression are essential for the new generation of high-performance open-surface microfluidic chips used in COVID-19 diagnosis and investigation, primary screening, in vitro enzyme reactions, environmental monitoring, nanomaterial synthesis, etc.

Advanced ovarian clear cell carcinoma with RAD50 mutation treated by PARP inhibitor pamiparib combined with anti-angiogenesis therapy: a case report.

Ovarian clear cell carcinoma (OCCC) is a relatively uncommon epithelial ovarian malignancy with unique clinical, histopathologic and genetic characteristics. Patients with advanced OCCC have poor outcomes and are resistant to standard chemotherapy. Targeted therapy offers a novel approach for treating OCCC. We report the case of a 45-year-old female patient with advanced OCCC who experienced relapse after standard treatment. Further, a frameshift mutation in the homologous recombination repair-related gene RAD50 (RAD50-p.I371Ffs*8) was identified by genetic testing. Next, the patient had received targeted combination therapy with poly (ADP-ribose) polymerase (PARP) inhibitor pamiparib and bevacizumab, achieving partial remission. Patient's symptoms improved significantly compared to before. To date, the patient has been followed up for more than half a year with favorable survival and high quality of life. The case report suggested that parmiparib-targeted therapy is a viable treatment option for advanced OCCC patients with RAD50 mutation.

Integrative transcriptome and whole-genome bisulfite sequencing analyses of a temperature-sensitive albino tea plant cultivar.

Green tea made from albino buds and leaves has a strong umami taste and aroma. The cultivar 'Zhonghuang 2' (ZH2, Camellia sinensis) is a natural mutant with young shoots that are yellow in spring and green or yellow-green in summer. However, the mechanism of leaf color change remains unclear. Here, we found that young shoots of ZH2 were yellow at low temperature (LT) and green at high temperature (HT), indicating that ZH2 is a temperature-sensitive cultivar. Transmission electron microscopy analysis showed that the grana in the chloroplasts of young shoots grown at LT were poorly stacked, which caused a lack of photoreactions and chlorophyll. RNA-seq results showed 1279 genes differentially expressed in the young shoots grown at LT compared with those at HT, including genes related to cytochrome synthesis, chloroplast development, photosynthesis, and DNA methylation. A whole-genome bisulfite sequencing assay revealed that the dynamics of DNA methylation levels in the CG, CHG, and CHH contexts decreased under LT, and the change was most obvious in the CHH context. Furthermore, 72 genes showed significant changes in both expression and DNA methylation levels, and most of them were related to cytochrome synthesis, chloroplast development, photosynthesis, transcription factors, and signaling pathways. These results demonstrate that DNA methylation is involved in the LT-regulated albino processes of ZH2. Changes in DNA methylation levels were associated with changes in gene expression levels, affecting the structure and function of chloroplasts, which may have a phenotypic impact on shoot and leaf color.

Novel beagle model of gastric local fibrotic target lesions for the evaluation and training of endoscopic techniques.

BACKGROUND: Novel endoscopic techniques used in the treatment of gastric lesions with local submucosal fibrosis need preclinical evaluation and training due to safety limitations. Therefore, the purpose of our study was to establish an animal model of gastric local fibrotic target lesions and assess its feasibility in the evaluation and training of endoscopic techniques. METHODS: In six experimental beagles, a 50% glucose solution was injected into three submucosal areas of the fundus, body, and antrum of the stomach to create gastric local fibrotic target lesions (experimental group). On post-injection day (PID) 7, the injection sites were assessed endoscopically to confirm the presence of submucosal fibrosis formation, and the dental floss clip traction assisted endoscopic submucosal dissection (DFC-ESD) procedure was performed on the gastric local fibrotic target lesions to confirm its feasibility after endoscopic observation. The normal gastric mucosa of six control beagles underwent the same procedure (control group). All the resected specimens were evaluated by histological examination. RESULTS: All 12 beagles survived without postoperative adverse events. On PID 7, 16 ulcer changes were observed at the injection sites (16/18) under the endoscope, and endoscopic ultrasonography confirmed the local submucosal fibrosis formation in all ulcer lesions. The subsequent DFC-ESD was successfully performed on the 32 gastric target lesions, and the mean submucosal dissection time in the ulcer lesions was greater than that in the normal gastric mucosa (15.3 ± 5.6 vs. 6.8 ± 0.8 min; P < 0.001). There was no difference in rates of en bloc resection, severe hemorrhage, or perforation between the two groups. Histological analysis of the ulcer lesions showed the absence of epithelial or muscularis mucosae and extensive submucosal fibrous tissue proliferations compared with normal gastric mucosa. Overall, endoscopists had high satisfaction with the realism and feasibility of the animal model. CONCLUSION: We developed a novel animal model of gastric local fibrotic target lesions to simulate difficult clinical situations, which strongly appeared to be suitable for the preclinical evaluation and learning of advanced endoscopic techniques.

Human Leukocyte Antigen Polymorphism HLA-A*24:02 is Associated with Acute Liver Disease in HBV-Infected Han Chinese Adults.

BACKGROUND: Whether polymorphic Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-DRB1 alleles were associated with acute liver disease after hepatitis B virus (HBV) infections was investigated. METHODS: In this study, from initially 100 participants in each group, HLA-A, HLA-B and HLA-DRB1 sequences were available from 86 acute hepatitis B (AHB) patients and from 84 HBV-resistant individuals (controls), using sequencing-based typing allele groups and alleles that exhibited differences in distribution between the case and control groups were subjected to chi-squared and logistic regression analyses to identify those associated with AHB. A dose response analysis was also performed on the effect of HLA-A*24:02 allele number on acute liver disease following HBV infection. RESULTS: The frequency distribution of HLA-B and HLA-DRB1 alleles in the control group were in Hardy-Weinberg Equilibrium (P > .05). HLA-A*24:02 (χ2 = 6.949, P = .008) occurred most frequently in the AHB and HLA-DRB1*12:02 (χ2 = 7.768, P = .005) in the control group. With adjustment for sex, the logistic regression model showed that the HLA-A*24:02 allele was significantly associated with AHB liver injury (P = .0326, OR = 2.270, 95% CI: 1.070-4.816), whereas the other HLA-A, HLA-B, and HLA-DRB1 alleles were not (P > .05). A linear response was observed for the association between HLA-A*24:02 allele number and acute liver disease after HBV infections (χ2 = 4.428, P = .025). CONCLUSION: The HLA-A*24:02 allele may influence the severity of the cellular response to HBV infection, increasing the elimination of HBV-infected hepatocytes. The HLA-A*24:02 allele may be a potential screening marker for identifying people or regional populations in China at higher risk of acute liver disease following HBV infection.

Red Blood Cell Distribution Width as a Potential Valuable Survival Predictor in Hepatitis B Virus-related Hepatocellular Carcinoma.

Objectives: Red blood cell distribution width (RDW) is a widely used clinical parameter recently deployed in predicting various cancers. This study aimed to evaluate the prognostic value of RDW in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods: We conducted a retrospective study of 745 patients with HBV-related HCC, 253 patients with chronic hepatitis B (CHB), and 256 healthy individuals to compare their hematological parameters and analyze their RDW levels. Potential risk factors for long-term all-cause mortality in patients with HBV-related HCC were predicted using Multivariate Cox regression. A nomogram was generated, and its performance was evaluated. Results: The RDW of patients with HBV-related HCC was significantly higher than that of those with CHB and healthy controls. In the former, splenomegaly, liver cirrhosis, larger tumor diameter, multiple tumor number, portal vein tumor thrombus, and lymphatic or distant metastasis were significantly increased, and the later the Child-Pugh grade and Barcelona clinic liver cancer stage, the higher the RDW. Furthermore, multivariate Cox regression analysis identified RDW as an independent risk factor for predicting long-term all-cause mortality in patients with HBV-related HCC. Finally, we successfully generated a nomogram incorporating RDW and validated its predictive ability. Conclusions: RDW is a potentially valuable hematological marker for predicting the survival and prognosis of patients with HBV-related HCC. The nomogram incorporating RDW can be used as an effective tool to plan the individualized treatment of such patients.

Genome-Wide Investigation of BAM Gene Family in Annona atemoya: Evolution and Expression Network Profiles during Fruit Ripening.

ß-amylase proteins (BAM) are important to many aspects of physiological process such as starch degradation. However, little information was available about the BAM genes in Annona atemoya, an important tropical fruit. Seven BAM genes containing the conservative domain of glycoside hydrolase family 14 (PF01373) were identified with Annona atemoya genome, and these BAM genes can be divided into four groups. Subcellular localization analysis revealed that AaBAM3 and AaBAM9 were located in the chloroplast, and AaBAM1.2 was located in the cell membrane and the chloroplast. The AaBAMs belonging to Subfamily I contribute to starch degradation have the higher expression than those belonging to Subfamily II. The analysis of the expression showed that AaBAM3 may function in the whole fruit ripening process, and AaBAM1.2 may be important to starch degradation in other organs. Temperature and ethylene affect the expression of major AaBAM genes in Subfamily I during fruit ripening. These expressions and subcellular localization results indicating ß-amylase play an important role in starch degradation.

Profiling the role of microorganisms in quality improvement of the aged flue-cured tobacco.

BACKGROUND: The aging process in the tobacco production, as in other food industries, is an important process for improving the quality of raw materials. In the spontaneous aging, the complex components in flue-cured tobacco (FT) improve flavor or reduce harmful compounds through chemical reactions, microbial metabolism, and enzymatic catalysis. Some believed that tobacco-microbe played a significant part in this process. However, little information is available on how microbes mediate chemical composition to improve the quality of FT, which will lay the foundation for the time-consuming spontaneous aging to seek ways to shorten the aging cycle. RESULTS: Comparing aged and unaged FT, volatile and non-volatile differential compounds (DCs) were multi-dimensionally analyzed with the non-targeted metabolomes based on UPLC-QTOP-MS (the ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry), GC-MS (gas chromatography-mass spectrometer) assisted derivatization and HP-SPME-GC/MS (headspace solid-phase micro-extraction assisted GC-MS). Products associated with the degradation pathways of terpenoids or higher fatty acids were one of the most important factors in improving FT quality. With the microbiome, the diversity and functions of microbial flora were analyzed. The high relative abundance function categories were in coincidence with DCs-related metabolic pathways. According to the correlation analysis, Acinetobacter, Sphingomonas and Aspergillus were presumed to be the important contributor, in which Aspergillus was associated with the highest number of degradation products of terpenoids and higher fatty acids. At last, the screened Aspergillus nidulans strain F4 could promote the degradation of terpenoids and higher fatty acids to enhance tobacco flavor by secreting highly active lipoxygenase and peroxidase, which verified the effect of tobacco-microbes on FT quality. CONCLUSIONS: By integrating the microbiome and metabolome, tobacco-microbe can mediate flavor-related substances to improve the quality of FT after aging, which provided a basis for identifying functional microorganisms for reforming the traditional spontaneous aging.

Spatial-temporal analysis of HIV/AIDS and syphilis in mainland China from 2007 to 2017.

Human immune deficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and syphilis are the most common sexually transmitted diseases (STDs) worldwide, as well as in China. The objective of this study is to describe the trend of spatial and temporal variation of HIV/AIDS and syphilis in mainland China from 2007 to 2017. Stratified analysis was conducted according to age and the GDP per capita. Estimated Annual Percentage Change (EAPC) was calculated and spatial autocorrelation analysis was used to evaluate the epidemiology and identify clusters. The morbidity of new HIV infection increased from 2.5034/100 000 in 2007 to 6.9247/100 000 in 2017, with an EAPC of 9.84 (95% confidence interval [CI]: 9.07-10.60). From 2007 to 2017, the morbidity of syphilis presented a significant upward trend from 15.8834/100 000 to 34.4867/100 000 (EAPC = 6.48, 95% CI: 4.23-8.73). The number of new HIV infections (205 084) and syphilis (921 279) were highest in the 20-30 years old group, where the incidence decreased with age over 20 years. In general, HIV and syphilis infection had the same incidence trend according to age and time stratification. The morbidity of new HIV infection was mainly reported from Xinjiang and southwestern China. As for syphilis, the highest was found in Zhejiang in Xinjiang and southeast coastal areas. Both HIV and syphilis infection showed a nonrandom positive correlation by Moran's I value. The High-High cluster areas of HIV infection were concentrated in southwestern and eastern China due to syphilis. A highly significant positive correlation was found between gross domestic product per capita and syphilis infection (p < 0.05) but was not associated with HIV infection. The incidence of AIDS/HIV and syphilis is increasing year by year, and a higher prevalence is found in younger individuals. More attention should be paid to HIV infection in the southwest, syphilis in southeast coastal areas, and both the two diseases in Xinjiang.

Overexpression of CENPL mRNA potentially regulated by miR-340-3p predicts the prognosis of pancreatic cancer patients.

BACKGROUND: In our previous study it was found that CENPL was overexpressed in hepatocellular carcinoma and significantly predicted patient's prognosis. However, the expression and prognostic value of CENPL in other gastrointestinal tumors remain unknown. Therefore, we investigated the expression and prognostic value of CENPL in esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), pancreatic adenocarcinoma (PAAD), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ). METHODS: In this study, Oncomine, GEPIA, OncoLnc, TIMER, cBioPortal, miRWalk and ENCORI databases were used to analyze the level of CENPL mRNA, prognostic value and potential regulatory mechanism of CENPL mRNA in tumors. The CENPL expression and clinicopathological data regarding PAAD were from the UCSC Xena database and univariate and multivariate Cox regression analyses were performed using R (Version 3.6.3). Immunohistochemical staining was used to verify the expression of CENPL protein in clinical specimens. Cytoscape (Version: 3.7.2) was used to visualize microRNA (miRNA) that potentially regulates CENPL. RESULTS: Gene differential expression analysis showed that CENPL mRNA was significantly overexpressed in ESCA, STAD, PAAD, COAD and READ (p < 0.01). The overexpression of CENPL mRNA was significantly correlated with the poor prognosis of PAAD patients (p < 0.05). However, there was no significant correlation between the level of CENPL mRNA and the prognosis of ESCA, STAD, COAD and READ patients (p > 0.05). Univariate and multivariate Cox regression analyses suggested that CENPL was a prognostic risk factor for PAAD. The mutation rate of CENPL in PAAD was 2.2% (17/850). There was no significant correlation between the CENPL expression and the infiltration levels of immune cells in PAAD (|Cor|< 0.5). Immunohistochemical staining showed that CENPL was overexpressed in 42% (11/26) of PAAD specimens, which was significantly higher compared with that in the normal tissues. The expression of miR-340-3p and miR-484 in PAAD were significantly lower than in the normal tissues (p < 0.05) and PAAD patients with lower expression of miR-340-3p had poorer prognosis (p < 0.05). CONCLUSION: CENPL potentially regulated by miR-340-3p, is overexpressed in PAAD and predicts patient's prognosis, suggestive of a diagnostic and prognostic value in PAAD patients.

Efficacy and safety of bicyclol for treating patients with idiosyncratic acute drug-induced liver injury: A multicenter, randomized, phase II trial.

BACKGROUND AND AIMS: Evidence for using bicyclol in drug-induced liver injury (DILI) is limited. This study aimed to explore the efficacy and safety of bicyclol in acute DILI. METHODS: This was a multicenter, randomized, double-blinded, double-dummy, active-controlled, superiority and phase II trial. Patients with idiosyncratic acute DILI were randomized 1: 1:1 to low-dose bicyclol (25 mg times a day [TID]), high-dose bicyclol (50 mg TID) and polyene phosphatidylcholine (control) groups. The primary endpoint was the decrease from baseline in serum alanine aminotransferase (ALT) levels at post-treatment for 4 weeks. RESULTS: Overall, 241 patients were included in the full analysis set, with 81, 82 and 78 patients in the low-dose bicyclol, high-dose bicyclol, and control groups respectively. ALT levels decreased across groups (-249.2 ± 151.1, -273.6 ± 203.1, and -180.8 ± 218.2 U/L in the low-dose bicyclol, high-dose bicyclol and control groups, respectively; both p < .001, the bicyclol-dependent groups vs. control group). The ALT normalization rates at weeks 1, 2, 4, 6 and 8 were higher in the bicyclol-dependent groups than in the control group (p = .002 at week 1 and all p < .001 at weeks 2, 4, 6 and 8 respectively). The median times to ALT normalization in the low-dose bicyclol, high-dose bicyclol and control groups were 29, 16 and 43 days respectively. Adverse events, serious adverse events and adverse drug reactions were similar across groups. CONCLUSIONS: Bicyclol (25 and 50 mg TID) appeared efficacious and safe for treating idiosyncratic acute DILI, while bicyclol 50 mg TID showed higher efficacy. TRIAL REGISTRATION NUMBER: www. CLINICALTRIALS: gov (registration no. NCT02944552).

Gallbladder-preserving polypectomy for gallbladder polyp by embryonic-natural orifice transumbilical endoscopic surgery with a gastric endoscopy.

BACKGROUND AND AIMS: Cholecystectomy is performed for most gallbladder polyps (GPs). However, cholecystectomy results concerning complications in some patients. For benign GPs, adoption of gallbladder-preserving surgery is worth to recommend. We describe our experiences performing gallbladder-preserving polypectomy for GPs by embryonic-natural orifice transumbilical endoscopic surgery (E-NOTES) with a gastric endoscopy. METHODS: This is a retrospective study of patients with GPs who underwent gallbladder-preserving polypectomy by E-NOTES with a gastric endoscopy from April 2018 to September 2019 in our hospital. The operative time, intraoperative hemorrhage, intraoperative and postoperative complications, gallbladder emptying function were obtained and analyzed. RESULTS: The procedure was performed successfully in all 12 patients with 5 cases of single polyp and 7 cases of multiple polyps. The range of GPs size was 2 mm to 15 mm. The mean operation time was (95.33 ± 23.08) minutes (55-135 min). There were no adverse events including heavy bleeding, mortality and conversion to open surgery during operation. All patients were discharged in 4-5 days after surgery without postoperative complications such as delayed bleeding, fever, peritonitis, intra-abdominal abscess and abdominal wall incisional hernia. All patients were followed up at 1, 3, 6, and 12 months postoperation who had almost no visible incision on the umbilical region, no recurrent GPs. The gallbladder emptying function decreased one month after surgery, and gradually improved 3, 6 and 12 months after surgery. CONCLUSION: E-NOTES gallbladder-preserving polypectomy is a safe and effective option for patients with GPs and is close to scar-free surgery which can be performed in routine clinical practice.