Effects of hypertensive disorders of pregnancy on the complications in very low birth weight neonates.

OBJECTIVE: This study was designed to investigate the effects of hypertensive disorders of pregnancy (HDP) on the complications in very low birth weight (VLBW) neonates. METHODS: We retrospectively included VLBW neonates (<37 weeks) who were delivered by HDP pregnant women with a body weight of < 1,500 g (HDP group) hospitalized in our hospital between January 2016 and July 2021. Gestational age matched VLBW neonates delivered by pregnant women with a normal blood pressure, with a proportion of 1:1 to the HDP group in number, served as normal control. RESULTS: Then we compared the peripartum data and major complications between HDP group and control. The body weight, prelabor rupture of membrane (PROM), maternal age, cesarean section rate, fetal distress, small for gestational age (SGA), mechanical ventilation, RDS, necrotizing enterocolitis (NEC) (≥2 stage), Apgar score at 1 min, and mortality in HDP group showed statistical differences compared with those of the control (all p < 0.05). To compare the major complications among HDP subgroups, we classified the VLBW neonates of the HDP group into three subgroups including gestational hypertension group (n = 72), pre-eclampsia (PE) group (n = 222), and eclampsia group (n = 14), which showed significant differences in the fetal distress, Apgar score at 1 min, SGA, ventilation, RDS and NEC (≥2 stage) among these subgroups (all p < 0.05). Multivariate regression analysis showed that eclampsia and PE were the independent risk factors for SGA and NEC, respectively. CONCLUSION: HDP was associated with increased incidence of neonatal asphyxia, fatal distress, SGA, mechanical ventilation, RDS, NEC and mortality. Besides, eclampsia and PE were independent risk factors for SGA and NEC.

Artificial intelligence-based diagnosis of standard endoscopic ultrasonography scanning sites in the biliopancreatic system: a multicenter retrospective study.

BACKGROUND: There are challenges for beginners to identify standard biliopancreatic system anatomical sites on endoscopic ultrasonography (EUS) images. Therefore, the authors aimed to develop a convolutional neural network (CNN)-based model to identify standard biliopancreatic system anatomical sites on EUS images. METHODS: The standard anatomical structures of the gastric and duodenal regions observed by EUS was divided into 14 sites. The authors used 6230 EUS images with standard anatomical sites selected from 1812 patients to train the CNN model, and then tested its diagnostic performance both in internal and external validations. Internal validation set tests were performed on 1569 EUS images of 47 patients from two centers. Externally validated datasets were retrospectively collected from 16 centers, and finally 131 patients with 85 322 EUS images were included. In the external validation, all EUS images were read by CNN model, beginners, and experts, respectively. The final decision made by the experts was considered as the gold standard, and the diagnostic performance between CNN model and beginners were compared. RESULTS: In the internal test cohort, the accuracy of CNN model was 92.1-100.0% for 14 standard anatomical sites. In the external test cohort, the sensitivity and specificity of CNN model were 89.45-99.92% and 93.35-99.79%, respectively. Compared with beginners, CNN model had higher sensitivity and specificity for 11 sites, and was in good agreement with the experts (Kappa values 0.84-0.98). CONCLUSIONS: The authors developed a CNN-based model to automatically identify standard anatomical sites on EUS images with excellent diagnostic performance, which may serve as a potentially powerful auxiliary tool in future clinical practice.

Green and efficient recycling method for spent Ni-Co-Mn lithium batteries utilizing multifunctional deep eutectic solvents.

Given the growing volume of discarded lithium-ion batteries (LIBs), the extraction and recovery of valuable metals through environmentally-friendly solvent processes have become crucial, but they remain challenging tasks. Deep eutectic solvent (DES), an innovative and green solvents, have demonstrated significant promise in the extraction of valued metal elements from spent LIBs. This work employed a multifunctional DES based on natural molecules dimethyl-beta-propiothetin (DMPT) and ethylene glycol (EG) for the efficient leaching of transition metal ions. Under the reduction effect of EG and the action of carboxyl groups and chloride ions in DMPT, the leaching rate of Li, Ni, Co, and Mn can reach 99.59%, 99.28%, 99.04%, and 99.45%, respectively. Furthermore, DFT calculations were employed to explore the microstructure of DES and its interactions with metal ions. The main active site in the DES molecule is near the chloride ion, and DES binds most strongly to Mn, followed by Co, and weakest to Ni. This work avoids the use of volatile acids and demonstrates great potential in extracting valuable metals, providing a sustainable and environment-friendly alternative for the efficient recycling of waste LIBs.

The Efficacy and Safety of Regimens for Helicobacter pylori Eradication Treatment in China: A Systemic Review and Network Meta-Analysis.

BACKGROUND: With Helicobacter pylori's increasing antibiotic resistance, evidence of more effective treatments is lacking in China, where H. pylori prevalence is nearly 50%. Thus, we performed a network meta-analysis to compare therapeutic regimens. METHODS: Data extracted from eligible randomized controlled trials from January 2000 to September 2021 were entered into a Bayesian hierarchical random-effects model to evaluate the efficacy and safety of H. pylori eradication regimens. RESULTS: This study included 101 trials involving 21,745 patients. Vonoprazan-bismuth-containing quadruple therapy (VBQT) ranked the highest [surfaces under cumulative ranking curve (SUCRA), 83.64%], followed by high-dose amoxicillin dual therapy (HDDT) [SUCRA, 79.70%, odds ratio (OR)=1.31, 95% credible interval (CrI) (0.36, 4.72)] and proton pump inhibitor-based bismuth-containing quadruple therapy (BQT) [SUCRA, 63.59%, OR=1.59, 95% CrI (0.48, 5.24)]. HDDT [OR=2.47, 95% CrI (1.51, 4.06)], BQT [OR=2.04, 95% CrI (1.69, 2.47)], concomitant quadruple nonbismuth therapy (CT) [OR=1.93, 95% CrI (1.19, 3.15)], and sequential therapy (ST) [OR=1.86, 95% CrI (1.50, 2.32)] had higher eradication rates than standard triple therapy (TT). ST (SUCRA, 82.52%) and VBQT (SUCRA, 83.89%) had the highest eradication rate before and after 2010 in the effectiveness ranking, respectively. Furthermore, the H. pylori eradication rate of patients receiving 14-day BQT treatment was higher than that of 10-day BQT regimen [OR=2.55, 95% CI (1.84, 3.53)] and 7-day BQT regimen [OR=3.64, 95% CI (2.64, 5.01)]. CONCLUSIONS: The TT regimen was not an optimal choice in China for H. pylori eradication; VBQT, HDDT, and BQT showed better efficacy. After 2010, there is a trend toward significance that VBQT provided a higher H. pylori eradication rate in China, but with only 1 randomized controlled trial. Thus, more supportive real-world data are needed to confirm its effectiveness.

Microvesicles from bone marrow-derived mesenchymal stem cells promote Helicobacter pylori-associated gastric cancer progression by transferring thrombospondin-2.

BACKGROUND: Our previous study found that bone marrow-derived mesenchymal stem cells (BMSCs) promote Helicobacter pylori (H pylori)-associated gastric cancer (GC) progression by secreting thrombospondin-2 (THBS2). Extracellular vesicles (EVs) are important carriers for intercellular communication, and EVs secreted by BMSCs have been shown to be closely related to tumor development. The aim of this study was to investigate whether BMSC-derived microvesicles (MVs, a main type of EV) play a role in H. pylori-associated GC by transferring THBS2. METHODS: BMSCs and THBS2-deficient BMSCs were treated with or without the supernatant of H. pylori for 12 h at a multiplicity of infection of 50, and their EVs were collected. Then, the effects of BMSC-derived MVs and THBS2-deficient BMSC-derived MVs on the GC cell line MGC-803 were assessed by in vitro proliferation, migration, and invasion assays. In addition, a subcutaneous xenograft tumor model, a nude mouse intraperitoneal metastasis model, and a tail vein injection metastasis model were constructed to evaluate the effects of BMSC-derived MVs and THBS2-deficient BMSC-derived MVs on GC development and metastasis in vivo. RESULTS: BMSC-derived MVs could be readily internalized by MGC-803 cells. BMSC-derived MVs after H. pylori treatment significantly promoted their proliferation, migration and invasion in vitro (all P < 0.05) and promoted tumor development and metastasis in a subcutaneous xenograft tumor model, a nude mouse intraperitoneal metastasis model, and a tail vein injection metastasis model in vivo (all P < 0.05). The protein expression of THBS2 was significantly upregulated after H. pylori treatment in BMSC-derived MVs (P < 0.05). Depletion of the THBS2 gene reduces the tumor-promoting ability of BMSC-MVs in an H. pylori infection microenvironment both in vitro and in vivo. CONCLUSION: Overall, these findings indicate that MVs derived from BMSCs can promote H. pylori-associated GC development and metastasis by delivering the THBS2 protein. Video Abstract.

L-Fucose promotes enteric nervous system regeneration in type 1 diabetic mice by inhibiting SMAD2 signaling pathway in enteric neural precursor cells.

BACKGROUND: Diabetes can lead to extensive damage to the enteric nervous system (ENS), causing gastrointestinal motility disorders. However, there is currently a lack of effective treatments for diabetes-induced ENS damage. Enteric neural precursor cells (ENPCs) closely regulate the structural and functional integrity of the ENS. L-Fucose, is a dietary sugar that has been showed to effectively ameliorate central nervous system injuries, but its potential for ameliorating ENS damage and the involvement of ENPCs in this process remains uncertain. METHODS: Genetically engineered mice were generated for lineage tracing of ENPCs in vivo. Using diabetic mice in vivo and high glucose-treated primary ENPCs in vitro, the effects of L-Fucose on the injured ENS and ENPCs was evaluated by assessing gastrointestinal motility, ENS structure, and the differentiation of ENPCs. The key signaling pathways in regulating neurogenesis and neural precursor cells properties, transforming growth factor-ß (TGF-ß) and its downstream signaling pathways were further examined to clarify the potential mechanism of L-Fucose on the injured ENS and ENPCs. RESULTS: L-Fucose improved gastrointestinal motility in diabetic mice, including increased defecation frequency (p < 0.05), reduced total gastrointestinal transmission time (p < 0.001) and bead expulsion time (p < 0.05), as well as enhanced spontaneous contractility and electric field stimulation-induced contraction response in isolated colonic muscle strips (p < 0.001). The decrease in the number of neurons and glial cells in the ENS of diabetic mice were reversed by L-Fucose treatment. More importantly, L-Fucose treatment significantly promoted the proportion of ENPCs differentiated into neurons and glial cells both in vitro and in vivo, accompanied by inhibiting SMAD2 phosphorylation. CONCLUSIONS: L-Fucose could promote neurogenesis and gliogenesis derived from ENPCs by inhibiting the SMAD2 signaling, thus facilitating ENS regeneration and gastrointestinal motility recovery in type 1 diabetic mice. Video Abstract.

Epidemiologic trends and survival of early-onset gastroenteropancreatic neuroendocrine neoplasms.

Background: The epidemiologic trends and survival related to early-onset gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have not been well explored. Methods: Trends in the incidence and incidence-based mortality of early-onset GEP-NENs between 1975 and 2018 were obtained from the Surveillance, Epidemiology, and End Results database, and were stratified by age, sex, race, tumor site, stage, and grade. Associated population data were used to determine overall survival (OS) and independent prognostic factors for patients with early-onset GEP-NENs. Results: A total of 17299 patients diagnosed with early-onset GEP-NENs were included in this study. Results revealed an increase in the incidence (5.95% per year, 95% confidence interval (CI), 5.75-6.14%) and incidence-based mortality (4.24% per year, 95% CI, 3.92-4.56%) for early-onset GEP-NENs from 1975 to 2018, with higher rates of increase than those of later-onset GEP-NENs (incidence: 4.45% per year, 95% CI, 4.38-4.53; incidence-based mortality: 4.13% per year, 95% CI, 3.89-4.37; respectively). Increases in incidence were observed across all age, races, tumor sites, grades, and stages, except for patients with unknown stage. Compared to those with later-onset GEP-NENs, a higher proportion of female gender (54.5% vs. 49.0%, p <0.001), well-differentiated tumor (31.1% vs. 28.0%, p <0.05), and localized disease (55.2% vs. 46.7%, p <0.05) were observed in the cohort of patients with early-onset GEP-NENs. Moreover, early-onset GEP-NENs exhibited a superior overall survival in comparison to later-onset GEP-NENs, irrespective of tumor site, grade, or stage (p <0.0001). Multivariable survival analysis identified that race, marital status, stage, grade, chemotherapy, and primary site were significantly correlated with OS in individuals with early-onset GEP-NENs. Conclusions: The incidence and incidence-based mortality rates of early-onset GEP-NENs have steadily increased over time, with higher rates of increase than those of later-onset GEP-NENs. The clinical characteristics and survival were different between early-onset and later-onset GEP-NENs groups. Race, marital status, stage, grade, chemotherapy, and primary site were independent prognostic factors for early-onset GEP-NENs. Further investigations are warranted to better understand the characteristics of this disease subgroup.

Predicting the survival of patients with pancreatic neuroendocrine neoplasms using deep learning: A study based on Surveillance, Epidemiology, and End Results database.

BACKGROUND: The study aims to evaluate the performance of three advanced machine learning algorithms and a traditional Cox proportional hazard (CoxPH) model in predicting the overall survival (OS) of patients with pancreatic neuroendocrine neoplasms (PNENs). METHOD: The clinicopathological dataset obtained from the Surveillance, Epidemiology, and End Results database was randomly assigned to the training set and testing set at a ratio of 7:3. The concordance index (C-index) and integrated Brier score (IBS) were used to compare the predictive performance of the models. The accuracy of the model in predicting the 5-year and 10-year survival rates was compared using the receiver operating characteristic curve, decision curve analysis (DCA) and calibration curve. RESULTS: This study included 3239 patients with PNENs in total. The DeepSurv model had the highest C-index of 0.7882 in the testing set and training set and the lowest IBS of 0.1278 in the testing set compared with the CoxPH, neural multitask logistic and random survival forest models (C-index = 0.7501, 0.7616, and 0.7612, respectively; IBS = 0.1397, 0.1418, and 0.1432, respectively). Moreover, the DeepSurv model had the highest accuracy in predicting 5- and 10-year OS rates (area under the curve: 0.87 and 0.90). DCA showed that the DeepSurv model had high potential for clinical decisions in 5- and 10-year OS models. Finally, we developed an online application based on the DeepSurv model for clinical use (https://whuh-ml-neuroendocrinetumor-app-predict-oyw5km.streamlit.app/). CONCLUSIONS: All four models analyzed above can predict the prognosis of PNENs well, among which the DeepSurv model has the best prediction performance.

Bone mesenchymal stem cells promote gastric cancer progression through TGF-ß1/Smad2 positive feedback loop.

AIMS: Bone marrow-derived mesenchymal stem cells (BMSCs) have been proven to be recruited into the tumor microenvironment and contribute to gastric cancer (GC) progression, but the underlying mechanism is still unclear. The purpose of this study is to explore the exact role and potential mechanism of BMSCs in the progression of GC. MATERIALS AND METHODS: Bioinformatics analyzed were used to clarify the correlation between TGF-ß1 and prognosis of gastric cancer. Cell co-culture were used to explore the interaction between gastric cancer cells (GCs) and BMSCs. Quantitative real time-PCR and Western blot assay were used to detect gene and protein expression, respectively. The biological characteristics of GCs and BMSCs were detected by immunofluorescence, Transwell migration, Elisa and invasion assay. Xenograft models in nude mice were constructed to evaluate GC development in vivo. KEY FINDINGS: TGF-ß1 was overexpressed in GC cells and tissues, and is positively related to the poor prognosis of patients. TGF-ß1 from GCs activated the Smad2 pathway in BMSCs, promoting their differentiation into carcinoma-associated fibroblasts (CAFs) and TGF-ß1 expression. Concomitantly, TGF-ß1 secreted by CAFs activate Smad2 signaling in GC cells, thus inducing their epithelial-mesenchymal transition (EMT) and TGF-ß1 secretion. BMSCs can dramatically promote the proliferation, migration, and invasion of GCs while blocking TGF-ß1/Smad2 positive feedback loop can reverse these effects. SIGNIFICANCE: The TGF-ß1/Smad2 positive feedback loop between GCs and BMSCs, promotes the CAFs differentiation of BMSCs and the EMT of GCs, resulting in the progression of GC.

A novel intelligent chromo capsule endoscope for the diagnosis of neoplastic lesions in the gastrointestinal tract.

Background: Chromoendoscopy has not been fully integrated into capsule endoscopy. This study aimded to develop and validate a novel intelligent chromo capsule endoscope (ICCE). Methods: The ICCE has two modes: a white-light imaging (WLI) mode and an intelligent chromo imaging (ICI) mode. The performance of the ICCE in observing colors, animal tissues, and early gastrointestinal (GI) neoplastic lesions in humans was evaluated. Images captured by the ICCE were analysed using variance of Laplacian (VoL) values or image contrast evaluation. Results: For color observation, conventional narrow-band imaging endoscopes and the ICI mode of the ICCE have similar spectral distributions. Compared with the WLI mode, the ICI mode had significantly higher VoL values for animal tissues (2.154 ± 1.044 vs 3.800 ± 1.491, P = 0.003), gastric precancerous lesions and early gastric cancers (2.242 ± 0.162 vs 6.642 ± 0.919, P < 0.001), and colon tumors (3.896 ± 1.430 vs 11.882 ± 7.663, P < 0.001), and significantly higher contrast for differentiating tumor and non-tumor areas (0.069 ± 0.046 vs 0.144 ± 0.076, P = 0.005). More importantly, the sensitivity, specificity, and accuracy of the ICI mode for early GI tumors were 95.83%, 91.67%, and 94.64%, respectively, which were significantly higher than the values of the WLI mode (78.33% [P < 0.001], 77.08% [P = 0.01], and 77.98% [P < 0.001], respectively). Conclusions: We successfully integrated ICI into the capsule endoscope. The ICCE is an innovative and useful tool for differential diagnosis based on contrast-enhanced images and thus has great potential as a superior diagnostic tool for early GI tumor detection.

Nomograms for Predicting Survival Outcomes in Patients with Neuroendocrine Neoplasms of the Gallbladder Undergoing Primary Tumor Resection: A Population-Based Study.

BACKGROUND: Neuroendocrine neoplasms of the gallbladder (GB-NENs) are a rare group of histologically heterogeneous tumors, and surgical resection of the primary tumor is the mainstream treatment at the moment. The current study aimed to establish and validate novel nomograms for patients with GB-NENs undergoing primary tumor resection to predict the 6-, 12-, and 18-month overall survival (OS) and cancer-specific survival (CSS). METHODS: Clinicopathological information of patients with GB-NENs undergoing primary tumor resection between 2004 and 2018 was derived from the Surveillance, Epidemiology, and End Results (SEER) database. Candidate prognostic factors were selected by Cox regression analyses, and the nomograms were constructed. Finally, concordance index (C-index), calibration plot, area under the curve from the receiver operating characteristic curve (AUC), and decision curve analysis (DCA) were utilized to assess the effective performance of the nomograms. RESULTS: A total of 221 patients with GB-NENs undergoing resection were enrolled in this retrospective study. Using the Cox regression analyses, age, pathological classification, tumor size, and SEER stage were identified as the independent prognostic factors of patients with GB-NENs undergoing resection, and nomograms were constructed. The C-indexes of OS and CSS in training dataset were 0.802 (95% CI: 0.757-0.848) and 0.846 (95% CI: 0.798-0.895), while those of internal validation dataset were 0.862 (95% CI: 0.802-0.922) and 0.879 (95% CI: 0.824-0.934), respectively. CONCLUSIONS: Taken together, the nomograms are accurate enough to predict the prognostic factors of GB-NEN patients undergoing resection, allowing for treatment decision-making and clinical monitoring for future clinical work.

Cardiovascular-Specific Mortality among Gastrointestinal Stromal Tumor Patients: A Population-Based Analysis.

Background: The overall risk of cardiovascular mortality (CVM) in cancer survivors has increased with time. The trend of CVM in patients with gastrointestinal stromal tumors (GISTs) remains unclear. This study is aimed at assessing the risks and independent predictors of CVM in GIST patients. Methods: Data of the GIST patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019). The standardized mortality ratio (SMR) was used to evaluate the risk of CVM, and a multivariate competing risk model was utilized to identify the predictors for CVM. Results: A total of 12,058 patients with GIST were included in this study, of whom 477 (4.0%) patients died of cardiovascular disease (CVD). The SMR for CVM among GIST patients was significantly higher than in the general population (SMR, 3.23, 95% CI: 2.97-3.52), and all categories of CVD were associated with a significantly elevated SMR. The cumulative mortality of CVD was the lowest among all causes of death, while the CVM was the second most common cause of death in patients ≥ 80 years when stratified by age at diagnosis. Furthermore, male sex, older age at diagnosis, White race, unmarried, earlier year of diagnosis, and not receiving chemotherapy were the poor prognostic factors for CVM. Conclusions: The CVM risk in GIST patients was significantly higher relative to the general US population. Timely screening and cardioprotective interventions should be implemented to prevent the occurrence of CVM in patients with GIST.

Clinicopathological characteristics of mixed neuroendocrine-non-neuroendocrine neoplasms in gastrointestinal tract.

BACKGROUND: In 2019, the World Health Organization (WHO) classification system updated the definition of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), previously known as mixed adenoneuroendocrine carcinomas (MANECs). The clinicopathological characteristics of this new definition remains to be clarified. METHODS: We analyzed the clinical data of 43 patients diagnosed with MiNENs in Wuhan Union Hospital from 2011 to 2020 according to the definition of MiNENs proposed in 2019. RESULTS: Among the 43 patients with MiNENs, the top two most common sites were stomach and colon, and 69.8% were males. Nearly half (21/43) of the patients were diagnosed at TNM stage III, and about 53.5% (23/43) of patients were the neuroendocrine neoplasm dominant type. Among the non-neuroendocrine tumor components of 43 MiNENs patients, adenocarcinoma accounted for 95.3% (41/43) and squamous cell carcinoma accounted for 4.7% (2/43)；95.3% (41/43) of the neuroendocrine neoplasm components were neuroendocrine carcinoma (NEC) and 4.7% (2/43) were neuroendocrine tumor (NET). Approximately 60.5% (26/43) neuroendocrine components had a Ki-67 index ≥ 55%. In addition, we further compared the prognosis of different subtypes of the MiNENs based on the neuroendocrine neoplasm component and non-neuroendocrine neoplasm component, and the results showed that there was no significant difference in survival between different subtypes of MiNENs (P > 0.05). CONCLUSIONS: MiNENs can exhibit diverse clinicopathological characteristics, and there is no significant difference in prognosis among MiNENs subtypes, indicating that the definition of MiNENs can well summarize the prognosis of this type of tumor.

The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation in Helicobacter pylori-associated gastritis by regulating ROS and autophagy.

BACKGROUND: The NLRP3 inflammasome activation is the molecular basis of Helicobacter pylori (Hp)-associated gastritis. Tripartite motif (TRIM) 31 is involved in diverse pathological events. However, whether TRIM31 plays a role in the activation of NLRP3 inflammasome in Hp infection is not clarified. METHODS: A mouse model of chronic Hp infection was established, and the gastric tissues were subjected to the polymerase chain reaction, western blotting, histopathological analysis, and RNA sequencing. The mitochondrial membrane potential and ROS in the human gastric epithelium GES-1 cells with or without Hp infection were measured by flow cytometry. GES-1 cells with or without TRIM31 knockdown were transfected with mCherry-EGFP-LC3 adenovirus. After rapamycin and bafilomycin A1 stimulation, autophagy flux in the above primed GES-1 cells was assessed by laser confocal microscope. Lysosomal acidification and expression levels of cathepsin B and cathepsin D in GES-1 cells with Hp infection were measured. RESULTS: NLRP3 inflammasome was activated in the gastric tissues of mice with chronic Hp infection in vivo and the GES-1 cells with Hp infection in vitro. TRIM31 was downregulated in Hp infection. TRIM31 negatively regulated the NLRP3 inflammasome activation. Enhanced ROS, impaired autophagy flux, and decreased expression of lysosomal cathepsin B and cathepsin D were observed in TRIM31-deficient GES-1 cells with Hp infection. In turn, inhibition of ROS led to the decreased expression of NLRP3 inflammasome. CONCLUSIONS: Together, our data identified that TRIM31 negatively regulated the activation of NLRP3 inflammasome in Hp-associated gastritis by affecting ROS and autophagy of gastric epithelial cells. Video abstract.

BMSCs Promote Differentiation of Enteric Neural Precursor Cells to Maintain Neuronal Homeostasis in Mice With Enteric Nerve Injury.

BACKGROUND & AIMS: Our previous study showed that transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) promoted functional enteric nerve regeneration in denervated mice but not through direct transdifferentiation. Homeostasis of the adult enteric nervous system (ENS) is maintained by enteric neural precursor cells (ENPCs). Whether ENPCs are a source of regenerated nerves in denervated mice remains unknown. METHODS: Genetically engineered mice were used as recipients, and ENPCs were traced during enteric nerve regeneration. The mice were treated with benzalkonium chloride to establish a denervation model and then transplanted with BMSCs 3 days later. After 28 days, the gastric motility and ENS regeneration were analyzed. The interaction between BMSCs and ENPCs in vitro was further assessed. RESULTS: Twenty-eight days after transplantation, gastric motility recovery (gastric emptying capacity, P < .01; gastric contractility, P < .01) and ENS regeneration (neurons, P < .01; glial cells, P < .001) were promoted in BMSCs transplantation groups compared with non-transplanted groups in denervated mice. More importantly, we found that ENPCs could differentiate into enteric neurons and glial cells in denervated mice after BMSCs transplantation, and the proportion of Nestin+/Ngfr+ cells differentiated into neurons was significantly higher than that of Nestin+ cells. A small number of BMSCs located in the myenteric plexus differentiated into glial cells. In vitro, glial cell-derived neurotrophic factor (GDNF) from BMSCs promotes the migration, proliferation, and differentiation of ENPCs. CONCLUSIONS: In the case of enteric nerve injury, ENPCs can differentiate into enteric neurons and glial cells to promote ENS repair and gastric motility recovery after BMSCs transplantation. BMSCs expressing GDNF enhance the migration, proliferation, and differentiation of ENPCs.

Artificial intelligence-based diagnosis of abnormalities in small-bowel capsule endoscopy.

BACKGROUND : Further development of deep learning-based artificial intelligence (AI) technology to automatically diagnose multiple abnormalities in small-bowel capsule endoscopy (SBCE) videos is necessary. We aimed to develop an AI model, to compare its diagnostic performance with doctors of different experience levels, and to further evaluate its auxiliary role for doctors in diagnosing multiple abnormalities in SBCE videos. METHODS : The AI model was trained using 280 426 images from 2565 patients, and the diagnostic performance was validated in 240 videos. RESULTS : The sensitivity of the AI model for red spots, inflammation, blood content, vascular lesions, protruding lesions, parasites, diverticulum, and normal variants was 97.8 %, 96.1 %, 96.1 %, 94.7 %, 95.6 %, 100 %, 100 %, and 96.4 %, respectively. The specificity was 86.0 %, 75.3 %, 87.3 %, 77.8 %, 67.7 %, 97.5 %, 91.2 %, and 81.3 %, respectively. The accuracy was 95.0 %, 88.8 %, 89.2 %, 79.2 %, 80.8 %, 97.5 %, 91.3 %, and 93.3 %, respectively. For junior doctors, the assistance of the AI model increased the overall accuracy from 85.5 % to 97.9 % (P  < 0.001, Bonferroni corrected), comparable to that of experts (96.6 %, P > 0.0125, Bonferroni corrected). CONCLUSIONS : This well-trained AI diagnostic model automatically diagnosed multiple small-bowel abnormalities simultaneously based on video-level recognition, with potential as an excellent auxiliary system for less-experienced endoscopists.

Analysis of AI image recognition approach for monitoring primary school students outdoor activity time in school / 中国学校卫生

Objective@#To develop a method that can continuously monitor duration of students outdoor activities for a long time, so as to provide data support for the relationship between outdoor activity duration and students health.@*Methods@#From April 28 to July 6, 2022, 1 168 students from a primary school in Shenzhen were selected. Fixed cameras were placed on the top of school classrooms, corridors and critical paths were used to identify student data and duration in the picture. And AI, cloud computing and other methods were used to measure students-non-classroom time instead of outdoor activity time in school.@*Results@#The average length of time spend on outdoor activities in school of the 24 pilot classes were 67.6-113.0 min, and showed a downward trend by grade ( F =42.74, P <0.05). The duration of outdoor activities among students was negatively correlated with the detection rate of myopia and overweight( r =-0.74, -0.45, P <0.05).@*Conclusion@#The data on outdoor activity time calculated by AI image recognition is basically in line with the reality. Monitoring students outdoor activity time at school through AI image recognition is feasible and popularized.

Risk of adenoma recurrence after polypectomy in patients younger than 50 years vs. 50 years old and over with diminutive or small adenomas.

Background and aims: Current studies have shown that polyp recurrence occurs after colonic adenomas polypectomy (AP), but the difference in recurrence risk between patients in patients older than 50 years and younger than 50 years has not been clearly studied. Methods: 490 patients after AP were enrolled in the study. The patients were classified according to age (<50 years old or ≥50 years old), and then further categorized according to the baseline adenoma characteristics: Group 1: 1-2 non-advanced adenomas (NAAs) 1-5 mm in size; Group 2: ≥3 NAAs, 1-5 mm; Group 3: 1-2 NAAs, 6-9 mm; Group 4: ≥3 NAAs, 6-9 mm; and Group 5: advanced adenomas. Results: During a mean follow-up interval of 2.52 years (2.51 years for ≥50 years old and 2.55 years for patients <50 years old), NAA recurrence was detected in 147 patients (30.0%). Overall, the hazard ratio (HR) for NAA recurrence after AP was higher in patients ≥50 years old than that in patients <50 years old (HR, 1.774, P = 0.003). For patients <50 years old, HRs (Group 2-5 vs. G1, respectively) for NAA recurrence were 0.744 (P = 0.773), 3.885 (P = 0.007), 5.337 (P = 0.003), and 3.334 (P = 0.015). For patients ≥50 years old, HRs (Group 2-5 vs. G1, respectively) for NAA recurrence were 1.033 (P = 0.965), 1.250 (P = 0.405), 2.252 (P = 0.015), and 1.887 (P = 0.009). For G1, the risk of NAA recurrence was significantly higher in patients ≥50 years old (HR, 2.932, P = 0.011) than that in patients <50 years old; for G2-G5, the risk was similar in the two age groups (P > 0.05). Conclusions: For patients <50 years old with less than 3 NAAs that are 1-5 mm in size, the recurrence rate of NAA is less than that of patients ≥50 years old with the same index colonoscopy findings. When the adenomas are ≥5 mm, or their number exceeds 3, they have similar recurrence risk as that for patients ≥50 years old.

The microRNA-520a-3p inhibits invasion and metastasis by targeting NF-kappaB signaling pathway in non-small cell lung cancer

Purpose: To identify the expression of miR-520a-3p and AKT1 in non-small cell lung cancer cells (NSCLC) and the mechanism in inhibiting cell invasion and metastasis by targeting NF-kappaB signaling pathway.Methods: Bioinformatics analysis and dual luciferase reporter gene assay were used to predict and verify the targeting relationship between miR-520a-3p and AKT1. EdU assay was used to detect the proliferation of NSCLC cells. Flow cytometry detected the apoptosis of NSCLC cells. Transwell assay tested the invasion ability of NSCLC cells. qRT-PCR measured the expression of miR-520a-3p and AKT1 mRNA in NSCLC cells; while western blotting was adopted to detect the protein expressions of AKT1, Ki67, CyclinD1, Bax, Bcl-2, MMP-2, MMP-9, NF-kB p65, IkBs kinase (IKK), NF-kB inducing kinase (NIK).Results: Bioinformatics analysis suggested that miR-520a-3p could target AKT1. miR-520a-3p could regulate the expression of AKT1 negatively. Compared to mimic-NC group, miR-520a-3p mimic group had increased expressions of miR-520a-3p and Bax, while decreased expressions of AKT1, Ki67, CyclinD1, Bcl-2, MMP-2, MMP-9, NF-kB p65, IKK and NIK, reduced cell proliferation, invasion, and increased cell apoptosis rate (all P < 0.05). Compared to inhibitor NC group, miR-520a-3p inhibitor group had decreased expressions of miR-520a-3p and Bax, but increased expressions of AKT1, Ki67, CyclinD1, Bcl-2, MMP-2, MMP-9, NF-kB p65, IKK and NIK, promoted cell proliferation, invasion, and suppressed cell apoptosis rate (all P < 0.05).Conclusion: Overexpression of miR-520a-3p can target and downregulate the expression of AKT1 to inhibit the invasion and metastasis of NSCLC via suppressing the activation of NF-kappaB signaling pathway. (AU)

High-quality genome assembly and pan-genome studies facilitate genetic discovery in mung bean and its improvement.

Mung bean is an economically important legume crop species that is used as a food, consumed as a vegetable, and used as an ingredient and even as a medicine. To explore the genomic diversity of mung bean, we assembled a high-quality reference genome (Vrad_JL7) that was ∼479.35 Mb in size, with a contig N50 length of 10.34 Mb. A total of 40,125 protein-coding genes were annotated, representing ∼96.9% of the genetic region. We also sequenced 217 accessions, mainly landraces and cultivars from China, and identified 2,229,343 high-quality single-nucleotide polymorphisms (SNPs). Population structure revealed that the Chinese accessions diverged into two groups and were distinct from non-Chinese lines. Genetic diversity analysis based on genomic data from 750 accessions in 23 countries supported the hypothesis that mung bean was first domesticated in south Asia and introduced to east Asia probably through the Silk Road. We constructed the first pan-genome of mung bean germplasm and assembled 287.73 Mb of non-reference sequences. Among the genes, 83.1% were core genes and 16.9% were variable. Presence/absence variation (PAV) events of nine genes involved in the regulation of the photoperiodic flowering pathway were identified as being under selection during the adaptation process to promote early flowering in the spring. Genome-wide association studies (GWASs) revealed 2,912 SNPs and 259 gene PAV events associated with 33 agronomic traits, including a SNP in the coding region of the SWEET10 homolog (jg24043) involved in crude starch content and a PAV event in a large fragment containing 11 genes for color-related traits. This high-quality reference genome and pan-genome will provide insights into mung bean breeding.