CircVDAC3 sequesters microRNA-592 and elevates EIF4E3 expression to inhibit the progression of gastric cancer.

BACKGROUND: Accumulating evidence has shown that circular RNAs (circRNAs) are involved in gastric cancer (GC) tumorigenesis. However, specific functional circRNAs in GC remain to be discovered, and their underlying mechanisms remain to be elucidated. METHODS: CircRNAs that were differentially expressed between GC tissues and controls were analyzed using a circRNA microarray dataset. The expression of circVDAC3 in GC was determined using quantitative real-time PCR (qRT-PCR), and the structural features of circVDAC3 were validated. Cell function assays and animal experiments were conducted to explore the effects of circVDAC3 on GC. Finally, bioinformatics analysis, fluorescent in situ hybridization, and dual luciferase assays were used to analyze the downstream mechanisms of circVDAC3. RESULTS: Our results showed that circVDAC3 was downregulated in GC and inhibited the proliferation and metastasis of GC cells. Mechanistically, circVDAC3 acts as a competing endogenous RNA (ceRNA) of miR-592 and deregulates the repression of EIF4E3 by miR-592. EIF4E3 is downregulated in GC and overexpression of miR-592 or knockdown of EIF4E3 in circVDAC3-overexpressing cells weakens the anticancer effect of circVDAC3. CONCLUSION: Our study provides evidence that circVDAC3 affects the growth and metastasis of GC cells via the circVDAC3/miR-592/EIF4E3 axis. Our findings offer valuable insights into the mechanisms underlying GC tumorigenesis and suggest novel therapeutic strategies.

An Automated Video Analysis System for Retrospective Assessment and Real-Time Monitoring of Endoscopic Procedures (with Video).

BACKGROUND AND AIMS: Accurate recognition of endoscopic instruments facilitates quantitative evaluation and quality control of endoscopic procedures. However, no relevant research has been reported. In this study, we aimed to develop a computer-assisted system, EndoAdd, for automated endoscopic surgical video analysis based on our dataset of endoscopic instrument images. METHODS: Large training and validation datasets containing 45,143 images of 10 different endoscopic instruments and a test dataset of 18,375 images collected from several medical centers were used in this research. Annotated image frames were used to train the state-of-the-art object detection model, YOLO-v5, to identify the instruments. Based on the frame-level prediction results, we further developed a hidden Markov model to perform video analysis and generate heatmaps to summarize the videos. RESULTS: EndoAdd achieved high accuracy (>97%) on the test dataset for all 10 endoscopic instrument types. The mean average accuracy, precision, recall, and F1-score were 99.1%, 92.0%, 88.8%, and 89.3%, respectively. The area under the curve values exceeded 0.94 for all instrument types. Heatmaps of endoscopic procedures were generated for both retrospective and real-time analyses. CONCLUSIONS: We successfully developed an automated endoscopic video analysis system, EndoAdd, which supports retrospective assessment and real-time monitoring. It can be used for data analysis and quality control of endoscopic procedures in clinical practice.

A scoring system to predict the technical difficulty of endoscopic resection for cardial submucosal tumors.

BACKGROUND AND AIM: Endoscopic resection has been successfully used for the removal of digestive submucosal tumors (SMTs). However, the cardia has been considered a challenging location for endoscopic resection due to its narrow lumen and sharp angle. The objective of this study was to establish a clinical scoring model to grade the technical difficulty of endoscopic resection for cardial SMTs. METHODS: A total of 246 patients who suffered cardial SMTs and received endoscopic resection were included in this retrospective study. All of them were randomized into the training cohort (n = 123) or internal validation cohort (n = 123). Potential predictors were analyzed using univariate analysis. Then, covariates with P < 0.05 were selected for the multivariate logistic regression model. The ß coefficients from the logistic regression model were used to create a scoring system for technical difficulty prediction by rounding the score to the nearest integer of the absolute ß coefficient value. RESULTS: The clinical score consisted of the following factors: male gender (2 points), extraluminal growth (3 points), and maximum diameter ≥3 cm (3 points). The scoring model demonstrated good discriminatory power, with an area under the receiver operating characteristic curve of 0.860 and a 95% confidence interval of 0.763-0.958. The model also showed a good goodness of fit in the Hosmer-Lemeshow test (P = 0.979). In the training cohort, the probability of encountering technical difficulty in the easy (score = 0), intermediate (score = 1-3), difficult (score = 4-6), and very difficult (score >6) categories was 0, 6.8%, 33.3%, and 100.0%, respectively; similarly, in the validation cohort, it was 0, 5.6%, 22.2%, and 50.0%, respectively. CONCLUSIONS: This scoring system could serve as a valuable tool for clinicians in predicting the technical difficulty of endoscopic resection for cardial SMTs.

Identification and characterization of circadian clock genes in the head transcriptome of Conopomorpha sinensis Bradley.

Conopomorpha sinensis Bradley is the most detrimental pest to litchi and longan in China. Adult eclosion, locomotion, mating and oviposition of C. sinensis usually occur at night, regulated by a circadian rhythm. Nevertheless, our understanding of the linkages between adult circadian rhythms and clock genes remains inadequate. To address this gap, transcriptomic analysis was conducted on female and male heads (including antennae) of C. sinensis using the Illumina HiSeq 6000 platform to identify major circadian clock-related genes. The annotated sequences were analyzed by BLASTx, and candidate clock genes were classified based on conservation, predicted domain architectures, and phylogenetic analysis. The analysis revealed a higher conservation of these genes among the compared moths. Further, the expression profile analysis showed a significant spatiotemporal and circadian rhythmic accumulation of some clock genes during development. The candidate clock genes were predominantly expressed in the head, highlighting their crucial function in circadian rhythm regulation. Moreover, CsinPer, CsinTim1, and CsinCry1 displayed similar dynamic expressions with a peak expression level in the 4th age adults, suggesting their involvement in regulation of courtship and mating behaviors. The CsinPer and CsinTim1 mRNA oscillated strongly with a similar phase, containing a peak expression just before the female mating peak. This work will greatly contribute to understanding the circadian clock system of C. sinensis and provide valuable information for further studies of the molecular mechanisms involved in rhythmicity in fruit-boring pests.

HNF1A induces glioblastoma by upregulating EPS8 and activating PI3K/AKT signaling pathway.

Despite the exact biological role of HNF1 homolog A (HNF1A) in the regulatory mechanism of glioblastoma (GBM), the molecular mechanism, especially the downstream regulation as a transcription factor, remains to be further elucidated. Immunohistochemistry was used to detect the expression and clinical relevance of HNF1A in GBM patients. CCK8, TUNEL, and subcutaneous tumor formation in nude mice were used to evaluate the effect of HNF1A on GBM in vitro and in vivo. The correction between HNF1A and epidermal growth factor receptor pathway substrate 8 (EPS8) was illustrated by bioinformatics analysis and luciferase assay. Further mechanism was explored that the transcription factor HNF1A regulated the expression of EPS8 and downstream signaling pathways by directly binding to the promoter region of EPS8. Our comprehensive analysis of clinical samples in this study showed that upregulated expression of HNF1A was associated with poor survival in GBM patients. Further, we found that knockdown of HNF1A markedly suppressed the malignant phenotype of GBM cells in vivo and in vitro as well as promoted apoptosis of tumor cells, which was reversed by upregulation of HNF1A. Mechanistically, HNF1A could significantly activate PI3K/AKT signaling pathway by specifically binding to the promoter regions of EPS8. Moreover, overexpression of EPS8 was able to reverse the apoptosis of tumor cells caused by HNF1A knockdown, thereby exacerbating the GBM progression. Correctively, our study has clarified the explicit mechanism by which HNF1A promotes GBM malignancy and provides a new therapeutic target for further clinical application.

Long-term outcomes of endoscopic resection for well-differentiated nonampullary duodenal neuroendocrine tumors.

BACKGROUND & AIMS: Nonampullary duodenal neuroendocrine tumors (NAD-NETs) are rare with limited evidence regarding endoscopic treatment. The study aimed to investigate the efficacy and safety of endoscopic resection of well-differentiated NAD-NETs and evaluate long-term outcomes, including local recurrence and metastasis. METHODS: A total of 78 patients with NAD-NETs who underwent endoscopic resection between January 2011 and August 2022 were included. The clinicopathologic characteristics and treatment outcomes were collected and analyzed. RESULTS: En bloc resection was achieved for 74 of the tumors (94.9%) and R0 resection was obtained in 68 of the tumors (87.2%). Univariate analysis identified tumors in the second part of the duodenum, tumor size ≥ 10 mm and muscularis propria invasion as risk factors for non-curative resection. Two patients with R1 resection (vertical margin involvement) and two patients with lymphovascular invasion underwent additional surgery. Four patients experienced adverse events (5.1%), including two cases of delayed bleeding and two cases of perforation, all successfully managed conservatively. During a median follow-up period of 62.6 months, recurrence and lymph node metastasis were only detected in one patient with R1 resection 3 months after the original procedure. CONCLUSION: Endoscopic resection is safe and effective and provides a favorable long-term outcome for patients with well-differentiated NAD-NETs without regional lymph node or distant metastasis.

Endoscopic resection for calcifying fibrous tumors of the gastrointestinal tract.

BACKGROUND: Calcifying fibrous tumors (CFTs) are rare mesenchymal lesions that can occur in various sites throughout the body, including the tubular gastrointestinal (GI) tract. AIM: To analyze the clinical findings of 36 patients with GI tract CFTs to provide guidance for diagnosis and treatment. METHODS: This retrospective study included 36 patients diagnosed with CFTs of the GI tract. We collected demographic and clinical information and conducted regular follow-ups to assess for local recurrence. RESULTS: The stomach was the most commonly involved site, accounting for 72.2% of the 36 CFTs. Endoscopic mucosal resection (n = 1, 2.8%), endoscopic submucosal dissection (n = 14, 38.9%), endoscopic full-thickness resection (n = 16, 44.4%), and submucosal tunneling endoscopic resection (n = 5, 13.9%) were used to resect calcifying fibrous tumors. Overall, 34 (94.4%) CFTs underwent complete endoscopic resections with a mean procedure time of 39.8 ± 29.8 min. The average maximum diameter of the tumors was 10.6 ± 4.3 cm. No complications, such as bleeding or perforation, occurred during an average hospital stay of 2.9 ± 1.2 d. In addition, two patients developed new growth of CFTs near the primary tumor sites, and none of the patients developed distant metastases during the follow-up period. CONCLUSION: GI tract CFTs are rare and typically benign tumors that can be effectively managed with endoscopic procedures.

Endoscopic features and treatments of gastric cystica profunda.

BACKGROUND: Gastric cystica profunda (GCP) represents a rare condition characterized by cystic dilation of gastric glands within the mucosal and/or submucosal layers. GCP is often linked to, or may progress into, early gastric cancer (EGC). AIM: To provide a comprehensive evaluation of the endoscopic features of GCP while assessing the efficacy of endoscopic treatment, thereby offering guidance for diagnosis and treatment. METHODS: This retrospective study involved 104 patients with GCP who underwent endoscopic resection. Alongside demographic and clinical data, regular patient follow-ups were conducted to assess local recurrence. RESULTS: Among the 104 patients diagnosed with GCP who underwent endoscopic resection, 12.5% had a history of previous gastric procedures. The primary site predominantly affected was the cardia (38.5%, n = 40). GCP commonly exhibited intraluminal growth (99%), regular presentation (74.0%), and ulcerative mucosa (61.5%). The leading endoscopic feature was the mucosal lesion type (59.6%, n = 62). The average maximum diameter was 20.9 ± 15.3 mm, with mucosal involvement in 60.6% (n = 63). Procedures lasted 73.9 ± 57.5 min, achieving complete resection in 91.3% (n = 95). Recurrence (4.8%) was managed via either surgical intervention (n = 1) or through endoscopic resection (n = 4). Final pathology confirmed that 59.6% of GCP cases were associated with EGC. Univariate analysis indicated that elderly males were more susceptible to GCP associated with EGC. Conversely, multivariate analysis identified lesion morphology and endoscopic features as significant risk factors. Survival analysis demonstrated no statistically significant difference in recurrence between GCP with and without EGC (P = 0.72). CONCLUSION: The findings suggested that endoscopic resection might serve as an effective and minimally invasive treatment for GCP with or without EGC.

Regulation of cellulase production via calcium signaling in Trichoderma reesei under PEG8000 stress.

In this study, the effect of polyethylene glycol 8000 (PEG8000) stress on cellulase biosynthesis in Trichoderma reesei CICC2626 via calcium signaling was investigated, and a plausible mechanism by which intracellular Ca2+ regulates the transcription of cellulase genes was proposed. The results indicated that the total cellulase (filter paper-hydrolyzing activity [FPase]), endoglucanase (carboxymethyl cellulase activity [CMCase]), and ß-glucosidase activities of the strain were 1.3-, 1.2-, and 1.3-fold higher than those of the control (no PEG8000 addition) at a final concentration of 1.5% (w/v) PEG8000. Moreover, the transcriptional levels of cellulase genes, protein concentrations, and biomass increased. With the synergistic use of commercial cellulase and T. reesei CICC2626 cellulase to hydrolyze alkali-pretreated rice straw, the released reducing sugar concentration reached 372.7 mg/g, and the cellulose content (22.7%, 0.32 g) was significantly lower than the initial content (62.5%, 1.88 g). Transcriptome data showed that 12 lignocellulose degradation-related genes were significantly upregulated in the presence of 1.5% PEG8000. Furthermore, the addition of Ca2+ inhibitors and deletion of crz1 (calcineurin-responsive zinc finger 1-encoding gene, which is related to the calcium signaling pathway) demonstrated that calcium signaling plays a dominant role in PEG8000-induced cellulase genes overexpression. These results revealed a link between PEG8000 induction and calcium signaling transduction in T. reesei CICC2626. Moreover, this study also provides a novel inducer for enhanced cellulase production. KEY POINTS: • Cellulase biosynthesis in Trichoderma reesei could be enhanced by PEG8000 • PEG8000 could induce a cytosolic Ca2+ burst in Trichoderma reesei • The activated calcium signaling was involved in cellulase biosynthesis.

Establishment of a TaqMan probe-based qPCR assay for detecting microsporidia Enterospora epinepheli in grouper.

Enterospora epinepheli is an intranuclear microsporidian parasite causing serious emaciative disease in hatchery-bred juvenile groupers (Epinephelus spp.). Rapid and sensitive detection is urgently needed as its chronic infection tends to cause emaciation as well as white faeces syndrome and results in fry mortality. This study established a TaqMan probe-based real-time quantitative PCR assays targeting the small subunit rRNA (SSU) gene of E. epinepheli. The relationship between the standard curve of cycle threshold (Ct) and the logarithmic starting quantity (SQ) was determined as Ct = -3.177 lg (SQ) + 38.397. The correlation coefficient (R2 ) was 0.999, and the amplification efficiency was 106.4%. The detection limit of the TaqMan probe-based qPCR assay was 1.0 × 101 copies/µL and that is 100 times sensitive than the traditional PCR method. There is no cross-reaction with other aquatic microsporidia such as Ecytonucleospora hepatopenaei, Nucleospora hippocampi, Potaspora sp., Ameson portunus. The intra-assay and inter-assay showed great repeatability and reproducibility. In addition, the test of clinical samples showed that this assay effectively detected E. epinepheli in the grouper's intestine tissue. The established TaqMan qPCR assays will be a valuable diagnostic tool for the epidemiological investigation as well as prevention and control of E. epinepheli.

Endoscopic resection of giant esophageal subepithelial lesions: experience from a large tertiary center.

BACKGROUND AND AIMS: Increased reports on endoscopic resection (ER) of esophageal giant subepithelial lesions (g-SELs) have emerged in recent years. The aim of this study was to evaluate the efficacy, technical difficulty, and safety through our single-center experience. METHODS: Seventy-five patients with g-SELs undergoing endoscopic resection were included in the training set. Clinicopathologic features, procedure-related characteristics, postprocedural outcomes, and follow-up data were analyzed. A predictive nomogram model for procedural difficulty was proposed based on the multivariable logistic regression analysis. Internal and external validations were conducted to verify the model performance. RESULTS: The overall en bloc resection rate was 93.3%. Intraoperative and postoperative adverse events occurred in 7 (9.3%) and 13 (17.3%) patients, respectively. No recurrence or metastasis was observed. Thirty-two (42.7%) patients underwent a difficult procedure. Age (adjusted odds ratio [aOR], .915; P = .004), maximal tumor diameter ≥8 cm (aOR, 9.896; P = .009), irregular shape (aOR, 4.081; P = .053), extraluminal growth pattern (aOR, 5.419; P = .011), and submucosal tunneling endoscopic resection (aOR, .109; P = .042) were found to be statistically or clinically significant factors for predicting endoscopic resection difficulty, based on which a nomogram model was developed. Internal and external validations of the nomogram via receiver-operating characteristic curves and calibration curves achieved favorable results. CONCLUSIONS: Endoscopic resection serves as a promising therapeutic option for esophageal g-SELs. A younger patient age, large tumor size, irregular shape, and extraluminal growth may indicate increased endoscopic resection difficulty, whereas a submucosal tunneling endoscopic resection procedure tends to be of lower difficulty. Our nomogram model performs well for predicting endoscopic resection difficulty for esophageal g-SELs.

Feasibility and safety of endoscopic resection for the jejunoileal lesions.

BACKGROUND: Endoscopic resection (ER) for jejunoileal lesions (JILs) has been technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and safety of ER for JILs. METHOD: We retrospectively investigated 52 patients with JILs who underwent ER from January 2012 to February 2022. We collected and analyzed clinicopathological characteristics, procedure-related parameters, outcomes, and follow-up data. RESULTS: The mean age was 49.4 years. Of the 52 JILs, 33 ileal tumors within 20 cm from the ileocecal valve were resected with colonoscopy, while 19 tumors in the jejunum or the ileum over 20 cm from the ileocecal valve received enteroscopy resection. The mean procedure duration was 49.0 min. The en bloc resection and en bloc with R0 resection rates were 86.5% and 84.6%, respectively. Adverse events (AEs) included one (1.9%) major AE (delayed bleeding) and five (9.6%) minor AEs. During a median follow-up of 36.5 months, two patients had local recurrence (3.8%), while none had metastases. The 5-year recurrence-free survival (RFS) and disease-specific survival (DSS) were 92.9% and 94.1%, respectively. Compared with the enteroscopy group, overall AEs were significantly lower in the colonoscopy group (P < 0.05), but no statistical differences were observed in RFS (P = 0.412) and DSS (P = 0.579). There were no significant differences in AEs, RFS, and DSS between the endoscopic submucosal dissection (ESD) and the endoscopic mucosal resection (EMR) group. CONCLUSIONS: ER of JILs has favorable short-term and long-term outcomes. Both ESD and EMR can safely and effectively resect JILs in appropriately selected cases.

Endoscopic management of duodenal perforation caused by foreign bodies in adults: A retrospective study.

BACKGROUND AND AIMS: Duodenal perforation caused by foreign bodies (FBs) is very rare but is an urgent emergency that traditionally requires surgical intervention. Several case reports have reported the successful endoscopic removal of duodenal perforating FBs. Here we aimed to evaluate the safety and efficacy of endoscopic management of duodenal perforating FBs in adults. METHODS: Between October 2004 and October 2022, 12,851 patients with endoscopically diagnosed gastrointestinal FBs from four tertiary hospitals in China were retrospectively reviewed. Patients were enrolled if they were endoscopically and/or radiographically diagnosed with duodenal perforating FBs. RESULTS: The incidence of duodenal total FBs and perforating FBs was 1.9% and 0.3%, respectively. Thirty-four patients were enrolled. Endoscopic removal was achieved in 25 patients (73.5%), and nine patients (26.5%) received surgery. For the endoscopic group, most perforating FBs were located in the duodenal bulb (36.0%) and descending part (28.0%). The adverse events included 3 mucosal injuries and 1 localized peritonitis. All patients were cured after conventional treatment. In the surgical group, most FBs were lodged in the descending part (55.6%). One patient developed localized peritonitis and one patient died of multiple organ failure. The significant features of FBs requiring surgery included FB over 10 cm, both sides perforation, multiple perforating FBs and massive pus overflow. CONCLUSION: Endoscopic removal of duodenal perforating FBs is safe and effective, and can be the first choice of treatment for experienced endoscopists. Surgical intervention may be required for patients with FBs over 10 cm, both sides perforation, multiple perforating FBs, or severe infections.

Ginsenoside F2-Mediated Intestinal Microbiota and Its Metabolite Propionic Acid Positively Impact the Gut-Skin Axis in Atopic Dermatitis Mice.

Atopic dermatitis (AD) is a complex inflammatory skin disease induced by multiple factors. AD can also cause intestinal inflammation and disorders of the gut microbiota. Ginseng is a kind of edible and medicinal plant; its main active components are ginsenosides. Ginsenosides have a variety of anti-inflammatory effects and regulate the gut microbiota; however, their role in AD and the underlying mechanisms are unclear. In this study, we found that intragastric administration of ginsenoside F2 improved AD-like skin symptoms and reduced inflammatory cell infiltration, serum immunoglobulin E levels, and mRNA expression of inflammatory cytokines in AD mice. 16s rRNA sequencing analysis showed that ginsenoside F2 altered the intestinal microbiota structure and enriched the short-chain fatty acid-producing microbiota in AD mice. Metabolomic analysis revealed that ginsenoside F2 significantly increased the propionic acid (Pa) content of feces and serum in AD mice, which was positively correlated with significant enrichment of Parabacteroides goldsteinii and Lactobacillus plantarum in the intestines. Pa inhibits inflammatory responses in the gut and skin of AD mice through the G-protein-coupled receptor43/NF-κB pathway, thereby improving skin AD symptoms. These results revealed, for the first time, the mechanism by which ginsenoside F2 improves AD through the Pa (a metabolite of intestinal microbiota)-gut-skin axis.

Markov modeling and performance analysis of infectious diseases with asymptomatic patients.

After over three years of COVID-19, it has become clear that infectious diseases are difficult to eradicate, and humans remain vulnerable under their influence in a long period. The presence of presymptomatic and asymptomatic patients is a significant obstacle to preventing and eliminating infectious diseases. However, the long-term transmission of infectious diseases involving asymptomatic patients still remains unclear. To address this issue, this paper develops a novel Markov process for infectious diseases with asymptomatic patients by means of a continuous-time level-dependent quasi-birth-and-death (QBD) process. The model accurately captures the transmission of infectious diseases by specifying several key parameters (or factors). To analyze the role of asymptomatic and symptomatic patients in the infectious disease transmission process, a simple sufficient condition for the stability of the Markov process of infectious diseases is derived using the mean drift technique. Then, the stationary probability vector of the QBD process is obtained by using RG-factorizations. A method of using the stationary probability vector is provided to obtain important performance measures of the model. Finally, some numerical experiments are presented to demonstrate the model's feasibility through analyzing COVID-19 as an example. The impact of key parameters on the system performance evaluation and the infectious disease transmission process are analyzed. The methodology and results of this paper can provide theoretical and technical support for the scientific control of the long-term transmission of infectious diseases, and we believe that they can serve as a foundation for developing more general models of infectious disease transmission.

Association of M-Type Phospholipase A2 Receptor Deposition in Kidney Tissue with Treatment Outcomes in Patients with Idiopathic Membranous Nephropathy.

Objective: The purpose of this study was to investigate the correlation between the deposition of M-type phospholipase A2 receptor (PLA2R) in the kidney tissues of patients with idiopathic membranous nephropathy (IMN). Method: We enrolled a total of 61 patients diagnosed with IMN in the past 8 years who were admitted at the Jinjiang Municipal Hospital and the 2nd Affiliated Hospital of Fujian Medical University. PLA2R immunofluorescence was used to stain kidney tissues, and all patients were treated with steroid combined with immunosuppressive agents or conservative regimens. The duration of follow-up was more than 48 weeks. Based on the deposition of PLA2R in kidney tissues, we divided the patients into the PLA2R Positive group and the PLA2R Negative group. Further, patients with PLA2R-positive kidney tissues were divided into "1+", "2+", and "3+" groups based on the extent of their PLA2R deposition, and we compared the therapeutic outcomes of the various groups. Results: At week 12 of follow-up, the partial remission rate of kidney tissues in the PLA2R Negative group was significantly higher than that in the Positive group (P = 0.004). Among the various deposition groups with PLA2R-positive kidney tissues, the complete remission rate of the "2+" group was higher than that of the "3+" group at weeks 24, 36, and 48 of follow-up (P < 0.05). In IMN patients treated with a combination regimen of steroid and tacrolimus, the complete remission rate in kidney tissues of the PLA2R Negative group was higher than that of the Positive group at weeks 24 and 48 of follow-up (P < 0.05). Conclusion: The overall effective rate of treatment in kidney tissues of PLA2R-negative patients was higher than that in the kidney tissues of PLA2R-positive patients. The varied levels of PLA2R deposition in kidney tissues were related to the treatment outcomes of IMN, and those with lower PLA2R deposition levels had better outcomes.

Risk factors for complications and incomplete resection after endoscopic resection for duodenal submucosal tumors.

BACKGROUND AND AIM: Endoscopic resection (ER) has been used to remove submucosal tumors (SMTs) in recent years; however, duodenal ER is associated with high rates of immediate or delayed bleeding and perforation. Whether ER can be recommended for the treatment of duodenal SMTs remains controversial. Therefore, we aimed to investigate the clinical outcomes associated with the ER of duodenal SMTs and to assess possible predictive factors for complications and incomplete resection. METHODS: This retrospective study included 141 patients with duodenal SMTs. The therapeutic outcomes from ER and procedure-related complications were analyzed. RESULTS: Of the 141 patients, 78.7% achieved complete resection and nine (6.4%) developed complications. The multivariate analysis suggested that location near the duodenal papilla (P = 0.010) and diameter exceeding 15 mm (P = 0.091) of duodenal SMTs were independent risk factors for complications in ER. Besides, submucosal fibrosis (P = 0.042), location near the duodenal papilla (P = 0.049), and irregular morphology (P = 0.067) were independent risk factors for incomplete resection. CONCLUSIONS: ER can be recommended as an effective and minimally invasive treatment for duodenal SMTs.

Management of delayed bleeding of upper gastrointestinal endoscopic submucosal tunneling procedures: a retrospective single-center analysis and brief meta-analysis.

OBJECTIVES: Delayed bleeding is a rare but important major adverse event (mAE) after endoscopic submucosal tunneling procedures (ESTP), which is scarcely reported. We aimed to characterize the clinical characteristics of delayed bleeding and provide better management of this mAE. METHOD: From August 2010 to October 2022, we reviewed 3852 patients with achalasia receiving peroral endoscopic myotomy (POEM) and 1937 patients with upper gastrointestinal tumors receiving submucosal tunneling endoscopic resection (STER). Among these, records of 22 patients (15 POEM, 7 STER) with delayed bleeding were collected. Clinical characteristics, treatment, and outcomes of delayed bleeding were analyzed. RESULTS: The mean age was 43.6 years. Ten patients (45.5%) were intratunnel bleeding, seven (31.8%) were intratunnel bleeding accompanied by mucosal bleeding, and five (22.7%) were mucosal bleeding. The most common accompanied symptoms were hematemesis, fever, and melena. The most common accompanied mAEs were fistula, pulmonary inflammation, and pleural effusion with atelectasis. The mean duration from ESTP to endoscopic intervention was 5.3 ± 4.9 days. Active bleeding was identified in 21 patients (95.5%). The bleeding was successfully controlled by electrocoagulation (19 cases), endoscopic clipping (six cases), and Sengstaken-Blakemore tube insertion (three cases), and no patient required surgical intervention. The mean hemostatic procedure duration was 61.8 ± 45.8 min. The mean post-bleeding hospital stay was 10.0 ± 6.2 days. A brief meta-analysis of previous studies showed the pooled estimate delayed bleeding rate after POEM, STER, and G-POEM was 0.4%. CONCLUSIONS: Delayed bleeding is uncommon and could be effectively managed by timely emergency endoscopic procedures without requiring subsequent surgical interventions.

USP10 promotes the progression of triple-negative breast cancer by enhancing the stability of TCF4 protein.

Investigating the role of ubiquitin-specific peptidase 10 (USP10) in triple-negative breast cancer (TNBC). Analyzed USP10 expression levels in tumors using public databases. Detected USP10 mRNA and protein levels in cell lines. Examined USP10 expression in tumor tissues from breast cancer patients. Conducted USP10 knockdown experiments and analyzed changes in cell proliferation and metastasis. Confirmed protein-protein interactions with USP10 through mass spectrometry, Co-IP, and fluorescence experiments. Assessed impact of USP10 on transcription factor 4 (TCF4) ubiquitination and validated TCF4's influence on TNBC cells. We initially identified a pronounced overexpression of USP10 across multiple tumor types, including TNBC. Subsequently, we observed a conspicuous upregulation of USP10 expression levels in breast cancer cell lines compared to normal breast epithelial cells. However, upon subsequent depletion of USP10 within cellular contexts, we noted a substantial attenuation of malignant proliferation and metastatic potential in TNBC cells. In subsequent experimental analyses, we elucidated the physical interaction between USP10 and the transcription factor TCF4, whereby USP10 facilitated the deubiquitination modification of TCF4, consequently promoting its protein stability and contributing to the initiation and progression of TNBC. Collectively, this study demonstrates that USP10 facilitated the deubiquitination modification of TCF4, consequently promoting its protein stability and contributing to the initiation and progression of TNBC.

Nutrient content and resorption efficiency of leaves of broad-leaved trees along altitudes in Wuyi Mountains, China.

To reveal the variation of leaf nutrient utilization strategies with altitude gradient in subtropical mountain broadleaved trees, 44 species of broadleaved trees at different altitudes (1400, 1600 and 1800 m) in Wuyi Mountains were selected to measure nutrient content, stoichiometric ratio, and nutrient resorption efficiency of green and senescent leaves, and analyzed their allometric growth relationships. The results showed that nitrogen (N) and phosphorus (P) contents in green leaves were significantly higher than those in senescent leaves, which increased with the increases of altitude. The average values of phosphorus resorption efficiency (PRE) and nitrogen resorption efficiency (NRE) were 48.3% and 34.9%, respectively. PRE was significantly higher than NRE. There was no significant difference in nutrient resorption efficiency with altitude. NRE had positive isokinetic growth with and mature leaf N content at low altitude (1400 m) and negative allometry growth with senescent leaf N content at high altitude (1800 m). PRE and N and P contents of senescent leaves had negative isokinetic growth at low altitude (1400 m) and negative allometry growth at high altitudes (1600 and 1800 m). PRE-NRE allometric growth index was 0.95 at each altitude. The nutrient contents of green and senescent leaves increased with the increases of altitude, but altitude did not affect nutrient resorption efficiency. Plants preferred to re-absorbed P from senescent leaves. Nutrient resorption efficiency of leaves at high altitude affected the nutrient status of senescent leaves.