Endoscopic Combined Drainage of One Giant and Multiple Small Pancreatic Pseudocysts: A Case Report.

A pancreatic pseudocyst (PPC) is a frequent complication of pancreatitis, often stemming from alcohol, gallstones, or hyperlipidemia. Endoscopic treatment of PPC has become the mainstream treatment. A case of one giant and multiple small PPCs was observed, manifesting as repeated abdominal bloating, abdominal pain, nausea, and vomiting after meals. Initial computed tomography scans revealed the presence of multiple PPCs. Despite ineffective medical treatment, the pseudocysts progressively increased. In response, we conducted a combined endoscopic intervention, involving Hot AXIOS (Boston Scientific, Marlborough, MA) stenting through endoscopic ultrasound-guided transmural drainage (EUS-TMD) and the placement of the endoscopic nasopancreatic drainage (ENPD) mimic stent through endoscopic retrograde pancreatography (ERP). Remarkably, after nine months of postoperative follow-up, the patient had no discomfort symptoms and the cyst disappeared. We conducted a literature review on endoscopic combined drainage for PPCs, which is still controversial. Our presented case serves as a demonstration that endoscopic combined drainage can effectively and successfully manage giant and multiple PPCs.

CCDC58 is a potential biomarker for diagnosis, prognosis, immunity, and genomic heterogeneity in pan-cancer.

Coiled-coil domain-containing 58 (CCDC58) is a member of the CCDC protein family. Similar to other members, CCDC58 exhibits potential tumorigenic roles in a variety of malignancies. However, there is no systematic and comprehensive pan-cancer analysis to investigate the diagnosis, prognosis, immune infiltration, and other related functions of CCDC58. We used several online websites and databases, such as TCGA, GTEx, UALCAN, HPA, CancerSEA, BioGRID, GEPIA 2.0, TIMER 2.0, and TISIDB, to extract CCDC58 expression data and clinical data of patients in pan-cancer. Then, the relationship between CCDC58 expression and diagnosis, prognosis, genetic alterations, DNA methylation, genomic heterogeneity, and immune infiltration level were determined. In addition, the biological function of CCDC58 in liver hepatocellular carcinoma (LIHC) was investigated. Pan-cancer analysis results showed that CCDC58 was differentially expressed in most tumors and showed excellent performance in diagnosis and prediction of prognosis. The expression of CCDC58 was highly correlated with genetic alterations, DNA methylation, and genomic heterogeneity in some tumors. In addition, the correlation analysis of CCDC58 with the level of immune infiltration and immune checkpoint marker genes indicated that CCDC58 might affect the composition of the tumor immune microenvironment. Enrichment analysis showed that CCDC58-related genes were mainly linked to mitosis, chromosome, and cell cycle. Finally, biological function experiments demonstrated that CCDC58 plays an important role in tumor cell proliferation and migration. CCDC58 was first identified as a pan-cancer biomarker. It may be used as a potential therapeutic target to improve the prognosis of patients in the future.

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.

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.

Mitochondria-targeted cyclometalated iridium (III) complexes: Dual induction of A549 cells apoptosis and autophagy.

In this study, we synthesized 4 cyclometalated iridium complexes using N-(1,10-phenanthrolin-5-yl)picolinamide (PPA) as the main ligand, denoted as [Ir(ppy)2PPA]PF6 (ppy = 2-phenylpyridine, Ir1), [Ir(bzq)2PPA]PF6 (bzq = benzo[h]quinoline, Ir2), [Ir(dfppy)2PPA]PF6 (dfppy = 2-(3,5-difluorophenyl)pyridine, Ir3), and [Ir(thpy)2PPA]PF6 (thpy = 2-(thiophene-2-yl)pyridine, Ir4). Compared to cisplatin and oxaliplatin, all four complexes exhibited significant anti-tumor activity. Among them, Ir2 demonstrated higher cytotoxicity against A549 cells, with an IC50 value of 1.6 ± 0.2 µM. The experimental results indicated that Ir2 primarily localized in the mitochondria, inducing a large amount of reactive oxygen species (ROS) generation, that decreased in mitochondrial membrane potential (MMP), reduced ATP production, and further impaired mitochondrial function, leading to cytochrome c release. Additionally, Ir2 caused cell cycle arrest at the S phase and induced apoptosis through the AKT-mediated signaling pathway. Further investigations revealed that Ir2 could simultaneously induce both apoptosis and autophagy in A549 cells, with the latter acting as a non-protective mechanism that promoted cell death. More importantly, Ir2 exhibited low toxicity to both normal LO2 cells in vitro and zebrafish embryos in vivo. Consequently, these newly developed Ir(III) complexes show great potential in the development of novel and low-toxicity anticancer agents.

Identification and application of a candidate gene AhAftr1 for aflatoxin production resistance in peanut seed (Arachis hypogaea L.).

INTRODUCTION: Peanut is susceptible to infection of Aspergillus fungi and conducive to aflatoxin contamination, hence developing aflatoxin-resistant variety is highly meaningful. Identifying functional genes or loci conferring aflatoxin resistance and molecular diagnostic marker are crucial for peanut breeding. OBJECTIVES: This work aims to (1) identify candidate gene for aflatoxin production resistance, (2) reveal the related resistance mechanism, and (3) develop diagnostic marker for resistance breeding program. METHODS: Resistance to aflatoxin production in a recombined inbred line (RIL) population derived from a high-yielding variety Xuhua13 crossed with an aflatoxin-resistant genotype Zhonghua 6 was evaluated under artificial inoculation for three consecutive years. Both genetic linkage analysis and QTL-seq were conducted for QTL mapping. The candidate gene was further fine-mapped using a secondary segregation mapping population and validated by transgenic experiments. RNA-Seq analysis among resistant and susceptible RILs was used to reveal the resistance pathway for the candidate genes. RESULTS: The major effect QTL qAFTRA07.1 for aflatoxin production resistance was mapped to a 1.98 Mbp interval. A gene, AhAftr1 (Arachis hypogaea Aflatoxin resistance 1), was detected structure variation (SV) in leucine rich repeat (LRR) domain of its production, and involved in disease resistance response through the effector-triggered immunity (ETI) pathway. Transgenic plants with overexpression of AhAftr1(ZH6) exhibited 57.3% aflatoxin reduction compared to that of AhAftr1(XH13). A molecular diagnostic marker AFTR.Del.A07 was developed based on the SV. Thirty-six lines, with aflatoxin content decrease by over 77.67% compared to the susceptible control Zhonghua12 (ZH12), were identified from a panel of peanut germplasm accessions and breeding lines through using AFTR.Del.A07. CONCLUSION: Our findings would provide insights of aflatoxin production resistance mechanisms and laid meaningful foundation for further breeding programs.

Exploring the methylation status of CFTR and PKIA genes as potential biomarkers for lung adenocarcinoma.

BACKGROUND: One of the most prevalent cancers in the world is lung cancer, with adenocarcinoma (LUAD) making up a significant portion of cases. According to the National Cancer Institute (NCI), there are new cases and fatality rates per 100,000 individuals as follows: New instances of lung and bronchial cancer occur annually at a rate of 50.0 per 100,000 persons. The yearly death rate for men and women is 35.0 per 100,000. DNA methylation is one of the earliest discovered and widely studied epigenetic regulatory mechanisms, and its abnormality is closely related to the occurrence and development of cancer. However, the prognostic value of DNA methylation and LUAD needs to be further explored to improve the survival prediction of LUAD patients. METHODS: The transcriptome data and clinical data of LUAD were downloaded from TCGA and GEO databases, and the Illumina Human Methylation450 array (450k array) data were downloaded from the TCGA database. Firstly, the intersection of the expressed genes of the two databases is corrected, the differential analysis is performed, and the methylation data is evaluated by the MethylMix package to obtain differentially methylated genes. Independent prognostic genes were screened out using univariate and multivariate Cox regression analysis, and a methylation prognostic model was developed using univariate Cox analysis and validated with the GSE30219 dataset in the GEO database. Survival analysis between methylation high-risk and low-risk groups was performed and a methylation-based gene prognostic model was constructed. Finally, the prediction of potential drugs associated with the LUAD gene signature using Drug Sensitivity Genomics in Cancer (GDSC). RESULTS: In this study, a total of 555 samples from the TCGA database and 307 samples from GSE30219 were included, and a total of 24 differential methylation driver genes were identified. Univariate and multivariate Cox regression analyzes were used to screen out independent prognostic genes, involving 2 genes: CFTR, PKIA. Survival analysis was different between the methylation high-risk group and the low-risk group, the CFTR high methylation group and the low methylation group were poor, and the opposite was true for PKIA. CONCLUSIONS: Our study revealed that the methylation status of CFTR and PKIA can serve as potential prognostic biomarkers and therapeutic targets in lung cancer.

Infection of sheep by Echinococcus multilocularis in Gansu, China: evidence from mitochondrial and nuclear DNA analysis.

BACKGROUND: In the normal life cycle of the parasite (Echinococcus multilocularis) that causes alveolar echinococcosis, domestic and wild carnivores act as definitive hosts, and rodents act as intermediate hosts. The presented study contributes to the research on the distribution and transmission pattern of E. multilocularis in China having identified sheep as an unusual intermediate host taking part in the domestic transmission of alveolar echinococcosis in Gansu Province, China. METHODS: From 2020 to 2021, nine whitish different cyst-like were collected from the liver of sheep in Gansu Province for examination. A near complete mitochondrial (mt) genome and selected nuclear genes were amplified from the cyst-like lesion for identification. To confirm the status of the specimen, comparative analysis with reference sequences, phylogenetic analysis, and network analysis were performed. RESULTS: The isolates displayed ≥ 98.87% similarity to E. multilocularis NADH dehydrogenase sub-unit 1 (nad1) (894 bp) reference sequences deposited in GenBank. Furthermore, amplification of the nad4 and nad2 genes also confirmed all nine samples as E. multilocularis with > 99.30% similarity. Additionally, three nuclear genes, pepck (1545 bp), elp-exons VII and VIII (566 bp), and elp-exon IX (256 bp), were successfully amplified and sequenced for one of the isolates with 98.42% similarity, confirming the isolates were correctly identified as E. multilocularis. Network analysis also correctly placed the isolates with other E. multilocularis. CONCLUSIONS: As a result of the discovery of E. multilocularis in an unusual intermediate host, which is considered to have the highest zoonotic potential, the result clearly demonstrated the necessity for expanded surveillance in the area.

A ferroptosis-related ceRNA network in hepatocellular carcinoma for potential clinical applications.

OBJECTIVE: To explore the competing endogenous RNA (ceRNA) network related to ferroptosis in hepatocellular carcinoma (HCC) and its promise for clinical application. METHODS: We obtained RNA sequencing data for HCC and relevant clinical information from The Cancer Genome Atlas (TCGA) database. To assess the involvement of the autophagy, pyroptosis, and ferroptosis pathways in HCC, we used single-sample Gene Set Enrichment Analysis (ssGSEA) to compute scores for each sample based on pre-defined gene sets. We conducted Weighted Gene Co-Expression Network Analysis (WGCNA) to effectively modularize lncRNA, miRNA, and mRNA. Through extensive correlation analyses, we pinpointed the most crucial ferroptosis-associated modules. Moreover, we utilized online prediction tools to construct a corresponding ceRNA network. To establish the reliability of our results, we randomly chose a ceRNA axis consisting of DNAJC27-AS1/miR-23b-3p/PPIF for experimental validation. We performed luciferase reporter assays to validate the binding sites of DNAJC27-AS1, miR-23b-3p, and PPIF. RESULTS: We found a significant correlation between the level of ferroptosis and the overall survival of patients with HCC. Thus, we constructed a comprehensive ferroptosis-related ceRNA network. Our experimental findings revealed that DNAJC27-AS1 and PPIF act as direct sponges of miR-23b-3p, and thus are capable of downregulating ferroptosis in HCC cells. CONCLUSION: The ferroptosis-associated ceRNA network presented in this study represents a valuable resource for advancing our understanding of the role of ferroptosis in HCC.

Risk factors analysis of surgical complications of hepatic hemangioma: a modified Clavien-Dindo classification-based study.

PURPOSE: There are few studies on the risk factors of postoperative complications after surgical treatment of hepatic hemangioma (HH). This study aims to provide a more scientific reference for clinical treatment. METHODS: The clinical characteristics and operation data of HH patients undergoing surgical treatment in the First Affiliated Hospital of Air Force Medical University from January 2011 to December 2020 were retrospectively collected. All enrolled patients were divided into two groups based on the modified Clavien-Dindo classification: Major group (Grade II/III/IV/V) and Minor group (Grade I and no complications). Univariate and multivariate regression analysis was used to explore the risk factors for massive intraoperative blood loss (IBL) and postoperative Grade II and above complications. RESULTS: A total of 596 patients were enrolled, with a median age of 46.0 years (range, 22-75 years). Patients with Grade II/III/IV/V complications were included in the Major group (n = 119, 20%), and patients with Grade I and no complications were included in the Minor group (n = 477, 80%). The results of multivariate analysis of Grade II/III/IV/V complications showed that operative duration, IBL, and tumor size increased the risk of Grade II/III/IV/V complications. Conversely, serum creatinine (sCRE) decreased the risk. The results of multivariate analysis of IBL showed that tumor size, surgical method, and operative duration increased the risk of IBL. CONCLUSIONS: Operative duration, IBL, tumor size, and surgical method are independent risk factors that should be paid attention to in HH surgery. In addition, as an independent protective factor for HH surgery, sCRE should attract more attention from scholars.

Identification of a stable major sucrose-related QTL and diagnostic marker for flavor improvement in peanut.

KEY MESSAGE: An InDel marker closely linked with a major and stable quantitative trait locus (QTL) on chromosome A08, qSUCA08.2, controlling sucrose content will benefit peanut flavor improvement. Sucrose is the main soluble sugar in mature peanut kernel, and its content is a key determinant of flavor. However, the genetic basis of sucrose content in peanut remains poorly understood, which limits the progress of flavor improvement. In the present study, two genomic regions (qSUCA08a and qSUCB06a) for sucrose content on chromosomes A08 and B06 were identified by QTL-seq in a RIL population derived from a cross between Zhonghua 10 and ICG 12625. In the interval of qSUCB06a, QTL qSUCB06.2 was detected through QTL mapping in a single environment. The qSUCA08a was further dissected into 3 adjacent genomic regions using linkage analysis including a major QTL qSUCA08.2 explaining 5.43-17.84% phenotypic variation across five environments. A 61-bp insertion at position 35,099,320 in the higher sucrose parent ICG 12625 was found in qSUCA08.2. An InDel marker SUC.InDel.A08 based on the insertion/deletion polymorphism was developed and validated within a natural population containing 172 peanut cultivars in two environments. The mean sucrose content of 93 cultivars with ICG 12625 allele was significantly higher than that of 79 cultivars with Zhonghua 10 allele. The qSUCA08.2 corresponding to a 2.11 Mb interval harbored 110 genes. Among these genes, a total of 19 genes were considered as candidate genes including 5 non-synonymous mutation genes and 14 differentially expressed genes during seed development. These results provide new insights into the genetic basis of sucrose regulation in peanut and benefit the breeding program for developing new varieties with excellent flavor.

M2 tumor-associated macrophage mediates the maintenance of stemness to promote cisplatin resistance by secreting TGF-ß1 in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a deadly gastrointestinal malignancy, and chemotherapy resistance is a key factor leading to its poor prognosis. M2 tumor-associated macrophages (M2-TAMs) may be an important cause of chemoresistance in ESCC, but its exact mechanism is still unclear. METHODS: In order to study the role of M2-TAMs in ESCC chemoresistance, CCK-8, clone formation assay, flow cytometric apoptosis assay, qRT-PCR, western blotting, and serum-free sphere formation assays were used. In vivo animal experiments and human ESCC tissues were used to confirm the findings. RESULTS: In vitro and in vivo animal experiments, M2-TAMs reduced the sensitivity of ESCC cells to cisplatin. Mechanistically, M2-TAMs highly secreted TGF-ß1 which activated the TGFßR1-smad2/3 pathway to promote and maintain the stemness characteristic of ESCC cells, which could inhibit the sensitivity to cisplatin. Using TGFß signaling inhibitor SB431542 or knockdown of TGFßR1 could reverse the cisplatin resistance of ESCC cells. In 92 cases of human ESCC tissues, individuals with a high density of M2-TAMs had considerably higher levels of TGF-ß1. These patients also had worse prognoses and richer stemness markers. CONCLUSION: TGF-ß1 secreted from M2-TAMs promoted and maintained the stemness characteristic to induce cisplatin resistance in ESCC by activating the TGFß1-Smad2/3 pathway.

Reduced Adenoma Miss Rate With 9-Minute vs 6-Minute Withdrawal Times for Screening Colonoscopy: A Multicenter Randomized Tandem Trial.

INTRODUCTION: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR. METHODS: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367). The primary outcome was the lesion-level AMR. RESULTS: The intention-to-treat analysis revealed that 9MF significantly reduced the lesion-level (14.5% vs 36.6%, P < 0.001) and participant-level AMR (10.9% vs 25.9%, P < 0.001), advanced adenoma miss rate (AAMR, 5.3% vs 46.9%, P = 0.002), multiple adenomas miss rate (20.7% vs 56.5%, P = 0.01), and high-risk adenomas miss rate (14.6% vs 39.5%, P = 0.01) of 6MF without compromising detection efficiency ( P = 0.79). In addition, a lower false-negative rate for adenomas ( P = 0.002) and high-risk adenomas ( P < 0.05), and a lower rate of shortening surveillance schedule ( P < 0.001) were also found in 9MF, accompanying with an improved ADR in the 9-minute vs 6-minute m-WT (42.3% vs 33.5%, P = 0.02). The independent inverse association between m-WT and AMR remained significant even after adjusting ADR, and meanwhile, 9-minute m-WT was identified as an independent protector for AMR and AAMR. DISCUSSION: In addition to increasing ADR, 9-minute m-WT also significantly reduces the AMR and AAMR of screening colonoscopy without compromising detection efficiency.

Catalytic DNA-Assisted Mass Production of Arbitrary Single-Stranded DNA.

Synthetic single-stranded (ss) DNA is a cornerstone for life and materials science, yet the purity, quantity, length, and customizability of synthetic DNA are still limiting in various applications. Here, we present PECAN, paired-end cutting assisted by DNAzymes (DNA enzymes or deoxyribozymes), which enables mass production of ssDNA of arbitrary sequence (up to 7000 nucleotides, or nt) with single-base precision. At the core of PECAN technique are two newly identified classes of DNAzymes, each robustly self-hydrolyzing with minimal sequence requirement up- or down-stream of its cleavage site. Flanking the target ssDNA with a pair of such DNAzymes generates a precursor ssDNA amplifiable by pseudogene-recombinant bacteriophage, which subsequently releases the target ssDNA in large quantities after efficient auto-processing. PECAN produces ssDNA of virtually any terminal bases and compositions with >98.5 % purity at the milligram-to-gram scale. We demonstrate the feasibility of using PECAN ssDNA for RNA in situ detection, homology-directed genome editing, and DNA-based data storage.

Value of EUS in determining infiltration depth of early carcinoma and associated precancerous lesions in the upper gastrointestinal tract.

Objective: The objective is to evaluate the value of EUS in the determination of infiltration depth of early carcinoma and precancerous lesions in the upper gastrointestinal tract and to analyze the various factors affecting the accuracy of EUS. Methods: One hundred and sixty-three patients diagnosed with early gastric cancer or early esophageal cancer, and associated precancerous lesions, who were seen in our hospital in the recent 10 years were selected. These patients received EUS before endoscopic submucosal dissection or surgery. With a pathological diagnosis as the gold standard, the accuracy, sensitivity, specificity, and misjudgment rate of EUS in determining the invasion depth were evaluated using the pathological stratification (mucosa, M1/2; muscularis mucosa, M3; submucosa, [SM]; and muscularis propria) or TN stratification (mucosa, T1a; SM, T1b), and the possible causes of miscalculation were analyzed. Results: Based on the pathological stratification, the overall accuracy of EUS was 78.5%, and the overestimation and underestimation rates were 17.8% and 3.7%, respectively. Based on the TN stratification, the overall accuracy of EUS was 81%, and the overestimation and underestimation rates were 16.6% and 2.5%, respectively. There was a significant difference between the groups in terms of overestimation and underestimation rates (P < 0.05), indicating that EUS was more likely to overestimate the depth. Univariate analysis showed that the factors affecting accuracy included lesion size, macroscopic features, sunken mucosa, mucosa with granular and nodular changes, and ulceration. Multivariate logistic regression analysis revealed that larger lesions, mucosa with granular and nodular changes, and ulceration were independent risk factors for the overestimation of infiltration depth by EUS. Conclusion: EUS is highly accurate in determining the infiltration depth of early cancer and precancerous lesions in the upper gastrointestinal tract. It also has a good reference value for treatment selection and prognostication. However, attention should be paid to its overestimation, especially accompanied by the aforementioned factors.

Genetic dissection of fatty acid components in the Chinese peanut (Arachis hypogaea L.) mini-core collection under multi-environments.

Peanut (Arachis hypogaea L.) is an important source of edible oil and protein for human nutrition. The quality of peanut seed oil is mainly determined by the composition of fatty acids, especially the contents of oleic acid and linoleic acid. Improving the composition of fatty acids in the seed oil is one of the main objectives for peanut breeding globally. To uncover the genetic basis of fatty acids and broaden the genetic variation in future peanut breeding programs, this study used genome-wide association studies (GWAS) to identify loci associated with target traits and developed diagnostic marker. The contents of eight fatty acid components of the Chinese peanut mini-core collection were measured under four environments. Using the phenotypic information and over one hundred thousand single nucleotide polymorphisms (SNPs), GWAS were conducted to investigate the genetics basis of fatty acids under multi-environments. Overall, 75 SNPs were identified significant trait associations with fatty acid components. Nineteen associations were repeatedly identified in multiple environments, and 13 loci were co-associated with two or three traits. Three stable major associated loci were identified, including two loci for oleic acid and linoleic acid on chromosome A09 [mean phenotypic variation explained (PVE): 38.5%, 10.35%] and one for stearic acid on B06 (mean PVE: 23%). According to functional annotations, 21 putative candidate genes related to fatty acid biosynthesis were found underlying the three associations. The allelic effect of SNP A09-114690064 showed that the base variation was highly correlated with the phenotypic variation of oleic acid and linoleic acid contents, and a cost-effective Kompetitive allele-Specific PCR (KASP) diagnostic marker was developed. Furthermore, the SNP A09-114690064 was found to change the cis-element CAAT (-) in the promoter of ahFAD2A to YACT (+), leading dozens of times higher expression level. The enhancer-like activity of ahFAD2A promoter was identified that was valuable for enriching the regulation mechanism of ahFAD2A. This study improved our understanding on the genetic architecture of fatty acid components in peanut, and the new effective diagnostic marker would be useful for marker-assisted selection of high-oleic peanut breeding.

Feasibility of same-day discharge following endoscopic submucosal dissection for esophageal or gastric early cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an established technique for the treatment of early gastrointestinal neoplasia. Generally, multi-day (M-D) admission is required for patients undergoing ESD due to potential complications. AIM: To evaluate the feasibility of a same-day (S-D) discharge strategy for ESD of the esophagus or stomach. METHODS: The data of patients who underwent esophageal or gastric ESD were retrospectively collected from January 2018 to December 2021 at Peking University Cancer Hospital. The propensity score matching (PSM) method was applied to balance the unevenly distributed patient baseline characteristics between the S-D and M-D groups. Intraoperative and postoperative parameters were compared between the matched groups. RESULTS: Among the 479 patients reviewed, 470 patients, including 91 in the S-D group and 379 in the M-D group, fulfilled the inclusion and exclusion criteria. Following PSM, 78 patients in each group were paired using the 1:1 nearest available score match algorithm. No significant difference was found between groups with respect to intraoperative and postprocedural major adverse events (AEs). Tumor size, complete resection rate, and procedural duration were comparable between the groups. The S-D group demonstrated a significantly shorter length of hospital stay (P < 0.001) and lower overall medical expenses (P < 0.001) compared with the M-D group. CONCLUSION: The S-D discharge strategy may be feasible and effective for esophagogastric ESD, and the procedural-related AEs can be managed successfully.

A Novel Oxidative Phosphorylation-Associated Gene Signature for Prognosis Prediction in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common type of malignant tumor with high morbidity and mortality. The oxidative phosphorylation (OXPHOS) metabolic pathway produces adenosine triphosphate (ATP) by delivering electrons to transmembrane protein complexes in the mitochondria. This research was dedicated to identifying an OXPHOS-associated signature for the assessment of prognosis of HCC patients. A total of 371 HCC patients from the Cancer Genome Atlas (TCGA) and 231 HCC patients from the International Cancer Genome Consortium (ICGC) with RNA expression data and clinical data were employed as construction and validation cohorts, respectively. The least absolute shrinkage and selection operator (LASSO) Cox regression was applied to establish a multigene signature in the TCGA cohort, and the ICGC cohort was used for validation. The prognostic value of the risk signature was evaluated using univariate and multivariate Cox regression, Kaplan-Meier curves, and receiver operating characteristic (ROC) curves. The potential enrichment of biological functions was investigated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Meanwhile, we analyzed the correlation between the risk score and the tumor microenvironment (TME). A five-gene signature including ATP6V0B, ATP6V1C1, ATP6V1E1, TIMM9, and UQCRH was identified by LASSO Cox regression to classify patients into low- and high-risk groups. ROC curve analysis indicated that the five-gene signature is a prospective prognostic factor in HCC patients. Univariate and multivariate Cox regression analyses demonstrated that the risk score was an independent prognostic factor for overall survival (OS). Functional analysis showed that differentially expressed genes (DEGs) between the low- and high-risk groups were enriched in mitosis and the cell cycle pathway. In addition, the five-gene signature was associated with innate immune cell infiltration, immune subtypes, and tumor stemness. A novel OXPHOS-associated gene signature can be used for prognostic prediction for patients with HCC.

Optimized dual therapy for treatment-naive patients of Helicobacter pylori infection: A large-scale prospective, multicenter, open-label, randomized controlled study.

BACKGROUND: The efficacy and safety of high-dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies among the dual therapies are required to explore more suitable regimens. This study compared the efficacy, adverse events, and patient compliance of three different high-dose dual regimens in treatment-naive patients of Helicobacter pylori (H. pylori) infection. MATERIALS AND METHODS: The study was a prospective, multicenter, open-label, randomized controlled trial, including H. pylori-infected treatment-naive patients at 12 tertiary hospitals in China. The eligible subjects received high-dose AMX and esomeprazole (ESO) dual therapy of different regimens. They were randomly assigned to group A (ESO 20 mg plus AMX 750 mg, Qid for 14 days), group B (ESO 40 mg Bid plus AMX 1 g Tid for 14 days), or group C (ESO 20 mg plus AMX 1 g, Tid for 14 days). The eradication rates, adverse events, and patient compliance of the three groups were compared. RESULTS: Between April 2021 and January 2022, a total of 1080 subjects were screened and 945 were randomized. The eradication rates in groups A, B, and C were 88.6% (95% CI 84.5%-91.9%), 84.4% (95% CI 80.0%-88.3%), and 86.7% (95% CI 82.4%-90.2%; p = .315), respectively, based on intention-to-treat analysis; 90.3% (95% CI 86.4%-93.3%), 85.5% (95% CI 81.1%-89.2%), and 87.8% (95% CI 83.6%-91.2%; p = .197), respectively, according to modified intention-to-treat analysis; and 90.4% (95% CI 86.5%-93.5%), 85.8% (95% CI 81.4%-89.5%), and 88.3% (95% CI 84.1%-91.7%; p = .202) in per-protocol analysis. History of antibiotics use in 2 years reduced eradication effect in group B (ESO 40 mg Bid, AMX 1 g Tid). The modified intention-to-treat eradication rates were 81.4% vs 90.0% among those with or without a history of antibiotics use in group B (p = .031). The adverse event rates were 13.7%, 12.7%, and 12.1% in groups A, B, and C, respectively (p = .834). Patient compliance of the three groups was similar. CONCLUSIONS: Two optimized AMX and PPI dual regimens (ESO 40 mg Bid or 20 mg Tid plus AMX 1 g Tid for 14 days) had similar efficacy, safety and compliance as compared with classical dual regimen (ESO 20 mg plus AMX 750 mg Qid for 14 days) in H. pylori-infected treatment-naive patients.

Expression and distribution of MTNR1A in the hypothalamus-pituitary-gonadal axis of Tibetan sheep during the estrous cycle.

The melatonin 1A receptor (MTNR1A) is a membrane receptor distributed across the mammalian gonadal axis-associated membrane. Melatonin (MT) can specifically bind with MTNR1A on the cell membrane and regulates mammalian reproductive activities. However, the role of MTNR1A in regulating the reproductive physiological activities of sheep in the Tibetan Plateau remains unclear. In this study, the MT content in Tibetan sheep blood during the estrous cycle was detected by ELISA. The distribution of MTNR1A in the hypothalamus-pituitary-gonadal axis (HPGA) was analyzed by immunohistochemistry and immunofluorescence. Western blot and qRT-PCR were used to detect dynamic changes of MTNR1A mRNA and protein expression, and the protein distributions in the HPGA. The results showed that the average secretion level of MT in Tibetan sheep blood was highest occurred during diestrus and the lowest during proestrus. Additionally, the secretion of MT at night was significantly higher than during the day. The immunopositive products of MTNR1A were primarily distributed around the glial cells in the dorsal hypothalamic nucleus region, chromophobe cells, and eosinophilic cytoplasm in the pituitary gland, follicular granular layer, follicular adventitia, tubal mucosa, cilia, endometrium, interstices, and glands in the uterus. The expression trends of MTNR1A mRNA and proteins in the HPGA during the estrous cycle were the same. The relative expression levels of MTNR1A mRNA and proteins in the hypothalamus and ovaries were the highest during proestrus and the lowest during metestrus; the highest during diestrus in the pituitary and oviducts; the highest during metestrus in the uterus. Collectively, the differences in the secretion of MT in Tibetan sheep blood and the expression of MTNR1A in HPGA suggest that they may be affected by steroid hormone secretion during the estrous cycle of Tibetan sheep, which has a potential impact on the regulation of animal estrous cycle.