Clinical manifestations, diagnosis and long-term prognosis of adult autoimmune enteropathy: Experience from Peking Union Medical College Hospital.

BACKGROUND: Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients. AIM: To improve overall understanding of this disease's diagnosis and prognosis. METHODS: We retrospectively analyzed the clinical, endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023, whose diagnosis was based on the 2007 diagnostic criteria. RESULTS: Diarrhea in AIE patients was characterized by secretory diarrhea. The common endoscopic manifestations were edema, villous blunting and mucosal hyperemia in the duodenum and ileum. Villous blunting (100%), deep crypt lymphocytic infiltration (67%), apoptotic bodies (50%), and mild intraepithelial lymphocytosis (69%) were observed in the duodenal biopsies. Moreover, there were other remarkable abnormalities, including reduced or absent goblet cells (duodenum 94%, ileum 62%), reduced or absent Paneth cells (duodenum 94%, ileum 69%) and neutrophil infiltration (duodenum 100%, ileum 69%). Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies. All patients received glucocorticoid therapy as the initial medication, of which 14/16 patients achieved a clinical response in 5 (IQR: 3-20) days. Immunosuppressants were administered to 9 patients with indications of steroid dependence (6/9), steroid refractory status (2/9), or intensified maintenance medication (1/9). During the median of 20.5 months of follow-up, 2 patients died from multiple organ failure, and 1 was diagnosed with non-Hodgkin's lymphoma. The cumulative relapse-free survival rates were 62.5%, 55.6% and 37.0% at 6 months, 12 months and 48 months, respectively. CONCLUSION: Certain histopathological findings, including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies, might be potential diagnostic criteria for adult AIE. The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications, which highlights the need for early diagnosis and novel medications.

Research advances in the molecular classification of gastric cancer.

Gastric cancer (GC) is a malignant tumor with one of the lowest five-year survival rates. Traditional first-line treatment regimens, such as platinum drugs, have limited therapeutic efficacy in treating advanced GC and significant side effects, greatly reducing patient quality of life. In contrast, trastuzumab and other immune checkpoint inhibitors, such as nivolumab and pembrolizumab, have demonstrated consistent and reliable efficacy in treating GC. Here, we discuss the intrinsic characteristics of GC from a molecular perspective and provide a comprehensive review of classification and treatment advances in the disease. Finally, we suggest several strategies based on the intrinsic molecular characteristics of GC to aid in overcoming clinical challenges in the development of precision medicine and improve patient prognosis.

Preoperative H. pylori Eradication Therapy Facilitates Precise Delineation in Early Gastric Cancer with Current H. pylori Infection.

INTRODUCTION: Early gastric cancer with current Helicobacter pylori infection (HpC-EGC) is common, but it is still unclear whether H. pylori eradication therapy (Hp-ET) or endoscopic submucosal dissection (ESD) should be performed first. We evaluated Hp-ETs short-term effects on horizontal boundary delineations of HpC-EGC in ESD. METHODS: Prospectively enrolled HpC-EGC patients were randomly assigned to eradication or control groups. Operation scopes of HpC-EGC lesions were delineated with marking dots at 5 mm out of the endoscopic demarcation line by an independent endoscopist, unaware of eradication status, before formal circumferential incision. As representatives, precise delineation rate, the shortest distance of all marking dots to the pathological demarcation line in all slices of one intact resected specimen (Dmin), and negative marking dot specimen rate were examined. RESULTS: Twenty-three HpC-EGC patients (25 lesions) were allocated to eradication group and 26 patients (27 lesions) were allocated to the control group with similar eradication success rates and all were differentiated type. With improving background mucosa inflammation after Hp-ET and similar gastritis-like epithelium rates, 10 lesions (40.0%) in the eradication group were of precise delineation compared to control group with 2 lesions (7.4%) (relative risk = 5.40, 95% CI 1.31-22.28). Dmin of eradication and control groups were 4.17 ± 2.52 mm and 2.67 ± 2.30 mm (p = 0.029), accompanied by 4 (14.8%) and none (0.0%) specimens that exhibited positive marking dots (p = 0.11), respectively. CONCLUSION: For HpC-EGC patients, administrating eradication medication before ESD is beneficial for the precise delineation of lesions and reducing the risk of positive horizontal resection margins.

A mutation-induced drug resistance database (MdrDB).

Mutation-induced drug resistance is a significant challenge to the clinical treatment of many diseases, as structural changes in proteins can diminish drug efficacy. Understanding how mutations affect protein-ligand binding affinities is crucial for developing new drugs and therapies. However, the lack of a large-scale and high-quality database has hindered the research progresses in this area. To address this issue, we have developed MdrDB, a database that integrates data from seven publicly available datasets, which is the largest database of its kind. By integrating information on drug sensitivity and cell line mutations from Genomics of Drug Sensitivity in Cancer and DepMap, MdrDB has substantially expanded the existing drug resistance data. MdrDB is comprised of 100,537 samples of 240 proteins (which encompass 5119 total PDB structures), 2503 mutations, and 440 drugs. Each sample brings together 3D structures of wild type and mutant protein-ligand complexes, binding affinity changes upon mutation (ΔΔG), and biochemical features. Experimental results with MdrDB demonstrate its effectiveness in significantly enhancing the performance of commonly used machine learning models when predicting ΔΔG in three standard benchmarking scenarios. In conclusion, MdrDB is a comprehensive database that can advance the understanding of mutation-induced drug resistance, and accelerate the discovery of novel chemicals.

Insights into the Oncogenic, Prognostic, and Immunological Role of BRIP1 in Pan-Cancer: A Comprehensive Data-Mining-Based Study.

Background: BRCA1 interacting helicase 1 (BRIP1), an ATP-dependent DNA helicase which belongs to an Iron-Sulfur (Fe-S) helicase cluster family with a DEAH domain, plays a key role in DNA damage and repair, Fanconi anemia, and development of several cancers including breast and ovarian cancer. However, its role in pan-cancer remains largely unknown. Methods: BRIP1 expression data of tumor and normal tissues were downloaded from the Cancer Genome Atlas, Genotype-Tissue Expression, and Human Protein Atlas databases. Correlation between BRIP1 and prognosis, genomic alterations, and copy number variation (CNV) as well as methylation in pan-cancer were further analyzed. Protein-protein interaction (PPI) and gene set enrichment and variation analysis (GSEA and GSVA) were performed to identify the potential pathways and functions of BRIP1. Besides, BRIP1 correlations with tumor microenvironment (TME), immune infiltration, immune-related genes, tumor mutation burden (TMB), microsatellite instability (MSI), and immunotherapy as well as antitumor drugs were explored in pan-cancer. Results: Differential analyses showed an increased expression of BRIP1 in 28 cancer types and its aberrant expression could be an indicator for prognosis in most cancers. Among the various mutation types of BRIP1 in pan-cancer, amplification was the most common type. BRIP1 expression had a significant correlation with CNV and DNA methylation in 23 tumor types and 16 tumor types, respectively. PPI, GSEA, and GSVA results validated the association between BRIP1 and DNA damage and repair, cell cycle, and metabolism. In addition, the expression of BRIP1 and its correlation with TME, immune-infiltrating cells, immune-related genes, TMB, and MSI as well as a variety of antitumor drugs and immunotherapy were confirmed. Conclusions: Our study indicates that BRIP1 plays an imperative role in the tumorigenesis and immunity of various tumors. It may not only serve as a diagnostic and prognostic biomarker but also can be a predictor for drug sensitivity and immunoreaction during antitumor treatment in pan-cancer.

Endoscopic mucosal resection using cold snare versus hot snare in treatment for 10-19 mm non-pedunculated colorectal polyps: protocol of a non-inferiority randomised controlled study.

INTRODUCTION: Cold polypectomy has the advantages of simple operation, less time-consuming and fewer complications. Guidelines have recommended cold snare polypectomy (CSP) to resect small polyps sized ≤5 mm and sessile polyps sized 6-9 mm. However, evidence is scarce regarding cold resection for non-pedunculated polyps sized ≥10 mm. Cold snare endoscopic mucosal resection (CS-EMR) combining CSP and submucosal injection was designed to improve the complete resection rate and reduce adverse events. We hypothesise that CS-EMR is non-inferior to conventional hot snare endoscopic mucosal resection (HS-EMR) in the resection of 10-19 mm non-pedunculated colorectal polyps. METHODS AND ANALYSIS: This study is a prospective, randomised, open-label, non-inferiority, single-centre trial. Outpatients scheduled to undergo a colonoscopy and present eligible polyps will be randomised to receive either CS-EMR or HS-EMR. The primary endpoint is the complete resection. Considering that HS-EMR of 10-19 mm colorectal polyps will yield a complete resection rate of at least 92% and a non-inferiority margin of -10%, a total of 232 polyps will be included (one-sided α, 2.5%; ß, 20%). The analyses are intended to evaluate first non-inferiority (lower limit 95% CI greater than -10% for group difference) and then superiority (lower limit 95% CI>0%) if non-inferiority is achieved. Secondary endpoints include en-bloc resection, the occurrence of adverse events, the use of endoscopic clips, resection time and cost. ETHICS AND DISSEMINATION: The study has been approved by the institutional review board of the Peking Union Medical College Hospital (No. K2203). All participants in the trial will provide written informed consent. The results of this trial will be published in an open-access way. TRIAL REGISTRATION NUMBER: NCT05545787.

Endoscopic ultrasound-guided tissue acquisition with or without rapid on-site evaluation for solid pancreatic lesions: five years of experience from a single center.

BACKGROUND: Endoscopic ultrasound (EUS)-guided tissue acquisition (TA) by EUS-guided fine needle aspiration (FNA) or fine needle biopsy (FNB) is a standard diagnostic procedure for solid pancreatic lesions. Whether rapid on-site evaluation (ROSE) should be used to support EUS-TA remains controversial. Here we assessed the diagnostic performance of EUS-TA with or without self-ROSE for solid pancreatic masses. METHODS: Three hundred and seventy EUS-TA cases with self-ROSE and 244 cases without ROSE were retrospectively enrolled between August 2018 and June 2022. All procedures including ROSE were performed by the attending endoscopist. Clinical data, EUS characteristics, and diagnostic performance for distinguishing benign from malignant solid pancreatic masses including accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared between groups. RESULTS: Self-ROSE improved the diagnostic accuracy of solid pancreatic lesions by 16.7% in the EUS-TA group (p < 0.001) and by 18.9% in the EUS-FNA alone group (p < 0.001). Self-ROSE also improved the diagnostic sensitivity by 18.6% in the EUS-TA group (p < 0.001) and by 21.2% in the EUS-FNA alone group (p < 0.001). Improvements in the diagnostic accuracy by self-ROSE in the EUS-FNB group were not significant. 2.2 ± 0.7, 2.4 ± 0.9, 2.3 ± 0.7, 2.5 ± 0.9, 2.1 ± 0.6, and 2.1 ± 0.7 needle passes were required in the EUS-TA, EUS-FNA, and EUS-FNB with or without self-ROSE groups, respectively. CONCLUSIONS: Self-ROSE significantly improved the accuracy and sensitivity of EUS-FNA alone and EUS-TA diagnosis of solid pancreatic lesions and helped to reduce needle passes during the procedure. Whether self-ROSE benefits EUS-FNB and whether EUS-FNB alone is comparable to EUS-FNA with self-ROSE require further clarification.

MetalProGNet: a structure-based deep graph model for metalloprotein-ligand interaction predictions.

Metalloproteins play indispensable roles in various biological processes ranging from reaction catalysis to free radical scavenging, and they are also pertinent to numerous pathologies including cancer, HIV infection, neurodegeneration, and inflammation. Discovery of high-affinity ligands for metalloproteins powers the treatment of these pathologies. Extensive efforts have been made to develop in silico approaches, such as molecular docking and machine learning (ML)-based models, for fast identification of ligands binding to heterogeneous proteins, but few of them have exclusively concentrated on metalloproteins. In this study, we first compiled the largest metalloprotein-ligand complex dataset containing 3079 high-quality structures, and systematically evaluated the scoring and docking powers of three competitive docking tools (i.e., PLANTS, AutoDock Vina and Glide SP) for metalloproteins. Then, a structure-based deep graph model called MetalProGNet was developed to predict metalloprotein-ligand interactions. In the model, the coordination interactions between metal ions and protein atoms and the interactions between metal ions and ligand atoms were explicitly modelled through graph convolution. The binding features were then predicted by the informative molecular binding vector learned from a noncovalent atom-atom interaction network. The evaluation on the internal metalloprotein test set, the independent ChEMBL dataset towards 22 different metalloproteins and the virtual screening dataset indicated that MetalProGNet outperformed various baselines. Finally, a noncovalent atom-atom interaction masking technique was employed to interpret MetalProGNet, and the learned knowledge accords with our understanding of physics.

A single-center experience on endoscopic ultrasonography-guided ethanol ablation of insulinomas.

BACKGROUND/OBJECTIVES: As the most frequent functional pancreatic neuroendocrine tumor, insulinomas may cause a plethora of symptoms and severe impairment in the living of patients by endogenous hyperinsulinemia and subsequent hypoglycemia. Surgery has been regarded as the first choice although a high risk of complications. Ethanol ablation is a promising non-surgical option that could achieve tumor shrinking in a short-term period. But the impact of symptom control and the long-term efficacy lack sufficient and good-quality evidence. METHODS: A total number of 14 endoscopic ultrasonography-guided ethanol ablations were performed in 9 patients between September 2016 and September 2018 in Peking Union Medical College Hospital. The data were collected and prospectively analyzed. RESULTS: The follow-up duration ranged from 21 to 1567 days in 9 patients, with a median of 994 days. 4 patients were free from relapse during a median follow-up of 1108 days (range: 994-1567 days). In 5 patients who suffered relapses, the median duration with symptom relief after the first ablation was 128 days (range: 13-393 days). If only repeated ablation was taken into consideration, the median duration with symptom relief was 26 days (range: 1-516 days). No complications happened during the procedures. The severe complication rate after the first ablation was 0.0% (0/9), compared to 7.14% (1/14) if each procedure was counted separately. The only severe complication documented was acute pancreatitis which was completely relieved after symptomatic treatment. CONCLUSIONS: For patients who are not suitable for surgical resections, endoscopic ultrasonography-guided ethanol ablation of insulinomas could be an effective and safe alternative to relieve symptoms of hypoglycemia.

Knockdown of GFAT disrupts chitin synthesis in Hyphantria cunea larvae.

Glutamine-fructose-6-phosphate transaminase (GFAT) has been reported to regulate the hexosamine biosynthetic pathway as the first rate-limiting enzyme. As a key enzyme that catalyzes the substrate of glycosylation modification, which has a wide-ranging effect on cellular functions. However, there are few studies on the relationship between GFAT and chitin metabolism in insects. In the present study, the GFAT gene from Hyphantria cunea was identified based on transcriptome and bioinformatic analysis. The role of HcGFAT in regulating development and chitin synthesis was analyzed by RNA interference (RNAi) in H. cunea larvae. The full-length HcGFAT gene (2028 bp) encodes a 676 amino acid (aa) polypeptide had typical structural features of the SIS and Gn_AT_II superfamily. Phylogenetic analyses showed that GFAT of H. cunea shares the highest homology and identity with GFAT of Ostrinia furnacalis. Expression profiles indicated that HcGFAT was expressed throughout larval, pupal and three tissues (midgut, fat body, epidermis), and highly expressed in the last instar of larvae and strongly expressed in epidermis among three tissues. Bioassay results showed that knockdown of HcGFAT repressed larval growth and development, resulting in a significant loss of larval body weight. Meanwhile, HcGFAT knockdown also significantly caused larval developmental deformity. Knockdown of HcGFAT regulated the expression of four other critical genes in the chitin synthesis pathway (HcGNA, HcPAGM, HcUAP, HcCHSA), and ultimately resulted in decreased chitin content in the epidermis. In summary, these findings indicated that GFAT plays a critical role in larval growth and development, as well as chitin synthesis in H. cunea.

Percutaneous aspiration and sclerotherapy of a giant simple hepatic cyst causing obstructive jaundice: A case report and review of literature.

BACKGROUND: Giant simple hepatic cysts causing intrahepatic duct dilatation and obstructive jaundice are uncommon. A variety of measures with different clinical efficacies and invasiveness have been developed. Nonsurgical management, such as percutaneous aspiration and sclerotherapy, is often applied. CASE SUMMARY: The case is a 39-year-old female with a 5-mo history of cutaneous and scleral icterus, loss of appetite, and dark urine. Lab tests showed jaundice and liver function abnormalities. Imaging revealed a giant simple hepatic cyst obstructing the intrahepatic bile ducts. A combination of percutaneous catheter aspiration and lauromacrogol sclerotherapy was successfully performed and the effects were satisfactory with the size of cyst decreasing from 13.7 cm × 13.1 cm to 3.0 cm × 3.0 cm. Further literature review presented the challenges of managing giant simple hepatic cysts that cause obstructive jaundice and compared the safety and efficacy of a combination of percutaneous aspiration and lauromacrogol sclerotherapy with other management strategies. CONCLUSION: Giant simple hepatic cysts can cause obstructive jaundice, and a combination of percutaneous catheter aspiration and sclerotherapy with lauromacrogol are suggested to treat such cases.

E74 knockdown represses larval development and chitin synthesis in Hyphantria cunea.

E74 is a key transcription factor induced by 20E, which plays a broad role in many physiological events during insect growth and development, including vitellogenesis, organ remodeling and new tissue formation, programmed cell death and metamorphosis. However, whether it is involved in regulating insect chitin biosynthesis remains largely unclear. Here, the E74 gene was identified for the first time from Hyphantria cunea, a notorious defoliator of forestry. Thereafter, the role of HcE74 in regulating growth, development and chitin synthesis in H. cunea larvae was evaluated. Bioinformatics analysis showed that HcE74 shared the highest identity (95.53%) with E74A of Spodoptera litura, which belonged to Ets superfamily. The results of RNAi bioassay showed that the larval mortality on 6 d after HcE74 knockdown was up to 51.11 ± 6.94%. Meanwhile, a distinct developmental deformity phenotype was found when HcE74 was silenced. These results indicated that HcE74 plays an important role in the development and molting of H. cunea larvae. Moreover, HcE74 knockdown also significantly decreased the expression of four key genes related to chitin synthesis, including glucose-6-phosphate isomerase (HcG6PI), UDP-N-acetylglucosamine pyrophosphorylase (HcUAP), chitin synthetase A (HcCHSA), and chitin synthetase B (HcCHSB). As a result, the content of chitin in midgut and epidermis decreased by 0.54- and 0.08-fold, respectively. Taken together, these results demonstrated that HcE74 not only plays a critical role in the growth and molting of H. cunea larvae, but also probably participates in the transcriptional regulation of genes involved in chitin biosynthesis.

Peripancreatic vascular involvement in patients with type 1 autoimmune pancreatitis.

Background: Type 1 autoimmune pancreatitis (AIP) is the pancreatic manifestation of IgG4-related disease. However, this benign disease can result in the peripancreatic vascular involvement (PVI) on occasion, which increases the difficulty of diagnosis and treatment of this clinical entity as well as for differentiating it from pancreatic malignancies. Methods: We retrospectively reviewed the information on demographics, clinical presentation, laboratory, imaging and endoscopic findings of 101 hospitalized patients with type 1 AIP treated in our department. All the patients were divided into non-PVI and PVI groups according to the first hospitalized medical data. Univariate and multivariate analyses were performed to analyse the potential predictive parameter(s) of PVI in AIP patients. Results: Among the 101 type 1 AIP patients, 52 (51.5%) exhibited PVI, with a male/female ratio 5.5:1. Their average age was 58.37±8.68 years old. Univariate analysis revealed that the location of pancreatitis lesions, including the pancreatic tail (P=0.010), the presence of splenomegaly (P=0.001) and the white blood cell (WBC) number in peripheral blood (P=0.020), were significantly associated with PVI. The location of pancreatitis lesions, including the pancreatic tail (P=0.023), and the presence of splenomegaly (P=0.010) were found to be independent predictors of the development of PVI by a multivariable regression analysis. A total of 18 out of 25 patients in PVI group who underwent corticosteroid treatment and no less than 6 months radiological follow-up showed improvement in vascular lesions, and no case exhibited exacerbation of PVI lesions during follow-up. Of 36 patients in non-PVI group who were followed up for no less than 6 months, only one case exhibited PVI. Conclusions: This retrospective study demonstrated that type 1 AIP was associated with a high proportion of PVI. Pancreatic tail involvement and splenomegaly may predict the PVI in type 1 AIP. PVI lesions are reversible in a subset of patients.

Metformin-induced AMPK activation suppresses larval growth and molting probably by disrupting 20E synthesis and glycometabolism in fall webworm, Hyphantria cunea Drury.

Metformin, considered to be a potent AMPK activator, is widely used for clinical therapy of cancer and diabetes due to its distinct function in regulating cell energy balance and body metabolism. However, the effect of metformin-induced AMPK activation on the growth and development of insects remains largely unknown. In the present study, we focused on the role of metformin in regulating the growth and development of Hyphantria cunea, a notorious defoliator in the forestry. Firstly, we obtained the complete coding sequences of HcAMPKα2, HcAMPKß1, HcAMPKγ2 from H. cunea, which encoded a protein of 512, 281, and 680 amino acids respectively. Furthermore, the phylogenetic analysis revealed that these three subunits were highly homologous with the AMPK subunits from other lepidopteran species. According to the bioassay, we found metformin remarkably restrained the growth and development of H. cunea larvae, and caused molting delayed and body weight reduced. In addition, expressions of HcAMPKα2, HcAMPKß1, and HcAMPKγ2 were upregulated 3.30-, 5.93- and 5.92-folds at 24 h after treatment, confirming that metformin activated AMPK signaling at the transcriptional level in H. cunea larvae. Conversely, the expressions of two vital Halloween genes (HcCYP306A1 and HcCYP314A1) in the 20E synthesis pathway were remarkably suppressed by metformin. Thus, we presumed that metformin delayed larval molting probably by impeding 20E synthesis in the H. cunea larvae. Finally, we found that metformin accelerated glycogen breakdown, elevated in vivo trehalose level, promoted chitin synthesis, and upregulated transcriptions of the genes in chitin synthesis pathway. Taken together, the findings provide a new insight into the molecular mechanisms by which AMPK regulates carbohydrate metabolism and chitin synthesis in insects.

Clip or Tattooing: A Comparative Study for Preoperative Colon Cancer Endoscopic Localization.

Background and Aim: Preoperative endoscopic markers have been extensively used for the localization of colonic neoplastic lesions in laparoscopic surgery. We conducted this respective cohort study to compare the localization accuracy of two commonly used endoscopic marker strategies (endoscopic clip plus abdominal plain film and endoscopic tattooing). Methods: Patients who received preoperative colonoscopy localization for colonic neoplasia and underwent an elective laparoscopic operation afterward between 2013 and 2020 were included in this retrospective study. The localization accuracy of the two endoscopic strategies was compared, and the predictors of successful endoscopic localization were identified by multivariate regression. Results: In total, 195 patients [average age 62.4 ± 9.2 years, 123 male (63.1%)] undergoing preoperative colonoscopy localization and subsequent laparoscopic colectomy for colonic neoplasms were included. Endoscopic localization was finally proven to be successful in 150 (76.9%) patients in the surgery. Compared to the tattooing group, patients who had successful localization for colonic lesions were fewer in the clip group (64 of 101 cases, 63.4% vs. 86 of 94 cases, 91.5%, p < 0.001). The multivariate regression analysis showed that the endoscopic tattooing strategy, endoscopic clip strategy, and lesion location were all predictors for successful localization (all with p < 0.001). Conclusion: Compared with endoscopic clip plus abdominal plain film, endoscopic tattooing had higher localization accuracy and less intraoperative colonoscopy counseling; the endoscopic clip strategy, tattooing strategy, and colonic lesion location were all predictors of successful endoscopic localization.

Endoscopic characteristics in predicting prognosis of biopsy-diagnosed gastric low-grade intraepithelial neoplasia.

BACKGROUND: Endoscopic biopsy can underestimate gastric malignancies as low-grade intraepithelial neoplasia (LGIN). Definitively diagnosed LGIN would progress. This study aimed to evaluate predictive factors to identify malignancies misdiagnosed as LGIN by biopsy and LGIN at high risk of progression. METHODS: The clinical records of patients diagnosed with gastric LGIN by endoscopic biopsy who underwent at least two endoscopies during the first year of follow-up between 2007 and 2017 were retrospectively collected. Three endoscopists reviewed photographs of the initial endoscopy, described lesion characteristics, and made endoscopic diagnoses. Logistic regression was used to analyze predictors to identify malignancies underestimated as LGIN. A receiver operating characteristic curve was used to evaluate the diagnostic accuracy of these predictors. Patient clinical outcomes of follow-up >1 year were collected. Kaplan-Meier estimates with log-rank tests and Cox proportional hazards regression were used to analyze predictors of progression. RESULTS: Overall, 48 of 182 (26.4%) patients were proven to have malignancies. A single lesion, a large lesion size, and marked intestinal metaplasia (IM) were independent predictors of initially misdiagnosed malignancies. The area under the curve of these predictors was 0.871, with a sensitivity of 68.7% and specificity of 92.5%. Twelve of 98 patients (12.2%) progressed during the 33-month median follow-up period. A whitish appearance, irregular margins, marked IM, and histological diagnosis of LGIN more than twice within the first year were predictors for progression. CONCLUSIONS: Lesions diagnosed as LGIN by biopsy with marked IM and other predictors above should be prudently treated for high potential to be malignancies or progress. Endoscopic follow-up with repeated biopsies within the first year is recommended.

3-Bromopyruvate-induced glycolysis inhibition impacts larval growth and development and carbohydrate homeostasis in fall webworm, Hyphantria cunea Drury.

As a typical glycolytic inhibitor, 3-bromopyruvate (3-BrPA) has been extensively studied in cancer therapy in recent decades. However, few studies focused on 3-BrPA in regulating the growth and development of insects, and the relationship and regulatory mechanism between glycolysis and chitin biosynthesis remain largely unknown. The Hyphantria cunea, named fall webworm, is a notorious defoliator, which caused a huge economic loss to agriculture and forestry. Here, we investigated the effects of 3-BrPA on the growth and development, glycolysis, carbohydrate homeostasis, as well as chitin synthesis in H. cunea larvae. To elucidate the action mechanism of 3-BrPA on H. cunea will provide a new insight for the control of this pest. The results showed that 3-BrPA dramatically restrained the growth and development of H. cunea larvae and resulted in larval lethality. Meanwhile, we confirmed that 3-BrPA caused a significant decrease in carbohydrate, adenosine triphosphate (ATP), pyruvic acid (PA), and triglyceride (TG) levels by inhibiting glycolysis in H. cunea larvae. Further studies indicated that 3-BrPA significantly affected the activities of hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), glucose 6-phosphate dehydrogenase (G6PDH) and trehalase, as well as expressions of the genes related to glycolysis, resulting in carbohydrate homeostasis disorder. Moreover, it was found that 3-BrPA enhanced 20-hydroxyecdysone (20E) signaling by upregulating HcCYP306A1 and HcCYP314A1, two critical genes in 20E synthesis pathway, and accelerated chitin synthesis by upregulating transcriptional levels of genes in the chitin synthesis pathway in H. cunea larvae. Taken together, our findings provide a novel insight into the mechanism of glycolytic inhibitor in regulating the growth and development of insects, and lay a foundation for the potential application of glycolytic inhibitors in pest control as well.

Predicting Malignancy of Biliary Stricture with a Nomogram in Patients with a Non-Malignant Endoscopic Tissue Diagnosis: A Retrospective Study.

PURPOSE: The accurate differentiation between benign and malignant biliary stricture is significant but challenging. Tissue diagnosis of biliary stricture by endoscopy sampling can provide excellent specificity but insufficient sensitivity. For patients with suspected malignant biliary stricture (MBS) but non-malignant was reported in endoscopy tissue samples, we constructed a nomogram to predict malignancy and improve the overall diagnostic performance. PATIENTS AND METHODS: 232 patients with suspected MBS and underwent endoscopy tissue sampling from January 2017 to December 2019 were included, among which 123 patients' endoscopy tissue samples were classified as non-malignant (including atypical, negative for malignancy, and nondiagnostic). Demographics, serum markers, radiological and sampling results of these 123 patients were collected to construct a nomogram using multivariate analysis. RESULTS: The nomogram was developed based on bilirubin, CA19-9, radiological result, and atypical sampling results and provided an AUC of 0.863 (95% CI 0.795-0.930) for predicting MBS. The specificity, sensitivity, and accuracy of endoscopy tissue diagnosis were 100.00%, 59.90%, and 68.53%, respectively. With the nomogram added, the overall diagnosis specificity, sensitivity, and accuracy were 95.24%, 89.20%, and 90.23%, respectively. CONCLUSION: The nomogram can predict malignancy in patients whose endoscopy tissue diagnoses were non-malignant. The overall diagnostic performance was improved with the nomogram added.

The role of EUS in diagnosing focal autoimmune pancreatitis and differentiating it from pancreatic cancer.

BACKGROUND AND OBJECTIVES: The clinical presentation of focal autoimmune pancreatitis (FAIP) and together with radiological overlap can mimic pancreatic cancer (PC). The aim of this study is to construct and validate a prediction model for differentiating FAIP from PC according to EUS characteristics. PATIENTS AND METHODS: Ninety patients with FAIP and 196 patients with PC, who consecutively underwent EUS at our center from January 2013 to December 2018, were retrospectively included in the study. The enrolled patients were randomly divided into either a derivation sample or a validation sample. According to EUS characteristics, multivariate stepwise logistic regression and receiver operating characteristics (ROC) analyses were used to construct a prediction model in derivation sample, and then, the efficacy was assessed in validation sample. RESULTS: EUS characteristics that were suggestive of FAIP included diffuse hypoechogenicity, hyperechoic foci/stands or lobularity (parenchymal heterogeneity), bile duct wall thickening and peripancreatic hypoechoic margin; and EUS features favoring PC included focal hypoechogenicity, absence of parenchymal heterogeneity, pancreatic duct dilation, and vessel involvement. The prediction model, with an area under the ROC curve of more than 0.95, had a good capability to distinguish FAIP from PC. By using the optimal cutoff value, the efficacy of model for diagnosing PC showed 83.7%-91.8% sensitivity and 93.3%-95.6% specificity. CONCLUSIONS: It is feasible to differentiate FAIP from PC based on EUS characteristics. The prediction model built in this study needs to be further confirmed by multicenter prospective researches.