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BackgroundPolycystic ovary syndrome (PCOS) is defined by oligo/anovulation, hyperandrogenism, and polycystic ovaries with uncertain pathogenesis. The proteome represents a substantial source of therapeutic targets, and their coding genes may elucidate the mechanisms underlying PCOS. However, reports on the profiles of the human plasma protein-coding genes and PCOS are limited. Here, we aimed to investigate novel biomarkers or drug targets for PCOS by integrating genetics and the human plasma proteome.MethodsOur study acquired the protein quantitative trait loci from DECODE Genetics, offering 4,907 proteins in 35,559 individuals while obtaining PCOS summary statistics by accessing the FinnGen biobank (1,639 cases and 218,970 controls) and the genome-wide association study catalog (797 cases and 140,558 controls). Herein, we sequentially used two-sample Mendelian randomization (MR) analyses and colocalization to verify the causal link between candidate proteins, their coding genes, and PCOS. Further PCOS data download was conducted by accessing the Gene Expression Omnibus and Zenodo platforms. Gene expression level analysis, pathway enrichment analysis, immune cell infiltration, and transcription factor prediction were performed, aiming at detecting specific cell types with enriched expression and exploring potential optimized treatments for PCOS.ResultsMR analysis revealed 243 protein-coding genes with a causal relationship to PCOS risk, of which 12 were prioritized with the most significant evidence. Through colocalization analysis, three key genes, CUB domain-containing protein 1 (CDCP1), glutaredoxin 2 (GLRX2), and kirre-like nephrin family adhesion molecule 2 (KIRREL2), were identified. Subsequently, the three genes were strongly related to immune function and metabolism in terms of biological significance. In single-cell analysis, the expression levels of genes in ovarian theca cells were explored.ConclusionOverall, three protein-coding genes (CDCP1, GLRX2, and KIRREL2) may be related to a higher PCOS risk, suggesting that they may be entry points for exploration of PCOS pathogenesis and treatment, warranting further clinical investigations.

Background/Aims: Early-stage gastroesophageal junction (GEJ) adenocarcinoma can be challenging to diagnose and treat promptly using endoscopy. This study aims to summarize the endoscopic characteristics of early GEJ adenocarcinoma and investigate their correlation with pathological grade and invasion depth. Materials and Methods: This retrospective case series study evaluated patients with early GEJ adenocarcinoma who underwent endoscopic or surgical resection at First Affiliated Hospital of Dalian Medical University between January 2016 and December 2022. Results: A total of 71 patients were included in the analysis, with 59 males and a median age of 67 years. The majority of the lesions were located on the posterior side of the GEJ (40.8%) or the lesser curvature side (29.6%). Siewert II lesions accounted for 71.8% of cases, with most occurring on the posterior side (49.0%) and Siewert III lesions mostly occurring on the lesser curvature side (42.9%). Siewert I lesions accounted for only 7.0%, and all originated from Barrett mucosa. Paris classification of Is (P = .015) or IIc (P = .015), lesion size ≥12 mm (P = .017), red color with subsquamous extension (P = .038), and disordered microsurface with local fusion (P < .001) were independently and positively correlated with pathological grade and invasion depth by multivariable ordinal logistic regression. Conclusion: The posterior side and lesser curvature of the GEJ are the high-incidence sites of GEJ adenocarcinoma. Both forward and backward views during endoscopy should be combined to detect the lesion. Endoscopic characteristics such as Is or IIc morphology, larger size, red color with subsquamous extension, and disordered microsurface with local fusion may indicate a higher pathological grade and deeper invasion.

Abstract No fully validated risk-stratification strategies have been established in China where colonoscopies resources are limited. We aimed to develop and validate a fecal immunochemical test (FIT)-based risk-stratification model for colorectal neoplasia (CN); 10,164 individuals were recruited from 175 centers nationwide and were randomly allocated to the derivation (n = 6776) or validation cohort (n = 3388). Multivariate logistic analyses were performed to develop the National Colorectal Polyp Care (NCPC) score, which formed the risk-stratification model along with FIT. The NCPC score was developed from eight independent predicting factors and divided into three levels: low risk (LR 0–14), intermediate risk (IR 15–17), and high risk (HR 18–28). Individuals with IR or HR of NCPC score or FIT+ were classified as increased-risk individuals in the risk-stratification model and were recommended for colonoscopy. The IR/HR of NCPC score showed a higher prevalence of CNs (21.8%/32.8% vs. 11.0%, P

BackgroundFew studies showed that mixed type early gastric cancer (EGC) relates to higher risk of lymph node metastasis. We aimed to explore the clinicopathological feature of GC according to different proportions of undifferentiated components (PUC) and develop a nomogram to predict status of lymph node metastasis (LNM) in EGC lesions.MethodsClinicopathological data of the 4,375 patients who underwent surgically resection for gastric cancer in our center were retrospectively evaluated and finally 626 cases were included. We classified mixed type lesions into five groups (M1:0% 0.05).ConclusionPUC level should be considered as one of the predicting risk factors of LNM in EGC. A nomogram that predicts the risk of LNM in EGC was developed.

Background. Here we aimed to evaluate and compare the efficacy and safety between partial full-thickness myotomy and circular muscle myotomy during POEM procedure in achalasia patients. Methods. Clinical data of achalasia of cardia (AC) patients who underwent POEM in our center during January 2014 to January 2015 was collected (34 cases). 19 patients who received partial full-thickness myotomy were assigned to group A and 14 patients who received circular muscle myotomy were assigned to group B. The procedure-related parameters between the two groups were compared. Symptom relief rate and postprocedure manometry outcomes were compared to evaluate the efficacy. Procedure-related adverse events and complications were compared to evaluate the safety. Results. (1) Mean operation times were significantly shorter in group A than group B (62.42±23.17 vs 87.86±26.44 min, p0.05). (3) Comparison of procedure-related adverse events and complications had no statistical differences (all p>0.05). Conclusion. Partial full-thickness myotomy had no significant differences in efficacy or safety with circular myotomy, but partial full-thickness myotomy significantly reduced the procedure time.

The incidence of colorectal cancer (CRC) has been increasing in recent years. Thus, the discovery of factors that can assist in alleviating CRC is urgently warranted. Methods: To identify a potential factor involved in the development of CRC, we screened the upregulated genes in tumor tissues through four datasets from an online database. The expression of reticulocalbin 1 (RCN1), a Ca2+-binding protein, was upregulated in the four datasets. Based on loss-offunction experiments, the effect of RCN1 on cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. The regulatory effect of RCN1 on apoptosis was evaluated through Annexin V-fluorescein 5-isothiocyanate (FITC)/propidium iodide (PI) staining assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay in RKO and SW480 cells. Activation of endoplasmic reticulum (ER) stress signaling pathways was confirmed by estimating the phosphorylation and expression of PRKR-like ER kinase (PERK), inositol-requiring kinase-1 (IRE1), transcription factor 6 (ACT6), and CCAAT/enhancer-binding protein-homologous protein (CHOP). The intracellular Ca2+ homeostasis regulated by RCN1 was determined through the detection of Ca2+ concentration and mitochondrial membrane potential (MMP) measurement. Moreover, whether inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) was involved in the regulation of RCN1 in CRC was verified through the depletion of IP3R1 in RKO cells. Results: Knockdown of RCN1 reduced cell viability and facilitated apoptosis in RKO and SW480 cells. Phosphorylation of PERK and IRE1, activation of ATF6, and upregulation of CHOP were induced by the absence of RCN1, suggesting that the unfolded protein response (UPR) was activated in CRC cells. The concentration of Ca2+ in mitochondria was increased after RCN1 depletion, followed by reduction in the MMP and release of cytochrome c from mitochondria to the cytoplasm in RKO and SW480 cells. Moreover, it was demonstrated that IP3R1 mediates the effect of RCN1 on apoptosis induced by ER stress in CRC cells. The downregulation of IP3R1 restored the RCN1 loss-induced apoptosis and the increased Ca2+ concentration. Conclusion: Taken together, our results confirmed that silencing of RCN1 disrupted intracellular Ca2+ homeostasis and promoted cell apoptosis caused by TG-induced ER stress by regulating IP3R1 and activating the UPR signaling pathways. [ABSTRACT FROM AUTHOR]