ABHD6 suppresses colorectal cancer progression via AKT signaling pathway.

Colorectal cancer (CRC) continues to be a prevalent malignancy, posing a significant risk to human health. The involvement of alpha/beta hydrolase domain 6 (ABHD6), a serine hydrolase family member, in CRC development was suggested by our analysis of clinical data. However, the role of ABHD6 in CRC remains unclear. This study seeks to elucidate the clinical relevance, biological function, and potential molecular mechanisms of ABHD6 in CRC. We investigated the role of ABHD6 in clinical settings, conducting proliferation, migration, and cell cycle assays. To determine the influence of ABHD6 expression levels on Oxaliplatin sensitivity, we also performed apoptosis assays. RNA sequencing and KEGG analysis were utilized to uncover the potential molecular mechanisms of ABHD6. Furthermore, we validated its expression levels using Western blot and reactive oxygen species (ROS) detection assays. Our results demonstrated that ABHD6 expression in CRC tissues was notably lower compared to adjacent normal tissues. This low expression correlated with a poorer prognosis for CRC patients. Moreover, ABHD6 overexpression impeded CRC cell proliferation and migration while inducing G0/G1 cell cycle arrest. In vivo experiments revealed that downregulation of ABHD6 resulted in an increase in tumor weight and volume. Mechanistically, ABHD6 overexpression inhibited the activation of the AKT signaling pathway and decreased ROS levels in CRC cells, suggesting the role of ABHD6 in CRC progression via the AKT signaling pathway. Our findings demonstrate that ABHD6 functions as a tumor suppressor, primarily by inhibiting the AKT signaling pathway. This role establishes ABHD6 as a promising prognostic biomarker and a potential therapeutic target for CRC patients.

Potential crosstalk between SPP1 + TAMs and CD8 + exhausted T cells promotes an immunosuppressive environment in gastric metastatic cancer.

BACKGROUND: Immunotherapy brings new hope to patients with advanced gastric cancer. However, liver metastases can reduce the efficacy of immunotherapy in patients. Tumor-associated macrophages (TAMs) may be the cause of this reduction in efficacy. SPP1 + TAMs are considered to have immunosuppressive properties. We aimed to investigate the involvement of SPP1 + TAMs in the metastasis of gastric cancer. METHODS: The single-cell transcriptome was combined with batched BULK datasets for analysis. Animal models were used to verify the analysis results. RESULTS: We reveal the interaction of SPP1 + TAMs with CD8 + exhausted T cells in metastatic cancer. Among these interactions, GDF15-TGFBR2 may play a key immunosuppressive role. We constructed an LR score to quantify interactions based on ligands and receptors. The LR score is highly correlated with various immune features and clinical molecular subtypes. The LR score may also guide the prediction of the efficacy of immunotherapy and prognosis. CONCLUSIONS: The crosstalk between SPP1 + TAMs and CD8 + exhausted T cells plays a key immunosuppressive role in the gastric metastatic cancer microenvironment.

Stomatin-like protein 2 promotes cell proliferation and survival under 5-Fluorouracil stress in hepatocellular carcinoma.

BACKGROUND: The crucial role of STOML2 in tumor progression has been documented recently in various cancers. Previous studies have shown that STOML2 promoted cancer cell proliferation, but the underlying mechanism is not fully illustrated. METHODS AND RESULTS: The expression and clinical relevance of STOML2 in pan-cancer was analyzed by TIMER2 web platform in pan-cancer. The prognostic significance of STOML2 in HCC was evaluated utilizing KM curve and a nomogram model. Signaling pathways associated with STOML2 expression were discovered by GSEA. CCK-8 assay was performed to evaluate the proliferative capacity of HCC cells after manipulating STOML2 expression. Flow cytometry was utilized to analyze cell cycle progression. Results indicated that increased STOML2 expression in HCC linked to unfavorable clinical outcomes. Cell cycle and cell division related terms were enriched under conditions of elevated STOML2 expression via GSEA analysis. A notable decrease in cell proliferation was observed in MHCC97H with STOML2 knocked-down, accompanied by G1-phase arrest, up-regulation of p21, down-regulation of CyclinD1 and its regulatory factor MYC, while STOML2 overexpression in Huh7 showed the opposite results. These results indicated that STOML2 was responsible for HCC proliferation by regulating the expression level of MYC/cyclin D1 and p21. Furthermore, an inverse correlation was found between STOML2 expression and 5-FU sensitivity. CONCLUSIONS: STOML2 promotes cell cycle progression in HCC which is associated with activation of MYC/CyclinD1/p21 pathway, and modulates the response of HCC to 5-FU.

A nomogram for prediction of ERCP success in patients with bile duct leaks: a multicenter study.

BACKGROUND: Bile duct leaks (BDLs) are serious complications that occurs after hepatobiliary surgery and trauma, leading to rapid clinical deterioration. Endoscopic retrograde cholangiopancreatography (ERCP) is the first-line treatment for BDLs, but it is not clear which patients will respond to this therapy and which patients will require additional surgical intervention. The aim of our study was to explore the predictors of successful ERCP for BDLs. METHODS: A retrospective analysis was conducted using data from six centers' databases. All consecutive patients who were clinically confirmed as BDLs were included in the study. Collected data were demographics, disease severity, and ERCP procedure characteristics. Univariate and multivariate analysis were used to select independent predictive factors that affect the outcome of ERCP for BDLs, and a nomogram was established. Calibration and ROC curves were used to evaluate the models. RESULTS: Four hundred and forty-eight consecutive patients were clinically confirmed as BDLs and 347 were excluded. In the 101 patients included patients, clinical success was achieved in 78 patients (77.2%). In logistic multivariable regression, two independent factors were negatively associated with the success of ERCP: SIRS (OR, 0.183; 95% CI 0.039-0.864; P = 0.032) and high-grade leak (OR 0.073; 95% CI 0.010-0.539; P = 0.010). Two independent factors were positively associated with the success of ERCP: leak-bridging drainage (OR 4.792; 95% CI 1.08-21.21; P = 0.039) and cystic duct leak (OR 6.193; 95% CI 1.03-37.17; P = 0.046). The prediction model with these four factors was evaluated using a receiver-operating characteristic (ROC) curve, which demonstrated an area under the curve of 0.9351. The calibration curve showed that the model had good predictive accuracy. CONCLUSION: Leak-bridging drainage and cystic duct leak are positive predictors for the success of ERCP, while SIRS and high-grade leak are negative predictors. This prediction model with nomogram has good predictive ability and practical clinical value, and may be helpful in clinical decision-making and prognostication.

The mediating and moderating effects of resilience on the relationship between sleep quality and psychological distress in Chinese women with infertility.

BACKGROUND: Research has widely indicated that the psychological distress experienced by infertile patients during fertility treatments may have a negative effect on the results of assisted reproduction. Although numerous studies have shown that psychological resilience and sleep quality are important influencing factors for psychological distress, the mediating mechanisms of psychological resilience in the relationship between sleep quality and psychological distress for Chinese women in particular remain unclear. Therefore, the current study investigates the association between sleep quality, resilience, and psychological distress in Chinese women with infertility and examines the mediating and moderating roles of resilience on the relationship between sleep quality and psychological distress. METHODS: In this cross-sectional study, a total of 595 women with infertility who were undergoing IVF-ET were recruited at the Reproductive Medicine, Shandong University, from April to November 2019. Participants were instructed to complete four questionnaires, including a questionnaire about socio-demographic and clinical-related information, the Pittsburgh Sleep Quality Index (PSQI), the 10-item Connor-Davidson Resilience Scale (CD-RISC-10), and the Kessler-10 (K10). Pearson's correlation analysis was conducted preliminarily to describe the relationships between sleep quality, resilience, and psychological distress. A mediation model and a moderated model were constructed and analyzed using the PROCESS macro for SPSS. The Johnson-Neyman (J-N) technique was then used to identify the regions of significance across the levels of moderator values. RESULTS: Patients in the sample had a high prevalence of psychological distress (48.6%, K10 scores > 22), and mediation analysis indicated that resilience played a partially mediating role in the relationship between sleep quality and psychological distress (indict effect = 0.072, P < 0.001). Moderation analysis indicated that resilience also moderated the association between sleep quality and psychological distress. CONCLUSIONS: Resilience may play a key role in the relationship between sleep quality and psychological distress. Our findings imply that resilience training may therefore be an effective component of psychological distress intervention in women with infertility.

Endoscopic segmentalized drainage of biliary tract obstruction complicated with duodenal stenosis.

Biliary obstruction is a common gastrointestinal disorder with many etiological factors, such as benign and malignant diseases of the biliary tract, pancreas, and liver. Endoscopic ultrasound guided biliary drainage provides a new method for the treatment of biliary obstruction when ERCP cannula fails.

Endoscopic treatment of postoperative intestinal stenosis combined with bilioenteric anastomotic stenosis.

Postoperative anastomotic stenosis is a common complication after biliary, pancreatic and gastrointestinal surgery, which may be caused by multiple factors such as tissue proliferation and cancer recurrence. Endoscopic therapy is often hampered when the lens is difficult to pass through. A patient with intestinal stricture complicated by bilioenterostomy stenosis was treated by superselection of guide wire and stent.

Endoscopic management of recurrent obstructive jaundice after EUS-guided biliary drainage.

EUS-GUIDED biliary drainage (EUS-BD) has recently gained widespread acceptance as a minimally invasive alternative method for biliary drainage. However, the risks of encountering recurrent biliary obstruction (RBO) after EUS-BD have increased due to the growing clinical experience of EUS-BD and prolonged prognosis of the underlying disease. Previous studies have shown that the incidence of RBO following EUS-BD ranges from 11% to 25%. Nevertheless, literature on the efficacy of reintervention of RBO after EUS-GUIDED hepaticogastrostomy (EUS-HGS) and case reports describing the procedural details of endoscopic reintervention following EUS-HGS are lacking.

Transduodenal accessory papillary Rendezvous technique assisted ERCP in the treatment of severe pancreatic duct stenosis caused by chronic pancreatitis in children.

Chronic pancreatitis in children is an irreversible inflammatory disease, which can cause intractable abdominal pain and abnormal internal and external secretion function of the pancreas, seriously affecting the growth and development of children and the quality of life. ERCP has become the first choice because of its good effect and less trauma. However, the severe stenosis of pancreatic duct caused by chronic pancreatitis may make ERCP more difficult. Here we used the rendezvous technique to assist ERCP to complete the treatment of severe pancreatic duct stenosis and abdominal pain.

EUS-guided bridging technique for treatment of biliary-enteric anastomotic stenosis after pancreaticoduodenectomy.

Biliary-enteric anastomotic stenosis is one of the main long-term complications after pancreaticoduodenectomy, with an incidence of 2%-8%. Although the relevant reports and studies are relatively few, the consequences such as biliary obstruction and refractory cholangitis seriously affect the quality of life of patients. In this case, the patient is not willing to receive conventional surgery again. This paper provides a bridge technique of EUS-guided Biliary Drainage (EUS-BD) to treat biliary-enteric anastomotic stenosis and solve the problem of obstructive jaundice in the patient.

External fistula internalization - Endoscopic ultrasound guided stent implantation between stomach and fistula in the treatment of refractory pancreatic cutaneous fistula.

Pancreatic cutaneous fistula is a complex condition, making it challenging to achieve favorable outcomes with conservative medical treatment. Surgical interventions often entail surgical risks and postoperative complications. Here, we present a case involving endoscopically guided stent placement between the stomach and the fistula. By internalizing the fistula, patients can potentially remove the external drainage tube, offering a novel endoscopic treatment approach for such cases.

A novel scoring system combining Modified Early Warning Score with biomarkers of monocyte distribution width, white blood cell counts, and neutrophil-to-lymphocyte ratio to improve early sepsis prediction in older adults.

OBJECTIVES: This study aims to investigate whether combining scoring systems with monocyte distribution width (MDW) improves early sepsis detection in older adults in the emergency department (ED). METHODS: In this prospective observational study, we enrolled older adults aged ≥60 years who presented with confirmed infectious diseases to the ED. Three scoring systems-namely quick sepsis-related organ failure assessment (qSOFA), Modified Early Warning Score (MEWS), and National Early Warning Score (NEWS), and biomarkers including MDW, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), were assessed in the ED. Logistic regression models were used to construct sepsis prediction models. RESULTS: After propensity score matching, we included 522 and 2088 patients with and without sepsis in our analysis from January 1, 2020, to September 30, 2021. NEWS ≥5 and MEWS ≥3 exhibited a moderate-to-high sensitivity and a low specificity for sepsis, whereas qSOFA score ≥2 demonstrated a low sensitivity and a high specificity. When combined with biomarkers, the NEWS-based, the MEWS-based, and the qSOFA-based models exhibited improved diagnostic accuracy for sepsis detection without CRP inclusion (c-statistics=0.842, 0.842, and 0.826, respectively). Of the three models, MEWS ≥3 with white blood cell (WBC) count ≥11 × 109/L, NLR ≥8, and MDW ≥20 demonstrated the highest diagnostic accuracy in all age subgroups (c-statistics=0.886, 0.825, and 0.822 in patients aged 60-74, 75-89, and 90-109 years, respectively). CONCLUSIONS: Our novel scoring system combining MEWS with WBC, NLR, and MDW effectively detected sepsis in older adults.

Critical Roles of Phosphoinositide 3-Kinase δ in the Humoral Immune Response to Trypanosoma congolense Infection.

PI3Kδ is critical in generating humoral and regulatory immune responses. In this study, we determined the impact of PI3Kδ in immunity to Trypanosoma congolense, an African trypanosome that can manipulate and evade Ab responses critical for protection. Upon infection with T. congolense, PI3KδD910A mice lacking PI3Kδ activity paradoxically show a transient enhancement in early control of parasitemia, associated with impaired production of regulatory IL-10 by B cells in the peritoneum. C57BL/6 wild-type (WT) mice treated with the PI3Kδ inhibitor (PI3Kδi) Idelalisib showed a similar transient decrease in parasitemia associated with reduced IL-10. Strikingly, however, we find that PI3KδD910A mice were ultimately unable to control this infection, resulting in uncontrolled parasitemia and death within 2 wk. Assessment of humoral responses revealed delayed B cell activation, impaired germinal center responses, and compromised Ab responses to differing degrees in PI3KδD910A and PI3Kδi-treated mice. To test the role of Abs, we administered serum from WT mice to PI3KδD910A mice and found that lethality was prevented by postinfection serum. Interestingly, serum from naive WT mice provided partial protection to PI3KδD910A mutants, indicating an additional role for natural Abs. Together our findings suggest that although PI3Kδ drives immune regulatory responses that antagonize early control of parasite growth in the peritoneum, it is also required for generation of Abs that are critical for protection from systemic trypanosome infection. The essential role of PI3Kδ for host survival of African trypanosome infection contrasts with findings for other pathogens such as Leishmania, underlining the critical importance of PI3Kδ-dependent humoral immunity in this disease.

Effects of morphine and P2Y inhibitor amongst patients with acute coronary syndrome: A meta-analysis of comparative studies.

BACKGROUND: P2Y inhibitor and morphine are widely used in caring for patients with the acute coronary syndrome (ACS), but there are some concerns about the combination use due to interaction in metabolism. Therefore, this study aimed to examine whether using morphine with antiplatelets in patients with ACS affects the clinical outcomes based on currently available evidence. METHODS: Three databases were searched for comparative studies on this topic by using relevant keywords of ACS and morphine. Two authors independently extracted study information, mortality, major adverse cardiac event (MACE), major bleeding, and length of hospital stay. Then, they evaluated the quality of evidence independently. Meta-analysis was planned to be conducted in random-effects model. Risk ratio (RR) was used for most outcomes except hospital stay, and Peto odds ratio (POR) was used if there were any zero cells. Pooled estimate was presented with 95% confidence interval (CI). RESULTS: Fourteen studies (n = 73,033) met eligibility criteria, and there was non-significant difference in mortality between antiplatelet with and without morphine (RR = 1.13, 95%CI: 0.78 to 1.64). Antiplatelet therapy without morphine significantly reduced the risk of MACE (RR = 0.78, 95%CI: 0.67 to 0.89; I-square = 0%), but increased the odds of major bleeding (POR = 1.87, 95%CI: 1.04 to 3.35; I-square = 0%) as compared with the combined use of antiplatelet therapy and morphine. CONCLUSION: In conclusion, there is no statistically significant difference in mortality in patients with ACS using morphine or not, but clinicians ought to make a trade-off between a lower risk of MACE and a higher risk of major bleeding before adding morphine to antiplatelet therapy.

Two-step approach for recurrent pancreatic pseudocysts: endoscopic ring drainage of the stent transpapillary combined with the posterior gastric wall.

Pancreatic pseudocyst is a complication of pancreatitis, with an incidence of about 5-16% and a incidence of about 20-40% in chronic pancreatitis. There are various ways to treat pancreatic pseudocysts, but the recurrence rate of cysts is as high as 23.9%. There are not many clinical options for the treatment of recurrent pseudocysts, and there is still a high recurrence of pseudocysts after EUS guided drainage alone. We present here a promising endoscopic treatment for patients with recurrent pancreatic pseudocyst.

EUS-guided Rendezvous technique for the treatment of choledocholithiasis with difficult cannulation.

It is not uncommon to encounter difficult cannulation during endoscopic retrograde cholangiopancreatography (ERCP), most of which can be performed by double-guide wire, pre-cut and other techniques. Endoscopic ultrasound-guided biliary drainage (EUS-BD) can be used as a remedial solution for ERCP failure. This article provides a very well experience in ERCP combine with EUS-RV technique in cases where the duodenal papilla is located above the medial diverticulum. At the same time, some skills of EUS-RV are provided for endoscopists.

A whole new challenge: EUS-guided transhepatic antegrade stone removal (TASR) for the treatment of multiple choledocholithiasis after total gastrectomy.

EUS-TASR is a derivative of EUS-BD and serves as a remedy when ERCP fails. EUS-BD technology is commonly used in the diagnosis and treatment of biliary tract and pancreatic diseases with anatomical changes of the digestive tract. This article provides an experience of EUS-TASR and a new challenge in the treatment of common bile duct stones after total gastrectomy.

The combination of eyeMax direct visualization system, EUS and ERCP for the precise treatment of intraductal papillary mucinous neoplasm.

Intraductal papillary mucinous neoplasm (IPMN) accounted for 5.0%~7.5% of pancreatic tumors and 21%~33% of cystic tumors. It usually occurs in people aged 60 to 70. The main treatment is surgical excision. The operation method is different according to the location of lesion, so we try our best to achieve accurate treatment. Here, we provide endoscopic ultrasonography combined with ERCP and eyeMax three endoscopic systems, so as to achieve accurate treatment of IPMN, which is recommended to the majority of endoscopists.

Thromboembolic Presentations among Patients Hospitalized to the Intensive Care Unit for Coronavirus Disease 2019 (COVID-19) - A Northern Taiwan Single Center Experience.

Coronavirus Disease 2019 (COVID-19) has been associated with a high thromboembolic risk among patients in intensive care units. Asian populations may share a similar thromboembolic risk, but with a higher prevalence of arterial thromboembolism than venous thromboembolism. To clarify this risk in Taiwan, this single-center retrospective study collected 27 consecutive intensive care unit patients with COVID-19 confirmed by polymerase chain reaction, with a median age of 67.6 years (male 81.5%). Twenty-three patients received prophylactic anticoagulation (85.2%), and there were four bleeding events (14.8%). Nine patients had thromboembolism (33.3%), including three with deep vein thrombosis, two with peripheral artery thromboembolism, and four with ischemic stroke. There were no significant clinical differences between the patients with or without thromboembolism. Initial serum ferritin [adjusted odds ratio (OR): 13.19, 95% confidence interval (CI): 1.01-172.07] and peak serum procalcitonin (adjusted OR: 18.93, 95% CI: 1.08-330.91) were associated with a higher risk of thromboembolism. Furthermore, prophylactic anticoagulation (adjusted OR: 0.01, 95% CI: < 0.001-0.55) was associated with a lower risk of thromboembolism. All cases of deep vein thrombosis and one peripheral artery thromboembolism occurred at intravascular catheter locations. No association between thromboembolism and survival was found (age-adjusted hazard ratio: 0.55, 95% CI: 0.10-2.95). In conclusion, the prevalence of COVID-19 thromboembolism among Taiwanese patients in intensive care units was high, even with prophylactic anticoagulation. Serum ferritin and procalcitonin may identify high-risk populations. Prophylactic anticoagulation may reduce the risk of thromboembolism with a manageable bleeding risk. Larger prospective studies are needed to clarify the risk of COVID-19 thromboembolism and its risk factors in the post-Omicron era.

Diagnostic test accuracy of pretreatment collateral score in predicting stroke outcomes after intra-arterial endovascular thrombectomy: a meta-analysis in DSA and CTA.

OBJECTIVES: This study compared the diagnostic accuracy of pretreatment circulation collateral scoring (CS) system using digital subtraction angiography (DSA) and computed tomography angiography (CTA) in predicting favorable functional outcome (FFO) after intra-arterial endovascular thrombectomy (IA-EVT). Subgroup analysis characterizing scoring systems within each category was additionally conducted. MATERIALS AND METHODS: We performed a diagnostic meta-analysis to assess the sensitivity and specificity of each CS system by using DSA and CTA, respectively. The hierarchical summary receiver operating characteristic curve (HSROC) models were used to estimate the diagnostic odds ratio (DOR) and area under the curve (AUC). The Bayes theorem was employed to determine posttest probability (PTP). RESULTS: In total, 14 and 21 studies were assessed with DSA and CTA, respectively. In DSA, the pooled sensitivity and specificity were 0.72 (95% CI, 0.63-0.79) and 0.61 (0.53-0.68), respectively, and in the HSROC model, the DOR was 3.94 (2.71-5.73), and the AUC was 0.71 (90.67-0.75). CTA revealed a pooled sensitivity and specificity of 0.74 (0.64-0.82) and 0.53 (0.44-0.62), respectively, and in the HSROC model, the DOR was 3.17 (2.34-4.50), and the AUC was 0.67 (0.63-0.71). With a pretest probability of 26.3%, the CS in DSA and CTA exhibited limited increase of PTPs of 39% and 36%, respectively, in detecting the FFO on day 90. CONCLUSION: DSA and CTA have comparable accuracy and are limited in predicting the functional outcome. The collateral score systems assessed with DSA and CTA were more suitable for screening than diagnosis for patients before IA-EVT. KEY POINTS: • Our study revealed the differences of various scoring systems for assessing collateral status. • DSA and CTA have comparable accuracy, but both imaging modalities played relatively limited roles in predicting functional outcome on day 90. • The collateral score systems assessed with DSA and CTA were more suitable for screening than diagnosis for patients before IA-EVT.