Risk factors and predictive nomograms for bedside emergency endoscopic treatment following endotracheal intubation in cirrhotic patients with esophagogastric variceal bleeding.

Data on emergency endoscopic treatment following endotracheal intubation in patients with esophagogastric variceal bleeding (EGVB) remain limited. This retrospective study aimed to explore the efficacy and risk factors of bedside emergency endoscopic treatment following endotracheal intubation in severe EGVB patients admitted in Intensive Care Unit. A total of 165 EGVB patients were enrolled and allocated to training and validation sets in a randomly stratified manner. Univariate and multivariate logistic regression analyses were used to identify independent risk factors to construct nomograms for predicting the prognosis related to endoscopic hemostasis failure rate and 6-week mortality. In result, white blood cell counts (p = 0.03), Child-Turcotte-Pugh (CTP) score (p = 0.001) and comorbid shock (p = 0.005) were selected as independent clinical predictors of endoscopic hemostasis failure. High CTP score (p = 0.003) and the presence of gastric varices (p = 0.009) were related to early rebleeding after emergency endoscopic treatment. Furthermore, the 6-week mortality was significantly associated with MELD scores (p = 0.002), the presence of hepatic encephalopathy (p = 0.045) and postoperative rebleeding (p < 0.001). Finally, we developed practical nomograms to discern the risk of the emergency endoscopic hemostasis failure and 6-week mortality for EGVB patients. In conclusion, our study may help identify severe EGVB patients with higher hemostasis failure rate or 6-week mortality for earlier implementation of salvage treatments.

A cross-sectional study: family communication, anxiety, and depression in adolescents: the mediating role of family violence and problematic internet use.

OBJECTIVE: The objective of this study is to explore the relationship between family communication, family violence, problematic internet use, anxiety, and depression and validate their potential mediating role. METHODS: The study population consisted of Chinese adolescents aged 12 to 18 years, and a cross-sectional survey was conducted in 2022. Structural equation models were constructed using AMOS 25.0 software to examine the factors that influence adolescent anxiety and depression and the mediating effects of problematic internet use and family violence. RESULTS: The results indicate that family communication was significantly and negatively related to family violence (ß = -.494, p < 0.001), problematic internet use (ß = -.056, p < .05), depression (ß = -.076, p < .01), and anxiety (ß = -.071, p < .05). And the finds also indicate that family violence mediated the relationships between family communication and depression (ß = -.143, CI: -.198 -.080), and between family communication and anxiety (ß = -.141; CI: -.198 -.074). Chain indirect effects between family communication and depression (ß = -.051; CI: -.081 -.030) or anxiety (ß = -.046; CI: -.080 -.043) via family violence and then through problematic internet use were also found in the present study. CONCLUSIONS: In conclusion, positive family communication is crucial in reducing anxiety and depression in adolescents. Moreover, problematic internet use and family violence mediate the effects of positive family communication on anxiety and depression. Therefore, improving family communication and promoting interventions aimed at reducing family violence and problematic internet use can help reduce anxiety and depression in adolescents, thus promoting their healthy development.

Prediction of base editor off-targets by deep learning.

Due to the tolerance of mismatches between gRNA and targeting sequence, base editors frequently induce unwanted Cas9-dependent off-target mutations. Here, to develop models to predict such off-targets, we design gRNA-off- target pairs for adenine base editors (ABEs) and cytosine base editors (CBEs) and stably integrate them into the human cells. After five days of editing, we obtain valid efficiency datasets of 54,663 and 55,727 off-targets for ABEs and CBEs, respectively. We use the datasets to train deep learning models, resulting in ABEdeepoff and CBEdeepoff, which can predict off-target sites. We use these tools to predict off-targets for a panel of endogenous loci and achieve Spearman correlation values varying from 0.710 to 0.859. Finally, we develop an integrated tool that is freely accessible via an online web server http://www.deephf.com/#/bedeep/bedeepoff . These tools could facilitate minimizing the off-target effects of base editing.

Relationship between illness perception and self-management behaviors among Chinese diabetic foot patients.

AIM: The aims of the present study are to describe the status of self-management behaviors and illness perception, and explore the relationship between illness perception and self-management behaviors among Chinese diabetic foot patients. METHODS: A cross-sectional study was conducted at the endocrinology department of a comprehensive tertiary hospital in Guangzhou, China. Data were collected on illness perception, self-management behaviors, and demographic and clinical characteristics over 9 months among 156 subjects. Data were analyzed using Pearson correlation analysis, univariate analysis and multiple linear regression analysis. RESULTS: Only 3.2% of participants maintained excellent self-management behaviors. Additionally, the participants perceived diabetic foot as chronic and could be well controlled through treatment. Multiple linear regression analysis revealed that illness perception was associated with self-management behaviors. CONCLUSIONS: Patient illness perception is an important factor influencing self-management behaviors. It may be helpful to improve self-management behaviors by tailoring the content of the intervention to fit the patients' illness perceptions.

Correlation between hepatic venous pressure gradient and portal pressure gradient in patients with autoimmune cirrhotic portal hypertension and collateral branches of the hepatic vein.

AIM: To assess the correlation and agreement between hepatic venous pressure gradient (HVPG) and portal pressure gradient (PPG) in patients with autoimmune liver diseases (ALD) and portal hypertension, and to investigate the extent to which hepatic vein collateralization affects the accuracy of this assessment. METHODS: Ninety-eight patients with ALD between 2017 and 2021 who underwent transjugular intrahepatic portosystemic shunt with conventional and innovative 15 mL pressurized contrast were selected to measure wedged hepatic venous pressure (WHVP) and portal venous pressure and to calculate the HVPG and PPG. Pearson's correlation was used for correlation analysis between the two groups. Bland-Altman plots were plotted to estimate the agreement between paired pressures. RESULTS: The r values of PPG and HVPG in the early, middle, late, and portal venous visualization were 0.404, 0.789, 0.807, and 0.830, respectively, and the R2 values were 0.163, 0.622, 0.651, and 0.690, respectively. The p value for the r and R2 values in the early group was 0.015, and the p values in the remaining groups were less than 0.001. Bland-Altman plots showed that patients in the portal venous visualization group had the narrowest 95% limits of agreement. The mean value of the difference was close to the zero-scale line. CONCLUSIONS: In patients with ALD, the correlation between the HVPG and PPG was good, and the later the collateral development, the better the correlation. Hepatic vein collateral was an essential factor in underestimating WHVP and HVPG, and the earlier the collateral appeared, the more obvious the underestimation.

Innovative angiography: a new approach to discover more hepatic vein collaterals in patients with cirrhotic portal hypertension.

BACKGROUND: The hemodynamics of patients with cirrhosis and portal hypertension are complex and variable. We aimed to investigate differences in venous pressures determined by innovative angiography and conventional angiography using balloon occlusion of the hepatic veins in patients with alcoholic cirrhosis and portal hypertension. METHODS: A total of 134 patients with alcoholic cirrhosis who fulfilled the inclusion criteria from June 2017 to June 2020 were included. During transjugular intrahepatic portosystemic shunt, conventional and innovative angiography were performed, and venous pressures were measured. A paired t-test and Pearson's correlation coefficient were used for analysis. RESULTS: Conventional and innovative hepatic angiography detected lateral branches of the hepatic vein in 26 (19.4%) and 65 (48.5%) cases, respectively (P < 0.001). Innovative angiography detected a total of 65 patients with lateral shunts, of whom 37 (56.9%) had initial shunts. The average wedged hepatic venous pressure and portal venous pressure of the initial lateral branches were 21.27 ± 6.66 and 35.84 ± 7.86 mmHg, respectively, with correlation and determination coefficients of 0.342 (P < 0.05) and 0.117, respectively. The mean hepatic venous pressure gradient and portal pressure gradient were 9.59 ± 7.64 and 26.86 ± 6.78 mmHg, respectively, with correlation and determination coefficients of 0.292 (P = 0.079) and 0.085, respectively. CONCLUSIONS: Innovative angiography reveals collateral branches of the hepatic veins more effectively than conventional angiography. Hepatic vein collateral branches are the primary factors leading to underestimation of wedged hepatic venous pressures and hepatic venous pressure gradients, with the initial hepatic vein collateral branches resulting in the most severe underestimations.

Timing of endoscopy for acute variceal bleeding in patients with cirrhosis (CHESS1905): A nationwide cohort study.

BACKGROUND: Endoscopy plays an important role in the management of acute variceal bleeding (AVB) in patients with cirrhosis. This study aimed at determining the optimal endoscopy timing for cirrhotic AVB. METHODS: Patients with cirrhosis with AVB across 34 university hospitals in 30 cities from February 2013 to May 2020 who underwent endoscopy within 24 hours were included in this study. Patients were divided into an urgent endoscopy group (endoscopy <6 h after admission) and an early endoscopy group (endoscopy 6-24 h after admission). Multivariable analysis was performed to identify risk factors for treatment failure. Primary outcome was the incidence of 5-day treatment failure. Secondary outcomes included in-hospital mortality, need for intensive care unit, and length of hospital stay. A propensity score matching analysis was performed. In addition, we performed an analysis, in which we compared the 5-day treatment failure incidence and the in-hospital mortality among patients with endoscopy performed at <12 hours and 12-24 hours. RESULTS: A total of 3319 patients were enrolled: 2383 in the urgent endoscopy group and 936 in the early endoscopy group. After propensity score matching, on multivariable analysis, Child-Pugh class was identified as an independent risk factor for 5-day treatment failure (HR, 1.61; 95% CI: 1.09-2.37). The incidence of 5-day treatment failure was 3.0% in the urgent endoscopy group and 2.9% in the early group ( p = 0.90). The in-hospital mortality was 1.9% in the urgent endoscopy group and 1.2% in the early endoscopy group ( p = 0.26). The incidence of need for intensive care unit was 18.2% in the urgent endoscopy group and 21.4% in the early endoscopy group ( p = 0.11). The mean length of hospital stay was 17.9 days in the urgent endoscopy group and 12.9 days in the early endoscopy group ( p < 0.05). The incidence of 5-day treatment failure in the <12-hour group was 2.3% and 2.2% in the 12-24 hours group ( p = 0.85). The in-hospital mortality was 2.2% in the <12-hour group and 0.5% in the 12-24 hours group ( p < 0.05). CONCLUSIONS: The data suggest that performance of endoscopy within 6-12 or within 24 hours of presentation among patients with cirrhosis with AVB led to similar treatment failure outcomes.

HBV-infected hepatocellular carcinoma can be robustly classified into three clinically relevant subgroups by a novel analytical protocol.

Liver cancer is the third leading cause of cancer-related death worldwide, and hepatocellular carcinoma (HCC) accounts for a relatively large proportion of all primary liver malignancies. Among the several known risk factors, hepatitis B virus (HBV) infection is one of the important causes of HCC. In this study, we demonstrated that the HBV-infected HCC patients could be robustly classified into three clinically relevant subgroups, i.e. Cluster1, Cluster2 and Cluster3, based on consistent differentially expressed mRNAs and proteins, which showed better generalization. The proposed three subgroups showed different molecular characteristics, immune microenvironment and prognostic survival characteristics. The Cluster1 subgroup had near-normal levels of metabolism-related proteins, low proliferation activity and good immune infiltration, which were associated with its good liver function, smaller tumor size, good prognosis, low alpha-fetoprotein (AFP) levels and lower clinical stage. In contrast, the Cluster3 subgroup had the lowest levels of metabolism-related proteins, which corresponded with its severe liver dysfunction. Also, high proliferation activity and poor immune microenvironment in Cluster3 subgroup were associated with its poor prognosis, larger tumor size, high AFP levels, high incidence of tumor thrombus and higher clinical stage. The characteristics of the Cluster2 subgroup were between the Cluster1 and Cluster3 groups. In addition, MCM2-7, RFC2-5, MSH2, MSH6, SMC2, SMC4, NCPAG and TOP2A proteins were significantly upregulated in the Cluster3 subgroup. Meanwhile, abnormally high phosphorylation levels of these proteins were associated with high levels of DNA repair, telomere maintenance and proliferative features. Therefore, these proteins could be identified as potential diagnostic and prognostic markers. In general, our research provided a novel analytical protocol and insights for the robust classification, treatment and prevention of HBV-infected HCC.

Direct observation of long-range chirality transfer in a self-assembled supramolecular monolayer at interface in situ.

Due to the interest in the origin of life and the need to synthesize new functional materials, the study of the origin of chirality has been given significant attention. The mechanism of chirality transfer at molecular and supramolecular levels remains underexplored. Herein, we study the mechanism of chirality transfer of N, N'-bis (octadecyl)-L-/D-(anthracene-9-carboxamide)-glutamic diamide (L-/D-GAn) supramolecular chiral self-assembled at the air/water interface by chiral sum-frequency generation vibrational spectroscopy (chiral SFG) and molecular dynamics (MD) simulations. We observe long-range chirality transfer in the systems. The chirality of Cα-H is transferred first to amide groups and then transferred to the anthracene unit, through intermolecular hydrogen bonds and π-π stacking to produce an antiparallel ß-sheet-like structure, and finally it is transferred to the end of hydrophobic alkyl chains at the interface. These results are relevant for understanding the chirality origin in supramolecular systems and the rational design of supramolecular chiral materials.

[Study on the correlation between PPG and HVPG in patients with portal hypertension].

Objective: To explore the correlation between portal vein pressure gradient (PPG) and hepatic vein pressure gradient (HVPG) in patients with portal hypertension (PHT). Methods: 752 cases with portal hypertension (PHT) who underwent transjugular intrahepatic portosystemic shunt (TIPS) and met the enrollment criteria between January 2016 to December 2019 were analyzed for hepatic vein, inferior vena cava and portal vein pressure. Paired t-test was used for analysis. Pearson correlation test was used to estimate correlation coefficient and coefficient of determination. P<0.05 were considered statistically significant. Results: Wedged hepatic vein pressure (WHVP), portal vein pressure (PVP), correlation coefficient, and coefficient of determination were 27.98±8.95 mmHg, 33.85±7.33 mmHg, 0.329 (P<0.001), and 0.108, respectively. HVPG, PPG,correlation coefficient, and coefficient of determination were 16.84±7.97 mmHg, 25.11±6.95 mmHg (P<0.001), 0.145, and 0.021 (P<0.001), respectively. The difference between HVPG and PPG was greater than 5 mmHg in 524 cases, accounting for 69.7%. The difference between HVPG and PPG was within 5 mmHg or basically equal in 228 cases, accounting for 30.3%. The correlation coefficient between free hepatic venous pressure (FHVP) and inferior vena cava pressure (IVCP) was 0.568 (P<0.001), and the coefficient of determination was 0.323. According to the presence or absence of hepatic venous collaterals after balloon occluded hepatic angiography, they were divided into two groups: 157 (20.9%) cases in the group with hepatic venous collaterals, and 595 (79.1%) cases in the group without hepatic venous collaterals. The parameters of the two groups were compared: WHVP (15.73±3.63) mmHg vs. (31.22±6.90) mmHg, P<0.001; PVP (31.69±8.70) mmHg vs. (34.42±6.81) mmHg, P<0.001; HVPG (7.18±4.40) mmHg vs. (19.40±6.62) mmHg, P<0.001; PPG (24.24±8.11) mmHg vs. (25.34±6.60) mmHg, P<0.001; free hepatic venous pressure (FHVP) (8.58±3.37) mmHg vs. (11.82±5.07) mmHg , P<0.001; inferior vena cava pressure (IVCP) (7.45±3.29) mmHg vs. (9.09±4.14) mmHg, P<0.001. Conclusion: The overall correlation is poor between HVPG and PPG. HVPG of most patients is not an accurate representation of PPG, and the former is lower than the latter. Hepatic venous collateral formation is one of the important reasons for the serious underestimation of HVPG values.

Transjugular intrahepatic portosystemic shunt with radioactive seed strand for main portal vein tumor thrombosis with cirrhotic portal hypertension.

BACKGROUND: Patients with hepatocellular carcinoma complicated with main portal vein tumor thrombosis (mPVTT) and cirrhotic portal hypertension (CPH) have an extremely poor prognosis, and there is a lack of a clinically effective treatment paradigm. AIM: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with radioactive seed strand for the treatment of mPVTT patients with CPH. METHODS: The clinical data of 83 consecutive patients who underwent TIPS combined with 125I seed strand placement for mPVTT and CPH from January 2015 to December 2018 were retrospectively reviewed. Procedure-related data (success rate, relief of portal vein pressure and CPH symptoms, and adverse events), PVTT response, and patient survival were assessed through a 2-year follow-up. RESULTS: The success rate was 100.0% without perioperative death or procedure-related severe adverse events. The mean portal vein pressure was significantly decreased after the procedure (22.25 ± 7.33 mmHg vs 35.12 ± 7.94 mmHg, t = 20.61, P < 0.001). The symptoms of CPH were all effectively relieved within 1 mo. The objective response rate of PVTT was 67.5%. During a mean follow-up of 14.5 ± 9.4 mo (range 1-37 mo), the cumulative survival rates at 6, 12 and 24 mo were 83.1%, 49.7%, and 21.8%, respectively. The median survival time was 12.0 ± 1.3 mo (95% confidence interval: 9.5-14.5). In multivariate Cox regression analysis, body mass index, Child-Pugh grade, cTNM stage, and PVTT response were independent prognostic factors (P < 0.05). CONCLUSION: TIPS combined with radioactive seed strand might be effective and safe in treating mPVTT patients with CPH.

Correlation between hepatic venous pressure gradient and portal venous pressure gradient in hepatitis B cirrhosis with different hepatic veins anatomy.

PURPOSE: The hepatic venous pressure gradient (HVPG) has been employed as the gold standard for indicating the portal venous pressure gradient (PPG) in the diagnosis of portal hypertension (PHT). However, little has been reported on whether the HVPG can accurately estimate the PPG in patients with hepatic vein collateral shunts. We aimed to explore the correlation between the HVPG and the PPG in hepatitis B cirrhosis patients with different hepatic vein anatomies. METHODS: A total of 461 hepatitis B cirrhosis patients with portal hypertension (PHT) who were treated with a transjugular intrahepatic portosystemic shunt (TIPS) between January 2016 and June 2020 were included. All patients underwent various venous pressure measurements and balloon-occluded compression hepatic venography during the TIPS operation. Agreements were evaluated by Pearson's correlation and the Bland-Altman method. Disagreements were assessed by paired t tests. RESULTS: The correlation coefficient (r) values (P < 0.001) between the HVPG and the PPG of the early (151 patients, 32.8 %), middle (73 patients, 15.8 %), late (46 patients, 10.0 %), portal vein (151 patients, 32.8 %), and no lateral branch development groups (40 patients, 8.7 %) were 0.373, 0.487, 0.569, 0.690, and 0.575, respectively; the determination coefficient (R2) values were 0.139, 0.238, 0.323, 0.475, and 0.330, respectively. According to the Bland-Altman method, agreement was the greatest in the portal vein development group, with the 95 % limits of agreement (95 % LoA, mean differences ± 1.96 SD) being the smallest. The differences were statistically significant (P < 0.05). CONCLUSION: The correlation between the HVPG and the PPG is the worst in early lateral branch development, followed by middle development, and the influence of lateral branches becomes significantly reduced in late development. Hepatic venous collateral formation is a vital factor for underestimation of the HVPG, which is the most accurate predictor of PPG in patients with portal vein development. Patients with no collateral channel development in the hepatic vein have a higher HVPG than PPG, which is an important reason for overestimation of the HVPG.

Bedaquiline and Linezolid improve anti-TB treatment outcome in drug-resistant TB patients with HIV: A systematic review and meta-analysis.

OBJECTIVES: We aimed to assess the effect of second-line anti-TB treatment and determine which drugs can achieve the greatest clinical benefit for DR-TB-HIV patients by comparing multiple chemotherapy regimens, to provide a basis for evidence-based practice. METHODS: We searched three electronic databases (PubMed, Web of Science and Cochrane) for related English studies published since 2010. A random-effect model was used to estimate the pooled result for the treatment outcomes. Subgroup analysis based on possible factors, such as ART, baseline CD4 T-cell count, treatment regimens, and profiles of drug resistance, was also conducted to assess factors for favorable outcome. Outcomes were treatment success and mortality. RESULTS: 38 studies, 40 cohorts with 9279 patients were included. The pooled treatment success, mortality, treatment failure, and default rates were 57.5 % (95 % CI 53.1-61.9), 21 % (95 % CI 17.8-24.6), 4.8 % (95 % CI 3.5-6.5), and 10.7 % (95 % CI 8.7-13.1), respectively, in patients with DR-TB and HIV co-infection. Subgroup analysis showed that BDQ and LZD based regimen, and ≥ 2 Group A drugs were associated with a higher treatment success rate. Besides, higher CD4 T-cell count at baseline was also correlated with higher treatment success rate, too. CONCLUSIONS: Suboptimal anti-TB outcomes underlining the need to expand the application of effective drugs and better regimen in high HIV setting. BDQ and LZD based all-oral regimen and early ART could contribute to higher treatment success, particularly among XDR-TB-HIV patients. Given that all included studies were observational, our findings emphasize the need for high-quality studies to further investigate the optimal treatment regimen for DR-TB-HIV.

Correlation of pressure gradient in three hepatic veins with portal pressure gradient.

BACKGROUND: The liver is one of the most important organs in the human body, with functions such as detoxification, digestion, and blood coagulation. In terms of vascular anatomy, the liver is divided into the left and the right liver by the main portal vein, and there are three hepatic efferent veins (right, middle, and left) and two portal branches. Patients with impaired liver function have increased intrahepatic vascular resistance and splanchnic vasodilation, which may lead to an increase in the portal pressure gradient (PPG) and cause portal hypertension (PHT). In order to measure the increased pressure gradient of portal vein, the hepatic venous pressure gradient (HVPG) can be measured to reflect it in clinical practice. The accuracy of PPG measurements is directly related to patient prognosis. AIM: To analyze the correlation between HVPG of three hepatic veins and PPG in patients with PHT. METHODS: From January 2017 to December 2019, 102 patients with PHT who met the inclusion criteria were evaluated during the transjugular intrahepatic portosystemic shunt procedure and analyzed. RESULTS: The mean HVPG of the middle hepatic vein was 17.47 ± 10.25 mmHg, and the mean HVPG of the right and left hepatic veins was 16.34 ± 7.60 and 16.52 ± 8.15 mmHg, respectively. The average PPG was 26.03 ± 9.24 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.15 and 0.02 (P = 0.164); 0.25 and 0.05 (P = 0.013); and 0.14 and 0.02 (P = 0.013), respectively. The mean wedged hepatic vein/venous pressure (WHVP) of the middle and left hepatic veins was similar at 29.71 ± 12.48 and 29.1 ± 10.91 mmHg, respectively, and the mean WHVP of the right hepatic vein was slightly lower at 28.01 ± 8.95 mmHg. The mean portal vein pressure was 34.11 ± 8.56 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.26 and 0.07 (P = 0.009); 0.38 and 0.15 (P < 0.001); and 0.26 and 0.07 (P = 0.008), respectively. The average free hepatic venous pressure (FHVP) of the right hepatic vein was lowest at 11.67 ± 5.34 mmHg, and the average FHVP of the middle and left hepatic veins was slightly higher at 12.19 ± 4.88 and 11.67 ± 5.34 mmHg, respectively. The average inferior vena cava pressure was 8.27 ± 4.04 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.30 and 0.09 (P = 0.002); 0.18 and 0.03 (P = 0.078); and 0.16 and 0.03 (P = 0.111), respectively. CONCLUSION: Measurement of the middle hepatic vein HVPG could better represent PPG. Considering the high success rate of clinical measurement of the right hepatic vein, it can be the second choice.

Pan-Cancer Single-Cell Analysis Reveals the Core Factors and Pathway in Specific Cancer Stem Cells of Upper Gastrointestinal Cancer.

Upper gastrointestinal cancer (UGIC) is an aggressive carcinoma with increasing incidence and poor outcomes worldwide. Here, we collected 39,057 cells, and they were annotated into nine cell types. By clustering cancer stem cells (CSCs), we discovered the ubiquitous existence of sub-cluster CSCs in all UGICs, which is named upper gastrointestinal cancer stem cells (UGCSCs). The identification of UGCSC function is coincident with the carcinogen of UGICs. We compared the UGCSC expression profile with 215,291 single cells from six other cancers and discovered that UGCSCs are specific tumor stem cells in UGIC. Exploration of the expression network indicated that inflammatory genes (CXCL8, CXCL3, PIGR, and RNASE1) and Wnt pathway genes (GAST, REG1A, TFF3, and ZG16B) are upregulated in tumor stem cells of UGICs. These results suggest a new mechanism for carcinogenesis in UGIC: mucosa damage and repair caused by poor eating habits lead to chronic inflammation, and the persistent chronic inflammation triggers the Wnt pathway; ultimately, this process induces UGICs. These findings establish the core signal pathway that connects poor eating habits and UGIC. Our system provides deeper insights into UGIC carcinogens and a platform to promote gastrointestinal cancer diagnosis and therapy.

Treatment Strategies in Emergency Endoscopy for Acute Esophageal Variceal Bleeding (CHESS1905): A Nationwide Cohort Study.

Background and Aims: Emergency endoscopy is recommended for patients with acute esophageal variceal bleeding (EVB) and their prognosis has improved markedly over past decades due to the increased specialization of endoscopic practice. The study aimed to compare outcomes following emergency endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) in cirrhotic patients with acute EVB. Methods: Cirrhotic patients with acute EVB who underwent emergency endoscopy were retrospectively enrolled from 2013 to 2020 across 34 university hospitals from 30 cities. The primary outcome was the incidence of 5-day rebleeding after emergency endoscopy. Subgroup analysis was stratified by Child-Pugh class and bleeding history. A 1:1 propensity score matching (PSM) analysis was performed. Results: A total of 1,017 and 382 patients were included in EIS group and EVL group, respectively. The 5-day rebleeding incidence was similar between EIS group and EVL group (4% vs. 5%, P = 0.45). The result remained the same after PSM (P = 1.00). Among Child-Pugh class A, B and C patients, there were no differences in the 5-day rebleeding incidence between the two groups after PSM (P = 0.25, 0.82, and 0.21, respectively). As for the patients with or without bleeding history, the differences between EIS group and EVL group were not significant after PSM (P = 1.00 and 0.26, respectively). Conclusion: The nationwide cohort study indicates that EIS and EVL are both efficient emergency endoscopic treatment strategies for acute EVB. EIS should not be dismissed as an economical and effective emergency endoscopic treatment strategy of acute EVB. ClincialTrials.gov number NCT04307264.

A Glycolysis-Related Gene Signature Correlates With the Characteristics of the Tumor Immune Microenvironment and Predicts Prognosis in Patients With Hepatocellular Carcinoma.

Aim: To develop a glycolysis-related gene signature that correlated with the characteristics of the tumor immune microenvironment and had good predictive power for overall survival (OS) in hepatocellular carcinoma (HCC). Methods: Gene expression profiles, RNA sequencing data, clinical characteristics and survival information for 407 patients with HCC and 58 healthy controls were downloaded from the TCGA database. GSEA 4.1.0 software was used to evaluate the glycolysis-related pathways enriched in HCC compared to normal liver tissue. Univariate Cox, Least Absolute Shrinkage, Selection Operator, and two-step multivariate Cox analyses were used to construct a glycolysis-related gene signature for prognostic prediction. The glycolysis-related gene signature was combined with clinical characteristics to generate a nomogram. Tumor-infiltrating immune cell profiles and PD-L1 protein expression in HCC tissues were investigated. Results: The gene expression profiles of HCC tissues were enriched in glycolysis-related pathways. A glycolysis-related gene signature was used to categorize patients as high-risk or low-risk, where high-risk patients had significantly worse OS. Receiver operating characteristic curves confirmed the predictive capability of the glycolysis-related gene signature for OS (AUC >0.80). There was a significant difference in M0 macrophage (p = 0.017), dendritic cell (p = 0.043), B cell (p = 0.0018), CD4 T cell (p = 0.003), Treg (p = 0.01) and mast cell (p = 0.02) content and PD-L1 protein expression (p = 0.019) between HCC tissues in patients in the high-risk and low-risk groups. Conclusion: We established a glycolysis-related gene signature for OS in HCC that was predictive in training and test TCGA cohorts and correlated with the characteristics of the HCC tumor immune microenvironment. The glycolysis-related gene signature may guide clinical decision-making concerning patient selection for immunotherapy in HCC.

A novel machine learning-based radiomic model for diagnosing high bleeding risk esophageal varices in cirrhotic patients.

BACKGROUND AND AIM: To develop and validate a novel machine learning-based radiomic model (RM) for diagnosing high bleeding risk esophageal varices (HREV) in patients with cirrhosis. METHODS: A total of 796 qualified participants were enrolled. In training cohort, 218 cirrhotic patients with mild esophageal varices (EV) and 240 with HREV RM were included to training and internal validation groups. Additionally, 159 and 340 cirrhotic patients with mild EV and HREV RM, respectively, were used for external validation. Interesting regions of liver, spleen, and esophagus were labeled on the portal venous-phase enhanced CT images. RM was assessed by area under the receiver operating characteristic curves (AUROC), sensitivity, specificity, calibration and decision curve analysis (DCA). RESULTS: The AUROCs for mild EV RM in training and internal validation were 0.943 and 0.732, sensitivity and specificity were 0.863, 0.773 and 0.763, 0.763, respectively. The AUROC, sensitivity, and specificity were 0.654, 0.773 and 0.632, respectively, in external validation. Interestingly, the AUROCs for HREV RM in training and internal validation were 0.983 and 0.834, sensitivity and specificity were 0.948, 0.916 and 0.977, 0.969, respectively. The related AUROC, sensitivity and specificity were 0.736, 0.690 and 0.762 in external validation. Calibration and DCA indicated RM had good performance. Compared with Baveno VI and its expanded criteria, HREV RM had a higher accuracy and net reclassification improvements that were as high as 49.0% and 32.8%. CONCLUSION: The present study developed a novel non-invasive RM for diagnosing HREV in cirrhotic patients with high accuracy. However, this RM still needs to be validated by a large multi-center cohort.

In Situ Probe Supramolecular Self-Assembly Dynamics and Chirality Transfer Mechanism at Air-Water Interface.

The study of supramolecular self-assembly dynamics and the chirality transfer mechanism is of importance to the rational design of potentially functional chiral supramolecular materials and an understanding of the origin of homochirality in biological systems. Herein, we study the supramolecular assemblies constructed by the tetrakis(4-sulfonatophenyl) porphyrin (TPPS) molecules' adsorption on the enantiomer chiral amphiphilic molecules (l-/d-G12) using sum-frequency generation (SFG) and second harmonic generation (SHG) spectra. We first establish a dynamic model that involved adsorption and assembly and obtained the dynamic parameters by fitting this model. We then propose the chiral transfer mechanism from the chiral center of the l-/d-G12 molecule to the whole supramolecular assembly. Finally, we put forward an explanation that the sulfonic acid group and the phenyl group on the TPPS molecule show homochirality, but the porphyrin ring forms J-aggregation and shows mirror-symmetric structural chirality in the l-/d-G12 and TPPS self-assembly at these processes.