Evaluation of Large Language Model Performance and Reliability for Citations and References in Scholarly Writing: Cross-Disciplinary Study.

BACKGROUND: Large language models (LLMs) have gained prominence since the release of ChatGPT in late 2022. OBJECTIVE: The aim of this study was to assess the accuracy of citations and references generated by ChatGPT (GPT-3.5) in two distinct academic domains: the natural sciences and humanities. METHODS: Two researchers independently prompted ChatGPT to write an introduction section for a manuscript and include citations; they then evaluated the accuracy of the citations and Digital Object Identifiers (DOIs). Results were compared between the two disciplines. RESULTS: Ten topics were included, including 5 in the natural sciences and 5 in the humanities. A total of 102 citations were generated, with 55 in the natural sciences and 47 in the humanities. Among these, 40 citations (72.7%) in the natural sciences and 36 citations (76.6%) in the humanities were confirmed to exist (P=.42). There were significant disparities found in DOI presence in the natural sciences (39/55, 70.9%) and the humanities (18/47, 38.3%), along with significant differences in accuracy between the two disciplines (18/55, 32.7% vs 4/47, 8.5%). DOI hallucination was more prevalent in the humanities (42/55, 89.4%). The Levenshtein distance was significantly higher in the humanities than in the natural sciences, reflecting the lower DOI accuracy. CONCLUSIONS: ChatGPT's performance in generating citations and references varies across disciplines. Differences in DOI standards and disciplinary nuances contribute to performance variations. Researchers should consider the strengths and limitations of artificial intelligence writing tools with respect to citation accuracy. The use of domain-specific models may enhance accuracy.

Development and validation of a novel preoperative clinical model for predicting lymph node metastasis in perihilar cholangiocarcinoma.

BACKGROUD: We aimed to develop a novel preoperative nomogram to predict lymph node metastasis (LNM) in perihilar cholangiocarcinoma (pCCA) patients. METHODS: 160 pCCA patients were enrolled at Lihuili Hospital from July 2006 to May 2022. A novel nomogram model was established to predict LNM in pCCA patients based on the independent predictive factors selected by the multivariate logistic regression model. The precision of the nomogram model was evaluated through internal and external validation with calibration curve statistics and the concordance index (C-index). Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate and determine the clinical utility of the nomogram. RESULTS: Multivariate logistic regression demonstrated that age (OR = 0.963, 95% CI: 0.930-0.996, P = 0.030), CA19-9 level (> 559.8 U/mL vs. ≤559.8 U/mL: OR = 3.162, 95% CI: 1.519-6.582, P = 0.002) and tumour diameter (OR = 1.388, 95% CI: 1.083-1.778, P = 0.010) were independent predictive factors of LNM in pCCA patients. The C-index was 0.763 (95% CI: 0.667-0.860) and 0.677 (95% CI: 0.580-0.773) in training cohort and validation cohort, respectively. ROC curve analysis indicated the comparative stability and adequate discriminative ability of nomogram. The sensitivity and specificity were 0.820 and 0.652 in training cohort and 0.704 and 0.649 in validation cohort, respectively. DCA revealed that the nomogram model could augment net benefits in the prediction of LNM in pCCA patients. CONCLUSIONS: The novel prediction model is useful for predicting LNM in pCCA patients and showed adequate discriminative ability and high predictive accuracy.

A Comparative Study of Laparoscopic and Open Approaches for Right Hemihepatectomy in Hepatocellular Carcinoma Patients: Safety and Short-Term Outcomes.

BACKGROUND Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths worldwide, with China reporting over half of global cases. While traditional open liver resection is effective, it often results in large incisions and significant complications. Laparoscopic hepatectomy, particularly for right hemi-hepatectomy, features smaller incisions and quicker recovery, but its widespread adoption is hindered by its procedural complexity and a steep learning curve. This study compares the safety and efficacy of laparoscopic versus open right hemi-hepatectomy with an anterior approach in 57 patients with HCC. MATERIAL AND METHODS The data of patients with HCC who underwent treatment at our center from January 2016 to December 2020 were retrospectively analyzed. RESULTS We included a total of 57 patients with histopathologically-confirmed HCC - 23 in the laparoscopic group and 34 in the open group. Operation time was significantly shorter in the open group than in the laparoscopic group (234.5±66.9 vs 297.0±74.9, P=0.002). Intraoperative bleeding was significantly less in the laparoscopic group (P=0.042). There were no statistically significant differences in postoperative complications between the 2 groups. Postoperative hospital stay was significantly shorter in the laparoscopic group (12 days vs 15 days, P=0.044). There was no significant difference in postoperative overall survival (OS) and disease-free survival (DFS) between the 2 groups (P>0.05). CONCLUSIONS In patients with hepatocellular carcinoma, the laparoscopic right hemi-hepatectomy with the anterior approach technique has the same safety and comparable short-term outcomes as open surgery.

A CDAHFD-induced mouse model mimicking human NASH in the metabolism of hepatic phosphatidylcholines and acyl carnitines.

Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of a cluster of conditions associated with lipid metabolism disorders. Ideal animal models mimicking the human NASH need to be explored to better understand the pathogenesis. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has recently been used to induce the NASH model, but the advantages are not established. NASH models were induced using the well-known traditional methionine- and choline-deficient (MCD) diet for 5 weeks and the recently used CDAHFD for 3 weeks. Liver phenotypes were analyzed to evaluate the differences in markers related to NASH. Lipidomics and metabolism analyses were used to investigate the effects of dietary regimens on the lipidome of the liver. The CDAHFD induced stronger NASH responses than the MCD, including lipid deposition, liver injury, inflammation, bile acid overload and hepatocyte proliferation. A significant difference in the hepatic lipidome was revealed between the CDAHFD and MCD-induced NASH models. In particular, the CDAHFD reduced the hepatic levels of phosphatidylcholines (PCs) and acylcarnitines (ACs), which was supported by the metabolism analysis and in line with the tendency of human NASH. Pathologically, the CDAHFD could effectively induce a more human-like NASH model over the traditional MCD. The hepatic PCs, ACs and their metabolism in CDAHFD-treated mice were down-regulated, similar to those in human NASH.

Impact of insomnia upon inflammatory digestive diseases and biomarkers: a two-sample mendelian randomization research on Europeans.

BACKGROUND: A number of observational studies indicate that insomnia is linked to inflammatory digestive diseases (IDDs). However, the definite relationship between insomnia and IDDs remains unclear. METHODS: We obtained the publicly available data from genome-wide association studies (GWAS) to conduct two-sample Mendelian randomization (MR) for association assessment. Five MR analysis methods were used to calculate the odds ratio (OR) and effect estimate, and the heterogeneity and pleiotropy tests were performed to evaluate the robustness of the variable instruments (IVs). RESULTS: One exposure and twenty outcome datasets based on European populations were included in this study. Using the inverse variance weighted method, we found insomnia was closely correlated with esophageal ulcer (OR = 1.011, 95%CI = 1.004-1.017, p = 0.001) and abdominal pain (effect estimate = 1.016, 95%CI = 1.005-1.026, p = 0.003). Suggestive evidence of a positively association was observed between insomnia and duodenal ulcer (OR = 1.006, 95%CI = 1.002-1.011, p = 0.009), gastric ulcer (OR = 1.008, 95%CI = 1.001-1.014, p = 0.013), rectal polyp (OR = 1.005, 95%CI = 1.000-1.010, p = 0.034), haemorrhoidal disease (OR = 1.242, 95%CI = 1.004-1.535, p = 0.045) and monocyte percentage (effect estimate = 1.151, 95%CI = 1.028-1.288, p = 0.014). No correlations were observed among other IDDs, phenotypes and biomarkers. CONCLUSIONS: Our MR study assessed the relationship between insomnia and IDDs/phenotypes/biomarkers in depth and revealed potential associations between insomnia and ulcers of the esophagus and abdominal pain.

Prognostic and Immune Infiltration Analysis of Transaldolase 1 (TALDO1) in Hepatocellular Carcinoma.

Background: Transaldolase 1 (TALDO1) deficiency was associated with hepatocellular carcinoma (HCC), but the association between TALDO1 and prognosis in HCC remains unclear. Material and Methods: RNA-seq and clinical data of HCC from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were analyzed. CCK8 and EdU assays were utilized to examine the effect of TALDO1 on HCC proliferation. Transwell assay was used to explore the effect of TALDO1 on HCC migration. Western Blot was applied to detected the expression levels of pathway-related proteins. Results: TALDO1 mRNA level was higher in HCC tissues than in control normal tissues in TCGA and GEO databases (P<0.001, P<0.001). Expression of TALDO1 mRNA was associated with histologic grade (P=0.021). Multivariate regression analysis revealed that high TALDO1 mRNA expression was an independent risk factor for prognosis (P<0.001). High expression of TALDO1 had poor overall survival (OS) (P=0.046). Additionally, Nomogram prognostic model of TALDO1 and clinicopathological parameters could predict the prognostic OS of HCC patients. Functional enrichment and immune infiltration analysis revealed that TALDO1 negatively regulates immune response. Furthermore, knockdown TALDO1 expression suppressed the proliferation and migration ability of HCC cells. Mechanistically, TALDO1 leaded to activation of the mitogen-activated protein kinase (MAPK) pathway and enhancement of epithelial-mesenchymal transition (EMT). Conclusion: Our findings demonstrated that TALDO1 could serve as a promising novel biomarker for HCC patients, which might modulate the immune microenvironment resulting in a poor prognosis.

Exploring the risk factors of early sepsis after liver transplantation: development of a novel predictive model.

Background: Sepsis is a severe and common complication of liver transplantation (LT) with a high risk of mortality. However, effective tools for evaluating its risk factors are lacking. Therefore, this study identified the risk factors of early post-liver transplantation sepsis and established a nomogram. Methods: We analyzed the risk factors of post-liver transplantation sepsis in 195 patients. Patients with infection and a systemic inflammatory response syndrome (SIRS) score ≥ 2 were diagnosed with sepsis. The predictive indicators were screened with the least absolute shrinkage and selection operator (LASSO) and collinearity analyses to develop a nomogram. The prediction performance of the new nomogram model, Sequential Organ Failure Assessment (SOFA) score, and Modified Early Warning Score (MEWS) was compared through assessment of the area under the curve (AUC), decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI). Results: The nomogram was based on postoperative heart rate, creatinine concentration, PaO2/FiO2 ratio < 400 mmHg, blood glucose concentration, and international normalized ratio. The AUC of the nomogram, the SOFA score, and MEWS were 0.782 (95% confidence interval CI: 0.716-0.847), 0.649 (95% CI: 0.571-0.727), and 0.541 (95% CI: 0.469-0.614), respectively. The DCA curves showed that the net benefit rate of the nomogram was higher than that of the SOFA score and MEWS. The NRI and IDI tests revealed better predictive performance for the nomogram than SOFA score and MEWS. Conclusion: Heart rate, creatinine concentration, PaO2/FiO2, glucose concentration, and international normalized ratio should be monitored postoperatively for patients at risk of post-liver transplantation sepsis. The nomogram based on the aforementioned risk factors had a better predictive performance than SOFA score and MEWS.

Short-Term Monitoring of Graft Regeneration in Partial Liver Transplantation Recipients.

BACKGROUND Liver regeneration after partial liver transplantation, including living donor liver transplantation and split liver transplantation, is important for successful transplantation. MATERIAL AND METHODS We retrospectively analyzed 68 patients who underwent partial liver transplantation and calculated their regeneration index (RI)-based difference in postoperative and preoperative liver volume. We collected clinical data of donors and recipients and analyzed the correlation between clinical characteristics and RI. According to the above results, the generalized estimating equation (GEE) model included white blood cell count (WBC), neutrophils, lymphocytes, platelets, prothrombin time (PT), and activated partial thromboplastin time (APTT) on Days 1, 3, and 7 after LT and was used to predict the RI. RESULTS The mean RI was 40%, which was used as the cutoff value to divide all patients to the high-RI group and the low-RI group. The percentage of Child-Pugh C patients was 44% in the high-RI group, which was significantly more than that (21%) in the low-RI group (P=0.038). Among the postoperative monitoring parameters, neutrophil (P=0.044) and platelet (P=0.036) levels declined in the high-RI group on Day 3, while APTT was higher on Day 1 compared to the low-RI group. The predictive model based on GEE analysis achieved a good effect, with the area under the receiver operating characteristic curve on Day 1 (0.681; 95% CI, 0.556-0.807) and Day 3 (0.705; 95% CI, 0.578-0.832) showing significant differences (P=0.010 and 0.004, respectively). CONCLUSIONS The combination of decreased counts of WBC, neutrophils, lymphocytes, and platelets, as well as elevated PT and APTT on Day 3 after LT showed a good capability to predict a higher rate of liver regeneration after partial liver transplantation.

Comparison of Postoperative Hemorrhage Risk After Partial Liver Transplantation Versus Whole Liver Transplantation: A Single-Center Experience.

BACKGROUND: We aimed to identify risk factors associated with reoperation for postoperative intraperitoneal hemorrhage (PIH) after orthotopic liver transplantation and investigate if partial liver transplantation (PLT) increases the risk of PIH. METHODS: We retrospectively analyzed the medical records of 304 consecutive recipients who underwent orthotopic liver transplantation at the Affiliated Lihuili Hospital, Ningbo University, from January 2016 to July 2022. Data were compared between recipients who experienced PIH requiring reoperation and those who did not. Subgroup propensity score matching analysis was performed to assess the impact of PLT on PIH risk. Neither prisoners nor participants who were coerced or paid were used in the study. RESULTS: Among the 304 recipients, 22 (7.2%) underwent reoperation for PIH. Multivariate analysis revealed that the recipient Model for End-Stage Liver Disease (MELD) score (odds ratio = 1.066, 95% CI [1.025-1.109], P = .001) and volume of intraoperative packed red blood cell transfusion (odds ratio = 1.089, 95% CI [1.032-1.481], P = .002) were independent risk factors for PIH. No significant differences were observed in the risk of PIH between PLT and whole liver transplantation. CONCLUSION: Preoperative MELD score and intraoperative packed red blood cell transfusion should be carefully considered to manage the risk of PIH in liver transplantation recipients. Partial liver transplantation, a crucial approach for addressing donor shortages, does not increase the risk of reoperation for PIH in recipients.

Longitudinal surveillance of three biomarkers to predict recurrence of hepatocellular carcinoma after radical resection.

BACKGROUND: Radical resection is a curative treatment for patients with hepatocellular carcinoma (HCC), but the incidence of recurrence remains high. We aimed to explore the performance of predicting HCC recurrence by longitudinal surveillance of the protein induced by vitamin K absence (PIVKA-II), alpha- fetoprotein (AFP), and lectin-reactive AFP (AFP-L3) during postoperative follow-up. METHODS: Patients who underwent radical resection for HCC at the Ningbo Medical Centre Lihuili Hospital between January 2015 and December 2020 were included. All enrolled patients regularly monitor PIVKA-II, AFP, AFP-L3 every 3 months during postoperative follow-up. The surveillance performance of PIVKA-II, AFP, AFP-L3 during follow-up for the prediction of HCC recurrence was compared in patients. The generalized estimation equation (GEE) was used to analyze the trends of the tumor biomarkers and interactions with time. Area under the receiver operator characteristic (AUROC) curves, the optimal cut-off value, the sensitivity and specificity were calculated to evaluate the performance of the three biomarkers. The recurrence-free survival (RFS) and overall survival (OS) of patients with any of the elevated biomarkers was analyzed by Kaplan-Meier curves and the log-rank test. Multivariate logistic regression models were used to analyze potential risk factors for recurrence. RESULTS: The GEE analysis indicated that PIVKA-II, AFP, AFP-L3 in the recurrence patients were higher than the no recurrence patients during follow-up, PIVKA-II and AFP showed increasing trends from 6 months before recurrence. In predicting recurrence, the AUROCs for PIVKA-II, AFP, AFP-L3 and their combination were 0.885, 0.754, 0.781 and 0.885 respectively, the optimal cut-off value for PIVKA-II, AFP, AFP-L3 was 29.5 mAU/ml, 10.7 ng/L, 1.5% respectively. The sensitivity in predicting recurrence for PIVKA-II, AFP, AFP-L3 and combination were 75.0, 54.7, 57.8 and 79.7% respectively. The RFS and the OS of patients with any of the biomarkers elevated during the follow-up was significantly shorter than that without elevated biomarkers ( P  < 0.001). Multivariate analysis showed that any of the biomarkers elevated was the independent risk factor of recurrence. CONCLUSION: Longitudinal surveillance of PIVKA-II, AFP and AFP-L3 can effectively predict recurrence of HCC after operation.

MTM-HCC at Previous Liver Resection as a Predictor of Overall Survival in Salvage Liver Transplantation.

OBJECTIVES: Salvage liver transplantation (sLT) is considered an effective method to treat hepatocellular carcinoma (HCC) recurrence. This multicenter research aimed to identify the prognostic factors associated with recurrence-free survival (RFS) and overall survival (OS) after sLT. MATERIAL AND METHODS: A retrospective analysis of 114 patients who had undergone sLT for recurrent HCC between February 2012 and September 2020 was performed. The baseline and clinicopathological data of the patients were collected. RESULTS: The 1-, 3-, and 5-year RFS rates after sLT were 88.9%, 75.2%, and 69.2%, respectively, and the OS rates were 96.4%, 78.3%, and 70.8%. A time from liver resection (LR) to recurrence < 1 year, disease beyond the Milan criteria at sLT and macrotrabecular massive (MTM)-HCC were identified as risk factors for RFS and were further identified as independent risk factors. A time from LR to recurrence < 1 year, disease beyond the Milan criteria at sLT and MTM-HCC were also risk factors for OS and were further identified as independent risk factors. CONCLUSIONS: Compared with primary liver transplantation (pLT), more prognostic factors are available from patients who had undergone LR. We suggest that in cases of HCC recurrence within 1 year after LR, disease beyond the Milan criteria at sLT and MTM-HCC patients, sLT should be used with caution.

Macrotrabecular-massive subtype-based nomogram to predict early recurrence of hepatocellular carcinoma after surgery.

OBJECTIVES: To analyze the predictive factors on early postoperative recurrence of hepatocellular carcinoma (HCC) and to establish a new nomogram to predict early postoperative recurrence of HCC. METHODS: A retrospective analysis of 383 patients who had undergone curative resection between February 2012 and September 2020 in our center was performed. The Kaplan-Meier method was used for survival curve analysis. Univariate and multivariate Cox regression were performed to identify independent risk factors associated with early recurrence, and a nomogram for predicting early recurrence of HCC was established. RESULTS: A total of 152/383 patients developed recurrence after surgery, of which 83 had recurrence within 1 year. Multivariate Cox regression analysis showed that preoperative alpha-fetoprotein level ≥400 ng/ml (P = 0.001), tumor diameter ≥5 cm (P = 0.009) and MVI (P = 0.007 and macrotrabecular-massive HCC (P = 0.003) were independent risk factors for early postoperative recurrence of HCC. The macrotrabecular-massive-based nomogram obtained a good C-index (0.74) for predicting early recurrence of HCC, and the area under the curve for predicting early recurrence was 0.767, which was better than the single American Joint Committee on Cancer T stage and Barcelona Clinic Liver Cancer stage. CONCLUSIONS: The nomogram based on macrotrabecular-massive HCC can effectively predict early postoperative recurrence of HCC.

Risk factors for acute rejection in liver transplantation and its impact on the outcomes of recipients.

OBJECTIVE: To determine the risk factors for acute rejection in liver transplantation and its impact on the outcomes of the recipients. METHODS: Clinicopathological data of 290 patients who underwent liver transplantation from January 2012 to December 2021 at our center were retrospectively evaluated. Patients were grouped into an acute rejection (AR) group and a normal (NM) group based on the confirmed histopathological diagnosis of acute rejection. Univariate and multivariate logistic regression were used to determine the risk factors for acute rejection. RESULTS: 244 patients were included in the study. Acute rejection occurred in 27 (11.1%) of the patients. Warm ischemia time (P = 0.137), cold ischemia time (P = 0.064) and chronic liver failure (P = 0.001) were potential risk factors for acute rejection. Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47-27.32) was the independent risk factor. There was no significant difference in overall survival between recipients with acute rejection and those without it (P = 0.985). The 1-, 3- and 5-year overall survival in the NM group was 98.1%, 85.7% and 78.6% respectively vs 88.9%, 82.5% and 82.5% respectively in the AR group. CONCLUSION: Acute rejection does not appear to affect the long-term survival of the recipients. Only chronic liver failure was an independent risk factor for acute rejection. Our findings further illustrate that contradictions still exist on which factors influence acute rejection in liver transplant recipients. SUMMARY: Clinicopathological data of 290 liver transplant recipients at our center between January 2012 and December 2021 were retrospectively evaluated to determine the risk factors for acute rejection and its impact on the outcomes of the recipients. 244 patients were included in the analysis. 27 of the 244 experienced acute rejection. Propensity score matching was performed to reduce the confounding effect. Patients were assigned to an acute rejection group (n = 27) and a normal group (n = 54). Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47-27.32) was the determined to be independent risk factor for acute rejection. Acute rejection did not appear to affect the long-term survival of the recipients and there was no significant difference in overall survival between the patients with acute rejection and those without it.

A new prognostic model predicting hepatocellular carcinoma early recurrence in patients with microvascular invasion who received postoperative adjuvant transcatheter arterial chemoembolization.

BACKGROUD: In this study, we aimed to develop a prognostic model to predict HCC early recurrence (within 1-year) in patients with microvascular invasion who received postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE). METHODS: A total of 148 HCC patients with MVI who received PA-TACE were included in this study. The modes were verified in an internal validation cohort (n = 112) and an external cohort (n = 36). Univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factors relevant to early recurrence. A clinical nomogram prognostic model was established, and nomogram performance was assessed via internal validation and calibration curve statistics. RESULTS: After data dimensionality reduction and element selection, multivariate Cox regression analysis indicated that alpha fetoprotein level, systemic inflammation response index, alanine aminotransferase, tumour diameter and portal vein tumour thrombus were independent prognostic factors of HCC early recurrence in patients with MVI who underwent PA-TACE. Nomogram with independent factors was established and achieved a better concordance index of 0.765 (95% CI: 0.691-0.839) and 0.740 (95% CI: 0.583-0.898) for predicting early recurrence in training cohort and validation cohort, respectively. Time-dependent AUC indicated comparative stability and adequate discriminative ability of the model. The DCA revealed that the nomogram could augment net benefits and exhibited a wider range of threshold probabilities than AJCC T stage. CONCLUSIONS: The nomogram prognostic model showed adequate discriminative ability and high predictive accuracy.

Undifferentiated Pancreatic Carcinomas, Clinical Features and Therapeutic Options: What We Know.

Undifferentiated pancreatic carcinomas are rare malignant tumors of the pancreas that are very aggressive and challenging to diagnose. The WHO categorizes them into undifferentiated osteoclast-like giant cell, sarcomatoid, and rhabdoid pancreatic carcinomas. Patients present with nonspecific symptoms such as jaundice, vague abdominal or back pain and itchy skin. Their histological characteristics include positive pan-cytokeratin mononuclear pleomorphic cells, osteoclast-like giant cells and CD68. Patients may have KRAS, TP53 and SMAD4 alterations, homozygous deletions of CDKN2A and CDKN2B, as well as INI1 deficiency. Surgical resection is the only curative treatment. Patients may benefit from postoperative adjuvant therapy. There are no widely accepted guidelines specific to this type of tumor; however, some chemotherapy regimens may be promising. The patient prognosis is mostly poor, especially in patients with unresectable tumors. However, several studies have shown patients achieving long-term survival with adjuvant therapy. In conclusion, although undifferentiated pancreatic carcinoma is rare and very aggressive, there is still potential for improved patient survival with proper diagnosis and treatment.

Development and validation of a nomogram to predict liver metastasis for pancreatic ductal adenocarcinoma after radical resection.

Objectives: This study aimed to develop and externally validate a nomogram for predicting liver metastasis after radical resection in patients with pancreatic ductal adenocarcinoma (PDAC). Methods: A total of 247 PDAC patients who underwent radical resection were retrospectively reviewed from January 2015 to March 2022 at Ningbo Medical Centre Lihuili Hospital Eastern Section, and used as a training cohort to develop the nomogram. 83 PDAC patients from the Ningbo Medical Centre Lihuili Hospital Xingning Section were enrolled as the validation cohort. The postoperative liver metastasis was recorded during the follow-up, and the liver metastasis-free survival was defined as the time from operation to the date of liver metastasis diagnosis or death. The nomogram was established based on independent prognostic factors selected by LASSO and multivariate Cox regression model. The performance was assessed using the concordance index (C-index) and calibration curves. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to determine the clinical utility of the nomogram model. Results: From the training cohort of 247 patients, a total of 132 patients developed liver metastasis during the follow-up, the 1-, 2- and 3- year liver metastasis-free survival were 52.4%, 43.5% and 40% respectively. The LASSO and multivariate Cox regression analysis indicated that postoperative CA125 (hazard ratio [HR] = 1.007, p <0.001), tumor differentiation (HR = 1.640, p = 0.010), tumor size (HR = 1.520, p = 0.029), lymph node ratio (HR = 1.897, p = 0.002) and portal/superior mesenteric/splenic vein invasion degree (PV/SMV/SV) (HR = 2.829, p <0.001) were the independent factors of liver metastasis. A nomogram with independent factors was developed and the C-index was 0.760 (95% confidence interval [CI], 0.720-0.799) and 0.739 (95% CI, 0.669-0.810) in the training and validation cohorts, respectively. The areas under curve (AUC) of the nomogram at 1-, 2- and 3-year were 0.815, 0.803 and 0.773 in the training cohort, and 0.765, 0.879 and 0.908 in the validation cohort, respectively, higher than those in TNM stage. Decision curve analysis (DCA) analysis revealed that the nomogram model provided superior net benefit in clinical utility. Liver metastasis-free survival curves showed a significant discriminatory ability for liver metastasis risk based on the nomogram (p <0.001). Conclusions: The nomogram showed high accuracy in predicting liver metastasis for PDAC after radical resection, and may serve as a clinical support tool to guide personalized and prescient intervention.

Predictive Value of the TP53 p.G245S Mutation Frequency for the Short-Term Recurrence of Hepatocellular Carcinoma as Detected by Pyrophosphate Sequencing.

Aims: We explored the relationship between the mutation at the p.G245S site in TP53 and the short-term recurrence of hepatocellular carcinoma (HCC). Materials and Methods: 101 HCC patients were included in this study. The TP53 p.G245S mutation frequency spectrum was examined by direct sequencing of genomic DNA from tissue specimens of HCC patients. Univariate and multivariate Cox regression analyses were performed to evaluate the independent prognostic factors of tumor recurrence. ROC curve analysis was applied to determine the cut-off value for the p.G245S mutation frequency and to verify the predictive ability of the Cox model compared with single risk factor indices. Results: A multivariate Cox regression analysis showed that TP53 p.G245S mutation frequency (HR = 1.231, 95% CI: 1.006-1.505, p = 0.043), AFP (HR = 2.432, 95% CI: 1.297-4.561, p = 0.006), MTM (HR = 2.656, 95% CI: 0.930-7.583, p = 0.068), and PVTT (HR = 14.297, 95% CI: 3.085-66.243, p = 0.001) were independent prognostic factors for short-term recurrence. The cut-off value for the TP53 p.G245S mutation frequency (18.5%) was determined by ROC analysis. A predictive model integrating the TP53 p.G245S mutation frequency with PVTT, MTM, and AFP values appears to an excellent predictive indicator of short-term recurrence in HCC patients (AUC = 0.849, 95% CI = 0.748-0.950, p = 0.000001). Survival analysis indicated that the probability of short-term recurrence-free survival was significantly different among different TP53 p.G245S mutation frequency, MTM, PVTT, and AFP risk groups (p < 0.05). Conclusion: The mutation frequency of the p.G245S site is a novel prognostic risk factor for the short-term recurrence of HCC.

A pan-cancer bioinformatic analysis of the carcinogenic role of SMARCA1 in human carcinomas.

SMARCA1is a mammalian imitation switch (ISWI) gene that encodes for SNF2L. SNF2L is involved in regulating cell transition from a committed progenitor state to a differentiated state. Although many papers have detailed the correlation between SMARCA1 and different cancers, no pan-cancer analysis has been conducted to date. We started by exploring the potential carcinogenic role of SMARCA1 across 33 carcinomas using the cancer genome atlas (TCGA) and the genotype-tissue expression (GTEx) databases. The expression of SMARCA1 was significantly elevated in some tumor types but not in others. There was a distinct relationship between SMARCA1 expression and patient prognosis. S116 phosphorylation levels were up-regulated in both lung adenocarcinoma and uterine corpus endometrial carcinoma. The expression level of SMARCA1 was positively correlated with cancer-associated fibroblasts infiltration in a number of tumors, such as colon adenocarcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma. It was also associated with CD8+ T-cell infiltration in head and neck squamous cell carcinoma and lung adenocarcinoma. Furthermore, SMARCA1 is involved in chromatin remodeling and protein processing-associated mechanisms. Our study presents an initial assessment and illustration of the carcinogenic role of SMARCA1 in different carcinomas.

Bile is a reliable and valuable source to study cfDNA in biliary tract cancers.

Objective: The aim of this study is to determine the clinical efficacy of bile-derived liquid biopsy compared with plasma and tumor tissue biopsy in patients with biliary tract carcinoma (BTC). Methods: A total of 13 patients with BTC were enrolled in this cohort. Tumor tissue, bile, and plasma samples were obtained and analyzed using next-generation sequencing for genomic profiling. Results: Bile and plasma samples were collected from all 13 patients, and 11 patients also had matched tumor tissues available. The cell-free DNA (cfDNA) concentration was significantly higher in the bile supernatant than in plasma (median: 1918 vs. 63.1 ng/ml, p = 0.0017). The bile supernatant and pellet had a significantly higher mean mutation allele frequency (MF) than plasma (median: 3.84% vs. 4.22% vs. 0.16%; p < 0.001). Genomic alterations were predominantly missense. Both bile supernatant and pellet had significantly more genomic alterations than plasma (average: 9.3 vs. 7.2 vs. 2.3 alterations per sample; p < 0.01). Among the top 10 most frequent genomic alterations, the consistency between bile supernatant and tumor tissue was 90.00% (18/20), that between bile pellet and tumor tissue was 85.00% (17/20), and that between the plasma and tissue was only 35.00% (7/20). MAF of both bile supernatant and pellet was positively correlated with that in tissue samples (ρ < 0.0001, spearman r = 0.777, and ρ < 0.0001, spearman r = 0.787, respectively), but no significant correlation with tissue was found in the plasma (ρ = 0.966, spearman r = 0.008). Furthermore, additional genomic alterations could be detected in bile supernatant and pellet than in tissue. Potential targets for targeted therapy were identified in bile supernatant and pellet. Regarding copy number variation (CNV) and chromosomal instability (CIN) detection, four additional CNVs from two patients were detected in the bile supernatant that was not detected in tissues (i.e., amplification of TERC, IL7R, RICTOR, and TERT). CIN was significantly higher in tumor tissue than in plasma. The CIN of the bile was also significantly higher than that of plasma. There was no significant difference in CIN between the tissue and the bile supernatant. Conclusion: The consistency of all genomic alterations and tumor tissue-determined genomic alteration in the bile supernatant/pellet was significantly higher than in plasma. Bile supernatants/pellets are better for genetic sequencing and may also have potential clinical value to guide targeted therapy and evaluate prognosis. Bile cfDNA may be a feasible substitute for tumor tissue in the genetic testing of patients with BTC.

Comprehensive bioinformatic analysis of MMP1 in hepatocellular carcinoma and establishment of relevant prognostic model.

Matrix metalloproteinase 1 (MMP1) encodes endopeptidases associated with degradation of multiple components of the extracellular matrix. This function has increasingly been considered to play a major proteolysis role in tumor invasion and metastasis. However, the relationship between MMP1 gene expression, tumor-immune microenvironment and prognosis in hepatocellular carcinoma patients remains mostly unclear. This study focused on a comprehensive analysis of MMP1 in hepatocellular carcinoma, specifically the prognosis and tumor-immune microenvironment. MMP1 expression was analyzed using TCGA database and clinical samples. MMP1 associated mechanisms, pathways, mutations and prognosis in hepatocellular carcinoma were evaluated. We also analyzed the tumor-immune microenvironment and corresponding treatments. Our research demonstrated that MMP1 expression was upregulated in patients with hepatocellular carcinoma and correlated with poor survival. A prognostic model was established and its performance evaluated. We also found and report various correlations between MMP1 and immune-related cells/genes, as well the potential therapeutic agents. These findings indicate that MMP1 can potentially be a promising prognostic biomarker and indicator of the tumor-immune microenvironment status in hepatocellular carcinoma.