Increased viral tolerance mediates by antiviral RNA interference in bat cells.

Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigate the antiviral RNA interference pathway in bat cells and discover that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs upon Sindbis virus infection that are missing in human cells. Disruption of Dicer function results in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors, such as retinoic acid-inducible gene I, with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.

Spatial transcriptomics in pancreatic cancer: Advances, prospects and challenges.

Pancreatic cancer remains one of the deadliest malignancies with an overall 5-year survival rate of 13 %. This dismal fact can be partly attributed to currently limited understanding of tumor heterogeneity and immune microenvironment. Traditional bulk-sequencing techniques overlook the diversity of tumor cells, while single-cell sequencing disorganizes the position localizing of cells in tumor microenvironment. The advent of spatial transcriptomics (ST) presents a novel solution by integrating location and whole transcript expression information. This technology allows for detailed observation of spatio-temporal changes across various cell subtypes within the pancreatic tumor microenvironment, providing insights into their potential functions. This review offers an overview of recent studies implementing ST in pancreatic cancer research, highlighting its instrumental role in investigating the heterogeneity and functions of tumor cells, stromal cells, and immune cells. On the basis, we also prospected and summarized the clinical application scenarios, technical limitations and challenges of ST technology in pancreatic cancer.

MiR-380 inhibits the proliferation and invasion of cholangiocarcinoma cells by silencing LIS1.

BACKGROUND: The objective of this study was to determine the role and regulatory mechanism of miR-380 in cholangiocarcinoma. METHODS: The TargetScan database and a dual-luciferase reporter assay system were used to determine if LIS1 was a target gene of miR-380. The Cell Counting Kit 8 assay, flow cytometry, and Transwell assay were used to detect the effects of miR-380 and LIS1 on the proliferation, S-phase ratio, and invasiveness of HCCC-9810/HuCCT1/QBC939 cells. Western blotting was used to determine the effect of miR-380 on MMP-2/p-AKT. Immunohistochemistry detected the regulatory effect of miR-380 on the expression of MMP-2/p-AKT/LIS1. RESULTS: Expression of miR-380 in cholangiocarcinoma was decreased but expression of LIS1 was increased. LIS1 was confirmed to be a target gene of miR-380. Transfection with miR-380 mimics inhibited the proliferation, S-phase arrest, and invasion of HCCC-9810/HuCCT1/QBC939 cells, and LIS1 reversed these inhibitory effects. miR-380 inhibitor promoted proliferation, S-phase ratio, and invasiveness of HCCC-9810/HuCCT1/QBC939 cells. si-LIS1 salvaged the promotive effect of miR-380 inhibitor. Overexpression of miR-380 inhibited expression of MMP-2/p-AKT/LIS1, but miR-380 inhibitor promoted their expression. CONCLUSION: An imbalance of miR-380 expression is closely related to cholangiocarcinoma, and overexpression of miR-380 inhibits the expression of MMP-2/p-AKT by directly targeting LIS1.

FOLFOXIRI plus cetuximab as conversion therapy for unresectable RAS/BRAF wild-type left-sided colorectal cancer with liver-limited metastases: a prospective dual-center pilot study.

Purpose: To explore the efficacy and safety of FOLFOXIRI plus cetuximab regimen as conversion therapy for patients with unresectable RAS/BRAF wild-type colorectal liver-limited metastases (CLM). Patients and methods: This was a dual-center, phase II trial with the rate of no evidence of disease (NED) achieved as the primary endpoint. All enrolled patients with initially unresectable left-sided RAS/BRAF wild-type colorectal liver-limited metastases received a modified FOLFOXIRI plus cetuximab regimen as conversion therapy. Results: Between October 2019 and October 2021, fifteen patients were enrolled. Nine patients (60%) achieved NED. The overall response rate (ORR) was 92.9%, and the disease control rate (DCR) was 100%. The median relapse-free survival (RFS) was 9 (95% CI: 0-20.7) months. The median progression-free survival (PFS) was 13.0 months (95% CI: 5.7-20.5), and the median overall survival (OS) was not reached. The most frequently occurring grade 3-4 adverse events were neutropenia (20%), peripheral neurotoxicity (13.3%), diarrhea (6.7%), and rash acneiform (6.7%). Conclusion: The FOLFOXIRI plus cetuximab regimen displayed tolerable toxicity and promising anti-tumor activity in terms of the rate of NED achieved and response rate in patients with initially unresectable left-sided RAS/BRAF wild-type CLM. This regimen merits further investigation.

SLC25A3 negatively regulates NLRP3 inflammasome activation by restricting the function of NLRP3.

The NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome activation plays a critical role in innate immune and pathogenic microorganism infections. However, excessive activation of NLRP3 inflammasome will lead to cellular inflammation and tissue damage, and naturally it must be precisely controlled in the host. Here, we discovered that solute carrier family 25 member 3 (SLC25A3), a mitochondrial phosphate carrier protein, plays an important role in negatively regulating NLRP3 inflammasome activation. We found that SLC25A3 could interact with NLRP3, overexpression of SLC25A3 and knockdown of SLC25A3 could regulate NLRP3 inflammasome activation, and the interaction of NLRP3 and SLC25A3 is significantly boosted in the mitochondria when the NLRP3 inflammasome is activated. Our detailed investigation demonstrated that the interaction between NLRP3 and SLC25A3 disrupted the interaction of NLRP3-NEK7, promoted ubiquitination of NLRP3, and negatively regulated NLRP3 inflammasome activation. Thus, these findings uncovered a new regulatory mechanism of NLRP3 inflammasome activation, which provides a new perspective for the therapy of NLRP3 inflammasome-associated inflammatory diseases.

Postoperative adjuvant chemotherapy is important for improving long-term survival in patients with colorectal cancer liver metastases undergoing simultaneous resection.

BACKGROUND AND AIM: A growing number of studies have demonstrated that neoadjuvant chemotherapy can improve the prognosis of patients with resectable colorectal liver metastases (CRLM). However, the routine use of postoperative adjuvant chemotherapy (POAC) for patients with CRLM after simultaneous resection remains controversial. This retrospective study investigated the impact of POAC on outcomes in patients with CRLM who underwent simultaneous resection of colorectal cancer tumors and liver metastases using propensity score matching (PSM) analysis. METHODS: From January 2009 to November 2020, patients with CRLM who underwent simultaneous resection were retrospectively enrolled. The confounding factors and selection bias were adjusted by 2:1 PSM. Patients were stratified into the POAC and non-POAC groups. Kaplan-Meier curves were utilized to compare overall survival (OS) and progression-free survival (PFS) between the groups. Univariate and multivariate Cox regression analyses were used to identify independent clinicopathological factors before and after PSM analysis. The utility of the model was evaluated using receiver operating characteristic (ROC) and calibration curves after PSM analysis. RESULTS: In total, 478 patients with resectable CRLM were enrolled and assigned to the POAC (n = 212, 60.9%) or non-POAC group (n = 136, 39.1%). After 2:1 PSM, there was no significant bias between the groups. Kaplan-Meier survival analysis revealed a significant effect of POAC on OS (P < 0.001) but not PFS. Multivariate Cox regression analysis identified T stage (T3-T4), lymph node metastasis, radiofrequency ablation during surgery, operative time ≥ 325 min, and the receipt of postoperative adjuvant chemotherapy (hazard ratio = 0.447, 95% confidence interval = 0.312-0.638, P < 0.001) as independent prognostic factors for OS. The areas under the ROC curves for the nomogram model for predicting 1-, 3-, and 5-year survival were 0.653, 0.628, and 0.678, respectively. Subgroups analysis suggested that POAC can enhance OS in patients with resectable CRLM with either low (1-2, P < 0.001) or high clinical risk scores (3-5, P = 0.020). CONCLUSIONS: Overall, this study identified POAC as a prognostic factor to predict OS in patients with CRLM undergoing simultaneous resection.

Analysis of textbook outcomes for ampullary carcinoma patients following pancreaticoduodenectomy.

BACKGROUND: Textbook outcomes (TOs) have been used to assess the quality of surgical treatment for many digestive tumours but not ampullary carcinoma (AC). AIM: To discuss the factors associated with achieving a TO and further explore the prognostic value of a TO for AC patients undergoing curative pancreaticoduodenectomy (PD). METHODS: Patients who underwent PD at the China National Cancer Center between 1998 and 2020 were identified. A TO was defined by R0 resection, examination of ≥ 12 Lymph nodes, no prolonged hospitalization, no intensive care unit treatment, no postoperative complications, and no 30-day readmission or mortality. Cox regression analysis was used to identify the prognostic value of a TO for overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to identify predictors of a TO. The rate of a TO and of each indicator were compared in patients who underwent surgery before and after 2010. RESULTS: Ultimately, only 24.3% of 272 AC patients achieved a TO. A TO was independently associated with improved OS [hazard ratio (HR): 0.443, 95% confidence interval (95%CI): 0.276-0.711, P = 0.001] and RFS (HR: 0.379, 95%CI: 0.228-0.629, P < 0.001) in the Cox regression analysis. Factors independently associated with a TO included a year of surgery between 2010 and 2020 (OR: 4.549, 95%CI: 2.064-10.028, P < 0.001) and N1 stage disease (OR: 2.251, 95%CI: 1.023-4.954, P = 0.044). In addition, the TO rate was significantly higher in patients who underwent surgery after 2010 (P < 0.001) than in those who underwent surgery before 2010. CONCLUSION: Only approximately a quarter (24.3%) of AC patients achieved a TO following PD. A TO was independently related to favourable oncological outcomes in AC and should be considered as an outcome measure for the quality of surgery. Further multicentre research is warranted to better elucidate its impact.

Hepatic arterial infusion chemotherapy versus sorafenib for advanced hepatocellular carcinoma with portal vein tumor thrombus: An updated meta-analysis and systematic review.

Background: Sorafenib was the first drug approved for advanced hepatocellular carcinoma (HCC). However, it is limited by poor efficacy for HCC with portal vein tumor thrombus (PVTT). Some studies suggested that hepatic artery infusion chemotherapy (HAIC) could provide survival benefits to patients with advanced HCC with PVTT. Aim: The study aimed to compare the efficacy of HAIC versus sorafenib in patients with HCC accompanied by PVTT. Methods: The PubMed, Embase, and Cochrane Library databases were searched for studies published until September 2022. Statistical analyses were performed using Stata SE 15 software. Results: Eight studies with 672 patients, 403 in the HAIC group and 269 in the sorafenib group, were included in the meta-analysis. The rates of complete response (RR=3.88, 95%CI:1.35-11.16, P=0.01), partial response (RR=3.46, 95%CI:1.94-6.18, P<0.0001), objective response rate (RR=4.21, 95%CI:2.44-7.28, P<0.00001) and disease control rate (RR=1.73, 95%CI:1.28-2.35, P=0.0004) were significantly higher in the HAIC group compared to the sorafenib group, whereas the progressive disease rate (RR=0.57, 95%CI:0.40-0.80, P=0.02) was significantly lower in the former. In contrast, the stable disease rate (RR=1.10, 95%CI (0.69-1.76), P=0.68) was similar in both groups. The overall survival (HR=0.50, 95%CI:0.40-0.63, P<0.05) and progression-free survival (HR=0.49, 95%CI:0.35-0.67, P<0.05) rates were significantly higher in the HAIC group compared to the sorafenib group. Conclusion: HAIC has better efficacy against HCC with PVTT than sorafenib and may be considered an alternative to the latter. However, more high-quality randomized control trials and longer follow-ups are needed to verify our findings.

At least 16 lymph nodes are recommended to examine during pancreaticoduodenectomy in ampullary adenocarcinoma.

The minimum number of lymph nodes to be examined during pancreaticoduodenectomy (PD) for patients with ampullary adenocarcinoma (AC) is still debatable due to limited clinical data. Therefore, here we explored the relationship between the number of examined lymph node (ELN) and the current N staging (American Joint Committee on Cancer staging system, AJCC, 8 edition) after PD for AC as well as determined the minimum number of examined lymph nodes (MNELN) to ensure the accurate detection of nodal involvement. Patients underwent PD for AC in the National Cancer Center cohort of China (NCC cohort of China) from 1998 to 2020 and in the Surveillance, Epidemiology, and End Results database (SEER database) from 2010 to 2018 were retrospectively reviewed, and a total of 452 eligible patients were included in this study. The MNELN was evaluated by binomial probability law and best survival separation methods. Furthermore, the cut-off value of MNELN was validated in the NCC cohort of China using Least Absolute Shrinkage and Selection Operator (LASSO) regression. Our analysis indicated that the median number of ELN was 14, and the number of ELN was positively correlated with N stage. The MNELN was 16, whereas the best survival separation of ELN was 38 in node-positive patients and 3 in node-negative patients. In the validation cohort, the number of 16 ELNs was identified as a predictive variable for lymph node metastasis with nonzero coefficients in the LASSO-logistic regression model. Together, we concluded that a greater number of ELN was associated with more accurate nodal status assessment in PD for AC patients. A minimum of 16 lymph nodes were required to during PD in AC patients.

Emergency versus delayed hepatectomy following transarterial embolization in spontaneously ruptured hepatocellular carcinoma survivors: a systematic review and meta-analysis.

BACKGROUND: Spontaneous rupture is a life-threatening complication of hepatocellular carcinoma (HCC). Recent trends in surgical treatments avoid emergency hepatectomy (EH) and favor emergency transarterial embolization (TAE) followed by delayed hepatectomy (DH). Still, there is debate on which is the better treatment option and whether delaying hepatectomy increases peritoneal metastasis. AIM: To provide evidence-based references for the optimal management of patients with spontaneously ruptured HCC by comparing the outcomes of EH and DH. METHODS: Literature on postoperative outcomes of EH and DH in patients with spontaneously ruptured HCC published between the date of the database establishment and May 2022, was identified in the PubMed, EMBASE, and Cochrane Library databases. Revman 5.3 software was used for statistical analyses. RESULTS: Nine publications were identified, including a total of 681 patients. Of those, 304 underwent EH, and 377 underwent TAE followed by DH. The meta-analysis results indicated that the in-hospital mortality rate in the EH patient group was significantly higher than that in the DH patient group (relative risk (RR) = 2.17, 95% confidence interval (CI) 1.03-4.57, p =0.04). There was no significant differences in the rates of postoperative complications (RR = 1.21, 95% CI 0.77-1.90, p = 0.40), postoperative hospital stay (WMD = - 0.64, 95% CI - 5.61-4.34, p = 0.80), recurrence (RR = 1.09, 95% CI 0.94-1.25, p = 0.27), peritoneal metastasis (RR = 1.06, 95% CI 0.66-1.71, p = 0.80), 1-year survival (RR = 0.91, 95% CI 0.80-1.02, p = 0.11), or 3-year survival (RR = 0.81, 95% CI 0.61-1.09, p = 0.17) in survivors between the two patient groups. CONCLUSION: The postoperative outcomes of the spontaneously ruptured HCC survivors who received EH were similar to those who received emergency TAE followed by DH. However, the in-hospital mortality rate was higher in EH patients. Based on the findings, DH with TAE first strategy might be considered over EH as the first line treatment modality. However, these findings await further validation by future high-quality studies.

Research progress of spontaneous ruptured hepatocellular carcinoma: Systematic review and meta-analysis.

Background: Spontaneously ruptured hepatocellular carcinoma (rHCC) with hemorrhage is characterized by rapid onset and progression. The aim of this systematic review was to explore the current studies on rHCC with hemorrhage and determine the optimum treatment strategy. Method: The PubMed, Web of Science, Embase, and the Cochrane Library databases were searched for studies reporting survival outcomes with comparison between emergency resection (ER) and transarterial embolization following staged hepatectomy (SH) were included by inclusion and exclusion criteria, the perioperative and survival data were statistically summarized using Review Manager 5.3 software. Result: A total of 8 retrospective studies were included, with a total sample size of 556, including 285 (51.3%) in the ER group and 271 (48.7%) in the SH group. The perioperative blood loss and blood transfusion volume in the SH group were less than those in the ER group, and there were no significant differences in the operative time, incidence of complications, mortality and recurrence rate of tumors between the two groups. The 1-, 2-, 3-year overall survival and 1-, 2-, 3-, 5-year disease-free survival of the ER group were not significantly different from those of the SH group, and the 5-year overall survival rate of ER group was lower than that of the SH group (hazard ratios=1.52; 95% confidence intervals: 1.14-2.03, P=0.005). Conclusion: There was no significant difference in the short-term efficacy of ER or SH in the treatment of ruptured HCC, and SH was superior to ER in the long-term survival.

Impact of Diabetes on Short-Term and Long-Term Outcomes of Ampullary Adenocarcinoma Patients after Curative Pancreatoduodenectomy.

BACKGROUND: Many studies have confirmed that diabetes was associated with prognosis in many malignant cancer types. However, the impact of diabetes on ampullary carcinoma (AC) has not been investigated. METHODS: A total of 266 AC patients in the National Cancer Center of China between January 1998 and December 2020 were retrospectively reviewed. The postoperative complication rate, postoperative recurrence rate, and long-term survival were compared between the diabetes group and the no diabetes group. RESULTS: A total of 32 AC patients (12.03%) were diagnosed with diabetes before surgery. In total, 111 patients (41.73%) had one or more postoperative complications, and there was no perioperative death. There was no statistically significant difference regarding postoperative complications between the diabetes group and the no diabetes group. Altogether, 120 patients (45.11%) experienced postoperative recurrence. Multivariate analysis revealed that diabetes was an independent risk factor for the recurrence (OR: 2.384, 95% CI: 1.065-5.336, p = 0.035), OS (HR: 1.597, 95% CI: 1.005-2.537, p = 0.047), and RFS (HR: 1.768, 95% CI: 1.068-2.925, p = 0.027) in AC patients after curative pancreatoduodenectomy. CONCLUSIONS: Diabetes may adversely affect the recurrence of patients with AC after curative pancreaticoduodenectomy, leading to an increased risk of poor prognosis in early-stage patients. Further studies involving a large sample size are needed to validate our results.

Long-term survival and pattern of recurrence in ampullary adenocarcinoma patients after curative Whipple's resection: a retrospective cohort study in the National Cancer Center in China.

Due to the low incidence of ampullary adenocarcinoma (AA), the recurrence patterns, risk factors for recurrence and post-recurrence treatment are still debated. The purpose of this study is to clarify such clinical issues based on the retrospective data at the National Cancer Center in China. Finally, one hundred and eighty-two AA patients after curative Whipple's resection from 1998 to 2019 were retrospectively reviewed. Among them, 27 patients had locoregional recurrence and 61 patients had systemic recurrence. However, no significant difference of clinicopathological features and survival were found between locoregional recurrence and distant metastasis. In the recurrence group, the 1-year, 2-year, and 3-year recurrence-free survival and overall survival were 59.1%, 29.5%, 10.2%, 88.6%, 61.6%, and 37.6%, respectively. AA patients with recurrence have a worse prognosis than those without recurrence, regardless of stage. In addition, we found that advanced T stage and lymphovascular invasion were two independent risk factors for RFS in AA patients after curative Whipple's resection. In conclusion, AA patients with recurrence have a poor prognosis. Advanced T stage and lymphovascular invasion were two independent risk factors for recurrence-free survival in AA patients after curative Whipple's resection. Nevertheless, further studies with larger sample sizes are needed to fully validate.

GRSF1 predicts an unfavorable prognosis and promotes tumorigenesis in lung adenocarcinoma based on bioinformatics analysis and in vitro validation.

Background: Effective biomarkers play a critical role in improving clinical approaches to treat lung adenocarcinoma (LUAD). However, many existing biomarkers have limitations due to a lot of factors, requiring the development of additional biomarkers to effectively predict the disease course and prognosis of LUAD. Guanine-rich RNA sequence binding factor 1 (GRSF1) participates in multiple biological processes, but its regulatory effect on LUAD remains unknown. The present study aimed to investigate the clinicopathological importance and biological role of GRSF1 in LUAD. Methods: The expression of GRSF1 was evaluated using multiple service portals. X-Tile software were used to determine the high and low GRSF1 groups and the relationships between GRSF1 expression and clinicopathological characteristics were then analyzed by R packages. Besides, prognostic significance was identified by the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Kaplan-Meier (K-M) Plotter. Overall survival (OS) and disease-free survival (DFS) was the main outcome of prognosis analysis. The DNA copy number alterations (CNAs) and methylations were calculated using cBioPortal and R packages. The co-expressed genes of GRSF1 were obtained from LinkedOmics, and functional networks were then constructed by R clusterProfiler. Additionally, cell counting kit 8 (CCK-8) and colony formation assays were applied to verify the proliferation effects of GRSF1 on LUAD cells. Results: GRSF1 was significantly upregulated in the LUAD tissues compared to the non-tumor lung tissues (all P<0.05), and its expression was significantly correlated with gender (χ2=6.873, P=0.009) and T classification (χ2=13.62, P=0.003). Higher GRSF1 expression indicated worse OS [hazards ratio (HR) =1.6, P=0.0022] and DFS (HR =1.4, P=0.043), which suggested that GRSF1 was an independent prognostic factor for LUAD. DNA gain/amplification and hypomethylation may also contribute to GRSF1 upregulation. The functional annotation showed that GRSF1 regulates tumorigenesis through several signaling pathways. The knockdown of GRSF1 significantly suppressed lung cancer cell proliferation in vitro. Conclusions: The high expression of GRSF1 indicated an unfavorable prognosis and was closely related to LUAD tumor occurrence and development, which could be used as an effective prognostic biomarker for patients suffering from LUAD.

Survival of Patients Subjected to Hepatectomy After Spontaneous Rupture of Hepatocellular Carcinoma: A Meta-analysis of High-quality Propensity Score Matching Studies.

Background: The spontaneous rupture of hepatocellular carcinoma (HCC) is associated with high mortality rates, and liver resection can provide better outcomes than other available treatments. However, the survival length of patients subjected to hepatectomy after spontaneous rupture of hepatocellular carcinoma remains controversial. Method: Articles reporting the comparison of the survival outcome between patients with rupture HCC (rHCC) and non-rupture HCC (nrHCC) from the inception until December 31, 2021 by PubMed, Web of Science, OVID, and the Cochrane Library databases were included. The high-quality propensity score matching analysis was used to investigate the impact of rupture on disease-free survival (DFS) and overall survival (OS) between the rHCC and nrHCC group with no heterogeneity. Result: A total of 606 patients from six cohort studies were included. The major baseline characteristics of the eligible patients were well balanced between rHCC and nrHCC group. The 1-, 3-, and 5-year hazard ratios of DFS were 3.45 (95% confidence interval [CI] 2.54-4.68), 3.63 (95% CI 2.87-4.60), and 3.72 (95% CI 2.93-4.72), respectively. The 1-, 3-, and 5-year hazard ratios of OS were 5.01 (95% CI 3.26-7.69), 5.49 (95% CI 4.08-7.39), and 4.20 (95% CI 3.20-5.51), respectively. Conclusion: The present meta-analysis demonstrated that the DSF and OS were significantly shorter in the rHCC group than in the nrHCC group, thus revealing that spontaneous HCC rupture was a predictor of poor survival.

Treatment of Metastatic Primary Extramammary Paget Disease With Combination Anlotinib and Tislelizumab: A Case Report and Review of the Literature.

Extramammary Paget's disease (EMPD) is a rare cutaneous neoplasm with distant metastases and a poor prognosis. We report the case of a 63-year-old male patient exhibiting stage IV primary EMPD with neuroendocrine differentiation, and harboring a somatic mutation in AMER1. After four cycles of Anlotinib combined with Tislelizumab, the patient achieved partial response for the metastatic lesions according to mRECIST1.1 criteria. Total positron emission tomography and computed tomography (PET-CT) scans revealed a significant reduction in SUV from 18.9 to 5.3, and the serum CEA decreased to normal levels after the treatment regimen. However, the patient developed fractures of the fourth and fifth thoracic vertebrae during the treatment. Therefore, percutaneous vertebroplasty was performed, and the patient experienced severe postoperative pneumonia and died from pulmonary encephalopathy and respiratory failure in June 2021. The overall and progression-free survival of the patient after diagnosis were 9 and 8 months, respectively. During the systemic treatment, the patient suffered grade 1 rash in the back and thigh and grade 1 hypertension. Nevertheless, the combination treatment of anlotinib and tislelizumab had a favorable clinical outcome and provided a survival advantage, and should be considered a therapeutic option for patients with AMER1-mutant metastatic EMPD.

Preoperative Concurrent Chemoradiotherapy Versus Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: Phase II Randomized Study.

Objective: We evaluated and compared the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) versus neoadjuvant chemotherapy (NACT) for locally advanced gastric cancer (LAGC) in a single-center randomized phase II trial. Methods: Patients with LAGC were enrolled and received either NACT or NACRT, followed by gastrectomy and adjuvant chemotherapy. The primary endpoint was an R0 resection rate. Results: We enrolled 75 patients: 75.7% (NACT, 28/37 patients) and 76.3% (NACRT, 29/38 patients) underwent surgery; R0 resection rates were 73.0% (27/37) and 73.7% (28/38), respectively. The NACRT group had significantly better major pathological response than the NACT group (37.9% vs 17.9%, p = 0.019). Between-group postoperative complications were not significantly different. The median follow-up was 59.6 months; 5-year overall survival (OS) rate was 50.1% (NACT) and 61.9% (NACRT); neither group reached the median OS; median progression-free survival was 37.3 and 63.4 months, respectively. Conclusions: S-1-based NACRT did not improve the R0 resection rate, although it presented better tumor regression with similar safety to NACT. Trial registration: ClinicalTrial.gov NCT02301481.

ASB17 Facilitates the Burst of LPS-Induced Inflammation Through Maintaining TRAF6 Stability.

ASB17, a member of the ankyrin repeat and SOCS box-containing protein (ASB) family, has been supposed to act as an E3 ubiquitin ligase. Actually, little is known about its biological function. In this study, we found that ASB17 knocking-out impaired the expression of the pro-inflammatory cytokines CCL2 and IL-6 in bone marrow-derived dendritic cells (BMDCs) stimulated by lipopolysaccharide (LPS), indicating an inflammation-promoting role of this gene. We reveal that ASB17 promotes LPS-induced nuclear factor kappa B (NF-κB) signal activation through interacting with TNF receptor-associated factor 6 (TRAF6) which is a crucial adaptor protein downstream of toll-like receptors (TLR). ASB17 via its aa177-250 segment interacts with the Zn finger domain of TRAF6. The interaction of ASB17 stabilizes TRAF6 protein through inhibiting K48-linked TRAF6 polyubiquitination. Therefore, we suggest that ASB17 facilitates LPS-induced NF-κB activation by maintaining TRAF6 protein stability. The inflammation enhancer role of ASB17 is recognized here, which provides new understanding of the activation process of inflammation and immune response.

Short- and long-term outcomes of laparoscopic vs open surgery for T2 gallbladder cancer: A systematic review and meta-analysis.

BACKGROUND: With the development of laparoscopic techniques, gallbladder cancer (GBC) is no longer a contraindication to laparoscopic surgery (LS). Although LS is recommended for stage T1 GBC, the value of LS for stage T2 GBC is still controversial. AIM: To evaluate the short- and long-term outcomes of LS in comparison to those of open surgery (OS) for stage T2 GBC. METHODS: We searched the PubMed, Embase, Cochrane Library, Ovid, Google Scholar, and Web of Science databases for published studies comparing the efficacy of LS and OS in the treatment of stage T2 GBC, with a cutoff date of September 2022. The Stata 15 statistical software was used for analysis. Relative risk (RR) and weighted mean difference (WMD) were calculated to assess binary and continuous outcome indicators, respectively. Begg's test and Egger's test were used for detecting publication bias. RESULTS: A total of five studies were included, with a total of 297 patients, 153 in the LS group and 144 in the OS group. Meta-analysis results showed that the LS group was better than the OS group in terms of operative time [WMD = -41.29, 95% confidence interval (CI): -75.66 to -6.92, P = 0.02], estimated blood loss (WMD = -261.96, 95%CI: -472.60 to -51.31, P = 0.01), and hospital stay (WMD = -5.67, 95%CI: -8.53 to -2.81, P = 0.0001), whereas there was no significant difference between the two groups in terms of blood transfusion (RR = 0.60, 95%CI: 0.31-1.15, P = 0.13), complications (RR = 0.72, 95%CI: 0.39-1.33, P = 0.29), number of lymph nodes retrieved (WMD = -1.71, 95%CI: -4.27 to -0.84, P = 0.19), recurrence (RR = 0.41, 95%CI: 0.06-2.84, P = 0.36), 3-year and 5-year overall survival (RR = 0.99, 95%CI: 0.82-1.18, P = 0.89 and RR = 1.02, 95%CI: 0.68-1.53, P = 0.92; respectively), and 3-year and 5-year disease-free survival (RR = 1.01, 95%CI: 0.84-1.21, P = 0.93 and RR = 1.15, 95%CI: 0.90-1.46, P = 0.26; respectively). CONCLUSION: The long-term outcomes of LS for T2 GBC are similar to those of OS, but LS is superior to OS in terms of operative time, intraoperative bleeding, and postoperative hospital stay. Nevertheless, these findings should be validated via high-quality randomized controlled trials and longer follow-ups.

Chinese expert recommendations on management of hepatocellular carcinoma during COVID-19 pandemic: a nationwide multicenter survey.

BACKGROUND: This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic. METHODS: A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic. RESULTS: 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the "face-to-face" visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC. DISCUSSION: During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery.