Evaluating the efficacy of laparoscopic radical antegrade modular pancreatosplenectomy in selected early-stage left-sided pancreatic cancer: a propensity score matching study.

BACKGROUND: Laparoscopic radical pancreatectomy is safe and beneficial for recectable pancreatic cancer, but the extent of resection for early-stage tumors remains controversial. METHODS: Consecutive patients with left-sided pancreatic cancer who underwent either laparoscopic radical antegrade modular pancreatosplenectomy (LRAMPS, n = 54) or laparoscopic distal pancreatosplecnectomy (LDP, n = 131) between October 2020 and December 2022 were reviewed. The preoperative radiological selection criteria were as follows: (1) tumor diameter ≤ 4 cm; (2) located ≥ 1 cm from the celiac trunk; (3) didn't invade the fascial layer behind the pancreas. RESULTS: After 1:1 propensity score matching (LRAMPS, n = 54; LDP, n = 54), baseline data were well-balanced with no differences. LRAMPS resulted in longer operation time (240.5 vs. 219.0 min, P = 0.020) and higher intraoperative bleeding volume (200 vs. 150 mL, P = 0.001) compared to LDP. Although LRAMPS harvested more lymph nodes (16 vs. 13, P = 0.008), there were no statistically significant differences in lymph node positivity rate (35.2% vs. 33.3%), R0 pancreatic transection margin (94.4% vs. 96.3%), and retroperitoneal margin (83.3% vs. 87.0%) rate. Postoperative complications did not significantly differ between the two groups. However, LRAMPS was associated with increased drainage volume (85.0 vs. 40.0 mL, P = 0.001), longer time to recover semi-liquid diet compared to LDP (5 vs. 4 days, P < 0.001) and increased daily bowel movement frequency. Tumor recurrence pattern and recurrence-free survival were comparable between the two groups, but the adjuvant chemotherapy regimens varied, and the completion rate of the 6-month intravenous chemotherapy was lower in the LRAMPS group compared to the LDP group (51.9% vs. 75.9%, P = 0.016). CONCLUSIONS: LRAMPS did not provide oncological benefits over LDP for left-sided pancreatic cancer within the selection criteria, but it increased operation time, intraoperative bleeding, and postoperative bowel movement frequency. These factors impacted the regimen selection and completion of adjuvant chemotherapy, consequently compromising the potential benefits of LRAMPS in achieving better local control.

Cancer immunometabolism: advent, challenges, and perspective.

For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, and discuss the ongoing and upcoming realities of clinical treatment. It is expected that future research will reduce the current limitations of immunotherapy and provide a positive hand in immune responses to exert a broader therapeutic role.

Multiscale and multiperception feature learning for pancreatic lesion detection based on noncontrast CT.

Background. Pancreatic cancer is one of the most malignant tumours, demonstrating a poor prognosis and nearly identically high mortality and morbidity, mainly because of the difficulty of early diagnosis and timely treatment for localized stages.Objective. To develop a noncontrast CT (NCCT)-based pancreatic lesion detection model that could serve as an intelligent tool for diagnosing pancreatic cancer early, overcoming the challenges associated with low contrast intensities and complex anatomical structures present in NCCT images.Approach.We design a multiscale and multiperception (MSMP) feature learning network with ResNet50 coupled with a feature pyramid network as the backbone for strengthening feature expressions. We added multiscale atrous convolutions to expand different receptive fields, contextual attention to perceive contextual information, and channel and spatial attention to focus on important channels and spatial regions, respectively. The MSMP network then acts as a feature extractor for proposing an NCCT-based pancreatic lesion detection model with image patches covering the pancreas as its input; Faster R-CNN is employed as the detection method for accurately detecting pancreatic lesions.Main results. By using the new MSMP network as a feature extractor, our model outperforms the conventional object detection algorithms in terms of the recall (75.40% and 90.95%), precision (40.84% and 68.21%), F1 score (52.98% and 77.96%), F2 score (64.48% and 85.26%) and Ap50 metrics (53.53% and 70.14%) at the image and patient levels, respectively.Significance.The good performance of our new model implies that MSMP can mine NCCT imaging features for detecting pancreatic lesions from complex backgrounds well. The proposed detection model is expected to be further developed as an intelligent method for the early detection of pancreatic cancer.

Efficacy of hepatectomy for hepatolithiasis using 3D visualization combined with ICG fluorescence imaging: A retrospective cohort study.

BACKGROUND: Hepatolithiasis is a complex condition that poses challenges and difficulties in surgical treatment. Three-dimensional visualization technology combined with fluorescence imaging (3DVT-FI) enables accurate preoperative assessment and real-time intraoperative navigation. However, the perioperative outcomes of 3DVT-FI in hepatolithiasis have not been reported. We aim to evaluate the efficacy of 3DVT-FI in the treatment of hepatolithiasis. METHODS: A retrospective analysis was performed on 128 patients who underwent hepatectomy for hepatolithiasis at the Department of Hepatobiliary Surgery, Zhujiang Hospital, between January 2017 and December 2022. Among them, 50 patients underwent hepatectomy using 3DVT-FI (3DVT-FI group), while 78 patients underwent conventional hepatectomy without 3DVT-FI (CH group). The operative data, postoperative liver function indices, complication rates and stone residue were compared between the two groups. RESULTS: There were no significant differences in preoperative baseline data between the two groups (p > 0.05). Compared with the CH group, the 3DVT-FI group exhibited lower intraoperative blood loss (140.00 ± 112.12 vs. 225.99 ± 186.50 mL, p = 0.001), and a lower intraoperative transfusion rate (8.0% vs. 23.1%, p = 0.027). The overall incidence of postoperative complications did not differ significantly (22.0% vs. 35.9%, p = 0.096). The 3DVT-FI group was associated with a lower immediate residual stone rate (16.0% vs. 34.6%, p = 0.021). There were no perioperative deaths in the 3DVT-FI group, while one perioperative death occurred in the CH group. CONCLUSIONS: The 3DVT-FI may offer significant benefits in terms of surgical safety, reduced intraoperative bleeding and decreased stone residue during hepatectomy for hepatolithiasis.

SMAD4 endows TGF-ß1-induced highly invasive tumor cells with ferroptosis vulnerability in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy prone to recurrence and metastasis. Studies show that tumor cells with increased invasive and metastatic potential are more likely to undergo ferroptosis. SMAD4 is a critical molecule in the transforming growth factor ß (TGF-ß) pathway, which affects the TGF-ß-induced epithelial-mesenchymal transition (EMT) status. SMAD4 loss is observed in more than half of patients with PDAC. In this study, we investigated whether SMAD4-positive PDAC cells were prone to ferroptosis because of their high invasiveness. We showed that SMAD4 status almost determined the orientation of transforming growth factor ß1 (TGF-ß1)-induced EMT via the SMAD4-dependent canonical pathway in PDAC, which altered ferroptosis vulnerability. We identified glutathione peroxidase 4 (GPX4), which inhibited ferroptosis, as a SMAD4 down-regulated gene by RNA sequencing. We found that SMAD4 bound to the promoter of GPX4 and decreased GPX4 transcription in PDAC. Furthermore, TGF-ß1-induced high invasiveness enhanced sensitivity of SMAD4-positive organoids and pancreas xenograft models to the ferroptosis inducer RAS-selective lethal 3 (RSL3). Moreover, SMAD4 enhanced the cytotoxic effect of gemcitabine combined with RSL3 in highly invasive PDAC cells. This study provides new ideas for the treatment of PDAC, especially SMAD4-positive PDAC.

Computed tomography and guidelines-based human-machine fusion model for predicting resectability of the pancreatic cancer.

BACKGROUND AND AIM: The study aims to develop a hybrid machine learning model for predicting resectability of the pancreatic cancer, which is based on computed tomography (CT) and National Comprehensive Cancer Network (NCCN) guidelines. METHOD: We retrospectively studied 349 patients. One hundred seventy-one cases from Center 1 and 92 cases from Center 2 were used as the primary training cohort, and 66 cases from Center 3 and 20 cases from Center 4 were used as the independent test dataset. Semi-automatic module of ITK-SNAP software was used to assist CT image segmentation to obtain three-dimensional (3D) imaging region of interest (ROI). There were 788 handcrafted features extracted for 3D ROI using PyRadiomics. The optimal feature subset consists of three features screened by three feature selection methods as the input of the SVM to construct the conventional radiomics-based predictive model (cRad). 3D ROI was used to unify the resolution by 3D spline interpolation method for constructing the 3D tumor imaging tensor. Using 3D tumor image tensor as input, 3D kernelled support tensor machine-based predictive model (KSTM), and 3D ResNet-based deep learning predictive model (ResNet) were constructed. Multi-classifier fusion ML model is constructed by fusing cRad, KSTM, and ResNet using multi-classifier fusion strategy. Two experts with more than 10 years of clinical experience were invited to reevaluate each patient based on their CECT following the NCCN guidelines to obtain resectable, unresectable, and borderline resectable diagnoses. The three results were converted into probability values of 0.25, 0.75, and 0.50, respectively, according to the traditional empirical method. Then it is used as an independent classifier and integrated with multi-classifier fusion machine learning (ML) model to obtain the human-machine fusion ML model (HMfML). RESULTS: Multi-classifier fusion ML model's area under receiver operating characteristic curve (AUC; 0.8610), predictive accuracy (ACC: 80.23%), sensitivity (SEN: 78.95%), and specificity (SPE: 80.60%) is better than cRad, KSTM, and ResNet-based single-classifier models and their two-classifier fusion models. This means that three different models have mined complementary CECT feature expression from different perspectives and can be integrated through CFS-ER, so that the fusion model has better performance. HMfML's AUC (0.8845), ACC (82.56%), SEN (84.21%), SPE (82.09%). This means that ML models might learn extra information from CECT that experts cannot distinguish, thus complementing expert experience and improving the performance of hybrid ML models. CONCLUSION: HMfML can predict PC resectability with high accuracy.

A simple and efficient strategy for cell-based and cell-free-based therapies in acute liver failure: hUCMSCs bioartificial liver.

Acute liver failure (ALF) is a life-threatening condition. Cell-based and cell-free-based therapies have proven to be effective in treating ALF; however, their clinical application is limited by cell tumorigenicity and extracellular vesicle (EV) isolation in large doses. Here, we explored the effectiveness and mechanism of umbilical cord mesenchymal stem cells (hUCMSCs)-based bioartificial liver (hUCMSC-BAL), which is a simple and efficient strategy for ALF. D-galactosamine-based pig and mouse ALF models were used to explore the effectiveness of hUCMSC-BAL and hUCMSC-sEV therapies. Furthermore, high-throughput sequencing, miRNA transcriptome analysis, and western blot were performed to clarify whether the miR-139-5p/PDE4D axis plays a critical role in the ALF model in vivo and in vitro. hUCMSC-BAL significantly reduced inflammatory responses and cell apoptosis. hUCMSC-sEV significantly improved liver function in ALF mice and enhanced the regeneration of liver cells. Furthermore, hUCMSC-sEV miRNA transcriptome analysis showed that miR-139-5p had the highest expression and that PDE4D was one of its main target genes. The sEV miR-139-5p/PDE4D axis played a role in the treatment of ALF by inhibiting cell apoptosis. Our data indicate that hUCMSC-BAL can inhibit cytokine storms and cell apoptosis through the sEV miR-139-5p/PDE4D axis. Therefore, we propose hUCMSC-BAL as a therapeutic strategy for patients with early ALF.

Fatal hepatic failure following atorvastatin treatment: A case report.

RATIONALE: Atorvastatin is a commonly used statin for the treatment of hypercholesterolemia in people at high risk for coronary, cerebrovascular, and peripheral artery disease. However, fatal liver failure due to atorvastatin treatment has been rarely reported, especially during the very short incubation period. PATIENT CONCERNS: A 63-year-old male patient was admitted due to unexplained chest pain. After admission, his liver function had decreased < 24 hours after taking 20 mg tablets of atorvastatin due to lacunar infarction, which was improved after drug withdrawal. The treatment regimen was restarted 15 days later, but within 16 hours, the patient developed multiple organ failure, including liver failure and renal failure. DIAGNOSES: The pathological results after 7 days indicated focal inflammatory necrosis, virus and autoimmune correlation tests were negative, which did not rule out drug-induced liver injury. Interventions: receiving artificial liver therapy, continuous renal replacement therapy and other organ support treatment. OUTCOMES: The patient died 18 days after admission. LESSONS: Statin idiosyncratic liver injury is very rare, but the consequences can be serious.

Research progress on the hematopoietic microenvironment in aplastic anemia.

Aplastic anemia (AA) is a disease of bone marrow hematopoietic failure, and the main clinical manifestation is pancytopenia. Its pathogenesis is still unclear. In recent years, more research has been done on its immune abnormalities to explain its pathogenesis and less on the hematopoietic microenvironment, but there are still some advances. This article summarizes the research on the hematopoietic microenvironment of AA in recent years to provide new ideas for the clinical treatment of AA.

Establishment of acute liver failure model in Tibetan miniature pig and verified by dual plasma molecular adsorption system.

BACKGROUND: Acute liver failure (ALF) is a severe liver disease with high morbidity and mortality rates. Animal models are important for research on ALF. This study aimed to establish a reproducible, Tibetan miniature pig model of D-galactosamine-induced ALF and verify it using a dual plasma molecular adsorption system (DPMAS). METHODS: Tibet miniature pigs were randomly divided into four groups (A, B, C, D) after catheterization. D-galactosamine (D-gal) at 0.45, 0.40, 0.35, and 0.35 g/kg body weight, respectively, was injected through the catheter. Group D was treated with DPMAS 48 h after D-gal administration. Vital signs and blood index values were recorded every 12 h after D-gal administration. H&E, TUNEL, Ki67, and Masson staining tests were performed. RESULTS: After D-gal administration, Tibetan miniature pigs developed different degrees of debilitation, loss of appetite, and jaundice. Survival times of groups A, B, C, and D were 39.7 ± 5.9, 53.0 ± 12.5,61.3 ± 8.1, and 61 ± 7 h, respectively. Blood levels of ALT, AST, TBIL, ammonia, PT, and inflammation factors significantly increased compared with baseline levels in the different groups (Ps < 0.05). Pathological results revealed a clear liver cell necrosis positive correlation with D-gal dose. However, DPMAS did not increase the survival time in ALF, ammonia, or liver cell necrosis. CONCLUSION: We successfully established a reproducible Tibetan miniature pig model of d-galactosamine-induced ALF, and we believe that a dosage of 0.35 g/kg is optimal.

A multimodal model fusing multiphase contrast-enhanced CT and clinical characteristics for predicting lymph node metastases of pancreatic cancer.

Objective.To develop a multimodal model that combines multiphase contrast-enhanced computed tomography (CECT) imaging and clinical characteristics, including experts' experience, to preoperatively predict lymph node metastasis (LNM) in pancreatic cancer patients.Methods.We proposed a new classifier fusion strategy (CFS) based on a new evidential reasoning (ER) rule (CFS-nER) by combining nomogram weights into a previous ER rule-based CFS. Three kernelled support tensor machine-based classifiers with plain, arterial, and venous phases of CECT as the inputs, respectively, were constructed. They were then fused based on the CFS-nER to construct a fusion model of multiphase CECT. The clinical characteristics were analyzed by univariate and multivariable logistic regression to screen risk factors, which were used to construct correspondent risk factor-based classifiers. Finally, the fusion model of the three phases of CECT and each risk factor-based classifier were fused further to construct the multimodal model based on our CFS-nER, named MMM-nER. This study consisted of 186 patients diagnosed with pancreatic cancer from four clinical centers in China, 88 (47.31%) of whom had LNM.Results.The fusion model of the three phases of CECT performed better overall than single and two-phase fusion models; this implies that the three considered phases of CECT were supplementary and complemented one another. The MMM-nER further improved the predictive performance, which implies that our MMM-nER can complement the supplementary information between CECT and clinical characteristics. The MMM-nER had better predictive performance than based on previous classifier fusion strategies, which presents the advantage of our CFS-nER.Conclusion.We proposed a new CFS-nER, based on which the fusion model of the three phases of CECT and MMM-nER were constructed and performed better than all compared methods. MMM-nER achieved an encouraging performance, implying that it can assist clinicians in noninvasively and preoperatively evaluating the lymph node status of pancreatic cancer.

Occult colon cancer with sepsis as the primary manifestation identified by bone marrow puncture: A case report.

BACKGROUND: Bone marrow metastasis is common in liver and lung cancer, but there are few reports on bone marrow metastasis in colon cancer. To date, there are no such reports from mainland China, and reports of bone marrow metastasis with septic shock as the main manifestation are even rarer. CASE SUMMARY: A 71-year-old woman with sepsis as the first symptom presented with high fever, low blood pressure and high inflammation indicators. Computed tomography (CT) examination revealed mild inflammation of the lungs and no obvious abnormalities in the abdomen. Blood culture suggested Escherichia coli, Aeromonas hydrophila and Aeromonas caviae infection. Antibiotic treatment significantly improved the patient's sepsis symptoms; however, her thrombocytopenia (TCP) could not be corrected despite repeated platelet transfusions. Many malignant cells were ultimately found following a bone marrow puncture smear, and further positron emission tomography/CT (PET/CT) examination confirmed that the malignant tumor in the ascending colon was accompanied by multiple metastases, including the liver and bones. Colon adenocarcinoma was confirmed by autopsy. CONCLUSION: Patients with advanced colon cancer may not have typical clinical symptoms, and sepsis may be the first symptom. When patients have severe TCP that cannot be explained by sepsis of intestinal origin, it is necessary to be aware of the possibility of bone marrow metastasis of intestinal tumors. As such patients often cannot tolerate endoscopy, bone marrow biopsy smears or biopsy tests for specialized cells can help obtain a diagnosis, especially in less developed countries where PET/CT is scarce.

In vitro safety and efficacy evaluation of a novel hybrid bioartificial liver system with simulated liver failure serum.

BACKGROUND: Acute liver failure (ALF), which can potentially be treated with an artificial liver, is a fatal condition. The purpose of this study was to evaluate the safety and effectiveness of a novel hybrid bioartificial liver system (NHBLS) using simulated liver failure serum in vitro. METHODS: The bioreactor in experimental group was cultivated with primary porcine hepatocytes, whereas in control group was not. Next, the simulated liver failure serum was treated using the NHBLS for 10 h. Changes in albumin (ALB), total bilirubin (TBIL), ammonia (Amm), total bile acid (TBA), creatinine (Cr), and blood urea nitrogen (BUN) were measured before treatment (0 h) and every 2 h during treatment. In addition, changes in NHBLS pressures, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lidocaine metabolism were also recorded. RESULTS: The NHBLS worked steadily without unexpected occurrences during the treatment. Blood culture showed no bacterial growth after 7 days, and the endotoxin level was less than 0.5 EU. The TBIL, TBA, Cr, and BUN levels in both groups were markedly lower than those at 0 h (p < 0.05). The Amm level in experimental group was significantly lower than that in control group (p < 0.05). NHBLS pressures were also stable, and the hepatocytes in the bioreactor functioned well. CONCLUSIONS: The preparation method for the simulated liver failure serum was optimized successfully, and the safety and effectiveness of the NHBLS in vitro were verified. Furthermore, the NHBLS significantly reduced the levels of Amm which can lead to hepatic encephalopathy.

Comprehensive Analysis of E3 Ubiquitin Ligases Reveals Ring Finger Protein 223 as a Novel Oncogene Activated by KLF4 in Pancreatic Cancer.

Pancreatic cancer is one of the major malignancies and causes of mortality worldwide. E3 ubiquitin-protein ligases transfer activated ubiquitin from ubiquitin-conjugating enzymes to protein substrates and confer substrate specificity in cancer. In this study, we first downloaded data from The Cancer Genome Atlas pancreatic adenocarcinoma dataset, acquired all 27 differentially expressed genes (DEGs), and identified genomic alterations. Then, the prognostic significance of DEGs was analyzed, and eight DEGs (MECOM, CBLC, MARCHF4, RNF166, TRIM46, LONRF3, RNF39, and RNF223) and two clinical parameters (pathological N stage and T stage) exhibited prognostic significance. RNF223 showed independent significance as an unfavorable prognostic marker and was chosen for subsequent analysis. Next, the function of RNF223 in the pancreatic cancer cell lines ASPC-1 and PANC-1 was investigated, and RNF223 silencing promoted pancreatic cancer growth and migration. To explore the potential targets and pathways of RNF223 in pancreatic cancer, quantitative proteomics was applied to analyze differentially expressed proteins, and metabolism-related pathways were primarily enriched. Finally, the reason for the elevated expression of RNF223 was analyzed, and KLF4 was shown to contribute to the increased expression of RNF233. In conclusion, this study comprehensively analyzed the clinical significance of E3 ligases. Functional assays revealed that RNF223 promotes cancer by regulating cell metabolism. Finally, the elevated expression of RNF223 was attributed to KLF4-mediated transcriptional activation. This study broadens our knowledge regarding E3 ubiquitin ligases and signal transduction and provides novel markers and therapeutic targets in pancreatic cancer.

UGT1A Gene Family Members Serve as Potential Targets and Prognostic Biomarkers for Pancreatic Cancer.

BACKGROUND: Pancreatic cancer (PC) is one of the most common cancers worldwide, with high mortality. The UGT1A gene family plays important roles in pharmacology and toxicology, contributing to interindividual differences in drug disposition. However, mRNA expression and prognostic value of the UGT1A gene family in PC have not been identified. METHODS: Oncomine, GEPIA2, DAVID 6.8, Metascape, Kaplan-Meier plotter, cBioPortal, GeneMANIA, TRRUST v2, TIMER, and R software were used in our study. RESULTS: The transcriptional levels of UGT1A1/3/6/8/9/10 in PC tissues were significantly higher than those in normal tissues. These results were further validated using five pairs of PC tumor tissues and adjacent nontumor tissues. A significant correlation was found between the expression of UGT1A1/6/10 and the pathological stage of PC. PC patients with lower transcriptional levels of UGT1A1/4/5/6/10 were associated with a better prognosis. The differentially expressed UGT1A gene family functions were primarily related to the glucuronidation pathway, cytokine-cytokine receptor interactions, and the ILK signaling pathway. Our data suggest that HNF1A, AHR, and CDX2 are key transcription factors for the UGT1A gene family. Furthermore, the expression levels of UGT1A1/3/8/9/10 were positively correlated with the activities of tumor-infiltrating immune cells, especially B cells. The expression levels of UGT1A6/9 were negatively correlated with macrophage infiltration levels. CONCLUSIONS: These results suggest that the UGT1A gene family could serve as a potential prognostic biomarker and target for PC. However, future studies are required to validate our findings and promote the clinical utility of the UGT1A gene family in PC.

TCGA and ESTIMATE data mining to identify potential prognostic biomarkers in HCC patients.

Hepatocellular carcinoma (HCC) is an aggressive form of cancer characterized by a high recurrence rate following resection. Studies have implicated stromal and immune cells, which form part of the tumor microenvironment, as significant contributors to the poor prognoses of HCC patients. In the present study, we first downloaded gene expression datasets for HCC patients from The Cancer Genome Atlas database and categorized the patients into low and high stromal or immune score groups. By comparing those groups, we identified differentially expressed genes significantly associated with HCC prognosis. The Gene Ontology database was then used to perform functional enrichment analysis, and the STRING network database was used to construct protein-protein interaction networks. Our results show that most of the differentially expressed genes were involved in immune processes and responses and the plasma membrane. Those results were then validated using another a dataset from a HCC cohort in the Gene Expression Omnibus database and in 10 pairs of HCC tumor tissue and adjacent nontumor tissue. These findings enabled us to identify several tumor microenvironment-related genes that associate with HCC prognosis, and some those appear to have the potential to serve as HCC biomarkers.

Frizzled-2 small interfering RNA protects hepatic BRL-3A cells against Hypoxia / Reoxygenation via modulation of autophagy.

BACKGROUND/AIMS: Autophagy plays a positive role in the prevention of liver damage after hepatic ischemia-reperfusion injury (HIRI); however, the molecular mechanism is still a mystery. Understanding the molecular events behind this injury may have important implications for devising proper strategies for managing liver injury. This study investigated the effects of Frizzled-2 expression on autophagy as well as Ca2+ concentration and apoptosis in BRL-3A cells. MATERIALS AND METHODS: BRL-3A cells exposed to the hypoxia/reoxygenation (H/R) condition were used as an in vitro HIRI hepatic cell model. The transfection of Frizzled-2 small interfering RNA (siRNA) or expression vector was performed to silence or overexpress Frizzled-2 in BRL-3A cells. The intracellular Ca2+ concentration was monitored by the fluorescence of Ca+. Western blot was used to detect autophagy-related proteins and apoptotic marker Caspase-3. The cellular autophagosome was observed by a transmission electron microscope. RESULTS: Beclin-1 and Atg7 expressions were considerably induced by H/R treatment, and this induction was attenuated by Frizzled-2 siRNA in BRL-3A cells. The LC3B-II/I ratio was inhibited by H/R treatment, although it was considerably induced by Frizzled-2 siRNA. The overexpression of Frizzled-2 induced intracellular Ca2+ concentration and expressed autophagy-related proteins and Caspase-3 except for the suppression of LC3B-II/I ratio in BRL-3A cells in the normoxia condition. CONCLUSION: The overexpression of Frizzled-2 mimicked H/R treatment and suppressed autophagy activity, whereas Frizzled-2 siRNA induced cellular autophagy and attenuated the H/R-induced hepatic injury in BRL-3A cells. These developments suggest that Frizzled-2 siRNA protects hepatic BRL-3A cells from the injury of H/R via autophagy modulation.

Inhibition of Frizzled-2 by small interfering RNA protects rat hepatic BRL-3A cells against cytotoxicity and apoptosis induced by Hypoxia/Reoxygenation / La inhibición de Frizzled-2 por ARN interferente pequeño protege a los hepatocitos BRL-3A de rata frente a la citotoxicidad y la apoptosis inducidas por hipoxia/reoxigenación

Frizzled-2 plays an important role in maintaining normal hepatic cell functionality. This study aimed to investigate the role of inhibition of Frizzled-2 in protecting rat liver BRL-3A cells from Hypoxia/Reoxygenation (H/R). In vitro H/R hepatic cell model was established by culturing BRL-3A cells under H/R condition. Frizzled-2 siRNA was transfected into BRL-3A cells to inhibit Frizzled-2 signaling. Wnt5a and Frizzled-2 were significantly increased in BRL-3A cells upon H/R treatment. H/R treatment induced cell cytotoxicity, the early apoptosis rate and the intracellular Ca2+ level in BRL-3A cells while silencing frizzled-2 gene decreased the H/R induced cell cytotoxicity, apoptosis and intracellular Ca2+ level. In vivo mice study further showed the up-regulation of Frizzled-2/Wnt 5 pathway and cleaved Caspase-3 expression in liver tissues under ischemia and reperfusion injury (IRI). In summary, inhibition of Frizzled-2 by its siRNA may protects BRL-3A cells by attenuating the H/R induced cell cytotoxicity and apoptosis

Frizzled-2 desempeña un papel importante en el mantenimiento de la funcionalidad normal de los hepatocitos. Este estudio tiene como objetivo analizar el papel de la inhibición de Frizzled-2 en la protección de los hepatocitos BRL-3A de rata de la hipoxia/reoxigenación (H/R). El modelo de hepatocitos H/R in vitro se demostró con el cultivo de células BRL-3A en condiciones de H/R. El ARNip de Frizzled-2 se transinfectó en células BRL-3A para inhibir la señalización de Frizzled-2. Wnt5a y Frizzled-2 aumentaron considerablemente en las células BRL-3A tras el tratamiento con H/R. El tratamiento con H/R provocó citotoxicidad celular, una tasa de apoptosis temprana y el nivel de Ca2+ intracelular en células BRL-3A mientras que el gen frizzled-2 silenciado redujo la citotoxicidad celular inducida por H/R, la apoptosis y el nivel de Ca2+ intracelular. El estudio in vivo con ratones mostró, además, la regulación al alza de la vía de Frizzled-2/Wnt 5 y la expresión de caspasa 3 escindida en tejidos hepáticos con lesión por isquemia y reperfusión (LIR). En resumen, la inhibición de Frizzled-2 por su ARNip puede proteger a las células BRL-3A al atenuar la citotoxicidad celular y la apoptosis inducida por H/R

Inhibition of Frizzled-2 by small interfering RNA protects rat hepatic BRL-3A cells against cytotoxicity and apoptosis induced by Hypoxia/Reoxygenation.

Frizzled-2 plays an important role in maintaining normal hepatic cell functionality. This study aimed to investigate the role of inhibition of Frizzled-2 in protecting rat liver BRL-3A cells from Hypoxia/Reoxygenation (H/R). In vitro H/R hepatic cell model was established by culturing BRL-3A cells under H/R condition. Frizzled-2 siRNA was transfected into BRL-3A cells to inhibit Frizzled-2 signaling. Wnt5a and Frizzled-2 were significantly increased in BRL-3A cells upon H/R treatment. H/R treatment induced cell cytotoxicity, the early apoptosis rate and the intracellular Ca2+ level in BRL-3A cells while silencing frizzled-2 gene decreased the H/R induced cell cytotoxicity, apoptosis and intracellular Ca2+ level. In vivo mice study further showed the up-regulation of Frizzled-2/Wnt 5 pathway and cleaved Caspase-3 expression in liver tissues under ischemia and reperfusion injury (IRI). In summary, inhibition of Frizzled-2 by its siRNA may protects BRL-3A cells by attenuating the H/R induced cell cytotoxicity and apoptosis.

Single-Port Laparoscopic Surgery Is Feasible and Safe for Hepatic Left Lateral Sectionectomy for Benign Liver Lesions.

BACKGROUND AND OBJECTIVES: The feasibility and safety of single-port laparoscopic surgery for left lateral liver lobectomy are largely unknown. This study is aimed at comparing the effectiveness and safety between single-port laparoscopic (SPL) and conventional multiport laparoscopic (CL) surgeries for hepatic left lateral sectionectomy. METHODS: A total of 65 patients receiving laparoscopic hepatic left lateral sectionectomy between January 2008 and July 2015 were included and divided into the SPL group (n = 40) and the CL group (n = 25). RESULTS: There was no significant difference in the operative time, estimated intraoperative blood loss, length of hospital stay, and incidences of postoperative complications (biliary leakage, hemorrhage, and contusion at incision) between groups (all P > 0.05). However, the SPL group had a significantly lower VAS pain score (at 24 h but not 7 days postoperation) and higher cosmetic satisfaction scores (at both 2 months and 6 months postoperation) than the CL group (all P < 0.01). Moreover, multivariate linear regression analysis further confirmed the superior pain score and cosmetic outcome in the SPL group. CONCLUSIONS: Single-port laparoscopic hepatic left lateral sectionectomy is a safe and feasible treatment for patients with lesions in the left hepatic lobe. Patients with benign lesions in the left hepatic lobe are more suitable to receive single-port laparoscopic hepatic left lateral sectionectomy than those with malignancies.