Assessing the suitability of video-assisted anal fistula treatment for obese patients compared to conventional surgery: a question worth investigating.

BACKGROUND AND AIMS: Video-assisted anal fistula treatment (VAAFT) is an innovative surgical approach enabling the direct visualization of the fistula tract structure. This study aims to assess the efficacy of VAAFT in comparison with that of traditional surgical methods and explore potential risk factors contributing to fistula recurrence to provide new recommendations for surgical selection. MATERIALS AND METHODS: Information was collected from 100 patients with complex anal fistula (CAF) in our hospital who underwent surgical treatment from January 2021 to January 2023. We compared the baseline information and surgical outcomes of two groups, analyzed the risk factors for fistula recurrence by using logistic regression analysis, and conducted further exploration by using the body mass index. RESULTS: Equal numbers of patients underwent VAAFT and traditional surgeries, and no significant differences in baseline information were observed. Patients who received VAAFT experienced less intraoperative bleeding (15.5 (14.0-20.0) vs. 32.0 (25.0-36.0)), shorter hospital stays (2.0 (2.0-2.5) vs. 3.0 (3.0-3.5)), reduced postoperative pain and wound discharge, but longer operative times (43.3 ± 6.9 vs. 35.0 (31.5-40.0)) compared with patients who underwent traditional surgeries. No significant differences in recurrence rates were found three and six months after operation (the p-values were 0.790 and 0.806, respectively). However, the Wexner scores of the VAAFT group were significantly low in the first follow-up (0 (0-1.0) vs. 2.0 (1.0-2.0)). Postoperative recurrence of fistulas may be associated with obesity (p-value = 0.040), especially in patients undergoing traditional surgeries (p-value = 0.036). CONCLUSION: VAAFT offers advantages, such as less pain, less trauma, and faster recovery, compared with traditional surgical treatment. Obese patients with CAF are prone to recurrence, and we recommend that they undergo VAAFT treatment rather than traditional surgeries.

PHF20L1 mediates PAX2 expression to promote angiogenesis and liver metastasis in colorectal cancer through regulating HIC1.

Colorectal cancer (CRC) is a common cancer with poor prognosis. The research was designed to explore the role of PHF20L1 in angiogenesis and liver metastasis in CRC and discuss its molecular mechanism. Expression levels of PHF20L1, HIC1 and PAX2 in CRC tissues collected from CRC patients were detected using qRT-PCR, WB and immunohistochemical staining. CRC cells were transfected with PHF20L1, HIC1 and PAX2 overexpression or knockdown vectors and the proliferation, apoptosis, EMT and angiogenesis of the cells were determined. WB was utilized to assess protein levels of PHF20L1, HIC1, PAX2 and angiogenesis factor (ANGPT2, FGF1, PDGFA and VEGFA). The role of PHF20L1 regulating tumor formation and liver metastasis in vivo was detected as well. PHF20L1 was observed to express at a high level of CRC tissues. PHF20L1 promoted CRC cell growth, EMT and angiogenesis, and inhibited cell apoptosis. Knockdown of PHF20L1 had opposite effects on CRC cells. PHF20L1 negatively regulated HIC1 expression to promote PAX2 expression, thus promoting CRC cell progression. The in vivo results showed that PHF20L1 contributed to tumor formation and liver metastasis. PHF20L1 increases PAX2 expression to promote angiogenesis in CRC by inhibiting HIC1, therefore facilitating CRC cell EMT and liver metastasis. Our finding may provide a novel insight for CRC pathogenesis.

Outcomes of adolescent and young patients with hepatocellular carcinoma after curative liver resection: a retrospective study.

BACKGROUND: The risk of HCC is documented to be age-related. The outcomes of young HCC patients on postoperative prognosis are not well understood. The study aims to compare the characteristic differences between adolescent and young (AYA) and non-AYA HCC patients. METHODS: We performed a retrospective analysis of the clinical and pathological findings and the survival of 243 HCC patients who underwent operations between 2007 and 2018. RESULTS: The AYA group had a higher AFP level and a higher prevalence of family history of HCC or other cancers than the non-AYA group (P < 0.01 and P < 0.05). AYA patients had more unfavorable pathological characteristics including bigger lesion size, microvascular invasion, portal vein invasion, and hepatic capsule invasion. They also had a more unfavorable Edmondson grade and less tumor capsule formation (P < 0.01). Age was an independent predictor of survival in HCC patients. AYA patients had poorer disease-free and overall survival than non-AYA patients did (P < 0.01). Patients under 30 years old had an even poorer disease-free survival than those aged 30-40 (P = 0.047). CONCLUSIONS: AYA patients exhibited a higher recurrence rate and disease-related death rate with more unfavorable pathological characteristics. Enhanced follow-up for young HCC patients should be applied.

Characterization of B cell-mediated PD-1/PD-L1 interaction in pancreatic cancer patients.

Pancreatic ductal adenocarcinoma (PDAC) is a common type of pancreatic cancer with one of the worst survival rate of all malignancies. Recent studies have identified that immunosuppressive B cells could employ the PD-1/PD-L1 pathway to suppress antitumour T cell responses; hence, we examined the expression and function of PD-L1 in B cells. We found that the PD-L1 expression was significantly enriched in tumour-infiltrating (TI) B cells than in peripheral blood (PB) B cells from the same patients. Additionally, the PB B cells from stage III and stage IV PDAC patients presented significantly higher PD-L1 than the PB B cells from healthy controls. High PD-L1 expression in PB B cells could be achieved by stimulation via CpG and less effectively via anti-BCR plus CD40L, but not by coculture with pancreatic cancer cell lines in vitro. Also, STAT1 and STAT3 inhibition significantly suppressed PD-L1 upregulation in stimulated B cells. CpG-stimulated PB B cells could inhibit the IFN-γ expression and proliferation of CD8 T cells in a PD-L1-dependent manner. Also, TI CD8 T cells incubated with whole TI B cells presented significantly lower IFN-γ expression and lower proliferation, than TI CD8 T cells incubated with PD-L1+  cell-depleted TI B cells, suggesting that PD-L1+  B cells could also suppress CD8 T cells in the tumour. Overall, this study identified that B cells could suppress CD8 T cells via PD-L1 expression, indicating a novel pathway of immuno-regulation in pancreatic cancer.

MicroRNA-191 acts as a tumor promoter by modulating the TET1-p53 pathway in intrahepatic cholangiocarcinoma.

Current treatment of intrahepatic cholangiocarcinoma (ICC) remains ineffective because knowledge of ICC carcinogenesis is unclear. Increasing evidence suggests that microRNAs (miRNAs), including miR-191, play an important role in tumorigenesis; but expression and biological functions of miR-191 in ICC remain to be established. This study investigated the functions and underlying mechanisms of miR-191 in ICC. ICC miRNA profiles were generated in five pairs of ICC and matched to normal bile duct tissues by next-generation sequencing technology; ICC miRNA profiles were verified in 18 pairs of ICC tissues and normal bile duct tissues by quantitative RT-PCR. The miR-191-associated mechanisms in ICC were investigated in vitro and in vivo, and clinical outcomes associated with miR-191 were correlated in 84 patients. Our results showed that miR-191 expression was significantly increased in ICC compared with the adjacent normal bile duct tissues (P < 0.001). Overexpression of miR-191 promoted proliferation, invasion, and migration of cholangiocarcinoma cells in vitro and in vivo. The elevated miR-191 expression reduced the expression level of ten-eleven translocation 1 (TET1)-a direct target gene of miR-191 in ICC, which catalyzes demethylation. The reduced TET1 expression level allowed the methylated CpG-rich regions at the p53 gene transcription start site stay methylated, leading to reduced p53 expression level, which compromises p53's anticancer vigor. Finally, miR-191 was found to be an independent risk factor for poor prognosis in patients with ICC (overall survival, hazard ratio = 3.742, 95% confidence interval 2.080-6.733, P < 0.001; disease-free survival, hazard ratio = 2.331, 95% confidence interval 1.346-4.037, P = 0.003). CONCLUSION: Our results suggest that overexpressed miR-191 is associated with ICC progression through the miR-191/TET1/p53 pathway. (Hepatology 2017;66:136-151).

Gracilibacillus eburneus sp.nov., a moderately halophilic bacterium isolated from Xinjiang province, China.

A novel Gram-staining positive, moderately halophilic, endospore-forming, motile, rod-shaped and strictly aerobic strain, designated YIM 93565T, was isolated from a salt lake in Xinjiang province of China and subjected to a polyphasic taxonomic study. Strain YIM 93565T grew in the range of pH 6.0-9.0 (optimum pH 7.0), 10-45 °C (optimum 35-40 °C) and at salinities of 2-24% (w/v) NaCl (optimum 7-10%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain YIM 93565T clustered with members of the genera Gracilibacillus and form a clade with Gracilibacillus bigeumensis KCTC 13130T (95.6% similarity) and Gracilibacillus halophilus DSM 17856T (94.9%), which was well separated from others. The DNA G + C content of this novel strain was 36.8 mol%. The major fatty acids were anteiso-C15:0, iso-C15:0, C16:0 and anteiso-C17:0 and its polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, one unidentified glycolipid and two unidentified phospholipids. The predominant menaquinone was MK-7. The cell-wall peptidoglycan was based on meso-diaminopimelic acid. Based on the results of phylogenetic, physiological and chemotaxonomic comparative analyses, the isolate is assigned to a novel species of the genus Gracilibacillus, for which the name Gracilibacillus eburneus sp. nov. is proposed, with the type strain YIM 93565T (= DSM 23710T = CCTCC AB 2013249T).

SIRT1 regulates oncogenesis via a mutant p53-dependent pathway in hepatocellular carcinoma.

BACKGROUND & AIMS: SIRT1 is a class III histone deacetylase that plays diverse roles in various cancers. However, the clinical significance of SIRT1 in hepatocellular carcinoma (HCC) remains unknown. METHODS: We analysed p53 mutations and the activation of SIRT1 in 252 hepatitis B virus-positive HCC cases. None of the patients had been subjected to pre-operative treatment. RESULTS: We examined 57 p53 mutations from 248 HCC tissues. Activated SIRT1 (phosphorylated form of Ser47), in the context of mutant p53, predicted a longer relapse-free survival (RFS) but not a longer overall survival (OS) (RFS: p = 0.007, OS: p = 0.280) in HCC tissues harbouring mutant p53. In multivariate analysis, activated SIRT1 remained a significant predictor of longer RFS (OR = 0.307, CI: 0.143-0.660, p=0.002). Analysis of 248 paired specimens revealed a significant correlation between activated SIRT1 (Ser47) and activated AMPK (Thr172) in HCC tissues harbouring mutant p53 (p = 0.003, n = 57). The combination of these 2 parameters was a powerful predictor for a good prognosis in these patients. In vitro, SIRT1 inactivation stimulated the growth of HCC cells, bearing mutated p53, by suppressing AMPK activity and subsequently enhancing mammalian target of rapamycin (mTOR) activity, resulting in induction of p70S6K1 activation in HCC cells. Metformin, an AMPK activator, more strongly suppressed cell growth in p53-mutant cell lines with inactive SIRT1 than in p53-mutant cell lines with active SIRT1. CONCLUSIONS: SIRT1 exerted anti-carcinogenic effects via the AMPK-mTOR pathway in HCC in the context of mutant p53. Metformin could be a therapeutic drug for HCC in patients with mutated p53, inactivated SIRT1, and AMPK expression.

Skermanella rubra sp. nov., a bacterium isolated from the desert of Xinjiang, China.

A Gram-negative, pink-coloured, rod-shaped, motile bacterium, designated YIM 93097(T), was isolated from the desert soil collected from Xinjiang province of China. Strain YIM 93097(T) was found to grow at 20-45 °C (optimum 28-37 °C), pH 5.0-7.0 (optimum pH 7.0) and 0-8 % (w/v) NaCl (optimum 1 %, w/v). Based on 16S rRNA gene sequence similarity studies, it belongs to the genus Skermanella. The 16S rRNA gene sequence similarity was identified to be 98.7 % to Skermanella xinjiangensis CCTCC AB 207153(T) while the DNA-DNA hybridization value was found to be only 48.1 %. The predominant isoprenoid quinone was determined to be Q-10. The major fatty acids were identified to be C16:0, C18:1 ω7c and summed feature 4 (consisting of C17:1 anteiso B/iso I). The major polar lipids were identified as phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, two unidentified phospholipids and one unidentified aminolipid. The DNA G+C content was found to be 67.2 mol %. The analysis of the genotypic and phenotypic data indicated that strain YIM 93097(T) belongs to a novel species of the genus Skermanella, for which the name Skermanella rubra sp. nov. is proposed. The type strain is YIM 93097(T) (=DSM 21389(T)=CCTCC AB 2015161(T)).

Hepatitis C virus infection and the risk of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma: evidence from a systematic review and meta-analysis of 16 case-control studies.

BACKGROUND: Studies investigating the association between hepatitis C virus (HCV) infections and the occurrence of cholangiocarcinoma (CCA), especially intrahepatic cholangiocarcinoma (ICC), have shown inconsistent findings. Although previous meta-analyses referred to HCV and CCA, they mainly focused on ICC rather than CCA or extrahepatic cholangiocarcinoma (ECC). Since then, relevant new studies have been published on the association between HCV and ICC. Since the different anatomic locations of CCA have distinct epidemiologic features and different risk factors, it is necessary to evaluate the relationship between HCV infection and ICC, ECC, and CCA. METHODS: Relevant studies were identified by searching PUBMED, EMBASE, and MEDLINE databases prior to 1 August 2013. Pooled risk estimates were calculated with random-effects models using STATA 11.0. RESULTS: A total of 16 case-control studies were included in the final analysis. Pooled risk estimates showed a statistically significant increasing risk of CCA (odds ratio (OR) = 5.44, 95% CI, 2.72 to 10.89). The pooled risk estimate of ICC (OR = 3.38, 95% CI, 2.72 to 4.21) was higher than that of ECC (OR = 1.75, 95% CI, 1.00 to 3.05). In a subgroup analysis, the pooled risk estimate of ICC in studies from North America was obviously higher than in Asia (6.48 versus 2.01). The Begg funnel plot and Egger test showed no evidence of publication bias. CONCLUSIONS: HCV infection is associated with the increasing risk of CCA, especially ICC.

Characterization of mesenchymal stem cells under the stimulation of Toll-like receptor agonists.

Infective factors cause the perpetuation of inflammation as a result of the permanent exposure of the immune system to exogenous or endogenous products of virus or bacteria. Mesenchymal stem cells (MSCs) can be exposed to this infective environment, which may change the characteristics and therapeutic potency of these MSCs. MSCs have the ability to repair damaged and inflamed tissues and regulate immune responses. In this study, we demonstrated that MSCs express functional Toll-like receptors (TLR) 3 and 4, the Toll-like receptor families that recognize the signals of viral and bacterial mimics, respectively. The specific stimulations did not affect the self-renewal and apoptosis capabilities of MSCs but instead promoted their differentiation into the adipocytes and osteoblasts with the TLR3 ligand. The reverse of these results were obtained with the TLR4 ligand. The migration of the MSCs to stimulate either of the two specific ligands was inhibited at different times, whereas the immunogenicity and immunosuppressive properties of the MSCs were not weakened unlike in the MSCs group. These results suggest that TLR3 and TLR4 stimulation affect the characterization of MSCs.

Establishment of a neutrophil extracellular trap-related prognostic signature for colorectal cancer liver metastasis and expression validation of CYP4F3.

Liver metastasis stands as the primary contributor to mortality among patients diagnosed with colorectal cancer (CRC). Neutrophil extracellular traps (NETs) emerge as pivotal players in the progression and metastasis of cancer, showcasing promise as prognostic biomarkers. Our objective is to formulate a predictive model grounded in genes associated with neutrophil extracellular traps and identify novel therapeutic targets for combating CRLM. We sourced gene expression profiles from the Gene Expression Omnibus (GEO) database. Neutrophil extracellular trap-related gene set was obtained from relevant literature and cross-referenced with the GEO datasets. Differentially expressed genes (DEGs) were identified through screening via the least absolute shrinkage and selection operator regression and random forest modeling, leading to the establishment of a nomogram and subtype analysis. Subsequently, a thorough analysis of the characteristic gene CYP4F3 was undertaken, and our findings were corroborated through immunohistochemical staining. We identified seven DEGs (ATG7, CTSG, CYP4F3, F3, IL1B, PDE4B, and TNF) and established nomograms for the occurrence and prognosis of CRLM. CYP4F3 is highly expressed in CRC and colorectal liver metastasis (CRLM), exhibiting a negative correlation with CRLM prognosis. It may serve as a potential therapeutic target for CRLM. A novel prognostic signature related to NETs has been developed, with CYP4F3 identified as a risk factor and potential target for CRLM.

Effects of total bilirubin on the prevalence of osteoporosis in postmenopausal women without potential liver disease.

It is still uncertain whether total bilirubin per se is a risk factor for osteoporosis in postmenopausal women and no study has so far examined this important issue. This study was designed to assess the sheer effects of total bilirubin on the prevalence of osteoporosis in postmenopausal women without potential liver disease. In the present study, postmenopausal female subjects without potential liver disease (n = 918) who underwent measurement of bone mineral density were enrolled. Correlation and logistic regression analysis were used to assess the relationship between total bilirubin and other variables. As a result, subjects with osteoporosis had a significantly lower total bilirubin level (P = 0.005). A 0.1 mg/dl increase in total bilirubin was associated with reduced odds ratio of the risk by 38 % for osteoporosis [OR 0.62 (95 % CI 0.52-0.88), P = 0.012] after adjustment for several variables. Total bilirubin was independently associated with BMD [coefficient = 0.41, 95 % CI (0.35-0.47), P < 0.001 for lumbar spine and coefficient = 0.44, 95 % CI (0.36-0.48), P < 0.001 for femur neck]. A positive correlation could be observed with significant difference between total bilirubin and z-score (r = 0.33, P < 0.001 for lumbar spine and r = 0.37, P < 0.001 for femur neck) and total bilirubin was positively correlated with serum calcium (r = 0.13, P < 0.001) as well. Therefore, this study demonstrates an independent inverse association between total bilirubin and the prevalence of osteoporosis in postmenopausal women without potential liver disease. Total bilirubin would be useful as a provisional new risk factor of osteoporosis in such a population.

Serum total bilirubin is inversely associated with brachial-ankle pulse wave velocity in men with hypertension.

Serum total bilirubin has been suggested to have the potential anti-inflammatory and antioxidant effects on the vasculature. This study was designed to investigate the association of bilirubin with brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness and cardiovascular disease. Hypertensive male subjects (n = 2,361) were classified into groups according to the 50th, 75th, and 95th percentiles of baPWV value. Correlation and regression analysis were used to assess the relationship between baPWV and other variables. Hypertensive subjects with baPWV above the 50th, 75th, and 95th percentiles had a significantly lower bilirubin level than those with baPWV under them (0.97 ± 0.40 vs. 1.00 ± 0.41 mg/dl, P < 0.001; 0.95 ± 0.39 vs. 0.99 ± 0.41 mg/dl, P = 0.001; 0.92 ± 0.36 vs. 0.99 ± 0.42 mg/dl, P = 0.048, respectively). Bilirubin is inversely related to baPWV (R (2) = 0.0032, P = 0.003) and C-reactive protein (CRP) (correlation coefficient = -0.13, P < 0.001). A 0.1 mg/dl increase in bilirubin was associated with a 19, 20, and 34 % reduced odds ratio for baPWV above the 50th, 75th, and 95th percentiles, respectively [odds ratio (OR) 0.77 (95 % confidence interval (CI) 0.62-0.95), P = 0.015; OR 0.80 (95 % CI 0.64-0.99), P = 0.044; OR 0.68 (95 % CI 0.45-1.00), P = 0.048, respectively] after adjustment for several variables. This study demonstrates an independent inverse association between bilirubin and baPWV in hypertensive men. Additionally, reduced CRP may be one of mediators on the mechanisms how bilirubin reduces baPWV.

SCF-FBXL8 contributes to liver metastasis and stem-cell-like features in colorectal cancer cells by mediating ubiquitination and degradation of TP53.

BACKGROUND: FBXL8 is a conserved F-box protein, belonging to the ubiquitin ligase complex, which promotes the development and progression of tumours. However, the regulation function and mechanism of FBXL8's involvement in colorectal cancer (CRC) remain unclear. METHODS: RT-PCR is used to detect gene expression levels. Protein levels were determined by western blotting and flow cytometry. The bindings of FBXL8 and p53 and ubiquitination levels were detected by cell transfection and immunoprecipitation. The transwell assay was used to measure the ability of cells to migrate and invade. Animal studies were used to verify the function of FBXL8 in vivo. RESULTS: The expression of FBXL8 was up-regulated in CRC tissues, and its overexpression was associated with poor prognosis in CRC patients. The up-regulation of FBXL8 promoted the proliferation, invasion and migration of CRC tumour cells and maintained the stem-cell characteristics of colorectal tumour cells. Further analysis demonstrated that FBXL8 targeted p53 and reduced its stability through ubiquitination. Knockout of FBXL8 down-regulated the proliferation, migration and stem-like properties of tumour cells. CRC mouse xenograft tumour model confirmed that FBXL8 gene knockout inhibited tumour formation and liver metastasis. CONCLUSION: FBXL8 was highly expressed in CRC. Mechanism studies have shown that FBXL8 degraded tumour suppressor gene p53 by ubiquitination. FBXL8 knockout inhibited the proliferation and stem characteristics of CRC cells, so SCF-FBXL8-TP53 has potential to be used as a therapeutic target for CRC in subsequent studies.

Misdiagnosis and delayed diagnosis of atypical autoimmune pancreatitis: Experience from clinical cases.

Autoimmune pancreatitis (AIP) is a fibro-inflammatory disease characterized by inflammation and fibrosis of the pancreas. It is a systemic disease that can affect multiple organs, including the bile ducts, kidneys, lungs, and other organs. However, due to its complex presentation, AIP is often challenging to diagnose, and misdiagnosis with pancreatic tumors can occur. In our study, we reviewed three cases of atypical AIP where patients had normal serum IgG4 levels, leading to initial misdiagnosis with pancreatic tumors. Delayed diagnosis resulted in irreversible pathologies such as retroperitoneal fibrosis. All three patients had bile duct involvement, and imaging findings were similar to those of tumors, further complicating the diagnosis. The correct diagnosis was confirmed only after diagnostic therapy. Our study aims to raise awareness of atypical AIP and improve diagnostic efficiency by analyzing the clinical characteristics of these patients.

LITAF inhibits colorectal cancer stemness and metastatic behavior by regulating FOXO1-mediated SIRT1 expression.

Lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF) is a transcription factor that activates the transcription of TNF-α and regulates the inflammatory response. LITAF has been found to have potential anti-cancer effects of in several tumors. However, the role of LITAF in colorectal cancer (CRC) remains unclear. Through a comprehensive pan-cancer analysis of the Cancer Genome Atlas (TCGA), LITAF was identified as a differentially downregulated gene in CRC. We hypothesized that LITAF may participate in the modulation of CRC progression. The present study was aimed to investigate the expression profile of LITAF in CRC and its effect on metastatic behavior and stemness as well as the underlying molecular mechanism. The expression profile of LITAF in CRC, and its relationship with the prognosis of CRC were explored using public databases. LITAF expression was detected by quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemistry. Furthermore, the effects of overexpression or knockdown of LITAF on cell proliferation, apoptosis, migration, invasion, and stemness of CRC cells were investigated in vitro. The regulatory effect of LITAF on forkhead Box O 1 (FOXO1)-sirtuin 1 (SIRT1) signaling axis was also explored. In addition, a xenograft mouse model was used to investigate the in-vivo role of LITAF. LITAF was downregulated in tumor tissues and its expression was associated with the prognosis, pathological stage and liver metastasis. In-vitro experiments confirmed that LITAF inhibited tumor cell proliferation, migration, invasion and stemness, and induced cell apoptosis. In vivo experiments demonstrated that LITAF inhibited the tumorigenicity and liver metastasis in tumor-bearing mice. Additionally, LITAF promoted FOXO1-mediated SIRT1 inhibition, thus regulating cancer stemness and malignant phenotypes. LITAF was silenced in CRC and it participated in the progression of CRC by inhibiting CRC cell stemness, and malignant phenotypes. Therefore, LITAF may serve as a novel biomarker of CRC prognosis.

The E3 ubiquitin ligase SCF (FBXW10)-mediated LATS2 degradation regulates angiogenesis and liver metastasis in colorectal cancer.

F-box and WD repeat domain containing 10 (FBXW10) is a member of the FBXW subgroup that contains the WD40 domain. FBXW10 has been rarely reported in colorectal cancer (CRC) and its mechanism is unclear. To investigate the role of FBXW10 in CRC, we conducted in vitro and in vivo experiments. Through the database and our clinical samples, we found that FBXW10 expression was up-regulated in CRC, and it was positively correlated with CD31 expression. CRC patients with high FBXW10 expression levels had a poor prognosis. Overexpression of FBXW10 up-regulated cell proliferation, migration and vascular formation, while knockdown of FBXW10 had the opposite effects. Studies on the mechanism of FBXW10 in CRC showed that FBXW10 could ubiquitinate large tumor suppressor kinase 2 (LATS2) and promote its degradation with the Fbox region of FBXW10 played an essential role in this process. In vivo studies demonstrated that knockout of FBXW10 inhibited tumor proliferation and reduced liver metastasis. In conclusion, our study proved that FBXW10 was significantly overexpressed in CRC and was involved in the pathogenesis of CRC by affecting angiogenesis and liver metastasis. Mechanistically, FBXW10 degraded LATS2 through ubiquitination. Therefore, FBXW10-LATS2 can be used as a therapeutic target for CRC in subsequent studies.

Dissecting cellular heterogeneity and intercellular communication in cholangiocarcinoma: implications for individualized therapeutic strategies.

Background: Cholangiocarcinoma is characterized by significant cellular heterogeneity and complex intercellular communication, which contribute to its progression and therapeutic resistance. Therefore, unraveling this complexity is essential for the development of effective treatments. Methods: We employed single-cell RNA sequencing (scRNA-seq) to investigate cellular heterogeneity and intercellular communication in cholangiocarcinoma and adjacent normal tissues from two patients. Distinct cell types were identified, and gene ontology analyses were conducted to determine enriched pathways. Moreover, cell-cell communications were analyzed using CellChat, a computational framework. Additionally, we performed sub-clustering analysis of T cells and fibroblasts. Results: The scRNA-seq analysis revealed distinct cell clusters and diverse cellular compositions of cholangiocarcinoma. CellChat analysis underscored an amplified outgoing signal from fibroblasts within the tumor, suggesting their pivotal role in the tumor microenvironment. Furthermore, T cell sub-clustering analysis revealed an active immune response within the tumor and new tumor-specific T cell clonotypes, suggesting scope for targeted immunotherapies. Moreover, fibroblast sub-clustering analysis indicated distinct functional states and highlighted the role of activated fibroblasts in shaping intercellular communication, particularly via CD99 and FN1 signaling. Conclusion: Our findings reveal the intricate cellular heterogeneity and dynamic intercellular communication in cholangiocarcinoma, providing valuable insights into disease progression and potential therapeutic strategies.

Analysis of lymph node spread and its prognostic significance in ampullary adenocarcinoma: A retrospective study.

Background: Nodal status is a vital prognostic factor for ampullary adenocarcinoma. This study was designed to evaluate the clinical significance of the positive nodes in this disease. Methods: Data from 110 patients who underwent curative pancreatoduodenectomy for ampullary adenocarcinoma between January 2007 and December 2018 were retrospectively collected and analyzed. Results: The median number of lymph nodes per patient was 32 (20-46). Metastatic lymph nodes were found in 84 (76.4%) patients. In patients with positive nodules, the most commonly involved nodes were the #13 (80.1%) and #17 (78.6%) nodes, followed by #12 (69.0%) and #8 nodes (57.1%). Patients with 3-4 positive nodes among #13, #17, #12, and #8 had lower survival rates than those with 0 or 1-2 nodes. Conclusion: Ampullary adenocarcinoma commonly spreads to #13, #17, #12, and #8 lymph nodes. These nodes affected the patients' survival rates dramatically.

Predictors and Recurrence Patterns After Radical Surgery in Ampulla of Vater Cancer: Comparative Analysis Between Early and Late Recurrence.

Objective: Tumor recurrence remains the main dilemma after surgical treatment of ampulla of Vater carcinoma. This study was designed to identify the prognostic factors and evaluate the recurrence patterns of ampulla of Vater cancer. Methods: A total of 286 patients who underwent surgical resection of ampulla of Vater cancer in two medical centers from January 2000 to October 2016 were collected. Data on clinicopathologic factors, survival rate, and recurrence patterns were retrospectively analyzed. Results: A total of 158 patients (55.2%) survived without evidence of recurrence (non-recurrence), whereas 65 (22.7%) and 63 patients (22.1%) suffered from recurrence of the disease within 12 months (early recurrence) and after 12 months (late recurrence), respectively. Early-recurrence patients exhibited a more advanced disease (advanced tumor stage, lymph node involvement, pancreas invasion, and late TNM stage) than late-recurrence patients. The first or primary location of cancer recurrence in 33 patients (25.8%) was locoregional. Metastasis developed in the liver in 30 patients (23.4%), peritoneum in 13 patients (10.2%), lungs in 10 patients (7.8%), and para-aortic or superior mesenteric artery lymph node in 10 patients (7.8%). Multiple metastases were observed in 26 patients (20.3%). Conclusion: The most common patterns of postoperative recurrence are locoregional and recurrent liver metastasis. The recurrence patterns with the worst prognosis are peritoneal and multiple metastases.