Development of a prognostic scoring system for hepatic vena cava Budd-Chiari syndrome with hepatocellular carcinoma

Background:Hepatocellular carcinoma(HCC)is a serious complication of hepatic vena cava Budd-Chiari syndrome(HVC-BCS)that significantly reduces the survival time of patients.Our study aimed to analyze the prognostic factors influencing the survival of HVC-BCS patients with HCC and to develop a prognostic scoring system.Methods:The clinical and follow-up data of 64 HVC-BCS patients with HCC who received invasive treatment at the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were retrospectively analyzed.Kaplan-Meier curves and log-rank tests were used to analyze the survival curve of patients and the difference in prognoses between the groups.Univariate and multivariate Cox regression analyses were performed to analyze the influence of biochemical,tumor,and etiological characteristics on the total survival time of patients,and a new prognostic scoring system was developed according to the regression coefficients of the independent predictors in the statistical model.The prediction efficiency was evaluated using the time-dependent receiver operating characteristics curve and concordance index.Results:Multivariate analysis showed that serum albumin level<34 g/L[hazard ratio(HR)=4.207,95%confidence interval(CI):1.816-8.932,P=0.001],maximum tumor diameter>7 cm(HR=8.623,95%CI:3.771-19.715,P<0.001),and inferior vena cava stenosis(HR=3.612,95%CI:1.646-7.928,P=0.001)were independent predictors of survival.A prognostic scoring system was developed according to the above-mentioned independent predictors,and patients were classified into grades A,B,C and D.Significant differences in survival were found among the four groups.Conclusions:This study successfully developed a prognostic scoring system for HVC-BCS patients with HCC,which is helpful for clinical evaluation of patient prognosis.

Comparison of biliary protein spectrum in gallstone patients with obesity and those with normal body weight

Background: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. Methods: Bile samples from 20 patients(10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling(TMT) and liquid chromatography-tandem mass spectrometry(LC-MS/MS), followed by further bioinformatic analysis. Results: Among the differentially expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor(PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APO A-Ⅰ and APO A-Ⅱ, were confirmed using enzyme-linked immunosorbent assay. Conclusions: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.

Identification of M2 macrophage-related genes for establishing a prognostic model in pancreatic cancer: FCGR3A as key gene

Background:Pancreatic ductal adenocarcinoma(PDAC)has a rich and complex tumor immune microenvironment(TIME).M2 macrophages are among the most extensively infiltrated immune cells in the TIME and are necessary for the growth and migration of cancers.However,the mechanisms and targets mediating M2 macrophage infiltration in pancreatic cancer remain elusive.Methods:The M2 macrophage infiltration score of patients was assessed using the xCell algorithm.Using weighted gene co-expression network analysis(WGCNA),module genes associated with M2 macrophages were identified,and a predictive model was designed.The variations in immunological cell patterns,cancer mutations,and enrichment pathways between the cohorts with the high-and low-risk were examined.Additionally,the expression of FCGR3A and RNASE2,as well as their association with M2 macrophages were evaluated using the HPA,TNMplot,and GEPIA2 databases and verified by tissue immunofluorescence staining.Moreover,in vitro cell experiments were conducted,where FCGR3A was knocked down in pancreatic cancer cells using siRNA to analyze its effects on M2 macrophage infiltration,tumor proliferation,and metastasis.Results:The prognosis of patients in high-risk and low-risk groups was successfully distinguished using a prognostic risk score model of M2 macrophage-related genes(p=0.024).Between the high-and low-risk cohorts,there have been notable variations in immune cell infiltration patterns,tumor mutations,and biological functions.The risk score was linked to the manifestation of prevalent immunological checkpoints,immunological scores,and stroma values(all p<0.05).In vitro experiments and tissue immunofluorescence staining revealed that FCGR3A can promote the infiltration or polarization of M2 macrophages and enhance tumor proliferation and migration.Conclusions:In this study,an M2 macrophage-related pancreatic cancer risk score model was established,and found that FCGR3A was correlated with tumor formation,metastasis,and M2 macrophage infiltration.

Long non-coding RNA GATA6-AS1 is mediated by N6-methyladenosine methylation and inhibits the proliferation and metastasis of gastric cancer

BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.

Management of distal cholangiocarcinoma with arterial involvement: Systematic review and case series on the role of neoadjuvant therapy

BACKGROUND The use of neoadjuvant therapy(NAT)in distal cholangiocarcinoma(dCCA)with regional arterial or extensive venous involvement,is not widely accepted and evidence is sparse.AIM To synthesise evidence on NAT for dCCA and present the experience of a highvolume tertiary-centre managing dCCA with arterial involvement.METHODS A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received NAT.All patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained database.Baseline characteristics,NAT type,progression to surgery and oncological outcomes were collected.RESULTS Twelve studies were included.The definition of“unresectable”locally advanced dCCA was heterogenous.Four studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement.R0 resection rate ranged between 0 and 100%but without survival benefit in most cases.Remaining studies considered either NAT in resectable dCCA or inclusive with extrahepatic CCA.The presented case series includes 9 patients(median age 67,IQR 56-74 years,male:female 5:4)referred for NAT for borderline resectable or locally advanced disease.Three patients progressed to surgery and 2 were resected.One patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months postoperatively.CONCLUSION Evidence for benefit of NAT is limited.Consensus on criteria for uniform definition of resectability for dCCA is required.We propose using the established National-Comprehensive-Cancer-Network®criteria for pancreatic ductal adenocarcinoma.

Augmented reality technology for preoperative planning and intraoperative navigation during hepatobiliary surgery: A review of current methods

Background: Augmented reality(AR) technology is used to reconstruct three-dimensional(3D) images of hepatic and biliary structures from computed tomography and magnetic resonance imaging data, and to superimpose the virtual images onto a view of the surgical field. In liver surgery, these superimposed virtual images help the surgeon to visualize intrahepatic structures and therefore, to operate precisely and to improve clinical outcomes.Data Sources: The keywords "augmented reality", "liver", "laparoscopic" and "hepatectomy" were used for searching publications in the Pub Med database. The primary source of literatures was from peer-reviewed journals up to December 2016. Additional articles were identified by manual search of references found in the key articles.Results: In general, AR technology mainly includes 3D reconstruction, display, registration as well as tracking techniques and has recently been adopted gradually for liver surgeries including laparoscopy and laparotomy with video-based AR assisted laparoscopic resection as the main technical application. By applying AR technology, blood vessels and tumor structures in the liver can be displayed during surgery,which permits precise navigation during complex surgical procedures. Liver transformation and registration errors during surgery were the main factors that limit the application of AR technology.Conclusions: With recent advances, AR technologies have the potential to improve hepatobiliary surgical procedures. However, additional clinical studies will be required to evaluate AR as a tool for reducing postoperative morbidity and mortality and for the improvement of long-term clinical outcomes. Future research is needed in the fusion of multiple imaging modalities, improving biomechanical liver modeling,and enhancing image data processing and tracking technologies to increase the accuracy of current AR methods.

Utilization of 3D printing technology in hepatopancreatobiliary surgery

The technology of three-dimensional(3D)printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering,industrial design,and biomedicine.In biomedical science,several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary surgery.For example,3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies,surgical simulation,intraoperative navigation,medical training,and patient education.Moreover,cancer models have been created using 3D printing technology for the research and selection of chemotherapy drugs.With the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery,we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.

Superiority of Laparoscopy in the Peritoneal Dialysis Catheter Reset Surgery

Peritoneal dialysis catheter surgery has been used in clinical treatment for nearly 40 years, and open surgery under local anesthesia is the conventional method. However, catheter displacement after open surgery is still the thorny issue during our clinical practice. Then the reset surgery is often required to be taken again. Nowadays, laparoscopic peritoneal dialysis catheter draws our attention due to its advantages of accurate positioning, smaller incision, and less pain, and its clinical application has been limited. While laparoscopic surgery is recognized, there are few relevant studies on whether there is difference during the catheter reset process between the two surgical approaches. In this study, we mainly discussed the rate of secondary catheter migration, the incidence of complications after catheter reset for two surgical approaches and the hospital stay as well as the total clinical cost for the two surgical approaches. In this study, we retrospectively analyzed 25 cases of end-stage renal disease, who received catheterization for peritoneal dialysis and regular peritoneal dialysis in our hospital from March 2010 to December 2013, and had a medical history of catheter migration. We collected the relevant clinical data for all patients. Fifteen patients selected laparoscopic catheter reset, and 10 patients selected the traditional surgical method for catheter reset by themselves. For all patients enrolled, we analyzed the incidence of secondary catheter migration and postoperative complications, hospitalization time, and total cost for different methods of reset. Through the studies above, we found that laparoscopic peritoneal dialysis catheter surgery offered accurate catheter location and a small incision that was easy to heal. Besides, the incidence of postoperative complications for the laparoscopic surgery was lower than that for traditional surgical approach for catheter reset. The average hospitalization time for laparoscopic surgery was shorter than that for the traditional surgical approach. The total cost of laparoscopic surgery was more than that of the traditional surgery. Therefore, the rational application of a laparoscopic peritoneal dialysis catheter and reset surgery can increase the success rate of peritoneal dialysis, reduce the complications, shorten hospitalization time of patients, and thus enhance patient＇s confidence to stick it out.

Artificial intelligence-based comprehensive analysis of immune-stemness-tumor budding profile to predict survival of patients with pancreatic adenocarcinoma

Objective:Pancreatic ductal adenocarcinoma(PDAC)is an aggressive malignancy.CD8^(+)T cells,cancer stem cells(CSCs),and tumor budding(TB)have been significantly correlated with the outcome of patients with PDAC,but the correlations have been independently reported.In addition,no integrated immune-CSC-TB profile for predicting survival in patients with PDAC has been established.Methods:Multiplexed immunofluorescence and artificial intelligence(AI)-based comprehensive analyses were used for quantification and spatial distribution analysis of CD8^(+)T cells,CD133^(+)CSCs,and TB.In vivo humanized patient-derived xenograft(PDX)models were established.Nomogram analysis,calibration curve,time-dependent receiver operating characteristic curve,and decision curve analyses were performed using R software.Results:The established‘anti-/pro-tumor’models showed that the CD8^(+)T cell/TB,CD8^(+)T cell/CD133^(+)CSC,TB-adjacent CD8^(+)T cell,and CD133^(+)CSC-adjacent CD8^(+)T cell indices were positively associated with survival of patients with PDAC.These findings were validated using PDX-transplanted humanized mouse models.An integrated nomogram-based immune-CSC-TB profile that included the CD8^(+)T cell/TB and CD8^(+)T cell/CD133^(+)CSC indices was established and shown to be superior to the tumor-nodemetastasis stage model in predicting survival of patients with PDAC.Conclusions:‘Anti-/pro-tumor’models and the spatial relationship among CD8^(+)T cells,CSCs,and TB within the tumor microenvironment were investigated.Novel strategies to predict the prognosis of patients with PDAC were established using AI-based comprehensive analysis and machine learning workflow.The nomogram-based immune-CSC-TB profile can provide accurate prognosis prediction for patients with PDAC.

The protective effects of Levilactobacillus brevis FZU0713 on lipid metabolism and intestinal microbiota in hyperlipidemic rats

Levilactobacillus brevis FZU0713, a potential probiotic previously isolated from the traditional brewing process of Hongqu rice wine, may have the beneficial effects on improving lipid metabolism. This study aimed to evaluate the in vivo protective effects and possible mechanism of L. brevis FZU0713 on the disturbance of lipid metabolism in hyperlipidemic rats fed a high-fat diet(HFD). Results showed that oral administration of L. brevis FZU0713 could significantly inhibit obesity, ameliorate the lipid metabolism disorder, including serum/liver biochemical parameters and hepatic oxidative stress in HFD-fed rats. Histopathological result also indicated that dietary intervention of L. brevis FZU0713 could reduce the accumulation of lipid droplets in liver induced by 8 weeks HFD feeding. Furthermore, L. brevis FZU0713 intervention significantly increased the fecal levels of short-chain fatty acids(SCFAs, including acetate, propionate, butyrate, isobutyrate, valerate and isovalerate)in HFD-fed rats, which may be closely related to the changes of intestinal microbial composition and metabolic function. Intestinal microbiota profiling by 16S rRNA gene sequencing revealed that L. brevis FZU0713 intervention significantly altered the relative abundance of Coprococcus, Butyricicoccus, Intestinimonas, Lachnospiraceae FCS020 group, Ruminococcaceae_NK4A214 group, Ruminococcaceae_UCG-005 and UCG-014 at genus levels. Based on Spearman's rank correlation coefficient, serum and liver lipid metabolism related biochemical parameters were positively correlated with genera Ruminococcus, Pediococcus and Lachnospiraceae, but negatively correlated with genera Pseudoflavonifractor, Butyricicoccus and Intestinimonas. Furthermore, liver metabolomics analysis demonstrated that L. brevis FZU0713 had a significant regulatory effect on the composition of liver metabolites in hyperlipidemic rats, especially the levels of some important biomarkers involved in the metabolic pathways of arachidonic acid metabolism, primary bile acid biosynthesis, amino sugar and nucleotide sugar metabolism, taurine and hypotaurine metabolism, biosynthesis of unsaturated fatty acid, fructose and mannose metabolism, tyrosine metabolism, etc. Additionally, oral administration of L. brevis FZU0713 significantly regulated the mR NA levels of liver genes(including Acat2, Acox1, Hmgcr, Cd36, Srebp-1c and Cyp7a1)involved in lipid metabolism and bile acid homeostasis. In conclusion, our findings provide the evidence that L. brevis FZU0713 has the potential to improve disturbance of lipid metabolism by regulating intestinal microflora and liver metabonomic profile. Therefore, L. brevis FZU0713 may be used as a potential probiotic strain to produce functional food to prevent hyperlipidemia.

Reoperation for heterochronic intraductal papillary mucinous neoplasm of the pancreas after bile duct neoplasm resection:A case report

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)and intraductal papillary mucinous neoplasm(IPMN)of the pancreas have similar pathological manifestations.However,they often develop separately and it is rare for both to occur together.Patients presenting with heterochronic IPMN after IPNB are prone to be misdiagnosed with tumor recurrence.CASE SUMMARY A 67-year-old male patient was admitted 8.5 years after IPNB carcinoma and 4 years after the discovery of a pancreatic tumor.A left hepatic bile duct tumor with distal bile duct dilatation was found 8.5 years ago by the computed tomography;therefore,a left hepatectomy was performed.The postoperative pathological diagnosis was malignant IPNB with negative cutting edge and pathological stage T1N0M0.Magnetic resonance imaging 4 years ago showed cystic lesions in the pancreatic head with pancreatic duct dilatation,and carcinoembryonic antigen continued to increase.Positron emission tomography showed a maximum standard uptake value of 11.8 in the soft tissue mass in the pancreatic head,and a malignant tumor was considered.Radical pancreatoduodenectomy was performed.Postoperative pathological diagnosis was pancreatic head IPMN with negative cutting edge,pancreaticobiliary type,stage T3N0M0.He was discharged 15 d after the operation.Follow-up for 6 mo showed no tumor recurrence,and quality of life was good.CONCLUSION IPNB and IPMN are precancerous lesions with similar pathological characteristics and require active surgery and long-term follow-up.

"Five steps four quadrants" modularized en bloc dissection technique for accessing hepatic hilum lymph nodes in laparoscopic pancreaticoduodenectomy

BACKGROUND Although en bloc dissection of hepatic hilum lymph nodes has many advantages in radical tumor treatment,the feasibility and safety of this approach for laparo-scopic pancreaticoduodenectomy(LPD)require further clinical evaluation and investigation.AIM To explore the application value of the"five steps four quadrants"modularized en bloc dissection technique for accessing hepatic hilum lymph nodes in LPD patients.METHODS A total of 52 patients who underwent LPD via the"five steps four quadrants"modularized en bloc dissection technique for hepatic hilum lymph nodes from April 2021 to July 2023 in our department were analyzed retrospectively.The patients'body mass index(BMI),preoperative laboratory indices,intraoperative variables and postoperative complications were recorded.The relationships between preoperative data and intraoperative lymph node dissection time and blood loss were also analyzed.RESULTS Among the 52 patients,36 were males and 16 were females,and the average age was 62.2±11.0 years.There were 26 patients with pancreatic head cancer,16 patients with periampullary cancer,and 10 patients with distal bile duct cancer.The BMI was 22.3±3.3 kg/m²,and the median total bilirubin(TBIL)concentration was 57.7(16.0-155.7)µmol/L.All patients successfully underwent the"five steps four quadrants"modularized en bloc dissection technique without lymph node clearance-related complications such as postoperative bleeding or lymphatic leakage.Correlation analysis revealed significant associations between preoperative BMI(r=0.3581,P=0.0091),TBIL level(r=0.2988,P=0.0341),prothrombin time(r=0.3018,P=0.0297)and lymph node dissection time.Moreover,dissection time was significantly correlated with intraoperative blood loss(r=0.7744,P<0.0001).Further stratified analysis demonstrated that patients with a preoperative BMI≥21.9 kg/m²and a TIBL concentration≥57.7μmol/L had significantly longer lymph node dissection times(both P<0.05).CONCLUSION The"five steps four quadrants"modularized en bloc dissection technique for accessing the hepatic hilum lymph node is safe and feasible for LPD.This technique is expected to improve the efficiency of hepatic hilum lymph node dissection and shorten the learning curve;thus,it is worthy of further clinical promotion and application.

Bioengineered skin organoids:from development to applications

Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.

“Hepatic hilum area priority,liver posterior first”:An optimized strategy in laparoscopic resection for type Ⅲ-Ⅳ hilar cholangiocarcinoma

BACKGROUND In recent years,pure laparoscopic radical surgery for Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma(HCCA)has been preliminarily explored and applied,but the surgical strategy and safety are still worthy of further improvement and attention.AIM To summarize and share the application experience of the emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”in pure laparoscopic radical resection for patients with HCCA of Bismuth-Corlette types Ⅲ and IV.METHODS The clinical data and surgical videos of 6 patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ who underwent pure laparoscopic radical resection in our department from December 2021 to December 2023 were retrospectively analyzed.RESULTS Among the 6 patients,4 were males and 2 were females.The average age was 62.2±11.0 years,and the median body mass index was 20.7(19.2-24.1)kg/m^(2).The preoperative median total bilirubin was 57.7(16.0-155.7)μmol/L.One patient had Bismuth-Corlette type Ⅲa,4 patients had Bismuth-Corlette type Ⅲb,and 1 patient had Bismuth-Corlette type Ⅳ.All patients successfully underwent pure laparoscopic radical resection following the strategy of“hepatic hilum area dissection priority,liver posterior separation first”.The operation time was 358.3±85.0 minutes,and the intraoperative blood loss volume was 195.0±108.4 mL.None of the patients received blood transfusions during the perioperative period.The median length of stay was 8.3(7.0-10.0)days.Mild bile leakage occurred in 2 patients,and all patients were discharged without serious surgery-related complications.CONCLUSION The emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”is safe and feasible in pure laparoscopic radical surgery for patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ.This strategy is helpful for promoting the modularization and process of pure laparoscopic radical surgery for complicated HCCA,shortens the learning curve,and is worthy of further clinical application.

C23 ameliorates carbon tetrachloride-induced liver fibrosis in mice

BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few reports on its role in liver fibrosis and the underlying mechanism is unknown.AIM To explore whether C23 plays a significant role in carbon tetrachloride(CCl4)-induced liver fibrosis.METHODS CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second week.Masson and Sirius red staining were used to examine changes in fiber levels.Inflammatory factors in the liver were detected and changes inα-smooth muscle actin(α-SMA)and collagen I expression were detected via immu-nohistochemical staining to evaluate the activation of hematopoietic stellate cells(HSCs).Western blotting was used to detect the activation status of the trans-forming growth factor-beta(TGF-β)/Smad3 axis after C23 treatment.RESULTS CCl4 successfully induced liver fibrosis in mice,while tumor necrosis factor-alpha(TNF-α),IL(interleukin)-1β,and IL-6 levels increased significantly and the IL-10 level decreased significantly.Interestingly,C23 inhibited this process.On the other hand,C23 significantly inhibited the activation of HSCs induced by CCl4,which inhibited the expression ofα-SMA and the synthesis of collagen I.In terms of mechanism,C23 can block Smad3 phosphorylation significantly and inhibits INTRODUCTION At present there is no specific and effective drug for treating liver fibrosis caused by acute or chronic injury.Although preclinical research has made breakthroughs,their suitability as clinical treatments is still unknown.The activation of hepatic stellate cells(HSCs)caused by chronic inflammation is a key process in the development of liver fibrosis and activated HSCs expressα-smooth muscle actin(α-SMA)and transdifferentiate into myofibroblasts with proliferation,migration and secretion abilities,synthesizing the extracellular matrix to deposit in the hepatocyte space and subse-quently forming liver fibrosis[1].Although therapeutic strategies have improved due to past few efforts there is no ideal treatment for hepatic fibrosis[2].Extracellular cold inducible RNA binding protein(CIRP)has been shown to play a role in various acute and chronic inflammatory diseases by promoting tissue inflammation and apoptosis and inducing fibrosis through its receptor Toll-like receptor 4(TLR4)[3].C23 is a recognized competitive inhibitor of CIRP that can competitively bind to CIRP receptors and reduce tissue damage in inflammatory diseases[4].C23 has been shown to significantly reduce serum tumor necrosis factor-alpha(TNF-α),IL(interleukin)-6 and IL-1βlevels.In addition,it can reduce tissue TLR4,TNF-α,IL-6 and IL-1βlevels and inhibit the colocalization of CIRP and TLR4,which plays a significant role in systemic inflammation[5].Re-search has shown that CIRP induces the inflammatory phenotype of lung fibroblasts in a TLR4-dependent manner[6].On the other hand,CIRP is associated with markers of fibrosis andα-SMA is significantly positively correlated with CIRP.Cirp-/-mice exhibit attenuated expression ofα-SMA and collagen(COL1A1 and COL3A1),decreased hydroxyproline content,decreased histological fibrosis scores,and improved pulmonary hypertension[7].C23 inhibited the release of TNF-α,the degradation of IκB and the nuclear translocation of NF-κB in CIRP-stimulated macrophages in a dose-dependent manner and C23 treatment significantly increased the serum levels of lactic dehydrogenase,alanine ami-notransferase,IL-6,TNF-αand IL-1βin septic CLP mice[8].Based on previous research we hypothesized that C23 might alleviate liver fibrosis by inhibiting acute and chronic inflammation.As a selective hepatotoxic chemical carbon tetrachloride(CCl4).can induce inflammation and activate HSCs,promoting liver fibrosis.This study reveals the role and mechanism of C23 in CCl4-induced liver fibrosis in mice.at room temperature for 30 minutes.The gray value of each group was calculated after chemiluminescence.

Biliary tract intraductal papillary mucinous neoplasm: Report of 19 cases

AIM: To gain a better understanding of biliary tract intraductal papillary mucinous neoplasm(BT-IPMN).METHODS: From January 2000 to December 2013, 19cases of BT-IPMN were retrospectively identified from a total of 343 biliary tract tumors resected in our single institution.Demographic characteristics, clinical data, pathology, surgical strategies, and long-term follow-up were analyzed.RESULTS: The mean age of the 19 BT-IPMN cases was 53.8 years(range: 25-74 years).The most common symptom was abdominal pain(15/19; 78.9%), followed by jaundice(7/19; 36.8%).Cholangitis was associated with most(16/19; 84.2%) of the BT-IPMN cases.Macroscopically visible mucin was detected in all 19 patients, based on original surgical reports.The most common abnormal preoperative imaging findings for BT-IPMN were bile duct dilation(19/19; 100%) and intraluminal masses(10/19; 52.6%).Thirteen(68.4%) cases involved the intrahepatic bile duct and hilum.We performed left hepatectomy in 11/19(57.9%), right hepatectomy in 2/19(10.5%), bile duct resection in 4/19(21.1%), and pancreatoduodenectomy in 1/19(5.3%) patients.One(5.3%) patient was biopsied and received a choledochojejunostomy because of multiple tumors involving the right extrahepatic and left intrahepatic bile ducts.Histology showed malignancy in 10/19(52.6%) patients.The overall median survival was 68 mo.The benign cases showed a non-significant trend towards improved survival compared to malignant cases(68 mo vs 48 mo, P = 0.347).The patient without tumor resection died of liver failure 22 mo after palliative surgery.CONCLUSION: BT-IPMN is a rare biliary entity.Complete resection of the tumor is associated with good survival, even in patients with malignant disease.

Addition of hepatectomy decreases liver recurrence and leads to long survival in hilar cholangiocarcinoma

AIM： To evaluate hepatic recurrence and prognostic factors for survival in patients with surgically resected hilar cholangiocarcinoma in a single institution over the last 13 years. METHODS： From 1994 to 2007, all patients with hilar cholangiocarcinoma referred to a surgical clinic were evaluated. Demographic data, tumor characteristics, and outcome were analyzed retrospectively. Outcome was compared in patients who underwent additional liver resection with resection of the tumor. RESULTS： Of the 69 patients submitted to laparotomy for tumor resection, curative resection （Ro resection） was performed in 40 patients, and palliative resection in 29. Thirty-one patients had only duct resection, and 38 patients had combined duct resection with liver resection including 34 total or part caudate lobes. Curative rates with the combined hepatectomy were significantly improved compared with those without additional hepatectomy （27/38 vs 13/31; X^2 = 5.94, P 〈 0.05）. Concomitant liver resection was associated with a decreased incidence of initial recurrence in liver one year after surgery （11/38 vs 23/31; X^2 = 13.98, P 〈 0.01）. The 3-year survival rate after Ro resection was 30.7% and was 10.5% for palliative resection. R0 resection improved the 3-year survival rate （30.7% vs 10.5%; X^2 = 12.47, P 〈 0.01）.CONCLUSION： Hepatectomy, especially including the caudate lobe combined with bile duct resection should be considered standard treatment to cure hilar cholangiocarcinoma.

Diagnostic value of elevated serum carbohydrate antigen 199 level in acute cholangitis secondary to choledocholithiasis

AIM To investigate the diagnostic value of abnormal serum carbohydrate antigen 199(CA199) level in acute cholangitis secondary to choledocholithiasis.METHODS In this retrospective cohort study, the clinical data of 727 patients with choledocholithiasis admitted to the Third Affiliated Hospital of Zunyi Medical College from June 2011 to June 2017 were collected. Among these patients, 258 patients had secondary acute cholangitis and served as observation group, and the remaining 569 choledocholithiasis patients served as the control group. Serum liver function indexes and tumor markers were detected in both groups, and the receiver operating characteristic(ROC) curves were constructed for markers showing statistical significances. The cutoff value, sensitivity, and specificity of each marker were calculated according to the ROC curves. RESULTS The results of liver function tests showed no significant differences between the two groups(P > 0.05). Tumor markers including serum CA125, CA153, carcinoembryonic antigen, and alpha fetoprotein levels were also not significantly different(P > 0.05); however, the serum CA199 level was significantly higher in the observation group than in the control group(P < 0.05). The ROC curve analysis showed that the area under the curve was 0.885(95%CI: 0.841-0.929) for CA199, and the cutoff value of 52.5 kU/L had the highest diagnostic accuracy, with a sensitivity of 86.8% and a specificity of 81.6%.CONCLUSION Abnormally elevated serum CA199 level has an important value in the diagnosis of acute cholangitis secondary to choledocholithiasis. It may be a specific inflammatory marker for acute cholangitis.

Primary squamous cell carcinoma of the liver associated with hepatolithiasis:A case report

Primary squamous cell carcinoma(SCC) of the liver is rare and reported sporadically.Up to date,only 24 such cases have been reported in the literature.It is associated with hepatic teratoma,congenital cysts,solitary benign non-parasitic hepatic cysts,hepatolithiasis/Caroli's disease or cirrhosis.We reported a case of primary SCC of the liver associated with multiple intrahepatic cholesterol gallstones.The patient underwent hepatectomy followed by radiotherapy,and has survived for over 19 mo without recurrence.

Xanthogranulomatous cholecystitis mimicking gallbladder carcinoma:An analysis of 42 cases

AIM: To review and evaluate the diagnostic dilemma of xanthogranulomatous cholecystitis(XGC) clinically.METHODS: From July 2008 to June 2014, a total of 142 cases of pathologically diagnosed XGC were reviewed at our hospital, among which 42 were misdiagnosed as gallbladder carcinoma(GBC) based on preoperative radiographs and/or intra-operative findings. The clinical characteristics, preoperative imaging, intra-operative findings, frozen section(FS) analysis and surgical procedure data of these patients were collected and analyzed.RESULTS: The most common clinical syndrome in these 42 patients was chronic cholecystitis, followed by acute cholecystitis. Seven(17%) cases presented with mild jaundice without choledocholithiasis. Thirtyfive(83%) cases presented with heterogeneous enhancement within thickened gallbladder walls on imaging, and 29(69%) cases presented with abnormal enhancement in hepatic parenchyma neighboring the gallbladder, which indicated hepatic infiltration. Intra-operatively, adhesions to adjacent organs were observed in 40(95.2%) cases, including the duodenum, colon and stomach. Thirty cases underwent FS analysis and the remainder did not. The accuracy rate of FS was 93%, and that of surgeon's macroscopic diagnosis was 50%. Six cases were misidentified as GBC by surgeon's macroscopic examination and underwent aggressive surgical treatment. No statistical difference was encountered in the incidence of postoperative complications between total cholecystectomy and subtotal cholecystectomy groups(21% vs 20%, P > 0.05).CONCLUSION: Neither clinical manifestations and laboratory tests nor radiological methods provide apractical and effective standard in the differential diagnosis between XGC and GBC.