A TLR4-Targeting Bioactive Peptide Hydrogel to Regulate Immune-Microenvironment for Diabetic Wound Repair.

Persistent inflammation and disrupted immunoregulation are critical factors in impeding diabetic wound healing. While immunoregulatory hydrogel dressings hold significant promise for clinical applications in diabetic wound healing, the current application often demands intricate interventions and high-cost treatments involving cytokines and cell therapies. The development of single component immunoregulatory hydrogels remains a complex challenge. To address this issue, an active peptide hydrogel with immunoregulatory properties targeting the TLR4/NF-kB pathway, aiming to promote rapid diabetic wound healing, is engineered. The hydrogel sequence comprises naphthalene derivative, phenylalanine, and glycine to modulate hydrophilic/hydrophobic characteristics. The amino group on arginine contributes to tissue adhesion and regulation of intermolecular forces, ultimately yielding stable gels. The results underscore the formation of the peptide hydrogel (NFA) via the physical crosslinking of self-assembled nanofibers in water, thereby affording both excellent injectability and tissue adhesion. Notably, NFA demonstrates significant potential in promoting wound healing in a mouse model with full-thickness wounds by regulating macrophage responses in the inflammatory microenvironment through the TLR4/NF-kB pathway.

From imaging to clinical outcome: dual-region CT radiomics predicting FOXM1 expression and prognosis in hepatocellular carcinoma.

Background: Liver cancer, especially hepatocellular carcinoma (HCC), remains a significant global health challenge. Traditional prognostic indicators for HCC often fall short in providing comprehensive insights for individualized treatment. The integration of genomics and radiomics offers a promising avenue for enhancing the precision of HCC diagnosis and prognosis. Methods: From the Cancer Genome Atlas (TCGA) database, we categorized mRNA of HCC patients by Forkhead Box M1 (FOXM1) expression and performed univariate and multivariate studies to pinpoint autonomous HCC risk factors. We deployed subgroup, correlation, and interaction analyses to probe FOXM1's link with clinicopathological elements. The connection between FOXM1 and immune cells was evaluated using the CIBERSORTx database. The functions of FOXM1 were investigated through analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). After filtering through TCGA and the Cancer Imaging Archive (TCIA) database, we employed dual-region computed tomography (CT) radiomics technology to noninvasively predict the mRNA expression of FOXM1 in HCC tissues. Radiomic features were extracted from both tumoral and peritumoral regions, and a radiomics score (RS) was derived. The performance and robustness of the constructed models were evaluated using 10-fold cross-validation. A radiomics nomogram was developed by incorporating RS and clinical variables from the TCGA database. The models' discriminative abilities were assessed using metrics such as the area under the curve (AUC) of the receiver operating characteristic curves (ROC) and precision-recall (PR) curves. Results: Our findings emphasized the overexpression of FOXM1 as a determinant of poor prognosis in HCC and illustrated its impact on immune cell infiltration. After selecting arterial phase CT, we chose 7 whole-tumor features and 3 features covering both the tumor and its surroundings to create WT and WP models for FOXM1 prediction. The WT model showed strong predictive capabilities for FOXM1 expression by PR curve. Conversely, the WP model did not demonstrate the good predictive ability. In our study, the radiomics score (RS) was derived from whole-tumor regions on CT images. The RS was significantly associated with FOXM1 expression, with an AUC of 0.918 in the training cohort and 0.837 in the validation cohort. Furthermore, the RS was correlated with oxidative stress genes and was integrated with clinical variables to develop a nomogram, which demonstrated good calibration and discrimination in predicting 12-, 36-, and 60-month survival probabilities. Additionally, bioinformatics analysis revealed FOXM1's potential role in shaping the immune microenvironment, with its expression linked to immune cell infiltration. Conclusion: This study highlights the potential of integrating FOXM1 expression and radiomics in understanding HCC's complexity. Our approach offers a new perspective in utilizing radiomics for non-invasive tumor characterization and suggests its potential in providing insights into molecular profiles. Further research is needed to validate these findings and explore their clinical implications in HCC management.

Efficacy of extracts from Datura Metel L. for Psoriasis: a meta-analysis of case series and single-arm studies.

BACKGROUND: Datura Metel L. has been used to treat psoriasis in China for a long time. The effect of extracts from Datura Metel L. for Psoriasis has not been previously confirmed. This study aimed to evaluate the efficacy of extracts from Datura Metel L. for patients with psoriasis. METHODS: PubMed, Cochrane Library, Embase, and other databases were searched from database inception until to September 1, 2021. A quality assessment and data extraction were performed by 2 independent reviews. We used a random-effects meta-analysis model to estimate the pooled curative effect, pooled odds ratio (OR), and 95% confidence intervals. RESULTS: Nine studies were included in Meta-analysis, including a total number of 1778 patients with psoriasis. The case cure rate of Datura Metel L. intravenous therapy was 0.48 (95% CI: 0.33, 0.62) and of Datura Metel L. oral therapy was 0.42 (95% CI: 0.17, 0.68), respectively. The case effective rate of Datura Metel L. intravenous therapy was 0.91 (95% CI: 0.84, 0.97) and of Datura Metel L. oral therapy was 0.94 (95% CI: 0.88, 0.99), respectively. CONCLUSIONS: The extracts from Datura Metel L. showed the potential to treat psoriasis, and intravenous therapy might be a promising treatment to cure psoriasis, which is likely affected by selection and publication bias, still need more high quality clinical studies.

Nanoparticles Mediated circROBO1 Silencing to Inhibit Hepatocellular Carcinoma Progression by Modulating miR-130a-5p/CCNT2 Axis.

Background: Circular RNAs (circRNAs) are becoming vital biomarkers and therapeutic targets for malignant tumors due to their high stability and specificity in tissues. However, biological functions of circRNAs in hepatocellular carcinoma (HCC) are still not well studied. Methods: Gene Expression Omnibus (GEO) database and qRT-PCR were used to evaluate expression of circROBO1 (hsa_circ_0066568) in HCC tissues and cell lines. CCK-8, colony formation, EdU staining, flow cytometry for cell cycle analysis, and xenograft model assays were performed to detect the circROBO1 function in vitro and in vivo. RNA pull-down, RNA immunoprecipitation (RIP), and Luciferase reporter assays were used to investigate the relationship among circROBO1, miR-130a-5p, and CCNT2. More importantly, we developed nanoparticles made from poly lactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG) chains as the delivery system of si-circROBO1 and then applied them to HCC in vitro and in mice. Results: circROBO1 was obviously upregulated in HCC tissues and cell lines, and elevated circROBO1 was closely correlated with worse prognosis for HCC patients. Functionally, knocking down circROBO1 significantly suppressed HCC cells growth in vitro and in mice. Mechanistically, circROBO1 acted as a competing endogenous RNA to downregulate miR-130a-5p, leading to CCNT2 expression upregulation. Furthermore, miR-130a-5p mimic or CCNT2 knockdown reversed the role of circROBO1 overexpression on HCC cells, which demonstrated that circROBO1 promoted HCC development via miR-130a-5p/CCNT2 axis. In addition, we developed nanoparticles loaded with si-circROBO1, named as PLGA-PEG (si-circROBO1) NPs, which significantly prevented the proliferation of HCC cells, and did not exhibit apparent toxicity to major organs in vivo. Conclusion: Our findings firstly demonstrate that circROBO1 overexpression promotes HCC progression by regulating miR-130a-5p/CCNT2 axis, which may serve as an effective nanotherapeutic target for HCC treatment.

Characterizing PTP4A3/PRL-3 as the Potential Prognostic Marker Gene for Liver Hepatocellular Carcinoma.

Background: A large number of cancer-related deaths in the world can be attributed to liver hepatocellular carcinoma (LIHC). The purpose of this study is to explore protein tyrosine phosphatase type IV A member 3 (PTP4A3/PRL-3) as a new and reliable biomarker to predict the prognosis of LIHC and determine the potential therapeutic targets or drugs that can be used for treating LIHC. Methods: We included three LIHC datasets with clinical information and expression profiles from public databases. The expression level of PTP4A3 was analyzed, and based on the results, the samples were divided into high- and low-expression groups. The Kaplan-Meier survival analysis method was used to determine the relationship between PTP4A3 and prognosis. The enrichment differences among the functional pathways associated with the high- and low-expression groups were determined using the gene set enrichment analysis (GSEA) method. Five methods were used to determine the differences among the tumor microenvironment in the low- and high-expression groups. The sensitivity of the low- and high-expression groups toward different drug treatment methods was predicted by analyzing the Tumor Immune Dysfunction and Exclusion (TIDE) scores and determining the biochemical half-maximal inhibitory concentration (IC50). Results: The expression levels of the LIHC and adjacent samples were analyzed, and it was observed that the expression level of PTP4A3 in tumor tissue was significantly higher than the expression level of the same gene in the adjacent samples. It was also inferred that it might be a cancer-promoting gene. It was concluded that high-expression results in a significantly poor prognosis. The high-expression group was significantly enriched in the tumor-related pathways, such as the PI3K-AKT signaling pathway. In addition, the results obtained by conducting immune infiltration analysis revealed a significant positive correlation between some immune scores and the gene PTP4A3. The drug KIN001-135 and gene PTP4A3 were also found to correlate positively with each other. CP466722, Pyrimethamine, AKT inhibitor VIII, Embelin, Cisplatin, QS11, Bexarotene, and Midostaurin negatively correlated with PTP4A3 associated with the three datasets. Moreover, the drugs Cisplatin, QS11, Midostaurin, and CP466722 were more sensitive toward the high-expression group than the low PTP4A3 expression group. Significant differences were observed in these cases. Conclusion: PTP4A3/PRL-3 is potentially associated with the progression, metastasis, and invasion of LIHC. The prognosis of LIHC patients is negatively impacted by the high-expression levels of the gene. The results indicate that PTP4A3/PRL-3 is an important prognostic factor for LIHC and is a new potential prognostic detection target. The discovery of the 8 drugs that were negatively associated with PTP4A3 provided a new direction that can be developed in the future for the treatment of LIHC.

Sirolimus increases the anti-cancer effect of Huai Er by regulating hypoxia inducible factor-1α-mediated glycolysis in hepatocellular carcinoma.

BACKGROUND: Glycolysis caused by hypoxia-induced abnormal activation of hypoxia inducible factor-1α (HIF-1α) in the immune microenvironment promotes the progression of hepatocellular carcinoma (HCC), leading to enhanced drug resistance in cancer cells. Therefore, altering the immunosuppressive microenvironment by imp-roving the hypoxic state is a new goal in improving cancer treatment. AIM: To analyse the role of HIF-1α, which is closely related to tumour proliferation, invasion, metastasis, and angiogenesis, in the proliferation and invasion of liver cancer, and to explore the HIF-1α pathway-mediated anti-cancer mechanism of sirolimus (SRL) combined with Huai Er. METHODS: Previous studies on HCC tissues identified the importance of HIF-1α, glucose transporter 1 (GLUT1), and lactate dehydrogenase A (LDHA) expression. In this study, HepG2 and Huh7 cell lines were treated, under hypoxic and normoxic conditions, with a combination of SRL and Huai Er. The effects on proliferation, invasion, cell cycle, and apoptosis were analysed. Proteomics and genomics techniques were used to analyze the HIF-1α-related signalling pathway during SRL combined with Huai Er treatment and its inhibition of the proliferation of HCC cells. RESULTS: High levels of HIF-1α, LDHA, and GLUT-1 were found in poorly differentiated HCC, with lower patient survival rates. Hypoxia promoted the proliferation of HepG2 and Huh7 cells and weakened the apoptosis and cell cycle blocking effects of the SRL/Huai Er treatment. This was achieved by activation of HIF-1α and glycolysis in HCC, leading to the upregulation of LDHA, GLUT-1, Akt/mammalian target of rapamycin (mTOR), vascular endothelial growth factor (VEGF), and Forkhead box P3 and downregulation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and p27. The hypoxia-induced activation of HIF-1α showed the greatest attenuation in the SRL/Huai Er (S50 + H8) group compared to the drug treatments alone (P < 0.001). The S50 + H8 treatment significantly downregulated the expression of mTOR and HIF-1α, and significantly reduced the expression of VEGF mRNA. Meanwhile, the combined blocking of mTOR and HIF-1α enhanced the downregulation of Akt/mTOR, HIF-1α, LDHA, and GLUT-1 mRNA and resulted in the downregulation of PTEN, p27, and VEGF mRNA (P < 0.001). CONCLUSION: SRL increases the anti-cancer effect of Huai Er, which reduces the promotion of hypoxia-induced HIF-1α on the Warburg effect by inhibition of the PI3K/Akt/mTOR-HIF-1α and HIF-1α-PTEN signalling pathways in HCC.

The anti-alcoholism drug disulfiram effectively ameliorates ulcerative colitis through suppressing oxidative stresses-associated pyroptotic cell death and cellular inflammation in colonic cells.

BACKGROUND: Oxidative stress, cell pyroptosis and inflammation are considered as important pathogenic factors for ulcerative colitis (UC) development, and the traditional anti-alcoholism drug disulfiram (DSF) has recently been reported to exert its regulating effects on all the above cellular functions, which makes DSF as ideal therapeutic agent for UC treatment, but this issue has not been fully studied. METHODS: Dextran sulfate sodium (DSS)-induced animal models in C57BL/6J mice and lipopolysaccharide (LPS)-induced cellular models in colonic cell lines (HT-29 and Caco-2) for UC were respectively established. Cytokine secretion was determined by ELISA. Cell viability and proliferation were evaluated by MTT assay and EdU assay. Real-Time qPCR, Western Blot, immunofluorescent staining assay and immunohistochemistry (IHC) were employed to evaluate gene expressions. The correlations of the genes in the clinical tissues were analyzed by using the Pearson Correlation analysis. RESULTS: DSF restrained oxidative stress, pyroptotic cell death and cellular inflammation in UC models in vitro and in vivo, and elimination of Reactive Oxygen Species (ROS) by N-acetyl-l-cysteine (NAC) rescued cell viability in LPS-treated colonic cells (HT-29 and Caco-2). Further experiments suggested that a glycogen synthase kinase-3ß (GSK-3ß)/Nrf2/NLRP3 signaling cascade played critical role in this process. Mechanistically, DSF downregulated GSK-3ß and NLRP3, whereas upregulated Nrf2 in LPS-treated colonic cells. Also, the regulating effects of DSF on Nrf2 and NLRP3 were abrogated by upregulating GSK-3ß. Moreover, upregulation of GSK-3ß abolished the protective effects of DSF on LPS-treated colonic cells. CONCLUSIONS: Taken together, data of this study indicated that DSF restrained oxidative damages-related pyroptotic cell death and inflammation via regulating the GSK-3ß/Nrf2/NLRP3 pathway, leading to the suppression of LPS-induced UC development.

Protein tyrosine phosphatase 1 protects human pancreatic cancer from erastin-induced ferroptosis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy due to the lack of early detection method, therapeutic drug and target. We noticed that the expression of Protein Tyrosine Phosphatase Mitochondria1(PTPMT1) is upregulated in PDAC. However, its role in pancreatic cancer remains unknown. METHODS: We first analyzed the expression of PTPMT1 from 50 PDAC patients. Secondly, the survival proportions of different PTPMT1-expressed patients were analyzed. Then, the role and mechanism of PTPMT1 in PDAC were studied by lentivirus transduction system. RESULTS: PTPMT1 was upregulated in PDAC and patients with high PTPMT1 expression displayed lower overall survival rate. Knockdown of PTPMT1 increased the sensitivity to erastin or RSL3 induced ferroptosis. Mechanically, knockdown of PTPMT1 resulted in upregulated Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) and downregulated Solute Carrier Family 7 Member 11 (SLC7A11). In addition, SLC7A11 was upregulated in PDAC tumor tissue and correlated positively with the expression of PTPMT1. However, the expression of ACSL4 was downregulated in PDAC and negatively correlated with the expression of PTPMT1. CONCLUSION: Our study demonstrates that PTPMT1 is upregulated in PDAC and PTPMT1 inhibits ferroptosis by suppressing the expression of ACSL4 and upregulating SLC7A11 in Panc-1 cells, suggesting PTPMT1 might be a potential prognosis biomarker and therapeutic target in PDAC.

Laparoscopic hepatectomy versus open hepatectomy for tumors located in right posterior segment: A single institution study.

OBJECT: With the gradual advancement of laparoscopic technology, surgeries can be successfully performed with the help of laparoscopy increasingly. This study initially explored the difference between laparoscopic right posterior sectionectomy (LRPS) and open right posterior sectionectomy (ORPS)of liver in our center, discussed the effectiveness, benefits and safety of LRPS and introduce some surgical techniques in our center. MATERIALS AND METHODS: We retrospectively analyze 96 cases of liver tumor located in the right posterior lobe of liver in our institution from January 2015 to January 2018. There were 46 cases performed the LRPS surgery and 50 cases performed the ORPS surgery. Through analysis of the perioperative outcomes of these two groups by a case control study, we compare the differences between these two groups. RESULTS: There was no significant difference between the LRPS and ORPS group in demographic and baseline characteristics before surgery. Patients in the LRPS group were significantly superior to ORPS in terms of postoperative liver function recovery, postoperative inflammatory factor level, pain sensation (3.03 ± 0.79 vs 4.58 ± 1.25), abdominal incision length (6.25 ± 2.34 vs 32.15 ± 3.21), carrying abdominal drainage tube time (3.26 ± 0.77 vs 4.83 ± 0.76), recovery of bowel function time (1.6 ± 0.61 VS 3.05 ± 0.85)and postoperative hospital stay (5.73 ± 0.99 vs 7.16 ± 0.95) (P < 0.05). CONCLUSION: Compared with the traditional ORPS, LRPS has the advantages of minor injury, faster recovery and mild inflammatory reaction. The LRPS is safe and feasible, and it should be gradually promoted in clinical practice.

PD-L1+NEUT, Foxp3+Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma.

Background: This presented study was aimed to evaluate the diagnostic and prognostic value of PD-L1+Neutrophils (PD-L1+NEUT) and neutrophil to lymphocyte ratio (NLR) based on our previous experience of Foxp3+Treg in transplantation. Methods: the NLR cutoff value of 1.79 was used to include 136 cases from the 204 patients with hepatocellular carcinoma (HCC) confirmed by clinical pathology, which were divided into highly-moderately and poorly differentiated HCC groups. The expressions of PD-L1+NEUT and Foxp3+Treg in peripheral blood and cancer tissue were detected with flow cytometry, meanwhile, PD-L1 and Foxp3 expressed in carcinoma and para-carcinoma tissues were marked by immunohistochemistry. Survival rates, including overall survival and disease-free survival, were calculated by the Kaplan-Meier curve and evaluated with the log-rank test. Finally, Cox risk regression model was used to analyze the independent risk factors for prognostic survival. Results: The level of PD-L1+NEUT, Foxp3+Treg, and NLR in peripheral blood of patients with poorly differentiated HCC were significantly increased (all P < .001). Both PD-L1+NEUT and NLR were positively correlated with Foxp3+Treg (r = 0.479, P = .0017; r = 0.58, P < .0001). The level of PD-L1+NEUT and Foxp3+Treg as well as PD-L1 and Foxp3 in cancer tissue and patients with poorly differentiated HCC were obviously increased (all P < .01), respectively. Cox regression analysis indicated that PD-L1+NEUT, NLR, and Foxp3+Treg were independent risk factors for the prognosis (P = .000, .000, .006) with a RR and 95%CI of 2.704-(2.155-3.393), 3.139-(2.361-4.173), 1.409-(1.105-1.798), respectively. Conclusion: PD-L1+NEUT, NLR, and Foxp3+Treg are independent risk factors for prognosis which maybe new marker of lower survival benefits.

Comparison of Perioperative and Oncological Outcomes of Hybrid and Totally Laparoscopic Pancreatoduodenectomy.

BACKGROUND Laparoscopic pancreatoduodenectomy (LPD) is a complicated procedure accompanied with high morbidity. Hybrid LPD is usually used as an alternative/transitional approach. This study aimed to prove whether the hybrid procedure is a safe procedure during a surgeon's learning curve of LPD. MATERIAL AND METHODS There were 48 hybrid LPD patients and 62 TLPD patients selected from January 2016 to December 2018; their demographics, surgical outcomes, and oncological data were retrospectively collected. Patient follow-up for the study continued until February 2020. RESULTS Patient demographics and baseline parameters were well balanced between the 2 groups. Intraoperative conditions, overall operation time was shorter for TLPD compared to hybrid LPD (407.79 minutes versus 453.29 minutes, respectively; P=0.035) and blood loss was less in TLPD patients compared to hybrid LPD patients (100.00 mL versus 300.00 mL, respectively; P<0.001). There was no difference in transfusion rates between the 2 groups (hybrid LPD 16.7% versus TLPD 4.8%; P=0.084). Postoperative outcomes and intensive care unit (ICU) stay was longer in the hybrid LPD patient group (hybrid LPD 1-day versus TLPD 0-day, P=0.002) and postoperative hospital stay was similar between the 2 groups (P=0.503). Reoperation rates, in-hospital, 30-day mortality, and 90-day mortality rates were comparable between the 2 groups (P=0.276, 1.000, 1.000, 0.884, respectively). Surgical site infection, bile leak, Clavien-Dindo classification (CDC) ≥3, delayed gastric emptying, grade B/C postoperative pancreatic fistulae, and grade B/C post pancreatectomy hemorrhage were not different between the 2 groups (P=0.526, 0.463, 0.220, 0.089, 0.165, 0.757, respectively). The tumor size, margin status, lymph nodes harvested, and metastasis were similar in the 2 groups (P=0.767, 0.438, 0.414, 0.424, respectively). In addition, the median overall survival rates were comparable between the 2 groups (hybrid LPD 29.0 months versus TLPD 30.0 months, P=0.996) as were the progression-free survival rates (hybrid LPD 11.0 months versus TLPD 12.0 months, P=0.373) CONCLUSIONS Hybrid LPD was comparable to TLPD. Hybrid LPD could be performed safely when some surgeons first started LPD (during the operative learning curve), while for skilled surgeons, TLPD could be applied initially.

Generation and application of patient-derived xenograft models in pancreatic cancer research.

OBJECTIVE: Pancreatic ductal adenocarcinoma cancer (PDAC) is one of the leading causes of cancer-related death worldwide. Hence, the development of effective anti-PDAC therapies is urgently required. Patient-derived xenograft (PDX) models are useful models for developing anti-cancer therapies and screening drugs for precision medicine. This review aimed to provide an updated summary of using PDX models in PDAC. DATA SOURCES: The author retrieved information from the PubMed database up to June 2019 using various combinations of search terms, including PDAC, pancreatic carcinoma, pancreatic cancer, patient-derived xenografts or PDX, and patient-derived tumor xenografts or PDTX. STUDY SELECTION: Original articles and review articles relevant to the review's theme were selected. RESULTS: PDX models are better than cell line-derived xenograft and other models. PDX models consistently demonstrate retained tumor morphology and genetic stability, are beneficial in cancer research, could enhance drug discovery and oncologic mechanism development of PDAC, allow an improved understanding of human cancer cell biology, and help guide personalized treatment. CONCLUSIONS: In this review, we outline the status and application of PDX models in both basic and pre-clinical pancreatic cancer researches. PDX model is one of the most appropriate pre-clinical tools that can improve the prognosis of patients with pancreatic cancer in the future.

Effect of laparoscopic splenectomy on portal vein thrombosis and serum YKL-40 in patients with cirrhotic portal hypertension.

INTRODUCTION AND OBJECTIVES: Laparoscopic splenectomy (LS) is a supportive intervention for cirrhotic patients. However, its efficacy for patients with cirrhotic portal hypertension (CPH) still needs clarification. Studies indicated YKL-40 might be effective targets for treatment of splenomegaly, however deeper insights are unclear. The aim of this study was to investigate the effect of LS on the formation of portal vein thrombosis (PVT) and serum levels of a fibrosis marker, YKL-40, in patients with CPH. MATERIALS AND METHODS: A total of 80 patients who underwent LS and 30 healthy controls were investigated in this study. Serum levels of YKL-40 were measured by enzyme-linked immunosorbent assay (ELISA). Demographic characteristics including age and gender were recorded. Clinicopathological and laboratory examinations included the severity of esophageal varices and the presence of viral hepatitis. The liver function was assessed according to the Child-Pugh classification. The incidence of PVT before and after operation was also monitored. RESULTS: Serum YKL-40 was significantly increased in CPH patients, and was associated with Child-Pugh score and HBV infection. Furthermore, elderly patients had an increased risk for postoperative PVT. Higher serum YKL-40 was observed in patients with thrombus at postoperative 7, 14 and 21 days than those without thrombus. CONCLUSIONS: LS could reduce serum YKL-40 levels and PVT progression and was a useful treatment for patients <40 years of age with CPH.

Delayed introduction of immunosuppressive regimens in critically ill patients after liver transplantation.

BACKGROUND: The manipulation of immunosuppression therapy remains challenging in patients who develop infectious diseases or multiple organ dysfunction after liver transplantation. We evaluated the outcomes of delayed introduction of immunosuppression in the patients after liver transplantation under immune monitoring with ImmuKnow assay. METHODS: From March 2009 to February 2014, 225 consecutive liver recipients in our institute were included. The delayed administration of immunosuppressive regimens was attempted in 11 liver recipients with multiple severe comorbidities. RESULTS: The median duration of non-immunosuppression was 12 days (range 5-58). Due to the infectious complications, the serial ImmuKnow assay showed a significantly low ATP level of 64±35 ng/mL in the early period after transplantation. With the development of comorbidities, the ImmuKnow value significantly increased. However, the acute allograft rejection developed when a continuous distinct elevation of both ATP and glutamyltranspeptidase levels was detected. The average ATP level measured just before the development of acute rejection was 271±115 ng/mL. CONCLUSIONS: The delayed introduction of immunosuppressive regimens is safe and effective in management of critically ill patients after liver transplantation. The serial ImmuKnow assay could provide a reliable depiction of the dynamics of functional immunity throughout the clinical course of a given patient.

Sirolimus treatment for cirrhosis or hepatocellular carcinoma patients accompanied by psoriasis after liver transplantation: A single center experience.

There is currently no consensus on the most suitable therapeutic approach for psoriasis (PS) co-existing with posthepatic cirrhosis (PCs) and hepatocellular carcinoma (HCC) following liver transplantation (LT). The present study provides an analysis of the therapeutic experience of such patients. Five LT recipients (two with PC and three with HCC) with accompanying PS were included. The induction program consisted of methylprednisolone plus basiliximab treatment. The initial postoperative treatment scheme consisted of tacrolimus (FK506) plus mycophenolate mofetil (MMF) and hormone; the latter was withdrawn 1 week after LT. The patients with PC had been using FK506 with or without a postoperative MMF program; the patients with HCC and recurrence of PS had been switched to a sirolimus (SRL)-based replacement therapy. Furthermore, all patients received anti-hepatitis B virus (HBV) therapy. The patients were followed up after 8.3±1.5 years. There was a positive correlation between HBV-DNA copy numbers, and psoriatic area and severity index (PASI) scores (r=0.97; P=0.006). The PASI scores were decreased significantly at 6 months following surgery compared with pre-transplantation (P<0.05). The patients who had received the FK506-based treatment experienced PS recurrence two years post-transplantation. The PASI scores increased significantly (P<0.05) and then declined gradually, maintaining a stable level (P<0.05) by 1 year after switching to the SRL-based treatment. The patients who had received the SRL-based treatment exhibited no recurrence of PS. The results of the present study suggest that SRL therapy provides a promising novel treatment method for patients with PS following LT that may be superior to tacrolimus treatment. When co-existing HBV is present pre-transplantation, regular injection of human hepatitis B immunoglobulin should be used to prevent the HBV from relapsing or aggravating the PS.

Perioperative and long-term outcomes of liver resection for hepatitis B virus-related hepatocellular carcinoma without versus with hepatic inflow occlusion: study protocol for a prospective randomized controlled trial.

BACKGROUND: The high prevalence of hepatitis B virus (HBV) imposes a huge burden of hepatocellular carcinoma (HCC) in Asia. Surgical resection remains an important therapeutic strategy for HCC. Hepatic inflow occlusion, known as the Pringle maneuver, is the most commonly used method of reducing blood loss during liver parenchymal transection. A major issue with this maneuver is ischemia-reperfusion injury to the remnant liver, and the hemodynamic disturbance it induces in the tumor-bearing liver raises an oncological concern. Given the technical advances in living donor liver transplantation, vascular occlusion in liver resection can be avoided in experienced hands. The aim of this study is to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC without versus with hepatic inflow occlusion. METHODS/DESIGN: This study will include eligible patients with HBV-related HCC elected for liver resection. Fifty-seven patients will be enrolled in each randomization arm to detect a 20 % difference in the serum level of total bilirubin on postoperative day 5 (80 % power and α = 0.05). The secondary endpoints include procedural parameters, perioperative liver function and inflammatory response, postoperative morbidity and mortality, and long-term outcomes. Patients will be followed for up to 5 years. Data will be statistically analyzed on an intention-to-treat basis. DISCUSSION: This prospective randomized controlled trial is designed to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC without versus with vascular occlusion. The clinical implications of these outcomes may change current surgical practice and fill the oncological gaps therein. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02563158 . Registered on 28 September 2015.

[Development of laparoscopic technology in biliary surgery in the past 23 years: a single-center experience].

OBJECTIVE: To summarize the 23-year experience of laparoscopic biliary surgery in General Hospital of PLA and evaluate the application of laparoscopic surgery in the treatment of biliary diseases. METHODS: We retrospectively analyzed the clinical data of 11 419 consecutive patients with biliary diseases undergoing laparoscopic surgery from April, 1992 and December, 2014. The disease spectrum was compared between patients treated before December 31, 2003 and those treated after the time point. RESULTS: The 11419 patients receiving laparoscopic surgery accounted for 56.3% of the total patients undergoing biliary surgeries during the 23 years, including 4701 male and 6718 female patients with a mean age of 50.9∓13.2 years (6-93 years). Most (80.83%) of the patients received laparoscopic surgery for gallbladder stones, and 12.53% patients had the operation for gallbladder polyps. The laparoscopic operation rate was 84.81% in patients with gallbladder stones and 34.91% in patients with extrahepatic bile duct stones, but remained low in patients with biliary carcinoma. In laparoscopic operations, laparoscopic cholecystectomy was the most frequent (96.18%) followed by operations for extrahepatic bile duct stones, in which primary suture accounted for 1.38%, traditional T tube drainage for 0.90% and laparoscopic transcystic duct exploration for 0.72%. For malignant tumors, laparoscopic technique was used mainly for the purpose of exploration (0.34%). The application of laparoscopic technique in biliary surgery tended to increase after the year 2004, especially for benign gallbladder diseases and extrahepatic bile duct stones (P<0.05). CONCLUSION: Laparoscopic technique in biliary surgery is gradually replacing the traditional open operation and becomes the gold standard for the treatment of benign biliary diseases.

[Clinicopathological characteristics and prognosis of solid pseudopapillary neoplasm of the pancreas: comparison between tumors ≤5 cm and larger tumors].

OBJECTIVE: To compare the clinicopathological characteristics and prognosis of patients with small (≤5 cm) solid pseudopapillary neoplasm of the pancreas (SPN) and those with large (>5 cm) SPNs. METHODS: We retrospectively analyzed the clinical characteristics, laboratory findings, radiological features, treatment and prognosis of 148 patients with histologically confirmed SPN between August, 2006 and December, 2014 and compared the data between patients with small SPNs (≤5 cm) and those with large SPNs (>5 cm). RESULTS: In the large SPN group, the female-to-male ratio was significantly higher than that in small SPN group (61/8 vs 56/23, P=0.009) and the patients were significantly younger in large SPN group (28.3±12.3 vs 33.0±11.4 years, P=0.016). Small SPNs (≤5 cm) typically presented as inhomogeneous solid or cystic tumors, while large SPNs (>5 cm) often appeared as homogeneous solid and cystic tumors, but they did not show any significant difference in aggressive behaviors (P=0.288). The 5-year disease-free survival of patients with small SPNs was 100%, and the 1-, 3-, and 5-year disease-free survival of patients with large SPNs was 98.6%, 94.9%, and 89.3%, respectively (P=0.030), showing no significant differences in the overall survival between the two groups. CONCLUSION: Small SPNs and large SPNs have different clinical characteristics. Even with complete resection, tumors larger than 5 cm are more likely to have tumor recurrence and metastasis, and close follow-up is recommended for these patients.

[Treatment and prognosis of solid pseudopapillary neoplasms with metastases or recurrence].

OBJECTIVE: To describe the treatment and prognosis of solid pseudopapillary neoplasms (SPN) with metastases or recurrence. METHODS: The clinical date of 24 patients with histological confirmed SPN with metastases or recurrence from January 2000 to April 2014 were retrospectively analyzed. There were 22 females and 2 males, with mean age of (36 ± 16) years. Fourteen patients had local recurrence or metastasis after surgery, with a mean time of recurrence (44 ± 29) months. Ten patients were defined SPN with distant metastasis at first admission. Nineteen patients underwent surgical resection, among them, 11 patients received complete resection. Nine cases underwent chemotherapy. Kaplan-Meier method was used to identify prognostic factors. RESULTS: Twenty-four patients were followed-up, 9 patients died. Median survival time was 47 months, and 1-year, 3-year, and 5-year survival was 91.7%, 65.1%, 49.6%, respectively. Age (χ(2) = 6.858, P = 0.009), primary tumor diameter (χ(2) = 4.322, P = 0.038), extrahepatic metastasis (χ(2) = 5.279, P = 0.022) and complete resection of metastases and recurrence (χ(2) = 4.666, P = 0.031) were important prognostic factors for survival (P < 0.05). CONCLUSIONS: For SPN with metastases or recurrence, good prognosis can also obtain after complete resection. Age, primary tumor diameter, extrahepatic metastasis and complete resection of metastases and recurrence are influence factors on prognosis of patients.

Application of a Gastroduodenal Artery Graft for Reconstruction of the Hepatic Artery during Radical Resection of Hilar Cholangiocarcinoma.

This paper was designed to evaluate a novel surgical procedure of using a gastroduodenal artery graft for reconstruction of the hepatic artery during radical resection of hilar cholangiocarcinoma, which is citation-free and self-contained. In this paper we retrospectively analyzed the clinical data, surgical procedure, and follow-up results in nine patients who underwent hepatic artery reconstruction using a gastroduodenal artery graft during their radical resection of hilar cholangiocarcinoma and no artery thrombosis or other surgical complications were found after operation with minimum follow-up duration of three months. We recommended that a gastroduodenal artery graft was shown to be a good choice for hepatic artery resection after radical resection of hilar cholangiocarcinoma.