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Robotic pancreaticoduodenectomy (RPD) has been reported to be safe and feasible for patients with pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head. This study aimed to analyze the surgical outcomes and risk factors for poor long-term prognosis of these patients.Data from patients who underwent RPD for PDAC of pancreatic head were retrospectively analyzed. Multivariate Cox regression analysis was used to seek the independent prognostic factors for overall survival (OS), and an online nomogram calculator was developed based on the independent prognostic factors.Of the 273 patients who met the inclusion criteria, the median operative time was 280.0 minutes, the estimated blood loss was 100.0 mL, the median OS was 23.6 months, and the median recurrence-free survival (RFS) was 14.4 months. Multivariate analysis showed that preoperative carbohydrate antigen 19-9 (CA19-9) [hazard ratio (HR) = 2.607, 95% confidence interval (CI): 1.560-4.354, P 0.001], lymph node metastasis (HR = 1.429, 95% CI: 1.005-2.034, P = 0.047), tumor moderately (HR = 3.190, 95% CI: 1.813-5.614, P 0.001) or poorly differentiated (HR = 5.114, 95% CI: 2.839-9.212, P 0.001), and Clavien-Dindo grade ≥ III (HR = 1.657, 95% CI: 1.079-2.546, P == 0.021) were independent prognostic factors for OS. The concordance index (C-index) of the nomogram constructed based on the above four independent prognostic factors was 0.685 (95% CI: 0.640-0.729), which was significantly higher than that of the AJCC staging (8th edition): 0.541 (95% CI: 0.493-0.589) (P 0.001).This large-scale study indicated that RPD was feasible for PDAC of pancreatic head. Preoperative CA19-9, lymph node metastasis, tumor poorly differentiated, and Clavien-Dindo grade ≥ III were independent prognostic factors for OS. The online nomogram calculator could predict the OS of these patients in a simple and convenient manner.

The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) remains poor even after radical pancreaticoduodenectomy (PD). The study aimed to develop and validate a novel preoperative prognostic model to accurately predict the long-term survival of patients with PDAC.Patients with PDAC of pancreatic head from Chinese PLA General Hospital were included. The preoperative PDAC model with contour plots was developed using a non-linear model in the training cohort and then tested in the validation cohort.Of 421 patients who met the inclusion criteria, 280 were in the training cohort and 141 in the validation cohort. Contour plots for preoperative PDAC model were established to visually predict the survival probabilities of these patients, based on preoperative carbohydrate antigen 19-9, preoperative fibrinogen to albumin ratio and pain symptoms. This model stratified patients into low- and high-risk groups with distinctly different long-term survival in the training cohort [median overall survival (OS) 32.1 vs. 17.5 months; median recurrence-free survival (RFS) 19.3 vs. 10.0 months, both P0.001] and the validation cohort (median OS 28.3 vs. 19.0 months; median RFS 17.5 vs. 11.2 months, both P0.001). Time-dependent receiver operating characteristic and decision curve analyses revealed that the model provided higher diagnostic accuracy and superior net benefit compared to other staging systems.This study constructed and validated a novel preoperative prognostic model that can accurately and conveniently predict the long-term survival of patients with resectable PDAC of pancreatic head. Besides, the model can screen high-risk patients with poor prognosis, which may provide references for personal treatment strategies in the future.

Establishing a stoke experimental model, which is better in line with the physiology and function of human brain, is the bottleneck for the development of effective anti-stroke drugs. A three-dimensional cerebral organoids (COs) from human pluripotent stem cells can mimic cell composition, cortical structure, brain neural connectivity and epigenetic genomics of in-vivo human brain, which provides a promising application in establishing humanized ischemic stroke model. COs have been used for modeling low oxygen condition-induced hypoxic injury, but there is no report on the changes of COs in response to in vitro oxygen-glucose deprivation (OGD)-induced damage of ischemic stroke as well as its application in testing anti-stroke drugs. In this study we compared the cell composition of COs at different culture time and explored the cell types, cell ratios and volume size of COs at 85 days (85 d-CO). The 85 d-CO with diameter more than 2 mm was chosen for establishing humanized ischemic stroke model of OGD. By determining the time-injury relationship of the model, we observed aggravated ischemic injury of COs with OGD exposure time, obtaining first-hand evidence for the damage degree of COs under different OGD condition. The sensitivity of the model to ischemic injury and related treatment was validated by the proven pan-Caspase inhibitor Z-VAD-FMK (20 μM) and Bcl-2 inhibitor navitoclax (0.5 μM). Neuroprotective agents edaravone, butylphthalide, P7C3-A20 and ZL006 (10 μM for each) exerted similar beneficial effects in this model. Taken together, this study establishes a humanized ischemic stroke model based on COs, and provides evidence as a new research platform for anti-stroke drug development.

The supplementary infomation containing Figure legends, five supplemental figures and 3 supplemental tables. Figure S1 The higher expression of hPCL3s correlated with the poor survival of HCC patients. Figure S2 hPCL3s did not promote the tumorigenesis in vivo. Figure S3 The effects of hPCL3s on the growth of Hep3B, Huh7 and PVTT cells in a 48-hour time window were evaluated using MTT assay. Figure S4 Screening the signal pathways affected by hPCL3s. Figure S5 The AAV delivered Flag-hPCL3s was dominantly expressed in the liver. Table S1 Primer sequences. Table S2 The correlation between the expression of hPCL3s and clinical feature (Tissue array 2). Table S3 Microarray data.

Two isoforms of human Polycomb-like protein 3 (hPCL3) have been reported as components of the nuclear Polycomb repressive complex 2 (PRC2), with the short isoform (hPCL3s) showing a dominant cytoplasmic localization. The function of cytoplasmic hPCL3s has, however, not been addressed. In this study, we report that hPCL3s is upregulated in clinical hepatocellular carcinoma (HCC) samples and its expression correlated with HCC clinical features. hPCL3s positively regulated the migration, invasion, and metastasis of HCC cells. hPCL3s interacted with components of the cytoplasmic β-catenin destruction complex, inhibited β-catenin degradation, and activated β-catenin/T-cell factor signaling. Downstream of the β-catenin cascade, IL6 mediated the motility-promoting functions of hPCL3s. Forced expression of hPCL3s in the liver of a HCC mouse model promoted tumorigenesis and metastasis. Taken together, these data show that hPCL3s promotes the metastasis of HCC by activating the β-catenin/IL6 pathway.Significance: hPCL3s has an oncogenic role in hepatocellular carcinoma by activating the β-catenin/IL6 signaling axis to promote metastasis. Cancer Res; 78(10); 2536–49. ©2018 AACR.

Background The presence of hepatic vein tumor thrombus (HVTT) is a major determinant of survival outcomes in hepatocellular carcinoma (HCC) patients. This study compared survival outcomes between liver resection (LR) and intensity-modulated radiation therapy (IMRT) in HCC patients with HVTT. Methods Data from patients who underwent LR or IMRT for HCC with HVTT at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. Their survival outcomes were compared before and after propensity score matching (PSM). Results Three hundred and seven HCC patients with HVTT who underwent either LR (n=140) or IMRT (n=167) were enrolled. PSM matched 82 pairs of patients. The overall survival (OS) and recurrence-free survival (RFS) rates were significantly higher for patients in the LR group than those in the IMRT group. On subgroup analysis, significantly better survival outcomes were obtained after LR than IMRT in patients with peripheral type of HVTT (pHVTT) and major type of HVTT (mHVTT). However, similar survival outcomes were obtained after LR and IMRT when the HVTT had developed into inferior vena cava tumor thrombus (IVCTT). Conclusions LR resulted in significantly better survival outcomes in HCC patients with HVTT when compared to IMRT. Once the HVTT had developed IVCTT, LR and IMRT resulted in similarly bad survival outcomes.

Pancreatic ductal adenocarcinoma (PDAC) is prone to relapse even after radical pancreaticoduodenectomy (PD) (including robotic, laparoscopic and open approach). This study aimed to develop an online nomogram calculator to predict early recurrence (ER) (within one year after surgery) and long-term survival in patients with PDAC.Patients with PDAC after radical PD were included. Univariate and multivariate logistic regression analysis was used to identify independent risk factors. An online nomogram calculator was developed based on independent risk factors in the training cohort and then tested in the internal and external validation cohorts.Of the 569 patients who met the inclusion criteria, 310, 155, and 104 patients were in the training, internal and external validation cohorts, respectively. Multivariate analysis revealed that preoperative carbohydrate antigen19-9 (CA19-9) [Odds Ratio (OR) 1.002; 95% confidence interval (CI) 1.001-1.003; P = 0.001], fibrinogen/albumin (FAR) (OR 1.132; 95% CI 1.012-1.266; P = 0.029), N stage (OR 2.291; 95% CI 1.283-4.092; P = 0.005), and tumor differentiation (OR 3.321; 95% CI 1.278-8.631; P = 0.014) were independent risk factors for ER. Nomogram based on the above four factors achieved good C-statistics of 0.772, 0.767 and 0.765 in predicting ER in the training, internal and external validation cohorts, respectively. Time-dependent ROC analysis (timeROC) and decision curve analysis (DCA) revealed that the nomogram provided superior diagnostic capacity and net benefit compared with other staging systems.This multi-center study developed and validated an online nomogram calculator that can predict ER and long-term survival in patients with PDAC with high degrees of stability and accuracy.

Monodispersed Fe3O4 magnetic particles adsorbed by amylase (such as citric acid (CA), carboxymethyl chitosan (CMCH) and β-cyclodextrin (CD)) were prepared by means of co-precipitation method. The absorption character of the samples was investigated by FT-IR, TG and VSM. It was found that the carboxyl (COOH groups) of amylase reacted with the hydroxyl (OH groups) on the surface of Fe3O4 particles, resulting in the formation of iron carboxylate that was adsorbed onto Fe3O4. The induction heating properties of the magnetic Fe3O4 nanoparticles in an alternating current magnetic field were also investigated and the thermo-magnetic stability in induction heating was discussed.

This study aims to investigate the expressions of matrix metalloproteinase-9 (MMP-9), estrogen receptor (ER), and progesterone receptor (PR) in thin endometrium.Patients who received treatment in our hospital between January 2018 and September 2020 were enrolled. Endometrial thickness was measured using transvaginal ultrasound; in patients with a midluteal phase endometrial thickness of7 mm, a sample of endometrial tissue was obtained using a hysteroscope, and the MMP-9, ER, and PR expressions were detected using immunohistochemistry. In addition, the number of endometrial glands was calculated in a complete field of view under a low-power (100×) microscope, and the serum estrogen and progesterone levels were determined. Following hormone therapy, the midluteal phase endometrial thickness was measured again using transvaginal ultrasound, and the patients were divided into two groups: the thin endometrium group and the normal endometrium group (The number of endometrial glands as well as the ER and MMP-9 expressions were lower in the thin endometrium group than in the normal endometrium group; the differences were statistically significant (Compared with other patients with thin endometrium, patients with refractory thin endometrium had a reduced the number of endometrial glands and significantly lower ER and MMP-9 expressions.

Background Microvascular invasion (MVI) is a major determinant of survival outcome for hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy of postoperative adjuvant Sorafenib (PA-Sorafenib) in HCC patients with MVI after R0 liver resection (LR). Methods The data of patients who underwent R0 LR for HCC with histologically confirmed MVI at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-Sorafenib were compared with those who underwent R0 LR alone. Propensity score matching (PSM) analysis was performed. Results 728 HCC patients had MVI in the resected specimens after R0 resection, with 581 who underwent LR alone and 147 patients who received in additional adjuvant sorafenib. PSM matched 113 patients in each of these two groups. The overall survival (OS) and recurrence free survival (RFS) were significantly better for patients in the PA-sorafenib group (for OS: before PSM, P = 0.003; after PSM, P = 0.007), (for RFS: before PSM, P = 0.029; after PSM, P = 0.001), respectively. Similar results were obtained in patients with BCLC 0-A, BCLC B and Child-Pugh A stages of disease. Conclusions PA-Sorafenib was associated with significantly better survival outcomes than LR alone for HCC patients with MVI.

OBJECTIVES This study aimed to perform a multicenter comparison between robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD). BACKGROUND Previous comparisons of RPD versus OPD have only been carried out in small, single-center studies of variable quality. METHODS Consecutive patients who underwent RPD (n = 1032) or OPD (n = 1154) at 7 centers in China between July 2012 and July 2020 were included. A 1:1 propensity score matching (PSM) was performed. RESULTS After PSM, 982 patients in each group were enrolled. The RPD group had significantly lower estimated blood loss (EBL) (190.0 vs 260.0 mL; P < 0.001), and a shorter postoperative 1length of hospital stay (LOS) (12.0 (9.0-16.0) days vs 14.5 (11.0-19.0) days; P < 0.001) than the OPD group. There were no significant differences in operative time, major morbidity including clinically relevant postoperative pancreatic fistula (CR-POPF), bile leakage, delayed gastric emptying, postoperative pancreatectomy hemorrhage (PPH), reoperation, readmission or 90-day mortality rates. Multivariable analysis showed R0 resection, CR-POPF, PPH and reoperation to be independent risk factors for 90-day mortality. Subgroup analysis on patients with pancreatic ductal adenocarcinoma (PDAC) (n = 326 in each subgroup) showed RPD had advantages over OPD in EBL and postoperative LOS. There were no significant differences in median disease-free survival (15.2 vs 14.3 months, P = 0.94) or median overall survival (24.2 vs 24.1 months, P = 0.88) between the 2 subgroups. CONCLUSIONS RPD was comparable to OPD in feasibility and safety. For patients with PDAC, RPD resulted in similar oncologic and survival outcomes as OPD.

Surgery is one of the main effective strategies for the treatment of solid tumors, but high postoperative recurrence is also the main cause of death in current cancer therapy. The prevention of postoperative hepatocellular carcinoma (HCC) recurrence is a clinical problem that needs to be solved urgently. At present, there are still some problems to be solved, such as, how to achieve free drugs to target the site of surgical resection; develop a strategy for the simultaneous administration of multiple drugs to inhibit postoperative recurrence; and provide the appropriate animal model that mimics the process of postoperative HCC recurrence. In this study, we used a facile and reproducible method to successfully prepare amphiphilic Janus nanoparticles (JNPs). In order to improve targeting of the JNPs to residual HCC cells after surgery, we modified the side of gold nanorods (GNRs) with lactobionic acid (LA), thus creating LA-JNPs. This provided an active and targeted co-delivery system for hydrophilic and hydrophobic drugs in separate rooms, thus avoiding mutual effects. Next, we established two models to simulate postoperative HCC recurrence: a subcutaneous postoperative recurrence model based on patient-derived tumor xenograft (PDX) tissues and a postoperative recurrence model of orthotopic HCC. By applying these models, the enhanced permeability and retention effect (EPR) based tumor targeting and LA based active targeting can jointly promote the enrichment and uptake of JNPs at tumor site. LA-JNPs represented an efficient targeting system for the co-delivery of Sorafenib/Doxorubicin with an optimized anti-recurrence effect and significantly improved the survival of mice during treatment for postoperative recurrence.

Background The surgical management of Mayo III/IV tumor thrombi is difficult and risky, and robotic surgery is even more difficult. The purpose of this study was to introduce the step-by-step and orderly lowering of the height of inferior vena cava tumor thrombus, which was the core technique of robot operation for Mayo III/IV tumor thrombus. Method A total of 18 patients were included in this study. The average tumor thrombus height was 2.4 cm above the level of the second porta hepatis (SPH), and 9 patients were prepared for cardiopulmonary bypass (CPB) before surgery. During the operation, the height of the tumor thrombus was lowered orderly for 2-3 times, and the blood flow blocking method was changed sequentially. The CPB was required when tumor thrombus in the atrium; After the height of the thrombus was lowered to the atrium entrance, CPB was stopped and the blood flow was blocked in the upper- and retro-hepatic inferior vena cava (IVC); After the tumor thrombus continued to descend to the lower part of the SPH, liver blood flow could be restored, and then, the blood flow was simply blocked in the retro-hepatic IVC to complete the removal of the thrombus and the repair or resection of the IVC. Finally, the diseased kidney and renal vein were removed. Results All operations were successfully completed, and 2 cases were transferred to laparotomy. Seven cases received CPB, while the other 11 did not. 15 patients underwent two times of the lowering of the tumor thrombus, 2 patients underwent one time and 1 patient underwent three times. The mean liver/IVC dissociation and vascular suspension time was 22.0 min. All patients had less than Clavien-Dindo grade III complications, no serious complications occurred during operation, and no patient died within 90 days. Conclusions The step-by-step and orderly decline of tumor thrombus height is the key to the success of robot Mayo III / IV tumor thrombus surgery. This method can shorten FPH and CPB time and improve the success rate of surgery.

PURPOSE To compare the survival outcomes of neoadjuvant three-dimensional conformal radiotherapy (RT) followed by hepatectomy with hepatectomy alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). PATIENTS AND METHODS A randomized, multicenter controlled study was conducted from January 2016 to December 2017 in patients with resectable HCC and PVTT. Patients were randomly assigned to receive neoadjuvant RT followed by hepatectomy (n = 82) or hepatectomy alone (n = 82). The modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines were used to evaluate the therapeutic effects of RT. The primary end point was overall survival. The expression of interleukin-6 (IL-6) in patients’ serum before RT and in surgical specimens was correlated with response to RT. RESULTS In the neoadjuvant RT group, 17 patients (20.7%) had partial remission. The overall survival rates for the neoadjuvant RT group at 6, 12, 18, and 24 months were 89.0%, 75.2%, 43.9%, and 27.4%, respectively, compared with 81.7%, 43.1%, 16.7%, and 9.4% in the surgery-alone group ( P < .001). The corresponding disease-free survival rates were 56.9%, 33.0%, 20.3%, and 13.3% versus 42.1%, 14.9%, 5.0%, and 3.3% ( P < .001). On multivariable Cox regression analyses, neoadjuvant RT significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone (hazard ratios, 0.35 [95% CI, 0.23 to 0.54; P < .001] and 0.45 [95% CI, 0.31 to 0.64; P < .001]). Increased expressions of IL-6 in pre-RT serum and tumor tissues were significantly associated with resistance to RT. CONCLUSION For patients with resectable HCC and PVTT, neoadjuvant RT provided significantly better postoperative survival outcomes than surgery alone. IL-6 may predict response to RT in these patients.

Background The effect of microvascular invasion (MVI) on the postoperative long-term prognosis of solitary small hepatocellular carcinoma remains controversial. We compared the long-term outcomes of MVI-positive and MVI-negative groups of patients with solitary small hepatocellular carcinoma. Methods The PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched to compare the long-term outcomes of MVI-positive and MVI-negative groups of patients with solitary small hepatocellular carcinoma from inception to November 1, 2018. The study outcomes, including overall survival (OS) and disease-free survival (DFS), were extracted independently by two authors. Results Fourteen studies involving 3033 patients were evaluated. A meta-analysis of all 14 studies suggested that the OS of the MVI-positive group was significantly worse than that of the MVI-negative group (HR = 2.39, 95% CI = 2.02–2.84, I2 = 22.8%; P Conclusion Microvascular invasion was a risk factor for poorer prognosis for solitary small hepatocellular carcinoma.

Portal vein tumor thrombus (PVTT) is one of the most serious forms of hepatocellular carcinoma (HCC) vessel metastasis and has a poor survival rate. However, the molecular mechanism of PVTT has not yet been elucidated. In this study, the molecular mechanism of AXL expressed in tumor-derived endothelial cells (TECs) in vessel metastasis was investigated. High AXL expression was observed in TECs, but not in the tumor cells of HCC patients with PVTT and this was associated with poor overall survival (OS) and disease-free survival (DFS). AXL overexpression was positively associated with CD 31 expression both in vitro and in vivo. AXL promoted the cell proliferation, tube formation, and migration of both TECs and normal endothelial cells (NECs). High expression of AXL in TECs promoted the cell migration, but not the proliferation of HCC cells. Further studies demonstrated that AXL promoted cell migration and tube formation through activation of the PI3K/AKT/SOX2/DKK-1 axis. AXL overexpression in HUVECs promoted tumor growth and liver or vessel metastasis of HCC in xenograft nude mice, which could be counteracted by treatment with R428, an AXL inhibitor. R428 reduced tumor growth and CD 31 expression in HCC in PDX xenograft nude mice. Therefore, AXL over-expression in TECs promotes vessel metastasis of HCC, which indicates that AXL in TECs could be a potential therapeutic target in HCC patients with PVTT.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with aggressive biological behaviour. Its rapid proliferation and tumour growth require reprogramming of glucose metabolism or the Warburg effect. However, the association between glycolysis‐related genes with clinical features and prognosis of PDAC is still unknown. Here, we used the meta‐analysis to correlate the hazard ratios (HR) of 106 glycolysis genes from MSigDB by the cox proportional hazards regression analysis in 6 clinical data sets of PDAC patients to form a training cohort, and a single group of PDAC patients from the TCGA, ICGC, Arrayexpress and GEO databases to form the validation cohort. Then, a glycolysis‐related prognosis (GRP) score based on 29 glycolysis prognostic genes was established in 757 PDAC patients from the training composite cohort and validated in 267 ICGC‐CA validation cohort (all P

BACKGROUND: Hepatocellular carcinoma (HCC) commonly occurs in patients with splenomegaly. This study aimed to investigate the impact of splenomegaly with or without splenectomy on long-term survival of HCC patients with portal vein tumor thrombus (PVTT) treated with liver resection (LR). METHODS: HCC patients with PVTT who underwent LR from 2005 to 2012 from 6 hospitals were retrospectively studied. The long-term overall survival (OS) and recurrence-free survival (RFS) were compared between patients with or without splenomegaly, and between patients who did or did not undergo splenectomy for splenomegaly. Propensity score matching (PSM) analysis was performed to match patients in a 1:1 ratio. RESULTS: Of 716 HCC patients with PVTT who underwent LR, 140 patients had splenomegaly (SM group) and 576 patients had no splenomegaly (non-SM group). The SM group was further subdivided into 49 patients who underwent splenectomy (SPT group), and 91 patients who did not received splenectomy (non-SPT group). PSM matched 140 patients in the SM group, and 49 patients in the SPT group. Splenomegaly was an independent risk factor of poor RFS and OS. The OS and RFS rates were significantly better for patients in the non-SM group than the SM group (OS: P

Background: Hepatic vein tumor thrombus (HVTT) is a significant poor risk factor for survival outcomes in hepatocellular carcinoma (HCC) patients. Currently, the widely used international staging systems for HCC are not refined enough to evaluate prognosis for these patients. A new classification for macroscopic HVTT was established, aiming to better predict prognosis. Methods: This study included 437 consecutive HCC patients with HVTT who underwent different treatments. Overall survival (OS) and time-dependent receiver operating characteristic (ROC) curve area analysis were used to determine the prognostic capacities of the new classification when compared with the different currently used staging systems. Results: The new HVTT classification was defined as: type I, tumor thrombosis involving hepatic vein (HV), including microvascular invasion; type II, tumor thrombosis involving the retrohepatic segment of inferior vena cava; and type III, tumor thrombosis involving the supradiaphragmatic segment of inferior vena cava. The numbers (percentages) of patients with types I, II, and III HVTT in the new classification were 146 (33.4%), 143 (32.7%), and 148 (33.9%), respectively. The 1-, 2-, and 3-year OS rates for types I to III HVTT were 79.5%, 58.6%, and 29.1%; 54.8%, 23.3%, and 13.8%; and 24.0%, 10.0%, and 2.1%, respectively. The time-dependent-ROC curve area analysis demonstrated that the predicting capacity of the new HVTT classification was significantly better than any other staging systems. Conclusions: A new HVTT classification was established to predict prognosis of HCC patients with HVTT who underwent different treatments. This classification was superior to, and it may serve as a supplement to, the commonly used staging systems.

Background Whether anesthesia type is associated with the surgical outcome of Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains to be determined. This study aims to investigate the impact of volatile inhalational anesthesia (INHA) versus total IV anesthesia (TIVA) on the survival outcomes in HCC patients with PVTT. Methods A cohort of in-patients whom were diagnosed of HCC with PVTT in Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from January 1, 2008 to December 24, 2012 were identified. Surgical patients receiving the INHA and TIVA were screened out. The overall survival (OS), recurrence-free survival (RFS) and several postoperative adverse events were compared according to anesthesia types. Results A total of 1513 patients were included in this study. After exclusions are applied, 263 patients remain in the INHA group and 208 in the TIVA group. Patients receiving INHA have a lower 5-year overall survival rate than that of patients receiving TIVA [12.6% (95% CI, 9.0 to 17.3) vs. 17.7% (95% CI, 11.3 to 20.8), P = 0.024]. Results of multivariable Cox-regression analysis also identify that INHA anesthesia is significantly associated with mortality and cancer recurrence after surgery compare to TIVA, with HR (95%CI) of 1.303 (1.065, 1.595) and 1.265 (1.040, 1.539), respectively. Subgroup analysis suggested that in more severe cancer patients, the worse outcome related to INHA might be more significant. Conclusion This retrospective analysis identifies that TIVA is associated with better outcomes compared with INHA. Future prospective studies clinical and translational studies are required to verify this difference and investigate underlying pathophysiology.

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in the world, however, no drug treatment has been approved for this disease. Thus, it is urgent to find effective therapeutic targets for clinical intervention. In this study, we find that liver-specific knockout of PPDPF (PPDPF-LKO) leads to spontaneous fatty liver formation in a mouse model at 32 weeks of age on chow diets, which is enhanced by HFD. Mechanistic study reveals that PPDPF negatively regulates mTORC1-S6K-SREBP1 signaling. PPDPF interferes with the interaction between Raptor and CUL4B-DDB1, an E3 ligase complex, which prevents ubiquitination and activation of Raptor. Accordingly, liver-specific PPDPF overexpression effectively inhibits HFD-induced mTOR signaling activation and hepatic steatosis in mice. These results suggest that PPDPF is a regulator of mTORC1 signaling in lipid metabolism, and may be a potential therapeutic candidate for NAFLD., Non-alcoholic fatty liver disease (NAFLD) has become a prevalent chronic liver disease, however, drugs to treat this disease are still lacking. Here, the authors show that PPDPF inhibits the development of hepatic steatosis by negatively regulating mTORC1-S6K-SREBP1 signaling, which provides a potential therapeutic candidate for NAFLD treatment.

Neuroepithelial cell transforming gene 1 (NET1), a member of the guanine nucleotide exchange factor family, is involved in various cancers, including gastric cancer, breast cancer and glioma. However, the role of NET1 in hepatocellular carcinoma (HCC) remains largely uncovered. In this study, we found that NET1 expression was upregulated in HCC, and that upregulated NET1 expression was closely associated with poor prognosis and some clinical characteristics in HCC patients. Whilst forced expression of NET1 in HCC cells was observed to significantly promote cell growth and metastasis in vitro and in vivo; downregulation of NET1 was shown to exhibit an opposite inhibitory effect. RNA-seq analysis and gene set enrichment analysis demonstrated that knockdown of NET1 significantly suppressed the level of Akt phosphorylation level and the expression of Akt downstream genes in HCC cells. Moreover, MK2206, a potent Akt inhibitor was shown to block the NET1-induced effects in HCC. Taken together, this study demonstrated that, through the Akt signaling pathway, NET1 plays an oncogenic role in HCC progression and metastasis. Hence, NET1 may potentially be used as a potential therapeutic target and prognostic marker of HCC.

Adipocyte fatty acid‐binding protein (FABP4) is abundant in macrophage and adipocyte. It is known to be involved in lipid metabolism. The role of FABP4 has been reported in various cancers, such as non‐small cell lung cancer, breast cancer, ovarian cancer, and prostatic cancer. However, its role remains unclear in hepatocellular carcinoma (HCC). In our study, we investigated the expression of FABP4 at both mRNA and protein levels, and by examining 175 cases of patients with cancer of the liver tissue microarray, the significance between the expression of FABP4 and clinical characteristics had been discussed. We found that FABP4 was lowly expressed in HCC tissues compared to the corresponding tissue adjacent, and the expression of FABP4 was significantly associated with the tumor size, PVTT, recurrence‐free survival and overall survival. Moreover, multivariate Cox regression analysis indicated that the expression of FABP4, Alb, AFP, HBsAg, and PVTT were independent risk factors for overall survival, and the expression of FABP4, AFP, GGT, tumor size, and encapsulation were independent risk factors for HCC recurrence. In addition, we revealed that FABP4 suppressed HCC cell proliferation and invasion in vitro. Moreover, overexpression of FABP4 led to inhibit tumor growth and decreased tumor volume in vivo. These phenotypes were associated with altered expression of Snail and p‐STAT3. Our studies thus suggest that FABP4 could be a potential target for HCC chemotherapy.

Multidrug resistance (MDR) is a major clinical obstacle in the successful treatment of patients with metastatic nasopharyngeal carcinoma (NPC). Results from previous studies suggest that microRNAs (miRNA) may be involved in promoting MDR in multiple cancer types. However, the role of miR‑125b in modulating the MDR of NPC is elusive. In the present study, miR‑125b expression in cisplatin (DDP) ‑resistant CNE2 cells (CNE2/DDP) was compared with parental counterparts, using reverse transcription‑quantitative polymerase chain reaction. A >3‑fold reduction in miR‑125b expression levels was observed in CNE2/DDP cells compared with parental CNE2 cells. Ectopic expression of miR‑125b by transfecting CNE2/DDP cells with miR-125b mimics, increased DDP‑induced cytotoxicity, apoptosis and chemosensitivity. By contrast, suppression of miR-125b by transfecting CNE2 cells with miR‑125b inhibitors, reduced DDP‑induced cytotoxicity and apoptosis, and facilitated cisplatin resistance. The results suggest that miR‑125b may regulate the sensitivity of NPC cells to DDP by modulating the expression levels of antiapoptotic factor B-cell CLL/lymphoma 2. Collectively, the results of the present study highlight miR‑125b as a potential therapeutic target for reversing MDR in NPC.