Liang Zhao’s research while affiliated with Nanjing University of Chinese Medicine and other places

The clinical significance of systemic inflammation assessed with laboratory analysis of blood samples has been validated in a variety of cancers. The present study was conducted to investigate prognostic significance of preoperative aspartate aminotransferase-to-platelet ratio index (APRI) for the outcome of hepatocellular carcinoma (HCC) patients receiving post-operative adjuvant transarterial chemoembolization (PATACE). A total of 201 patients who underwent PATACE were retrospectively analyzed. A nomogram for HCC was developed using predictors based on multivariate Cox models, and bootstrapping was performed for validation. According to the ROC curve, which was used to divide patients into two cohorts: High APRI group (APRI>1.02) and Low APRI group (APRI≤1.02). In subgroup survival analysis, patients with a relatively low APRI had significantly longer disease-free survival (DFS) and overall survival (OS) than patients with a relatively high APRI, regardless of Barcelona Clinic Liver Cancer (BCLC) stages (BCLC 0/A or BCLC B/C, both P<0.05); while in China liver cancer staging I/II and TNM I/II stage patients, relatively low APRI was associated with improved DFS and OS (both P<0.05). Multivariate Cox models demonstrated that APRI and BCLC stages were independent prognostic factors of DFS and OS (both P<0.05). Nomograms for DFS and OS were constructed, respectively. Calibration curve analysis showed that the standard curve fitted well with the predicted curve. Time-receiver operating characteristic curve analysis revealed that the nomogram had high efficiency. Decision curve analysis demonstrated the high clinical value of the nomogram. APRI is an independent prognostic factor of DFS and OS in HCC patients receiving PATACE, and the combination of APRI with the HCC staging system can refine risk stratification to provide a more accurate prognostic assessment for the outcome of patients receiving PATACE.

Purpose This study aims to explore the pivotal mediating role of adenosine monophosphate–activated protein kinase (AMPK) in liver tight junctions and liver regeneration of a partial hepatectomy (PH) mouse model. Methods A 70% PH mouse model was used. Firstly, mice were randomly divided into sham, 70% PH, AMPK-activated, and AMPK-inhibited groups. Then serum levels of alanine aminotransferase, aspartate transaminase, total bilirubin, direct bilirubin, albumin, and prealbumin were tested on postoperative days 1, 2 and 3. Furthermore, the expression of tight junction proteins like occludin, claudin-3, and ZO-1, together with bile salt export pump (BSEP), which reflects liver function, and AMPK were measured by Western blot and quantitative real-time polymerase chain reaction. Moreover, the expression of tight junction proteins, BSEP, and Ki-67 were examined by immunohistochemistry. Results After 70% PH, without intervention, the changes in expression of hepatic tight junction proteins (occludin, claudin-3, and ZO-1) were consistent with that of BSEP, which could reflect liver function. After treatment with AMPK activator, the high expression status of tight junction proteins occurred in advance and was maintained stably and for a longer time. It was beneficial to liver function and liver regeneration was promoted at early periods and enhanced continuously after PH. Conclusions Activation of AMPK could effectively enhance the expression of hepatic tight junction proteins after PH. Therefore, it could speed up the recovery of liver function and promote liver regeneration especially early after PH.

Immunoglobulin-like transcript (ILT) 4 is an inhibitory immune receptor of the immunoglobulin superfamily, which could deliver inhibitory signals and induce immunosuppression. The significance of the expression of ILT4 in mDCs subsets in patients with hepatocellular carcinoma (HCC) remains unclear. In this study, the frequency of mDCs subsets in the peripheral blood of 121 patients with HCC and 103 normal controls, and in the tumor and tumor free liver tissues (TFL) of 43 HCC patients was analyzed by flow cytometry. Then, the expressions of ILT4 in mDCs subsets in the microenvironment of liver cancer were also analyzed. Results showed that the percentage of CD1c⁺ subset was dramatically decreased in peripheral blood mononuclear cells (PBMCs) of HCC patients compared with normal controls, and also significantly decreased in tumor tissue compared with the TFL. The decreased of CD1c⁺ subset in blood could be a diagnostic factor for HCC with the area under the receiver operating characteristic curve 0.975 (P < 0.01). The percentage of ILT4⁺CD1c⁺ subset was dramatically increased in tumor than that of TFL and blood. There were significant correlations between the percentage of ILT4⁺ in CD1c⁺ subset in tumor and that of in blood. The percentage of ILT4⁺CD1c⁺ subset in tumor tissue was strongly associated with the Edmondson-Steiner stage in HCC (P = 0.03). Furthermore, the capacity of ILT4⁺CD1c⁺ subset producing IFN-γ was lower than ILT4⁻ CD1c subset in PBMC of HCC patients following Poly I:C stimulation. Taken together, the increased ILT4⁺CD1c⁺ subset in tumor tissue might play an important role in immune suppression for patients with HCC.

The present retrospective study aimed to investigate the mid-term safety and efficacy of hepatectomy combined with microwave ablation of the partial spleen for treatment of liver cancer complicated with hypersplenism. A retrospective analysis was performed on 23 patients who underwent hepatectomy combined with microwave ablation of the partial spleen for liver cancer, complicated with hypersplenism that was secondary to cirrhosis. The splenic and ablated volumes were calculated according to a contrast-enhanced computed tomography scan prior to and 2 weeks after the operation. Complete blood count and liver function tests were examined prior to and following the surgery, and complications and changes in the blood tests were monitored for 6 months. Over this period of investigation, the splenic volume was reduced by a mean value of 34.0%. The levels of serum alanine aminotransferase and aspartate aminotransferase were increased on the first day after the operation (P<0.05), although they recovered to the normal level within 1 week (P<0.05). The total level of bilirubin increased slightly, along with moderately decreased levels of albumin and cholinesterase on the first day, although these changes were not significant compared with the baseline (P>0.05). The white blood cell count was persistently significantly higher compared with the baseline over the course of the 6 months (P>0.05). The platelet count did not increase significantly for the first week after the operation (P>0.05); however, it was revealed to be significantly increased 1 month after the surgery (P<0.05). No significant complications were occurred during the follow-up period. In conclusion, hepatectomy combined with microwave ablation of the spleen was demonstrated to be a safe and effective procedure for patients with liver cancer and hypersplenism in the mid-term.

Sorafenib is the standard therapeutic strategy for recurrent hepatocellular carcinoma (HCC) following hepatectomy. However, only few patients truly benefit from this therapy. Thus, new strategies combined with sorafenib are urgently required. We herein present the case of a patient with hepatic and extrahepatic HCC recurrence following hepatectomy, who was treated by combined sorafenib, focused ultrasound knife and DRibbles-pulsed dendritic cell (DC) vaccine. Enzyme-Linked ImmunoSpot assay (ELISPOT) and intracellular staining (ICS) analysis were used to detect the secretion of interferon (IFN)-γ by T cells at different timepoints of the vaccine in order to evaluate the patient's specific T-cell response to SMMC-7721-derived DRibbles vaccine. The α-fetoprotein level decreased from 103,295 to 5 ng/ml and the patient displayed improved liver function, an Eastern Cooperative Oncology Group performance status score of 0, remission of liver metastases and disappearance of the lung metastases 8 months post-combination therapy. The computed tomography scan revealed the disappearance of liver metastases 2 years post-combination therapy. The ELISPOT data revealed a low antigen-specific T-cell response 4 weeks after the first vaccine cycle and the response decreased to nearly zero prior to the second cycle. However, high antigen-specific T-cell response was observed 2 weeks after the second vaccine cycle and did not decrease, even after 10 months, which was consistent with the result of the ICS analysis, which demonstrated that most of the secreted IFN-γ was produced by CD4+ T cells, whereas a low CD8+ T-cell response was observed (0.429 vs. 0.0665%, respectively). Our results demonstrated that antigen-specific T-cell response aimed to treat recurrent HCC may be induced through stimulation by the DC-DRibbles vaccine. The success of the treatment supports the combination of sorafenib, focused ultrasound knife and DC-DRibbles vaccine as a therapeutic strategy for patients with HCC recurrence following hepatectomy.

This study is to estimate the association between polymorphisms in the tumor necrosis factor alpha (TNF-α) gene and pulmonary tuberculosis susceptibility (pTB). Studies were identified by searching PubMed and ISI web of Knowledge. The strength of association between the TNF-α gene and pTB susceptibility was assessed by odds ratios. Totals of 18 studies including 2, 735 cases and 3, 177 controls were identified referring to four single-nucleotide polymorphisms: -308G>A, -863C>A, -857C>T and -238G>A. The significantly associations were found between -308G>A (Dominant model: OR 0.53, 95% CI 0.35-0.81, P=0.004; Homozygote model: OR 0.51, 95% CI 0.33-0.78, P=0.002), -238G>A (Dominant model: OR 0.33, 95% CI 0.18-0.57, P<0.001) and pTB susceptibility. The results showed that the variant genotype of TNF-α -308G>A was protective in pooled groups of patients with pTB in the dominant genetic model (OR 0.16, 95% CI 0.06-0.39, P<0.001), the homozygote comparison (OR 0.14, 95% CI 0.06-0.36, P<0.001) in African, while that was with -238G>A in the dominant genetic model (OR 0.31, 95% CI 0.18-0.56, P<0.001) in Asian. Our meta-analysis suggest TNF-α -308G>A and -238G>A polymorphisms increases the risk of pTB susceptibility regardless of ethnicity and HIV statue. In Asian population, the significantly association with pTB is TNF-α -238G>A, while TNF-α -308G>A is in African population.

Background: To induce and collect tumor-derived autophagosomes (DRibbles) from tumor cells as an antitumor vaccine by inhibiting the functions of proteasomes and lysosomes. Methods: Dendritic cells (DCs) generated from peripheral blood mononuclear cell (PBMC) of hepatocellular carcinoma (HCC) patients were cocultured with DRibbles, and then surface molecules of DCs, as well as surface molecules on DCs, were determined by flow cytometry. Meanwhile, immune responses of the DCs-DRibbles were examined by mixed lymphocyte reactions. Results: DRibbles significantly induced the expression of CD80, CD83, CD86 and HLA-DR on DCs. The enzyme-linked immunosorbnent assay (ELISA) showed that IFN-γ levels after vaccination increased than before in most patients, but CD8+ proportion of PBMC increased only in nine patients. Higher levels of IFN-γ were detected in the CD8+ cells than CD4+ T cells. These results suggested that DCs-DRibbles vaccine could induce antigen-specific cellular immune response on HCC and could prime strong CD8+ T cell responses, supporting it as a tumor vaccine candidate. Conclusions: Our results demonstrate that HCC/DRibbles-pulsed DCs immunotherapy might be deployed as an effective antitumor vaccine for HCC immunotherapy in clinical trials.

To investigate the preoperative risk factors of portal venous thrombosis (PVT) after splenectomy and gastric pericardial devascularization in patients with liver cirrhosis and portal hypertension. Clinical data was collected for 127 patients who underwent splenectomy and gastric pericardial devascularization for portal hypertension at our hospital between January 2010 and December 2012.The patient data were analyzed retrospectively according to patient status of presence or absence of PVT postoperatively.The preoperative risk factors of PVT were statistically analyzed. There were no significant differences between the postoperative PVT-positive and-negative groups in regards to sex, age, receipt of emergency surgery, presence of ascites, admission to hospital for upper gastrointestinal bleeding, grade of esophageal-gastric varices, Child-Pugh classification, spleen vein diameter, liver function (as determined by levels of alanine aminotransferase, total bilirubin, direct bilirubin, albumin, globulin, cholinesterase, and gamma-glutamyltransferase), renal function (as determined by creatinine level), and coagulation function (as determined by prothrombin time, prothrombin activity degree, activated partial thromboplastin time, international normalized ratio, fibrinogen, thrombin time, and antithrombin III).However, there were significant differences between the groups for the parameters of postoperative PVT presence, upper gastric bleeding history, aspartate aminotransferase level, and blood urea nitrogen level (all P less than 0.05).Portal vein diameter and history of upper gastric bleeding were both identified as independent risk factors for PVT (P less than 0.05).Incidence of postoperative PVT was higher in patients who had portal vein diameter more than13.15 mm (cutoff value of 13.75 mm) and in patients who had a history of upper gastric bleeding. Portal vein diameter and history of upper gastric bleeding were independent risk factors for PVT occurrence after splenectomy and gastric pericardial devascularization in patients with liver cirrhosis and portal hypertension.

To compare radiofrequency ablation (RFA) or microwave ablation (MWA) and transcatheter arterial chemoembolization (TACE) with RFA or MWA monotherapy in hepatocellular carcinoma (HCC). A prospective, randomized, controlled trial was conducted on 94 patients with HCC ≤7 cm at a single tertiary referral center from June 2008 to June 2010 at the Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Southeast University. The patients were randomly assigned into the TACE-RFA or TACE-MWA (combined treatment group) and the RFA-alone or MWA-alone groups (control group). The primary end point was overall survival. The secondary end point was recurrence-free survival, and the tertiary end point was adverse effects. Until the time of censor, 17 patients in the TACE-RFA or TACE-MWA group had died. The median follow-up time of the patients who were still alive for the TACE-RFA or TACE-MWA group was 47.5±11.3 months (range, 29 to 62 months). The 1-, 3- and 5-year overall survival for the TACE-RFA or TACE-MWA group was 93.6%, 68.1% and 61.7%, respectively. Twenty-five patients in the RFA or MWA group had died. The median follow-up time of the patients who were still alive for the RFA or MWA group was 47.0±12.9 months (range, 28 to 62 months). The 1-, 3- and 5-year overall survival for the RFA or MWA group was 85.1%, 59.6% and 44.7%, respectively. The patients in the TACE-RFA or TACE-MWA group had better overall survival than the RFA or MWA group [hazard ratio (HR), 0.526; 95% confidence interval (95% CI), 0.334-0.823; P=0.002], and showed better recurrence-free survival than the RFA or MWA group (HR, 0.582; 95% CI, 0.368-0.895; P=0.008). RFA or MWA combined with TACE in the treatment of HCC ≤7 cm was superior to RFA or MWA alone in improving survival by reducing arterial and portal blood flow due to TACE with iodized oil before RFA.