Molecular targeted therapy and immunotherapy in advanced hepatocellular carcinoma: a systematic review and Bayesian network meta-analysis based on randomized controlled trials.

OBJECTIVE: The aim of this study was to compare and rank different targeted therapies or immunotherapies for advanced hepatocellular carcinoma based on efficacy. METHODS: A systematic search of the PubMed, EMBASE, and Cochrane Library databases was conducted. All systematic treatment regimens that reported comparisons with sorafenib were included in this analysis. The primary outcome measures were overall survival (OS) and progression-free survival (PFS), and other outcome measures included the objective response rate (ORR) and safety analysis according to reported treatment-related adverse events. RESULTS: A total of 29 RCTs involving 13376 patients were included in the analysis, including 10 single-agent therapies and 17 combination therapies. Compared with sorafenib, sintilimab plus IBI305 (HR: 0.57, 95% CI: 0.43-0.75), camrelizumab plus rivoceranib (HR: 0.62, 95% CI: 0.49-0.78), and atezolizumab plus bevacizumab (HR: 0.66, 95% CI: 0.52-0.83) ranked in the top three in terms of OS. CONCLUSIONS: PD-1/PD-L1 inhibitors combined with anti-vascular endothelial growth factor (anti-VEGF)-targeting drugs have shown better therapeutic effects in the systematic treatment of patients with advanced hepatocellular carcinoma, and the combination of targeted and immune therapy modes should be further developed.

Exploration of the impact of multimode thermal therapy versus radiofrequency ablation on CD8+ T effector cells of liver malignancies based on single cell transcriptomics.

Introduction: Multimode thermal therapy (MTT) is an innovative interventional therapy developed for the treatment of liver malignancies. When compared to the conventional radiofrequency ablation (RFA), MTT typically offers improved prognosis for patients. However, the effect of MTT on the peripheral immune environment and the mechanisms underlying the enhanced prognosis have yet to be explored. The aim of this study was to further investigate the mechanisms responsible for the difference in prognosis between the two therapies. Methods: In this study, peripheral blood samples were collected from four patients treated with MTT and two patients treated with RFA for liver malignancies at different time points before and after the treatment. Single cell sequencing was performed on the blood samples to compare and analyze the activation pathways of peripheral immune cells following the MTT and RFA treatment. Results: There was no significant effect of either therapy on the composition of immune cells in peripheral blood. However, the differential gene expression and pathway enrichment analysis demonstrated enhanced activation of T cells in the MTT group compared to the RFA group. In particular, there was a remarkable increase in TNF-α signaling via NF-κB, as well as the expression of IFN-α and IFN-γ in the CD8+ effector T (CD8+ Teff) cells subpopulation, when compared to the RFA group. This may be related to the upregulation of PI3KR1 expression after MTT, which promotes the activation of PI3K-AKT-mTOR pathway. Conclusion: This study confirmed that MTT could more effectively activate peripheral CD8+ Teff cells in patients compared with RFA and promote the effector function, thus resulting in a better prognosis. These results provide a theoretical basis for the clinical application of MTT therapy.

Prediction of outcomes by diffusion kurtosis imaging in patients with large (≥5 cm) hepatocellular carcinoma after liver resection: A retrospective study.

Purpose: To evaluate preoperative diffusion kurtosis imaging (DKI) in predicting the outcomes of large hepatocellular carcinoma (HCC) after liver resection (LR). Materials and methods: From January 2015 to December 2017, patients with a large (≥5cm) HCC who underwent preoperative DKI were retrospectively reviewed. The correlations of the mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) with microvascular invasion (MVI) or histological grade were analyzed. Cox regression analyses were performed to identify the predictors of recurrence-free survival (RFS) and overall survival (OS). A nomogram to predict RFS was established. P<0.05 was considered as statistically significant. Results: A total of 97 patients (59 males and 38 females, 56.0 ± 10.9 years) were included in this study. The MK, MD, and ADC values were correlated with MVI or histological grade (P<0.01). With a median follow-up time of 41.2 months (range 12-69 months), 67 patients (69.1%) experienced recurrence and 41 patients (42.3%) were still alive. The median RFS and OS periods after LR were 29 and 45 months, respectively. The 1-, 3-, and 5-year RFS and OS rates were 88.7%, 41.2%, and 21.7% and 99.0%, 68.3%, and 25.6%, respectively. MK (P<0.001), PVT (P<0.001), and ADC (P=0.033) were identified as independent predictor factors for RFS. A nomogram including the MK value for RFS showed the best performance, and the C-index was 0.895. Conclusion: The MK value obtained from DKI is a potential predictive factor for recurrence and poor survival, which could provide valuable information for guiding the efficacy of LR in patients with large HCC.

Research advances in the structures and biological activities of secondary metabolites from Talaromyces.

The genus Talaromyces belongs to the phylum Ascomycota of the kingdom Fungi. Studies have shown that Talaromyces species yield many kinds of secondary metabolites, including esters, terpenes, steroids, alkaloids, polyketides, and anthraquinones, some of which have biological activities such as anti-inflammatory, bacteriostatic, and antitumor activities. The chemical constituents of fungi belonging to the genus Talaromyces that have been studied by researchers over the past several years, as well as their biological activities, are reviewed here to provide a reference for the development of high-value natural products and innovative uses of these resources.

Three-dimensional diabetic macular edema thickness maps based on fluid segmentation and fovea detection using deep learning.

AIM: To explore a more accurate quantifying diagnosis method of diabetic macular edema (DME) by displaying detailed 3D morphometry beyond the gold-standard quantification indicator-central retinal thickness (CRT) and apply it in follow-up of DME patients. METHODS: Optical coherence tomography (OCT) scans of 229 eyes from 160 patients were collected. We manually annotated cystoid macular edema (CME), subretinal fluid (SRF) and fovea as ground truths. Deep convolution neural networks (DCNNs) were constructed including U-Net, sASPP, HRNetV2-W48, and HRNetV2-W48+Object-Contextual Representation (OCR) for fluid (CME+SRF) segmentation and fovea detection respectively, based on which the thickness maps of CME, SRF and retina were generated and divided by Early Treatment Diabetic Retinopathy Study (ETDRS) grid. RESULTS: In fluid segmentation, with the best DCNN constructed and loss function, the dice similarity coefficients (DSC) of segmentation reached 0.78 (CME), 0.82 (SRF), and 0.95 (retina). In fovea detection, the average deviation between the predicted fovea and the ground truth reached 145.7±117.8 µm. The generated macular edema thickness maps are able to discover center-involved DME by intuitive morphometry and fluid volume, which is ignored by the traditional definition of CRT>250 µm. Thickness maps could also help to discover fluid above or below the fovea center ignored or underestimated by a single OCT B-scan. CONCLUSION: Compared to the traditional unidimensional indicator-CRT, 3D macular edema thickness maps are able to display more intuitive morphometry and detailed statistics of DME, supporting more accurate diagnoses and follow-up of DME patients.

An atlas of dynamic peripheral blood mononuclear cell landscapes in human perioperative anaesthesia/surgery.

BACKGROUND: The number of patients receiving anaesthesia is increasing, but the impact of general anaesthesia on the patient's immune system remains unclear. The aim of the present study is to investigate dynamics of systemic immune cell responses to anaesthesia during perioperative period at a single-cell solution. METHODS: The peripheral blood mononuclear cells (PBMCs) and clinical phenomes were harvested and recorded 1 day before anaesthesia and operation, just after anaesthesia (0 h), and 24 and 48 h after anaesthesia. Single-cell sequencing of PBMCs was performed with 10× genomics. Subsequently, data analysis was performed with R packages: Seurat, clusterProfiler and CellPhoneDB. RESULTS: We found that the cluster of CD56+ NK cells changed at 0 h and the cluster of monocytes increased at 24 and 48 h after anaesthesia. The characteristic genes of CD56+ NK cells were mainly enriched in the Jak-STAT signalling pathway and in cell adhesion molecules (24 h) and carbon metabolism (48 h). The communication between CD14+ monocytes and other cells decreased substantially 0 and 48 h after operation. The number of plasma cells enriched in protein export in men was substantially higher than that in women, although the total number in patients decreased 24 h after operation. CD14+ monocytes dominated that cell-cell communications appeared in females, while CD8+ NKT cells dominated that cell-cell communications appeared in male. The number of plasma cells increased substantially in patients with major surgical trauma, with enrichments of pentose phosphate pathway. The communications between plasma cells with other cells varied between surgical severities and anaesthetic forms. The intravenous anaesthesia caused major alterations of cell types, including CD14+ monocytes, plasmas cells and MAIT cells, as compared with inhalation anaesthesia. CONCLUSION: We initially reported the roles of perioperative anaesthesia/surgery in temporal phenomes of circulating immune cells at a single-cell solution. Thus, the protection against immune cell changes would benefit the recovery from anaesthesia/surgery.

Clinical Outcomes and Predictors in Patients With Unresectable Colorectal Cancer Liver Metastases Following Salvage Percutaneous Radiofrequency Ablation: A Single Center Preliminary Experience.

PURPOSE: The purpose of this study was to investigate the clinical efficacy of salvage percutaneous radiofrequency ablation in patients with unresectable colorectal cancer liver metastases. METHODS: The cohort consisted of 81 patients with 126 colorectal cancer liver metastases who underwent radiofrequency ablation between January 2012 and September 2016. The clinical data and ablation data were retrospectively analyzed. The local tumor progression-free survival, overall survival, and prognostic factors were analyzed using the log-rank test and Cox regression model. RESULTS: The technique success rate was 99.21%. The primary efficacy rate was 100% at the 1-month follow-up. Minor complications were observed in 2 patients, which recovered within 1 week. The median local tumor progression-free survival time of all patients was 29.8 months. The absence of subsequent chemotherapy was an independent predictor of a shorter local tumor progression-free survival time (P < 0.001, hazard ratio: 2.823, 95% confidence interval: 1.603, 4.972). The median overall survival time was 26.8 months. A lesion size greater than 3 cm (P = 0.011, hazard ratio: 2.112, 95% confidence interval: 1.188, 3.754) and the presence of early local tumor progression (P = 0.011, hazard ratio: 2.352, 95% confidence interval: 1.217, 4.545) were related to a shorter survival time. CONCLUSIONS: Percutaneous radiofrequency ablation is safe in patients with colorectal cancer liver metastases refractory from chemotherapy. Subsequent chemotherapy is important to enhance local control. Small lesions and favorable early responses are related to prolonged overall survival.

Magnetic Resonance Diffusion Kurtosis Imaging versus Diffusion-Weighted Imaging in Evaluating the Pathological Grade of Hepatocellular Carcinoma.

PURPOSE: To investigate the diagnostic efficacy of diffusion kurtosis imaging (DKI) and conventional diffusion-weighted imaging (DWI) for pathological grading. METHODS: From December 2015 to January 2017, consecutive patients suspected of having hepatocellular carcinoma (HCC) without prior treatment were prospectively enrolled in this study. MRI examinations were performed before surgical treatment. HCC patients confirmed by surgical pathology were included in the study. The mean diffusivity (MD) values, mean kurtosis (MK) values, and apparent diffusion coefficient (ADC) were calculated. The differences and correlations of these parameters among different pathological grades were analyzed. The diagnostic efficiency of DKI and DWI for predicting high-grade HCC was evaluated by receiver operating characteristic (ROC) curves. Logistic regression analyses were used to evaluate the predictive factors for pathological grade. RESULTS: A total of 128 patients (79 males and 49 females, age: 56.9±10.9 years, range, 32-80) with primary HCC were included: grade I: 22 (17.2%) patients, grade II: 37 (28.9%) patients, grade III: 43 (33.6%) patients, grade IV: 26 (20.3%) patients. The MK values of stage I, II, III, and IV were 0.86±0.13, 1.06±0.11, 1.27±0.17, and 1.57±0.13, respectively. The MK values were significantly higher in the high-grade group than in the low-grade group and were positively correlated with pathological grade (rho =0.7417, P<0.001). The MK value demonstrated a larger area under the curve (AUC), with a value of 0.93 than the MD value, which had an AUC of 0.815 (P<0.001), and ADC, which had an AUC of 0.662 (P=0.01). The MK value (>1.19), ADC (≤1.29×10-3 mm2/s), and HBV (+) were independent predictors for the pathological grade of HCCs. CONCLUSION: The MK values derived from DKI and the ADC values obtained from traditional DWI were more valuable than the MD values in predicting the histological grade of HCCs and could potentially guide clinical treatment before surgery.

CT-guided cryoablation for unresectable pelvic recurrent colorectal cancer: a retrospective study.

OBJECTIVE: The study aimed to investigate the efficacy of computed tomography (CT)-guided cryoablation debulking of unresectable pelvic recurrent colorectal cancer (CRC). PATIENTS AND METHODS: From January 2013 to April 2016, 30 patients (18 males and 12 females; aged 57.8±10.5 years) with unresectable pelvic recurrent CRC who had previously received radiotherapy or chemotherapy were included. A total of 35 tumors ranging from 1.2 to 6.3 cm underwent cryoablation. Tumor response was evaluated 1 month after cryoablation according to the Modified Response Evaluation Criteria in Solid Tumors. Logistic regression was used to analyze the risk factors for tumor response. Degree of pain palliation was also determined using the Numerical Rating Scale. Cox proportional hazard models were used to identify predictors of outcomes. RESULTS: Cryoablation was successfully performed in all patients. Complete response (CR) was achieved for 27 tumors in 23 patients and partial response was achieved for eight tumors in seven patients 1 month after cryoablation. The rate of CR was 77.14%, and tumor size was an independent risk factor for CR. Pain relief was satisfactory in 21 symptomatic patients (P<0.001), and the median duration of pain relief was 6.0 months (95% CI: 2.67-9.33). Serum carcinoembryonic antigen (CEA) was significantly decreased after cryoablation in 15 patients with elevated CEA (P=0.005). The median progression-free survival (PFS) was 10.0 months (95% CI: 4.43-15.67). Multivariate analysis revealed that tumor size (HR =3.089, P<0.001), sex (HR =0.089, P=0.002), and elevated CEA (HR =7.015, P=0.002) were independent predictors of PFS. CONCLUSION: CT-guided cryoablation is a safe and effective therapeutic option for pelvic recurrent CRC. Tumor size is an important predictor of poor outcomes.

Ubiquitin-specific protease 22 enhances intestinal cell proliferation and tissue regeneration after intestinal ischemia reperfusion injury.

BACKGROUND: Intestinal ischemia reperfusion (I/R) injury is a serious but common pathophysiological process of many diseases, resulting in a high mortality rate in clinical practice. Ubiquitin-specific protease 22 (USP22) acts as regulator of cell cycle progression, proliferation, and tumor invasion. Depleted USP22 expression has been reported to contribute to arrested cell cycle and disrupted generation of differentiated cell types in crypts and villi. However, the role of USP22 in intestinal damage recovery has not been investigated. Therefore, elucidation of the underlying mechanism of USP22 in intestinal I/R injury may help to improve the tissue repair and patient prognosis in clinical practice. AIM: To investigate the role of USP22 in intestinal cell proliferation and regeneration after intestinal I/R injury. METHODS: An animal model of intestinal I/R injury was generated in male Sprague-Dawley rats by occlusion of the superior mesenteric artery followed by reperfusion. Chiu's scoring system was used to grade the damage to the intestinal mucosa. An in vitro model was developed by incubating rat intestinal epithelial IEC-6 cells in hypoxia/reoxygenation conditions in order to simulate I/R in vivo. siRNA and overexpression plasmid were used to regulate the expression of USP22. USP22, Cyclin D1, and proliferating cell nuclear antigen (PCNA) expression levels were measured by Western blot analysis and immunohistochemistry staining. Cell survival (viability) and cell cycle were evaluated using the Cell Counting Kit-8 and flow cytometry, respectively. RESULTS: USP22 expression was positively correlated with the expression levels of PCNA and Cyclin D1 both in vivo and in vitro, which confirmed that USP22 was involved in cell proliferation and intestinal regeneration after intestinal I/R injury. Decreased levels of Cyclin D1 and cell cycle arrest were observed in the USP22 knockdown group (P < 0.05), while opposite results were observed in the USP22 overexpression group (P < 0.05). In addition, increased expression of USP22 was related to improved intestinal pathology or IEC-6 cell viability after I/R or hypoxia/reoxygenation. These results suggested that USP22 may exert a protective effect on intestinal I/R injury by regulating cell proliferation and facilitating tissue regeneration. CONCLUSION: USP22 is correlated with promoting intestinal cell proliferation and accelerating intestinal tissue regeneration after intestinal I/R injury and may serve as a potential target for therapeutic development for tissue repair during intestinal I/R injury.

Hypoxia-induced HMGB1 expression of HCC promotes tumor invasiveness and metastasis via regulating macrophage-derived IL-6.

Hypoxia is associated with the progression of hepatocellular carcinoma through promotion of spontaneous metastasis but the mechanism remains unclear. Here, we hypothesis that tumor cell-derived HMGB1 orchestrates macrophages infiltration and promotes metastasis of HCC via enhancing macrophage-secreted IL-6 under hypoxia. HMGB1 expression was robustly exacerbated in tumors of HCC patients with PVTT. Meanwhile, hypoxia exposure gave rise to HMGB1 expression in hepatoma cells of human and mouse in a HIF-1α-dependent manner and subsequently induced the infiltration and reprogramming of macrophages to augment the expression of Il-6. Further study demonstrated macrophage-derived IL-6 enhanced the invasiveness and metastasis of murine HCC cells. Therefore, our study provides a novel understanding of the relationship between tumor cells and tumor associated macrophages (TAMs) in the context of hypoxia.

Image-guidedcryoablation in unresectable or recurrent advanced colorectal cancer: a retrospective study.

Purpose: The present study retrospectively analyzed thesafety and efficacy of computed tomography (CT)-guided cryoablationin the treatment ofunresectable or recurrent advanced colorectal cancer, which did not respond well to or experienced progression with radiotherapy or chemotherapy. Materials and Methods: From January 2013 to April 2015, 31 lesions in 27 patients (16 males, 11 females; mean age of 57.2 years) with pelvic unresectableadvanced or recurrent colorectal cancer were included in the study. The tumor diameter was approximately 3.37 ±1.41 cm. The primary tumor included 25 rectal cancers, 1 sigmoid colon adenocarcinoma, and 1 ileocecal mucinous adenocarcinoma. Cryoablation was performed with 17-gauge cryoprobes and monitored by 64-slice spiral CT. Follow-up was carried out by contrast-enhanced magnetic resonance imaging (MRI). The treatment efficacy was evaluated by symptom palliation, decreased carcinoembryonic antigen (CEA) serum level, and tumor response. Results: The cryoablation procedure was well-tolerated in all patients without major complications or procedure-related mortality. Long-term complications included abscess formation (1 patient), skin frostbite and post-sacrum antrum formation (1 patient). Pain relief was satisfactory in patients with perineal pain (P<0.001), and the median time of pain relief was 3.0 months. Complete ablations were obtained in 22 lesions of 18 patients, while 9 lesions in 9 patients underwent incomplete ablation. The median time to local recurrence for lesions with complete ablations was 15.0 months, and that to the progression of tumors with incomplete ablation was 4.0 months. Conclusion: CT-guided cryoablation is a minimally invasive, safe, and effective therapeutic option for unresectableadvanced or recurrent colorectal cancer. The treatment is well-tolerated by patients, and pain relief is achieved rapidly.

Overexpression of Transforming Acidic Coiled Coil­Containing Protein 3 Reflects Malignant Characteristics and Poor Prognosis of Glioma.

Gliomas are malignant primary brain tumors with poor prognosis. Recently, research was indicative of a tight connection between tumor malignancy and genetic alterations. Here, we propose an oncogenic implication of transforming acidic coiled-coil-containing protein 3 (TACC3) in gliomas. By comprehensively analyzing the Chinese glioma genome atlas (CGGA) and publicly available data, we demonstrated that TACC3 were overexpressed along with glioma grade and served as an independent negative prognostic biomarker for glioma patients. Functions' annotations and gene sets' enrichment analysis suggested that TACC3 may participate in cell cycle, DNA repair, epithelium-mesenchymal transition and other tumor-related biological processes and molecular pathways. Patients with high TACC3 expression showed CD133⁺ stem cell properties, glioma plasticity and shorter overall survival time under chemo-/radio-therapy. Additionally, a TACC3 associated the miRNA-mRNA network was constructed based on in silico prediction and expression pattern, which provide a foundation for further detection of TACC3-miRNA-mRNA axis function. Collectively, our observations identify TACC3 as an oncogene of tumor malignancy, as well as a prognostic and motoring biomarker for glioma patients.

CT-guided Hookwire localization before video-assisted thoracoscopic surgery for solitary ground-glass opacity dominant pulmonary nodules: radiologic-pathologic analysis.

The optimal screening or treatment strategies of solitary pulmonary nodules especially ground-glass opacities (GGOs) remain controversial. With CT-guided Hookwire localization, it is accurate to find the small lesions during video-assisted thoracoscopic surgery (VATS). In this study, we evaluate the efficiency and safety of CT-guided Hookwire localization of GGO-dominant (GGO component > 50%) pulmonary nodules before VATS and investigate the correlation between the radiologic features and pathology. From April 2008 to April 2014, a total of 273 patients with solitary GGO-dominant pulmonary nodules were included. Tumor size was 12.4 ± 5.7 mm in diameter, including 208 pulmonary adenocarcinomas and 65 benign nodules. Dislodgement occurred in six patients (2.20%) during surgery. Postoperative complications included asymptomatic needle track hemorrhage (27.1%), minimal pneumothorax (5.9%) and hemoptysis (0.4%). In 208 (76.2%) pulmonary adenocarcinomas, 82 nodules showed ≥90% GGO and 126 showed 50%≤GGO<90%, while 84 nodules staged as T1aN0M0, 96 staged as T1bN0M0, and 28 staged as T1cN0M0. The multivariable analysis demonstrated that 50%≤GGO<90% (HR=2.459, 95% CI: 1.246-4.853, P=0.010), speculation (HR=3.911, 95% CI: 1.966-7.663, P<0.001), lobulation (HR=4.582, 95% CI: 2.149-9.767, P<0.001) and vascular convergence (HR=4.096, 95% CI: 1.132-14.824, P=0.032) were the independent risk factors to identification of the malignant GGO-dominant pulmonary nodules. In conclusions,CT-guided Hookwire localizati for GGO-dominant pulmonary nodules before VATS is a safe and effective procedure for accurate diagnosis and resection of indeterminate solitary pulmonary nodules.

Percutaneous microwave ablation combined with synchronous transcatheter arterial chemoembolization for the treatment of colorectal liver metastases: results from a follow-up cohort.

BACKGROUND: The purpose of this study was to retrospectively evaluate the therapeutic efficacy and safety of ultrasound-guided percutaneous microwave ablation (MWA) combined with synchronous transcatheter arterial chemoembolization (TACE) in patients with colorectal liver metastases (CRLM). PATIENTS AND METHODS: A retrospective analysis was performed in 30 patients who were treated with ultrasound-guided percutaneous MWA combined with synchronous TACE for colorectal cancer liver metastases from November 2011 to December 2014 in Zhongshan Hospital, Fudan University. The response of the tumor to treatment was evaluated by follow-up computed tomography and/or magnetic resonance imaging. Local tumor control, procedure-related complications, and long-term survival data were analyzed. RESULTS: A total of 30 patients with 43 tumors ranging in size from 1.4 cm to 10.0 cm were analyzed. The patients' mean age was 61.6±10.3 years (range, 44.0-78.0 years). The median follow-up time was 26.5±10.4 months (range, 13.3-50.6 months). The complete ablation rate was 81.4% (35/43 lesions) for CRLM. Complete response was achieved in eight cases (26.7%), and partial response was achieved in 17 cases (56.7%) 1 month after the procedure. The objective response rate (complete response + partial response) was 83.4%. Progression-free survival and overall survival were 5.0 months and 11.0 months, respectively. The 12-month and 24-month survival rates were 46.7% and 25.4%, respectively. A total of 22 patients succumbed during follow-up due to tumor progression. No major complications or perioperative mortalities were recorded. CONCLUSION: Ultrasound-guided percutaneous MWA combined with synchronous TACE therapy is a safe and effective modality for patients with CRLM.

Combination Therapies in the Management of Large (≥ 5 cm) Hepatocellular Carcinoma: Microwave Ablation Immediately Followed by Transarterial Chemoembolization.

PURPOSE: To evaluate the safety and efficacy of microwave (MW) ablation combined with transarterial chemoembolization in a single stage for the treatment of large (≥ 5 cm) hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From March 2013 to January 2015, 66 patients (54 men and 12 women; mean age, 54 y; range, 29-83 y) with 72 large HCC lesions were included in this study. Eighteen (27.3%) had Barcelona Clinic Liver Cancer class B disease, and 48 (72.7%) had class C disease. Seventy-nine percent of patients (n = 52) had hepatitis B virus infection. The average tumor size was 9.0 cm ± 3.9, ranging from 5 to 19 cm. MW ablation was performed under ultrasound guidance, immediately followed by chemoembolization. Local tumor response, progression-free survival (PFS), and overall survival (OS) were assessed. RESULTS: The technique was successfully performed in all patients. Complete response (CR) was achieved in 28 cases (42.4%), and partial response (PR) was achieved in 34 cases (51.5%) at 1 month after the procedure. The objective response rate (ie, CR plus PR) was 93.9%. Median PFS and OS times were 9 months and 21 months, respectively. The 6-, 12-, and 18-month OS rates were 93.9%, 85.3%, and 66.6%, respectively. Hemorrhage was detected in three patients and arteriovenous fistula in two patients after MW ablation; all were promptly treated with embolization. There were no liver abscesses, bile-duct injuries, or other major procedure-related complications. CONCLUSIONS: MW ablation immediately followed by chemoembolization is safe and effective in the treatment of large HCC lesions.

[Effects of Different AM Fungi on Quantity and Enzyme Activity of Rhizosphere Soil Microorganism of Paris polyphylla var. yunnanensis].

Objective: To investigate the rhizosphere soil microorganism and enzyme activity after Paris polyphylla var. yunnanensis inoculated Arbuscular Mycorrhizal( AM) fungi,which provide the technological condition for artificial cultivation of Paris polyphylla var. yunnanensis. Methods: By the method of combining the greenhouse pot inoculation trials with laboratory analysis, The effects of inoculation with 28 AM fungi on rhizosphere soil microorganism and soil enzyme activities of Paris polyphylla var. yunnanensis under sterilized soil conditions were observed. Results: There were certain mutualistic selection between Paris polyphylla var. yunnanensis and AM fungi. After induction treatment with AM fungi, different AM fungi had various effects on the quantity, microbial biomass carbon and soil enzyme activities of rhizosphere soil microorganism of Paris polyphylla var. yunnanensis. With application of AM fungi,the amount of culturable fungi from rhizosphere soil of Paris polyphylla var. yunnanensis were decreased,while the culturable bacteria and actinomycetes showed a rising trend,and increased the diversity index,the content of biomass carbon and protease,urease,phosphatase,catalase and invertase activities of rhizosphere soil microorganism. Conclusion: Applying AM fungi when artificial cultivate Paris polyphylla var. yunnanensis,by which can impel rhizosphere microorganism of Paris polyphylla var. yunnanensis to transform from low-fertile"fungus types"to high-fertile"bacterial forms",and raise fungi diversity and enzymatic activity of rhizosphere soil microorganism,it is helpful to maintain the stability and harmoniousness of microecosystem on rhizosphere of Paris polyphylla var. yunnanensis,which certify the efficiency and the possibility of spreading AM inoculum during artificial cultivation in the field.

Antitumor activity of adenoviral vector containing T42 and 4xT42 peptide gene through inducing apoptosis of tumor cells and suppressing angiogenesis.

The T42 peptide, generated from two active fragments of tumstatin, has been shown to have anti­tumor activity. The adenoviral vector is the most frequently used vector in research and clinical trials for gene therapy. In the present study, the anti­tumor activity of the T42 peptide and quadruple T42 (4xT42) peptide adenoviral vectors were elucidated for the first time, to the best of our knowledge. Human embryonic kidney 293 cells were infected with plasmid adenovirus (pAd)­enhanced green fluorescent protein (EGFP)­T42 or pAd­EGFP­4xT42 and the expression of the T42 and 4xT42 genes was confirmed by the identification of GFP expression and reverse transcription polymerase chain reaction experiments. The anti­cancer effects of pAd­EGFP­T42 and pAd­EGFP­4xT42 on breast cancer cells in vivo and in vitro were subsequently investigated. The results indicated that the packaging of the recombinant adenoviruses with the viral titer was successful, following purification at 5x109 plaque forming units/ml. The results also revealed that the recombinant adenoviruses promoted apoptosis in MCF­7 breast cancer cells and inhibited cancer growth. Through the analysis of caspase­3, B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein expression, it was demonstrated that the T42/4xT42 peptide may induce apoptosis via the mitochondrial pathway. In addition, mouse xenograft experiments confirmed that the T42 peptide inhibited tumor growth and reduced angiogenesis in vivo. In conclusion, the results of the present study indicated that the T42 and 4xT42 peptide genes, transfected by a recombinant adenovirus, may provide a potential novel strategy for the treatment of breast cancer.

Circulating tumor cells in the central and peripheral venous compartment - assessing hematogenous dissemination after transarterial chemoembolization of hepatocellular carcinoma.

The aims of this study were to assess the effect of transarterial chemoembolization (TACE) on circulating tumor cells (CTCs) in the peripheral blood and right atrium of patients with HCC and to evaluate whether perioperative shedding of CTCs affects time to progression of HCC. Before and after TACE, peripheral and right atrial blood samples (7.5 mL) were collected from 42 patients with HCC. CTCs were enriched using EpCAM antibody-conjugated magnetic beads. The number of CTCs was 0-30 and 0-54 in peripheral blood before and after TACE, respectively (P=0.166), and 0-65 and 0-98 in the right atrium before and after TACE, respectively (P=0.102). The number of CTCs was significantly different between the two samples both before (P=0.007) and after (P=0.021) TACE. There was no difference in time to progression between patients with and without an increase in the number of CTCs after TACE in either sample (P>0.05 for both). There were more CTCs in right atrial blood than in peripheral blood. The numbers of CTCs in both samples remained unchanged after TACE. Shedding of tumor cells did not affect time to progression of disease in patients with HCC.

Inhibitory effect of baicalin on collagen-induced arthritis in rats through the nuclear factor-κB pathway.

This study focused on the potential therapeutic effect of baicalin on collagen-induced arthritis (CIA) in rats and the underlying mechanisms. The CIA rats were injected with baicalin (50, 100, or 200 mg/kg) once daily for 30 days. The rats were monitored for clinical severity of arthritis, and joint tissues were used for radiographic assessment and histologic examination. We quantified tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in experimental animals and used Western blots to assess levels of protein abundance, phosphorylation, and acetylation of nuclear factor (NF)-κB p65 and sirtuin 1 (sirt1) protein expression in joint tissues. Human fibroblast-like synoviocytes from rheumatoid arthritis (HFLS-RA) were adopted in further mechanistic investigations. Baicalin intraperitoneal injection for 30 days dose-dependently blocked clinical manifestations of CIA, such as functional impairment and swollen red paws. Meanwhile, it alleviated collagen-induced joint inflammation injury and inhibited the secretion of TNF-α and IL-1ß in both rat synovium and HFLS-RA. Further mechanistic investigations revealed that baicalin suppresses NF-κB p65 protein expression and phosphorylation in synovial tissue and human-derived synoviocytes. Moreover, the acetylation of NF-κB p65 was downregulated by baicalin, which negatively correlates with the baicalin-induced upregulation of sirt1 expression in the same conditions. The data indicate that CIA in rats can be alleviated by baicalin treatment via relieving joint inflammation, which is related to the suppression of synovial NF-κB p65 protein expression and the elevation of its deacetylation by sirt1.