Combination of Ablation and Immunotherapy for Hepatocellular Carcinoma: Where We Are and Where to Go.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and is increasing in incidence. Local ablative therapy plays a leading role in HCC treatment. Radiofrequency (RFA) is one of the first-line therapies for early local ablation. Other local ablation techniques (e.g., microwave ablation, cryoablation, irreversible electroporation, phototherapy.) have been extensively explored in clinical trials or cell/animal studies but have not yet been established as a standard treatment or applied clinically. On the one hand, single treatment may not meet the needs. On the other hand, ablative therapy can stimulate local and systemic immune effects. The combination strategy of immunotherapy and ablation is reasonable. In this review, we briefly summarized the current status and progress of ablation and immunotherapy for HCC. The immune effects of local ablation and the strategies of combination therapy, especially synergistic strategies based on biomedical materials, were discussed. This review is hoped to provide references for future researches on ablative immunotherapy to arrive to a promising new era of HCC treatment.

[Effects of Renshenjian Decoction on blood and urine metabonomics in type 2 diabetes rats based on ~1H-NMR].

Proton nuclear magnetic resonance(~1H-NMR) is used to investigate the effect of Renshenjian Decoction on serum and urine metabolism of type 2 diabetic rats with insulin resistance induced by high-sugar and high-fat diet combined with low-dose streptozotocin(STZ). After the successful establishment of the insulin resistance model of type 2 diabetes, administration for 35 days, the serum and urine of rats were taken. Once the ~1H-NMR data have been collected and processed, PCA and OPLS-DA were used to analyze them. The results show that: compared with the blank group, the contents of methionine, taurine, α-glucose and ß-glucose in the serum of the model group increased significantly(P<0.001), while the contents of 3-hydroxybutyric acid, lactic acid and unsaturated fatty acids decreased significantly(P<0.01). In the model group, the contents of trimethylamine oxide, glycine, α-glucose, ß-glucose, taurine and phosphocholine in urine increased significantly(P<0.05), while the contents of creatine, lactic acid, acetic acid and citric acid decreased significantly(P<0.05). Compared with the model group, the contents of 3-hydroxybutyric acid and unsaturated fatty acids in serum of rats in the treatment group increased significantly(P<0.05), while the contents of taurine, α-glucose and ß-glucose decreased significantly(P<0.01). In the treatment group, the contents of lactic acid, taurine and creatine in urine increased significantly(P<0.05), while the contents of trimethylamine oxide, glycine, α-glucose, ß-glucose and phosphocholine decreased significantly(P<0.01). The results show that Renshenjian Decoction can regulate metabolic disorder and promote the metabolic phenotype to return to the normal range. It displayed therapeutic effect on type 2 diabetic rats with insulin resistance and provided a certain scientific basis for the biological basic research of Renshenjian Decoction by improving insulin resistance in diabetes mellitus.

Novel Strategy for Predicting Conduction Abnormalities During Transcatheter Closure of Perimembranous Ventricular Septal Defect in Adults.

BACKGROUND: In this study we evaluated the feasibility and efficacy of predicting conduction system abnormalities under 3-dimensional (3D) electroanatomic mapping guidance during transcatheter closure of perimembranous ventricular septal defects (pmVSDs) in adults.Methods and Results:The distribution of the His-Purkinje system (HPS) close to the margins of pmVSDs in the left ventricle was identified using 3D electroanatomic mapping and near-field HPS was further confirmed by different pacing protocols. Of the 20 patients in the study, 17 (85%) were successfully treated by transcatheter intervention. The minimum distance between the margins of the pmVSD and near-field HPS, as measured by 3D electroanatomic mapping, ranged from 1.3 to 3.9 mm (mean [± SD] 2.5±0.7 mm). Five patients with a minimum distance <2 mm had a higher risk (3/5; 60%) for adverse arrhythmic events, whereas patients with a distance >2 mm were at a much lower risk (1/15; 6.7%) of procedure-related conduction block (P=0.032). No other adverse events were recorded during the follow-up period (median 30 months). CONCLUSIONS: A minimum distance between the pmVSD and near-field HPS <2 mm was associated with a relatively high risk of closure-related conduction block. 3D electroanatomic mapping may be helpful in guiding decision making for transcatheter closure and reduce the incidence of adverse arrhythmic events.

[Effects of Renshenjian decoction on pancreatic metabonomic profiles in insulin resistance rats based on ¹H-NMR metabonomics].

Pancreas metabonomic profiles of the type 2 diabetic rats' induced by streptozotocin(STZ) and high-sugar, high fat diet on the treatment of Renshenjian decoction(RSJD) after 8 weeks were investigated.In this study, 48 Rats were randomly divided into four groups: normal control (NC), Pathological model (PM), Renshenjian decoction(RSJD 3.76 g·kg⁻¹) and glimepiride control (GC 0.04 mg·kg⁻¹). They are induced insulin resistance model of type 2 diabetes mellitus by streptozotocin(STZ) after 4 weeks' high-sugar, high fat diet except for NC. After sucessful modeling, they are given intragastric administration respectively with same amount of saline, RSJD and glimepiride in 4 weeks. At the end of the 8th week, the pancreatic tissue of rats in each group was collected, and the ¹H-NMR spectrum was collected after being treated by certain method, and analyzed by principal component analysis (PCA). Compared with NC's rats, we found PM's a significant elevation in the level of leucine/isoleucine, valine, lactic acid, creatine but reduction in the level of inose and less obvious changes in the level of creatine, cholic acid, taurine in pancreatic extract. After having been recieved RSJD, reduction level in leucine/isoleucine, valine, alanine, creatine, choline, taurine are also found in pancreatic extract of RSJD's rats, together with the increase of creatinine and tryptophan levels. The results showed that RSJD could regulate the level of amino acids in pancreas of IR rats, promoting a recovery in the process of metabolism. It's helpful to simulate the metabolic changes of IR rats via ¹H-NMR for a further understanding to study the mechanism how RSJD treat IR rats.

[Network Pharmacological Studies of Puerariae Radix in Improving Insulin Resistance].

Objective: To investigate the active components and potential mechanism of Puerariae Radix in improving insulin resistance by using network pharmacological method. Methods: Key target proteins related with insulin resistance were selected based on molecular docking technology, and then took the selected components with 31 target proteins of four pathways for docking. Meanwhile, component-target proteins network was established to network analysis by software Cytoscape 3. 2. 1. Results: 19 compounds had close interactions with four pathways such as AMPK. There were 13 compositions can verify through literature, which revealing that active ingredients and potential molecular mechanism of Puerariae Radix in improving insulin resistance, preliminarily. Conclusion: The network pharmacological method is helpful to explore the possible active components in Puerariae Radix and elucidate the mechanism.