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Objective: Thermal ablation poses challenges in the surgical resection (SR) of small hepatocellular carcinoma (HCC), and its therapeutic outcomes for larger lesions remain debated. Methods: This retrospective study evaluated 729 patients with HCC meeting the Milan criteria, who were treated with curative SR or microwave ablation (MWA) between 2008 and 2014. Overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and local tumor progression (LTP) were compared after propensity score matching (PSM). Co-variates associated with OS, CSS, LTP, and DFS were identified. The risk of death and tumor progression were compared. Results: During the median follow-up of 78.6 months, 253 patients were included in each group after PSM. For tumors ≤ 3.0 cm and 3.1–4.0 cm, MWA achieved comparable results in terms of OS, CSS, DFS, and LTP. For tumors 4.1–5.0 cm, MWA had lower OS, CSS, and DFS rates (all P < 0.05) than SR. Higher LTP rates were observed in the MWA group for tumors 4.1–5.0 cm, although the difference was not significant (P = 0.18). Complication rates (P = 0.41) were similar, but MWA led to less estimated blood loss (P < 0.01) and shorter postoperative hospitalization times (P < 0.01). Conclusions: MWA achieved comparable long-term oncologic outcomes with SR for ≤ 4 cm HCC, with lower complication rates and faster recovery.

Hepatocellular carcinoma recurrence and metastasis after microwave ablation (MWA) are challenges in the clinic. This study showed that mannose-derived carbon dots (Man-CDs) could effectively capture several "danger signals" (DS) after MWA treatment and then deliver DS specifically to dendritic cells (DCs). This improved delivery of DS to DCs enhanced the processing and presentation of tumor-associated antigens by DCs. The results demonstrated that intratumoral injection of Man-CDs after MWA therapy elicited a potent tumor-specific immune response and finally led to the effective suppression of both primary and distant tumors. MWA + Man-CD treatment could efficiently reject tumor cell rechallenge in vivo. This study demonstrated that Man-CD nanoparticles are effective adjuvants that can improve MWA therapy by eliciting a tumor-specific immune response.

Background Symptomatic aseptic necrosis (SAN) followed by nodule rupture is a kind of severe complications after thermal ablation for benign thyroid nodules (BTN). No studies are available to evaluate its pathologic process, clinical manifestations, risk factors and effectiveness of therapies after microwave ablation (MWA). Methods From 2012 to 2019, 398 patients who received MWA for BTN were retrospectively reviewed. Clinical data included baseline patient characteristics, imaging features (internal vascularity and the proportion of the solid component), ablation power and time, complications and prognosis were collected and documented. Results Ten patients (2.51%) experienced post-MWA SAN, eight patients with nodule rupture and the other two without. The mean time from MWA to SAN symptom was 8.6 days and to rupture was 16.3 days. The initial symptoms of SAN patients were neck bulging, swelling and discomfort. Patients would go through nodule rupture once the nodule contents extended into the extrathyroidal area with the discontinuity of the anterior thyroid capsule, and fistula formed unavoidably in this condition. Incision drainage was effective for rupture and early treatment of non-steroidal anti-inflammatory drug might cure the early-stage SAN. Multivariate analysis showed sex (OR = 0.13; 95% CI: 0.03, 0.61; p=.03) was the risk factor leading to SAN and males were more vulnerable to SAN. Conclusion SAN after MWA came earlier and initially illustrated as neck bulging, swelling and discomfort. Early detection and early treatment might prevent the rupture of nodules. Once the breakdown of thyroid capsule occurred, rupture of ablated nodules out of skin was unavoidable and invasive procedures might be the most effective treatment.

Objective To prospectively evaluate the efficacy of microwave ablation (MWA) for benign breast lesions (BBLs) ≥2 cm and explore the possible factors associated with the volume reduction rate (VRR) of ablated lesions. Materials and methods From November 2013 to December 2017, a total of 80 patients with 104 biopsy-proved BBLs larger than 2 cm in size underwent MWA. After the procedure, patients were followed up via physical and imaging examination consisting of contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI). Possible factors associated with 12-month VRR were assessed, including basic patient characteristics, index lesions and parameters of ablation technique. Results The mean tumor size was 2.6 ± 0.6 cm (ranging 2.0–6.3 cm). Of the 104 lesions, 70 were fibroadenomas, 27 adenosis and 7 fibrocystic changes. Post-procedure CEUS or contrast-enhanced MRI showed that all lesions were completely ablated. No immediate or delayed complications were observed. All patients were followed up for more than 12 months (median follow-up 12.5 months). After MWA, the ablated lesion volume decreased significantly by 12 months (p

To analyze the influence of tumor location, including tumor adjacency and located segments on long-term survival outcomes for patients with solitary hepatocellular carcinoma (HCC) after microwave ablation (MWA). This retrospective study evaluated 850 patients. The hepatic segments where the tumor is located, tumor adjacency (important tissues adjacent to tumor) and other clinical characteristics were collected. Overall survival (OS), local tumor progression (LTP) and disease-free survival (DFS) were compared and analyzed. Influence of tumor location was evaluated by multi-models and the effect of adjacency for OS, LTP, and DFS in different segments was analyzed by stratification analysis. The OS, LTP, and DFS rates were similar in different hepatic segments, so were in high risk and safe locations. In multi-models, HCC in segment 8 showed lower death rate of 43% than that in segment 2 (HR 0.57; P = 0.01) and tumors in segment 6 seemed to have lower LTP rate. Tumors in high-risk locations were risk factors for OS, LTP, and DFS compared with tumors in safe locations, but all differences were not significant in different models. The effects of tumor adjacency on survival outcomes among subgroups of segments were limited. The tumor adjacency was not a prognostic factor of survival outcomes for patients with solitary tumors after MWA, but tumors in segment 8 seemed to better OS rate than tumors in other segments.

Objective: To explore the association between cholecystectomy and the prognostic outcomes of patients with hepatocellular carcinoma (HCC) who underwent microwave ablation (MWA). Methods: Patients with HCC (n = 921) who underwent MWA were included and divided into cholecystectomy (n = 114) and non-cholecystectomy groups (n = 807). After propensity score matching (PSM) at a 1:2 ratio, overall survival (OS) and disease-free survival (DFS) rates were analyzed to compare prognostic outcomes between the cholecystectomy (n = 114) and non-cholecystectomy groups (n = 228). Univariate and multivariate Cox analyses were performed to assess potential risk factors for OS and DFS. Major complications were also compared between the groups. Results: After matching, no significant differences between groups were observed in baseline characteristics. The 1-, 3-, and 5-year OS rates were 96.5%, 82.1%, and 67.1% in the cholecystectomy group, and 97.4%, 85.2%, and 74.4% in the non-cholecystectomy group (P = 0.396); the 1-, 3-, and 5-year DFS rates were 58.4%, 34.5%, and 26.6% in the cholecystectomy group, and 73.6%, 44.7%, and 32.2% in the non-cholecystectomy group (P = 0.026), respectively. The intrahepatic distant recurrence rate in the cholecystectomy group was significantly higher than that in the non-cholecystectomy group (P = 0.026), and the local tumor recurrence and extrahepatic recurrence rates did not significantly differ between the groups (P = 0.609 and P = 0.879). Multivariate analysis revealed that cholecystectomy (HR = 1.364, 95% CI 1.023-1.819, P = 0.035), number of tumors (2 vs. 1: HR = 2.744, 95% CI 1.925-3.912, P < 0.001; 3 vs. 1: HR = 3.411, 95% CI 2.021-5.759, P < 0.001), and γ-GT levels (HR = 1.003, 95% CI 1.000-1.006, P < 0.024) were independent risk factors for DFS. The best γ-GT level cut-off value for predicting median DFS was 39.6 U/L (area under the curve = 0.600, P < 0.05). A positive correlation was observed between cholecystectomy and γ-GT level (r = 0.108, 95% CI -0.001-0.214, P = 0.047). Subgroup analysis showed that the DFS rates were significantly higher in the non-cholecystectomy group than the cholecystectomy group when γ-GT ≥39.6 U/L (P = 0.044). The 5-, 10-, 15-, 20-, and 25-year recurrence rates from the time of cholecystectomy were 2.63%, 21.93%, 42.11%, 58.77%, and 65.79%, respectively. A significant positive correlation was observed between cholecystectomy and the time from cholecystectomy to recurrence (r = 0.205, 95% CI 0.016-0.379, P = 0.029). There were no significant differences in complications between groups (P = 0.685). Conclusions: Patients with HCC who underwent cholecystectomy were more likely to develop intrahepatic distant recurrence after MWA, an outcome probably associated with increased γ-GT levels. Moreover, the recurrence rates increased with time.

To evaluate the clinical efficacy of microwave ablation (MWA) of benign breast lesions (BBLs) and compare the learning curves of international radiologists (IRs) and surgeons. In total, 440 patients with 755 clinicopathologically confirmed BBLs from 5 centers were prospectively enrolled from February 2014 to July 2018. Technical success, complications, volume reduction ratio (VRR), palpability, and cosmetic satisfaction after ablation were analyzed. In addition, the ablation time (AT) and energy (AE) with the number of procedures were analyzed for learning curve evaluation. The mean maximum diameter was 1.7 ± 0.6 cm. The complete ablation rate reached 100%, including 45.8% lesions adjacent to the skin, pectoralis, or areola. After a median follow-up of 13.7 months, the 12-month VRR of all lesions was 97.9%, and that for 1.0- to 2.0-cm and ≥ 2.0-cm lesions was 98.6% and 96.9%, respectively. A total of 55.9% of BBLs became nonpalpable (palpable in 85.7% of cases before MWA) by both the clinician and patient. The cosmetic and minimally invasive satisfaction rates were good or excellent in 98.4% and 94.5% of patients, respectively. The median AT/cm3 and AE/cm3 decreased as experience increased. The AE/cm3 of the IR with 5 years of experience was lower than that of the IR with 1 year of experience and the surgeons, while the AT/cm3 of surgeons was comparable with that of the IR with 5 years of experience at relatively mature phase. Ultrasound-guided percutaneous MWA is a valuable technique for the treatment of BBLs. Trial registration: ClinicalTrials.gov (NCT02860104) • Ultrasound-guided percutaneous microwave ablation has the potential to become a valuable technique for the treatment of benign breast lesions. • A skilled interventional radiologist shows a rapid improvement in mastering the technique.

Purpose Our purpose is to assess the efficacy and safety of percutaneous US-guided microwave ablation (MWA) for cervical metastatic lymph nodes from papillary thyroid carcinomas (PTC). Methods In total, 37 patients with 98 cervical metastatic lymph nodes from PTC were enrolled in this retrospective study. Among them, 8 had subtotal thyroidectomy, 4 lobectomy, 2 no operation, and the rest total thyroidectomy. A multipoint and multiplane fixed ablation method was used. Monitoring of ablation process and clinical follow-up consisted of US or CEUS. Results All 98 metastatic lymph nodes successfully treated in a single session with 100% complete ablation. The average longest and shortest diameter of the tumors were reduced from 13.21 ± 5.86 mm to 6.74 ± 5.66 mm (p =.00) and from 9.29 ± 4.09 mm to 4.31 ± 3.56 mm (p =.00) at the final follow-up. There were no evidence of recurrence at ablated sites. The common intraoperative complications were a burning sensation and pain. Only 3 patients had vagal reflex. Conclusions US-guided MWA can effectively control cervical metastatic lymph nodes from PTC. MWA may become an alternative therapy in selected PTC patients with cervical lymph node metastasis.

Purpose To identify the beneficial body mass index (BMI) for patients with hepatocellular carcinoma (HCC) to achieve longer survival time following curative microwave ablation (MWA). Methods This retrospective study evaluated 474 patients with solitary primary HCC who underwent MWA. BMI at initial admission and other characteristics were collected. The associations of the BMI with the overall survival (OS) and disease-free survival (DFS) were analyzed by Cox proportional hazards regression analysis in multiple models. A two-piecewise linear regression model was applied to examine the threshold effect of the BMI on OS and DFS by maximized log likelihood method. The threshold level was determined by using trial and error. Results Patients with a normal BMI range achieved improved survival outcomes but similar DFS in multiple models. In the model with adjustments of the age, size, and Charlson score, patients with BMI ≤ 22.9 and ≤24.9 kg/m2 exhibited a lower death rate than patients with BMI ≤18.5 kg/m2 (p

Purpose To compare acute kidney injury (AKI) incidence between nephron sparing surgery (NSS) and microwave ablation (MWA) for T1a RCC patients, reveal the effect of AKI on survival prognosis, construct AKI nomogram and use Law of Total Probability for survival probability (SP) prediction. Materials and methods Patients were studied retrospectively after NSS (n = 1267) or MWA (n = 210) from January 1, 2011 to June 30, 2017. Using one to one Propensity Score Matching (PSM), 158 pairs of patients were identified for the cohort study. AKI incidence, risk factors and impact on survival outcomes were analyzed using Chi-square test, logistic and cox regression analysis. AKI risk and SP were predicted by nomogram and Law of Total Probability. The performance of the nomogram was assessed with respect to its discrimination, calibration, and clinical usefulness. Results AKI occurred more commonly in NSS (27.85%) cohort, when compared to MWA (17.72%) cohort (p = 0.032), but treatment modality was not independently predictive of AKI occurrence (odds ratio [OR]: 0.598; 95% confidence interval [CI]: 0.282–1.265; p = 0.178). The 5-yr overall survival (OS) was lower in AKI patients (73.5%) compared with non-AKI patients (94.8%; p 0.86, excellent calibration and net benefits at the decision curve analysis with probabilities ≥5%. SP predicted by Law of Total Probability was comparable to actual OS. Conclusion AKI was an early indicator for poor overall survival in RCC patients. It can be predicted by several oncological parameters. Nomogram and Law of Total Probability can accurately predict AKI risk and SP.

OBJECTIVES To investigate the effect of heat shock protein 90 (HSP90) modulation on tumor necrosis, apoptosis, tumor growth delay, and end point survival by combining microwave ablation (MWA) with an HSP90 inhibitor in a nude mouse model. METHODS This study was approved by the Ethics Committee. Forty mice with HepG2 subcutaneous xenograft tumors (10 ± 1 mm) were randomized into 4 groups: (1) no treatment, (2) MWA only, (3) the HSP90 inhibitor ganetespib only, and (4) ganetespib combined with MWA. Tumors were harvested 24 hours after treatment, and gross coagulation diameters were measured. The effect of ganetespib on HSP90 and caspase 3 expression in the periablational rim was assessed. Another 40 mice with the same tumors and groupings were observed after treatment. Tumor growth curve and Kaplan-Meier survival analyses were performed with a tumor diameter of 2.2 cm and 40 days of survival as the defined survival end points. RESULTS Combination treatment significantly increased the coagulation size compared to tumors treated with MWA or ganetespib alone (P

Aim: This study aimed to develop indocyanine green- and doxorubicin-loaded liposomes (DILPs) as theranostic nanoplatform for the detection of hepatocellular carcinoma (HCC) and as an efficient chemotherapeutic to enhance microwave ablation. Materials & methods: DILPs were synthesized and thoroughly characterized. Biocompatibility, tumor uptake and accumulation, and synergistic ablation-chemotherapeutic efficiency were systematically explored in them. In addition, human HCC surgical samples were used to test the affinity of DILPs for HCC. Results: The combination of microwave ablation and DILPs enhanced the ablation efficiency of HCC with apparent tumor inhibition. DILPs exhibited excellent diagnostic ability and could detect 2.5-mm HCC lesions via optoacoustic tomography imaging. DILPs had better affinity for human HCC surgical samples compared with normal liver tissue. Conclusion: Theranostic DILPs could serve as promising nanoparticles for treatment and management of HCC in the clinic.

Hepatocellular carcinoma (HCC) with metastatic disease is associated with a low survival in clinical practice. Many curative options including liver resection, transplantation, and thermal ablation are effective in local but limited for patients with distant metastasis. In this study, the efficacy, specificity, and safety of P-selectin targeted delivery and microwave (MW) responsive drug release is investigated for development of HCC therapy. By encapsulating doxorubicin (DOX) and MW sensitizer (1-butyl-3-methylimidazolium-l-lactate, BML) into fucoidan conjugated liposomal nanoparticles (TBP@DOX), specific accumulation and prominent release of DOX in orthotopic HCC and lung metastasis are achieved with adjuvant MW exposure. This results in orthotopic HCC growth inhibition that is not only 1.95-fold higher than found for nontargeted BP@DOX and 1.6-fold higher than nonstimuli responsive TP@DOX but is also equivalent to treatment with free DOX at a 10-fold higher dose. Furthermore, the optimum anticancer efficacy against distant lung metastasis and effective prevention of widespread dissemination with a prolonged survival is described. In addition, no adverse metabolic events are identified using the TBP@DOX nanodelivery system despite these events being commonly observed with traditional DOX chemotherapy. Therefore, administering TBP@DOX with MW exposure could potentially enhance the therapeutic efficacy of thermal-chemotherapy of HCC, especially those in the advanced stages.

PurposeTo compare the therapeutic outcomes between open surgical resection (OSR) and percutaneous microwave ablation (PMWA) for colorectal liver metastasis (CRLM) ≤3 cm.MethodsIn this retrospective study, 200 consecutive patients with 306 CRLMs were reviewed. Overall survival (OS), disease-free survival (DFS), local tumour progression (LTP), intrahepatic distant recurrence, and extrahepatic metastasis were analysed to compare the therapeutic efficacy. Cox proportional hazards regression analysis was used to identify the prognostic factors for OS and DFS. Major complications and postoperative hospital stay were also assessed.ResultThe 1-, 3-, and 5-year OS rates were 91.6%, 64.1%, and 46.3%, respectively, in the PMWA group and 89.7%, 62.4% and 44.7%, respectively, in the OSR group (P=0.839). The 1-, 3-, and 5-year DFS rates were 61.9%, 44.8%, and 41.3%, respectively, in the PMWA group and 58.1%, 24.4%, and 18.3%, respectively, in the OSR group (P =0.066). The two groups had comparable 5-year cumulative rates of intrahepatic distant recurrence (P=0.627) and extrahepatic metastasis (P=0.884). The 5-year cumulative LTP rate was lower in the OSR group than in the PMWA group (P=0.023). The rate of major complications was higher in the OSR group than in the PMWA group (P =0.025), and the length of hospital stay after treatment was shorter in the PMWA group (PConclusionThere were no significant differences in OS or DFS between the two groups. PMWA was associated with increased LTP, fewer postoperative days and fewer major complications.

The individual decision-making reference of Microwave ablation (MWA) for T1a RCC treatment is not clear, and it may not benefit all the patients equally. Therefore, we quantitatively evaluated the distinct survival benefits of patients with T1a RCC stratified by survival predictors.A total of 237 patients with T1a RCC who underwent MWA over the last 16 years were retrospectively reviewed for survival benefit analysis. Cox proportional hazard models were used to control for the prognostic variables of OS, CSS, and PFS. Survival rates were calculated using the Kaplan-Meier method and compared by log-rank analysis. Linear extrapolation was used to compute median survival periods.The OS benefit was significantly dependent on age (HR:2.499, 95% CI: 1.245-5.016, p = 0.010) and age-adjusted Charlson comorbidity index (CCI) score (HR:3.956, 95% CI, 1.409-11.110, p = 0.009). OS in patients aged75 years or with an age-adjusted CCI score7 was significantly prolonged (44.68, 65.55 months) compared to OS in patients aged ≥75 years or with CCI score ≥7 (p 0.001 for both). PFS benefit was significantly dependent on age-adjusted CCI (HR:3.325, 95% CI, 1.390-7.956, p = 0.007), patient type (HR:0.4, 95% CI, 0.214-0.745, p = 0.004), and tumour growth pattern (HR:12.562, 95% CI, 1.552-101.696, p = 0.018). PFS in incipient patients was significantly prolonged (33.75 months) compared to that in the relapsed patients (p = 0.037). Patients with an age-adjusted CCI score7 or without tumour protruding into the renal pelvis, lived free from recurrence or metastasis (55.69 or 101.61 months) longer than that in patients with an age-adjusted CCI score ≥7 or with tumour protruding into the renal pelvis (p 0.01 for both). None of the variables was associated with CSS benefit.The OS and PFS benefits from MWA were not equal for all T1a RCC patients. Age ≥75 years and age-adjusted CCI ≥ 7 significantly shortened OS. Age-adjusted CCI ≥ 7, relapsed RCC, and RCC protruding into the renal pelvis significantly shortened the PFS period. For a better survival prognosis, appropriate patient triage is still needed.

Purpose: To investigate the accuracy and robustness of machine learning(ML) model using clinical data extracted directly from electronic health records for predicting the recurrence risk after microwave ablation(MWA). Methods: Between August 2005 and December 2019, 1574 HCC patients who subsequently underwent MWA from four hospitals were reviewed. Data were assigned to the training, internal and external validation set, respectively. Apart from traditional logistic regression(LR), three ML models including (Random Forest, Support Vector Machine and eXtreme Gradient Boosting[XGBoost]) were built and validated in the predictive ability with area under receiving operator characteristic (AUC). SHapley Additive exPlanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) algorithm were performed to realize their interpretability. Results: After 26.2 months of median follow-up period(interquartile range, 6.3, 160.7 months), 51.9%(817/1574) patients occur recurrence. The predictive abilities of three ML models outperformed LR (P < 0.05 for all). When 9 variables were trained simultaneouly using recursive feature elimination with cross-validation, the XGBoost model achieved top predictive ability with AUC value (0.75, 95% CI [confidence interval]: 0.72-0.78) in training set, (0.74, 95% CI: 0.69-0.80) in internal set and (0.76, 95% CI: 0.70-0.82) in external validation set among all models, and it was interpreted depending on the visualization of risk factors by the SHAP and LIME algorithms. The predictive system of post-ablation recurrence risk stratification was provided on online (http://114.251.235.51:8001/) based on XGboost analysis. Conclusions: The XGBoost model based on clinical data can effectively predict recurrence risk after MWA, which can contribute to surveillance, prevention and treatment strategies for HCC. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: This retrospective, multi-center study protocol was approved by the Ethics Committee of all participating institutions

Ethnopharmacological relevance Clinical trials have demonstrated that Trametes robinophila Murr (Huaier granule) can inhibit recurrence and metastasis after hepatocellular carcinoma (HCC) resection, but its efficacy as an adjuvant therapy after thermal ablation of early HCC is unknown. Aim of the study To analyze the prognostic value and side effects of Huaier granules in HCC patients undergoing thermal ablation. Materials and methods Clinical information from 340 eligible subjects with early-stage HCC who were admitted to our department from September 1, 2008 to January 1, 2019 was extracted from the electronic medical record database. They were divided into the thermal ablation + TCM group and the thermal ablation group. Differences in their overall survival (OS), progression-free survival (PFS), extrahepatic metastatic rate (EMR), and therapeutic side effects (TSEs) between the two groups were compared. Beneficiaries of the integrated treatment and adequate treatment length were predicted. Results The median follow-up was 32.5 months (range 2–122 months). The 1-year, 3-year and 5-year OS rates in the integrated treatment group and the control group were 93.2% vs. 92.6%, 54.5% vs. 51.4% 23.5% vs. 19.7% (P = 0.110, HR 0.76(0.54–1.07)). The 1-year, 3-year and 5-year PFS rates were 78.8% vs. 69.4%, 50.6% vs. 40.6%, 35.3% vs. 26.5%, respectively (P = 0.020, HR 0.67(0.48–0.94)). The median OS (35 vs. 31 months) and PFS (24 vs. 12.5 months) were longer in the integrated treatment group. The EMR in the integrated treatment group was significantly lower than that in the control group (p = 0.018, HR 0.49 (0.27–0.89)). Patients with any two of the following three factors might be predicted to be beneficiaries of the integrated treatment, including younger than 65 years (p = 0.039, HR 0.704 (0.504–0.983)), single tumor (p = 0.035, HR 0.698 (0.499–0.975), and tumor size ≤3 cm (p = 0.029, HR 0.690 (0.495–0.964). Patients with continuous oral administration of TCM following ablation had a lower probability of recurrence and metastasis within 2 years (p = 0.015, HR 0.67 (0.49–0.93)). Although the integrated treatment group reported a higher incidence of nausea and emesis, there were no significant differences between the two groups. Conclusion TCM following ablation may prolong PFS and suppress recurrence in patients with HCC, with continuous oral administration for more than 2 years maybe experience a greater benefit. The TSEs of the treatment are mild and can be tolerated.

Objectives Wedelolactone exhibits regulatory effects on some inflammatory diseases. However, the anti‐inflammatory mechanism of wedelolactone has not been entirely unravelled. Therefore, the present study focuses on investigating the mechanism of wedelolactone on NLRP3 inflammasome in macrophages and its influence on MSU‐induced inflammation. Materials and Methods BMDM, J774A.1 and PMA‐differentiated THP‐1 macrophages were primed with LPS and then stimulated with ATP or nigericin or MSU crystal in the presence or absence of wedelolactone. The cell lysates and supernatants were collected to detect NLRP3 inflammasome components such as NLRP3, ASC and caspase 1, as well as pyroptosis and IL‐1β production. In addition, the anti‐inflammatory effects of wedelolactone on MSU‐induced peritonitis and arthritis mice were also evaluated. Results We found that wedelolactone broadly inhibited NLRP3 inflammasome activation and pyroptosis and IL‐1β secretion. Wedelolactone also block ASC oligomerization and speck formation. The inhibitory effects of wedelolactone were abrogated by PKA inhibitor H89, which also attenuated wedelolactone‐enhanced Ser/Thr phosphorylation of NLRP3 at PKA‐specific sites. Importantly, wedelolactone could abate MSU‐induced IL‐1β production and neutrophils migration into peritoneal cavity, and reduced caspase 1 (p20) and IL‐1β expression in the joint tissue of MSU‐induced arthritis. Conclusion Our results indicate that wedelolactone promotes the Ser/Thr phosphorylation of NLRP3 to inhibit inflammasome activation and pyroptosis partly through potentiating PKA signalling, thus identifying its potential use for treating MSU‐induced peritonitis and gouty arthritis., Wedelolactone is a major active ingredient of the traditional medicinal herb eclipta, which demonstrates a broad‐spectrum inhibition effect on NLRP3 inflammasome activation triggered by multiple stimuli. Wedelolactone suppresses NLRP3 inflammasome assembly, pyroptosis and IL‐1β secretion through heightening PKA‐dependent NLRP3 phosphorylation. Importantly, wedelolactone could alleviate NLRP3‐related inflammation in MSU‐induced peritonitis and gouty arthritis.

Background: Central intraductal papilloma (IDP) has a low risk of cancer evolution; therefore, surgical treatment of IDP is controversial. We sought to validate ultrasound (US)-guided percutaneous microwave ablation (MWA) for minimally invasive treatment of IDP. Methods: Thirteen women with central IDP, including six with nipple discharge, underwent US-guided core needle biopsy and MWA from December 2016 to November 2017. Lesions histologically diagnosed as benign IDP were included. The hydro-dissection technique was used to protect the nipple during the entire ablation procedure. We evaluated and recorded data of complete ablation, volume reduction, and complications. Results: MWA was successfully performed in all patients, with 100% complete ablation, assessed by magnetic resonance imaging or contrast-enhanced US. Mean tumor size was 13.5 ± 4.1 (7.0–20.0) mm; the mean ablation time was 1.4 (0.7–10.3) min. At the median 13.7-month follow-up, mean lesion sizes at 3, 6, and 12 months after MWA were all significantly smaller than that at baseline. Total volume reduction rates were 52.3 ± 18.2% (range, 24.2–81.8%), 72.6 ± 23.1% (range, 39.4–95.9%), and 92.9 ± 7.5% (range, 75.0–100%) at 3-, 6-, and 12-month follow-up, respectively, with significant differences (p

Objectives: Acute kidney injury (AKI) is a recently observed side effect in patients after microwave ablation (MWA) of hepatocellular carcinoma (HCC) and is associated with negative outcomes. The aim of this study is to explore the risk factors of affecting the occurrence of AKI (stages 1b, 2, and 3), because they have a higher mortality rate than patients with AKI (stage 1a) and without AKI.Materials and methods: In this retrospective study, a total of 1,214 patients with HCC who were treated with MWA under ultrasound (US) guidance in our department between January 2005 and November 2017 were enrolled. We evaluated the influence of 20 risk factors. Univariate and multivariate analysis were used for statistical analysis. The possible risk factors of AKI after MWA for HCC were summarized.Results: AKI, AKI (stage 1a), and AKI (stages 1b, 2, and 3) after MWA were found in 34, 15, and 19 patients (2.80, 1.24, and 1.57%), respectively. Among 34 patients with AKI, 10 cases with AKI (stage 1a) and 6 cases with AKI (stages 1b, 2, and 3) recovered before their discharge without any treatment for AKI and 9 cases with AKI (stages 1b, 2, and 3) with further treatment. Four cases who had chronic renal failure before MWA of liver accepted renal dialysis. By univariate analysis, the number of antenna insertions (P = 0.027, OR = 3.3), MWA time ≥20 min (P = 0.029, OR = 4.3), creatinine (Cr)-pre above the upper limit of the reference value (P < 0.001, OR = 35.5), albumin (Alb)-pre (P = 0.030, OR = 0.9), and red blood cell (RBC)-pre (P < 0.001, OR = 0.3) were significant risk factors. By multivariate analysis, Cr-pre ≥ 110 μmol/L (P < 0.001, OR = 31.4) and MWA time ≥20 min (P = 0.043 OR = 9.9) were the independent risk factors.Conclusion: AKI (stages 1b, 2, and 3) is a relatively serious complication after MWA for HCC, which is related to MWA time and Cr-pre. It requires attention by clinicians. So it is of great necessity to assess the Cr-pre level and reduce the MWA time to

The left ventricular diastolic time constant (Tau) cannot be practically measured non-invasively. Thus, the aim of this study was to investigate a new method for the evaluation of Tau using continuous-wave (CW) Doppler in dogs with mitral regurgitation. Guided by ultrasound, we created 12 beagle models of mitral regurgitation and acute ischemic left ventricular diastolic dysfunction. Raw audio signals of the CW Doppler spectra were collected, and new mitral regurgitation Doppler spectra were observed after computer re-processing. The new Doppler spectra contour line was constructed using MATLAB (Version R2009), and two time intervals, t1–t2 and t1–t3, were measured on the descending branch of the mitral regurgitation Doppler spectrum and were substituted into Bai's equation group. The Doppler-derived Tau (Tau-d) was resolved and compared with the simultaneous catheter-derived Tau (Tau-c). No significant difference (p > 0.05) between Tau-d (49.33 ± 18.79 ms) and Tau-c (48.76 ± 17.60 ms) was found. A correlation analysis between Tau-d and Tau-c suggested a strong positive relationship (r = 0.85, p = 0.000). Bland-Altman plots of Tau-d and Tau-c revealed fair agreement. Compared with previous non-invasive approaches, this method is simpler and more accurate. There is a strong positive relationship and fair agreement between Tau-d and Tau-c.

Background Hyperthermia has been proposed as a promising treatment modality for its advantageous profiles such as mini/non-invasiveness, good tolerability and cost-effectiveness. Quick development of nanotechnology in recent years has greatly broadened the application area of hyperthermia and endowed it with attractive new functions. This review aims to present an overview of different nanostructures mediated hyperthermia in terms of external stimuli source. Methods We performed to review for the development and current status of nanostructure-mediated hyperthermia, by searching MEDLINE, EMBASE, and Cochrane Library database for identification of relevant articles. Results In the present study, the systemic results of hyperthermia mediated by nanostructures were researched, and five different kinds of external sources were found and listed in this review. The brief mechanism and commonly explored nanostructures were introduced and then combined therapies of nanostructure-mediated hyperthermia stimulated by different external sources were investigated. Finally, challenges with current nanostructures mediated hyperthermia were discussed in order to give advice to the future development of nanostructure-mediated hyperthermia. Conclusions Despite all the achievements the new technology of nanostructure-mediated hyperthermia have made in pre-clinical animal experiments, there are still much to be pursued in the further development to be biocompatible, effective and precise.

Background: The diagnosis performance of B-mode ultrasound (US) for focal liver lesions (FLLs) is relatively limited. The aim of this study was to develop a deep convolutional neural network of US (DCNN-US) for aiding radiologists in classification of malignant from benign FLLs with high sensitivity and specificity. Methods: This prospective multicentre study was conducted in 13 hospitals with different levels in China. Patients who had non-cystic FLLs with pathological results were enrolled. The FLLs from 11 hospitals were randomly divided into training and internal validations (IV) cohorts with a 4:1 ratio for developing and evaluating DCNN-US. Diagnostic performance of the model was verified using external validation (EV) cohort from another two hospitals. Three models were developed by using lesion (ModelLesion, ModelL), liver background images (Model Lesion+Background, ModelL B) and clinical factors (ModelLesion+Background +clinic, ModelL BC) to diagnose FLLs, respectively. The diagnosis value of DCNN-US was compared with that of contrast enhanced computed tomography (CT)/magnetic resonance image (MRI) and 236 radiologists, respectively. Findings: We enrolled 24,343 US images of 2,143 patients to develop and test DCNN-US model. The diagnostic area under the curve (AUC) values of ModelL B increased 6% than ModelL, and Model L BC increased nearly 11% than ModelL B. The AUC of ModelLBC for FLLs were 0.925 (95% CI: 0.886–0.963), and 0.924 (95% CI: 0.889–0.959) in the IV and EV cohorts, respectively. The diagnostic sensitivity and specificity of ModelL BC were superior to 15-year skilled radiologists (86.5% vs 76.1%, and 85.5% vs 75.9%, respectively) (both p

Background Developing new strategies to reduce the output power of microwave (MW) ablation while keeping anti-tumor effect are highly desirable for the simultaneous achievement of effective tumor killing and avoidance of complications. We find that mild MW irradiation can significantly increase intracellular Ca2+ concentration in the presence of doxorubicin hydrochloride (DOX) and thus induce massive tumor cell apoptosis. Herein, we designed a synergistic nanoplatform that not only amplifies the intracellular Ca2+ concentration and induce cell death under mild MW irradiation but also avoids the side effect of thermal ablation and chemotherapy. Results The as-made NaCl–DOX@PLGA nanoplatform selectively elevates the temperature of tumor tissue distributed with nanoparticles under low-output MW, which further prompts the release of DOX from the PLGA nanoparticles and tumor cellular uptake of DOX. More importantly, its synergistic effect not only combines thermal ablation and chemotherapy, but also obviously increases the intracellular Ca2+ concentration. Changes of Ca2+ broke the homeostasis of tumor cells, decreased the mitochondrial inner membrane potential and finally induced the cascade of apoptosis under nonlethal temperature. As such, the NaCl–DOX@PLGA efficiently suppressed the tumor cell progression in vivo and in vitro under mild MW irradiation for the triple synergic effect. Conclusions This work provides a biocompatible and biodegradable nanoplatform with triple functions to realize the effective tumor killing in unlethal temperature. Those findings provide reliable solution to solve the bottleneck problem bothering clinics about the balance of thermal efficiency and normal tissue protection.

Purpose: To compare the clinical efficacy of ultrasound-guided percutaneous microwave ablation (MWA) and parathyroidectomy for primary hyperparathyroidism. Methods: In an observational retrospective study, we compared the outcomes in patients with primary hyperparathyroidism who underwent ultrasound-guided MWA with the outcomes in those who underwent surgical resection (SR). The primary outcome was cure rate. Secondary outcomes were the rate of complications, and the difference of the treatment parameters of two treatment methods. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. Results: Among 108 patients who met inclusion criteria, 28 patients who underwent ultrasound-guided MWA (MWA group) and 28 who underwent SR (SR group) had similar propensity scores and were included in the analyses. There was no significant difference in the cure rate between MWA group and SR group (82.1% vs. 89.3%, p = .705). Patients who underwent MWA had significantly less estimated blood loss and shorter surgical time than those who underwent SR (p

// Jian-ping Dou 1 , Jie Yu 1 , Xiao-huan Yang 1 , Zhi-gang Cheng 1 , Zhi-yu Han 1 , Fang-yi Liu 1 , Xiao-ling Yu 1 and Ping Liang 1 1 Department of Interventional Ultrasound, Chinese People's Liberation Army (PLA) General Hospital, Beijing, 100853, China Correspondence to: Ping Liang, email: liangping301@126.com Keywords: hepatocellular carcinoma, microwave ablation, vessel, prognosis, propensity score matching Received: August 20, 2016 Accepted: February 01, 2017 Published: February 24, 2017 ABSTRACT The aim of this study was to retrospectively compare the long-term efficacy of MW ablation as a curative therapy for hepatocellular carcinoma(HCC) adjacent to large vessels(≥3 mm) with that in safe location. Between 2010 and 2016, 406 patients diagnosed with early-stage HCC at Chinese PLA general hospital were enrolled. One-to-one matched pairs between the vessel group and the safe group were generated using propensity score matching. The associations of treatment strategy with overall survival and local tumor progression were determined by Cox regression. Before matching, 113 patients were classified into the vessel group and 293 patients were classified into the vessel group. The patients in the vessel group were more frequently classified as larger tumor size (P

Microwave (MW) therapy, as a promising type of thermal therapy, has been attracting more and more attention from scientists. The combination of thermal and chemotherapy is of great significance in the latest studies of synergistic tumor therapy. However, the research on the MW therapy mechanism, especially the nonthermal effect applied in the combined cancer therapy, is not thorough enough. Pleasantly, we have discovered that nonthermal MW irradiation can promote the cellular uptake of nanoparticles and anticancer drugs via experiments in vitro and in vivo. Therefore, multifunctional nanoplatforms have been designed for enhanced tumor inhibition by loading ionic liquids (ILs), doxorubicin hydrochloride (DOX), and phase change materials (PCMs) into ZrO2 hollow nanoparticles. PCMs act as MW switches. The as-made IL-DOX-PCM@ZrO2 nanoplatforms were injected into H22-tumor-bearing mice via the tail vein. Mild microwave irradiation (0.9 W, 450 MHz) was then applied. The thermal effect of MW could cause the temp...

Treatment for liver tumors in the caudate lobe is challenging because of their location and complex anatomy. This study was intended to evaluate the feasibility, efficacy and tolerability of ultrasound-guided percutaneous microwave (MW) ablation for treating hepatocellular carcinoma (HCC) in the caudate lobe. From December 2011 to May 2015, a total of 20 patients (mean age: 62 ± 11 y) with HCC in the caudate lobe were enrolled in this study. Patient characteristics and tumor features were analyzed. The epigastric approach, intercostal approach and the combination were used in 4, 14 and 2 patients, respectively. Contrast-enhanced ultrasound (CEUS) guidance and temperature monitoring were applied as ancillary techniques. Ethanol injection was performed for tumors adjacent to the inferior vena cava or hepatic hilum. Contrast images were performed to evaluate treatment response after ablation. Technical success, technique efficacy, local tumor progression and complications were documented. Technique efficacy was achieved in 18 patients (18/20, 90%). Two patients received (125)I brachytherapy as palliative therapy for residual tumors that could not be ablated technically after the first ablation. Technical success was achieved in 16 patients (16/20, 80%). In 2 patients, ablation was completed after two sessions. CEUS was applied in 5 patients and temperature monitoring in 2 patients. Eight patients received an ethanol injection during ablation. Eleven patients achieved a minimum 5-mm safety margins. Local tumor progression was detected in 3 patients (16.7%, 3/18) during a median follow-up of 18.4 mo (range: 3-45 mo). Tumors in these 3 patients were all larger than 2.0 cm. No major or minor complications were observed. In conclusion, ultrasound-guided percutaneous microwave ablation combined with CEUS, temperature monitoring, and ethanol injection is a tolerable and relatively effective treatment for HCC in the caudate lobe.

This prospective study was to evaluate clinical outcomes of microwave ablation (MWA) of benign breast tumors with minimum 12 months follow up.With approval of the institutional ethics committee and written informed consent, 56 patients with 107 biopsy-proved breast benign tumors were recruited from November, 2013 to April, 2017. MWA with ultrasound (US) guidance was performed under local anesthesia. During the procedure, pull-back technique was used for tumors larger than 1.0 cm in diameter and hydro-dissection technique was used for tumors adjacent to skin, pectoralis and areola. Clinical outcomes were followed up by physical examination and medical images including US, contrast enhanced US and MR.The maximum diameter of these tumors was 1.6 ± 0.8 cm. MWA was successfully performed with the median 120 s of duration (ranging 20-1100 s). Technical success was achieved in all patients. At the median follow-up of 20.5 months (ranging 12-53 months), the mean volume reduction ratios (mVRRs) of tumors were 77.1 ± 8.2%, 84.3 ± 10.6%, 93.3 ± 8.2% at follow-up of 12, 18, 24 months (p .0001), respectively. Compared with 92% of masses were palpable before ablation, mass palpabilities were 40%, 11%, 5% at follow-up of 12, 18, 24 months (p .001), respectively. Cosmetic satisfaction was reported excellent or good in 100% of patients.As a safe and effective minimally invasive modality for inactivating benign breast tumors in situ, MWA achieved optimistic clinical outcomes on volume reduction and cosmetic satisfaction after minimum 12 months follow-up.

To retrospectively review long-term oncologic outcomes after ultrasound (US)-guided percutaneous microwave ablation (MWA) of T1a renal cell carcinoma (RCC) and to identify the incidence and risk factors that predict local tumor progression (LTP) after MWA of RCC.The present study was approved by the institutional review board. A total of 162 patients with 171 RCC nodules (mean size, 2.6 ± 0.8 cm; range, 0.6-4.0 cm) were treated by MWA between April 2006 and January 2017. The influence of eight factors (age; sex; longest tumor diameter; tumor number, location and pathology type; ablation power and time) affecting the risk of LTP was assessed. Univariate Kaplan-Meier and Cox proportional hazard models were used for statistical analysis.LTP occurred in five patients (5 tumors) after US-guided percutaneous MWA of stage T1a RCC. The overall occurrence of LTP was 2.9% per tumor and 3.0% per patient with a median follow-up of 45.5 months. Among the 162 patients, there were no instances of LTP-related deaths; however, 20 patients died of other diseases. All patients with LTP survived through follow-up. The survival rate of LTP-free patients at 1, 3 and 5 years were 98.7%, 89.5% and 82.1%, respectively (p = .38). Univariate and multivariate analysis identified tumor location to be the only independent predictor of LTP.US-guided percutaneous MWA for T1a RCC achieved a relatively low LTP incidence rate. Tumors adjacent to the renal pelvis or bowel increased the potential of LTP occurrence.

Microwave (MW) hyperthermia has received great attention as an emerging green tumor thermotherapy. In this work, layered MoS2 nanoflowers were prepared through a simple bottom-up hydrothermal process. By coating MoS2 nanoflowers with bovine serum albumin (BSA-MoS2), BSA-MoS2 exhibits low biotoxicity and excellent microwave susceptive properties in vitro. Meanwhile, the heating effect improvement by the layered structure was confirmed via a computer-simulated experiment. Finally, layered BSA-MoS2 nanoflowers are designed as MW hyperthermia susceptible agents for in vivo cancer therapy with 100% tumor elimination via MW irradiation at 1.8 W, 450 MHz.

Microwave ablation (MWA) is a promising minimally invasive therapy that has been widely used to treat hepatocellular carcinoma (HCC). However, the efficiency of MWA in treating HCC is evidently limited by the incomplete ablation of large tumors and tumors in high-risk locations. Here, we report the value of using liposomes packed with sodium chloride (NaCl-LPs) as effective thermo-seeds for MWA of HCC. The prepared liposomes exhibited excellent heat conversion ability by showing a more rapid temperature increase than free NaCl medium, blank liposomes or water under microwave irradiation. The high efficiency of this new microwave sensitization strategy was fully demonstrated in vitro in subcutaneous and orthotopic tumors. The results showed that MWA combined with NaCl-LPs clearly enhanced the ablation efficiency, leading to apparent tumor inhibition and low recurrence. What's more, we verified the susceptibility of NaCl-LPs on orthotopic tumors. Based on the unique properties of NaCl-LPs, sublethal MWA was used to mimic the transitional zone, and large-scale necrosis was observed in tumors combined with NaCl-LPs. In addition, HE staining and blood hematology analysis revealed no noticeable toxicity of NaCl-LPs in vivo, which confirmed that NaCl-LPs possessed good biocompatibility.The effective nanoparticles could play a valuable role in enhancing the thermo-sensitizing effect of MWA for achieving better therapeutic efficacy.

To evaluate the feasibility, efficacy, and safety of microwave ablation (MWA) in the treatment of hepatocellular carcinoma associated with Budd–Chiari syndrome (BCS) after transarterial chemoembolization (TACE). A total of 10 patients (mean 50.0 ± 7.5 years) with 15 BCS-associated HCC lesions were retrospectively evaluated. All patients received MWA treatment for residual tumors after 1 to 3 sessions of TACE. The diagnosis of residual tumors was confirmed by at least two types of enhanced imaging. CEUS images were performed to confirm the residual lesions and guide the placement of antenna before MWA. Thermal monitoring and artificial pleural effusion or ascites were used to guarantee ablative accuracy and safety for patients with tumors adjacent to vital structures. Technical success, technique efficacy, local tumor progression, survival rate, and the incidence of complications were comprehensively analyzed. Technical success and technique effectiveness were achieved in all patients. Thirteen lesions achieved complete ablation for the first time, and 2 lesions needed two sessions. Thermal monitoring was used in 2 patients, artificial pleural effusion was used in 1 patient, and artificial ascites in 2 patients. In a median follow-up of 34.5 months (range 21–52 months), no LTP was founded in all patients. Intrahepatic recurrence was found in 5 patients. 1-, 2-, 3-, and 4-year survival rates were 100%, 100%, 74.1%, and 37.0%, respectively. No major or minor complications were observed. Microwave ablation is a feasible and effective way to treat residual tumors after TACE treatment in patients with BCS-associated HCC.

Aim To explore the risk factors predicting haemoglobinuria after ultrasound-guided percutaneous microwave ablation (MWA) of liver tumours and discuss the treatments and outcomes. Materials and methods The present study comprised 2,829 patients admitted for liver tumours treated with MWA from Jan 2011 to April 2017. Ethics committee approval was waived and informed consent for treatment procedures were obtained from the patients. Haemoglobinuria after MWA was found in 149 patients. The influence of 19 risk factors was assessed. Binary logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis. The treatments and outcomes of patients with haemoglobinuria were summarised. Results By univariate analysis, histopathology, liver cirrhosis, MWA volume, MWA energy, and MWA duration were significant risk factors. By multivariate analysis and ROC curve, MWA energy, duration, and volume were identified as predictors of haemoglobinuria after MWA. Drug treatments including kidney protection, adequate hydration, alkalisation of urine, and diuresis were administrated to the patients with haemoglobinuria. One patient progressed to acute kidney injury (AKI) while others had good clinical outcomes. Conclusion Haemoglobinuria is a controllable side effect after MWA of liver tumours, which is related to high MWA energy, long MWA duration, and great MWA volume. It usually caused few side effects on renal function with correct treatment.

Combining photothermal therapy (PTT) with clinical technology to kill cancer via overcoming the low tumor targeting and poor therapy efficiency has great potential in basic and clinical researches. A brand-new MoS2 nanostructure is designed and fabricated, i.e., layered MoS2 hollow spheres (LMHSs) with strong absorption in near-infrared region (NIR) and high photothermal conversion efficiency via a simple and fast chemical aerosol flow method. Owing to curving layered hollow spherical structure, the as-prepared LMHSs exhibit unique electronic properties comparing with MoS2 nanosheets. In vitro and in vivo studies demonstrate their high photothermal ablation of cell and tumor elimination rate by single NIR light irradiation. Systematic acute toxicity study indicates that these LMHSs have negligible toxic effects to normal tissues and blood. Remarkably, minimally invasive interventional techniques are introduced to improve tumor targeting of PTT agents for the first time. To explore PTT efficiency on orthotopic transplantation tumors, New Zealand white rabbits with VX2 tumor in liver are used as animal models. The effective elimination of tumors is successfully realized by PTT under the guidance of digital subtraction angiography, computed tomography, and thermal imaging, which provides a new way for tumor-targeting delivery and cancer theranostic application.

Background Innate immunity to viruses involves receptors such as RIG-I, which senses viral RNA and triggers an IFN-β signaling pathway involving the outer mitochondrial membrane protein MAVS. However, the functional status of MAVS phosphorylation remains elusive. Methodology/Principal Findings Here we demonstrate for the first time that MAVS undergoes extensive tyrosine phosphorylation upon viral infection, indicating that MAVS phosphorylation might play an important role in MAVS function. A tyrosine-scanning mutational analysis revealed that MAVS tyrosine-9 (Y9) is a phosphorylation site that is required for IFN-β signaling. Indeed, MAVS Y9F mutation severely impaired TRAF3/TRAF6 recruitment and displayed decreased tyrosine phosphorylation in response to VSV infection compared to wild type MAVS. Functionally, MAVS Y9 phosphorylation contributed to MAVS antiviral function without interfering with its apoptosis property. Conclusions/Significance These experiments identify a novel residue of MAVS that is crucially involved in the recruitment of TRAF3/TRAF6 and in downstream propagation of MAVS signaling.

Background The calcification of blood vessels correlates with increased morbidity and mortality in patients with atherosclerosis, diabetes, and end-stage kidney disease. Increased inflammasome activation has been shown to play an important role in the pathogenesis of atherosclerosis. However, the contribution of inflammasome activation on the development of vascular calcification has not been investigated. Methods β-Glycerophosphate (β-GP) was used as a procedure to induce extensive artery calcification in primary vascular smooth muscle cells (VSMCs). Analysis of the levels of Nalp3 inflammasome complex was performed by quantitative real-time PCR and western blotting. The effect of Nalp3 deficiency on VSMC calcification was examined after transfecting Nalp3 siRNA into cultured VSMCs. Results We demonstrated for the first time that the mRNA levels of Nalp3 inflammasome complex including Nalp3, ASC and caspase1 were upregulated in calcifying VSMCs, resulting in increased IL-1β secretion. Inhibition of inflammasome activation by Nalp3 RNA interference reduced IL-1β secretion and inhibited VSMC calcification. Further analysis of clinical popliteal artery specimens showed an upregulation of inflammasome complex mRNA levels (4/5) and caspase1 activity (5/5) compared with their non-calcified adjacent tissues, indicating that Nalp3 inflammasome was tightly correlated with arterial calcification disease. Conclusion Our findings indicate that activation of the Nalp3-mediated inflammatory response pathway is an important venue associated with host response and pathogenesis of VSMC calcification.