Correlations of RENAL, PADUA and NePhRO Scores With Complications and Outcomes in Patients After CT-Guided Microwave Ablation of Renal Tumors.

OBJECTIVE: This retrospective study aimed to access the correlations of RENAL, PADUA and NePhRO scores with operative complications, chronic kidney disease (CKD) upstaging, and oncologic outcomes after CT-guided percutaneous Microwave Ablation (MWA) of renal tumors in order to determine their status as independent predictors of outcomes after MWA. This study also aimed to generally evaluate the efficacy of MWA in treating renal tumors. METHODS: From January 2017 to December 2019, 18 patients with 27 renal tumors who had undergone simultaneous biopsy and MWA were recruited in this single-center retrospective study. Data collection included tumor characteristics, procedural protocols, complications, CKD upstaging data, local tumor control data and overall survival. All lesions were evaluated using RENAL, PADUA and NePhRO scores, and further analysis was performed to determine whether the scores were correlated with operative complications, CKD upstaging, local tumor control and overall survival. RESULTS: The minor and major complication rates were 16.7% and 0%, respectively. Two patients with solitary kidney experienced CKD upstaging. Local tumor recurrence was identified in one type of tumor (3.7%) in the first year of follow-up. L. parameter (P = .031), longitudinal (polar) location score (P = .011), Ne. parameter (P = .036), number of kidneys (P = .005), and number of lesions (P = .008), were predictive factors significantly associated with the occurrence of complications. Besides, CKD upstaging was associated with A. parameter (P = .032) and urinary collecting system score (P = .028). RENAL, PADUA, and NePhRO scores were significantly correlated with complications, overall survival, and CKD upstaging, respectively (P < .05). CONCLUSION: CT-guided percutaneous MWA was found to be a valuable alternative in the treatment of renal tumors for selected patients. Furthermore, RENAL, PADUA and NePhRO scores were not independent predictors of outcomes of MWA.

Effects of Oral Vitamin C Supplementation on Liver Health and Associated Parameters in Patients With Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial.

Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent hepatic disorder worldwide, and an unhealthy lifestyle is the leading risk factor for its occurrence. Vitamin C (VC) has been suggested to protect NAFLD, whereas evidence from randomized controlled trials (RCTs) is sparse. In this study, we aimed to investigate the potential benefits of VC supplementation daily on liver health and associated parameters in patients with NAFLD. In this double-blind, RCT, 84 patients with NAFLD, aged 18-60 years old, were assigned to 12 weeks of oral treatment with either low (250 mg/day, n = 26), medium (1,000 mg/day, n = 30), or high (2,000 mg/day, n = 28) doses of VC supplements. After the intervention, the Medium group had a more significant decrease in aspartate aminotransferase [Medium, -5.00 (-10.25, -1.75) vs. High, -2.50 (-7.75, 0.00), P = 0.02] and alanine aminotransferase [Medium, -8.00 (-18.00, -1.75) vs. High, -3.50 (-13.75, 4.25), P = 0.05; Medium vs. Low, -3.00 (-9.00, 5.50), P = 0.031]. The levels of other indicators of liver health, such as gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, and direct bilirubin were decreased after the intervention but comparable among the three groups and so did the parameters of glucose metabolism, such as fasting insulin, fasting glucose, and homeostasis model assessment for insulin resistance. The plasma level of VC in patients and total adiponectin and high molecular weight (HMW) adiponectin levels were also elevated but not in a dose-dependent manner. Meanwhile, analysis of fecal microbiota composition showed an increase in the alpha diversity (Abundance-based Coverage Estimator (ACE), Shannon, chao1, and Simpson) both in the Low and the Medium groups. A total of 12 weeks of VC supplementation, especially 1,000 mg/day, improved liver health and glucose metabolism in patients with NAFLD. The elevated plasma levels of VC, total and HMW adiponectin, and the improvement of intestinal microbiota may have made some contributions.

Analysis of Acanthopanax giraldii Harms Polysaccharide II Composition and Its Immune-Protective Role in a Cyclophosphamide-Induced Immunosuppressive Mice Model.

Acanthopanax giraldii Harms is commonly used in traditional Chinese medicine to treat rheumatism, improve joints, and strengthen muscles and bones. The polysaccharides present in A. giraldii Harms contain major bioactive substances, which have antioxidant, anticancer, and antiviral activities. In this study, the structural characterization of the homogeneous polysaccharide isolated from A. giraldii Harms, known as AHP-II, and its immunomodulatory effects in vivo will be studied. High-performance ion chromatography (HPIC) and high-performance gel permeation chromatography (HPGPC) based analyses revealed that AHP-II was composed of various monosaccharides, which included rhamnose, arabinose, galactose, glucose, mannose, galacturonic acid, and glucuronic acid in molar ratios of 29.5 : 24.6 : 23.8 : 4.4 : 5.7 : 8.8 : 3.1, respectively, and had a collective molecular weight of 80.21 × 103 Da. Fourier-transform infrared (FTIR) spectroscopy indicated the presence of a pyranose ring and ß-type glycosidic linkages in AHP-II. In addition, immunomodulatory effect analyses of AHP-II that used a cyclophosphamide-induced immunosuppressive mouse model demonstrated that its treatment could significantly restore spleen and thymus indices, promote the proliferation of splenic lymphocytes, elevate CD4+ T lymphocyte percentage and CD4+ : CD8+ ratio in the spleen, promote macrophage phagocytosis, and restore cytokines (IL-6, TNF-α, IgM, and IgG) levels. These results suggested that AHP-II could potentially be used as natural immunomodulator and as an alternative treatment to reduce chemotherapy-induced immunosuppression.

Hypoxia-Overcoming Breast-Conserving Treatment by Magnetothermodynamic Implant for a Localized Free-Radical Burst Combined with Hyperthermia.

For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.

Ferrous ions doped layered double hydroxide: smart 2D nanotheranostic platform with imaging-guided synergistic chemo/photothermal therapy for breast cancer.

Developing simple and efficient nanotheranostic platforms with behavior responsive to the acid microenvironment of a tumor is of great significance for accurate tumor diagnosis and therapy. In this study, a smart 2D nanotheranostic platform has been successfully fabricated by doping functional ferrous ions into as-synthesized MgAl-layered double hydroxide (LDH) with doxurubicin (DOX) loading to form Fe-LDH/DOX NPs, which achieved magnetic resonance imaging (MRI)-guided synergistic chemo/photothermal therapy for breast cancer. The doping of ferrous ions into Fe-LDH/DOX enabled a strong photo-induced heating ability with a high photothermal conversion efficiency of 45.67%, which could be combined with the antitumor drug DOX to achieve the synergistic effect of photothermal therapy (PTT) and chemotherapy for killing tumor cells. Additionally, its in vitro pH-dependent degradation behavior and T2-weighted MRI effect revealed that the as-prepared Fe-LDH/DOX is sensitive to the tumor acid microenvironment. Most importantly, the growth rate of tumors in 4T1 bearing mice could be effectively inhibited after the synergistic treatment of PTT and chemotherapy by Fe-LDH/DOX. These results show that doping functional metal ions into LDH NPs may open a novel approach to fabricating an LDH NP-based nanotheranostics platform with advanced diagnostic and therapeutic performances.

Cryoablation, high-intensity focused ultrasound, irreversible electroporation, and vascular-targeted photodynamic therapy for prostate cancer: a systemic review and meta-analysis.

Cryoablation (CA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and vascular-targeted photodynamic therapy (VTP) have been evaluated as novel strategies for selected patients with prostate cancer (PCa). We aim to determine the current status of literature regarding the clinical outcomes among these minimally invasive therapies. A systematic search of PubMed, EMBASE, and the Cochrane Library for all English literature published from January 2001 to December 2019 was conducted to identify studies evaluating outcomes of CA, HIFU, IRE or VTP on PCa. Proportionality with 95% confidence intervals (CIs) was performed using STATA version 14.0. 56 studies consisting of 7383 participants were found to report data of interest and fulfilled the inclusion criteria in the final meta-analysis. The pooled proportions of positive biopsy after procedure were 20.0%, 24.3%, 24.2%, and 36.2% in CA, HIFU, IRE and VTP, respectively. The pooled proportions of BRFS were 75.7% for CA and 74.4% for HIFU. The pooled proportions of CSS were 96.1%, 98.2%, and 97.9% for CA, HIFU, and IRE, respectively. The pooled proportions of OS were 92.8% for CA and 85.2% for HIFU. The pooled proportions of FFS were 64.7%, 90.4%, and 76.7% for CA, IRE and VTP, respectively. The pooled proportions of MFS were 92.8% for HIFU and 99.1% for IRE. This meta-analysis shows that CA, HIFU, IRE, and VTP are promising therapies for PCa patients with similar clinical outcomes. However, further larger, well-designed randomized controlled trials are required to confirm this assertion.

[Diagnosis and Treatment Recommendation and Exploration for Critical and Refractory Adverse Effects Related to Immunocheckpoint Inhibitors].

The application of immunological checkpoint inhibitors (ICIs) has modified many treatment strategies of malignant tumors, which has become a milestone in cancer therapy. The principle of action can be explained as "brake theory". After releasing the brakes by ICIs, unprecedented systemic toxicities, even some refractory and fatal immune-related adverse effects (irAEs) may develop. In this article, we summarized the recommended treatments of grade 3-4 severe irAEs in the latest European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN)/American Society of Clinical Oncology (ASCO), Society for Immunotherapy of Cancer (SITC) and Chinese Society of Clinical Oncology (CSCO) guidelines and consensus. We also performed a systemic review of case reports and reviews of irAEs up to May 20, 2019 in PubMed and Chinese journals. Successful applications of specific immunosuppressive drugs and stimulating factors beyond the above guidelines and consensus were supplemented and highlighted, including agents blocking interleukin 6 (IL-6), rituximab, anti-tumor necrosis factor-α (TNFα) monoclonal antibody (mAb), anti-integrin 4 mAb, Janus kinase inhibitors, thrombopoietin receptor agonists and antithymocyte globulin (ATG) etc. We put some concerns of using high-dose steroids for long-term, and emphasize the secondary infections, tumor progression, and unavailability of ICI re-challenge during steroid treatment. We propose the "De-escalation Therapy" principle for severe and refractory irAEs, and suggest that immunosuppressive drugs specifically targeting cytokines should be used as early as possible. Many irAEs in the era of immunotherapy are unprecedented compared with traditional chemotherapy and small-molecule targeted therapy, which is a big challenge to oncologists. Therefore, the establishment of multidisciplinary system is very important for the management of cancer patients.

Binding of the polysaccharide from Acanthopanax giraldii Harms to toll-like receptor 4 activates macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine, Acanthopanax giraldii Harms, is commonly used to treat arthralgia due to wind, cold and dampness, as well as weakness in the feet and knees. Its other reported effects include eliminating flatulence, strengthening muscles and bones, and delaying aging. The polysaccharides in A. giraldii Harms are the major bioactive substances that confer the herb's antioxidant properties as well as anticancer and antiviral effects. AIMS OF THE STUDY: To elucidate the underlying mechanism and signaling cascade involved in the homogeneous A. giraldii Harms polysaccharide II (AHP-II)-mediated immunomodulation of mice macrophages. MATERIALS AND METHODS: The phagocytosis of neutral red and the production of nitric oxide, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were measured to determine AHP-II-induced macrophage activation. Confocal microscopy and flow cytometry were used to confirm the binding of AHP-II to macrophages. The involvement of Toll-like receptor (TLR) 4 in AHP-II-induced macrophage activation was demonstrated using antibody blocking and macrophages from C3H/HeJ TLR4-mutant mice. Western blotting was used to map AHP-II-induced downstream signaling pathways. RESULTS: AHP-II increased the phagocytosis of macrophages and the release of nitric oxide, IL-6 and TNF-α cytokines. Direct, saturable and reversible binding of AHP-II to macrophages was observed, while it can be inhibited by the anti-TLR4 antibody. In addition, the presence of the anti-TLR4 antibody inhibited AHP-II-induced macrophage IL-6 and TNF-α production in the peritoneal macrophages of C3H/HeJ mice. Moreover, AHP-II-TLR4-stimulated macrophages activate the downstream intracellular ERK and JNK/nuclear factor (NF)-κB signaling pathways. In addition, the AHP-II-mediated regulation of IL-6 and TNF-α production from macrophages was greatly affected by specific ERK, JNK and NF-κB inhibitors. CONCLUSION: Our study elucidated the immunomodulatory mechanism of AHP-II in macrophage activation and identified TLR4 as the main receptor coordinating AHP-II binding. Our findings suggest AHP-II may be used as a novel immunopotentiator for medical purposes.