Rationale for immune checkpoint inhibitors plus targeted therapy for advanced renal cell carcinoma.

Renal cell carcinoma (RCC) is a frequent urological malignancy characterized by a high rate of metastasis and lethality. The treatment strategy for advanced RCC has moved through multiple iterations over the past three decades. Initially, cytokine treatment was the only systemic treatment option for patients with RCC. With the development of medicine, antiangiogenic agents targeting vascular endothelial growth factor and mammalian target of rapamycin and immunotherapy, immune checkpoint inhibitors (ICIs) have emerged and received several achievements in the therapeutics of advanced RCC. However, ICIs have still not brought completely satisfactory results due to drug resistance and undesirable side effects. For the past years, the interests form researchers have been attracted by the combination of ICIs and targeted therapy for advanced RCC and the angiogenesis and immunogenic tumor microenvironmental variations in RCC. Therefore, we emphasize the potential principle and the clinical progress of ICIs combined with targeted treatment of advanced RCC, and summarize the future direction.

Deep learning-based arterial subtraction images improve the detection of LR-TR algorithm for viable HCC on extracellular agents-enhanced MRI.

PURPOSE: To determine the role of deep learning-based arterial subtraction images in viability assessment on extracellular agents-enhanced MRI using LR-TR algorithm. METHODS: Patients diagnosed with HCC who underwent locoregional therapy were retrospectively collected. We constructed a deep learning-based subtraction model and automatically generated arterial subtraction images. Two radiologists evaluated LR-TR category on ordinary images and then evaluated again on ordinary images plus arterial subtraction images after a 2-month washout period. The reference standard for viability was tumor stain on the digital subtraction hepatic angiography within 1 month after MRI. RESULTS: 286 observations of 105 patients were ultimately enrolled. 157 observations were viable and 129 observations were nonviable according to the reference standard. The sensitivity and accuracy of LR-TR algorithm for detecting viable HCC significantly increased with the application of arterial subtraction images (87.9% vs. 67.5%, p < 0.001; 86.4% vs. 75.9%, p < 0.001). And the specificity slightly decreased without significant difference when the arterial subtraction images were added (84.5% vs. 86.0%, p = 0.687). The AUC of LR-TR algorithm significantly increased with the addition of arterial subtraction images (0.862 vs. 0.768, p < 0.001). The arterial subtraction images also improved inter-reader agreement (0.857 vs. 0.727). CONCLUSION: Extended application of deep learning-based arterial subtraction images on extracellular agents-enhanced MRI can increase the sensitivity of LR-TR algorithm for detecting viable HCC without significant change in specificity.

Comparison of quantitative volumetric analysis and linear measurement for predicting the survival of Barcelona Clinic Liver Cancer 0- and A stage hepatocellular carcinoma after radiofrequency ablation.

PURPOSE: The prognostic role of the tumor volume in patients with hepatocellular carcinoma (HCC) at the Barcelona Clinic Liver Cancer (BCLC) 0 and A stages remains unclear. This study aims to compare the volumetric measurement with linear measurement in early HCC burden profile and clarify the optimal cut-off value of the tumor volume. METHODS: The consecutive patients diagnosed with HCC who underwent initial and curative-intent radiofrequency ablation (RFA) were included retrospectively. The segmentation was performed semi-automatically, and enhanced tumor volume (ETV) as well as total tumor volume (TTV) were obtained. The patients were categorized into high- and low-tumor burden groups according to various cutoff values derived from commonly used diameter values, X-tile software, and decision-tree analysis. The inter- and intra-reviewer agreements were measured using the intra-class correlation coefficient. Univariate and multivariate time-to-event Cox regression analyses were performed to identify the prognostic factors of overall survival. RESULTS: A total of 73 patients with 81 lesions were analyzed in the whole cohort with a median follow-up of 31.0 (interquartile range: 16.0­36.3). In tumor segmentation, excellent consistency was observed in intra- and inter-reviewer assessments. There was a strong correlation between diameter-derived spherical volume and ETV as well as ETV and TTV. As opposed to all linear candidates and 4,188 mm3 (sphere equivalent to 2 cm in diameter), ETV >14,137 mm3 (sphere equivalent to 3 cm in diameter) or 23,000 mm3 (sphere equivalent to 3.5 cm in diameter) was identified as an independent risk factor of survival. Considering the value of hazard ratio and convenience to use, when ETV was at 23,000 mm3, it was regarded as the optimal volumetric cut-off value in differentiating survival risk. CONCLUSION: The volumetric measurement outperforms linear measurement on tumor burden evaluation for survival stratification in patients at BCLC 0 and A stages HCC after RFA.

Fabrication of Carbon-Based Quantum Dots via a "Bottom-Up" Approach: Topology, Chirality, and Free Radical Processes in "Building Blocks".

The discovery of carbon-based quantum dots (CQDs) has allowed opportunities for fluorescence bioimaging, tumor diagnosis and treatment, and photo-/electro-catalysis. Nevertheless, in the existing reviews related to the "bottom-up" approaches, attention is mainly paid to the applications of CQDs but not the formation mechanism of CQDs, which mainly derived from the high complexities during the synthesis of CQDs. Among the various synthetic methods, using small molecules as "building blocks", the development of a "bottom-up" approach has promoted the structural design, modulation of the photoluminescence properties, and control of the interfacial properties of CQDs. On the other hand, many works have demonstrated the "building blocks"-dependent properties of CQDs. In this review, from one of the most important variables, the relationships among intrinsic properties of "building blocks" and photoluminescence properties of CQDs are summarized. The topology, chirality, and free radical process are selected as descriptors for the intrinsic properties of "building blocks". This review focuses on the induction and summary of recent research results from the "bottom-up" process. Moreover, several empirical rules pertaining thereto are also proposed.

Synergistic Effect of Oxygen- and Nitrogen-Containing Groups in Graphene Quantum Dots: Red Emitted Dual-Mode Magnetic Resonance Imaging Contrast Agents with High Relaxivity.

Contrast agents (CAs) in magnetic resonance imaging generally involve the dissociative Gd3+. Because of the limited ligancy of Gd3+, the balance between Gd3+ coordination stability (reducing the concentration of dissociative Gd3+) and increases in the number of coordination water molecules (enhancing the relaxivity) becomes crucial. Herein, the key factor of the synergistic effect between the O- and N-containing groups of graphene quantum dots for the structural design of CAs with both high relaxivity and low toxicity was obtained. The nitrogen-doped graphene quantum dots (NGQDs) with an O/N ratio of 0.4 were selected to construct high-relaxivity magnetic resonance imaging (MRI)-fluorescence dual-mode CAs. The coordination stability of Gd3+ can be increased through the synergetic coordination of O- and N-containing groups. The synergetic coordination of O- and N-containing groups can result in the short residency time of the water ligand and achieve high relaxivity. The resulting CAs (called NGQDs-Gd) exhibit a high relaxivity of 32.04 mM-1 s-1 at 114 µT. Meanwhile, the NGQDs-Gd also emit red fluorescence (614 nm), which can enable the MRI-fluorescence dual-mode imaging as the CAs. Moreover, the bio-toxicity and tumor-targeting behavior of NGQDs-Gd were also evaluated, and NGQDs-Gd show potential in MRI-fluorescence imaging in vivo.

CT-based skeletal muscle loss for predicting poor survival in patients with hepatocellular carcinoma experiencing curative hepatectomy plus adjuvant transarterial chemoembolization: a preliminary retrospective study.

BACKGROUND: To evaluate the prognostic value of skeletal muscle index (SMI) and its change in patients with hepatocellular carcinoma (HCC) experiencing curative hepatectomy plus adjuvant transarterial chemoembolization (TACE). MATERIALS AND METHODS: A total of 62 patients with HCC who underwent adjuvant TACE after curative hepatectomy were analysed retrospectively. Skeletal muscle area at the third lumbar level was quantitated using computed tomography images and was normalized for height squared to obtain skeletal muscle index (SMI). Skeletal muscle loss (SML) over 6 months was computed with two SMIs before and after hepatectomy plus adjuvant TACE. Correlation analyses were preformed to investigate factors associated with SML. The curves of cause-specific survival (CSS) were analysed using the Kaplan-Meier method. A Cox proportional hazards model was used to assess prognostic factors. RESULTS: Low SMI was diagnosed in 23(37.1%) patients preoperatively. The median SML standardized by 6 months was - 1.6% in the entire cohort. Liver cirrhosis and microvascular invasion correlated negatively with SML, respectively (r = - 0.320, P = 0.002; r = - 0.243, P = 0.021). Higher SML (< - 2.42%) predicted a significant reduction in CSS (P = 0.001), whereas low SMI did not(P = 0.687). Following the multivariate analysis for CSS, AFP > 400 ng/ml (HR, 5.643; 95%CI, 3.608-17.833; P < 0.001) and SML < - 2.42%(HR, 6.586; 95%CI, 3.610-22.210; P < 0.001) were independent predictors for poor CSS. CONCLUSIONS: Skeletal muscle loss during hepatectomy plus adjuvant TACE was remarkable. Higher SML was an independent risk factor for CSS in patients with HCC, especially those with liver cirrhosis.

Cytokine storm and targeted therapy in hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome. The central pathogenesis is an explosive cytokine storm characterized by a significant increase in proinflammatory cytokines, including IL-1ß, IL-6, IL-18, IFN-γ, and TNF-α. Meanwhile, negative regulatory factors, such as IL-10 and TGF-ß, are also related to the production of HLH. Exploring the specific mechanism of cytokine storms could provide ideas regarding targeted therapy, which could be helpful for early treatment to reduce the mortality of HLH. Although some research has focused on the advantages of targeted therapies, there is still a lack of a comprehensive discourse. This article attempts to summarize the mechanisms of action of various cytokines and provide a therapeutic overview of the current targeted therapies for HLH.

The endoplasmic reticulum stress-mediated unfolded protein response protects against infection of goat endometrial epithelial cells by Trueperella pyogenes via autophagy.

Trueperella pyogenes is an important bacterial pathogen of a wide range of domestic and wild animals. Autophagy plays a key role in eliminating T. pyogenes in a process that is dependent on mechanistic target of rapamycin (mTOR). The endoplasmic reticulum (ER) stress response also is critical for autophagy regulation. However, the relationship between ER stress and T. pyogenes is uncharacterized and the intracellular survival mechanisms of T. pyogenes have not been investigated adequately. In this study, we show that T. pyogenes invades goat endometrial epithelial cells (gEECs). Meanwhile, we observed that GRP78 was upregulated significantly, and that unfolded protein response (UPR) also were activated after infection. Additionally, treatment with activators and inhibitors of ER stress downregulated and upregulated, respectively, intracellular survival of T. pyogenes. Blocking the three arms of the UPR pathway separately enhanced T. pyogenes survival and inflammatory reaction to different levels. We also show that LC3-labeled autophagosomes formed around the invading T. pyogenes and that autolysosome-like vesicles were visible in gEECs using transmission electron microscopy. Moreover, tunicamycin did not inhibit the intracellular survival of T. pyogenes under conditions in which autophagy was blocked. Finally, severe challenge with T. pyogenes induced host cell apoptosis which also may indicate a role for ER stress in the infection response. In summary, we demonstrate here that ER stress and UPR are novel modulators of autophagy that inhibit T. pyogenes intracellular survival in gEECs, which has the potential to be developed as an effective therapeutic target in T. pyogenes infectious disease.

Lipid Droplets, the Central Hub Integrating Cell Metabolism and the Immune System.

Lipid droplets (LDs) are commonly found in various biological cells and are organelles related to cell metabolism. LDs, the number and size of which are heterogeneous across cell type, are primarily composed of polar lipids and proteins on the surface with neutral lipids in the core. Neutral lipids stored in LDs can be degraded by lipolysis and lipophagocytosis, which are regulated by various proteins. The process of LD formation can be summarized in four steps. In addition to energy production, LDs play an extremely pivotal role in a variety of physiological and pathological processes, such as endoplasmic reticulum stress, lipid toxicity, storage of fat-soluble vitamins, regulation of oxidative stress, and reprogramming of cell metabolism. Interestingly, LDs, the hub of integration between metabolism and the immune system, are involved in antitumor immunity, anti-infective immunity (viruses, bacteria, parasites, etc.) and some metabolic immune diseases. Herein, we summarize the role of LDs in several major immune cells as elucidated in recent years, including T cells, dendritic cells, macrophages, mast cells, and neutrophils. Additionally, we analyze the role of the interaction between LDs and immune cells in two typical metabolic immune diseases: atherosclerosis and Mycobacterium tuberculosis infection.

Modified Microcoil for Preoperative Localization of Solitary Pulmonary Nodules: A Prospective, Single-Arm, Multicenter Clinical Study.

PURPOSE: To evaluate the efficacy and safety of placement of a modified microcoil for precise preoperative localization of solitary pulmonary nodules (SPNs) before video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: This prospective, single-arm, multicenter study included patients who underwent computed tomography (CT)-guided modified microcoil insertion prior to SPN resection by VATS between January 2018 and June 2018. The patient demographics, nodule characteristics, and histopathologic findings were recorded. The primary endpoints included efficacy and safety. RESULTS: A total of 96 patients (41 men and 55 women; mean age, 59.3 years ± 8.9) with 96 SPNs were eligible for enrolment in the study. The mean maximal transverse diameter of the nodules was 10.3 mm ± 5.2 (range, 8-20 mm). The mean time between CT-guided microcoil insertion and the start of the surgical procedure was 14.6 hours (range, 12-24 hours). The duration of the preoperative CT-guided microcoil localization procedure was 29 minutes ± 9 (range, 10-35 minutes), and the intraoperative fluoroscopy time was 0.7 minutes ± 0.7 (range, 0.5-3 minutes). The clinical success rate was 96.9% (93/96), and all nodules were successfully resected using VATS. One patient experienced asymptomatic pneumothorax, but there were no cases of pulmonary hemorrhage. CONCLUSIONS: SPN localization with the modified microcoil is feasible and safe. The modified microcoil can facilitate the thoracoscopic resection of SPNs.

Graphene Quantum Dots with Pyrrole N and Pyridine N: Superior Reactive Oxygen Species Generation Efficiency for Metal-Free Sonodynamic Tumor Therapy.

Those responsible for the development of sonosensitizers are faced with a dilemma between high sonosensitization efficacy and good biosecurity that limited the development of sonodynamic therapy (SDT). Herein, inspired by the intriguing therapeutic features of SDT and the potential catalytic activity of graphene quantum dots, the potential of N-doped graphene quantum dots (N-GQDs) to act as a sonosensitizer is demonstrated. The superior sonosensitization effect of N-GQDs is believed to be three to five times higher than that of traditional sonosensitizers (such as porphyrin, porphyrin Mn, porphyrin Zn, TiO2 , etc.). More importantly, the sonochemical mechanism of N-GQDs is revealed. Pyrrole N and pyridine N are believed to form catalytic centers in sonochemical processing of N-GQDs. This knowledge is important from the perspective of understanding the structure-dependent SDT enhancement of carbon nanostructure. Moreover, N-GQDs modified by folic acid (FA-N-GQDs) show a high marker rate for tumor cells (greater than 96%). Both in vitro and in vivo therapeutic results have exhibited high tumor inhibition efficiency (greater than 90%) of FA-N-GQDs as sonosensitizers while the oxidative stress response of tumor cells is activated through the PEX pathway and induced apoptosis via the p53 pathway.

Imaging Cellular Aerobic Glycolysis using Carbon Dots for Early Warning of Tumorigenesis.

Early warning of tumor formation is crucial for the classification, treatment, and prognosis of tumor patients. Here, a new strategy is reported, aimed at realizing this goal based on imaging aerobic glycolysis processes using nitrogen-doped carbon dots (N-CDs) as fluorescent probes. The intensity of the photoluminescence emitted by the N-CDs is specifically enhanced by nicotinamide adenine dinucleotide (NAD+ , oxidized) in the physiological environment. The N-CDs allow a few (five to ten) abnormal cells in spontaneous hepatocellular carcinoma models to be identified before the in situ development of tumor tissue. The N-CD probes can also distinguish tumor cells from normal cells and be used to evaluate their proliferation activity (with a specificity of up to 96.15% in 13 types of tumor cells and 90.90% in orthotopic xenograft models). The N-CDs are successfully used to monitor the invasion of tumor cells into neighboring tissues and body fluids in 49 clinical samples (with a sensitivity up to 79.31%). These included three vitreous body samples (from patients with retinoblastoma), 42 urine samples (22 patients clinically diagnosed with urothelium carcinoma and 20 healthy persons), and four hydrothorax samples (from patients with metastatic lesions).

Enhancing the magnetic relaxivity of MRI contrast agents via the localized superacid microenvironment of graphene quantum dots.

The design of contrast agents (CAs) with high magnetic relaxivities is a key issue in the field of magnetic resonance imaging (MRI). The traditional strategy employed is aimed at optimizing the structural design of the magnetic atoms in the CA. However, it is difficult to obtain an agent with magnetic relaxivity over 100 mM-1 s-1 using this approach. In this work, we demonstrate that modulation of the localized superacid microenvironment of certain CAs (Gd3+ loaded polyethylene glycol modified graphene oxide quantum dots or 'GPG' for short) can effectively enhance the longitudinal magnetic relaxivities (r1) by accelerating proton exchange. r1 values of a series of GPGs are significantly increased by 20-30 folds compared to commercially available CAs over a wide range of static magnetic field strengths (e.g. 210.9 mM-1 s-1vs. 12.3 mM-1 s-1 at 114 µT, 127.0 mM-1 s-1vs. 4.9 mM-1 s-1 at 7.0 T). GPG aided MRI images is then acquired both in vitro and in vivo with low biotoxicities. Furthermore, folic-acid-modified GPG is demonstrated suitable for MRI-fluorescence dual-modal tumor targeting imaging in animals with more than 98.3% specific cellular uptake rate.

Polarizing Graphene Quantum Dots toward Long-Acting Intracellular Reactive Oxygen Species Evaluation and Tumor Detection.

The evaluation of intracellular reactive oxygen species (ROS) would greatly deepen the understanding of cell metabolism/proliferation and tumor detection. However, current long-acting level tracking techniques for intracellular ROS remain unsuited to practical applications. To solve this problem, we synthesized cyclotriphosphazene-doped graphene quantum dots (C-GQDs) whose quantum yield is highly sensitive to ROS (increased by 400% from 0.12 to 0.63). Electron cloud polarization of oxidized cyclotriphosphazene rings in C-GQDs is confirmed to account for this novel optical property by density functional theory calculations and experimental results. In combination with excellent biological stability, C-GQDs achieve a long-acting evaluation of intracellular ROS level (more than 72 h) with an accuracy of 98.3%. In addition, recognition rates exceeding 90% are demonstrated to be feasible for eight kinds of tumor cell lines cultured with C-GQDs, which can also be expanded to in vivo detection. C-GQDs also show a high recognition rate (82.33%) and sensitivity (79.65%) for tumor cells in blood samples.

Personal exposure to fine particulate matter (PM2.5) of pregnant women during three trimesters in rural Yunnan of China.

Little is known about fine particulate matter (PM2.5) exposure among pregnant women in rural China. This study aims to characterize exposure to PM2.5 among pregnant women in rural China, and investigate potential risk factors of personal exposure to PM2.5. The data were obtained from a birth cohort study that enrolled 606 pregnant women in Xuanwei, a county known for its high rates of lung cancer. The personal exposure to PM2.5 was measured using small portable particulate monitors during each trimester of pregnancy. Participants were interviewed using structured questionnaires that sought information on risk factors of PM2.5 exposure. The daily exposure to PM2.5 among the pregnant women ranged from 19.68 to 97.08 µg/m3 (median = 26.08). Exposure to PM2.5 was higher in winter and autumn than other seasons (p < 0.05); higher during the day than during the night (p < 0.001); and greater during cooking hours than during the rest of the day (p < 0.001). Using a mixed effects model, domestic solid fuel for cooking (ß = 1.75, p < 0.001), winter and autumn (ß = 2.96, p < 0.001), cooking ≥ once per day (ß = 1.58, p < 0.05), heating with coal (ß = 1.69, p < 0.001), secondhand smoke exposure (ß = 1.59, p < 0.001) and township 1(ß = 2.39, p < 0.001) were identified as risk factors for personal exposure to PM2.5 of pregnant women throughout pregnancy. Indirect effects of season and township factors on personal PM2.5 exposure were mediated by heating, cooking and domestic fuel using. In conclusion, PM2.5 levels in Xuanwei exceeded WHO guidelines. Seasonal and township factors and individual behaviors like domestic solid fuel using for cooking, heating with coal and secondhand smoke exposure are associated with higher personal PM2.5 exposure among pregnant women in rural China.

Photocatalytic Polymerization from Amino Acid to Protein by Carbon Dots at Room Temperature.

The chemical origins of life have been widely accepted at the present stage. However, the idea that amino acids further react to produce peptides and proteins remains an unsatisfactory explanation, because producing polypeptides via spontaneous reaction of amino acids in solution is extremely difficult. It is also necessary to further answer whether amino acids can form longer peptide chains as well as specific chiral structures and so on under this same reaction mechanism. Carbon dots (CDs) have been intensively researched over the past years due to their unique chemical and physical properties. Here, we demonstrate the photocatalytic polymerization of amino acids into polypeptides and proteins using CDs as a photocatalyst, in which the synthetic conditions required are only room temperature (or as low as -20 °C) and aqueous conditions along with light irradiation, which are very mild and easy to satisfy. We even obtain a protein with tertiary structures, namely an artificial insulin with the biological function to reduce the blood sugar of the laboratory mice. The innovation of using CDs to initiate amino acids to condense into polypeptides is based on strong adsorption (e.g., hydrogen bonding), the acidity of the -OH surface functional groups, and the photogenerated protons/holes, which are the fundamental factors for polypeptide or even ternary structure protein formation by means of capturing and condensing the amino acids as well as forming the S-S bonds.

Discrepancy between Self-Reported and Urine Cotinine-Verified Environmental Tobacco Smoke Exposure among Rural Pregnant Women in China.

Prenatal exposure to environmental tobacco smoke (ETS) is the most modifiable risk factor associated with adverse child-health outcomes. However, few longitudinal studies are implemented to compare the rates of discrepancy between self-reported (SR) and urinary cotinine (UC)-verified ETS exposure during the three trimesters of pregnancy, especially in rural areas. The objectives of this study were to assess the discrepancy between SR and UC-verified ETS exposure among rural women employing three measures throughout pregnancy, and to explore predictors related to these differences. This study used a prospective prenatal cohort consisting of 420 pregnant women whose ETS exposure was entirely evaluated by both SR and UC verification across three trimesters of pregnancy. Environmental tobacco exposure was assessed via SR verification, and was validated using the limit of detection for UC. The discrepancy rates were determined for each trimester. Multivariate logistic regression was used to assess the predictors associated with these differences. The discrepancy rates between SR and UC verification were 25.2%, 17.1%, and 20.5% (first, second, and third trimester, respectively). The highest inconsistency occurred in the first trimester. After adjusting for confounding factors, the following variables were found to have statistically significant associations with the discrepancy rate between SR and UC-verified ETS exposure: the number of smokers in the family and household income for all three trimesters, township site for the second and third trimester, and gravidity for the last trimester. The SR rate of ETS exposure among rural pregnant women is underreported, while the UC-verified rate is higher. More smokers in the family and gravidity may increase the risk of ETS exposure for pregnant women. Biochemical validation is warranted throughout pregnancy for the adoption of home-smoking bans and the promotion of community-based smoke-free programs.

[Increased expressions of programmed death 1 (PD-1) and its ligands in peripheral CD3(+) T cells and CD19(+) B cells in patients with hepatocellular carcinoma].

Objective To investigate the changes of programmed death 1 (PD-1) and ligands, as well as interferon-γ (IFN-γ) in peripheral blood mononuclear cells (PBMCs) of patients with hepatocellular carcinoma (HCC). Methods The peripheral blood was collected from 15 early HCC patients, 13 progressive HCC patients and 12 healthy volunteers. PBMCs was isolated from the peripheral blood. The expressions of PD-1, PD-L1 and PD-L2 in PBMCs were detected by flow cytometry; the serum level of IFN-γ was determined by ELISA; the correlation of PD-1 and IFN-γ was analyzed with Pearson's correlation and One-way ANOVA. Results The expression levels of PD-1, PD-L1 and PD-L2 in CD3(+) T cells and CD19(+) B cells and serum IFN-γ level in progressive HCC patients were significantly higher than those in the healthy group and early HCC patients. The expression levels of PD-1, PD-L1 and PD-L2 in the CD3(+) T cells and CD19(+) B cells of the HCC patients were positively correlated with IFN-γ. Conclusion The expression levels of PD-1, PD-L1 and PD-L2 increase in the PBMCs of HCC patients; PD-1 and PD-L1 are correlated with IFN-γ level.

A new approach to accelerate orthodontic tooth movement in women: Orthodontic force application after ovulation.

Tooth movement occurs as a consequence of periodontal tissue remodeling. The goal of every orthodontist is to investigate better approaches to accelerate tooth movement. Estrogen, by binding with its receptors in periodontal tissue, regulates the remodeling of alveolar bones, promotes bone formation, and inhibits bone resorption. Estrogen secretion in vivo is characterized by a nearly lunar rhythm. The estrogen expression level is low during menstruation and the luteal phase, and reaches the highest at 1-2days before ovulation. Estrogen physiological fluctuations can cause physiological fluctuations in the serum markers of bone turnover. Therefore, orthodontic therapy should be planned according to the menstrual cycle since tooth movement, under the application of force, is faster during low estrogen levels. In this paper, we propose a hypothesis that application of orthodontic force after each ovulation may promote tooth movement, thereby shortening the course of orthodontic treatment.

Image-based guidance for minimally invasive surgical atrial fibrillation ablation.

PURPOSE: Atrial fibrillation (AF) is the most common arrhythmia and results in an increased risk of ischaemic stroke. Recently, a European consortium has developed a new ablation device for minimally invasive surgical AF treatment. The device is controlled by a medical robot. Due to the minimal invasive usage, surgery using the new device needs appropriate navigation support. In this paper, we describe an image-based navigation application to guide the new device intraoperatively. METHODS: The navigation procedure is based on intraoperative ultrasound. Variations in the position of the ablation device are transferred from the software controlling the robot to the navigation system. Due to the flexibility of the ablation device, a deformation model predicts the behaviour during repositioning. Ablation lines are interactively planned. Actually burned ablation lines are visualized during surgery. Several in vitro and ex vivo experimental set-ups were built up to test the feasibility. RESULTS: The navigation workflow was implemented into navigation software using well-known open-source software toolkits. The navigation system has been integrated and tested successfully within the overall system. The ablation device could be localized on in vitro and ex vivo ultrasound images. CONCLUSION: The performed trials proved the applicability of the navigation procedure. More in vivo tests are currently being performed to make the new device and the described navigation procedure ready for clinical use.