The Relationship between Angiotensin-Neprilysin Treatment, Echocardiographic Parameters, and NT-proBNP Levels in HFpEF Patients with Acute Decompensated Heart Failure.

Background: The valsartan-sacubitril therapy improved the outcomes of patients with acute decompensated heart failure (ADHF) of a reduced ejection fraction (HFrEF). In ADHF patients with preserved ejection fraction (HFpEF), it is not yet clear whether the same treatment regimen may be safely used to treat ADHF. Methods: For this study, HFpEF patients hospitalized due to ADHF were enrolled. Following hemodynamic stabilization, patients were randomized into two groups that were treated with enalapril or sacubitril-valsartan. In this trial, the primary efficacy outcomes were changes in echocardiographic parameters and NT-proBNP levels from baseline to 8 weeks treatment. Results: ARNI treatment resulted in a significant decrease in NT-proBNP levels and an increase in LVEF in patients with HFpEF. However, HFpEF patients that underwent ARNI treatment achieved better outcomes than did patients that underwent ACEI treatment. Conclusion: Sacubitril-valsartan treatment, which lowered NT-proBNP levels and improved cardiac function, was more effective in HFpEF patients with acute decompensated heart failure than enalapril.

Alterations in Immune Response Profile of Tumor-Draining Lymph Nodes after High-Intensity Focused Ultrasound Ablation of Breast Cancer Patients.

Previous studies have revealed that high-intensity focused ultrasound (HIFU) ablation can trigger an antitumor immune response. The aim of this study was to investigate immune response in tumor-draining lymph nodes (TDLNs) after HIFU treatment. Forty-eight female patients with biopsy-confirmed breast cancer were divided into a control group and an HIFU group. In the control group, 25 patients underwent modified radical mastectomy, but 23 patients in the HIFU group received HIFU ablation of primary cancer, followed by the same operation. Using HE and immunohistochemical staining, the immunologic reactivity pattern and immune cell profile were assessed in paraffin-embedded axillary lymph nodes (ALNs) in all patients. The results showed that ALNs presented more evident immune reactions in the HIFU group than in the control group (100% vs. 64%). Among the ALNs, 78.3% had mixed cellular and humoral immune response, whereas 36% in the control group showed cellular immune response. The numbers of CD3+, CD4+, NK cell, and activated CTLs with Fas ligand+, granzyme+ and perforin+ expression were significantly higher in the ALNs in the HIFU group. It was concluded that HIFU could stimulate potent immune response and significantly increase T cell, activated CTLs and NK cell populations in the TDLNs of breast cancer.

Impact of COVID-19 Pandemic on Mechanical Reperfusion in ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Multicenter Retrospective Study From a Non-epicenter Region.

Objective: The COVID-19 pandemic placed heavy burdens on emergency care and posed severe challenges to ST-segment-elevation myocardial infarction (STEMI) treatment. This study aimed to investigate the impact of COVID-19 pandemic on mechanical reperfusion characteristics in STEMI undergoing primary percutaneous coronary intervention (PPCI) in a non-epicenter region. Methods: STEMI cases undergoing PPCI from January 23 to March 29 between 2019 and 2020 were retrospectively compared. PPCI parameters mainly included total ischemic time (TIT), the period from symptom onset to first medical contact (S-to-FMC), the period from FMC to wire (FMC-to-W) and the period from door to wire (D-to-W). Furthermore, the association of COVID-19 pandemic with delayed PPCI risk was further analyzed. Results: A total of 14 PPCI centers were included, with 100 and 220 STEMI cases undergoing PPCI in 2020 and 2019, respectively. As compared to 2019, significant prolongations occurred in reperfusion procedures (P < 0.001) including TIT (420 vs. 264 min), S-to-FMC (5 vs. 3 h), FMC-to-W (113 vs. 95 min) and D-to-W (83 vs. 65 min). Consistently, delayed reperfusion surged including TIT ≥ 12 h (22.0 vs.3.6%), FMC-to-W ≥ 120 min (34.0 vs. 6.8%) and D-to-W ≥ 90 min (19.0 vs. 4.1%). During the pandemic, the patients with FMC-to-W ≥ 120 min had longer durations in FMC to ECG completed (6 vs. 5 min, P = 0.007), FMC to DAPT (24 vs. 21 min, P = 0.001), catheter arrival to wire (54 vs. 43 min, P < 0.001) and D-to-W (91 vs. 78 min, P < 0.001). The pandemic was significantly associated with high risk of delayed PPCI (OR = 7.040, 95% CI 3.610-13.729, P < 0.001). Conclusions: Even in a non-epicenter region, the risk of delayed STEMI reperfusion significantly increased due to cumulative impact of multiple procedures prolongation.

Spatial variation characteristics of vegetation phenology and its influencing factors in the subtropical monsoon climate region of southern China.

Understanding the response mechanism of ecosystems to climate change and human disturbance can be improved by analyzing the spatial patterns of vegetation phenology and its influencing factors. Because the diverse phenological patterns are impacted by cloud cover contamination issues in the satellite observations, there are few remote sensing phenological research data in subtropical monsoon climate regions. To better understand the horizontal and vertical changes of vegetation phenology in these regions and how it may be affected by climatic factors and topographical features, we first extracted vegetation phenological information (such as start of growth season (SOS), end of growth season (EOS) and length of growth season (LEN)) from a reconstructed MODIS EVI time-series data. We then used geographic detectors to identify the influencing factors of phenology in different elevation zoning areas. We have found that in the Xiangjiang River Basin: 1) gradual changes in the longitudinal or latitudinal gradient of vegetation phenology were not obvious. Instead of horizontal changes, the variation pattern of phenology was similar to the striped river network of the Xiangjiang River. Earlier SOS mainly appeared in the areas far away from the river; later SOS appeared in the midstream and downstream reaches.2) Elevation played an important role in the regional differentiation of phenology. Boundaries at elevations of 320 m and 520 m distinctly separated the region into plain, hilly, and mountain vegetation phenological characteristics. 3) The impacts of climatic factors were quite different in the three vertical zoning areas. Precipitation was the most crucial factor affecting SOS both in plain and mountain areas. There was no significant factor affecting EOS in the plain area, but temperature had an essential effect on EOS in the mountain area. The hilly areas had a concentrated growth period with no significant factors affecting phenology. These findings highlight the importance of elevation in phenology at a watershed scale, enhance our understanding of the impact of climate changes on subtropical ecosystems, and provide a reference for further land-use change monitoring.

Characteristics and sources of atmospheric pollutants in typical inland cities in arid regions of central Asia: A case study of Urumqi city.

The arid zone of central Asia secluded inland and has the typical features of the atmosphere. Human activities have had a significant impact on the air quality in this region. Urumqi is a key city in the core area of the Silk Road and an important economic center in Northwestern China. The urban environment is playing an increasingly important role in regional development. To study the characteristics and influencing factors of the main atmospheric pollutants in Urumqi, this study selected Urumqi's daily air quality index (AQI) data and observation data of six major pollutants including fine particulate matter (PM2.5), breathable particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3_8h) from 2014 to 2018 in conjunction with meteorological data to use a backward trajectory analysis method to study the main characteristics of atmospheric pollutants and their sources in Urumqi from 2014 to 2018. The results showed that: (1) From 2014 to 2018, the annual average of PM2.5, PM10, SO2, NO2 and CO concentrations showed a downward trend, and O3_8h concentrations first increased, then decreased, and then increased, reaching the highest value in 2018 (82.15 µg·m-3); The seasonal changes of PM2.5, PM10, SO2, NO2 and CO concentrations were characterized by low values in summer and fall seasons and high values in winter and spring seasons. The concentration of O3_8h, however, was in the opposite trend, showing the high values in summer and fall seasons, and low values in winter and spring seasons. From 2014 to 2018, with the exception of O3_8h, the concentration changes of the other five major air pollutants were high in December, January, and February, and low in May, June, and July; the daily changes showed a "U-shaped" change during the year. The high-value areas of the "U-shaped" mode formed around the 50th day and the 350th day. (2) The high-value area of AQI was from the end of fall (November) to the beginning of the following spring (March), and the low-value area was from April to October. It showed a U-shaped change trend during the year and the value was mainly distributed between 50 and 100. (3) The concentrations of major air pollutants in Urumqi were significantly negatively correlated with precipitation, temperature, and humidity (P<0.01), and had the highest correlation coefficients with temperature. (4) Based on the above analysis results, this study analyzed two severe pollution events from late November to early December. Analysis showed that the PM2.5/PM10 ratio in two events remained at about 0.1 when the pollution occurred, but was higher before and after the pollution (up to 1.46). It was shown that the pollution was a simple sandstorm process. Backward trajectory analysis clustered the airflow trajectories reaching Urumqi into 4 categories, and the trajectories from central Asia contributed the maximum values of average PM2.5 and PM10 concentrations.

Effects of a High Dose of the Contrast Medium Iodixanol on Renal Function in Patients Following Percutaneous Coronary Intervention.

Iodixanol is associated with lower rates of contrast-induced acute kidney injury (CI-AKI). However, the effects of high volumes of iodixanol on renal function after percutaneous coronary intervention (PCI) have not been fully elucidated. This study evaluates the effects of high-dose (>300 mL) iodixanol on renal function within 72 hours of PCI. We retrospectively reviewed 676 consecutive patients who received high-dose (>300 mL) iodixanol during PCI between October 2015 and December 2017 in 4 centers. Logistic regression analysis was used to identify significant independent predictors for CI-AKI. The incidence of CI-AKI was 3.5% (23/651). In patients administered 300 to 500 mL and >500 mL iodixanol, the incidence of CI-AKI was 3.9% and 1.7%, respectively. In patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, the incidence of CI-AKI was 2.6%. In high-risk and very high-risk patients, stratified by the Mehran risk score, the incidence of CI-AKI was 3.3% and 4.3%, respectively. In patients received high-dose iodixanol (>300 mL), logistic regression analysis demonstrated that female sex, chronic kidney disease, and eGFR were independent risk factors for CI-AKI, but contrast volume was not. The administration of high (300-500 mL) and very high (>500 mL) dose of iodixanol is associated with low rates of CI-AKI.

DPP-4 Inhibitor Linagliptin Ameliorates Oxidized LDL-Induced THP-1 Macrophage Foam Cell Formation and Inflammation.

INTRODUCTION: Atherosclerosis is one of the major causes of cardiovascular diseases. Lipid uptake and accumulation in macrophages play a major role in atherosclerotic plaque formation from its initiation to advanced atheroma formation. The dipeptidyl peptidase-4 (DPP-4) inhibitor Linagliptin is commonly used to lower blood glucose in type 2 diabetes patients. Recent studies report that Linagliptin has cardiovascular protective and anti-inflammatory effects. METHODS: THP-1 macrophage cells were treated with 100 nM PMA for 72 hour to induce foam cell formation. The differentiated cells were exposed to 100 µg/mL ox-LDL in the presence or absence of the DPP-4 inhibitor Linagliptin. The expression levels of DPP-4 and inflammatory cytokines were detected by RT-PCR, ELISA, and Western blot experiments. The cellular ROS level was measured by staining the cells with the fluorescent probe DCFH-DA. The separation of lipoprotein fractions was achieved by high-performance liquid chromatography (HPLC). The cells were labeled with fluorescent-labeled cholesterol to measure cholesterol efflux, and lipid droplets were revealed by Nile red staining. RESULTS: The presence of Linagliptin significantly reduced ox-LDL-induced cytokine production (IL-1ß and IL-6) and ROS production. Linagliptin ameliorated ox-LDL-induced lipid accumulation and impaired cholesterol efflux in macrophages. Mechanistically, this study showed that Linagliptin mitigated ox-LDL-induced expression of the scavenger receptors CD36 and LOX-1, but not SRA. Furthermore, Linagliptin increased the expression of the cholesterol transporter ABCG1, but not ABCA1. CONCLUSION: Linagliptin possesses a potent inhibitory effect on THP-1 macrophage-derived foam cell formation in response to ox-LDL. This effect could be mediated through a decrease in the expression of CD36 and LOX-1 on macrophages and an increase in the expression of the cholesterol transporter ABCG1. This study indicates that the DPP-4 inhibitor Linagliptin plays a critical role in preventing foam cell formation in vitro. However, future research using an atherosclerotic animal model is necessary to determine its effectiveness and to prove its potential implication in the prevention and treatment of atherosclerosis.

The diagnostic value of circulating microRNAs as biomarkers for coronary artery disease: A meta­analysis.

OBJECTIVE: In recent years, research on microRNAs (miRNAs) associated with coronary artery disease (CAD) has attracted considerable attention. However, findings of these studies on the validity of circulating miRNAs in CAD diagnosis are controversial. A meta-analysis was therefore conducted to determine the potential value of miRNAs as biomarkers in CAD diagnosis. METHODS: Relevant documents on miRNAs expression levels in the diagnosis of CAD were searched and collected from Pubmed, Embase, and Web of Science. They were collected from the time of inception of the database till January 31, 2020. A meta-analysis was conducted using Stata14.0 software. Forest maps were studied and a comprehensive evaluation of the diagnostic value of the expression levels of mRNAs in CAD was conducted using statistical indicators such as the summary receiver operating characteristic curve. RESULTS: Overall, 14 studies were included, with 38 data sets, involving 29 miRNAs with 846 cases and 898 controls. The meta-analysis revealed that the average sensitivity and specificity of miRNAs for CAD diagnosis were 0.80 (0.75-0.84) and 0.78 (0.75-0.81), respectively. The positive likelihood, negative likelihood, and diagnostic odds ratios were 3.7 (3.1-4.4), 0.26 (0.21-0.33), and 14 (10-21), respectively, and the area under the curve was 0.85 (0.82-0.88). Subgroup analysis revealed that the accuracy in the Asian population was higher than that in the non-Asian population. Multiple miRNAs may be more diagnostically accurate than single miRNAs. MiRNAs in whole blood were more accurate than those in plasma, serum, and peripheral blood mononuclear cells. The diagnostic performance of the quantitative real-time polymerase chain reaction group was better than that of the qPCR group. CONCLUSION: According to our study, miRNAs may be a new, non-invasive diagnostic tool for the diagnosis of CAD. As a screening tool in clinical practice, it has potential diagnostic value and is worthy of clinical promotion. Considering the number and quality of the studies included in this meta-analysis, the above conclusion requires more quality research to verify it.

Correction: Climatic and topographic variables control soil nitrogen, phosphorus, and nitrogen: Phosphorus ratios in a Picea schrenkiana forest of the Tianshan Mountains.

[This corrects the article DOI: 10.1371/journal.pone.0204130.].

Climatic and topographic variables control soil nitrogen, phosphorus, and nitrogen: Phosphorus ratios in a Picea schrenkiana forest of the Tianshan Mountains.

Knowledge about soil nitrogen (N) and phosphorus (P) concentrations, stocks, and stoichiometric ratios is crucial for understanding the biogeochemical cycles and ecosystem function in arid mountainous forests. However, the corresponding information is scarce, particularly in arid mountainous forests. To fill this gap, we investigated the depth and elevational patterns of the soil N and P concentrations and the N: P ratios in a Picea schrenkiana forest using data from soil profiles collected during 2012-2017. Our results showed that the soil N and P concentrations and the N: P ratios varied from 0.15 g kg-1 to 0.56 g kg-1 (average of 0.31 g kg-1), from 0.09 g kg-1 to 0.16 g kg-1 (average of 0.12 g kg-1), and from 2.42 g kg-1 to 4.36 g kg-1 (average of 3.42 g kg-1), respectively; additionally, values significantly and linearly decreased with soil depth. We did not observe a significant variation in the soil N and P concentrations and the N: P ratios with the elevational gradient. In contrast, our results revealed that the mean annual temperature and mean annual precipitation exhibited a more significant influence on the soil N and P concentrations and the N: P ratios than did elevation. This finding indicated that climatic variables might have a more direct impact on soil nutrient status than elevation. The observed relationship among the soil N and P concentrations and the N: P ratios demonstrated that the soil N was closely coupled with the soil P in the P. schrenkiana forest.

Nowhere to invade: Rumex crispus and Typha latifolia projected to disappear under future climate scenarios.

Future climate change has been predicted to affect the potential distribution of plant species. However, only few studies have addressed how invasive species may respond to future climate change despite the known effects of plant species invasion on nutrient cycles, ecosystem functions, and agricultural yields. In this study, we predicted the potential distributions of two invasive species, Rumex crispus and Typha latifolia, under current and future (2050) climatic conditions. Future climate scenarios considered in our study include A1B, A2, A2A, B1, and B2A. We found that these two species will lose their habitat under the A1B, A2, A2A, and B1 scenarios. Their distributions will be maintained under future climatic conditions related to B2A scenarios, but the total area will be less than 10% of that under the current climatic condition. We also investigated variations of the most influential climatic variables that are likely to cause habitat loss of the two species. Our results demonstrate that rising mean annual temperature, variations of the coldest quarter, and precipitation of the coldest quarter are the main factors contributing to habitat loss of R. crispus. For T. latifolia, the main factors are rising mean annual temperature, variations in temperature of the coldest quarter, mean annual precipitation, and precipitation of the coldest quarter. These results demonstrate that the warmer and wetter climatic conditions of the coldest season (or month) will be mainly responsible for habitat loss of R. crispus and T. latifolia in the future. We also discuss uncertainties related to our study (and similar studies) and suggest that particular attention should be directed toward the manner in which invasive species cope with rapid climate changes because evolutionary change can be rapid for species that invade new areas.

[Cu30I16(mtpmt)12(µ(10-S4))]: an unusual 30-membered copper(I) cluster derived from the C-S bond cleavage and its use in heterogeneous catalysis.

The Cu(I)-mediated C-S bond cleavage of 5-methyl-4-(p-tolyl)pyrimidine-2-thiol (mtpmtH) gave one 30-nuclear cluster [Cu30I16(mtpmt)12(µ10-S4)], one polymeric complex [(bmtpms)Cu-(µ-I)]n and one tetranuclear complex [(bmptmds){Cu(µ-I)}2]2; the 30-nuclear cluster displayed excellent catalytic performances in the coupling reactions of N-heterocycles and arylboronic acids and could be recycled and reused.

[Water storage capacity of qinghai spruce (Picea crassifolia) forest canopy in Qilian Mountains].

By the methods of direct measurement and regression analysis, this paper estimated the water storage capacity of Picea crassifolia forest canopy in Guantan in Qilianshan Mountains, based on the observed throughfall and the laboratory experimental data about the water storage capacity of various canopy components in 2008. Due to the impacts of various factors, differences existed in the canopy water storage capacity estimated by the two methods. The regression analysis was mainly impacted by the measurement approaches of the throughfall, the maximum water storage capacity estimated being 0.69 mm, whereas the direct measurement was mainly impacted by tree height, diameter at breast height, plant density, and leaf area index, with the estimated maximum water storage capacity being 0.77 mm. The direct measurement showed that the maximum water storage capacity per unit area of the canopy components of the forest was in the order of barks (0.31 mm) > branches (0.28 mm) > leaves (0.08 mm).

[Spatial distribution characteristics of the biomass and carbon storage of Qinghai spruce (Picea crassifolia) forests in Qilian Mountains].

This paper estimated the biomass and carbon storage and their spatial distributions of Qinghai spruce (Picea crassifolia) forests in Qilian Mountains, based on the field investigation, forest map, and meteorological data, and with the help of GIS technology. In 2008, the biomass of the forests was averagely 209.24 t x hm(-2), with a total biomass of 3.4 x 10(7) t. Due to the difference of water and thermal condition, there existed great differences in the biomass of Qinghai spruce within the Mountains. The biomass increased by 3.12 t x hm(-2) with increasing 1 degrees longitude and decreased by 3.8 t x hm(-2) with increasing 1 degrees latitude, and decreased by 0.05 t x hm(-2) with the elevation increasing 100 m. The carbon density of the forests ranged from 70.4 to 131.1 t x hm(-2), averagely 109.8 t x hm(-2), and the average carbon density was 83.8 t x hm(-2) for the young forest, 109.6 t x hm(-2) for the middle age forest, 122 t x hm(-2) for the near-mature forest, 124.2 t x hm(-2) for the mature forest, and 117.1 t x hm(-2) for the over-mature forest. The total carbon storage of Qinghai spruce forests in the study area was 1.8 x 10(7) t.

[Spatial distribution of Tamarix ramosissima aboveground biomass and water consumption in the lower reaches of Heihe River, Northwest China].

Based on the field observation on the Tamarix ramosissima populations in the lower reaches of Heihe River, the relationship models between the aboveground biomass of T. ramosissima and its morphological features (basal diameter, height, and canopy perimeter) were built. In the mean time, the land use/cover of the study area was classified by the decision tree classification with high resolution image (QuickBird), the distribution of T. ramosissima was extracted from classification map, and the morphological feature (canopy perimeter) of T. ramosissima was calculated with ArcGIS 9.2. On the bases of these, the spatial distribution of T. ramosissima aboveground biomass in the study area was estimated. Finally, the spatial distribution of the water consumption of T. ramosissima in the study area was calculated by the transpiration coefficient (300) and the aboveground biomass. The results showed that the aboveground biomass of T. ramosissima was 69644.7 t, and the biomass per unit area was 0.78 kg x m(-2). Spatially, the habitats along the banks of Heihe River were suitable for T. ramosissima, and thus, this tree species had a high biomass. The total amount of water consumption of T. ramosissima in the study area was 2.1 x 10(7) m3, and the annual mean water consumption of T. ramosissima ranged from 30 mm to 386 mm.

Increased infiltration of activated tumor-infiltrating lymphocytes after high intensity focused ultrasound ablation of human breast cancer.

BACKGROUND: Previous studies have shown that high intensity focused ultrasound (HIFU) ablation can induce a distinct inflammatory reaction with marked infiltration of lymphocytes after direct tumor destruction. In this study, we investigated the status of tumor-infiltrating lymphocytes (TILs) after HIFU ablation of human breast cancer and explored mechanisms that may be involved in HIFU-triggered, antitumor immune response. METHODS: A total of 48 female patients with biopsy-proven breast cancer were divided randomly into 1 of 2 groups: control group (n = 25), in which only modified radical mastectomy was performed, or HIFU group (n = 23), in which HIFU ablation of the primary breast cancer was performed prior to modified radical mastectomy. Using semiquantitative immunohistochemical analysis, tumor-infiltrating T lymphocytes and subsets, B lymphocytes, and natural killer (NK) cells were assessed in all patients. Expression of Fas ligand (FasL), granzyme, and perforin on TILs was also studied in both groups. RESULTS: TILs infiltrated along the margins of the ablated region in all HIFU-treated neoplasms, and the numbers of tumor-infiltrating CD3, CD4, CD8, CD4/CD8, B lymphocytes, and NK cells was increased significantly in the HIFU group. The number of FasL(+), granzyme(+), and perforin(+) TILs was significantly greater in the HIFU group than in the control group. CONCLUSION: HIFU ablation induced marked infiltration of CD3, CD4, CD8, B lymphocytes, and NK cells in the treated breast lesions. The number of FasL(+), granzyme(+), and perforin(+) TILs was significantly increased after HIFU treatment.

Activation of tumor-infiltrating antigen presenting cells by high intensity focused ultrasound ablation of human breast cancer.

Previous studies have shown that high intensity focused ultrasound (HIFU) ablation can trigger activation of host antitumor responses after direct tumor destruction. The goal of this study was to investigate the status and functions of tumor-infiltrating antigen presenting cells (APCs) after HIFU ablation of human breast cancer, and to explore the mechanisms regarding HIFU-enhanced antitumor response. Forty-eight women with biopsy-proven breast cancer were divided randomly into a control group (n = 25) and a HIFU group (n = 23). Patients in the control group received modified radical mastectomy, and those in the HIFU group underwent HIFU ablation of primary breast cancer, followed by modified radical mastectomy within 1-2 weeks. Using immunohistochemical analysis, tumor-infiltrating dendritic cells (DCs), macrophages, B lymphocytes and expression of HLA-DR and costimulatory molecules on DCs and macrophages were assessed in all patients. The results showed that APCs infiltrated along the margins of the ablated regions in all HIFU-treated tumors, and numbers of tumor-infiltrating DCs, macrophages and B lymphocytes increased significantly in the HIFU group. Compared with the values in the control group, the percentage of DCs and macrophages expressing HLA-DR, CD80 and CD86 was significantly greater in the HIFU group. There were statistically significant differences between numbers of S-100(+) HLA-DR(+), S-100(+) CD80(+), S-100(+) CD86(+), CD68(+) HLA-DR(+), CD68(+) CD80(+) and CD68(+) CD86(+) cells in the control and HIFU groups, respectively. It was concluded that HIFU ablation induces significant infiltration of APCs within the residual tumor debris in patients with breast cancer, and most of the tumor-infiltrating DCs and macrophages were activated after HIFU ablation.

Changes in circulating immunosuppressive cytokine levels of cancer patients after high intensity focused ultrasound treatment.

Immunosuppression in a patient with malignant tumor is a major obstacle in cancer treatment. In this study, we investigated changes in the circulating level of all measured immunosuppressive cytokines in patients with malignancy before and after high intensity focused ultrasound (HIFU) treatment. Fifteen patients with solid malignancy were enrolled in this study and an enzyme-linked immunoabsorbent assay (ELISA) method was used to measure serum level of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), transforming growth factor-beta2 (TGF-beta2), interleukin 6 (IL-6) and interleukin 10 (IL-10), respectively before and 1 wk after HIFU treatment. Among them, seven patients had distant metastasis and the remaining eight had no metastasis. All patients received one-session HIFU treatment for primary cancer, including complete ablation in eight patients without metastasis, and partial ablation in seven patients with metastases. The results showed that serum immunosuppressive cytokine levels decreased after HIFU treatment, and there were significant decreases of VEGF, TGF-beta1, and TGF-beta2 before and after HIFU treatment. Compared with the values in the metastatic patients, serum levels of immunosuppressive cytokines were significantly lower in the nonmetastatic patients after HIFU treatment. It is concluded that HIFU can decrease tumor-secreted immunosuppressive cytokine production in addition to its direct tumor destruction. This change may lessen tumor-induced immunosuppression and renew antitumor immunity after HIFU in cancer patients.

Expression of tumor antigens and heat-shock protein 70 in breast cancer cells after high-intensity focused ultrasound ablation.

BACKGROUND: Previous results have shown that high-intensity focused ultrasound (HIFU) ablation can potentially activate a host antitumor immunity. The goal of this study was to investigate whether the tumor antigens expressed on breast cancer cells may be preserved after HIFU treatment, and to explore the potential mechanisms regarding the enhanced antitumor response. METHODS: The primary lesion in 23 patients with biopsy-proven breast cancer were treated with HIFU, then submitted to modified radical mastectomy. By using biotin-streptavidin-peroxidase immunohistochemical technology, a variety of cellular molecules expressed on breast cancer cells, including tumor antigens and heat-shock protein 70 (HSP-70), were stained in all breast specimens. A complete absence of staining was recorded as negative, and immunoreaction of the tumor cells was considered to be positive for antigen expression. RESULTS: Nuclear positivity of breast cancer cells for proliferating cell nuclear antigen, estrogen receptor, and progesterone receptor was detected in 0%, 9%, and 9% of the treated samples, respectively. The positive rate of cytoplasmic staining for matrix metalloproteinase 9, carbohydrate antigen 15-3, vascular endothelial growth factor, transforming growth factors beta1 and beta2, interleukin 6, and interleukin 10 was 0%, 52%, 30%, 57%, 70%, 48%, and 61% in the treated cancer cells, respectively. The positive rate of cellular membrane staining for epithelial membrane antigen, CD44v6, and HSP-70 was 100%, 0%, and 100% in the zones of treated cancer cells, respectively. CONCLUSIONS: After HIFU ablation, some tumor antigens remained in the tumor debris. This could provide a potential antigen source to stimulate antitumor immune response.

Heat fixation of cancer cells ablated with high-intensity-focused ultrasound in patients with breast cancer.

BACKGROUND: High-intensity-focused ultrasound (HIFU) is a noninvasive thermal ablation technique. This study reports the use of histological techniques for the pathological assessment of HIFU effects in patients with breast cancer. METHODS: Twenty-three patients with biopsy-proven breast cancer underwent HIFU treatment for primary breast lesion. Mastectomy was performed on all patients after HIFU. By using histological examinations, the surgical specimens were assessed to explore HIFU effects on breast cancer. RESULTS: Coagulation necrosis of targeted tumors was confirmed by microscopy in 23 patients. Tumor cells presented typical characteristics of coagulation necrosis in the peripheral region of the ablated tumor in all patients. However, in 11 of 23 patients, hematoxylin and eosin staining showed normal cellular structure in the central ablated tumor. By using electronic microscopy and nicotinamide adenine dinucleotide-diaphorase stain, those who had normal-appearing cancer cells were not viable. CONCLUSIONS: HIFU can cause the heat fixation of ablated tumor through thermal effect.