Search

Minimally invasive thermal therapy is a successful alternative treatment to surgery in solid tumors with high complete ablation rates, however, tumor recurrence remains a concern. Central memory CD8 + T cells (T CM ) play important roles in protection from chronic infection and cancer. Here we find, by single-cell RNA analysis of human breast cancer samples, that although the memory phenotype of peripheral CD8 + T cells increases slightly after microwave ablation (MWA), the metabolism of peripheral CD8 + T cells remains unfavorable for memory phenotype. In mouse models, glycolysis inhibition by 2-deoxy-D-glucose (2DG) in combination with MWA results in long-term anti-tumor effect via enhancing differentiation of tumor-specific CD44 hi CD62L + CD8 + T CM cells. Enhancement of CD8 + T CM cell differentiation determined by Stat-1, is dependent on the tumor-draining lymph nodes (TDLN) but takes place in peripheral blood, with metabolic remodeling of CD8 + T cells lasting the entire course of the the combination therapy. Importantly, in-vitro glycolysis inhibition in peripheral CD8 + T cells of patients with breast or liver tumors having been treated with MWA thrice leads to their differentiation into CD8 + T CM cells. Our work thus offers a potential strategy to avoid tumor recurrence following MWA therapy and lays down the proof-of-principle for future clinical trials., (© 2024. The Author(s).)

Background: Despite great advances in the treatment of breast cancer, innovative approaches are still needed to reduce metastasis. As a minimally invasive local therapy (not standard therapy for breast cancer), microwave ablation (MWA) has been attempted to treat breast cancer, but the local effect and immune response induced by MWA have seldom been reported., Methods: The clinical study was performed to determine the complete ablation rate of MWA for early-stage breast cancer. Secondary endpoints included safety and antitumor immune response. 35 subjects from this clinical study were enrolled in the current report, and the local effect was determined by pathological examinations or follow-up. To investigate MWA-induced immune response, patients treated with surgery (n=13) were enrolled as control, and blood samples were collected before and after MWA or surgery. The immune cell populations, serum cytokines, secretory immune checkpoint molecules, and T-cell receptor sequencing were analyzed., Results: Of 35 enrolled patients, 32 (91.4%) showed complete ablation. Compared with surgery, MWA induced significantly increased levels of inducible co-stimulator (ICOS)+ activated CD4+ T cells and serum interferon gamma, indicating a shift in the Th1/Th2 balance toward Th1. The activated ICOS pathway was involved in the MWA-induced adaptive immune response. T-cell receptor sequencing revealed MWA of primary tumor activated T lymphocytes expansion and recognized some cancer-specific antigens. Moreover, CD4+ effector memory T-cell response was induced by MWA, and the immune response still existed after surgical resection of the ablated tumor., Conclusions: MWA may not only be a promising local therapy but also a trigger of antitumor immunity for breast cancer, opening new avenues for the treatment of breast cancer. Combinatorial strategy using additional agents which boost MWA-induced immune response could be considered as potential treatment for clinical study for early breast cancer therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We aimed to investigate the exact role of residual thermal energy following microwave ablation (MWA) and radiofrequency ablation (RFA) at the final ablation and transition zones and determine whether residual thermal energy could be dissipated by subsequent cooling-circulation., Methods: In an ex vivo study, MWA and RFA were performed on fresh porcine liver, and central and border temperatures were compared. In an in vivo study, MWA and RFA were performed to the livers of New Zealand white rabbits. Tissue samples were stained with α-NADH-diaphorase. The coagulation zones (NADH-negative) and transition zones (lightly NADH-stained) of different groups were compared at different time points., Results: In the ex vivo model, the residual thermal energy after MWA and RFA could be dispersed by subsequent cooling-circulation due to the temperature decreasing rapidly. In the in vivo study, the coagulation volume in the ablation group was larger than that in the cooling-circulation group (P < 0.05) 2 days after ablation. In the ablation group, the damaged zone (the transition zone plus the coagulation zone) on α-NADH-diaphorase-stained images increased rapidly within 2 hours after ablation and slowly reached the maximum on day 2. However, the damaged zones did not change significantly at the three time points observed in the cooling-circulation group., Conclusion: The residual thermal energy in MWA and RFA induced secondary damage beyond the direct coagulation zone, and it could be dissipated by subsequent cooling-circulation, contributing to smaller ablation and transition zones.

Purpose: To determine the characteristics of ultrasound (US) imaging of completely ablated cases and the effects of duration and clinical experience on accurate microwave ablation (MWA) for the treatment of benign breast tumours., Methods: With written informed consent and approval of the institutional ethics committee, patients with symptomatic or palpable benign breast tumours (longest diameter, 7-32 mm), to whom MWA (2450 MHz) was performed, were enrolled in this prospective nonrandomised study. US and contrast-enhanced US (CEUS) images were applied for follow-up and analysed., Results: Forty-seven consecutive patients with 52 completely ablated tumours were enrolled. Of these 52 tumour ablations in US, 16 ablations were defined as concentric type, and 36 were defined as nonconcentric type. Of these 52 ablations, 7 cases were defined as nonaccurate ablation with the largest margin ≥10 mm in US. The nonaccurate ablation rate in the training group (the first consecutive 30 cases, 7/30) was significant higher than that (the last 22 cases, 0/22) in the practiced group (p = 0.016). Of 38 completely ablated cases (9 mm < the longest diameter <20 mm), the average largest margin in >70 s group was significant larger than that in <70 s group (p = 0.019)., Conclusions: Experience was important for accurate MWA in the treatment of benign breast tumour, and at least 30 cases training was recommended. Nevertheless, clinical trials are still required to validate our findings in the future.

Objective: To investigate microwave-induced morphological and functional injury of natural killer (NK) cells and uncover their mechanisms., Methods: NK-92 cells were exposed to 10, 30, and 50 mW/cm2 microwaves for 5 min. Ultrastructural changes, cellular apoptosis and cell cycle regulation were detected at 1 h and 24 h after exposure. Cytotoxic activity was assayed at 1 h after exposure, while perforin and NKG2D expression were detected at 1 h, 6 h, and 12 h after exposure. To clarify the mechanisms, phosphorylated ERK (p-ERK) was detected at 1 h after exposure. Moreover, microwave-induced cellular apoptosis and cell cycle regulation were analyzed after blockade of ERK signaling by using U0126., Results: Microwave-induced morphological and ultrastructural injury, dose-dependent apoptosis (P < 0.001) and cell cycle arrest (P < 0.001) were detected at 1 h after microwave exposure. Moreover, significant apoptosis was still detected at 24 h after 50 mW/cm2 microwave exposure (P < 0.01). In the 30 mW/cm2 microwave exposure model, microwaves impaired the cytotoxic activity of NK-92 cells at 1 h and down regulated perforin protein both at 1 h and 6 h after exposure (P < 0.05). Furthermore, p-ERK was down regulated at 1 h after exposure (P < 0.05), while ERK blockade significantly promoted microwave-induced apoptosis (P < 0.05) and downregulation of perforin (P < 0.01)., Conclusion: Microwave dose-dependently induced morphological and functional injury in NK-92 cells, possibly through ERK-mediated regulation of apoptosis and perforin expression., (Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced immune responses are mostly weak, and the immunomodulation effects of MWA in breast cancer are unclear. Immunostimulant OK-432 can induce tumor-specific T-cell responses and may augment the immunity induced by MWA., Methods: We treated 4T1 breast cancer bearing BALB/c mice with MWA, OK-432, MWA plus OK-432, or left without treatment. Survival time was evaluated with the Kaplan-Meyer method comparing survival curves by log-rank test. On day 25 after ablation, surviving mice received tumor rechallenge, and the rechallenged tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses in ablated tissues and spleens. The tumor-specific immunity was assessed by enzyme-linked immunospot assays. Besides, the cytokine patterns were identified from enzyme-linked immunosorbent assay., Results: Microwave ablation plus OK-432 resulted in longer survival than single treatment and protect most surviving mice from tumor rechallenge. Both local and systemic T-cell responses were induced by MWA and were further enhanced by subsequent administration of OK-432. Moreover, the combination of MWA and OK-432 induced stronger tumor-specific immune responses than MWA alone. In addition, OK-432 and MWA synergistically promoted the production of Th1-type but not Th2-type cytokines, and polarized T-cell responses to Th1-dominant state., Conclusions: The T-cell immune responses were activated by MWA in breast cancer. Furthermore, the combination of MWA and OK-432 induced Th1-type response and elicited specific antitumor immunity.

Background: Microwave therapy is a minimal invasive procedure and has been employed in clinical practice for the treatment of various types of cancers. However, its therapeutic application in non-small-cell lung cancer and the underlying mechanism remains to be investigated. This study aimed to investigate its effect on Lewis lung carcinoma (LLC) tumor in vivo., Methods: Fifty LLC tumor-bearing C57BL/6 mice were adopted to assess the effect of microwave radiation on the growth and apoptosis of LLC tumor in vivo. These mice were randomly assigned to 10 groups with 5 mice in each group. Five groups were treated by single pulse microwave at different doses for different time, and the other five groups were radiated by multiple-pulse treatment of a single dose. Apoptosis of cancer cells was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Western blotting was applied to detect the expression of proteins., Results: Single pulse of microwave radiation for 5 min had little effect on the mice. Only 15-min microwave radiation at 30 mW/cm2 significantly increased the mice body temperature (2.20 ± 0.82)°C as compared with the other groups (0.78 ± 0.29 °C, 1.24 ± 0.52 °C, 0.78 ± 0.42 °C, respectively), but it did not affect the apoptosis of LLC tumor cells significantly. Continous microwave radiation exposure, single dose microwave radiation once per day for up to seven days, inhibited cell division and induced apoptosis of LLC tumor cells in a dose- and duration-dependent manner. It upregulated the protein levels of p53, Caspase 3, Bax and downregulated Bcl-2 protein., Conclusions: Multiple exposures of LLC-bearing mice to microwave radiation effectively induced tumor cell apoptosis at least partly by upregulating proapoptotic proteins and downregulating antiapoptotic proteins. Continuous radiation at low microwave intensity for a short time per day is promising in treating non-small-cell lung cancer., Competing Interests: There are no conflicts of interest.

Purpose: The aim of this study was to explore whether doxorubicin hydrochloric (DOX) combined with microwave ablation (MWA) is more effective at increasing tumour coagulation and prolonging end-point survival in a VX2 rabbit breast cancer model than each intervention individually., Methods: New Zealand white rabbits with VX2 tumours were placed into treatment groups as follows: MWA (20 W for 5 min and 40 W for 5 min), intravenous injection of 4 mg/kg DOX, and combined therapy. Tumours were analysed at 4 h and 24 h after treatment to determine the temporal quantities of cleaved caspase-3 and Hsp70 using immunohistochemical staining and Western blots. Tumour coagulation areas were compared at 24 h after treatment., Results: No significant difference in tumour coagulation was found between DOX-MWA and 40W-MWA (mean 4.52 cm(2) ± 0.48 (SD), 4.08 cm(2) ± 0.36, respectively; P > 0.05). A significant difference between tumour coagulation was found for DOX-MWA and 20W-MWA (mean 4.52 cm(2) ± 0.48 (SD), 1.69 cm(2) ± 0.34 cm(2), respectively; p < 0.01). Cleaved caspase-3 and Hsp70 demonstrated low level expression at 4 h and 24 h in the DOX group. Cleaved caspase-3 showed low expression at the coagulation margin in the 20W-MWA group, was highly expressed in DOX-MWA group, and continued to increase with time. Hsp70 in the 20W-MWA group increased significantly at the coagulation margin but demonstrated low expression in the DOX-MWA group at 4 h and 24 h. The animals in the combined treatment group had a longer survival time (mean 78.33 days ± 8.07 SD) than the 20W-MWA group (mean 57.17 days ± 8.77, p < 0.01) or the DOX group (mean 35.17 days ± 7.63, p < 0.01)., Conclusion: A combination of DOX and MWA could increase tumour coagulation and end-point survival better than single therapy, which had some connection with the elevated expression of cleaved caspase-3 and low Hsp70 expression at the coagulation margin.

Microwaves have been suggested to induce neuronal injury and increase permeability of the blood-brain barrier (BBB), but the mechanism remains unknown. The role of the vascular endothelial growth factor (VEGF)/Flk-1-Raf/MAPK kinase (MEK)/extracellular-regulated protein kinase (ERK) pathway in structural and functional injury of the blood-brain barrier (BBB) following microwave exposure was examined. An in vitro BBB model composed of the ECV304 cell line and primary rat cerebral astrocytes was exposed to microwave radiation (50 mW/cm(2), 5 min). The structure was observed by scanning electron microscopy (SEM) and the permeability was assessed by measuring transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) transmission. Activity and expression of VEGF/Flk-1-ERK pathway components and occludin also were examined. Our results showed that microwave radiation caused intercellular tight junctions to broaden and fracture with decreased TEER values and increased HRP permeability. After microwave exposure, activation of the VEGF/Flk-1-ERK pathway and Tyr phosphorylation of occludin were observed, along with down-regulated expression and interaction of occludin with zonula occludens-1 (ZO-1). After Flk-1 (SU5416) and MEK1/2 (U0126) inhibitors were used, the structure and function of the BBB were recovered. The increase in expression of ERK signal transduction molecules was muted, while the expression and the activity of occludin were accelerated, as well as the interactions of occludin with p-ERK and ZO-1 following microwave radiation. Thus, microwave radiation may induce BBB damage by activating the VEGF/Flk-1-ERK pathway, enhancing Tyr phosphorylation of occludin, while partially inhibiting expression and interaction of occludin with ZO-1.

Purpose: Combination of percutaneous microwave ablation (PMWA) and intravenous injection of 131I-hypericin(IIIH) may bear potential as a mini-invasive treatment for tumor. The objective of this study was to assess the effect of PMWA and IIIH in breast tumor growth., Methods: Ten New Zealand White rabbits bearing VX2 breast carcinomas were randomly divided into two groups (each 5 examples) and processed using PMWA followed by IIIH and IIIH alone. The IIIH activity was evaluated using planar scintigraphy, autoradiography and biodistribution analysis. The maximum effective safe dose of IIIH was found through 48 rabbits with VX2 breast tumor, which were randomized into six groups (n=8 per group). Subsequently, a further 75 rabbits bearing VX2 breast solid tumors were randomly divided into five groups (each 15 examples) and treated as follows: A, no treatment group; B, PMWA alone; C, IIIH alone; D, PMWA+IIIH×1 (at 8 h post-PMWA); and E, PMWA+IIIH×2 (at 8 h and at 8 days post-PMWA). The therapeutic effect was assessed by measurement of tumor size and performation of positron emission tomography/computed tomograph (PET/CT) scans, liver and renal function tests and Kaplan-Meier survival analysis., Results: The planar scintigraphy findings suggested a significant uptake of 131I in necrotic tumor tissue. The autoradiography gray scales indicated higher selective uptake of IIIH by necrotic tissue, with significant differences between the groups with and those without necrotic tumor tissue (P<0.05). The maximum effective safe dose of IIIH was 1 mCi/kg. The PET/CT scans and tumor size measurement suggested improvements in treatment groups at all time points (P<0.01). Significant differences were detected among Groups A, B, D and E (P<0.05). Lower levels of lung metastasis were detected in Groups D and E (P<0.05). There were no abnormalities in liver and renal functions tests or other reported side effects., Conclusion: IIIH exhibited selective uptake by necrotic tumor tissue. Sequential therapy involving PMWA+IIIH was successfully inhibiting tumor growth and prolonging survival.

Recent studies have highlighted the important role of the postsynaptic NMDAR-PSD95-CaMKII pathway for synaptic transmission and related neuronal injury. Here, we tested changes in the components of this pathway upon microwave-induced neuronal structure and function impairments. Ultrastructural and functional changes were induced in hippocampal neurons of rats and in PC12 cells exposed to microwave radiation. We detected abnormal protein and mRNA expression, as well as posttranslational modifications in the NMDAR-PSD95-CaMKII pathway and its associated components, such as synapsin I, following microwave radiation exposure of rats and PC12 cells. Thus, microwave radiation may induce neuronal injury via changes in the molecular organization of postsynaptic density and modulation of the biochemical cascade that potentiates synaptic transmission., (© 2015 S. Karger AG, Basel.)

Objective: The aim of this study is to investigate whether microwave exposure would affect the N-methyl-D-aspartate receptor (NMDAR) signaling pathway to establish whether this plays a role in synaptic plasticity impairment., Methods: 48 male Wistar rats were exposed to 30 mW/cm2 microwave for 10 min every other day for three times. Hippocampal structure was observed through H&E staining and transmission electron microscope. PC12 cells were exposed to 30 mW/cm2 microwave for 5 min and the synapse morphology was visualized with scanning electron microscope and atomic force microscope. The release of amino acid neurotransmitters and calcium influx were detected. The expressions of several key NMDAR signaling molecules were evaluated., Results: Microwave exposure caused injury in rat hippocampal structure and PC12 cells, especially the structure and quantity of synapses. The ratio of glutamic acid and gamma-aminobutyric acid neurotransmitters was increased and the intracellular calcium level was elevated in PC12 cells. A significant change in NMDAR subunits (NR1, NR2A, and NR2B) and related signaling molecules (Ca2+/calmodulin-dependent kinase II gamma and phosphorylated cAMP-response element binding protein) were examined., Conclusion: 30 mW/cm2 microwave exposure resulted in alterations of synaptic structure, amino acid neurotransmitter release and calcium influx. NMDAR signaling molecules were closely associated with impaired synaptic plasticity., (Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Microwave-induced learning and memory deficits in animal models have been gaining attention in recent years, largely because of increasing public concerns on growing environmental influences. The data from our group and others have showed that the injury of mitochondria, the major source of cellular adenosine triphosphate (ATP) in primary neurons, could be detected in the neuron cells of microwave-exposed rats. In this study, we provided some insights into the cellular and molecular mechanisms behind mitochondrial injury in PC12 cell-derived neuron-like cells. PC12 cell-derived neuron-like cells were exposed to 30 mW/cm(2) microwave for 5 min, and damages of mitochondrial ultrastructure could be observed by using transmission electron microscopy. Impairments of mitochondrial function, indicated by decrease of ATP content, reduction of succinate dehydrogenase (SDH) and cytochrome c oxidase (COX) activities, decrease of mitochondrial membrane potential (MMP), and increase of reactive oxygen species (ROS) production, could be detected. We also found that hypoxia-inducible factor-1 (HIF-1α), a key regulator responsible for hypoxic response of the mammalian cells, was upregulated in microwave-exposed neuron-like cells. Furthermore, HIF-1α overexpression protected mitochondria from injury by increasing the ATP contents and MMP, while HIF-1α silence promoted microwave-induced mitochondrial damage. Finally, we demonstrated that both ERK and PI3K signaling activation are required in microwave-induced HIF-1α activation and protective response. In conclusion, we elucidated a regulatory connection between impairments of mitochondrial function and HIF-1α activation in microwave-exposed neuron-like cells. By modulating mitochondrial function and protecting neuron-like cells against microwave-induced mitochondrial injury, HIF-1α represents a promising therapeutic target for microwave radiation injury.

Purpose: To prospectively assess MR imaging evaluation of the ablation zone and pathological changes after microwave ablation (MWA) in breast cancer., Materials and Methods: Twelve enrolled patients, diagnosed with non-operable locally advanced breast cancer (LABC), were treated by MWA and then neoadjuvant chemotherapy, followed by surgery. MR imaging was applied to evaluate the effect of MWA. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were applied to analyze the ablated area., Results: All MWA procedures were performed successfully under local anesthesia. For a mean duration of 2.15 min, the mean largest, middle and smallest diameters in the ablated zone 24-h post-ablation in MR imaging were 2.98 cm ± 0.53, 2.51 cm ± 0.41 and 2.23 cm ± 0.41, respectively. The general shape of the ablation zone was close to a sphere. The ablated area became gradually smaller in MR imaging. No adverse effects related to MWA were noted in all 12 patients during and after MWA. HE staining could confirm the effect about 3 months after MWA, which was confirmed by TEM., Conclusions: 2 min MWA can cause an ablation zone with three diameters larger than 2 cm in breast cancer, which may be suitable for the local treatment of breast cancer up to 2 cm in largest diameter. However, the long-term effect of MWA in the treatment of small breast cancer should be determined in the future., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: To explore the impact of microwave radiation on GC-2spd cells., Methods: We exposed cultured GC-2spd cells to microwave radiation at the average power densities of 0, 10 and 30 mW/cm2 for 15 minutes and, from I to 24 hours after the exposure, we observed the changes in cell proliferation, histology and ultrastructure, cell apoptosis, and cAMP content by MTIT, light microscopy, electron microscopy, flow cytometry and ELISA., Results: Compared with the control group, the GC-2spd cells showed a significant decrease in proliferation ability at 1 -24 hours after 10 and 30 mW/cm2 microwave radiation, except at 12 hours after 30 mW/cm2 radiation (P <0.05 or P <0.01), with reduced length and number of cell enation and increased intra cytoplasm vacuoles. The rate of cell apoptosis (%) was significantly increased in the 10 and 30 mW/cm2 groups at 6 hours (4.56 +/- 2.09 vs 14.59 +/- 1.09 and 8.48 +/- 1.73, P <0.05 or P <0.01) , with agglutination and margin translocation of chromatins and obvious dilation of endo cytoplasmic reticula. The cAMP content (nmol/g) in the GC-2spd cells was remarkably reduced in the 10 and 30 mW/cm2 groups at 6 and 24 hours (2.77 +/-0.24 vs 1.65+/- 0. 17 and 1.96+/-0.10, 3.02 +/-0.47 vs 2.13 +/-0.33 and 1.69 +/-0.27, P <0.05 or P <0.01)., Conclusion: Microwave radiation at 10 and 30 mW/cm2 may cause injury to GC-2spd cells, which is manifested by decreased content of intracellular cAMP, reduced activity of cell proliferation, and increased rate of cell apoptosis.

This paper is aimed to study the effect of ADL on expression of β1-AR and M2-AchR in myocardial cells of rats exposed to microwave radiation. Immunohistochemistry, Western blot and image analysis were used to detect the expression of β1-AR and M2-AchR in myocardial cells at 7 and 14 d after microwave exposure. The results show that the expression level was higher in microwave exposure group and 0.75 g/(kg•d) ADL group than in sham operation group and significantly lower in 1.5 and 3.0 g/(kg•d) ADL groups than in microwave group. So we have a conclusion that the expression of β1-AR and M2-AchR is down-regulated in myocardial cells of rats exposed to microwave radiation. ADL can protect rats against microwave-induced heart tissue injury., (Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: For complete tumor ablation in different tissues, it is necessary to investigate the exact coagulation zone of microwave ablation in different tissues. The aim of this study was to compare the extent of microwave ablation zone in muscle, liver and adipose tissue in ex vivo porcine models and assess the shape of microwave coagulation zone among these tissues., Materials and Methods: Microwave ablations were performed in ex vivo porcine muscle, liver and adipose tissue using 2450-MHz cooled-shaft microwave antenna. The content of water, fat and protein in these three tissues was determined. Two power increments (40 and 80 W) and five time increments (1, 3, 5, 7, and 10 minutes) were used in this study. Diameters and shapes of the ablation zones were assessed on gross specimens., Results: The average percentages of water, fat and protein in these three tissues were significantly different (P < 0.001), respectively. The long-axis and short-axis diameters among these three tissues at each time-power combination were not significantly different (P > 0.05). The coagulation zones were all elliptical in muscle, liver and adipose tissue. When microwave ablation was performed in the tissue containing both muscle and adipose tissue, the coagulation zone was also elliptical. Regardless of the output power, the ellipticity index (EI) value of 1 minute treatment duration was higher than that of 10 minutes treatment duration (P < 0.05). Furthermore, the EI value did not decrease significantly when the treatment duration was more than 5 minutes (P > 0.05)., Conclusion: The extent of microwave ablation zones was not significantly different among completely different tissues. Microwave ablations with ≥ 5 minutes time duration can induce coagulation zones with clinical desirable shape. Future clinical studies are still required to determine the role of microwave ablation in different tissues.

There has been growing public concern regarding exposure to microwave fields as a potential human health hazard. This study aimed to identify sensitive biochemical indexes for the detection of injury induced by microwave exposure. Male Wistar rats were exposed to microwaves for 6 min per day, 5 days per week over a period of 1 month at an average power density of 5 mW/cm(2) (specific absorption rate of 2.1 W/kg). Urine specimens were collected over 24 h in metabolic cages at 7 days, 21 days, 2 months, and 6 months after exposure. (1)H NMR spectroscopy data were analyzed using multivariate statistical techniques. Urine metabolic profiles of rats after long-term microwave exposure were significantly differentiated from those of sham-treated controls using principal component analysis or partial least squares discriminant analysis. Significant differences in low molecular weight metabolites (acetate, succinate, citrate, ketoglutarate, glucose, taurine, phenylalanine, tyrosine, and hippurate) were identified in the 5 mW/cm(2) microwave exposure group compared with the sham-treated controls at 7 days, 21 days, and 2 months. Metabolites returned to normal levels by 6 months after exposure. These data indicated that these metabolites were related to the perturbations of energy metabolism particularly in the tricarboxylic acid cycle, and the metabolism of amino acids, monoamines, and choline in urine represent potential indexes for the detection of injury induced by long-term microwave exposure.

Background: Percutaneous microwave coagulation (PMC) has been accepted as a promising modality in the treatment of tumors in well-vascularized tissues such as liver tumors and hysteromyoma. However, PMC for treatment of tumors in low blood-flow tissues has been seldom reported. The aim of this study was to determine the feasibility and safety of PMC for the treatment of tumors in low blood-flow tissues in a rabbit model., Methods: Fifteen rabbits with VX2 tumors implanted subcutaneously underneath the right second nipple were divided into a PMC group (n = 9) and a control group (n = 6). PMC was performed with output power of 40 W for one to two minutes. The therapeutic efficacy was evaluated by magnetic resonance imaging (MRI), physical examinations, survival rate, and histology. The cosmetic outcome after PMC was also assessed., Results: In the PMC group, tumor eradication was achieved in six rabbits (66.7%) without any evidence of tumor recurrence and metastasis as proven by MRI and histological examinations. The mean greatest and shortest tumor diameters of these six rabbits were 1.83 and 1.33 cm, respectively. Slight epidermal burns, which proved reversible, were found in seven rabbits (77.8%). The PMC group had a significantly longer survival than those in the control group (P = 0.0097). The four rabbits with coagulated tumors survived more than three months with their tumors becoming nonpalpable and undetectable by MRI and histological examinations., Conclusions: PMC is feasible and safe in the treatment of tumors in low blood-flow tissues in a rabbit model. Attention should be paid to avoid skin burns with PMC.

Purpose: To determine the feasibility of percutaneous microwave coagulation (PMC) for the treatment of small solitary breast cancers., Materials and Methods: With approval of the institutional ethics committee and written informed consent, 41 patients with core-needle-biopsy-proved breast cancers 3.0 cm or less in diameter accessed by using ultrasonography (US) were recruited. US-guided PMC was performed with general anesthesia, followed immediately by mastectomy. Histochemical staining with α-nicotinamide adenine dinucleotide, reduced (NADH)-diaphorase was used to determine cell viability and the extent of PMC lesions., Results: The mean tumor volume was 5.26 cm(3) ± 3.80 (standard deviation), with a range from 0.09 to 14.14 cm(3). PMC was successfully performed in all cases, with complete tumor ablation as assessed by using US. The mean time to reach complete ablation was 4.48 minutes, ranging from 3 to 10 minutes. With microscopic examination, 37 of 41 cases (90%; 95% confidence interval [CI]: 76.9%, 97.3%) showed complete tumor coagulation, as observed by using α-NADH-diaphorase staining. Of 38 cases diagnosed with invasive ductal carcinoma, 36 cases (95%; 95% CI: 82.3%, 99.4%) showed complete tumor coagulation. Slight thermal injuries to the skin and pectoralis major muscle, which proved reversible, were found in three cases., Conclusion: US-guided PMC of small solitary breast cancers is feasible. Nevertheless, larger-scale clinical trials are still needed to validate PMC for adoption into a standard clinical practice.

Objective: To analyze the effects of long-term microwave exposure on hippocampal structure and function in the rat., Methods: Experiments were performed on 184 male Wistar rats (three exposure groups and a sham group). Microwaves were applied daily for 6 min over 1 month at average power densities of 2.5, 5, and 10 mW/cm2. Learning and memory abilities were assessed by Morris water maze. High performance liquid chromatography was used to detect neurotransmitter concentrations in the hippocampus. Hippocampal structures were observed by histopathological analysis., Results: Following long-term microwave exposure there was a significant decrease in learning and memory activity in the 7 d, 14 d, and 1 m in all three microwave exposure groups. Neurotransmitter concentrations of four amino acids (glutamate, aspartic acid, glycine, and gamma-aminobutyric acid) in hippocampus were increased in the 2.5 and 5 mW/cm2 groups and decreased in the 10 mW/cm2 group. There was evidence of neuronal degeneration and enlarged perivascular spaces in the hippocampus in the microwave exposure groups. Further, mitochondria became swollen and cristae were disordered. The rough endoplasmic reticulum exhibited sacculated distension and there was a decrease in the quantity of synaptic vesicles., Conclusion: These data suggest that the hippocampus can be injured by long-term microwave exposure, which might result in impairment of cognitive function due to neurotransmitter disruption.

Objective: To study the protective effects of AduoLa Fuzhenglin(ADL) on the heart injury induced by microwave exposure in rats., Methods: One hundred forty male Wistar rats were divided randomly into 5 groups: control, microwave radiation, 0.75 g x kg(-1) d(-1) ADL, 1.50 g x kg(-1) d(-1) ADL and 3.00 g x kg(-1) d(-1) ADL pretreatment groups. Rats in three ADL pretreatment groups were administrated by ADL per day for 2w then exposed to 30 mW/cm2 microwaves for 15 min. The left ventricle blood of rats was obtained at 7 d and 14 d after exposure to microwaves, and the blood Ca2+, AST and CK were detected with Coulter automatic biochemical analyzer, then the histological changes and ultrastructure of heart were observed under light and electron microscopes., Results: At 7 d and 14 d after exposure to microwaves, the blood Ca2+, AST and CK concentrations significantly increased (P<0.05 or P<0.01) as compared with controls; Heart muscle fibers showed wavilness, endotheliocyte karyopyknosis, anachromasis; The mitochondria swelling and cavitation, intercalary dies blurred in radiation groups. The changes in 0.75 g x kg(-1) d(-1) ADL pretreatment group were similar to the radiation group, but in 1.50 g x kg(-1)d(-1) and 3.00 g x kg(-1) d(-1) ADL pretreatment groups, above indexes of rats significantly reduced as compared with microwaves group (P<0.05); also the blood Ca2+, AST, CK contents were significantly lower than those in microwave group (P<0.05); The heart showed a tendency to improve., Conclusion: Microwave radiation (30 mW/cm2) can cause the blood Ca2+, AST and CK turbulence, and heart injury in the histology and ultrastructure; ADL at the dosages of 1.50 g x kg(-1) d(-1) and 3.00 g x kg(-1) d(-1) has a protective effects on the heart injury induced by microwave in rats.

Objective: To investigate the effect of long-term microwave radiation on male reproduction in rats., Methods: A total of 100 male Wistar rats were exposed to microwave radiation with average power density of 0, 2.5, 5 and 10 mW/cm2 for 4 weeks, 5 times a week and 6 minutes per time. Changes in serum testosterone, testicular index, histology and ultrastructure, and the percentage of teratospermia in the epididymis were observed dynamically at 6 h, 7 d, 14 d, 28 d and 60 d after the exposure., Results: There was a significant decrease in serum testosterone concentration at 28 d after microwave radiation at 2.5, 5 and 10 mW/cm2 ([10.20 +/- 4.31] ng/ml, [5.56 +/- 3.47] ng/ml and [7.53 +/- 4.54] ng/ml) and at 60 d at 10 mW/cm2 ( [15.95 +/- 9.54] ng/ml), as compared with the control group ([23.35 +/- 8.06] ng/ml and [31.40 +/- 9.56] ng/ml) (P < 0.05 or P < 0.01). No significant changes were found in the testis index at 6 h -60 d after microwave radiation at the three doses, but different degrees of degeneration, necrosis and shedding of spermatogenic cells, thinning of spermatogenic epithelia, and decrease or deletion of spermatozoa were observed, and more obvious at 28 d and 60 d. Swelling and cavitation of mitochondria in all spermatogenic cells, agglutination and margin translocation of nuclear chromatin in the spermatogonial and Leydig cells were seen at 7 d and 60 d after 5 mW/cm2 microwave radiation. The rate of teratospermia of the epididymis was increased, more obviously at 7 d after 2.5, 5 mW/cm2, 60 d after 5 mW/cm2, and 7 d, 28 d and 60 d after 10 mW/cm2 microwave radiation (P < 0.05 or P < 0.01)., Conclusion: Long-term microwave radiation may cause injury to male reproduction, which is positively correlated with the radiation dose, and has an obvious late effect.

Objective: To explore the changes in the expressions of the tight junction related protein occludin and junctional adhesion molecule-1 (JAM-1) of the blood-testis barrier and their significance in rats after microwave radiation., Methods: Eighty male Wistar rats were exposed to microwave radiation with average power density of 0, 10, 30 and 100 mW/cm2 for five minutes, and dynamic changes in the expressions of testicular occludin and JAM-1 were observed by Western blot and image analysis at 6 h, 1 d, 3 d, 7 d and 14 d after the radiation., Results: There was a significant down-regulation in the expression of the occludin protein at 3 - 7 d, 6 h - 7 d and 6 h - 14 d (P < 0. 05), as well as in that of JAM-1 at 3 - 7 d, 1 - 7 d and 1-14 d (P < 0.05) after exposure to 10, 30 and 100 mW/cm2 microwave radiation., Conclusion: The decreased protein expressions of occludin and JAM-1 may play an important role in the microwave radiation induced-damage to the blood-testis barrier.

Objective: To investigate the expression of aquaporin 4 (AQP4) after microwave exposure and the correlation with the brain injury by radiation., Methods: 70 male rats were exposed to microwave whose average power density was 0, 10, 30 and 100 mW/cm(2) respectively. Rats were sacrificed at 6 h, 1 d, 3 d and 7 d after exposure. Immunohistochemistry and Western blot were used to detect the expression of AQP4 in protein level in rat hippocampus, and the expression of AQP4 in gene level was measured by in situ hybridization and RT-PCR., Results: The expression of AQP4 in rat hippocampus was abnormal after 10, 30, 100 mW/cm(2) microwave exposure. The protein level showed increased at first and then recovered at 10 and 30 mW/cm(2) groups, while increased progressively in 100 mW/cm(2) group within 14 d (P < 0.01). The gene expression of AQP4 was increased (0.51 +/- 0.02) at the beginning (6 h) and then regained after 10 mW/cm(2) microwave exposure, while in 30 and 100 mW/cm(2) groups, it rose to the peak at 7 d (0.46 +/- 0.02 and 0.43 +/- 0.08) and didn't get back (P = 0.004; P = 0.012)., Conclusion: Microwave radiation can increase the expression of AQP4 in rat hippocampus. The change might participate in the process of increasing permeability of blood-brain barrier and lead to the brain edema after microwave radiation.

Objective: To explore whether microwave radiation may cause injury of primary cultured Sertoli cells., Methods: The model of primary cultured Sertoli cells in vitro was established, which was radiated by microwave with average power density 0, 30 and 100 mW/cm(2) for five minutes. The changes of cell cycle, apoptosis and death, and intracellular Ca2+ concentration in the Sertoli cells were measured at sixth hours through Annexin V-PI double labeling and Fluo-3-AM labeling, flow cytometry combined with laser scanning confocal microscopy after microwave exposure., Results: The numbers of Sertoli cells were obviously reduced in G0-G1 and G2-M phase (62.57% +/- 3.22% and 8.25% +/- 1.75%) and increased in S phase (29.17% +/- 4.87%) compared with the control groups (79.18% +/- 0.24%, 11.17% +/- 0.50% and 9.64% +/- 0.62%) (P < 0.05 or P < 0.01), but the changes of rate of apoptosis and death and intracellular Ca2+ concentration showed no difference at 6 h after exposure to 30 mW/cm(2) microwave. There was a significant increase in the Sertoli cell counts of G0-G1 phase (87.69% +/- 1.32%), and decrease in the Sertoli cell counts of G2-M and S phase (7.41% +/- 0.60% and 4.87% +/- 0.91%) (P < 0.01). There was also a significant increase in intracellular Ca2+ concentration and rate of apoptosis and death (P < 0.05 or P < 0.01) at 6 h after exposure to 100 mW/cm(2) microwave., Conclusion: 100 mW/cm(2) microwave radiation may cause growth inhibition and increase of apoptosis and death in the primary cultured Sertoli cells. The increase of intracellular Ca2+ concentration is one of the injury mechanisms.

Aim: To investigate the effect of microwave radiation on expression and phosphorylation of synapsin I and to discover the mechanism by research on the change of expression of BDNF and its receptor, TrkB., Methods: PC12 cells were exposed to microwave with average power density being 30 mW/cm(2). HPLC was used to detect the release of amino acids; RT-PCR, Western blot and immunocytochemistry were used to detect the expressions of synapsin I, BDNF and TrkB; immune co-precipitation was used to study the interaction of BDNF and TrkB., Results: It resulted in the decrease of the release of Asp, Glu, GABA and Gly at 1 h (P<0.01) after radiation. Protein of synapsin I was decreased in 9 h-2 d (P<0.01 or P<0.05); its mRNA was decreased in 3-9 h and increased at 1 d (P<0.01 or P<0.05); its phosphorylation was decreased at 3 h, increased at 1 d, and decreased at 2 d again (P<0.01 or P<0.05) after radiation. Protein of BDNF was decreased at 3 h and increased in 1-2 d (P<0.01 or P<0.05); its mRNA were decreased in 3-9 h, increased at 1d, and decreased at 2 d again (P<0.01 or P<0.05) after radiation. Protein of TrkB was increased in 3 h-1 d (P<0.01 or P<0.05); its mRNA decreased at 3 h and 2 d (P<0.01) after radiation. The interaction between BDNF and TrkB was increased in 3-9 h, but decreased in 1-2 d (P<0.01 or P<0.05) after radiation., Conclusion: Microwave radiation can induce the decrease of the release of amino acids and the expression and phosphorylation of synapsin I, and the abnormality of expressions and interaction of BDNF and TrkB in PC12 cells. The factors might play a role in the injury and repair of information transmission in PC12 cells.

Objective: To determine the effect of high power microwave (HPM) radiation on the structure and function of blood-testis barrier (BTB) in rats., Methods: One hundred and sixty-six male Wistar rats were treated by heart perfusion of lanthanum-glutaraldehyde solution and tail vein injection of evans blue (EB) at 6 h, 1, 3, 7 and 14 d after exposed to 0, 10, 30 and 100 mW/cm2 HPM radiation for 5 minutes, the structural change of BTB and distribution of lanthanum or EB observed through the light microscope, electron microscope and laser scanning confocal microscopy (LSCM)., Results: Testicular interstitial edema, vascular congestion or hyperemia with accumulation of plasma proteins and red blood cells in the inner compartment of seminiferous tubules were observed after exposure to HPM. The above-mentioned pathological changes were aggravated at 1-7 d and relieved at 14 d after radiation, obviously more severe in the 30 and 100 mW/cm2 exposure groups than in the 10 mW/cm2. Both lanthanum precipitation and EB were deposited in the inner compartment., Conclusion: HPM radiation may damage the structure and increase the permeability of BTB.

Objective: To investigate the effect of microwave radiation on synaptic structure, characteristic of synaptosome, the contents and release of neurotransmitters in hippocampus in Wistar rats., Methods: Wistar rats were exposed to microwave radiation with average power density of 30 mW/cm(2). Electron telescope was used to study the change of the synaptic structure at 6 h after radiation and to identify synaptosome. Flow cytometry and electron spin resonance were used to study the change of the concentration of Ca(2+) in synapse and the fluidity of membrane proteins of synaptosome. High performance liquid chromatography (HPLC) and spectrophotometer were used to study the changes of contents and release of amino acids and acetylcholine in hippocampus., Results: Microwave radiation of 30 mW/cm(2) caused deposits of synapse vesicle, elongation of active zone, the increase of thickness of postsynaptic density (PSD) and curvature, and perforation of synapse. The concentration of Ca(2+) in synapse (P<0.01) and tc of membrane proteins (P<0.01) of synaptosome increased contents of glutamic acid and glycine (P<0.01) and release of GABA increased the increase of contents and release of acetylcholine, and activity of acetyl cholinesterase (P<0.01) increased., Conclusion: Microwave radiation can induce the injure of synaptic structure and function of hippocampus, and then induce the disorder of the ability of learning and memory in rats.

Objective: To explore the injury effect and mechanism of hypothalamic neurons after high power microwave (HPM) exposure., Methods: Primarily cultured hypothalamic neurons were exposed to 10 and 30 mW/cm(2) HPM, and the inverted phase contrast microscope (IPCM) and flow cytometry (FCM) were employed to detect the injury of cells and change of mitochondrion membrane potential (MMP) and Ca(2+) in the cytoplasm of neurons., Results: The ratio of apoptosis was significantly higher than that of the sham exposure (P < 0.05) induced by 10 and 30 mW/cm(2) HPM and necrosis increased significantly (P < 0.05) in the group of 30 mW/cm(2) at 6 h after exposure. The content of Ca(2+) in the cytoplasm of neuron cells increased (P < 0.01) while MMP decreased significantly (P < 0.01) after radiation of 30 mW/cm(2) HPM at 6 h after exposure., Conclusion: Apoptosis is one of the major death ways of hypothalamic neurons. The overloading of Ca(2+) and the decline of MMP are involved in the process.

Objective: To explore the pathological characteristics and the dynamic change regularity of the testis induced by high power microwave (HPM) radiation., Methods: One hundred and sixty-five male Wistar rats were exposed to 0, 3, 10, 30 and 100 mW/cm2 HPM radiation for five minutes, and changes of testicular morphology and teratogenic ratio of epididymal spermatozoa were observed through light microscope and electron microscope at 6 h, 1, 3, 7, 14, 28 and 90 d after radiation., Results: Injury of testicular spermatogenic cells in rats might be induced by 3 to approximately 100 mW/cm2 HPM radiation, and the main pathological changes were degeneration, necrosis, shedding of spermatogenic cells, formation of multinuclear giant cells, decrease or loss of sperm and interstitial edema. Injury of spermatogenic cells underwent such phases as death and shedding, cavitation, regeneration and repair, characterized by being focalized, inhomogenous and phased. And the severity of pathological changes of the testis increased with power density. There was only scattered degeneration, necrosis, shedding of spermatogenic cells in the seminiferous tubule one day after 3 mW/cm2 radiation, and the pathological changes six hours after 10 mW/cm2 radiation was similar to those one day after 3 mW/cm2 radiation, but with the formation of multinuclear giant cells, and the above-mentioned pathological changes aggravated from one day to seven days after radiation. There was a significant increase in degeneration, necrosis, shedding of spermatogenic cells, as well as a significant decrease in spermatozoa and focal necrosis in simple seminiferous tubules six hours after 30 and 100 mW/cm2 radiation, and the subsequent changes were similar to those of 10 mW/cm2 radiation. There was a significant increase in teratogenic ratio of epididymal spermatozoa at 3 d, 1 to approximately 7 d, 6 h to approximately 7 d after 3, 10, 30 and 100 mW/cm2 microwave radiation respectively (P < 0.01 or P < 0.05)., Conclusion: HPM radiation may cause injury of testicular spermatogenic cells in rats, which has a positive correlation to radiation dosage and time.

Objective: To investigate the effect of high power microwave (HPM) radiation on the expression of beta(1)-adrenergic receptor (beta(1)-AR) and M(2)-muscarinic acetylcholine receptor (M(2)-AchR) in cardiomyocytes., Methods: S-band HPM device of mean power density 2 approximately 90 mW/cm(2) was used to irradiate 150 healthy Wistar male rats. Immunohistochemistry and image analysis were used to study the pathological characteristics of heart tissue and the expression of beta(1)-AR and M(2)-AchR., Results: Radiation of over 10 mW/cm(2) made myocardial fibers disordered in arrangement, degeneration even sarcoplasm condensation, Pace cells necrosis, and Purkinje cells lysis in a dose-dependent manner (r = 0.968, P < 0.05). beta(1)-AR expression in endocardium, membrane and cytoplasm of myocardium of left ventricle was increased on d1 after radiation, peaked on d3 (P < 0.05) and recovered on d14. M(2)-AchR expression was peaked on d1 (P < 0.01) and recovered on d14., Conclusion: Certain degree intensity of HPM radiation may cause heart injury, and increased expressions of beta(1)-AR and M(2)-AchR, which may play an important role in the pathophysiology of heart injury induced by HPM.

Objective: To study the changes of morphology and function in rat hippocampus induced by high power microwave (HPM) radiation., Methods: Fifty male Wistar rats were radiated by HPM. Then their learning and memory abilities were tested with Y maze and were sacrificed 6 h, 1 d, 3 d and 7 d after radiation. The hippocampus was taken out to study the basic pathologic changes, apoptosis and the expressions of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) by means of HE staining, Nissel body staining, in situ terminal end labeling and immunohistochemistry., Results: The learning and memory abilities of rats reduced significantly after HPM radiation. HPM also resulted in rarefaction, edema and hemangiectasia of hippocampus, nervous cells degeneration and necrosis, decrease or disappearance of Nissel bodies. The injuries were more serious in field CA4 and dentate gyrus, which showed dose-effect relationship, and were progressively aggravated within 7 days. The apoptosis cells were significantly increased. NSE was increased in neurons. The NSE positive areas were also seen in the interstitial matrix and blood vessels. GFAP was increased in astrocytes, which became shorter and thicker., Conclusion: HPM can damage the abilities of learning and memory and results in morphologic changes in hippocampus. The major pathologic changes are degeneration, apoptosis and necrosis of neurons and edema in interstitium. NSE and GFAP play an important role in the pathologic process.

Minimally invasive thermal therapy is a successful alternative treatment to surgery in solid tumors with high complete ablation rates, however, tumor recurrence remains a concern. Central memory CD8+ T cells (TCM) play important roles in protection from chronic infection and cancer. Here we find, by single-cell RNA analysis of human breast cancer samples, that although the memory phenotype of peripheral CD8+ T cells increases slightly after microwave ablation (MWA), the metabolism of peripheral CD8+ T cells remains unfavorable for memory phenotype. In mouse models, glycolysis inhibition by 2-deoxy-D-glucose (2DG) in combination with MWA results in long-term anti-tumor effect via enhancing differentiation of tumor-specific CD44hiCD62L+CD8+ TCM cells. Enhancement of CD8+ TCM cell differentiation determined by Stat-1, is dependent on the tumor-draining lymph nodes (TDLN) but takes place in peripheral blood, with metabolic remodeling of CD8+ T cells lasting the entire course of the the combination therapy. Importantly, in-vitro glycolysis inhibition in peripheral CD8+ T cells of patients with breast or liver tumors having been treated with MWA thrice leads to their differentiation into CD8+ TCM cells. Our work thus offers a potential strategy to avoid tumor recurrence following MWA therapy and lays down the proof-of-principle for future clinical trials. Central memory CD8+ T cells (Tcm) are important for lasting anti-tumour immunity and their differentiation is determined by underpinning transcriptional and metabolic regulation. Authors here show that although microwave ablation (MWA) cancer therapy induces T cells to acquire some of the gene expression features of Tcms, but the full metabolic remodeling required for functionality is only achieved if glycolysis is inhibited simultaneously. [ABSTRACT FROM AUTHOR]

There has been growing public concern regarding exposure to microwave fields as a potential human health hazard. This study aimed to identify sensitive biochemical indexes for the detection of injury induced by microwave exposure. Male Wistar rats were exposed to microwaves for 6 min per day, 5 days per week over a period of 1 month at an average power density of 5 mW/cm (specific absorption rate of 2.1 W/kg). Urine specimens were collected over 24 h in metabolic cages at 7 days, 21 days, 2 months, and 6 months after exposure. H NMR spectroscopy data were analyzed using multivariate statistical techniques. Urine metabolic profiles of rats after long-term microwave exposure were significantly differentiated from those of sham-treated controls using principal component analysis or partial least squares discriminant analysis. Significant differences in low molecular weight metabolites (acetate, succinate, citrate, ketoglutarate, glucose, taurine, phenylalanine, tyrosine, and hippurate) were identified in the 5 mW/cm microwave exposure group compared with the sham-treated controls at 7 days, 21 days, and 2 months. Metabolites returned to normal levels by 6 months after exposure. These data indicated that these metabolites were related to the perturbations of energy metabolism particularly in the tricarboxylic acid cycle, and the metabolism of amino acids, monoamines, and choline in urine represent potential indexes for the detection of injury induced by long-term microwave exposure. [ABSTRACT FROM AUTHOR]