Using RegGAN to generate synthetic CT images from CBCT images acquired with different linear accelerators.

BACKGROUND: The goal was to investigate the feasibility of the registration generative adversarial network (RegGAN) model in image conversion for performing adaptive radiation therapy on the head and neck and its stability under different cone beam computed tomography (CBCT) models. METHODS: A total of 100 CBCT and CT images of patients diagnosed with head and neck tumors were utilized for the training phase, whereas the testing phase involved 40 distinct patients obtained from four different linear accelerators. The RegGAN model was trained and tested to evaluate its performance. The generated synthetic CT (sCT) image quality was compared to that of planning CT (pCT) images by employing metrics such as the mean absolute error (MAE), peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM). Moreover, the radiation therapy plan was uniformly applied to both the sCT and pCT images to analyze the planning target volume (PTV) dose statistics and calculate the dose difference rate, reinforcing the model's accuracy. RESULTS: The generated sCT images had good image quality, and no significant differences were observed among the different CBCT modes. The conversion effect achieved for Synergy was the best, and the MAE decreased from 231.3 ± 55.48 to 45.63 ± 10.78; the PSNR increased from 19.40 ± 1.46 to 26.75 ± 1.32; the SSIM increased from 0.82 ± 0.02 to 0.85 ± 0.04. The quality improvement effect achieved for sCT image synthesis based on RegGAN was obvious, and no significant sCT synthesis differences were observed among different accelerators. CONCLUSION: The sCT images generated by the RegGAN model had high image quality, and the RegGAN model exhibited a strong generalization ability across different accelerators, enabling its outputs to be used as reference images for performing adaptive radiation therapy on the head and neck.

The Study of the Rescale Method of the Spectrum Shifting in X-Ray Fluorescence Well Logging.

The X-ray fluorescence well logging technology is a significant method that can make quantitative analysis orsemi-quantitative analysis on the wellface. This method is very important to mineral exploration. The spectrum shifting is often observed in the X-rayfluorescence well logging because the temperature in the well changes acutely. The hardware is used to release the spectrum shifting and the software method is used to rescale the tiny spectrum shifting. There are too manyspectra to be rescaled in a well logging task by manually. In this paper, an auto method to rescale spectrum shifting, via the expert system model which is based on the special process to rescale spectrum shifting in manual, is presented. The symmetric zero-area conversion method, which is not sensitive to the changes of the baseline, is used to research the peaks. And then, the characteristic peaks will be identified by the standard errors, automatically. The prior knowledge (the last energy scale) and the gauss probability density function are used to analyze the peaks qualitatively and confirm the energy of characteristic peaks. Then the least square method is applied energy calibration. The singular deviation point, away from the calibrationline, will be rejected and the energy ratio will be obtained again. This method is applied for rescaling spectrum shifting in 322 spectra and obtains a satisfactory achievement.

[Influence of the Experiment Energy Dispersive X-Ray Fluorescence Measurement of Uranium by Different Excitation Source].

Aiming at the self-excitation effect on the interference of measurements which exist in the process of Energy dispersive X-ray fluorescence method for uranium measurement. To solve the problem of radioactive isotopes only used as excitation source in determination of uranium. Utilizing the micro X-ray tube to test Self-excitation effect to get a comparison of the results obtained by three different uranium ore samples--109 Cd, 241 Am and Mirco X-ray tube. The results showed that self-excitation effect produced the area measure of characteristic X-ray peak is less than 1% of active condition, also the interference of measurements can be negligible. Photoelectric effect cross-section excited by 109 Cd is higher, corresponding fluorescence yield is higher than excited by 241 Am as well due to characteristics X-ray energy of 109 Cd, 22.11 & 24.95 KeV adjacent to absorption edge energy of L(α), 21.75 KeV, based on the above, excitation efficiency by 109 Cd is higher than 241 Am; The fact that measurement error excited by 241 Am is significantly greater than by 109 Cd is mainly due to peak region overlap between L energy peaks of uranium and Scattering peak of 241 Am, 26.35 keV, These factors above caused the background of measured Spectrum higher; The error between the uranium content in ore samples which the X-ray tube as the excitation source and the chemical analysis results is within 10%. Conclusion: This paper come to the conclusion that the technical quality of uranium measurement used X-ray tube as excitation source is superior to that in radioactive source excitation mode.

[Research on the Background Subtraction Method for X-Ray Fluorescence Spectrum with X-Ray Tube Excitation].

X-ray tube is the most commonly used equipment in X-ray fluorescence spectrum analysis as excitation source whose primary spectrum has become a major source of the background of X-ray fluorescence spectrum. Background subtraction should go before further analysis of this spectrum. The accuracy of the estimation of the background directly affect the results of subsequent processing steps. In this paper, the tube excitation component of X fluorescence spectrum is analyzed with an estimation method of background intensity against their background characteristics, and structuring theoretical spectral lines based on the measured spectral lines in order to evaluate the effect of spectral processing algorithms. The method utilizes the measured X-ray fluorescence spectrum which does not contain the characteristic peak of the spectrum, In order to estimate the composition of the original spectrum of the X-ray tube. It uses the spectrum that contains the continuous background for interpolating the entire measured spectrum, thereby avoiding overlapping the spectral characteristic peaks or improperly estimating full width at half maximum. This paper compared SNIP, Fourier transform method and the background subtraction method using the measured spectral lines. Using this method to estimate the background is closer to the theoretical background. The results showe that the method for X-ray fluorescence spectrum by X-ray tube excitation is accurate in this article, this method can be used to deduct continuous background, and good applied effectiveness has been achieved in the background subtraction of the actually measured X-ray fluorescence spectrometry.

[Analyzer Design of Atmospheric Particulate Matter's Concentration and Elemental Composition Based on ß and X-Ray's Analysis Techniques].

Monitoring atmospheric particulate matter requires real-time analysis, such as particulate matter's concentrations, their element types and contents. An analyzer which is based on ß and X rays analysis techniques is designed to meet those demands. Applying ß-ray attenuation law and energy dispersive X-ray fluorescence analysis principle, the paper introduces the analyzer's overall design scheme, structure, FPGA circuit hardware and software for the analyzer. And the analyzer can measure atmospheric particulate matters' concentration, elements and their contents by on-line analysis. Pure elemental particle standard samples were prepared by deposition, and those standard samples were used to set the calibration for the analyzer in this paper. The analyzer can monitor atmospheric particulate matters concentration, 30 kinds of elements and content, such as TSP, PM10 and PM2.5. Comparing the measurement results from the analyzer to Chengdu Environmental Protection Agency's monitoring results for monitoring particulate matters, a high consistency is obtained by the application in eastern suburbs of Chengdu. Meanwhile, the analyzer are highly sensitive in monitoring particulate matters which contained heavy metal elements (such as As, Hg, Cd, Cr, Pb and so on). The analyzer has lots of characteristics through technical performance testing, such as continuous measurement, low detection limit, quick analysis, easy to use and so on. In conclusion, the analyzer can meet the demands for analyzing atmospheric particulate matter's concentration, elements and their contents in urban environmental monitoring.

[The Study of Advanced Fundamental Parameter Method in EDXRFA].

The X-ray Fluorescence Analysis(XRFA) is an important and efficient method on the element anylsis and is used in geology, industry and environment protection. But XRFA has a backdraw that the determination limit and accuracy are effected by the matrix of the sample. Now the fundamental parameter is usually used to calculate the content of elements in XRFA, and it is an efficient method if the matrix and net area of characteristic X-ray peak are obtained. But this is invalide in in-stu XRFA. Also the method of net area and the "black material" of sample are the key point of the fundamental parameter method when the Energy Dispersive X-ray Fluorescence Analysis(EDXRFA) method is used in the low content sample. In this paper a advanced fundamental parameter method is discussed. The advanced fundamental parameter method includes the spectra analysis and the fundamental parameter method, which inserts the overlapping peaks separation method into the iteration process of the fundamental parameter method. The advanced method can resolve the net area and the quantitative analysis. The advanced method is used to analyse the standard sample. Compare to the content obtained from the coefficient method, the precision of Cu, Ni and Zn is better than coeffieciency method. The result shows that the advanced method could improve the precision of the EDXRFA, so the advanced method is better than the coefficient method.

[Analyse Output Specurum in Miniature Transmission X-Ray Tube of Aluminum Window and Silver Target by MC Simulation].

The miniature transmission X-ray tube is widely used in energy dispersive X-ray Fluorescence Analysis (EDXRFA). The miniature transmission X-ray tube with a small, low power consumption, X-ray emission efficiency that can be made the excitation source of handheld X-ray energy dispersive fluorescence analyzer. Beryllium (Be) is the most commonly used X-ray window material. But beryllium is expensive and toxic. At the same time set filtering window by aluminum (Al) to reducing low-energy scattering rays. This paper be adopted Al for exit window material of miniature transmission X-ray tube, achieve high-energy rays transmission and low-energy scattered radiation shielding, at the same time reduce production cost and difficulty. The present paper simulate the X-ray tube output spectrum of silver (Ag) target and aluminum window with different thickness by MCNP5. We consider the X-ray of low energy part is completely shielded when aluminum windows thickness is greater than 1.5 mm. We can conclude that 2 µm and 0.8 mm are the best combination of target thickness and aluminum windows through comparative analysis of existing research results. Then we can get flux of high energy part is big and low energy part is small when the target is 2 µm thick Ag and the window is 0.8 mm thick Al.

[Application of the racial algorithm in energy dispersive X-ray fluorescence overlapped spectrum analysis].

In the energy dispersive X-ray fluorescence spectrum analysis, scintillation detector such as NaI (Tl) detector usually has a low energy resolution at around 8%. The low energy resolution causes problems in spectral data analysis especially in the high background and low counts condition, it is very limited to strip the overlapped spectrum, and the more overlapping the peaks are, the more difficult to peel the peaks, and the qualitative and quantitative analysis can't be carried out because we can't recognize the peak address and peak area. Based on genetic algorithm and immune algorithm, we build a new racial algorithm which uses the Euclidean distance as the judgment of evolution, the maximum relative error as the iterative criterion to be put into overlapped spectrum analysis, then we use the Gaussian function to simulate different overlapping degrees of the spectrum, and the racial algorithm is used in overlapped peak separation and full spectrum simulation, the peak address deviation is in +/- 3 channels, the peak area deviation is no more than 5%, and it is proven that this method has a good effect in energy dispersive X-ray fluorescence overlapped spectrum analysis.

[Research on spectral characteristic of miniature X-ray tube and determination of beryllium window thickness].

Applying Monte Carlo method, the present paper simulates the emitted X-ray spectrum of miniature X-ray tube with thirteen thickness of beryllium window in the range from 50 to 500 microm. By analyzing the characteristic of the spectrums, the reasonable choice of thickness of beryllium window relies on the application and for the beryllium window it is not the thinner the better. Taking in-situ EDXRF as an example, though the emission X-ray intensity is higher as the thickness of the beryllium window becomes thinner, the proportion of useless low-energy X-ray (<5 keV) intensity to all energy X-ray intensity also is higher (>20%). The accuracy of in-situ EDXRF will be reduced when the high-throughput low-energy X-ray enters the detector. Therefore, this paper puts forward several parameters as judgment index for beryllium window thickness, which is described as follows: 1)The intensity ratios of the K-series X-ray to middle-energy (5-25 keV) bremsstrahlung and middle-high-energy (5-50 keV) bremsstrahlung (F1 and F3); 2)The intensity ratios of useless low-energy X-ray (<5 keV) to middle-energy (5-25 keV) X-ray and middle-high-energy (5-50 keV) X-ray (F2 and F4), it can reflect the relative intensity of useless low-energy X-ray. The simulation results demonstrate that with the increase in the beryllium window thickness, the value of F1 (F3) improves slowly, and the value of F2 (F4) decreases rapidly. In addition to the judgment index discussed above, and considering the X-ray shielded by beryllium window, the beryllium window of miniature X-ray tube can be determined. Based on simulation analysis, the thickness of around 250 microm is appropriate to miniature X-ray tube applied in the in-situ EDXRF. Comparing the emitted spectrum with 50 microm-thick beryllium window, 71.66% of low-energy X-rays are shielded, only 21.31% of X-rays with energy from 5 to 50 keV is shielded, the intensity ratio of low-energy X-ray to total energy X-ray is less than 10%, and the intensity proportion of K-series X-ray to middle-high energy X-ray maintains a high level. In other words, when the mobile X-ray source with 250 microm beryllium window is used in the in-situ EDXRF, proportion of effective signal is higher, and effect of energy resolution of the detection is least; Moreover, the relative intensity of the excitation spectral scattering background, which is obtained by detection for specimen excitation analysis, will remain at low level, thus to ensure the precision of the result of element analysis. For the beryllium window in the application of radiation therapy, the thicker the better. At this time, low-energy X-ray flux maintains a high level, and it can ensure that radiation dose is concentrated on treatment tissue.

A review of 210Pb and 210Po in moss.

Among environment contaminants, 210Pb and 210Po have gained significant research attention due to their radioactive toxicity. Moss, with its exceptional adsorption capability for these radionuclides, serves as an indicator for environmental 210Pb and 210Po pollution. The paper reviews a total of 138 articles, summarizing the common methods and analytical results of 210Pb and 210Po research in moss. It elucidates the accumulation characteristics of 210Pb and 210Po in moss, discusses current research challenges, potential solutions, and future prospects in this field. Existing literature indicates limitations in common measurement techniques for 210Pb and 210Po in moss, characterized by high detection limits or lengthy sample processing. The concentration of 210Pb and 210Po within moss display substantial variations across different regions worldwide, ranging from

Apatinib plus hepatic arterial infusion of oxaliplatin and raltitrexed for hepatocellular carcinoma with extrahepatic metastasis: phase II trial.

Most patients with advanced hepatocellular carcinoma (HCC) ultimately experience tumor progression after first-line systemic therapies. Systemic therapy is generally recommended as second-line treatment for advanced HCC in the major guidelines. Combining apatinib with hepatic arterial infusion chemotherapy (HAIC) likely drives synergistic activity on advanced HCC with extrahepatic metastasis. This phase II trial (ChiCTR2000029082) aimed to assess efficacy and safety of this combination in patients with HCC with extrahepatic metastasis who have progressed after first-line systemic therapies. The primary end point was the objective response rate (ORR). The secondary endpoints were progress-free survival (PFS), disease control rate (DCR), 6- and 12-month survival rates, overall survival (OS), and adverse events (AEs). Thirty-nine patients received oral treatment with apatinib, and hepatic artery infusion oxaliplatinplus raltitrexed. Per RECIST v1.1, the ORR and DCR was 53.8% and 89.7% in the patients population, respectively. The median PFS and OS was 6.2 months and 11.3 months, respectively. The 6- and 12-month survival rates were 81.7% and 44.1%, respectively. All AEs were manageable by medication or dose modifications. Apatinib plus HAIC for second-line therapy in advanced HCC with extrahepatic metastasis shows promising efficacy and manageable toxicities.

Dose tracking assessment for magnetic resonance guided adaptive radiotherapy of rectal cancers.

BACKGROUND: Magnetic resonance-guided adaptive radiotherapy (MRgART) at MR-Linac allows for plan optimisation on the MR-based synthetic CT (sCT) images, adjusting the target and organs at risk according to the patient's daily anatomy. Conversely, conventional linac image-guided radiotherapy (IGRT) involves rigid realignment of regions of interest to the daily anatomy, followed by the delivery of the reference computed tomography (CT) plan. This study aims to evaluate the effectiveness of MRgART versus IGRT for rectal cancer patients undergoing short-course radiotherapy, while also assessing the dose accumulation process to support the findings and determine its usefulness in enhancing treatment accuracy. METHODS: Nineteen rectal cancer patients treated with a 1.5 Tesla MR-Linac with a prescription dose of 25 Gy (5 Gy x 5) and undergoing daily adapted radiotherapy by plan optimization based on online MR-based sCT images, were included in this retrospective study. For each adapted plan ([Formula: see text]), a second plan ([Formula: see text]) was generated by recalculating the reference CT plan on the daily MR-based sCT images after rigid registration with the reference CT images to simulate the IGRT workflow. Dosimetry of [Formula: see text] and[Formula: see text]was compared for each fraction. Cumulative doses on the first and last fractions were evaluated for both workflows. The dosimetry per single fraction and the cumulative doses were compared using dose-volume histogram parameters. RESULTS: Ninety-five fractions delivered with MRgART were compared to corresponding simulated IGRT fractions. All MRgART fractions fulfilled the target clinical requirements. IGRT treatments did not meet the expected target coverage for 63 out of 94 fractions (67.0%), with 13 fractions showing a V95 median point percentage decrease of 2.78% (range, 1.65-4.16%), and 55 fractions exceeding the V107% threshold with a median value of 15.4 cc (range, 6.0-43.8 cc). For the bladder, the median [Formula: see text] values were 18.18 Gy for the adaptive fractions and 19.60 Gy for the IGRT fractions. Similarly the median [Formula: see text] values for the small bowel were 23.40 Gy and 25.69 Gy, respectively. No statistically significant differences were observed in the doses accumulated on the first or last fraction for the adaptive workflow, with results consistent with the single adaptive fractions. In contrast, accumulated doses in the IGRT workflow showed significant variations mitigating the high dose constraint, nevertheless, more than half of the patients still did not meet clinical requirements. CONCLUSIONS: MRgART for short-course rectal cancer treatments ensures that the dose delivered matches each fraction of the planned dose and the results are confirmed by the dose accumulation process, which therefore seems redundant. In contrast, IGRT may lead to target dose discrepancies and non-compliance with organs at risk constraints and dose accumulation can still highlight notable dosimetric differences.

[Study on the effect of target thickness on output spectrum in transmission anode micro X-ray tube by MC method].

The transmission anode micro X-ray tube is a key component of energy dispersive X-ray Fluorescence Analysis (EDXRFA) as exciting source. So in EDXRFA we hope to get the primary X-ray spectrum which is simply distributed. In the present paper, the authors used the Monte Carlo (MC) method to study the spectrum character of the transmission anode micro X-ray tube with different thickness of target. We cut the spectrum into high energy (5keV-50keV) part and low energy (< 5 keV) part and compared them to each other. The result showed that the flux of high energy part is big and the flux of low energy part is small when the electron energy is 50 keV and the target is 4 microm thick Ag. This is better for EDXRFA.

[Application of in situ micro energy dispersive X-ray fluorescence analysis in mineralogy].

Thirteen rock samples were collected for studying the variation of element content in the mineral during the alteration process from Xinjiang, China. The IED-6000 in situ micro energy dispersive X-ray fluorescence developed by CDUT was applied to get chemical and physical data from minerals. The non-destructive spectrometer is based on a low-power Mo-anode X-ray tube and a Si-PIN peltier cooled X-ray detector. The unique design of the tube's probe allows very close coupling of polycapillary and makes the use of micro-area measurement feasible and efficient. The spectrometer can be integrated into any microscope for analysis. The long axis diameter of beam spot is about 110 microm. According to micro-EDXRF measurement, the tetrahedrite was corrected to pyrite, improving the efficiency and accuracy of the mineral identification. The feldspar of mineralized rock sample is rich in Cu and Zn which can be used as prospecting indicator elements. Element content of Cr, Mn and Co shows negative correlation with the degree of mineralization.

[Research on the peak search method based on improved simulated annealing model for x-ray fluorescence spectrum].

In energy dispersive X-ray fluorescence analysis technical analysis, the spectrum information processing has been being the focus of researches, spectrum smooth, peak-search, and peak area processing are the top priority, tA peak search method is based on simulated annealing algorithm principle, and to establish a new search peak model algorithm, this algorithm uses the advantages of the global convergence properties of simulated annealing and the Metropolis criterion is used as a peak valley judgment basis. A new decision criteria on peak valley array is used in this method, too. At the same time, convergence is taken from both ends of the spectrum channel address, it ends up when convergence reaches to the same optimal solution. This paper compared the algorithm with the simple comparison method, third derivative method, and the contrast experiment results, showing that this algorithm has a strong ability on X-ray fluorescence spectrum peak-search and a certain value in the actual production.

[Research on the application of principal component analysis and improved BP neural network to the determination of Fe and Ti contents in geological samples].

Aiming at forecasting elemental contents in geological samples accurately, a principal component analysis and improved BP (PCA-BP) neural network theory is proposed in the present work. The samples from west Tianshan were measured through X-ray fluorescence measurement method, and the X-Ray fluorescence counts of each element such as Fe, Ti, V, Pb, Zn, etc. were input to the PCA-BP neural network as input variables to forecast Fe and Ti contents in uncertified geological samples quantitatively. The results show that the PCA-BP neural network can give an ideal result, and the relative error between the forecast data and chemical analysis data is less than 3%. This method provides a new and effective approach to forecasting elemental contents in geological samples.

Analysis of the Differential Expression and Antiviral Activity of Porcine Interferon-α In Vitro.

Porcine interferon α (poIFN-α) is a crucial cytokine that can prevent and treat viral infections. Seventeen functional porcine IFN-α subtypes were found in the porcine genome. In this study, multiple sequence alignment was performed to analyze IFN-α protein structure and function. Phylogenetic tree analysis of the poIFN gene family defined the evolutionary relationship of various subtypes. PoIFN-αs, including poIFN-α1-17, were expressed in an Escherichia coli expression system. The antiviral activities of these IFN-α proteins against vesicular stomatitis virus (VSV) and pseudorabies virus (PRV) were examined in PK-15 cells. We found that the antiviral activity of different poIFN-α molecules greatly differed as follows: the poIFN-α14 and 17 subtypes had the greatest antiviral activities against VSV and PRV in PK-15 cells, poIFN-α1, 2, 3, and 8 exhibited lower biological activities, and poIFN-α4, 5, 6, 7, 9, 10, 11, 12, 13, and 16 had minimal or no effect in the tested target cell‒virus systems. Moreover, our studies demonstrated that the antiviral activity of IFN-α was positively correlated with the induction of IFN-stimulated genes, such as 2'-5' oligoadenylate synthetase 1 (OSA1), interferon-stimulated gene 15 (ISG15), myxoma resistance protein 1 (Mx1), and protein kinase R (PKR). Thus, our experimental results provide important information about the antiviral functions and mechanism of poIFN-α.

A gamma ray sourceless efficiency calibration method based on the Boolean operation of the ray deposition process.

The general sourceless efficiency calibration has two major methods, Monte Carlo simulation and numerical calculation. Monte Carlo simulation as an important method to address the efficiency calibration in complex measurement systems, despite it being highly accurate, but inefficient and time-consuming. And although the numerical calculation is computationally efficient, its accuracy is highly influenced by the multiple Compton scattering of rays in sensitive body, and it is difficult to deal with complex measurement systems. To solve the above problems, this paper proposes a discrete numerical calculation combined with the graphical Boolean operations method for sourceless efficiency calibration. The method starts with a Monte Carlo simulation to obtain the rays deposition process in an infinite sensitive body and record deposition locations as a matrix; then, for different measurement systems, discrete numerical calculations are used to rapidly obtain the transmission process of rays to the sensitive body of the detector; finally, the two are combined to obtain the detection efficiency of the rays by using graphical Boolean operations. For the given two test models, the error between the measured and calculated results of 241Am, 137Cs, 60Co at 60 positions is within -3.61∼9.71%, and the error between the measured and calculated results of the soil source is within -1.27 to 4.26%, indicating that the method has high reliability in sourceless efficiency calibration. And in comparison with Monte Carlo simulations, it is found that the method has a good agreement with Monte Carlo simulation in efficiency calibration and the computational speed has been greatly improved.

Research of nuclide identification method based on background comparison method.

Radioactive material inspection in public is important to nuclear safety, and it is also the key security for holding large-scale events, while fast and efficient means of detecting radioactive materials are an important technical guarantee for nuclear safety. In this paper, energy and time distribution characteristics information of the natural background and target nuclide gamma particles are used to improve the sequential background comparison method. By using those energy and time distribution characteristics information, with the half-life and characteristic gamma-ray energy and branching ratio information of the nuclide, the response time and the identification accuracy of extremely low radioactive nuclides detected under natural-radiation background can be improved. Based on the theoretical research, the particle event acquisition device with the LaBr3(Ce) detector was used to carry out the experimental verification, and the results show that, this method can identify 137Cs (characteristic energy of 0.662 MeV，8700 Bq，the position relative to the detector is 30 cm) in 6.2 s, and identify 60Co (characteristic energy of 1.173 MeV and 1.332 MeV, 4500 Bq, the position relative to the detector is 15 cm) in 5.9 s. Experiments prove that the improved background comparison-based sequential Bayesian method can identify low radioactivity radionuclides under natural-radiation background rapidly.

Tacrolimus improves the proteinuria remission in patients with refractory IgA nephropathy.

BACKGROUND: Tacrolimus has been reported to be effective in refractory nephrotic syndrome, such as focal segmental glomerulosclerosis and membranous nephropathy. Some IgA nephropathy (IgAN) patients with massive proteinuria showed resistance to steroids and/or cytotoxic immunosuppressants based on the supportive therapy with renin- angiotensin system blockade. The efficacy and safety of tacrolimus in such refractory IgAN patients are extremely ambiguous, and the mechanism of tacrolimus improving proteinuria remission needs to be investigated. METHODS: 14 refractory IgAN patients were enrolled. The patients received tacrolimus (0.05-0.1 mg/kg/day) and prednisone (0.5 mg/kg/day) for at least 6 months. Synaptopodin and calcineurin expression were detected in renal tissues of patients who received re-biopsy. A puromycin aminonucleoside (PAN)-induced human podocyte injury model was applied to investigate the possible role of tacrolimus in proteinuria remission. RESULTS: Of the 14 patients enrolled, 3 were withdrawn because serum creatinine increased over 30% baseline. In 11 patients treated with tacrolimus over 6 months, 9 showed complete or partial remission and 7 achieved remission within 1 month. In renal tissues, the expression of calcineurin increased while synaptopodin decreased and recovered partially after tacrolimus therapy. In an in vitro study, F-actin disrupted in human podocytes after stimulation of PAN, while calcineurin increased and synaptopodin decreased. After co-treatment with tacrolimus the reorganization of F-actin and the expression of calcineurin and synaptopodin recovered. CONCLUSIONS: Tacrolimus showed a rapid proteinuria remission in refractory IgAN patients. The possible mechanism of tacrolimus to proteinuria remission might be podocyte cytoskeleton stabilization through inhibition of calcineurin expression.