The LMIT: Light-mediated minimally-invasive theranostics in oncology.

Minimally-invasive diagnosis and therapy have gradually become the trend and research hotspot of current medical applications. The integration of intraoperative diagnosis and treatment is a development important direction for real-time detection, minimally-invasive diagnosis and therapy to reduce mortality and improve the quality of life of patients, so called minimally-invasive theranostics (MIT). Light is an important theranostic tool for the treatment of cancerous tissues. Light-mediated minimally-invasive theranostics (LMIT) is a novel evolutionary technology that integrates diagnosis and therapeutics for the less invasive treatment of diseased tissues. Intelligent theranostics would promote precision surgery based on the optical characterization of cancerous tissues. Furthermore, MIT also requires the assistance of smart medical devices or robots. And, optical multimodality lay a solid foundation for intelligent MIT. In this review, we summarize the important state-of-the-arts of optical MIT or LMIT in oncology. Multimodal optical image-guided intelligent treatment is another focus. Intraoperative imaging and real-time analysis-guided optical treatment are also systemically discussed. Finally, the potential challenges and future perspectives of intelligent optical MIT are discussed.

Automatic Segmentation of Laser-Induced Injury OCT Images Based on a Deep Neural Network Model.

Optical coherence tomography (OCT) has considerable application potential in noninvasive diagnosis and disease monitoring. Skin diseases, such as basal cell carcinoma (BCC), are destructive; hence, quantitative segmentation of the skin is very important for early diagnosis and treatment. Deep neural networks have been widely used in the boundary recognition and segmentation of diseased areas in medical images. Research on OCT skin segmentation and laser-induced skin damage segmentation based on deep neural networks is still in its infancy. Here, a segmentation and quantitative analysis pipeline of laser skin injury and skin stratification based on a deep neural network model is proposed. Based on the stratification of mouse skins, a laser injury model of mouse skins induced by lasers was constructed, and the multilayer structure and injury areas were accurately segmented by using a deep neural network method. First, the intact area of mouse skin and the damaged areas of different laser radiation doses are collected by the OCT system, and then the labels are manually labeled by experienced histologists. A variety of deep neural network models are used to realize the segmentation of skin layers and damaged areas on the skin dataset. In particular, the U-Net model based on a dual attention mechanism is used to realize the segmentation of the laser-damage structure, and the results are compared and analyzed. The segmentation results showed that the Dice coefficient of the mouse dermis layer and injury area reached more than 0.90, and the Dice coefficient of the fat layer and muscle layer reached more than 0.80. In the evaluation results, the average surface distance (ASSD) and Hausdorff distance (HD) indicated that the segmentation results are excellent, with a high overlap rate with the manually labeled area and a short edge distance. The results of this study have important application value for the quantitative analysis of laser-induced skin injury and the exploration of laser biological effects and have potential application value for the early noninvasive detection of diseases and the monitoring of postoperative recovery in the future.

Comparative study on effects of single and multiple oral administration of mungbean (Phaseolus radiatus L.) seed extract on the pharmacokinetics of aconitine by UHPLC-MS.

The study was aimed to investigate the effects of single and multiple oral administration of mungbean (Phaseolus radiatus L.) seed extract (ME) on the pharmacokinetics of aconitine in rats. The Sprague-Dawley rats were randomly divided into three groups (six rats each group). In group 1, rats were orally administered 500 µg/kg aconitine after receiving a single oral dose of 1 g/kg ME. In group 2, rats were orally administered with 500 µg/kg aconitine at day 7 of treatment with 1 g/kg/day ME. In group 3, rats were orally administered with 500 µg/kg aconitine. Blood samples were collected at different time points (0.083, 0.25, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 and 10.0 h). The concentration of aconitine in rats plasma was determined by a fully validated ultra-high-performance liquid chromatography coupled with mass spectrometry method. The results showed that single and multiple oral co-administration of ME significantly altered the pharmacokinetic parameters of aconitine.

Comparative pharmacokinetics of five saponins after intravenous administration of TSFS injection and TSFS injection plus TFFG in rats under different physiological states.

Sanqi is a popular traditional Chinese medicine and commonly used for promoting blood circulation and removing blood stasis. Notoginsenoside R1, ginsenoside Rg1, Re, Rb1 and Rd are the major active constituents of Sanqi. The purpose of the study was to investigate the pharmacokinetic behavior of the five active constituents from total saponin from Sanqi when it was used in the blood stasis animals or in combination with Gegen. The concentrations of the five active constituents in rat plasma were determined by an ultra-HPLC-ESI-MS/MS method. The main pharmacokinetic parameters were calculated and statistically analyzed using the unpaired student's t-test. It was found that the pharmacokinetic parameters of notoginsenoside R1, ginsenoside Rg1 and Rb1 represented a statistically significant difference (P<0.05) between the normal rats and the blood stasis rats after administration of total saponin from Sanqi (TSFS). And there were statistically significant differences (P<0.05) in the pharmacokinetic parameters of all the five constituents between administration of TSFS alone and combined with total flavonoid from Gegen (TFFG) in blood stasis rats. It suggested that the pharmacokinetic behavior of the active constituents from TSFS could be changed when it was used in blood stasis animals or in combination with TFFG.

Pharmacokinetics, tissue distribution and excretion study of dictamnine, a major bioactive component from the root bark of Dictamnus dasycarpus Turcz. (Rutaceae).

Dictamnine is an herbal ingredient isolated from the root bark of Dictamnus dasycarpus Turcz. (Rutaceae). The present study was aimed at the development of an ultra-high performance liquid chromatography-tandem mass spectrometry method to quantify the concentration of dictamnine in rat plasma and tissues for the in vivo pharmacokinetics, tissue distribution and excretion study. Biological samples were processed with protein precipitation. Skimmianine was chosen as internal standard. The chromatographic separation was carried out on a Thermo Syncronis C18 column (2.1mm×50mm, 1.7µm) with an isocratic mobile phase consisting of methanol and 0.1% formic acid water (75:25, v/v). The detection was accomplished by using positive ion electrospray ionization in multiple reaction monitoring (MRM) mode. The MS/MS ion transitions were monitored at m/z 200.0→129.0 for dictamnine and 260.3→227.1 for IS, respectively. An excellent linearity was observed over the concentration range from 0.5 to 250ng/mL. The lower limit of quantification (LLOQ) was 0.5ng/mL for dictamnine. The developed method was rapid, accurate, and highly sensitive and selective. It was successfully applied to the in vivo pharmacokinetics, tissue distribution and excretion study of dictamnine in rats after oral or intravenous administration of dictamnine.

Pharmacokinetic comparisons of puerarin, daidzin and the glucuronide metabolite of puerarin after administration of total flavonoid from Gegen alone and total flavonoid from Gegen combined with total saponin from Sanqi in rats under different physiological states.

Gegen is one of the most commonly used traditional Chinese medicines for promoting blood circulation and removing blood stasis. Puerarin and daidzin are the main active constituents of Gegen. Puerarin is mainly metabolized in rats by glucuronidation and the major metabolite from rat urine has been identified as puerarin-7-O-glucuronide through semi-preparative HPLC isolation and then spectroscopic analysis. The study investigated the pharmacokinetic behavior of puerarin-7-O-glucuronide (without enzymatic hydrolysis), puerarin and daidzin when total flavonoid from Gegen was administered in normal and blood stasis animals or in blood stasis animals alone or in combination with Sanqi. The plasma samples were processed by protein precipitation with methanol, and chromatographed on a Thermo Syncronis C18 column (10cm×2.1mm, 1.7µm) by gradient elution at a flow rate of 0.25mL/min, and detected with a triple quadrupole tandem mass spectrometer by selected reaction monitoring via electrospray ionization source with positive ionization mode. An unpaired Student's t-test was used for the statistical comparison of the main pharmacokinetic parameters. There were statistically significant differences (P<0.05) in the pharmacokinetic parameters of puerarin-7-O-glucuronide, puerarin and daidzin involving the AUC, CL and Vd not only between normal rats and blood stasis rats after administration of total flavonoid from Gegen, but also between administration of total flavonoid from Gegen alone and in combination with total saponin from Sanqi in blood stasis rats. The results obtained suggest that the pharmacokinetic behavior of puerarin-7-O-glucuronide, puerarin and daidzin are changed when total flavonoid from Gegen was administered in blood stasis animals or in combination with total saponin from Sanqi.

Simultaneous determination of limonin, dictamnine, obacunone and fraxinellone in rat plasma by a validated UHPLC-MS/MS and its application to a pharmacokinetic study after oral administration of Cortex Dictamni extract.

A rapid and selective ultra high performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of four major ingredients in Cortex Dictamni extract, including limonin, dictamnine, obacunone and fraxinellone in rats plasma. Nimodipine was used as the internal standard. Following extraction by methyl tert-butyl ether, the analytes were separated on a Thermo Syncronis C18 column by a gradient elution within a runtime of 9min. The mobile phase consisted of A (methanol) and B (2mmol/L ammonium acetate in water). The detection was accomplished by using positive ion electrospray ionization in multiple reaction monitoring mode. The method was linear for all analytes over investigated range with all correlation coefficients greater than 0.998. The lower limits of quantification were 9.18ng/mL for limonin, 12.0ng/mL for dictamnine, 16.05ng/mL for obacunone and 4.59ng/mL for fraxinellone. The intra- and inter-day precision (RSD%) was within 10% and the accuracy (RE%) ranged from -12.9% to 9.7%. This rapid and sensitive method was fully validated and successfully applied to the pharmacokinetic study of limonin, dictamnine, obacunone and fraxinellone in the rat plasma after oral administration of Cortex Dictamni extract.