Novel discovery of schisandrin A regulating the interplay of autophagy and apoptosis in oligoasthenospermia by targeting SCF/c-kit and TRPV1 via biosensors

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10-15 g/L, and the quantitative limit reached 1.0 × 10-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (KD) of 5.701 × 10-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a KD of up to 4.181 × 10-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

Data-driven engineering framework with AI algorithm of Ginkgo Folium tablets manufacturing

Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate Cpk integrated Bootstrap-t. The Cpk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.

Study on the trial and pilot process optimization of insomnia granules / 国际中医中药杂志

Objective To optimize a method for extracting traditional Chinese medicine composition with insomnia,and to prepare the insomnia granules for quality control.Methods The optimal extraction process was screened by orthogonal test using high-performance liquid chromatography with geniposide as the evaluation index.The particle size,bulk density,angle of repose,moisture,solubility,hygroscopicity and loading difference of the insomnia granule were evaluated,and the difference between the trial test and the pilot test were analyzed to comprehensively monitor the quality of the insomnia granule.Results The best extraction process was to add 10 times of water and cooked it three times for 1.5 hours each time.The average yield rate of dry extract of the pilot test and trial test was 22.10％,15.52％,and the average yield of powder was 84.96％ and 93.12％,respectively.The conversion rate from the pilot test to the trial test is 76.97％.Both the trial test and the pilot test particles met the quality requirements of the 2015 edition of the pharmacopoeia.Conclusions The preparation method of the insomnia granules is simple and the quality is uniform.The results of the pilot scale showed that the conversion rate is high,the quality is controllable,and the technical feasibility of industrial production is obtained.

The value of three-dimensional speckle tracking echocardiography in detecting severe multi-vessel coronary artery stenosis / 中华超声影像学杂志

Objective To evaluate the diagnosis value of three-dimensional speckle tracking echocardiography ( 3D-STE) in severe multi-vessel coronary stenosis at resting state . Methods Ninety-one patients with chest tightness ,chest pain ,other related clinical symptoms ,and suspected coronary heart disease were enrolled and underwent coronary angiography ( CAG ) , two and three-dimensional echocardiography(2D-STE ,3D-STE) . According to CAG results ,the patients were divided into 3 groups:severe multi-vessel stenosis group ( n = 38 ) ,severe single-vessel stenosis group ( n = 22 ) ,and control group ( n =31) . All patients underwent two and three-dimensional echocardiography .3D-STE was applied to obtain left ventricular global longitudinal strain ( 3D GLS) ,global circumferential strain ( 3D GCS) ,global area strain (3D GAS) and global radial strain(3D GRS) . Receiver operating curve analysis was conduct to evaluate the diagnosis value of 3D-STE in severe multi-vessel coronary stenosis at resting state . Results 3D GLS ,3D GCS ,3D GAS and 3D GRS were decreased in the severe multi-vessel group and single-vessel stenosis group compared to those in the control group( P <0 .05) ;and greater decreases was observed in the severe multi-vessel stenosis group( P <0 .001) . Furthermore ,3D GLS and 3D GAS in the severe multi-vessel stenosis group were lower than those in severe single-vessel stenosis group( P <0 .05) . ROC curve showed that the cutoff value for 3D GLS was ≤ -11％ with a measurement sensitivity of 84 .2％ and cutoff value for 3D GAS was ≤ -20％ with a measurement specificity of 79 .3％ . A joint diagnostic test showed that the sensitivity was increased when 3D GLS was combined with at least one other parameters . Conclusions 3D-STE shows a great diagnostic potential when applied to detect severe multi-vessel coronary stenosis . Moreover ,GLS and GAS may act as more valuable indicators .

New sensor technologies in quality evaluation of Chinese materia medica: 2010-2015

New sensor technologies play an important role in quality evaluation of Chinese materia medica (CMM) and include near-infrared spectroscopy, chemical imaging, electronic nose and electronic tongue. This review on quality evaluation of CMM and the application of the new sensors in this assessment is based on studies from 2010 to 2015, with prospects and opportunities for future research.

Left ventricular volume and mitral annular motion under different occluders for atrial septal defect occlusion:an evaluation by real-time three-dimensional echocardiography / 中国组织工程研究

BACKGROUND:Occluder closure of atrial septal defect exhibits clear function, safety and efficiency advantages ＜br> OBJECTIVE:Using real-time three-dimensional echocardiography (RT-3DE) technique to evaluate the effect of atrial septal defect occlusion using different occluders on left ventricular structure and motion of the mitral annulus. ＜br> METHODS:Thirty-seven cases diagnosed as atrial septal defect underwent atrial septal defect occlusion, including 20 males and 17 females, aged 20-60 years. The occluder was chosen individual y according to defect size and edge hardness. Conventional and RT-3DE examinations were performed at 1 day prior to occlusion, 1 and 3 months after occlusion. ＜br> RESULTS AND CONCLUSION:Four of 37 patients were withdrawn from the study because of poor RT-3DE results. The other 33 patients harvested good occlusion results. At 1 and 3 months after occlusion, left ventricular end diastolic volume, left ventricular end systolic volume, left atrial end diastolic volume, left atrial end systolic volume were significantly increased (P＜0.05). Moreover, the more increase in these parameters occurred at 3 months after occlusion (P＜0.05). There were no significant changes in left ventricular ejection fraction and mitral annular displacement at three different time points. Left ventricular volume change rate and left atrial volume change rate were positively correlated to the type of occluders, while there was no correlation between endocardial cushion stump and mitral annular displacement. These findings suggest that atrial septal defect occlusion can increase the volume of the left ventricle and left atrium, but exhibit no effect on the motion of the mitral annulus.

Study on Drug Pair of Cassia Twig and White Peony Root by HPLC/MS Analysis Based on Theory of“Xin-Gan Hua-Yang and Suan-Gan Hua-Yin” / 世界科学技术-中医药现代化

This article was aimed to study the different clinical characteristics using drug pair of Cassia twig and white peony root with the contents ratio of 1:1 and 1:2. Based on the different clinical treatment of drug pair of Cas-sia twig and white peony root, different compositional ingredients in ratio of 1:1 and 1:2 were illuminated by HPLC/MS method. The drug pair of Cassia twig and white peony roots in ratio of 1:1 and 1:2 and single herbs were ex-tracted for HPLC/MS analysis. A protocol was followed, including acetonitrile - 0.1% acetic acid with gradient elution, positive mode, 350℃ capillary temperature and 300℃ vaporization temperature. The results showed that Procyanidol B2 and 2-Hydroxy cinnamal dehyde can be extracted from single Cassia twig, but 2-Hydroxy cinna-mal dehyde cannot be detected in drug pair. It showed the contents of Procyanidol B2 in 1:1 ratio was more than 1:2 ratio. Simultaneously, Palbinone, paeoniflorin sulfonate, 1,2,3,6-Tetra-O-galloyl-β-D-glucose, Paeoniflorin, Pae-oniflorin isomers, Benzoylpaeo-niflorin, and Benzoyl Paeoniflorin isomers can also be dissolved in white peony root. In addition, the contents of 1,2,3,6-Tetra-O-galloyl-β-D-glucose, Paeoniflorin, Benzoylpaeo-niflorin, and Benzoyl Paeoniflorin isomers in 1:1 were more than 1:2. The contents of Palbinone, paeoniflorin sulfonate and Paeoniflorin isomers in 1:2 were more than 1:1. It was concluded that Procyanidol B2, 1,2,3,6-Tetra-O-galloyl-β-D-glucose, Paeoniflorin, Benzoylpaeo-niflorin and Benzoyl Paeoniflorin isomers in 1:1 were more than 1:2. The contents of Pal-binone, Paeoniflorin sulfonate and Paeoniflorin isomers in 1:2 were more than 1:1. It provided a scientific basis for traditional Chinese medicine treatment using rational drug pair.

Optimization of Near Infrared Variable Selection Method Based on Multivariate Detection Limit / 世界科学技术-中医药现代化

This study was aimed to optimize the near infrared (NIR) variable selection method based on multivariate detection limit (MDL). Using Qing-Kai-Ling (QKL) injection as object, three variable selection methods (interval par-tial least-squares, iPLS; backward interval partial least squares, BiPLS; moving window interval partial least squares, mwPLS) were used to establish the PLS models of baicalin in QKL injection, respectively. The prediction ability of different variable selection method was compared. MDL of all models were calculated in contrast to the MDL value of full spectra PLS model, to select optimal variable selection method. The results showed that different variable selec-tion methods had different prediction ability. Among them, iPLS had the best performance which determination coef-ficient of prediction (Rpre2) and the root mean square errors of prediction (SEP) were 0.996 5 and 602.3 μg·mL-1, re-spectively. All MDLs of different variable selection methods were reduced compared with the full spectra PLS model. The value of iPLS was the lowest comes to be 1.19 μg·mL-1. The results above indicated that the best variable se-lection method for baicalin in QKL injection was iPLS. MDL theory took the error of calibration and validation set and the leverage of external sample into account, which can comprehensively evaluate model detection performance compared to the classic chemical indicator parameters. This method was particularly suitable for the variable selec-tion method optimization of NIR quantitative model of low concentration sample such as Chinese herbal medicine.

Rapid Assessment of Critical Quality Attributes of Chinese Materia Medica：Visualization Technology of Near Infrared Chemical Imaging / 世界科学技术-中医药现代化

Near infrared chemical imaging (NIR-CI) is an emerging technology for rapidly analyzing the critical quality attribute of Chinese materia medica (CMM). It integrates NIR spectroscopy with chemical imaging. In this paper, it provided a systematic introduction to NIR-CI, such as the core part of instrument, the reliability, transformation, analysis and application of high-dimensional data acquisition. In addition, current studies of NIR-CI application in pharmaceutical field were analyzed. Finally, future opportunities and challenges of NIR -CI applications in the quality control of CMM preparation were prospected.

Study on Rapid Elemental Analysis of Tibetan Medicine “GTso Thal” by LIBS Technique / 世界科学技术-中医药现代化

Laser-induced breakdown spectroscopy (LIBS) was applied to perform qualitative research on Tibetan medicine “GTso Thal” in order to establish a rapid element analysis method . The Nd: YAG laser with the funda-mental frequency at 1064 nm was used. A high-power laser beam was focused on the surface of the sample. The spectrometer and CCD was used to detect its spectrum signals. Based on the National Institute of Standards and Technology (NIST) database, emission spectrum characteristics were differentiated. The LIBS spectra of “GTso Thal”showed multi-elements including Hg, Ca, Na, As, Fe, Mg, Al, K, Li, Pb, Ag, Au and S. Among them, Hg, Pb, Ag and Au were heavy mental elements. The results demonstrated that LIBS was a viable technique for analysis of Ti-betan medicine “GTso Thal”. LIBS provided reliable elemental analysis on Tibetan medicine “GTso Thal”. The de-tection was real-time, rapid and in situ. It had prospects in the elemental analysis of ethnic medicine study. LIBS had broad application prospects.

A Study on Model Performance for Ethanol Precipitation Process of Lonicera japonica by NIR Based on Bagging-PLS and Boosting-PLS algorithm / 分析化学

ToprovidethemethodologyforrapidqualityevaluationofLonicerajaponica,wehaveestablished the stable quantitative model of near infrared spectroscopy ( NIR) . The performance of Bagging partial least squares (Bagging-PLS) model and Boosting partial least squares (Boosting-PLS) model was compared with that partial least squares ( PLS ) model based on the NIR data of ethanol precipitation process of Lonicera japonica. On this basis, the performance of these two models after variables selection was also studied by the methods of siPLS ( synergy interval partial least squares ) and CARS ( competitive adaptive reweighted sampling) . The experimental results showed that the prediction performance of Bagging-PLS and Boosting-PLS models was superior to PLS model with the latent factor of 10 . The band of 820-1029 . 5 nm and 1030-1239. 5 nm for the first batch was selected by the method of siPLS. In addition, the band of 820-1029. 5 nm and 1030-1239. 5 nm was selected for the second batch sample in the same method. Furthermore, the method of CARS was taken to select variables for the two batches samples with 5-fold cross-validation and 10-fold cross-validation. And the lowest RMSECV( root mean square error of cross-validation) values were used to take subset. Compared to the model performance without the method of CARS, the RMSEP value of the Bagging-PLS model and Boosting-PLS model for the concentration of chlorogenic acid reduced by 0 . 02-0 . 04 g/L and rp(correlation coefficient of prediction)value increased by 4%-5%. Generally, Bagging-PLS and Boosting-PLS could be regarded as rapid prediction methodsfor NIR quantitative models of ethanol precipitation process of Lonicera japonica.

Impact of sample data repeatability on NIR calibration model / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the impact of repeated data acquisition on the stability of NIR quantitative calibration model, and make a preliminary analysis on reasons for the impact.</p><p><b>METHOD</b>Yinhuang decoction was used as the subject, and NIR spectrum samples were collected. By reference to HPLC's determination value, the baicalin quantitative calibration model was established by using recursive least square algorithm to detect cumulative-LVs curve of latent variables. The impact of calibration model caused by repetitive samples was explained in latent variance space.</p><p><b>RESULT</b>After averaging the repetitive spectrum samples, quantitative prediction model, which was built by optimal method of spectrum pretreatment, showed the ideal prediction result (RMSECV = 1.824). The area under the cumulative-LVs curve of latent variables was obviously larger than other modeling methods, i. e., this model is more stable.</p><p><b>CONCLUSION</b>Averaging of multiple measurements can dramatically improve the predictive ability of the model and make the model more stable.</p>

Study on morphology and function of mitral valve leaflets and mitral annulus in patients with mild mitral regurgitation by real-time three-dimensional echocardiography / 中华超声影像学杂志

Objective To measure the parameters of mitral valve leaflets and mitral annulus in patientswithmildmitralregurgitation( MR )byreal timethree-dimensionaltransesophagealechocardiography (RT-3D-TEE),and explored the mechanism of MR.MethodsFifty-seven MR subjects were selected and twenty-eight subjects without mitral regurgitation were served as control group,all subjects were examined by RT-3D-TEE and acquired image,mitral valve quantification (MVQ) software was used for post-processing.Mitral annulus parameters (H/DAIPm,E2D,θAv-Mv,mitral annulus θnpa) and mitral valve leaflets parameters(A3DE,L2DAIPm,VA1-3tentVp1-3tentVtentHtentθnpa ) at the end of systolic were measured.The results of two groups were compared,and the most affected parameters to mild mitralregurgitation were selected.Results Compared with control group,VA3tent was decreased,mitral annulus θnpa and L2DAIPm increased,and the mitral valve leaflets θnpa was independently correlation factor of mild mitral regurgitation.ConclusionsThe mitral annulus geometry to flat in subjects with mild MR,the mitral valve local area is increased in subjects with mild MR,the mitral valve leaflets θnpa is independently correlation factor of mild mitral regurgitation.

Observation of urokinase targeted microbubbles dissolved the thromb in vivo by electron microscope / 中华超声影像学杂志

Objective To study the change of thrombosis in rabbits arteries by electron microscope after thromb was lyses by urokinase targeted microbubbles.Methods A total of 24 rabbits with plateletrich thrombi in the femoral artery were randomized into 4 treatment groups (n = 6) :(1) ultrasound alone (US) ; (2) urokinase alone (UK); (3) ultrasound, non-targeted microbubble and urokinase (US + M + UK) ;(4) ultrasound, platelet-targeted microbubble and urokinase (US + R + UK).Urokinase targeted microbubbles were in conjunction with the surface of commercial microbubbles (SonoVue) by direct conjugation method.US was simultaneously applied transcutaneously over the thrombus up to 30 min.The thrombolytic effect was based on ultrasound, blood flow and histological observations at 120 min post treatment.Results US + R + UK group was completed recanalization (P ＜ 0.001).Scanning electron microscope examination showed thrombosis of the fiber network structure damage.Conclusions The main electron microscope change of RGDS urokinase targeted microbubbles dissolve thromb is thrombus fibrin network structure damage and fibrin dissolution.

Study of left atrial appendage function in patients with atrial fibrillation by three-dimensional echocardiography and speckle tracking imaging / 中华超声影像学杂志

Objective To evaluate left atrial appendage regional function and movement changes of systolic and diastolic in patients with atrial fibrillation by speckle tracking imaging(STI) and real-time three-dimensional transesophageal echocardiography(RT-3D TEE).Methods Sixty-seven patients underwent RT-3D TEE was divided into 24 controls,22 paroxysmal atrial fibrillation,21 persistent atrial fibrillation.Left atrial appendage was divided into basal,middle and apical segment.Left atrial appendage emptying fraction of the overall (LAA-EF),basal emptying fraction (B-EF),middle emptying fraction (M-EF) and apical emptying fraction (A-EF) was measured by three-dimensional volume measurement.Each segment systolic strain rate (SRS) and diastolic strain rate (SRD) was measured by STI.Results LAA-EF,B-EF,M-EF,A-EF of paroxysmal atrial fibrillation and persistent atrial fibrillation group were lower than those of the control group,and persistent atrial fibrillation group was the lowest in the three groups.Compared with the control group,SRS and SRD of left atrial appendage basal,middle,apical segment was lower in paroxysmal atrial fibrillation group and persistent atrial fibrillation group,and persistent atrial fibrillation group decreased more significantly.Conclusions Paroxysmal atrial fibrillation and persistent atrial fibrillation can lead to left atrial appendage global or local systolic and diastolic function to reduce,and persistent atrial fibrillation decreased more significantly.

Assessment of left ventricular time-related deformations in post-infarction rats by ultrasound speckle tracking imaging / 中华超声影像学杂志

Objective To evaluate left ventricular (LV) remodeling and function after acute myocardial infarction (MI) in rats using speckle tracking imaging (STI). Methods The left anterior descending coronary was ligated to induce MI in twenty normal rats. One day after creation of MI, fifty survivals based on the diagnostic criteria of MI were divided into 4 groups as follows:pre-infarction, 1 day,4weeks,and 8 weeks after MI. Echocardiography was performed to evaluate the changes of left ventricularfunction in rats. M-mode and two-dimensional cross-sectional echocardiography data were acquired at the papillary muscle level and digitally stored for further analysis. Circumferential strain rate(SRcir) and radial strain rate(SRrad) indexes were measured by STI software for each animal. Results One day after MI,indexes of SRcir and SRrad in anterior and lateral segments were significantly decreased (P ＜0.01, for both). Four weeks after MI,compared with baseline,SRrad and SRcir were decreased in all segments ( P ＜0.01). Eight weeks after MI, however, SRrad and SRcir showed no significant difference compared with 4weeks group. Conclusions STI can correctly identify LV dysfunction in rats and can be used for serial assessment of cardiac remodeling in rats models.