Ultrasound-optimized hydrogel scaffold used to promote transdermal delivery of gold nanoparticles / 中国组织工程研究

BACKGROUND:Gold nanoparticles are of great significance in the development of multifunctional transdermal drug delivery systems.Smaller gold nanoparticles can penetrate the dermis through the intercellular pathway,but are limited to their easy agglomeration and colloidal morphology,which makes it difficult to exert effects on low delivery efficiency. OBJECTIVE:To develop an ultrasound-optimized hydrogel delivery system by combining phase change nanodroplets with bio-adhesive hydrogel for percutaneous delivery of gold nanoparticles. METHODS:The ultrasound-responsive nanodroplets loaded with gold nanoparticles were prepared by the emulsion solvent evaporation method and loaded into the polydopamine-modified methylacryloyl gelatin hydrogel to prepare a composite hydrogel scaffold.The structure and chemical composition of the ultrasound-responsive nanogold carrier were characterized.The microstructure,porosity,permeability,rheology,in vitro hemostasis,and antibacterial properties of the composite hydrogel were characterized.The cell compatibility of the hydrogel scaffold was evaluated by live/dead staining,and the optimization effects of low-intensity pulsed ultrasound on the permeability,porosity,and mechanical properties of hydrogel were evaluated. RESULTS AND CONCLUSION:(1)Transmission electron microscopy and ultraviolet-visible spectroscopy proved the successful construction of nanogold carriers.The particle size and potential results demonstrated that the synthesized nanoscaled ultrasonic responsive carrier had good stability.(2)Live/dead cell staining proved that the prepared composite hydrogel scaffold had certain biocompatibility.(3)Scanning electron microscopy exhibited that the prepared composite hydrogel scaffold had a porous network structure,and numerous pores of about 2 μm appeared inside the macropores after the addition of nanodroplets and ultrasonic irradiation.The permeability experiment displayed that low-intensity pulsed ultrasound could optimize the porosity and permeability of hydrogel materials.The hemostatic performance of the composite hydrogel scaffold was better than that of the hemostatic sponge and polydopamine@methylacrylylated gelatin hydrogel scaffold.Under the irradiation of low-intensity pulsed ultrasound,the composite hydrogel scaffolds had good antioxidant effects and antibacterial properties.(4)Thermal imaging results manifested that gold nanoparticles were encapsulated in ultrasound-responsive nanobubbles,and more uniform dispersion could be obtained under ultrasonic excitation.(5)The results of the mechanical property test demonstrated that the storage modulus of the hydrogel increased before and after loading gold nanoparticles-nanodroplets,which showed stronger mechanical properties.The elongation at break was 122%,and the ductility was better than that without gold nanoparticles-nanodroplets(P<0.05).(6)These findings indicate that the composite hydrogel scaffold has good biocompatibility,antibacterial property,oxidation resistance,and hemostatic effect.

Study on the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis / 中国药房

OBJECTIVE To explore the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis （HF）. METHODS Intragastrical administration of carbon tetrachloride was given to induce HF model. By observing the pathological changes in liver tissue， mRNA and protein expressions of HF indexes [α-smooth muscle actin （α-SMA）， collagen type Ⅰ] and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） pathway-related factors were detected， and the improvement effects and possible mechanism of low-dose， medium-dose and high-dose （50， 100， 200 mg/kg） of alcoholic extract from S. comosa on HF model rats were investigated. Drug-containing serum was prepared by intragastrical administration of alcoholic extract from S. comosa at a concentration of 1 800 mg/（kg·d） （calculated by the amount of raw material）. The effects of drug- containing serum of alcoholic extract from S. comosa on the expression of miRNA-21 were observed through the intervention of HSC-T6 cells with low， medium and high concentrations of drug-containing serum of alcoholic extract from S. comosa （diluted to 10%， 15%， 20%）. miRNA-21 mimics or inhibitors were used to transfect HSC-T6 cells， and the mRNA and protein expressions of factors related to the PI3K/Akt signaling pathway were detected. RESULTS The results of in vivo experiments showed that low， medium and high doses of alcoholic extract from S. comosa significantly ameliorated the histopathological changes in liver tissue of HF rats， and the percentage of collagen was significantly reduced （P＜0.01）； mRNA and protein expressions of the indicators related to HF as well as PI3K and Akt were significantly reduced （P＜0.01）， and mRNA and protein expressions of phosphatase and tensin homolog deleted on chromosome ten （PTEN） were increased in liver tissue of rats （P＜0.01）. The results of in vitro experiments showed that drug-containing serum of alcoholic extract from S. comosa significantly inhibited the expression of miRNA-21 at low， medium and high concentrations （P＜0.01）； whereas after transfection with miRNA-21 mimics， it was found that miRNA-21 mimics significantly increased mRNA and protein expressions of PI3K and Akt （P＜0.01）， while significantly decreased mRNA and protein expressions of PTEN （P＜0.01）； after transfection with miRNA-21 inhibitor， the changes of above indexes were opposite to the above results （P＜0.01）. CONCLUSIONS Alcoholic extracts of S. comosa may inhibit the PI3K/Akt signaling pathway by affecting the expression of miRNA-21， so as to achieve the effect of anti-hepatic fibrosis.

Short-term prognostic predictive value of deep-learning assisted quantitative myocardial contrast echocardiography in ST-elevated myocardial infarction after primary percutaneous coronary intervention / 中华超声影像学杂志

Objective:To explore the prognostic predictive value of deep neural network (DNN) assisted myocardial contrast echocardiography (MCE) quantitative analysis of ST-elevated myocardial infarction (STEMI) patients after successful percutaneous coronary intervention(PCI).Methods:A retrospective analysis was performed in 97 STEMI patients with thrombolysis in myocardial infarction-3 flow in infarct vessel after primary PCI in Renmin Hospital of Wuhan University from June to November 2021. MCE was performed within 48 h after PCI. Patients were followed up to 120 days. The adverse events were defined as cardiac death, hospitalization for congestive heart failure, reinfarction, stroke and recurrent angina. The framework consisted of the U-net and hierarchical convolutional LSTMs. The plateau myocardial contrast intensity (A), micro-bubble rate constant (β), and microvascular blood flow (MBF) for all myocardial segments were obtained by the framework, and then underwent variability analysis. Patients were divided into low MBF group and high MBF group based on MBF values, the baseline characteristics and adverse events were compared between the two groups. Other variables included biomarkers, ventricular wall motion analysis, MCE qualitative analysis, and left ventricular ejection fraction. The relationship between various variables and prognosis was investigated using Cox regression analysis. The ROC curve was plotted to evaluate the diagnostic efficacy of the models, and the diagnostic efficacy of the models was compared using the integrated discrimination improvement index (IDI).Results:The time-cost for processing all 3 810 frames from 97 patients was 377 s. 92.89% and 7.11% of the frames were evaluated by an experienced echocardiographer as "good segmentation" and "correction needed". The correlation coefficients of A, β, and MBF ranged from 0.97 to 0.99 for intra-observer and inter-observer variability. During follow-up, 20 patients met the adverse events. Multivariate Cox regression analysis showed that for each increase of 1 IU/s in MBF of the infarct-related artery territory, the risk of adverse events decreased by 6% ( HR 0.94, 95% CI =0.91-0.98). There was a 4.5-fold increased risk of adverse events in the low MBF group ( HR 5.50, 95% CI=1.55-19.49). After incorporating DNN-assisted MCE quantitative analysis into qualitative analysis, the IDI for prognostic prediction was 15% (AUC 0.86, sensitivity 0.78, specificity 0.73). Conclusions:MBF of the area supplied by infarct-related artery after STEMI-PCI is an independent protective factor for short-term prognosis. The DNN-assisted MCE quantitative analysis is an objective, efficient, and reproducible method to evaluate microvascular perfusion. Assessment of culprit-MBF after PCI in STEMI patients adds independent short-term prognostic information over qualitative analysis.It has the potential to be a valuable tool for risk stratification and clinical follow-up.

Postsystolic shortening and early systolic lengthening to diagnose myocardial microvascular dysfunction in patients with ST-segment elevation myocardial infarction after emergency percutaneous coronary intervention / 中华超声影像学杂志

Objective:To investigate the diagnostic value of postsystolic shortening (PSS) and early systolic lengthening (ESL) on myocardial microvascular dysfunction in patients with ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI).Methods:A total of 83 patients with STEMI who received emergency PCI in Renmin Hospital of Wuhan University from June to October 2021 were retrospectively collected. All patiets underwent two-dimensional echocardiography and myocardial contrast echocardiography (MCE) within 7 days after PCI. The patients were divided into global normal perfusion group and poor perfusion group according to global myocardial perfusion score index (MPSI). Left ventricular myocardium was divided into left anterior descending branch (LAD), left circumflex branch (LCx) and right coronary artery (RCA) regions, which were divided into regional normal perfusion group and poor perfusion group based on whether there were segments with microvascular dysfunction. Left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were measured by modified biplane Simpson method. Tomtec software was used to obtain conventional echocardiographic parameters, global longitudinal strain (GLS), as well as PSS and ESL parameters including postsystolic index (PSI), duration of postsystolic shortening (PSSduration), early systolic index (ESI) and duration of early systolic lengthening (ESLduration). Differences of parameters of global normal and poor perfusion groups, as well as regional normal and poor perfusion groups were compared. ROC curve was used to analyze the diagnostic value of PSS and ESL parameters and GLS in myocardial regions with microvascular dysfunction.Results:Significant differences were observed in LVEF, LVESV, GLS, PSI, ESI and PSSduration between global poor perfusion group and global normal perfusion group (all P<0.05). Compared with regional normal perfusion group, PSI, ESI and ESLduration of LAD and LCx regions, as well as PSI of RCA region in regional poor perfusion group were increased (all P<0.05). For GLS in different myocardial regions, LAD-GLS was the only parameter that decreased in regional poor perfusion group compared to regional normal perfusion group ( P<0.05). ROC curve analysis showed LAD-PSI, LAD-GLS, LCx-PSI, LCx-ESLduration and RCA-PSI were valuable parameters for diagnosis of myocardial microvascular dysfunction in different regions, among which LAD-PSI had the highest area under curve (AUC=0.809). Conclusions:PSS and ESL parameters are helpful for early diagnosis of myocardial microvascular dysfunction in STEMI patients after PCI, and can provide regional myocardial perfusion information according to the blood supply of different coronary arteries.

Spatio-temporal variations and coupling of human activity intensity and ecosystem services based on the four-quadrant model on the Qinghai-Tibet Plateau.

Human activities have an impact on the structure and function of ecosystems, which in turn affects ecosystem service (ES) supply and demand. Based on the four-quadrant model of human activities and ecosystem services, this study evaluated the ecological quality at the county scale on the Qinghai-Tibet Plateau (QTP). Results showed: (1) Human activity intensity (HAI) showed great spatio-temporal variations across the QTP. The mean HAI was low overall and increased by 4% during 2000-2015. HAI in more than 13% of the area of the QTP showed an increasing trend and high HAI levels were mainly distributed in the eastern and central parts. A low HAI level occupied the majority of the study area and declined during the period. (2) The mean ES balance declined during the period and exhibited great spatial variations, with the higher ES balance mainly distributed in the mid-eastern cities of the QTP. The ES balance in approximately 68% of the cities decreased, indicating the ESs were in degradation, with demand exceeding supply. (3) Approximately 98% of the study area, including 205 counties, was in the first, second and fourth quadrant, and only 2% was in the third quadrant, indicating that ecological quality became better overall on the QTP. During 2000-2015, 87.14% of counties were nearly unchangeable-these were distributed in the most regions of the QTP, and only 9.79% and 3.08% of counties were improving and degrading, respectively, mainly distributed in the mid-eastern regions. The change implied that the ecosystems were basically in a stable state and the environment greatly improved on the QTP from 2000 to 2015. This study contributes to exploring the effect of human activity on ecosystem service, thereby providing credible guidance for regional ecosystem management.

Berberine prevents primary peritoneal adhesion and adhesion reformation by directly inhibiting TIMP-1

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical morbidity. Enterolysis at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary adhesion. Here we studied the preventive effects of different approaches of berberine treatment for primary adhesion, and its effects on adhesion reformation compared to Interceed. We found the primary adhesion was remarkably prevented by berberine through intraperitoneal injection 30 min before abrasive surgery (pre-berberine) or direct addition into injured cecum immediately after the surgery (inter-berberine). Rats with adhesion reformation had a more deteriorative collagen accumulation and tissue injury in abrasive sites than rats with primary adhesion. The dysregulated TIMP-1/MMP balance was observed in patients after surgery, as well as adhesion tissues from primary adhesion or adhesion reformation rats. Inter-berberine treatment had a better effect for adhesion reformation prevention than Interceed. Berberine promoted the activation of MMP-3 and MMP-8 by directly blocking TIMP-1 activation core, which was reversed by TIMP-1 overexpression in fibroblasts. In conclusion, this study suggests berberine as a reasonable approach for preventing primary adhesion formation and adhesion reformation.

Long noncoding RNA SNHG14 facilitates colorectal cancer metastasis through targeting EZH2-regulated EPHA7.

Accumulating evidence suggested the participation of long noncoding RNAs (lncRNAs) in regulating various biological processes so as to affecting cancer progression. However, the functional role of most lncRNAs in colorectal carcer (CRC) is still largely covered. In the present study, we disclosed SNHG14 as a carcinogene in CRC development, as it was low-expressed in normal colon tissues but markedly upregulated in CRC cell lines. Besides, SNHG14 contributed to CRC cell proliferation, motility and EMT in vitro, and inhibition of it confined CRC tumor growth and liver metastasis in vivo. Next, the mechanistic investigations confirmed that SNHG14-promoted CRC progression was mediated by EPHA7, which was negatively regulated by SNHG14 in CRC via an EZH2-dependent way. Importantly, EZH2 was proved as a transcription factor of EPHA7 and functioned as a repressor in EPHA7 transcription by enhancing methylation on EPHA7 promoter. Meanwhile, SNHG14 increased EZH2 expression in CRC via stabilizing its mRNA by interacting with FUS, and via freeing its mRNA from miR-186-5p-induced silence. All in all, our observations demonstrated that SNHG14 serves as a facilitator in CRC through targeting EZH2-repressed EPHA7 by enhancing EZH2 via recruiting FUS and absorbing miR-186-5p, indicating a promising new road for CRC diagnosis and treatment.

Effects of alendronate on the function of osteoblasts / 生物医学工程学杂志

To provide a support to the clinical application of alendronate (Alen) on cytology, we studied the effects of Alen on the function of osteoblasts. In this experiment, we observed the influence of MG63 cell line co-incubation with Alen at concentrations of 1 x 10(-9) mol/L, 1 x 10(-7) mol/L or 1 x 10(-5) mol/L on the osteoblastic function (proliferation, cell morphology, alkali phosphatase (ALP) activity, expression of type I collagen and effect of calcium deposition). The proliferation, cell morphology, ALP activity and type I collagen synthesis of MG63 were not affected by Alen at concentration of 1 x 10(-9) mol/L and 1 x 10(-7) mol/L, but the ALP activity as well as type I collagen production were promoted at higher concentration (1 x 10(-5) mol/L). The calcium deposition of MG63 could be increased at the lower concentration (1 x 10(-9) mol/L), while it was inhibited at the higher concentration. In conclusion, Alen at low concentration can promote the mineralization ability of osteoblasts to a certain extent, and this benefits the bone formation.

Anti-tumor activity of safflower polysaccharide (SPS) and effect on cytotoxicity of CTL cells, NK cells of T739 lung cancer in mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study the anti-tumor activity of SPS in vivo and in vitro and the cytotoxicity of CTL cells, NK cells of T739 lung cancer in mice.</p><p><b>METHOD</b>The transplanted tumor model of S180 Sarcoma was established with KM mouse. The SPS was adminished i.p. for 10 d, the tumor weight was detected. The transplanted tumor model of LA795 lung cancer was established with T739 mouse and SPS was adminished i.p. for 10 d and the tumor weight and the cytotoxicity of CTL cells, NK cells were detected. The Anti-tumor activity of SPS on three types of tumor cells in vitro was observed with trypan blue exclusion staining.</p><p><b>RESULT</b>SPS 40 mg x kg(-1) can significantly inhibit the growth of S180 Sarcoma in mice and inhibitory rate was 51.33% (P<0.01). It can also inhibit the growth of LA795 lung cancer in mice and the tumor volume was reduced obviously for 3.29 mm3 (P<0.05). It can remarkably enhance the cytotoxicity of splenic CTL cells, NK cells in tumor-bearing (P<0.05).</p><p><b>CONCLUSION</b>SPS have anti-tumor effects, the mechanism of the anti-tumor activity may be related to enhance the cytotoxicity of CTL cell and NK cell.</p>

Acoustic Reflex Growth Function in Noise Induced Hearing Loss / 听力学及言语疾病杂志

Objective To explore the effects of noise exposure on acoustic reflex growth function (ARGF).Methods 106 ears of 57 industrial workers that exposed to high level continuous noise during their work day were divided into three groups according to pure-tone threshold average (PTA): normal hearing group, mild hearing loss group and moderately severe hearing loss group. The control group consisted of 50 ears of 25 young persons with normal hearing. The contralateral acoustic reflex thresholds (ART) were obtained from all individuals.1 000 Hz pure-tone stimuli was wsed to elicit the acoustic reflex at hearing levels from ART to 125 dB in 5 dB steps during ascending intensity level runs. The growth functions were observed as changes in acoustic reactance with increases in activator-signal intensity level.Results The noise exposed groups had smaller acoustic reflex dynamic ranges, smaller acoustic reactance growth magnitudes and shallow slopes compared with those of the control group. Data showed that there were significant differences among the control and the noise exposed groups (P0.05).Conclusion The influence of noise exposure on ARGF is significant. The results of this study suggest that ARGF could be used in the monitoring of the noise-induced hearing loss as an indicator of subtle alterations of the hearing function.