OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

【Objective】 To explore the diagnostic value of platelet long non-coding RNA (lncRNA) as a biomarker for early screening of lung adenocarcinoma (LUAD). 【Methods】 The GSE183635 and GSE89843 datasets, which contained the platelet transcriptome of LUAD and healthy controls, were used for differential analysis, and the intersection of the differentially expressed lncRNA(DElncRNA) of the two datasets was taken. The expression levels of DElncRNA in LUAD tissues and normal control tissues were analyzed using GEPIA2. The expression levels of LINC01088 in platelets of 51 healthy controls and 54 LUAD patients were detected by quantitative Real-time PCR (qRT-PCR), and the diagnostic ability of each index was evaluated by ROC curve. 【Results】 8 DElncRNAs and 1 265 DElncRNAs were obtained from GSE183635 and GSE89843 datasets, respectively. The key DElncRNA LINC01088 was selected after intersection. GEPIA2 analysis showed that the expression level of LINC01088 in LUAD tissues was lower than that in normal lung tissues (P<0.05). Platelet LINC01088 was significantly downregulated in patients with LUAD and early-stage LUAD than in healthy controls(P<0.001). The area under the curve (AUC) of platelet LINC01088 in the diagnosis of LUAD was 0.755, the sensitivity was 81.1%, and the specificity was 67.9%. The AUC for early LUAD diagnosis was 0.727, the sensitivity was 80.0%, and the specificity was 67.9%. The AUC of the combined diagnostic model composed of platelet LINC01088 and carcinoembryonic antigen (CEA) for LUAD diagnosis was 0.807, the sensitivity was 89.2%, and the specificity was 71.4%. The AUC for early LUAD was 0.770, the sensitivity was 86.7%, and the specificity was 71.4%. The combined diagnostic model of platelet LINC01088 and CEA was superior to CEA in the diagnosis of LUAD and early LUAD (Z=-2.288, -2.34, both P<0.05). 【Conclusion】 LINC01088 is down-regulated in platelets of LUAD patients. Platelet LINC01088 may be a biomarker for early screening and diagnosis of LUAD.

Objective:To explore the expression and importance of Piezo1, E-cadherin, and Vimentin in nasal polyps patients. Methods:Thirty-five patients undergoing endoscopic sinus surgery under general anesthesia were streamed into 20 cases of nasal polyps（NP group） and 15 cases of simple septoplasty without any sinus disease（Control group）. Immunofluorescence staining and Western Blot were applied to detect the protein level of Piezo1, E-cadherin, and Vimentin in NP tissues and nasal polyp-derived primary human nasal epithelial cells（pHNECs）. Also, BEAS-2B cell lines were treated with human TGF-β1 protein to establish epithelial mesenchymal transition（EMT） model in vitro and quantitative real-time polymerase chain reaction were used to calculate Piezo1 and above biomarkers in the model. Results:Compared with control group, Piezo1 and Vimentin showed higher level while E-cadherin was lower in NP tissues and pHNECs.In EMT model in vitro, Piezo1 and Vimentin were demonstrated higher expression with decreased level of E-cadherin. Conclusion:The tendency of Piezo1 is consistent with the mesenchymal-related biomarker Vimentin, going against with epithelial-related biomarker E-cadherin, implying its involvement with EMT process in nasal polyps.
Humans ; Biomarkers/metabolism* ; Cadherins/metabolism* ; Chronic Disease ; Epithelial-Mesenchymal Transition ; Nasal Polyps/metabolism* ; Rhinosinusitis ; Sinusitis ; Transforming Growth Factor beta1/metabolism* ; Vimentin/metabolism*

【Objective】 To investigate the effects of platelet activation pathways on the characterization of platelet-derived extracellular vesicles(PEVs). 【Methods】 Whole blood from healthy donors was prepared into platelet suspension by centrifugation. Platelets were randomly divided into six groups, the ctrl group added no extra stimulus, and the other five groups were treated with collagen, adenosine diphosphate(ADP), thrombin, Ca²⁺ ionophore and freeze-thaw cycles (F-T) to activate platelets. Platelet-derived exosomes(PEXOs) and microvesicles(PMVs) were isolated by differential centrifugations, and then were determined by nano-flow cytometry and electron microscopy. The protein markers of PEXOs also were identified by western-blot. The protein concentration and content of PEXOs were also detected. 【Results】 CD9, CD81, TSG101 proteins were detected in all of the PEXOs, which had no calnexin. Both PEXOs and PMVs had CD41; PEXOs were cup-holder-like bilayer membrane vesicles under a transmission electron microscope, while PMVs were irregular membranous structure; 85%-95% of PEXOs were<100nm, 87%-94% of PMVs were 100-300nm. The concentration of exosomes and microvesicles in the F-T group was the highest(205.67±65.27 and 102.73±15.48), followed by the Ca²⁺ ionophore group(44.42±17.07 and 11.4±4.81). Although in the same size range, the numbers of PEVs induced by different activation conditions varied. The protein concentration of PEXOs in the F-T group(1.11±0.51) was higher than that in the control group(0.32±0.39), ADP group(0.41±0.31) and thrombin group(0.38±0.37), while the total protein(125.40±58.32) was higher than that in other three groups(the ctrl group 25.53±25.96 vs ADP group 37.21±15.73 vs thrombin group 36.28±24.18 vs Ca²⁺ ionophore group 47.09±23.29). 【Conclusion】 The biological characteristics of PEVs are affected by platelets activation pathways, whose ability to induce protein-packing into exosomes may also be relevant to the particle size. The freeze-thaw cycles can induce high concentrations of extracellular vesicles, which may be an ideal method for the preparation of PEVs.

Currently, the public’s concern for health has unprecedentedly increased, while some institutions find it difficult to carry out health lectures. Overall, health lectures play an important role, but they face some practical challenges at the operational level, involving lecture objectives, public demands, communication methods, dissemination channels, and foothold methods. In the era of new media, health science popularization lectures are still an effective means of persuasion today, but traditional lecture methods need to be endowed with new connotations, and made shifts and adjustments. Health science popularization lectures should make the following shifts. First, the lecture objectives should turn to "extensive use", stepping out of the limitations of popular science knowledge, and promoting the public to proactively seek health knowledge and information. Second, the lecture content should turn to the integration of physical and mental, designing courses from the perspective of physical and mental, enhancing communication among people, and promoting trust between individuals. Third, the lecture effect should turn to enjoyment, breaking the prejudice against the lecture effect and taking the enjoyment and interest stimulation as the important goal of health science popularization. Fourth, the speaker should turn to "professionalization", establishing a team of professional health lecturers. At the operational level, it is necessary to strictly control the entry and exit of health lecturers to create a lecture brand, segment the audience to organize homogeneous audiences, tell good stories and enhance emotional narration, plan holistically and achieve full-media three-dimensional communication, and scientifically evaluate and emphasize long-term effects.

Objective To evaluate the application value of fetal heart echocardiography intelligent navigation (5D Heart) in the display of key diagnostic elements in five rapid screening fetal echocardiographic views.Methods Three hundred and eighty-four 3D volume datasets of 220 normal singleton fetuses in the second and third trimesters were acquired.After processing the datasets using 5D Heart,five rapid screening views were acquired,and 21 key diagnostic elements of the five cardiac diagnostic sections were graded.The 2 test was used to compare the difference in the key diagnostics elements of the five rapid screening views between 5D heart and the traditional technique.Pearson correlation was used to compare the detection rate of key diagnostic elements between 5D Heart technique and traditional two-dimensional echocardiography in normal fetuses and fetuses with congenital heart disease.The rank sum test was used to detect the consistency and reliability of the results.Results A total of 384 fetal volume datasets were obtained from 220 fetuses,of whom 317 heart volume datasets were available for analysis,with a success rate of 82.6％.There was no difference in the key diagnostic elements of the five rapid screening views between 5D heart and the traditional technique (x2=5.17,P=0.27).Compared with the abnormal fetal heart group (89.6％),the detection rate of diagnostic elements in the normal fetal heart group was 85.2％ (r=0.94,P=0.02).No significant differences were found when comparing the grading results of one observer in different periods of time,the grading results between two experienced doctors,or the grading results among the experienced doctor and one relatively inexperienced doctor (P ＞ 0.05).Conclusions Fetal cardiac ultrasound intelligent navigation technique has high reliability and repeatability in obtaining fetal rapid screening views and displaying fetal elemental diagnostic information.It has tremendous potential in standardized data collection and analysis of cardiac diagnostic sections in fetuses with congenial heart disease,as well as in training and teaching,remote medical consultation,and screening in primary hospitals.

Objective To evaluate the effectiveness of spatio-temporal image correlation with M-mode display ( STIC-M ) in monitoring fetal left ventricular systolic function in fetuses with congenital heart disease(CHD) . Methods Five hundred and thirty-six normal fetuses and 34 fetuses with CHD( 29 without hydrops and 5 with hydrops) were involved in the study . Left ventricular fractional shortening ( LVFS) was measured using STIC-M . The data of normal fetuses was used to construct reference ranges of LVFS for assessment of fetuses with CHD . Results The LVFS of the normal fetuses [ range :26 .8％ - 42 .9％ , mean :( 34 .9 ± 4 .1) ％ ] was negatively correlated with gestational age ( r = - 0 .16 , P < 0 .001) . Compared with the normal controls ,LVFS was significantly decreased in CHD fetuses with hydrops ( P < 0 .001) . However ,there was no significant difference in LVFS between normal controls and CHD fetuses without hydrops ( P > 0 .05) . Conclusions STIC-M is a new method that can be used to measure LVFS to evaluate fetal ventricular systolic function . The fetal ventricular contractile function of CHD fetuses without hydrops may not be damaged or is in compensation stage . The fetuses with cardiac hydrops generally become lower .

Objective To evaluate the feasibility and value of automated cardiac motion quantitation (aCMQ) for measuring the global and regional longitudinal strain of left ventricle in fetuses . Methods One hundred and eighteen normal fetuses were divided into 4 groups by gestational age ,standard four-chamber view clips were collected ,the global and segmental longitudinal peak systolic strain of the left ventricle were measured by aCMQ ,the variabilities of interobserver and intraobserver were analyzed . Results The success rate of aCMQ analysis was 89% . There was no significant correlation between the gestational age and the global and segmental longitudinal peak strain of the left ventricle ( r were 0 .00－0 .14 ,all P ＜0 .05) . The base and middle segmental strain values of left ventricular free wall were similar to that of the interventricular septum ( P ＞0 .05) . The strain of the apex segment was higher than those of the base and middle segment ( P ＜ 0 .05) . Interobserver and intraobserver variability showed a small bias among the observers . Conclusions aCM Q is a feasible and reproducible approach to quantitatively evaluate normal cardiac function of fetus and may have potential in fetuses with congenital heart diseases .

Objective To evaluate the application value of real-time three-dimensional echocardiography (RT-3D TEE) in nonvalvular atrial fibrillation patients after transcatheter left atrial appendage closure (LAAC) with the Amplatzer Cardiac Plug (ACP).Methods The two-dimensional transesophageal echocardiography (2D TEE) and RT-3D TEE were performed in selected patients to measure the diameter of left atrial appendage ostium and landing zone,to observe left atrial appendage morphology and lobular distribution.These were also performed to guide the whole process of transcatheter LAAC with ACP,which included the atrial septal puncture,sheathing canal cruise,occluder device implantation,and verifying the stability of occluder device and releasing the device.It involved observing ACP occluder morphology,location,stability,surrounding residual shunt,whether influencing the mitral valve and left superior pulmonary vein flow,and pericardial effusion.Results A total of 15 patients (100％) successfully underwent LAAC with the ACP.The maximum diameter of left atrial appendage ostium by 2D-TEE measurement during operation was (20.5 ± 2.9)mm,located at 135°.The diameter of left atrial appendage landing zone was (17.1 ± 2.8) mm,located at 45°;(18.0 ± 4.0) mm,located at 90°;(22.1 ± 4.7)mm,located at 135°,respectively.The left atrial appendage morphology:2 had one leaf and 13 had two leaves or more,including 2 cases of bifoliate short neck shape.In 15 patients,6 cases of cauliflower type,2 cases of wind sock type,3 cases of chicken wing type,2 cases of cactus type and 2 cases of complex type.The proximal left atrial appendage morphology:3 cases of boot type,2 cases of wide mouth type,6 cases of narrow mouth type,2 cases of straight tube type,and 2 cases of bifoliate short neck type.There was no obvious residual shunt in all the patients at immediately post-operation.Conclusions In the transcatheter LAAC with the ACP,RT-3D TEE has important application value in the preoperative selection of patients,the choice of appropriate occluder,guidance of full-process monitoring during operation,the postoperative effect evaluation and so on.

Membrane type-1 matrix metalloproteinase (MT1-MMP or MMP14) plays the pivotal role in tumor development and metastasis, so it is a promising drug target in malignancy. To acquire MT1-MMP specific binding peptides, we first analyzed MMPs sequences to find the divergent and specific sequence of MT1-MMP by bioinformatics approach, then set the specific sequence as the sense peptide target and designed antisense peptide library. Finally, by means of molecular docking, molecular dynamics simulation and in vitro cell assays, we screened the antisense peptide library against MT1-MMP and further studied the obtained specific peptides. Here, we identified the divergent and specific sequence of AYIREGHE (Named MT1-loop) located in MT1-MMP loop by multiple sequence alignment and established the antisense peptides library with capacity of 1 536 sequences. After two rounds of virtual screening, we obtained five antisense peptides with Rerankscores in the top for further screening. They all interacted with MT1-MMP, and docked well at the active site composed of MT1-loop sequence. Analysis of the affinities of these five antisense peptides to other MMPs (MMP1-3, MMP7-13, MMP14 HPX, MMP16) revealed that the peptide FVTFPYIR was more specific to MT1-MMP. Molecular dynamics simulation showed that the peptide FVTFPYIR might affect the stability of MT1-MMP and thus have effects on its activities. Meanwhile, the peptide FVTFPYIR could specifically inhibit the growth of MG63 and MDA-MB-231 tumor cells both of which expressed MT1-MMP. The work provides a new insight and way for the development of antitumor lead peptides targeting MT1-MMP.
Amino Acid Sequence ; Humans ; Matrix Metalloproteinase 14 ; chemistry ; Molecular Dynamics Simulation ; Neoplasms ; Peptide Library ; Peptides ; chemistry