As a pleiotropic cytokine, interleukin-6 (IL-6) participates in many physiological activities in vivo. IL-6 plays an important role in the physiology and pathology of chronic inflammation, autoimmune diseases, tumors and other diseases through diverse mechanisms. At present, inhibitors targeting IL-6/IL-6R have been shown to improve treatments for some inflammatory diseases such as rheumatoid arthritis and systemic juvenile idiopathic arthritis. IL-6 binds to a specific receptor to activate the downstream JAK/STAT3 signaling pathway. However abnormally activated STAT3 often appears in various types of malignant tumors and participates in the occurrence and development of tumors. In addition, studies have shown that IL-6 is a key factor in the cytokine storm associated with COVID-19 patients. The physiological participation of IL-6/STAT3 pathway in complex diseases makes this pathway become a research hotspot for drug discovery. Therefore, we summarize the latest research progress of small molecular inhibitors on IL-6/STAT3 signaling pathway, in order to provide a reference for the development of IL-6/STAT3 related drug in the future.

Objective To investigate the consistency of the anatomical parameters of left atrial appendage (LAA) based on three-dimensional transesophageal echocardiography (3D-TEE) and CT of 3D print datasource by the post-processing of DICOM data.Methods Sixty-three patients with atrial fibrillation in our hospital who underwent 3D-TEE and cardiac CT examination were selected and the original DICOM data of the LAA were obtained.The volume images of LAA were acquired by the postprocessing of Mimics software.After measuring and evaluating the anatomical parameters,the differences of parameters between TEE and CT were compared and the consistency of the two methods was evaluated.Results The data of 63 patients with atrial fibrillation obtained by 3D-TEE and CT were successfully post-treated and the detailed anatomical parameters of LAA were obtained.Morphological parameters:the Kappa values of the anatomical shape and opening shape of the LAA based on the 3D-TEE and CT data were 91.0%,69.3%,respectively.Measurement parameters:the area,perimeter,long axis,short axis of ostiums of LAA,and depth of LAA by CT were larger than those by 3D-TEE(all P<0.05).The post-processing results showed that 57 patients (90.5%) had significant bending of LAA′s main lobe in the 3D-TEE group and CT group,the difference in the measurements of the angle of the first bend and the distance from the first bend of the LAA to the orifice of the 57 cases between by 3D-TEE and CT were no statistical significance (P>0.05).LAA′measurements of 3D-TEE was concordant well with CT′s by Bland-Altman analysis.Conclusions In agreement with CT,3D-TEE can also be used as a datasource for 3D printing by evaluating spatial morphology of the LAA.

Objective:To meet the individualized needs of residents in standardized residency training of cardiac intervention specialty for cardiac ultrasound teaching, to construct a bionic 3D printing model of ultrasound source, and to discuss its application value in ultrasound teaching and simulation exercises.Methods:Sixty residents majored in cardiovascular medicine receiving standardized residency training of ultrasound in ultrasound imaging department of Renmin Hospital of Wuhan University were randomized into experimental group and control group in average. The experimental group adopted ultrasound bionic 3D printing heart model combined with problem-based learning (PBL) teaching method, and the control group adopted traditional multimedia PPT combined with PBL teaching method. At the end of teaching activities, theoretical examination, operation assessment and questionnaire survey were conducted to evaluate and compare the teaching effect between the two groups. SPSS 21.0 software was performed for t test. Results:The theoretical examination scores of the experimental group and the control group were (81.4±8.2) points and (74.8±9.4) points, respectively, P=0.002, and the operation assessment scores were (89.1±5.6) points and (71.5±8.8) points, respectively, P<0.001. The questionnaire survey showed that the experimental group had better feedbacks than the control group in the aspects of mastery of heart anatomy knowledge, learning experience, learning interest, learning efficiency, understanding of interventional heart disease, clinical skills of interventional operation and overall satisfaction (all P<0.05). Conclusions:Ultrasound bionic 3D printing combined with PBL teaching method can help strengthen the mastery of cardiac anatomy knowledge, promote the learning experience of cardiac ultrasound and improve the skills of interventional operation. The teaching effect is significant and the students' satisfaction is high.

OBJECTIVE:To study the time-effect and dose-effect of paeonol on the apoptosis of knee osteoarthritis(OA)artic-ular chondrocyte in rabbits and the mRNA expression of its related protein Bcl-2 and Bax. METHODS:60 big-ear rabbits were ran-domly divided into normal (normal saline) group,model (normal saline) group,paeonol high-dose,medium-dose and low-dose groups and triamcinolone acetonide(positive drug)group,with 10 rabbits in each group. Except for normal group,OA model was induced by right knee anterior cruciate ligament (ACLT) and the medial meniscus 1/3 resection in those groups. After modeling, different doses of paeonol(0.8,0.4,0.2 mg/kg),triamcinolone acetonide 0.2 mg/kg were injected into right articular cavity twice a week. 4 weeks and 8 weeks after administration,articular cartilage specimens were collected. Ultrapathological structure changes of articular chondrocytes were observed by electron microscope. Apoptosis of cartilage cell was observed by TUNEL and apoptotic index was calculated. mRNA expression of apoptosis related genes of Bcl-2 and Bax in articular cartilage tissue of rabbits were de-tected by in situ hybridization technique. RESULTS:Compared with normal group,articular chondrocyte of model group showed early and middle stage apoptosis morphology change after 4 and 8 weeks,and apoptosis index increased significantly and the mRNA expression of Bcl-2 and Bax was up-regulated (P<0.01);4 and 8 weeks later after administration,compared with model group,apoptosis index decreased and mRNA expression of Bax was down-regulated in paeonol groups,while mRNA expression of Bcl-2 was up-regulated(P<0.05 or P<0.01). Electron microscopy ultrastructural observation showed articular chondrocyte of pae-onol high-dose and middle-dose groups were in early stage of apoptosis.CONCLUSIONS:Paeonol can slow down articular chondro-cyte degeneration and destroy in OA model rabbits in time and dose dependently. Its mechanism may be associated with expression up-regulation of Bcl-2 and expression down-regulation of Bax.

Objective To evaluate the feasibility and accuracy of three-dimensional (3D) printed left atrial appendage (LAA) models based on 3D transesophageal echocardiography (3D-TEE) data and the application value for treating special anatomic LAA.Methods Data of 18 patients of atrial fibrillation who were underwent LAA occlusion were retrospectively analyzed,including 3D-TEE and CT volume data of the patients.The 3D-TEE data of the LAA were post-processed and a flexible material was used to print the LAA model by 3D printer.The morphological classification and lobulated classifications of LAAs were assessed by the 3D printed models.The measurements of long axis,short axis and depth of LAAs were also performed.And the measurement and classification results were compared with those based on 3D-TEE and CT volume images.A occluder release test was performed on the 3D printed models for patients with challenging LAA morphology.Results For all 18 patients,3D-TEE full volume data of the LAA were successfully reprocessed and printed as 3D LAA models.The consistency of morphological classifications and lobulated classifications of LAAs based on 3D printed models and cardiac CT were 0.92 and 0.83,respectively.No significant differences of LAA ostium dimensions (long axis and short axis) and depth were found between the measurement results based on 3D printed models and 3D-TEE (all P＞0.05).A simulation of LAA occlusion rehearsal was successfully performed on 3D models of two challenging cases.Conclusion The echocardiographic 3D printing technique has high feasibility and accuracy,and can be promising for personalized planning in cases of transcatheter special morphological LAA occlusion.

Objective:To understand and compare the online learning effect of students majoring in stomatology and dental technology under the background of COVID-19 epidemic prevention and control, and to analyze the advantages and challenges of online teaching, so as to provide reference for the reform of teaching mode of stomatology education.Methods:A questionnaire survey on online learning was carried out among 267 students majoring in stomatology and 92 students majoring in dental technology in Chongqing Medical University. The results were statistically analyzed by SPSS 21.0, and chi-square test or rank sum test was used to count the data.Results:Computers and mobile phones are the main tools for students to study online. 52.92% of students used computers and 38.72% used smart phones. About 80% of the students said that they could adapt to online learning, and there was no statistical difference between the students of two majors. The online learning time of students majoring in stomatology was mainly 4-6 hours, while that of students majoring in dental technology was 2-4 hours, with statistical significance. However, the latter were more likely to ask questions to teachers than the former, and the proportion of students who often asked questions to teachers was 29.35% and 20.60%, respectively, with statistical significance. A small number of students of both majors failed log on the platform to learn and complete all the teaching materials on time. More than 50% of the students thought that online teaching was not as effective as offline teaching, and offline teaching was more conducive to mastering curriculum knowledge, without statistical differences between the students of two majors. They thought that the unsmooth learning platform, poor network conditions at home, and insufficient teaching materials prepared by teachers were the main reasons that affected the online learning effect.Conclusion:The online teaching is an important and also an advisable way to maintain teaching activities during the epidemic prevention and control of COVID-19. It will be the direction of further research on the education and teaching reform to make full use of information technology, combine the advantages of online teaching and traditional classroom teaching, and actively explore the blended teaching mode from the perspective of specialty and course characteristics.

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC₅₀) and selectivity index (SI) values of 2.36 μmol·L^-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (K_D) value of 1.36 μmol·L^-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

OBJECTIVETo study the effect of Tangshenkang Granule (TG) containing serum on renal mesangial cells' (RMCs) proliferation and TGF-β1/Smad2/3 pathway in the high glucose condition.

METHODSTwelve SD rats were randomly divided into four groups, i.e., the low dose TG group, the middle dose TG group, the high dose TG group, and the blank control group, 3 in each group. After 7-day gastrogavage via portal vein blood, rats were sacrificed and their serum samples were collected. RMCs were cultured in common rat serum and TG containing serum respectively. The proliferation of mesangial cells was determined by methly thiazolyl tetrazolium (MTT) assay to determine the optimal TG containing serum concentration. Expression levels of TGF-β1 mRNA and protein were determined by real time quantitative PCR and ELISA. Smad2/3 protein expression and phosphorylation were determined by Western blot and immunofluorescence.

RESULTSTG containing serum at different doses could inhibit high glucose induced RMC cells' proliferation, TGF-β1 over-expression and Smad2/3 phosphorylation.

CONCLUSIONTG containing serum could inhibit high glucose induced RMC cells' proliferation, and its mechanism might be possibly associated with inhibiting TGF-β1/Smad2/3 signaling pathway.

Animals ; Cell Proliferation ; Drugs, Chinese Herbal ; pharmacology ; Glucose ; Mesangial Cells ; Phosphorylation ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Serum ; Signal Transduction ; Smad2 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

To establish HPLC specific chromatogram and its correlation with the protection effect of Shuanghuanglian on MDCK (Madin-Darby canine kidney) cell injury induced by influenza A virus( H1N1). Nine recipes of Shuanghuanglian based on the official prescription were prepared according to orthogonal test for HPLC analysis and MDCK cells protection experiment separately (cytopathic effect (CPE) method was used for observing the virus infectivity and MTT staining results were used as the determining indexes for drug concentration selection and analyzing cell viability). The results suggested that all the other Shuang-Huang-Lian recipes except recipe1 demonstrate protecting effect on MDCK cell injury induced by influenza A virus (P < 0.01, P < 0.001). Stepwise regression analysis was used for analyzing the relationships between HPLC fingerprint and the protecting effect of Shuanghuanglian on influenza A virus induced MDCK cell injury. Peak 2, 3, 6, 8 and 12 were found to be strongly related with anti-influenza A virus efficacy. Stepwise regression analysis of recipes data and efficacy data showed that Lonicerae Japonicae Flos and Forsythiae Fructus were positively associated with the protecting effect of cells injury. From HPLC fingerprints, we found that peak 2, 3, 12 were from Lonicerae Japonicae Flos and peak 6, 8 were from Forsythiae Fructus. Four peaks were identified through comparing the retention time between the standard and Shuanghuanglian recipes, and they were chlorogenicacid, cryptochlorogenic acid, forsythoside B and 3,4-dicaffeoylquinic acid respectively. Caffeic acid derivatives in Lonicerae Japonicae Flos and Forsythiae Fructus were found to be greatly correlated with anti-influenza A virus efficacy and maybe the substance basis of Shuanghuanglian.
Animals ; Antiviral Agents ; analysis ; pharmacology ; Chromatography, High Pressure Liquid ; methods ; Dogs ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Forsythia ; chemistry ; Influenza A Virus, H1N1 Subtype ; drug effects ; physiology ; Lonicera ; chemistry ; Madin Darby Canine Kidney Cells ; Scutellaria baicalensis ; chemistry