Objective: To determine the main components of Astragalus membranaceus (Fisch.) Bge (A. membranaceus, Huang Qi), Astragaloside IV (AIV) and Astragalus polysaccharides (AP), to characterize their properties, evaluate their in vivo efficacy, and to analyze drug diffusion using dissolving microneedle (DMN) technology in vivo. Methods: Respectively, AIV- and AP-loaded DMNs comprising chitosan (CTS) and polyvinyl alcohol (PVA) were prepared via dual-mold forming. Their morphology, mechanical properties, in vivo solubility, and skin irritation characteristics were tested. In vivo efficacy was assessed in cyclophosphamide-induced immunosuppressed mice, in vivo diffusion of AIV and AP by DMNs and conventional methods was compared, and the rheological properties of AIV-CTS-PVA and AP-CTS-PVA mixtures were measured. Results: Subcutaneous dissolution and absorption of AIV-CTS-PVA and AP-CTS-PVA microneedles (MNs) at low doses (50%–17% of intraperitoneal AIV injection and 12%–4% of intravenous AP injection) reduced the spleen index and acid phosphatase activity in immunosuppressed mouse models, increased the thymus index, and achieved equivalent or better systemic therapeutic effects. Compared with injections, AIV and AP achieved controllable solid-liquid conversion through delivery with CTS-PVA MNs, resulting in highly localized aggregation within 48 h, reducing the initial explosive effect of the drug, and achieving stable and slow drug release. Conclusion The present study enhances our understanding of the efficacy and remote effects of drug-loaded DMNs from a traditional Chinese medicine (TCM) perspective, thereby promoting the development of precise and efficient delivery of TCM and further expanding the drug-loading range and application scenarios for DMNs.

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.
Biocompatible Materials/metabolism* ; HMGB1 Protein/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Bone Substitutes/metabolism* ; Dendritic Cells/metabolism*

The chemical complexity of traditional Chinese medicines (TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform (TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included: (1) selection of herbal drugs of target based on TCMs knowledge base; (2) chemome profiling of TCMs extract library by LC‒MS; (3) cytological profiling of TCMs extract library by high-content cell-based imaging; (4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes; (5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs (Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089 mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.

Objective:To summarize the clinical outcomes and experience of redo median sternotomy on proximal aortic repair. Investigate the relationship between first operation and reoperation, reoperation indications, cardiopulmonary bypass strategy, intraoperative technical details, early and mid-term postoperative results.Methods:There were 28 patients underwent 29 times of redo median sternotomy on proximal aorta from April 2017 to December 2019. There were 23 males (79.3%) with an average age of (45.1±12.7) years (26-79 years), 15 Marfan syndrome (15/29, 51.7%) and 3 Behcet's disease (3/29, 10.3%). The primary operation included aortic valve or mitral valve replacement, Bentall procedure, ascending aortic replacement, simultaneous abdominal aortic replacement, Sun's procedure and coronary artery bypass grafting. The indications for reoperation were: aortic root aneurysm or coronary artery aneurysm, anastomotic leakage, perivalvular leakage due to inflammatory aortic disease, acute or chronic type A aortic dissection and aortic root abscess, aortic arch aneurysm. The surgical methods were Bentall, Cabrol, wheat, aortic valve sparing root replacement with replantation, anastomotic leakage repair, CABG, total arch replacement + stent elephant trunk implantation (Sun's procedure), ascending aorta to abdominal aorta bypass, abdominal aortic replacement.Results:One patient (3.4%) died in hospital because of severe postoperative pulmonary complications, consolidation of both lungs, ARDS and hypoxia. Postoperative low cardiac output was occurred in 2 cases (6.9%), 1 case was cured by ECMO, and 1 case died half a year after operation during follow up period. Re-exploration for postoperative hemorrhage was occurred in three cases (10.3%). Renal failure requires dialysis was 3 cases (10.3%), and transient paresis was 1 cases (3.4%), respectively. All of them were recovered before discharge. During the follow-up period, one patient died of multiple organ failure due to low cardiac output, and one patient underwent total thoracoabdominal aortic replacement. One patient underwent Cabrol for aneurysm of the coronary artery after Bentall procedure. One year later, type A dissection occurred again and Sun's procedure was performed through a median sternotomy.Conclusion:Reoperation of proximal aorta after cardiac and aortic surgery is safe and effective, with good short-term and medium-term results. Comprehensive preoperative evaluation, successful sternotomy, establishment of cardiopulmonary bypass and effective organ protection are the key to successful operation. Patients with aortic diseases, especially Marfan syndrome, are more likely to undergo reoperation. Close follow-up and timely reoperation are necessary to avoid aortic rupture. Sun's procedure is suitable for redo complex arch operation.

Objective:To summarize our clinical experience in the treatment of aortic root aneurysm by aortic valve sparing root replacement.Methods:From May 2017 to October 2019, a total of 20 patients with aortic root aneurysm underwent aortic valve sparing root replacement by reimplantation method. There were 17 males and 3 females, with an average age of(35.6±15.8) years(12-63 years). There were 11 cases of Marfan syndrome, 5 cases of bicuspid aortic valve, and 1 case of redo operation. The preoperative diameter of ascending aorta was(40.6±9.7)mm, the diameter of aortic sinus was(52.2±9.2)mm, and the diameter of aortic valve ring was(27.1±3.6)mm. There were 10 cases of no or mild regurgitation, 5 cases of moderate regurgitation and 5 cases of severe regurgitation. In the whole group of patients, the root replacement of aortic valve was retained by reimplantation, and the artificial graft were selected as: 26, 28 and 30mm straight vessels, 1, 3 and 6 cases, respectively, 26 and 28mm artificial graft with valsalva sinus, 4 and 6 cases, respectively. During the operation, aortic valve cusp repair was performed in 6 cases, such as plication of the free margin( 4 cases), decalcification(1 case) and raphe release(1 case).Results:None of the patients died in hospital or underwent rethoracotomy for hemostasis. During the operation, the duration of CPB time was(171.0±25.6) minutes and the duration of cross-clamp time was(134.0±23.2) minutes. There were 12 cases of aortic valve regurgitation and 8 cases of mild regurgitation. The mean follow-up was(15.1±9.8) months(4-33 months). During the follow-up period, there were 2 cases with moderate aortic regurgitation no need reoperation, while the rest of the patients had no or mild regurgitation. There are no patients undergoing reoperation. During the follow-up, 1 patient suffered coronary artery embolism in left circumflex artery and recovered after medicine treatment.Conclusion:Reimplantation with aortic valve sparing root replacement is safe and effective in the treatment of aortic root aneurysm, and the early and mid-term follow-up results are satisfactory, which can avoid anticoagulation-related complications and is suitable for young patients.

Objective:To investigate the expression and significance of T helper cell 17 (Th17), soluble intercellular adhesion molecule-1 (sICAM-1) and coagulation function in patients with infectious endocarditis(IE).Methods:From December 2016 to December 2018, IE patients in Beijing Anzhen Hospital Affiliated to Capital Medical University who met the inclusion criteria were selected for cardiac surgery to analyze prospectively, 38 IE patients were selected as the observation group, and 30 healthy people were selected as the control group.The concentrations of serum Th17 related factors (IL-1β, IL-6, IL-17 and IL-21), sICAM-1 and coagulation index(P selectin(sP-SLT)) were measured by enzyme-linked immunosorbent assay(ELISA) and the difference between the two groups were statistically analyzed.Results:The concentrations of serum IL-1β, IL-6, IL-17 and IL-21((29.88±6.49), (14.89±3.31), (21.89±3.01), (563.26±67.36) ng/L) in the observation group were significantly higher than those in the control group((16.56±4.11), (7.52±2.34), (12.91±1.01), (423.38±56.49) ng/L)(all P<0.05). The level of serum sICAM-1 and sP-SLT ((1 247.57(581.39, 1 794.66) μg/L, (60.29±6.61) mg/L)in the observation group were significantly higher than those in the control group((837.28(405.68, 954.47) μg/L, (27.37±5.56) mg/L), and the difference was statistically significant( Z=12.37, t=22.30, all P<0.05). The level of serum IL-1β, IL-6, IL-17 and IL-21 in patients with postoperative infective endocarditis((16.19±4.07), (7.73±2.40), (13.83±0.94), (425.33±52.12) ng/L) were significantly lower than those before operation((29.88±6.49), (14.89±2.31), (21.89±3.01), (563.26±67.36) ng/L), and the differences were statistically significant(t values were 11.02, 13.25, 15.76, 9.98, all P<0.05). The levels of sICAM-1 and sP-SLT1 in patients with postoperative infective endocarditis((901.46(472.15, 1276.58) μg/L, (30.70±5.31) mg/L) were significantly lower than those before operation((1 057.26±463.06) μg/L, (60.29±6.61) mg/L)and the differences were statistically significant( Z=11.16, t=21.51, P<0.05). Conclusion:Th17 related factors, sICAM-1 and sP-SLT were highly expressed in IE patients, and the concentrations of these factors decreased after operation, suggesting that the above factors may be used as related factors for the diagnosis and prognosis of IE patients.

Objective:To study the virological and serological indicators before treatment and 24 weeks after treatment to predict the partial virological response (PVR) of 48-week entecavir (ETV) treatment, and formulate early clinical adjustment treatment plans for HBeAg-positive CHB patients.Methods:HBeAg-positive CHB-na?ve patients diagnosed in the Department of Infectious Diseases, Shengjing Hospital, China Medical University, who were treated with oral ETV monotherapy from January 2018 were enrolled. The groups were divided according to the test results of HBV DNA at 48 weeks. Among them, HBV DNA < 20 IU/ml was the complete viral response (CVR) group, and HBV DNA ≥ 20 IU/ml was the PVR group. The virological and serological indexes of the two groups before treatment and 24 weeks after treatment were compared. ROC curve univariate analysis and multivariate logistic regression were performed to find out the early predictors of PVR in HBeAg-positive CHB patients receiving ETV therapy for 48 weeks.Results:As of July 2020, a total of 90 cases had completed 48 weeks of treatment, including 50 cases of CVR (55.56%) and 40 cases of PVR (44.44%). Before treatment and at 24 weeks of treatment, HBsAg, HBeAg and HBV DNA in the PVR group were significantly higher than those in the CVR group ( P < 0.001). Univariate analysis showed that HBV DNA quantification (AUC = 0.961, P < 0.001, PPV = 97.06%, NPV = 87.50%) and HBeAg quantification (AUC = 0.883, P < 0.001, PPV = 90.63%, NPV = 81.03%) had higher predictive value at 24 weeks of treatment. Multivariate analysis showed that HBeAg > 1.952 log 10 S/CO ( OR = 3.177, 95% CI: 1.261 ~ 8.267, P = 0.018) and HBV DNA > 2.205 log 10 IU / ml ( OR = 43.197, 95% CI: 6.858 ~ 272.069, P < 0.001) were independent predictors of PVR at 24 weeks of treatment, and their combination had the best predictive effect. Conclusion:In HBeAg-positive CHB patients receiving ETV treatment for 48 weeks, HBV DNA combined with HBeAg quantification can be an early predictor of PVR at 24 weeks. Additionally, patients with both HBV DNA and HBeAg > 2 log 10 at 24 weeks of treatment must wait 48 weeks to obtain CVR, so it is recommended that treatment strategies should be adjusted at this time.

Objective To evaluate the safety and efficiency in aortic root disease .Methods From April 2017 to April 2018,46 cases of aortic root disease accepted DavidⅠ[20 cases, 15 males and 5 females, aged(39.6 ±15.8)years, aortic root diameter was(58.3 ±4.4)mm] or Bentall[26 cases, 22 males and 4 females, aged(50.8 ±12.6)years,aortic root diam-eter was(59.5 ±5.0)mm], the data in the peri-operation and heart function in recent period after operation.Results No mortality was observed in the study.Morbidity occurred in both group was comparable.Mean cross-clamp time(129.5 ±28.6) min vs.(94.3 ±35.3)min(P<0.05).Blood transfusion(342.0 ±476.4)ml vs.(330.8 ±651.3)ml(P>0.05).ICU sta-ying time(1.0 ±0.2)day vs.(1.1 ±0.3)day(P>0.05).At the latest visit(10.5 ±6.8)months in David Ⅰ, no obviously regurgitation of aortic valve were observed 0.75 ±0.44 vs 1.0 ±1.3(P>0.05).Conclusion Except for the prolonged cross-clamp time, David Ⅰ is safely and effective in aortic root disease compared with Bentall in peri-operative period .The long term results need further follow-up.

Objective: To summarize experience and result in surgical treatment of Stanford type A intramural hematoma. Methods: 60 patients with Stanford type A intramural hematoma were operated from February 2015 to August 2017. Surgery was indicated in complicated cases with penetrating ulcer or ulcer-like projection in ascending aorta, maximum aorta diameter≥50 mm, progressive maximum aortic wall thickness≥10 mm, pericardial or pleural effusion, persistent or recurrent pain. Aortic valve regurgitation. In our group, 46 patients recieved ascending aorta replacement+ Sun' s procedure. 6 patients recieved Bentall+ Sun' s procedure. 4 patients recieved asceding aorta+ hemiarch replacement. 2 patients recieved Bentall+ hemiarch replacement. 2 patients recieved asceding aorta replacement. Results: In the whole group, there was 1(1.7%)operative death because of multiple organ failure after operation. Hyoxemiaoccured in 5(8.3%) patients, 2(3.3%) patients occurred new renal failure and required CRRT treatment, cerebrovascular complication occurred in 1 (1.7%)patient, re-sternotomy due to bleeeding occured in 1 (1.7%)patient and paraplegia occured in 1(1.7%) patient after operation. but they recoved quickly after proper treatment. During follow up period, there were 4 cases need reintervention, including TEVAR for type B dissection at 3 months and distal stent-graft new entry at 1 year. Two other reinterventions were performed for endoleak by interventional occlusion. During the follow-up, hematoma absorption rates after treatment 1、3 and 6 months were 68.6%, 84.7% and 94.8%. Conclusion Given the dynamic evolution of acute type A IMH pre-operative accurate indications and the proper surgical strategy maybe the keys for success.

Objective To construct a model of small caliber vascular endothelial growth factor(VEGF) in tissue engineering,to investigate the performance of the sustained-release microspheres and vascular stent,and to provide materials and theoretical basis for animal experiment.Methods The sheep carotid arteries were treated with a cellular reagents,the cellular conditions and the stent properties were observed.Preparation of sustained release microspheres containing VEGF,particle size,encapsulation efficiency,drug loading and release curve were measured.The effective combination of the slow release microsphere and the vascular stent was used in the freeze drying technology.The rat vascular endothelial cells grown in tissue engineered blood vessel model release lumen,observe the growth of endothelial cells.Results After the treatment,the original performance of the vascular stent can be maintained.The average particle size of the microspheres was (9.8 ± 6.0) μm,which could be released slowly in 20 days,and the release rate was 70％.Microspheres can effectively with the tissue.engineering blood vessel tight binding.Rat vascular endothelial cells can grow in the vascular stent surface.Conclusion Using Triton X-100,DNA/RNA ribozyme for acellular reagent,stent performance is good.PLGA microspheres have good sustained release performance,and constructing appropriate tissue engineered small caliber vascular release model by using freeze drying technology can make the stent compact structure.