Isoproterenol pre-treatment improve the therapeutic efficacy of cardiosphere-derived cells transplantation for myocardial infarction.

Background: This study aimed to investigate the effect of isoproterenol pre-treatment on the therapeutic efficacy of cardiosphere-derived cells (CDCs) transplantation for myocardial infarction (MI). Methods: Thirty 8-week-old male Sprague-Dawley (SD) rat model of MI was generated by ligation of the left anterior descending artery. The MI rats were treated with PBS (MI group, n=8), CDCs (MI + CDC group, n=8) and isoproterenol pre-treated CDCs (MI + ISO-CDC group, n=8), respectively. In the MI + ISO-CDC group, CDCs were pre-treated by 10-6 M isoproterenol and the cultured for additional 72 h, then injected to the myocardial infraction area like other groups. At 3 weeks after the operation, echocardiographic, hemodynamic, histological assessments and Western blot were performed to compare the CDCs differentiation degree and therapeutic effect. Results: Isoproterenol treatment (10-6 M) simultaneously inhibited proliferation and induced apoptosis of CDCs, up-regulated proteins of vimentin, cTnT, α-sarcomeric actin and connexin 43, and down-regulated c-Kit proteins (all P<0.05). The echocardiographic and hemodynamic analysis demonstrated that the MI rats in the two CDCs transplantation groups had significantly better recovery of cardiac function than the MI group (all P<0.05). MI + ISO-CDC group had better recovery of cardiac function than the MI + CDC group, although the differences did not reach significant. Immunofluorescence staining showed that the MI + ISO-CDC group had more EdU-positive (proliferating) cells and cardiomyocytes in the infarct area than the MI + CDC group. MI + ISO-CDC group had significantly higher protein levels of c-Kit, CD31, cTnT, α-sarcomeric actin and α-SMA in the infarct area than the MI + CDC group. Conclusions: These results suggested that in CDCs transplantation, isoproterenol pre-treated CDCs can provide a better protective effect against MI than the untreated CDCs.

Analyzing the Relationship between Supervisors and Post-Graduates Based on Differential Game Theory.

A healthy relationship between supervisors and postgraduates is critical for their academic achievements and personal development. This paper quantitatively discusses such a relationship from the viewpoint of differential game theory. First, a mathematic model was established to describe the evolutionary dynamics of the academic level of the supervisor-postgraduate community, which is related to the two parties' positive and negative efforts. Then, the objective function aimed at maximizing the individual and total benefit of the community was constructed. After that, the differential game relationships in the non-cooperative, cooperative and Stackelberg scenarios were formulated and solved. A comparison of the three game scenarios showed that the optimal academic level and total benefit of the community were 22% higher in the cooperative scenario than in the non-cooperative and Stackelberg game scenarios. Moreover, the influence of model parameters on the game results was analyzed. The results indicate that, for the supervisor-led Stackelberg game, when the sharing cost ratio is increased to a specific level, the supervisor's optimal benefit will not be further improved.

Cytomegalovirus seroprevalence, infection, and disease in Chinese thoracic organ transplant recipients: a retrospective cohort study.

BACKGROUND: Cytomegalovirus (CMV) infection is a leading cause of morbidity and mortality after transplantation. This study aimed to investigate CMV seroprevalence, infection, and disease in Chinese thoracic organ transplant recipients. METHODS: The clinical data of the patients who underwent lung and/or heart transplantation between January 2015 and October 2020 were retrospectively collected from four transplantation centers in China. RESULTS: A total of 308 patients were analyzed. The CMV serostatus was donor positive (D+) recipient negative (R-) in 19 (6.17%) patients, D+/R+ in 233 (75.65%), D-/R+ in 36 (11.69%), and D-/R- in 20 (6.50%). CMV DNAemia was detected in 52.3% of the patients and tissue-invasive CMV disease was diagnosed in 16.2% of the patients. Only 31.8% of the patients adhered to the postdischarge valganciclovir therapy. The D+/R- serostatus (odds ratio [OR]: 18.32; 95% confidence interval [CI]:1.80-188.68), no valganciclovir prophylaxis (OR: 2.64; 95% CI: 1.05-6.64), and higher doses of rabbit anti-human thymocyte globulin (> 2 mg/kg) (OR: 4.25; 95% CI: 1.92-9.42) were risk factors of CMV disease. CONCLUSION: CMV seroprevalence was high in Chinese thoracic organ transplant donors and recipients. The low adherence rate to the postdischarge CMV prophylaxis therapy in Chinese patients is still an unresolved issue.

Trade-Off between COVID-19 Pandemic Prevention and Control and Economic Stimulus.

The coronavirus disease 2019 (COVID-19) pandemic has posed a severe threat to public health and economic activity. Governments all around the world have taken positive measures to, on the one hand, contain the epidemic spread and, on the other hand, stimulate the economy. Without question, tightened anti-epidemic policy measures restrain people's mobility and deteriorate the levels of social and economic activity. Meanwhile, loose policy measures bring little harm to the economy temporarily but could accelerate the transmission of the virus and ultimately wreck social and economic development. Therefore, these two kinds of governmental decision-making behaviors usually conflict with each other. With the purpose of realizing optimal socio-economic benefit over the full duration of the epidemic and to provide a helpful suggestion for the government, a trade-off is explored in this paper between the prevention and control of the epidemic, and economic stimulus. First, the susceptible-infectious-recovered (SIR) model is introduced to simulate the epidemic dynamics. Second, a state equation is constructed to describe the system state variable-the level of socio-economic activity dominated by two control variables. Specifically, these two variables are the strengths of the measures taken for pandemic prevention and control, and economic stimulus. Then, the objective function used to maximize the total socio-economic benefit over the epidemic's duration is defined, and an optimal control problem is developed. The statistical data of the COVID-19 epidemic in Wuhan are used to validate the SIR model, and a COVID-19 epidemic scenario is used to evaluate the proposed method. The solution is discussed in both static and dynamic strategies, according to the knowledge of the epidemic's duration. In the static strategy, two scenarios with different strengths (in terms of anti-epidemic and economic stimulus measures) are analyzed and compared. In the dynamic strategy, two global optimization algorithms, including the dynamic programming (DP) and Pontryagin's minimum principle (PMP), respectively, are used to acquire the solutions. Moreover, a sensitivity analysis of model parameters is conducted. The results demonstrate that the static strategy, which is independent of the epidemic's duration and can be easily solved, is capable of finding the optimal strengths of both policy measures. Meanwhile, the dynamic strategy, which generates global optimal trajectories of the control variables, can provide the path that leads to attaining the optimal total socio-economic benefit. The results reveal that the optimal total socio-economic benefit of the dynamic strategy is slightly higher than that of the static strategy.

Anesthetic management of heart and lung transplantation: analysis of 14 cases in a single center.

Background: Aggressive management of heart and lung transplant (HLTx) requires a team of specialists with dedicated expert to improve long-term outcomes. This study aimed to summarize practical experiences of anesthetic management in HLTx operations. Methods: This study retrospectively analyzed the anesthesia-related clinical records of 14 cases of HLTx performed from September 2015 to October 2019. Preoperative diagnoses included congenital heart disease with pulmonary arterial hypertension, idiopathic pulmonary arterial hypertension with right heart failure, end-stage cor pulmonale, dilated cardiomyopathy, end-stage heart failure with pulmonary arterial hypertension, congenital heart disease, and lung transplant failure. All recipients received intravenous-inhalation general anesthesia with single-lumen endotracheal intubation, Swan-Ganz catheterization, and transesophageal echocardiography (TEE). Results: All 14 cases of HLTx were completed successfully and the patients were transferred to the intensive care units (ICUs). The postoperative data of the 14 patients were collected from 1 month to 4 years: seven cases survived the first year, four cases died in the short term (within 30 days), and one case died within 24 h. As at the end of November 2019, eight cases were reported dead (the longest survival was 2 years 1 month and 22 days). Four cases used extracorporeal membrane oxygenation (ECMO) for cardiopulmonary support. Conclusions: The success of the HLTx was attributed to the joint efforts of the entire transplantation team. The anesthesiology team was required for experiences in anesthesia for HLTx. The key to anesthesia management was the in-depth participation in preoperative discussions and assessments. Preventing the exacerbation of right heart failure and pulmonary arterial hypertension is critical during the induction of anesthesia. Regulation and support are crucial from the withdrawal of cardiopulmonary bypass (CPB) to within 1 h of the circulation and respiratory functions undertaken independently by the donor heart and lungs.

Multimodal echocardiography in the diagnosis of masses localized to the proximal portions of pulmonary arteries.

Proximal pulmonary artery masses are exceedingly rare, and their diagnosis and therapy are important and challenging for clinicians. This study reviews our experience exploring the value of a combination of transthoracic echocardiography and contrast echocardiography for the differential diagnosis of proximal pulmonary artery masses. Between January 2018 and June 2021, 44 patients diagnosed with a mass attached to the major pulmonary artery and straddling the bilateral pulmonary arteries or pulmonary valve on transthoracic echocardiography were referred to this study. Contrast echocardiography was performed in 17 patients. Masses were diagnosed based on their site of attachment, shape, size, mobility, hemodynamic consequences on transthoracic echocardiography, and tissue perfusion on contrast echocardiographic perfusion imaging. Pathological data were collected from medical records and analyzed. The most frequent location of proximal pulmonary artery masses was the major pulmonary artery trunk. Twelve patients underwent complete mass resection, whereas nine patients underwent percutaneous pulmonary artery biopsy puncture and had a pathological diagnosis. Another 24 patients were confirmed with the validation methods. Contrast echocardiography has good sensitivity and specificity for differentiating thrombi from pulmonary artery sarcomas (PAS). The mass types were distributed as follows: thrombi (19, 43%), PAS (15, 34%), metastatic tumors (6, 14%), vegetations (3, 7%), and primary benign lesions (1, 2%). The majority of proximal pulmonary artery masses were thrombi or PAS. A combination of transthoracic echocardiography and contrast echocardiography offers advantages in the early identification of proximal pulmonary masses and provides clinically important information about the characteristics of masses, especially for differentiating thrombi from PAS.

Non-In Situ Technique of Heart-Lung Transplantation: Case Series and Technique Description.

PURPOSE: Heart-lung transplantation (HLTx) is a life-saving treatment option for patients with advanced cardiopulmonary failure. However, posterior mediastinal bleeding and phrenic nerve damage are still intraoperative challenges for the traditional surgical method. This study reports an innovative non-in situ HLTx performed in our center, preventing posterior mediastinal bleeding and phrenic nerve damage effectively. DESCRIPTION: Between September 2015 and September 2020, 12 patients without previous heart surgery underwent a traditional HLTx and were deemed a control group, and 3 patients underwent an innovative non-in situ HLTx. The operative time, cold ischemic time, intraoperative bleeding, intraoperative transfusion, and the intensive care unit and hospital lengths of stay were assessed between traditional HLTx and non-in situ HLTx. EVALUATION: The innovative non-in situ HLTx was successfully performed in the 3 patients. We found that the intensive care unit and hospital lengths of stay, total surgical time, cold ischemic time, intraoperative bleeding, and intraoperative transfusion were decreased in the 3 patients compared with the traditional surgical method. CONCLUSION: Non-in situ HLTx may decrease posterior mediastinal bleeding and phrenic nerve damage effectively.

Simultaneous transthoracic intervention for multiple cardiac defects in children.

BACKGROUND: Transthoracic intervention for isolated congenital heart disease (CHD) has been well tested for its technological feasibility and is increasingly used in clinical practice. We aimed to present our experience in simultaneous transthoracic intervention for multiple cardiac lesions in a series of pediatric patients. METHODS: Between March 2015 and December 2019, 20 patients with multiple CHD were referred to this study; mean age was 18.8±8.6 (range, 4-36) months. The transthoracic echocardiography (TTE) diagnosis was atrial septal defect (ASD) and perimembranous ventricular septal defect (pmVSD) in 7 patients, patent ductus arteriosus (PDA) and ASD in 6, pmVSD and PDA in 2, pmVSD and valvular pulmonary stenosis (PS) in 2, ASD and PS in 2, and doubly committed subarterial VSD (dcsVSD) and PS in 1 patient. These patients underwent simultaneous transthoracic interventions with transesophageal echocardiography guidance. The procedure sequence was PS→VSD→PDA→ASD. Electrocardiography and TTE were scheduled at discharge and follow-ups. RESULTS: All patients were occluded successfully without any thoracotomy conversion. Operation time was 56-120 (mean, 75±13) minutes. A 1.5-2.0-cm median sternum incision was performed in 6 ASD&PDAs, 2 ASD&PSs, and 1 dcsVSD&PS. In 11 other patients, a 1.5-2.0-cm incision in the inferior sternum was made and the chest closed with a drain. There were no serious complications before discharge and at follow-up. CONCLUSIONS: Simultaneous transthoracic intervention for multiple cardiac defects in children is feasible with good short-term outcomes. For different lesions, the appropriate surgical incision and operational sequence can render the intervention minimally invasive and safer.

Efficacy of transthoracic device closure versus traditional surgical repair on atrial septal defects: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To compare the effects of transthoracic device closure and traditional surgical repair on atrial septal defect systemically. Methods    A systematic literature search was conducted using the PubMed, EMbase, The Cochrane Library, VIP, CNKI, CBM, Wanfang Database up to July 31, 2018 to identify trials according to the inclusion and exclusion criteria. Quality was assessed and data of included articles were extracted. The meta-analysis was conducted by RevMan 5.3 and Stata 12.0 software. Results    Thirty studies were identified, including 3 randomized controlled trials (RCTs) and 27 cohort studies involving 3 321 patients. For success rate, the transthoracic closure group was lower than that in the surgical repair group (CCT, OR=0.34, 95%CI 0.16 to 0.69, P=0.003). There was no statistical difference in mortality between the two groups (CCT, OR=0.43, 95%CI 0.12 to 1.52, P=0.19). Postoperative complication occurred less frequently in the transthoracic closure group than that in the surgical repair group (RCT, OR=0.30, 95%CI 0.12 to 0.77,  P=0.01; CCT, OR=0.27, 95%CI 0.17 to 0.42, P<0.000 01). The risk of postoperative arrhythmia in the transthoracic closure group was lower than that in the surgical repair group (CCT, OR=0.56, 95%CI 0.34 to 0.90, P=0.02). There was no statistical difference in the incidence of postoperative residual shunt in postoperative one month (CCT, OR=4.52, 95%CI 0.45 to 45.82, P=0.20) and in postoperative one year (CCT, OR=1.03, 95%CI 0.29 to 3.68, P=0.97) between the two groups. Although the duration of operation (RCT MD=–55.90, 95%CI –58.69 to –53.11, P<0.000 01; CCT MD=–71.68, 95%CI -– 79.70 to –63.66, P<0.000 01), hospital stay (CCT, MD=–3.31, 95%CI –4.16, –2.46, P<0.000 01) and ICU stay(CCT, MD=–10.15, 95%CI –14.38 to –5.91, P<0.000 01), mechanical ventilation (CCT, MD=–228.68, 95%CI –247.60 to – 209.77, P<0.000 01) in the transthoracic closure group were lower than those in the traditional surgical repair group, the transthoracic closure costed more than traditional surgical repair during being in the hospital (CCT, MD=1 221.42, 95%CI 1 124.70 to 1 318.14, P<0.000 01). Conclusion    Compared with traditional surgical repair, the transthoracic closure reduces the hospital stay, shortens the length of ICU stay and the duration of ventilator assisted ventilation, while has less postoperative complications. It is safe and reliable for patients with ASD within the scope of indication.

Anatomic and surgical factors affecting the switch from minimally invasive transthoracic occlusion to open surgery during ventricular septal defect repair.

BACKGROUND: This study aimed to investigate the specific causes for switching patients from minimally invasive transthoracic occlusion to surgical repair under cardiopulmonary bypass (CPB). By retrospectively analyzing 340 cases, we sought to provide the clinical reference for improving the success rate of minimally invasive transthoracic device closure of ventricular septal defect (VSD). METHODS: Among the 340 patients who underwent transthoracic closure of VSDs in the past 3 years at our hospital, 26 patients needed to be switched to surgical repair under CPB due to failure of transthoracic closure. We investigated the causes by retrospectively analyzing the findings from preoperative transthoracic echocardiography (TTE), intraoperative transesophageal echocardiography (TEE) and surgical exploration. RESULTS: Among the 340 patients who underwent transthoracic closure of VSDs, 26 patients (7.65%) were switched to surgical repair under CPB, which included 11 cases of membranous aneurysm (13.10%), 13 cases of perimembranous type (6.22%) and 2 cases of intracristal type (5.00%) according to their anatomic classifications. Among the 186 patients who underwent transthoracic closure during the first 17 months, 20 patients (10.75%) were switched to surgical repair under CPB. The main causes were failure of the delivery system to pass through the VSD in 7 patients, obvious residual shunts after releasing the occluder in 5 patients, significant shedding or shifting after releasing the occluder in 4 patients, significant regurgitation in adjacent valves in 3 patients and severe intraoperative complication (bleeding) in 1 patient. Among the 154 patients who underwent transthoracic closure during the late 17 months, 6 patients (3.90%) were switched to surgical repair under cardiopulmonary bypass. The main causes were significant residual shunts after releasing the occluder in 3 patients, significant regurgitation in adjacent valves in 2 patients after releasing the occluder and failure of the delivery system to pass through the VSD in 1 patient. CONCLUSIONS: Among all the anatomic classifications, membranous aneurysm VSD had the highest risk for switching from minimally invasive transthoracic closure to surgical repair under CPB. During the early period, the surgeons were not yet skilled with the minimally invasive transthoracic closure procedure, and the main causes of switching to surgical repair under CPB were that the delivery system could not pass through the ventricular septal defect and significant residual shunts persisted after releasing the occluder. In contrast, in the late period, the surgeons were skilled with the minimally invasive transthoracic closure procedure, and the main causes were significant residual shunts and obvious regurgitation in adjacent valves after releasing the occluder.

Percutaneous trans-jugular vein closure of atrial septal defect with steerable introducer under echocardiographic guidance.

BACKGROUND: The aim of this study is to discuss a novel surgical approach of percutaneous trans-jugular vein closure of atrial septal defect (ASD) with steerable introducer under echocardiographic guidance. METHODS: From January 2015 to June 2015, ten ASD patients underwent percutaneous trans-jugular vein ASD closure, the occluder placement could be perpendicular to the plane of ASD using the steerable introducer. RESULTS: All cases succeeded. The average procedure time was 27.4±5.6 minutes; and the average intracardiac operation time was 6.7±5.2 minutes. No patient showed the residual shunt after the procedure. There was no clinical death, no arrhythmia, no hemolysis, no infection, no jugular vein damage or occlusion during patients' hospitalization. The post-operation follow up after one month of the operation showed that there was no residual shunt, no falling off or detachment of occluders or other complications. CONCLUSIONS: It is a new surgical method with easy operation, mild damage and wider indication. Compared with the traditional percutaneous and transthoracic closure of ASD, it has obvious advantages.

Boron nitride nanosheets as barrier enhancing fillers in melt processed composites.

In this work we have used melt-processing to mix liquid-exfoliated boron-nitride nanosheets with PET to produce composites for gas barrier applications. Sonication of h-BN powder, followed by centrifugation-based size-selection, was used to prepare suspensions of nanosheets with aspect ratio >1000. The solvent was removed to give a weakly aggregated powder which could easily be mixed into PET, giving a composite containing well-dispersed nanosheets. These composites showed very good barrier performance with oxygen permeability reductions of 42% by adding just 0.017 vol% nanosheets. At low loading levels the composites were almost completely transparent. At higher loading levels, while some haze was introduced, the permeability fell by ∼70% on addition of 3 vol% nanosheets.

In vitro and in vivo study of thymosin alpha1 biodegradable in situ forming poly(lactide-co-glycolide) implants.

The purpose of this study was to develop poly(lactide-co-glycolide) (PLGA) based in situ forming implants (ISFI) for controlled release of thymosin alpha 1 (Talpha1). The ISFI was prepared by dissolving PLGA in N-methyl-2-pyrrolidone (NMP) or mixtures of NMP and triacetin. Talpha1 microparticles, prepared by spray-freeze drying method with chitosan or bovine serum albumin as a protectant, were suspended in PLGA solutions. The effects of Talpha1 pre-encapsulation, PLGA molecular weight, PLGA concentration and organic solvents composition on the in vivo Talpha1 release were evaluated by subcutaneously injecting Talpha1-loaded ISFI into Sprague-Dawley Rats. The pharmacological efficacy of Talpha1-loaded ISFI was examined using immunosuppressive BALB/c mice induced by cyclophosphamide. The ISFI composed of Talpha1 pre-encapsulated with chitosan, higher molecule-weight PLGA at higher concentration and more triacetin showed a lower initial release and a longer sustained release period. The optimal prescription of our study showed a low initial release of 29.3% (24 h), followed by a slow and continuous drug release up to 28 d in vivo. An in vitro release device was designed to mimic the in vivo release of Talpha1, and good correlation was observed between the in vitro and in vivo releases, with the linear correlation coefficient of 0.9899. Talpha1-loaded ISFI showed low cytotoxicity as tested by CCK-8 assay. Talpha1-loaded ISFI significantly increased the thymic index and spleen index of immunosuppressive mice. These results suggest that the ISFI is a suitable system for controlled release of Talpha1.