OBJECTIVE To identify core genes associated with the treatment of coronary heart disease （CHD） with Tongmai yangxin pills， and predict their potential immunological and metabolic mechanisms. METHODS Mendelian randomization （MR） analysis was conducted using protein quantitative trait loci （pQTL） data from the UK Biobank and Icelandic，and data from genome- wide association study to screen core genes related to Tongmai yangxin pills in the treatment of CHD. Gene expression changes were further validated using transcriptomic sequencing data. Mediation analyses of immune cells and plasma metabolites were subsequently performed to explore the downstream regulatory networks of these core genes. RESULTS A total of 62 positive pQTL genes showed significant causal associations with CHD. MR analysis combined with transcriptomic sequencing validation identified three core genes FAM3D，OXT， and ENPP5-associated with Tongmai yangxin pills in the treatment of CHD. The transcriptomic sequencing results showed that after treatment with Tongmai yangxin pills， the expression levels of FAM3D and OXT were significantly reduced （P＜0.01）， while the expression level of ENPP5 was significantly increased （P＜0.05）. Mediation analyses between immune cells and plasma metabolites indicated that these genes may positively or negatively regulate CHD through immune pathways involving regulatory T cells and myeloid dendritic cells expressing CD11c and CD62L， as well as through metabolic pathways related to lipid and fatty acid metabolism， cholesterol metabolism， and bile acid metabolism. CONCLUSIONS This study identified FAM3D，OXT， and ENPP5 as core genes associated with the treatment of CHD by Tongmai yangxin pills， which may exert therapeutic effects via modulation of immune cells and plasma metabolic pathways involving fatty acids and bile acids.

Mitral valve replacement is one of the most common heart valve surgeries in China. In recent years, with the increase in degenerative valve diseases, older patients, and the progress of anti-calcification technology of biological valves, the proportion of mitral valve biological valve replacement has been increasing year by year. After the damage of traditional mitral valve biological valves, re-operation of valve replacement with thoracotomy is required. However, the adhesion between the heart and sternum, as well as the damage caused by cardiopulmonary bypass and cardiac arrest, can cause significant trauma to elderly patients and those with multiple organ dysfunction, leading to increased mortality and complication rates. In recent years, interventional valve surgery, especially transcatheter valve-in-valve surgery, has developed rapidly. This procedure can correct the damaged mitral valve function without stopping the heart, but there are still many differences between its technical process and conventional aortic valve replacement surgery. Therefore, organizing and writing multicenter expert recommendations on the technical process of transcatheter valve-in-valve surgery for damaged mitral valve biological valves is of great significance for the training and promotion of this technology.

In recent years, wearable devices have seen a booming development, and the integration of wearable devices with clinical settings is an important direction in the development of wearable devices. The purpose of this study is to establish a prediction model for postoperative pulmonary complications (PPCs) by continuously monitoring respiratory physiological parameters of cardiac valve surgery patients during the preoperative 6-Minute Walk Test (6MWT) with a wearable device. By enrolling 53 patients with cardiac valve diseases in the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, the grouping was based on the presence or absence of PPCs in the postoperative period. The 6MWT continuous respiratory physiological parameters collected by the SensEcho wearable device were analyzed, and the group differences in respiratory parameters and oxygen saturation parameters were calculated, and a prediction model was constructed. The results showed that continuous monitoring of respiratory physiological parameters in 6MWT using a wearable device had a better predictive trend for PPCs in cardiac valve surgery patients, providing a novel reference model for integrating wearable devices with the clinic.
Humans ; Lung ; Walking/physiology* ; Walk Test ; Heart Valves/surgery* ; Postoperative Period ; Postoperative Complications/etiology*

The technique of transcatheter aortic valve implantation has become increasingly mature. Although the transapical approach has a certain degree of minimally invasive trauma, it still has the characteristics such as heart beating without cardiopulmonary bypass, and the low technical requirements of catheter guide wire. In particular, the valve path is short and coaxial, which is easy to manipulate, and pure regurgitation and stenosis can be easily operated and are not subject to the limit of peripheral artery stenosis. It is still one of China's main approaches for transcatheter aortic valve replacement. Its perioperative management still has specific features and differs from the femoral artery approach. In addition, there is little relevant literature abroad. Therefore, domestic experts in this field were organized to discuss the development of perioperative management specifications to provide reference and techniques support for developing this field in China and further improve the quality of clinical operation and perioperative management. It will provide more safe and more effective medical services to these patients.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Humans ; Adult ; Serum Albumin, Human ; Consensus ; Cardiac Surgical Procedures ; Thoracic Surgery

Objectives:To investigate the correlation of serum lipoprotein-associated phospholipase A2 (Lp-PLA2) with intra-stent restenosis (ISR) after drug-eluting stent (DES) implantation.Methods:A total of 227 patients with coronary artery disease, who were diagnosed with severe epicardial coronary stenosis by coronary angiography (CAG) and treated by percutaneous coronary intervention (PCI) and DES implantation were enrolled in our study. After follow-up for 1-1.5 years, the CAG was performed and the patients were divided into ISR group and non-ISR (nISR) group according to the consequence of CAG. Biochemical data and multiple serum inflammatory factors such as Lp-PLA2, hypersensitive C-reactive protein (hs-CRP), interleukin 2 (IL-2), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were analyzed before the CAG. Multivariate logistic regression and multiple linear regression were used to analyze the influencing factors of stent restenosis after DES implantation.Results:The level of serum Lp-PLA2 and the proportion of hypertension in ISR group were significantly higher than those in nISR group, and the level of high density lipoprotein cholesterol (HDL-C) was significantly lower than that in nISR group (all P<0.05), but there was no significant difference in other biochemical indexes and inflammatory factors between the two groups (all P>0.05). The minimum lumen diameter of stent segment in ISR group was significantly lower than that in nISR group ( t=14.975, P<0.01), and the stenosis degree of stent segment diameter was significantly higher than that in nISR group ( P<0.01). Multivariate logistic regression analysis showed that Lp-PLA2 remained an independent predictor for ISR (1.011, 95% CI: 1.005-1.017). Only the serum levels of Lp-PLA2 had linear relationship with the degree of ISR by multivariate linear regression analysis ( β=0.790, P<0.01). Conclusions:Serum Lp-PLA2 level is independently associated with an increased risk of ISR in patients with coronary heart disease.

Objective    To investigate the morbidity of postoperative pulmonary complications (PPCs) in patients after transcatheter tricuspid valve replacement (TTVR). Methods    A prospective cohort study enrolled 19 patients who were diagnosed with severe or greater tricuspid regurgitation in West China Hospital from October 11, 2020 to March 1, 2021, and would receive TTVR using LuX-valve for valve replacement. The patients were divided into a PPCs group and a non-PPCs group according to the presence of PPCs. The incidence of PPCs after tricuspid valve intervention between the two groups was compared. Results    Of 19 patients diagnosed with severe or greater tricuspid regurgitation registered in the database, 17 met the inclusion criteria, including 15 females and 2 males, with a mean age of 68.4±8.0 years. PPCs occurred in 9 of 17 (52.9%) patients. At discharge, compared with the non-PPCs group, the PPCs group had a longer postoperative hospital stay [11.0 (10.0, 17.0) d vs. 7.5 (7.0, 8.0) d, P=0.01], longer ICU stay [72.0 (45.5, 95.0) h vs. 20.5 (16.0, 22.8) h, P<0.01], and more hospital cost [74.3 (65.9, 98.3) thousand yuan vs. 52.6 (44.2, 57.4) thousand yuan, P<0.01]. At 30 days of follow-up, the PPCs group was found that the rate of New York Heart Association cardiac function≥class Ⅲ (66.7% vs. 12.5%, P<0.01) was higher, the six-minute walk distance (170.2±169.3 m vs. 377.9±80.5 m, P<0.01) was shorter and Kansas City Cardiomyopathy Questionnaire heart failure score (40.9±31.2 vs. 80.4±5.8, P<0.01) was less than those of the non-PPCs group. Conclusion    PPCs are common in the patients undergoing TTVR and severely affect patients' cardiac function, exercise function and quality-of-life recovery. Proactive preoperative intervention as well as early postoperative rehabilitation management should be provided to those at high risk of PPCs.

Objective     To evaluate the early clinical effect of reimplantation in the treatment of bicuspid aortic valve (BAV) with aortic root aneurysm. Methods     The clinical data of 25 patients with BAV and aortic root aneurysm [mean diameter: 45-63 (52.68±5.55) mm] undergoing reimplantation in West China Hospital from November 2019 to May 2021 were retrospectively reviewed. There were 22 males and 3 females. The mean age was 15-65 (50.00±13.10) years and body surface area was 1.79±0.23 m2. Results    The pathological classification of BAV malformation was confirmed during the operation: Type 0 in 3 patients and Type 1 in 22 patients. There were 12 patients undergoing cusp central plication, and 2 patients were sutured with a closed fusion crest. Postoperative valve leaflet coaptation height was 0.78±0.15 cm, and effective height was 1.27±0.19 cm. In operation, maximum aortic valve flow velocity was 1.65±0.42 m/s, pressure difference was 5.46±3.05 mm Hg, and aortic valve annulus diameter was 21.32±0.95 mm. Cardiopulmonary bypass time was 225.84±35.34 min, and aortic block time was 189.60±26.51 min. In-hospital time was 11.64±3.07 d, ICU stay time was 2.64±0.99 d, and mechanical ventilation time was 1.48±0.87 d. The follow-up time was 17.20±4.70 months, and no death or major complications occurred during the follow-up in all patients. The cardiac function of the patients significantly improved postoperatively (P≤0.05). Echocardiography suggested that 12 patients had no aortic regurgitation, 10 minor aortic regurgitation, 3 mild aortic regurgitation, and no patients with moderate or more severe regurgitation. The diameter of the aortic sinus, left ventricular end-diastolic diameter and volume decreased during the follow-up, compared to preoperative ones (P≤0.05). The maximum flow velocity of the aortic valve was 1.54±0.36 m/s, and the pressure difference was 5.17±2.38 mm Hg during the follow-up. Conclusion    Reimplantation technology has a good clinical effect for highly selective BAV patients. It can effectively avoid long-term postoperative anticoagulation, but the maximum flow rate after surgery is slightly increased, which may be related to the configuration of BAV itself. While compared with valve replacement, the effect is still worthy of recognition.

Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) μg/L, which reached a peak of 0.85(0.12, 3.01) μg/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) μg/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.