Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

Advancements in artificial intelligence(AI)and emerging technologies are rapidly expanding the exploration of chemical space,facilitating innovative drug discovery.However,the transformation of novel compounds into safe and effective drugs remains a lengthy,high-risk,and costly process.Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development.Despite this need,no comprehensive tool currently supports systematic evaluation and efficient screening.Here,we present druglikeFilter,a deep learning-based framework designed to assess drug-likeness across four critical dimensions:1)physicochemical rule evaluated by systematic determination,2)toxicity alert investigated from multiple perspectives,3)binding affinity measured by dual-path analysis,and 4)compound synthesizability assessed by retro-route prediction.By enabling automated,multidimensional filtering of compound libraries,druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates,which can be freely accessed at https://idrblab.org/drugfilter/.

Objective To explore the impact of adipokine metabolism on coronary microvascular dysfunction(MVD)and the clinical application value of Shexiang Tongxin dropping pill(STDP).Methods From Sep.2018 to Dec.2019,41 patients with coronary heart disease in Department of Cardiology,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled and divided into non-MVD group(20 cases)and MVD group(21 cases);29 MVD patients were randomly divided into basic treatment group(14 cases)and STDP group(15 cases)with basic treatment or additional STDP treatment for 3 months;and the patient's complaints,blood biochemical indicators,expression levels of plasma inflammatory factors and adipokines were analyzed.A myocardial ischemia-reperfusion model was established in male C57BL/6 mice aged 12-14 weeks.Mice were divided into sham operation group,ischemia-reperfusion(IR)group(normal saline gavage),and IR+STDP group(STDP gavage),with 5 mice in each group.The levels of plasma inflammatory factors were measured by enzyme-linked immunosorbent assay,the microvascular occlusion of the heart tissue was measured by thioflavin-S staining,and the differential expression proteins between the IR group and IR+STDP group were explored by proteomics analysis and verified by Western blotting.Results Compared with the non-MVD group,the MVD group showed a significant increase in plasma leptin level([9.89±2.42]μg/L vs[4.76±1.02]μg/L,P＜0.01),a significant decrease in adiponectin level([5.02±1.3]pg/mL vs[7.19±1.76]pg/mL,P＜0.05),and a significant increase in resistin level([9.20±2.03]μg/L vs[5.70±1.32]μg/L,P＜0.05).Pearson correlation analysis showed a positive correlation between leptin levels and MVD(r=0.82 and P＜0.01).Receiver operating characteristic curve analysis showed that the area under curve value of plasma leptin was 0.855(sensitivity 0.714,specificity 0.867,and optimal cutoff value＞9.395 μg/L).After 3 months of treatment,compared with the basic treatment group,the improvement rates of symptoms of chest distress and chest pain in the STDP group were significantly higher(73.3％[11/15]vs 21.4％[3/14]),and the levels of plasma leptin,interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were significantly lower([11.36±0.54]μg/L vs[12.12±0.85]μg/L,[3.96±1.76]pg/mL vs[8.65±1.29]pg/mL,[24.82±3.07]ng/mL vs[32.45±3.32]ng/mL,all P＜0.05).In animal studies,compared with the IR group,the mice in the IR+STDP group showed a 45％reduction in no-reflow area(P＜0.01)and a 23％reduction in low-reflow and no-reflow areas(P＜0.05)after myocardial ischemia-reperfusion;the expression levels of IL-6 and TNF-α were significantly decreased([378.25±19.66]pg/mL vs[457.32±32.01]pg/mL,[289.71±47.62]pg/mL vs[371.28±41.05]pg/mL,both P＜0.05).Proteomic analysis showed that the expression levels of von Willebrand factor(vWF)and intercellular cell adhesion molecule-1(ICAM-1)in the cardiac tissue of mice in the IR+STDP group were significantly lower than those in the IR group.Western blotting results also showed that the expression levels of vWF and ICAM-1 in the IR+STDP group were significantly lower than those in the IR group(both P＜0.01).Conclusion MVD patients have abnormal adipokine metabolism and high plasma leptin.STDP can improve clinical symptoms of MVD patients,reduce the plasma leptin level and inflammatory indicators,and the mechanism may be related to its antiplatelet and anti-inflammatory effects.

Objective To assess the safety of transeptal puncture(TSP)guided by transthoracic echocardiography(TEE)in percutaneous transcatheter closure of patent foramen ovale(PFO).Methods From March 2022 to December 2022,our department performed TSP guided by TEE in 45 patients with PFO who were unable to pass through the PFO with transcatheter standard technique.After guiding the delivery of the sheath,the foramen ovale was occluded.Results PFO closure with TSP technique guided by transthoracic echocardiography was successfully finished in all the 45 patients,with an operative time of(15.0±3.7)min.No complications such as arrhythmia or cardiac perforation happened immediately and at 12 h after surgery.All the patients recovered and were discharged on the next day after surgery.All the 45 patients were followed up by outpatient echocardiography and dynamic electrocardiogram at 3 months after surgery,and no complications such as intracardiac shunt,pericardial effusion,atrial fibrillation,aortic regurgitation,or arrhythmia were observed.Conclusion TSP guided by TEE is safe and feasible,and it can be used as a supplementary method for complex PFO.

Objective:To explore the safety and effectiveness of axillary-coronary artery bypass (ACAB) of anterolateral incision multi-vessel coronary artery bypass surgery (MICS-CABG).Methods:Patients who underwent coronary artery bypass surgery in Peking University Third Hospital from May 2020 to December 2022 were included. 48 and 158 patients were included in MICS-ACAB and OPCABG group respectively. The mean age of the OPCABG group was (64.72±8.27) years old, and the male proportion was 77.2%(122 cases). The mean age of the MICS-ACAB group was (71.42±7.77) years old, and the male proportion was 79.2%(38 cases). Major adverse cardiovascular and cerebrovascular events (MACCE, including stroke, death, myocardial infarction and revascularization) and postoperative PCS scores of SF-36 were selected as the primary endpoint. The surgical complications and angiography patency rate of grafts were recorded to evaluate the clinical effects of MICS-ACAB.Results:The median number of bypass graft in two groups was 3. There were no significant differences in perioperative MACCE, re-operation rate, renal failure and lenth of postoperative hospital stay between two groups( P>0.05). 85.4% of patients reveived angiography assessment before discharge. There was no significant difference in graft patency between the MICS-ACAB group and OPCABG group (95.2% vs 88.8%, P=0.368). The results of propensity score matching analysis were consistent with the above conclusions. Both univariate analysis and multiple linear regression showed that MICS-ACAB could improve the PCS score of SF-36 at 7 days after surgery[(31.77±5.97) scores vs. (29.45±6.31) scores, P=0.025]. Conclusion:The safety of MICS-ACAB is satisfactory, which can achieve the completely revascularization and the patency rate of grafts is desirable. This procedure can significantly improve quality of life of patients in early postoperative period.

Objective    To compare and analyze the postoperative quality of life in patients after minimally invasive coronary artery bypass grafting (MICABG) and conventional median thoracotomy off-pump coronary artery bypass grafting surgery (OPCABG). Methods    From November 2015 to January 2018, 94 patients who underwent MICABG in the Peking University Third Hospital were included in the MICABG group. During the same period 441 patients who received OPCABG were included in the OPCABG group. The patients were matched by using propensity score matching method with a ratio of 1∶1. The quality of life was compared between two groups at 1 month, 6 months and 12 months after the surgery using SF-36 scale. Results    A total of 82 patients were matched for each group. In the MICABG group, there were 66 males and 16 females with a mean age of 62.6±8.2 years. In the OPCABG group, there were 67 males and 15 females with a mean age of 63.2±13.2 years. One month after the operation, the physical health assessment (PCS) and mental health assessment (MCS) of the MICABG group were higher than those of the OPCABG group (50.3±10.6 points vs. 46.1±10.3 points, P=0.011; 59.5±9.3 points vs. 54.2±11.0 points, P=0.002). Scores of these following five dimensions: general health, physical functioning (PF), role-physical, social functioning (SF), role-emotion in the MICABG group were higher than those in the OPCABG group, while the score of body pain was inferior to that in the OPCABG group, and the differences were statistically significant (P<0.05). Six months after the surgery, the PCS and MCS of the two groups were not statistically different (80.0±13.1 points vs. 77.8±12.4 points, P=0.271; 81.6±13.5 points vs. 80.4±11.2 points, P=0.537). However, the scores of PF and SF in the MICABG group were still higher than those in the OPCABG group (P<0.05). Twelve months after the surgery, there was no statistical difference in the score of each dimension between the two groups (P>0.05). Conclusion    The improvement of quality of life within 6 months after MICABG is better than that of OPCABG, and it is similar between the two groups at 12 months after the surgery, indicating that MICABG has a certain effect of improving the short-term quality of life after the surgery, and the long-term quality of life is comparable to conventional surgery.

Objective    To analyze the feasibility of using triangular-sail technique that allows intermittent two-lung ventilation during minimally invasive coronary artery bypass grafting (MICS CABG). Methods    The clinical data of 207 patients with MICS CABG in our cardiac center from January 2019 to November 2020 were retrospectively analyzed. These patients were divided into two groups. A group OLV included 111 patients who underwent one-lung ventilation during surgery, while a group TLV included 96 patients who underwent intermittent two-lung ventilation. The triangular-sail technique was used in the group TLV. This simple technique isolated the operative field from lung lobes with the traction of pericardial adipose tissue. The preoperative data and perioperative clinical data of the two groups were compared and analyzed. Results    There was no statistical difference in basic preoperative data between the two groups. The operation time in the OLV group was shorter than that in the TLV group (296.7±57.3 min vs. 334.1±87.0 min, P=0.000), and the duration of postoperative mechanical ventilation and ICU stay were not statistically different between the two groups. There was also no statistical difference in the incidence of pneumothorax or atelectasis between the two groups. Conclusion    The triangular-sail technique is simple and easy to implement. The technique allows intermittent two-lung ventilation during MICS CABG procedure.

Objective    To investigate the safety and effectiveness of the multi-artery graf tstrategy for coronary bypass (MICS-CABG) with small incision in the left chest, and to provide experience for the promotion of this technique. Methods    The clinical data of 64 patients with MICS-CABG in Department of Cardiac Surgery of Peking University Third Hospital from December 2015 to November 2019 were retrospectively analyzed. There were 54 males and 10 females, aged 36-77 (61.1±8.7) years. The left lateral thoracic incision (5-8 cm) was made through the 5th intercostal incision, and the operation was performed under off-pump CABG. With the help of the chest wall suspension device and the heart fixator, the proximal anastomosis of the ascending aorta, anastomosis of the target vessels of the left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) systems were completed. The number of grafts was 2-4 (2.3±0.5) including 2 grafts in 45 patients, 3 grafts in 17 patients and 4 grafts in 2 patients. Three patients were treated with percutaneous intervention (PCI) hybridization and 62 patients were treated with total artery bypass graft. Coronary angiography was performed within 7 days after the operation to evaluate the graft patency rate. The incidence of major adverse cardiac and cerebrovascular events (MACCE) was recorded in the follow-up. The MACCE rate was calculated by Kaplan-Meier method. Results    None of the patients was transferred to thoracotomy and no intra-aortic balloon counterpulsation (IABP) or extracorporeal membrane oxygenation (ECMO) was used during the operation.  Incision infection was in 1 patient and reoperation in 2 patients (all were postoperative hemorrhage). Within 30 days after surgery, MACCE occurred in 1 patient, including 1 patient of non-fatal myocardial infarction. The overall patency rate of angiography bypass was 96.2%, and the patency rate of anterior descending branch bypass was 98.2%. Follow-up was performed from 12 to 60 months (median follow-up time was 28 months). The loss rate was 7.8% (5/64). The incidence of MACCE was 84.9% (95%CI 79.5%-90.3%). Conclusion    The MICS-CABG can achieve completed re-vascularization and totally artery-CABG and the short-term and medium-term clinical results of the operation are good.

Objective:To examine the safety and efficacy of minimally invasive coronary surgery-coronary artery bypass grafting (MICS-CABG).Methods:From the first case in November 2015 to November 2019, a total of 244 cases of MICS-CABG were performed in Department of Cardiovascular Surgery, Peking University Third Hospital. There were 197 males and 47 females, aging (62.3±8.7)years (range: 36 to 88 years). The operations were performed via the 5 th intercostal space of left thoracic lateral incision (length: 4 to 5 cm extended for 8 to 10 cm), and were performed under off-pump, with the help of the chest wall suspension device and cardiac fixator. The proximal anastomosis on ascending aorta and the distal anastomosis of left anterior descending branch, circumflex branch and right coronary system were completed according to procedure. In all 244 cases, the proportion of 2 grafts was 53.7% (131 cases), 3 grafts was 36.1% (88 cases), 4 grafts was 9.8% (24 cases) and 5 grafts was 0.4% (1 case). The average of grafts was 2.6±0.7 (range: 2 to 5). The proportion of hybrid was 14.3% (35 cases), sequential bypass procedure was 43.0% (105 cases) and multiple artery grafts was 25.4% (62 cases). The perioperative complications of the patients were collected, the patency rate of the grafts was evaluated by coronary angiography or CT within 7 days after the operation, and main adverse cardiovascular and cerebrovascular events (MACCE) were followed up. The survival curve was drawn by Kaplan-Meier method, and the 1-year MACCE rate was calculated by survival analysis. Results:All cases had no transition to thoracotomy and cardiopulmonary bypass procedure, and no cases needed intra aortic balloon pumping and extracorporeal membrane oxygenation during the operation.There were 2 cases of poor incision healing, and reoperation was performed in 10 cases (6 cases of postoperative bleeding, 2 cases of incision debridement, and 2 cases of grafts problems). The rate of MACCE in 30 days was 2.6% (10 cases), which contained 3 cases of death (2 cases of grafts occlusion, 1 case of serious hemorrhage after thoracic puncture drainage), 3 cases of stroke and 5 cases of non-fatal myocardial infarction. By the re-examination of angiography in 7 days after operation, the overall patency of the grafts was 96.1%, and the patency of the left anterior descending was 98.6%. Kaplan-Meier survival analysis was conducted for 235 patients (96.3%) with 1 to 36 months follow-up results, and the 1-year MACCE rate was 5.6% (95 %CI: 4.2% to 7.0%) . There was no significant difference among the incidences of MACCE at each stage of learning curve. Surgeon could reduce the operation time and complete more anastomosis with the accumulation of experience after the early 30 cases. Conclusions:MICS-CABG can safely achieve completed revascularization, which has good operative effects in short and medium-long term. There is no significant risk in the early cases of learning curve.

Objective:To examine the safety and efficacy of minimally invasive coronary surgery-coronary artery bypass grafting (MICS-CABG).Methods:From the first case in November 2015 to November 2019, a total of 244 cases of MICS-CABG were performed in Department of Cardiovascular Surgery, Peking University Third Hospital. There were 197 males and 47 females, aging (62.3±8.7)years (range: 36 to 88 years). The operations were performed via the 5 th intercostal space of left thoracic lateral incision (length: 4 to 5 cm extended for 8 to 10 cm), and were performed under off-pump, with the help of the chest wall suspension device and cardiac fixator. The proximal anastomosis on ascending aorta and the distal anastomosis of left anterior descending branch, circumflex branch and right coronary system were completed according to procedure. In all 244 cases, the proportion of 2 grafts was 53.7% (131 cases), 3 grafts was 36.1% (88 cases), 4 grafts was 9.8% (24 cases) and 5 grafts was 0.4% (1 case). The average of grafts was 2.6±0.7 (range: 2 to 5). The proportion of hybrid was 14.3% (35 cases), sequential bypass procedure was 43.0% (105 cases) and multiple artery grafts was 25.4% (62 cases). The perioperative complications of the patients were collected, the patency rate of the grafts was evaluated by coronary angiography or CT within 7 days after the operation, and main adverse cardiovascular and cerebrovascular events (MACCE) were followed up. The survival curve was drawn by Kaplan-Meier method, and the 1-year MACCE rate was calculated by survival analysis. Results:All cases had no transition to thoracotomy and cardiopulmonary bypass procedure, and no cases needed intra aortic balloon pumping and extracorporeal membrane oxygenation during the operation.There were 2 cases of poor incision healing, and reoperation was performed in 10 cases (6 cases of postoperative bleeding, 2 cases of incision debridement, and 2 cases of grafts problems). The rate of MACCE in 30 days was 2.6% (10 cases), which contained 3 cases of death (2 cases of grafts occlusion, 1 case of serious hemorrhage after thoracic puncture drainage), 3 cases of stroke and 5 cases of non-fatal myocardial infarction. By the re-examination of angiography in 7 days after operation, the overall patency of the grafts was 96.1%, and the patency of the left anterior descending was 98.6%. Kaplan-Meier survival analysis was conducted for 235 patients (96.3%) with 1 to 36 months follow-up results, and the 1-year MACCE rate was 5.6% (95 %CI: 4.2% to 7.0%) . There was no significant difference among the incidences of MACCE at each stage of learning curve. Surgeon could reduce the operation time and complete more anastomosis with the accumulation of experience after the early 30 cases. Conclusions:MICS-CABG can safely achieve completed revascularization, which has good operative effects in short and medium-long term. There is no significant risk in the early cases of learning curve.