With the rapid development of artificial intelligence technology,small molecule generation models have emerged as a significant research direction in the field of drug discovery.These models,including Generative Adversarial Networks(GANs),Variational Autoencoders(VAEs),and diffusion models,have proven to possess remarkable capabilities in optimizing drug properties and generating complex molecular structures.This article comprehensively analyzes the application of the aforementioned advanced technologies in the drug discovery process,demonstrating how they supplement and enhance traditional drug design methods.At the same time,it addresses the challenges facing current methods in terms of data quality,model complexity,computational cost,and generalization ability,with a prospect of future research directions.

Objective To investigate the role of preoperative 3D printing simulation technology in the interventional endovascular exclusion of Stanford B aortic dissection.Methods A retrospective study protocol was used to select 76 patients with Stanford B-type aortic dissection who underwent endovascular isolation surgery in our hospital from January 2019 to January 2021 in the study.Among them,40 patients underwent simulated surgery with preoperative 3D printing simulation technology(simulation group)and another 36 patients received conventional endovascular isolation surgery(control group).The two groups were compared in terms of the.cardiac ultrasound indicators,the true and false lumen diameters,and the complication rates of the proximal aortic rupture plane,stent end plane,and abdominal trunk artery plane at different times before and after surgery.Results As com-pared to the control group,the simulation group showed significantly longer surgical time,extracorporeal circulation time,aortic occlusion time,and ICU stay time(all P<0.05).After the operation,the true lumen diameter of the proximal aortic rupture plane,stent end plane,and abdominal trunk artery plane were significantly increased in two groups at months 1,3,and 6(P<0.05),but the false lumen diameter of the proximal aortic rupture plane,stent end plane,and abdominal trunk artery plane were significantly decreased(P<0.05)compared to preoperative levels.The LVEF and FS of the two groups were significantly increased 6 months after surgery(P<0.05).Conclusion The preoperative 3D printing simulation technology in the interventional endovascular isolation of Stanford B aortic dissection can ensure the surgical effect.It can achieve the same surgical effect as the traditional procedures and importantly it can reduce the difficulty of operation and shorten the operation time.

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

The incidence of valvular heart disease (VHD) increases with age, and its principal therapy is valve replacement. However, in recent years, the emergence of transcatheter interventions has changed the traditional therapy, making high-risk patients of surgery see dawn of hope. 3D printing technology has developed rapidly since it was applied to the medical field in 1990. Moreover, it has been widely applied in many surgical majors via refined reduction technology. However, the application of 3D printing technology in cardiovascular surgery is still in the preliminary stage, especially in the field of VHD. This article aims to review basic principles of 3D printing technology, its advantages in the therapy of VHD, and its current status of clinical application. Furthermore, this article elaborates current problems and looks forward to the future development direction.

Objective    To evaluate the clinical value of three-dimensional (3D) printing model in accurate and minimally invasive treatment of double outlet right ventricle (DORV). Methods    From August 2018 to August 2019, 35 patients (22 males and 13 females) with DORV aged from 5 months to 17 years were included in the study. Their mean weight was 21.35±8.48 kg. Ten patients who received operations guided by 3D printing model were allocated to a 3D printing model group, and the other 25 patients who received operations without guidance by 3D printing model were allocated to a non-3D printing model group. Preoperative transthoracic echocardiography and CT angiography were performed to observe the location and diameter of ventricular septal defect (VSD), and to confirm the relationship between VSD and double arteries. Results    The McGoon index of patients in the 3D printing model group was 1.91±0.70. There was no statistical difference in the size of VSD (13.20±4.57 mm vs. 13.40±5.04 mm, t=−0.612, P=0.555), diameter of the ascending aorta (17.10±2.92 mm vs. 16.90±3.51 mm, t=0.514, P=0.619) or diameter of pulmonary trunk (12.50± 5.23 mm vs. 12.90±4.63 mm, t=−1.246, P=0.244) between CT and 3D printing model measurements. The Pearson correlation coefficients were 0.982, 0.943 and 0.975, respectively. The operation time, endotracheal intubation time, ICU stay time and hospital stay time in the 3D printing model group were all shorter than those in the non-3D printing model group (P<0.05). Conclusion    The relationship between VSD and aorta and pulmonary artery can be observed from a 3D perspective by 3D printing technology, which can guide the preoperative surgical plans, assist physicians to make reasonable and effective decisions, shorten intraoperative exploration time and operation time, and decrease the surgery-related risks.

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation

It is significant to establish scene ECG database which improves the automatic diagnostic function of electrocardiograph under different application scenarios. We built the ECG database in different scene according to the hospital level (grade 3, grade 2, grade 1) and clinical environment (intensive care and acute wards, outpatient clinics and general wards). Sample size was obtained according to the incidence of various ECG diagnoses. The database covers ECG signal, ECG waveform, ECG characteristic values, ECG diagnostic results by experts and clinical information of patients etc. It not only provides important reference for electrocardiograph manufacturers to evaluate and test the parameters of automatic diagnosis under different clinical scene, but also provides valuable scientific research and teaching resources for medical workers.
Databases, Factual ; Electrocardiography ; Humans

Objective: To observe the effect of edaravone combining ulinastatin on brain protection in patients of type A aortic dissection (AAD) after total arch replacement. Methods: A total of 60 AAD patients with total arch replacement in our hospital from 2014-09 to 2016-01 were prospectively studied. Based on peri-operative application of edaravone and ulinastatin, the patients were divided into 2 groups: EU group: 1) the patients received ulinastatin 300000 U/8h and edaravone 0.5mg/Kg/12h from administration to 3 days post-operation, 2) during cardiopulmonary bypass, the patients received ulinastatin 300000 U/2h and edaravone 0.5mg/Kg; Control group, the patients had no such treatment.n=30 in each group. The following items were observed:①operative condition;②blood levels of speciifc brain injury markers as S-100 and neuron speciifc enolase (NSE) at different time points: beginning of surgery (T0), opening aorta clamp (T1), right after cardiopulmonary bypass (T2), entering ICU (T3), 24h post-operation (T4) and 3 days post-operation (T5); ③post-operative condition. Results:①Durations of operation, cardiopulmonary bypass, cardiac arrest and bilateral antegrade selective cerebral perfusion (BACP), the frequency of BACP and UACP (unilateral antegrade selective cerebral perfusion), the lowest rectal temperature and blood levels of S-100, NSE at T0 were similar between 2 groups.②Compared with Control group, EU group had decreased S-100 and NSE from T1 to T5,P<0.05.③The in-hospital and ventilation time, frequency of PND and TND, the patients with CSS score≥16 before discharge and the in-hospital death rate were similar between 2 groups,P>0.05. Conclusion: Edaravone combining ulinastatin had brain protective effect in AAD patients after total arch replacement;it may reduce blood speciifc brain injury markers while the clinical signiifcance should be further investigated.

Objective To evaluate left ventricular myocardial function altemation by three-dimensional speckle tracking imaging (3D-STI) after surgical aortic valve replacement (AVR) in severe aortic stenosis (AS) patients with preserved left ventricular ejection fraction (LVEF),and discuss its clinical value.Methods Forty patients with severe aortic stenosis who were hospitalized or outpatient in Nanjing First Hospital Affiliated to Nanjing Medical University during the period of October 2014 to October 2016 (AS group),and forty healthy volunteers (normal control group) were enrolled in this study.Normal control group underwent conventional echocardiography and 3D-STI measurement,while the AS group underwent conventional echocardiography and 3D-STI measurement at preoperative,1 week postoperative and 3 months postoperative,then we obtained left ventricular end-diastolic diameter (LVEDD),left ventricular end-systolic diameter (LVESD),interventricular septum thickness diameter (IVSd),left ventricular posterior wall thickness diameter (LVPWd),left ventricular ejection fraction (LVEF),global longitudinal strain (GLS),global circumferential strain (GCS),global radial strain (GRS),global area strain (GAS) strain and 3D-strain.The independent sample t test was used to compare the difference of conventional ultrasound parameters and 3D-STI parameters between AS preoperative patients and healthy controls,AS patients at 3 months postoperative and healthy controls.The single factor analysis of variance was used to compare the difference of conventional ultrasound parameters and 3D-STI parameters in severe patients at preoperative,1 week postoperative and 3 months postoperative.LSD-t test was used to compare in different AS groups.Results Compared with normal control group,IVSD,LVPWD and GCS of severe AS patients increased significantly (t=13.824,11.298 and-6.584,all P ＜ 0.001),GLS,GRS and 3D-Strain decreased significantly (t=10.221,-6.237 and-5.674,all P ＜ 0.001),LVEDD,LVESDand GAS had no significant difference.Compared with preoperative AS patients,LVEF,GLS,GAS and GCS decreased significantly (t=-2.205,-2.093,-2.034 and-3.152,all P ＜ 0.05 or 0.01) at 1 week postoperative,LVEDD,LVESD,IVSD,LVPWD,GRS and 3D-strain had no significant difference at 1 week postoperative;GLS,GRS and 3D-strain increased significantly (t=5.446,-4.923 and-4.388,all P ＜ 0.05 or 0.01) at 3 months postoperative,GCS,IVSD and LVPWD decreased significantly (t=-3.988,4.794 and 4.211,all P ＜ 0.05 or 0.01) at 3 months postoperative,LVEDD,LVESD,LVEF and GAS had no significant difference at 3 months postoperative.Compared with AS patients at 1 week postoperative,LVEF,GLS,GRS,GAS and 3D-strain increased significantly (t=-2.631,7.383,-4.719,2.923 and-4.154,all P ＜ 0.05 or 0.01) at 3 months postoperative,GCS,IVSD and LVPWD decreased significantly (t=-2.109,4.747 and 4.323,all P ＜ 0.05 or0.01) at 3 months postoperative.But in AS patients at 3 months postoperative,IVSD,LVPWD,GLS and GCS were still higher than those of normal control group (t=9.809,7.066,4.752 and-2.553,all P ＜ 0.001 or ＜ 0.05),LVEDD,LVESD,LVEF,GRS,GAS and 3D-strain had no significant difference.Conclusion The alternation of left ventricular myocardial function have a certain characteristic before and after aortic valve replacement in severe aortic stenosis patients with preserved LVEF,and 3D-STI can evaluate it more accurately.

Aberrant activation of the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(PKB,Akt)-mammalian target of rapamycin(mTOR) pathway is commonly observed in human cancer and is critical for cell survival, proliferation and differentiation.A variety of small molecule inhibitors targeting PI3K-Akt-mTOR pathway are under clinical studies.This review will summarize the recent studies in terms of the PI3K-Akt-mTOR signaling pathway and cancer,research progress of the antitumor activity possessed by PI3K-Akt-mTOR inhibitors,as well as the recent research in the related field conducted by our group.