The rapid advancements in artificial intelligence(AI)and computational sciences,particularly through the introduction of artificial intelligence drug design(AIDD)and computer-aided drug design(CADD)technologies,have revolutionized pathways in drug development.These include techniques such as natural language processing,image recognition,deep learning,and machine learning.By employing advanced algorithms and data processing techniques,these technologies have significantly enhanced the efficiency and success rate of R&D processes.In drug discovery,AI technologies have accelerated the identification of drug targets,screening of candidate drugs,pharmacological assessments,and quality control,effectively reducing R&D risks and costs.This article delves into the application of AIDD and CADD in drug development,analyzing their roles in enhancing the success rates and efficiencies of drug design,exploring their future trends,and addressing the potential challenges.

Esophageal cancer is a common malignant tumor of digestive tract.Remarkable regional difference is a prominent feature of the clinical epidemiology of esophageal cancer.They are mainly manifested in incidence rate,incidence type,onset age,and gene mutation.These differences may be related to dietary habits,lifestyle,and environmental factors.In recent years,research on the regional differences in esophageal cancer has gradually deepened.This article summarizes the differences in incidence rate,incidence type,gene mutations,epigenetics,risk factors,and prognosis of esophageal cancer in different regions,including Asia(China,India,Japan,and other countries),Europe,America(the United States),Africa,and other regions.Understanding these differences can help doctors and public health experts understand the risk factors and causes of esophageal cancer and further develop highly effective prevention and treatment strategies to reduce the occurrence and mortality rate of this malignancy.

Malignant pleural mesothelioma(MPM)is a rare,highly aggressive,and lethal tumor with poor prognosis.Its survival period ranges from four months to one year,and the 5-year survival rate is only about 10%.MPM is highly resistant to chemotherapy,and conventional treatments such as cisplatin combined with pemetrexed or raltitrexed only have a certain effect in about 20%of patients.In recent years,with the continuous in-depth understanding of the genetic variation characteristics of MPM,some progress has been made in the molecular mechanism underlying the chemotherapy resistance of MPM.This article will summarize the research progress of the molecular mechanism underlying the chemotherapy resistance of MPM,including BAP1 gene mutation,microRNA,MTA1-mediated DNA damage repair pathway,GITR-GITRL pathway,TGFa pathway,tumor stem cell,EGFR,and PTEN.The aim of this work is to provide a reference for exploring new therapeutic targets and combined treatment options for MPM.

Implementation strategy is a method or technique that enhances the adoption,implementation,and routine practice of evidence-based interventions in real-world healthcare situations,and is an important part of evidence transformation.Implementation mapping provides a practical tool for developing implementation strategies.This review introduces the concept and features and implementation steps of implementation mapping,commonly used theories,frameworks and models,and its application in evidence transformation and featureand application projects,in order to promote the use of implementation mapping in domestic evidence transformation research.

Stroke is a disease with a high disability rate， and often leads to limb dysfunction， especially upper limb motor dysfunction， which significantly affects the patients’ abilities and quality of life. With patients' increasing demand for functional recovery， various therapeutic techniques of rehabilitation medicine have been rapidly developed. As an important active central intervention technology， motor imagery training can be initiated by the patient's brain and activate the sensorimotor network to accelerate the repair of limb functions. The development of preventive medicine has promoted the continuous evolution of the concept of rehabilitation. The strategies of full cycle functional protection and disability prevention have been improved and developed in the clinical and scientific research practice of upper limb rehabilitation after stroke. The motor imagery training can activate the upper limb motor neural network in the early stage of stroke to prevent functional loss； In the recovery period， it can accelerate the neural function remodeling and reduce the upper limb disability； In the later stage after stroke， it can improve the performance of upper limb function in daily life， thus helping patients return to family life and society. This article reviews the research progress in recent years in China and abroad in the application of motor imagery training for the full cycle function protection and disability prevention of stroke.

Objective:To analyze the clinical characteristics of monkeypox patients.Methods:The clinical data and laboratory findings of 4 patients with monkeypox patients diagnosed at Yiwu Central Hospital in July 2023 were analyzed. Herpes fluid and skin tissue samples were collected, the viruses were isolation and cultured in African green monkey kidney cells (Vero) and identified with whole gene sequencing.Results:All four patients were male, aged 24-35 years. All patients had male-to-male behavior within 21 days before onset of the disease. Among them, one patient has AIDS and one patient has syphilis. Four patients presented with perineal skin lesions with itching, and 3 patients were found to have enlarged lymph nodes upon admission. Laboratory testing: lymphocyte abnormality (4.57×10 9/L) in 1 case; increased procalcitonin (0.25 ng/mL) in 1 case; elevated IL-10 levels ( 7.11 ng/L and 9.42 ng/L) in 2 cases; increased IL-6 (66 ng/L) and IL-4 (3.24 ng/L) in 1 case, respectively. One case had abnormal myocardial zymogram with a elevated lactate dehydrogenase level of 313 U/L. The monkeypox virus was isolated from lesion tissue and herpes fluid, and the whole gene sequencing identified it as the B. 1.3 subtype of the IIb evolutionary branch, exhibiting typical pathological effects on Vero cells. Conclusion:The clinical manifestations of the 4 monkeypox patients confirmed in Zhejiang province are mild, patients had a definitive history of male-to-male sexual behavior and the virus strains belong to the B. 1.3 lineage of the IIb evolutionary branch.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

Cardiovascular disease is a leading cause of death in Chinese population. It is of great significance to further explore the pathogenesis of cardiovascular diseases. Ferroptosis is a recently discovered iron-dependent and non-apoptotic form of regulated cell death, which exerts a regulatory role in a variety of biological events. Some studies have shown that ferroptosis plays an important role in the development of cardiovascular diseases. According to newly scientific reports, we summarized the mechanism and regulation in ferroptosis, and reviewed the results of ferroptosis in common cardiovascular diseases such as cardiac ischemia-reperfusion/myocardial infarction, cardiomyopathy, cardiac hypertrophy, atherosclerosis and abdominal aortic aneurysm.

Objective:To summarize the experience of the precise prevention and control strategy of novel coronavirus infection in the pediatric intensive care unit(PICU)during the epidemic of the Omicron variant.Methods:A retrospective analysis was performed on the strategies and management experience of precise prevention and control of novel coronavirus infection in PICU at Pediatric Hospital of Fudan University from March 1 to May 10, 2022.Results:According to the national and Shanghai novel coronavirus infection prevention and control standards, the PICU in our hospital, in accordance with the specialty characteristics of PICU, cooperated with the hospital′s department of infection and medical department to jointly construct a precise ward management strategy for the outbreak of the omicron mutants infection.Precise prevention and control management strategies were formulated from four aspects: the admission process of critically ill children, the division of PICU ward areas and nosocomial infection protection, the reception management system for children′s family members, and the " bubble management" system for PICU staff, and run them for 3 months.During the epidemic, there was no nosocomial infection of novel coronavirus infection in children or medical staff.During the period, a total of 140 critically ill children were admitted, including 87 cases transferred from the general ward in the hospital, 48 cases from the emergency department(non-febrile, 3 cases transferred by the transfer team), four cases from fever clinic, and one case from control ward.Four of the critically ill children had no emergency nucleic acid test report when they were admitted to the PICU.Among the 140 critically ill children, 54 patients received mechanical ventilation, 18 patients received blood purification, and two patients were monitored after liver transplantation.Seventy-eight (55.7%) children had underlying diseases.Conclusion:During the current round of novel coronavirus epidemic in Shanghai, PICU in our hospital formulated the admission and ward management procedures for critically ill children, which ensured the prevention and control of nosocomial infection of novel coronavirus, and at the same time ensured the treatment of critically ill children to the greatest extent.

Objective:To prospectively investigate the prevalence of heparin-induced thrombocytopenia (HIT) in critically ill children during extracorporeal membrane oxygenation(ECMO) and explore the clinical characteristics and prognosis of HIT during ECMO.Methods:A total of 22 critically ill children, who had received ECMO support for more than 96 hours in the Intensive Care Unit at the Children′s Hospital of Fudan University from March 2019 to December 2020, were enrolled.According to the 4T score and the heparin/platelet factor 4(PF4) antibody, children whose 4T scores were not less than 6 and heparin/ PF4 antibodies were positive, were classified into HIT group ( n=6), and non-HIT group ( n=16). The clinical outcomes and the incidence of thrombotic events were compared between two groups. Results:The incidence of HIT during ECMO in critically ill children was 27% in this study.The incidence of thrombosis in the ECMO circuit in the HIT group was higher (100% vs.63%, P=0.133), and the average time to the first thrombosis in ECMO circuit in the HIT group was shorter than that in the non-HIT group (3.70 d vs.5.44 d, P=0.06). During the first 14 days of ECMO, the proportion of children with thrombotic events no less than twice was higher in the HIT group (67% vs.19%, P=0.054). There was no significant difference regarding the survival rate at 28 days after ECMO withdrawal between two groups (33% vs.50%, P=0.664). Conclusion:The prevalence of HIT during ECMO in critically ill children is high.Thrombosis events tend to occur earlier and more extensively in children with HIT during ECMO.No significant effect of HIT on the survival rate of children during ECMO is found.Whether HIT has effect on the survival rate of children with ECMO requires a prospective and large clinical study.