Background::We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse model.Methods::In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups ( n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and hiPSC-CMs. Results::After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMs via enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significantly suppressed the production of malondialdehyde and lactate dehydrogenase and the reduction in glutathione content induced by hypoxia in both HUVECs and hiPSC-CMs in vitro. Conclusions::MLB significantly enhanced the potential of hiPSC-CMs in repairing injured myocardium by improving endothelial cell function via the NF-κB/ICAM1 pathway and inhibiting hiPSC-CMs apoptosis via the DUSP2/STAT3 pathway.

Objective:To investigate the effects of Longmu Anshen prescription on microglia(MG)polarization in the medial prefrontal cortex(mPFC)and anxiety behavior of chronic restraint stress(CRS)mice.Methods:Forty-eight healthy male KM mice were randomly divided into normal group,paroxetine hydrochloride group and Longmu Anshen prescription high,middle and low dose groups.From the 15th day,after 30 minutes of CRS every day,the normal group and the model were given distilled water by gavage,the paroxetine hydrochloride group was given paroxetine hydrochloride(2.6 mg/kg)by gavage,and the traditional Chinese medicine group was given Longmu Anshen prescription at high,medium and low doses(4.16,2.08,1.04 g/kg)by gavage for 21 days.The changes of anxiety behavior in mice were evaluated by light-dark boxes experiment and elevated plus maze;ELISA was used to detect IL-1β,IL-6,TNF-α and IL-10 levels;protein expression of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1)in mice mPFC tissue were detected by Western blot;mRNA expression of ionized calcium binding adaptor molecule-1(Iba-1),iNOS and Arg-1 in mice mPFC tissue were detected by RT-PCR;the protein expression of Iba-1 in mice hippocampal tissue was detected by immuno-histochemistry(IHC).Results:Compared with normal group,the residence time in the light boxes,the number of times of shuttle between the light-dark boxes,the percentage of times of entering the open arm(OE%)and the percentage of time spent in the open arm(OT%)of mice in model group were significantly reduced(P<0.01);moreover,in the mPFC tissue of the model group mice,the protein and mRNA expressions of Iba-1 and iNOS were significantly increased(P<0.01),and the levels of IL-1β,IL-6 and TNF-α were significantly increased(P<0.01),while the protein and mRNA expressions of Arg-1 were significantly decreased(P<0.01),and the level of IL-10 was significantly decreased(P<0.01).Compared with model group,the residence time in the light boxes,the number of shuttles between the light-dark boxes,the OE%and OT%of mice in the paroxetine hydrochloride group and the high and medium dose groups of Longmu Anshen prescription were significantly increased(P<0.01);the expression levels of Iba-1 and iNOS protein and mRNA in mPFC tissue were significantly decreased(P<0.05,P<0.01),and the levels of IL-1β,IL-6 and TNF-α were significantly decreased(P<0.01),while the expression levels of Arg-1 protein and mRNA were significantly increased(P<0.01).IL-10 level was significantly increased(P<0.01).Conclusion:Longmu Anshen prescription can inhibit the activation of MG in mPFC tissues of CRS mice and may reduce nerve inflammation and increase the level of anti-inflammatory cytokines by regulating the polarization phenotype of M1/M2,thereby ameliorate CRS-induced anxiety behavior.

In recent years,the emergence of technologies such as machine learning,natural language processing,artificial neural networks,and computer vision has provided essential means for the rapid development of artificial intelligence(AI).Compared to the extensive application of AI in fields like urology and cardiothoracic surgery,the use of AI in hernia and abdominal wall surgery remains very limited.Currently,AI in hernia and abdominal wall surgery is mainly applied in preoperative risk factor analysis,disease-assisted diagnosis,surgical complexity prediction,imaging analysis,robotic/non-robotic intraoperative assistance,postoperative complication and recurrence prediction,as well as education,training,and management.These applications hold great importance for improving the diagnosis and treatment of hernia and abdominal wall diseases.This paper summarizes the current application scenarios of AI in hernia and abdominal wall surgery,reviews the status of Al applications in this field at home and abroad,and discusses future development directions,aiming to provide a reference for advancing hernia and abdominal wall surgery.

In November 2023, the seventh National Nucleic Acid Vaccine Conference was held to deeply discuss the immune mechanism, safety risks, advantages, and disadvantages of nucleic acid vaccines, and review the safety and effectiveness of COVID-19 vaccines developed by nucleic acid vaccine technology. Some prospectives were formed in the meeting that in the post-pandemic era, nucleic acid vaccine technology will play a role in the following areas: dealing with pathogens that are difficult to be prevented by traditional vaccines, promoting the upgrading of traditional live attenuated vaccines, contributing to the development of multivalent and combined vaccines, and rapid response to emerging and re-emerging infectious diseases. These views point out the direction for the future development of nucleic acid vaccine technology.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Flash radiotherapy (FLASH-RT) is an advanced radiotherapy technique known for its ultra-high dose rate (>40 Gy/s) irradiation. Preclinical studies have demonstrated that FLASH-RT is highly effective in reducing radiation damage to normal tissues, while still effectively killing tumors. This wider therapeutic window in terms of dose rate makes FLASH-RT a promising and disruptive technique for the future of radiotherapy. However, the biological mechanisms underlying FLASH-RT are not yet fully understood, and there are multiple technical challenges to be addressed before its clinical application. In this article, we provide a brief overview of the recent research progress in FLASH-RT, covering its biological mechanisms, preclinical studies, and the status and challenges in clinical application, aiming to offer valuable reference and inspiration for the future translation of FLASH-RT into clinical practice.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Background Atmospheric fine particulate matter (PM_2.5) can disrupt the metabolic homeostasis of the liver and accelerate the progression of liver diseases, but there are few studies on the effects of sub-chronic PM_2.5 exposure on the liver metabolome. Objectives To investigate the effects of sub-chronic exposure to concentrated PM_2.5 on hepatic metabolomics in mice by liquid chromatography-mass spectrometry (LC-MS), and to identify potentially affected metabolites and metabolic pathways. Methods Twelve male C57BL/6J (6 weeks old) mice were randomly divided into two groups: a concentrated PM_2.5 exposure group and a clean air exposure group. The mice were exposed to concentrated PM_2.5 using the "Shanghai Meteorological and Environmental Animal Exposure System" at Fudan University. The exposure duration was 8 h per day, 6 d per week, for a total of 8 weeks. The mice's liver tissues were collected 24 h after the completion of exposure. LC-MS was performed to assess changes in the hepatic metabolome. Orthogonal partial least squares discriminant analysis and t-test were employed to identify differentially regulated metabolites between the two groups under the conditions of variable important in projection (VIP)≥1.0 and P<0.05. Metabolic pathway enrichment analysis was performed using MetaboAnalyst 5.0 software and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results A total of 297 differentially regulated metabolites were identified between the concentrated PM_2.5 exposure group and the clean air group. Among these metabolites, 142 were upregulated and 155 were downregulated. A total of 38 metabolic pathways were altered, with 7 pathways showing significant perturbation (P<0.05). These pathways involved amino acid metabolism, glucose metabolism, nucleotide metabolism, as well as cofactor and vitamin metabolism. The 7 significant metabolic pathways were pantothenic acid and coenzyme A biosynthesis; purine metabolism; amino sugar and nucleotide sugar metabolism; arginine biosynthesis; alanine, aspartate and glutamate metabolism; aminoacyl-tRNA biosynthesis; and fructose and mannose metabolism. Conclusion The results from metabolomics analysis suggest that sub-chronic exposure to PM_2.5 may disrupt hepatic energy metabolism and induce oxidative stress damage. Aspartic acid, succinic acid, ornithine, fumaric acid, as well as purine and xanthine derivatives, were identified as potential early biomarkers of hepatic response to sub-chronic PM_2.5 exposure.

BackgroundMajor depressive disorder is one of the most disabling mental diseases. Currently， medication in combination with physiotherapy and psychotherapy remains the most commonly used treatment modality for the disease， whereas only a few randomized controlled studies have been conducted on physiotherapy， and even fewer studies have focused on medication combined with physiotherapy. ObjectiveTo explore the efficacy and safety profile of repetitive transcranial magnetic stimulation （rTMS） versus modified electroconvulsive therapy （MECT） in combination with antidepressants in the treatment of major depressive disorder， so as to provide an optimized treatment plan for patients with major depressive disorder. MethodsPatients with major depressive disorder （n=335） hospitalized in Shandong Daizhuang Hospital from January 1， 2019 to April 30， 2023 were included， all of whom met the diagnostic criteria of the International Classification of Diseases， tenth edition （ICD-10）. Depending on their disease condition， patients were subjected to either MECT in combination with drugs （n=141） or rTMS in combination with drugs （n=194） after admission. Depressive symptoms were assessed using Hamilton Depression Scale-24 item （HAMD-24） at the baseline and the end of the 1^st， 2^nd， 3^rd and 4^th week of treatment， and the adverse reactions were documented in patient's medical records. ResultsAnalysis of variance on HAMD-24 revealed a significant effect of time （F=3.081， P=0.042）， but no effect of group （F=1.023， P=0.313）， and the interaction effect between the time and the groups was not statistically significant （F=1.642， P=0.191）. No statistical difference was reported between two groups in response rate and full remission rate （P>0.05）. Throughout the course of treatment， 58 cases （41.13%） of recent memory impairment and 74 cases （52.48%） of headache or neck muscle pain occurred in MECT combined with drugs group， and 27 cases （13.92%） in rTMS combined with drugs group experienced headache or head skin discomfort. ConclusionAntidepressants in combination with rTMS or MECT show equivalent efficacy in the treatment of major depressive disorder， while rTMS combined with antidepressants demonstrates a superior safety profile compared to MECT.

Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.