BACKGROUND:Agomelatine is a clinically proven treatment for neuropsychiatric symptoms,such as anxiety and depression.Furthermore,our previous study has demonstrated that agomelatine ameliorates cognitive behaviors,hippocampal synaptic plasticity,and brain pathology in a mouse model of Alzheimer's disease.However,it remains unclear whether agomelatine can improve anxiety and depression-like behaviors in Alzheimer's disease model mice. OBJECTIVE:To investigate the improving effects of agomelatine on anxiety-and depression-like behaviors in APP/PS1 transgenic mice and its underlying molecular mechanisms. METHODS:(1)Eighteen APP/PS1 transgenic mice were randomly divided into model control group(n=9)and model intervention group(n=9).Another wild-type mice were randomized into control group(n=9)and intervention group(n=9).Model intervention group and intervention group were intraperitoneally injected with 10 mg/kg agomelatine per day for 31 continuous days.Behavioral experiments,including the elevated cross maze and forced swimming tests,and mRNA sequencing of the hippocampus were then performed.(2)Mouse hippocampal neuronal cell lines(HT22)and brain microvascular endothelial cell lines(bEnd.3)were cultured and divided into four groups:blank group without any drug,drug group with 20 μmol/L agomelatine,model group with 10 μmol/L β-amyloid 1-42,and experimental group with 10 μmol/L β-amyloid 1-42+20 μmol/L agomelatine.After 24 hours of incubation,protein expression of S416p-tau and S9p-GSK3β in HT22 cells was detected by immunoblotting,and protein expression of low-density lipoprotein receptor-related protein 1 and glycosylation end-product receptor in bEnd.3 cells was detected by immunoblotting. RESULTS AND CONCLUSION:In the elevated plus maze test,the time spent in the open arms(P＜0.01)and the entries into open arms(P＜0.05)in the mice of model control group were evidently lower than those in the control group,whereas those were obviously increased in the model intervention group compared with the model control group(P＜0.05).Forced swimming test results showed that the immobile time exhibited a marked increase in the model control group compared with the control group(P＜0.05),but it was significantly decreased in the model intervention group compared with the model control group(P＜0.05).Hippocampal tissue mRNA sequencing showed that agomelatine enhanced the expression of low-density lipoprotein receptor-related protein 1 in the hippocampus of APP/PS1 mice.Western blot analysis revealed that the level of S416p-tau in HT22 cells was higher in the model group than the blank group(P＜0.05),while it was markedly decreased in the experimental group compared with the model group(P＜0.05);the level of S9p-GSK3β in HT22 cells was higher in the drug group than the blank group(P＜0.05)as well as higher in the experimental group than the model group(P＜0.05).Moreover,the expression of low-density lipoprotein receptor-related protein 1 in bEnd.3 cells was higher in the experimental group than the model group(P＜0.05).To conclude,agomelatine can alleviate anxiety-and depression-like behaviors in Alzheimer's disease mice by promoting the clearance of β-amyloid and phosphorylated tau.

Objective To analyze the virus subtypes, molecular evolutional and molecular transmission network features of the first confirmed mpox case in Huai’an City, Jiangsu Province, so as to provide insights into understanding of the transmission and evolution dynamics of mpox virus and formulation of the mpox control strategy in the city. Methods Genomic DNA was extracted from swabs of the first confirmed mpox case’s skin lesions in Huai’an City, and the amplicon sequencing library was constructed using the hypersensitive mpox virus whole-genome capture kit. High-throughput sequencing was performed using the GridION X5 nanopore sequencer on the Nanopore sequencing platform, and single nucleotide polymorphism (SNP) analysis of mpox virus genome sequences was performed following sequence assembly. In addition, phylogenetic analysis, genetic genealogy and molecular traceability analysis were performed. Results The virus whole genome sequence of the first confirmed mpox case was successfully obtained by high-throughput sequencing, with a full length of 197 182 bp, and was named hMpxV/China/JS-HA01/2023, which belonged to the clade IIb (West African clade) lineage B.1.3. Compared with the mpox virus reference sequence MPXV-M5312_HM12_Rivers-001 (GenBank accession number: NC_063383), the genome sequence of the Huai’an virus isolate carried 86 SNPs, including 40 SNPs in the coding region as non-synonymous mutations and 73 SNPs as nucleotide mutations caused by APOBEC3 (APOBEC3). Of the 97 mpox virus gene sequences, 79 sequences were included in the molecular network (81.44%), and the threshold of the genetic distance accessed to the network was 0.35/10⁵. There were two large molecular transmission clusters and one scattered cluster in the molecular transmission network of the mpox virus, andthehMpxV/China/JS-HA01/2023 sequence was located in the large cluster. The 97 gene sequences formed 92 haplotypes, including three shared haplotypes Hap_4, Hap_6 and Hap_38, and an exclusive haplotype Hap_1 of hMpxV/China/JS-HA01/2023 generated from mutation of the exclusive haplotype Hap_43, while the exclusive haplotype Hap_43 was generated from mutation of the shared haplotype Hap_38. Conclusions The whole genome sequence of the mpox virus isolated from the first confirmed mpox case in Huai’an City has been successfully obtained, and the molecular evolutionary and molecular transmission network characteristics of the virus have been preliminarily understood.

Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System X_c^--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

There is a substantial unmet need for treatments in the field of pediatric rare diseases, and investigator initiated trial(IIT) provide a critical pathway for testing and developing new drugs or treatment strategies. However, healthcare institutions, when conducting such research, must address compliance risks related to project approval, contract management, data protection, and conflict of interest management. This study aims to analyze the particularities and challenges of IIT in pediatric rare diseases, review relevant regulations and regulatory requirements, and provide healthcare institutions with a reference framework for compliance risk management to maximize the benefits of IIT. Based on literature review, analysis of laws and regulations, practical work experience, and frameworks from other institutions, we summarize the unique aspects of pediatric rare disease IIT in terms of participant characteristics, innovative technologies, and organizational structures.On this basis, targeted compliance management recommendations are proposed, which include establishing a risk rating and full-cycle risk monitoring mechanism, a consent and ethical review mechanism tailored to pediatric participants, a robust contract management mechanism, a comprehensive data security management mechanism, and a multidisciplinary team and multi-channel compensation mechanism. The study concludes that healthcare institutions, funders, and other collaborating entities should implement compliance management in line with the characteristics of IIT to ensure the safety and effectiveness of research and facilitate innovation and development in the treatment of pediatric rare diseases.

To summarize the clinical experience of Professor LIU Shangyi in treating pruritus vulvae. It is believed that women have the physiological characteristics of liver and kidney as the root， and their pubic area is easily attacked by wind-dampness pathogenic qi， so the core mechanism of pruritus vulvae is proposed as wind-dampness accumulation and deficiency of liver and kidney. The core treatment method is to dispel wind-dampness and nourish the liver and kidneys， and modify the Danggui Decoction （当归饮子） to form a self-prescribed Yinyang Formula （阴痒方） as the basic prescription to treat pruritus vulvaen.

To analyze the disease burden of hypertension in the elderly population from 1990 to 2021 and to predict future trends in China and globally, thereby providing insights for public health decision-making regarding older adults with hypertension in China.

BACKGROUND: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time. METHODS: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed. RESULTS: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results. CONCLUSION This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.

BACKGROUND: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time. METHODS: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed. RESULTS: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results. CONCLUSION This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.

BACKGROUND: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time. METHODS: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed. RESULTS: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results. CONCLUSION This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.

BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.