OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

The breakthrough progress of implantable brain-computer interfaces (iBCIs) technology in the field of clinical trials has attracted widespread attention from both academia and industry. The development and advancement of this technology have provided new solutions for the rehabilitation of patients with movement disorders. However, challenges from many aspects make it difficult for iBCIs to further implement and transform technologies. This paper illustrates the key challenges restricting the large-scale development of iBCIs from the perspective of system implementation, then discusses the latest clinical application progress in depth, aiming to provide new ideas for researchers. For the system implementation part, we have elaborated the front-end signal collector, signal processing and decoder, then the effector. The most important part of the front-end module is the neural electrode, which can be divided into two types: piercing and attached. These two types of electrodes are newly classified and described. In the signal processing and decoder section, we have discussed the experimental paradigm together with signal processing and decoder for the first time and believed that the experimental paradigm acts as a learning benchmark for decoders that play a pivotal role in iBCIs systems. In addition, the characteristics and roles of the effectors commonly used in iBCIs systems, including cursors and robotic arms, are analyzed in detail. In the clinical progress section, we have divided the latest clinical progress into two categories: functional rehabilitation and functional replacement from the perspective of the application scenarios of iBCIs. Functional rehabilitation and functional replacement are two different types of application, though the boundary between the two is not absolute. To this end, we have first introduced the corresponding clinical trial progress from the three levels: application field, research team, and clinical timeline, and then conducted an in-depth discussion and analysis of their functional boundaries, in order to provide guidance for future research. Finally, this paper mentions that the key technical challenges in the development of iBCIs technology come from multiple aspects. First of all, from the signal acquisition level, high-throughput and highly bio-compatible neural interface designing is essential to ensure long-term stable signal acquisition. The electrode surface modification method and electrode packaging were discussed. Secondly, in terms of decoding performance, real-time, accurate, and robust algorithms have a decisive impact on improving the reliability of iBCIs systems. The third key technology is from the perspective of practicality, we believe that the signal transmission mode of wireless communication is the trend of the future, but it still needs to overcome challenges such as data transmission rate and battery life. Finally, we believe that issues such as ethics, privacy, and security need to be addressed through legal, policy, and technological innovation. In summary, the development of iBCIs technology requires not only the unremitting efforts of scientific researchers, but also the participation and support of policymakers, medical professionals, technology developers, and all sectors of society. Through interdisciplinary collaboration and innovation, iBCIs technology will achieve wider clinical applications in the future and make important contributions to improving the quality of life of patients.

Objective To investigate the effect of scutellarin(STR)on the proliferation and migration of human prostate cancer cell line(PC-3)and its underlying mechanism.Methods PC-3 cells were divided into low-dose STR group,medium-dose STR group,high-dose STR group,colivelin(STAT3 activator)group,high-dose STR+colivelin group and control group.CCK-8 assay and colony formation experiments were applied to detect cell prolif-eration;Scratch experiment was applied to detect cell migration;Transmission electron microscopy was applied to observe the mitochondrial ultrastructure of PC-3 cells.The intracellular free Fe2+,malondialdehyde(MDA)content and reactive oxygen species(ROS)levels were detected by colorimetric method;RT-qPCR was applied to detect the mRNA expression of member 11 of solute vector family(SLC7A11),proliferating cell nuclear antigen(PCNA)and matrix metalloproteinase-9(MMP-9)in cells;Western blot was used to detected p-STAT3 and GPX4 proteins in cells.Results Compared to control group,the mitochondrial structure of PC-3 cells in the low-dose STR group,medium-dose STR group and high-dose STR group was significantly disrupted.The A450 value,colony formation rate,scratch healing rate,PCNA,SLC7A11,MMP-9 mRNA expression,and p-STAT3,GPX4 protein all reduced.While Fe2+,MDA content,and that ROS level increased with dose-dependent way(P＜0.05).Compared with control group,the destruction of mitochondrial structure in cells from colivelin group improved;The A450 value,colony formation rate,scratch healing rate,PCNA,SLC7A11,MMP-9 mRNA expression and p-STAT3,GPX4 protein all increased,while Fe2+MDA content,and ROS level decreased(P＜0.05).Compared with high-dose STR group,the damage of mitochondrial structure in PC-3 cells in the high-dose STR+colivelin group was re-duced.The A450 value,colony formation rate,scratch healing rate,PCNA,SLC7A11,MMP-9 mRNA expression,and p-STAT3,GPX4 protein increased,while Fe2+,MDA content and ROS level decreased(P＜0.05).Conclusions The mechanism by of STR reducing proliferation and migration of prostate cancer cells is potentially related to the inhibition of STAT3/GPX4 pathway.

Interventions for endometriosis(EMs)include surgical excision of lesions and hormonal therapy,which usually have limited efficacy and adverse drug reactions.Traditional Chinese medicine(TCM)has the multi-component and multi-target characteristics,which can help patients achieve good clinical benefits by intervening in different parts of the disease.In this paper,we briefly discuss the modern pharmacology of Sanlang and Curcuma longa,and deeply summarize the possible mechanisms of action of TCM monomer and classical compound extracts and their active ingredients through signal pathways in inflammation,immune system,angiogenesis,hormone regulation,etc.,so as to provide theoretical bases for the clinical use of TCM monomers,drug-to-drug groups and compounds in the treatment of EMs.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Objective To explore the value of functional magnetic resonance imaging(MRI)techniques,including intravoxel incoherent motion(IVIM),T1 mapping,and T2 mapping,in assessing the microstructural and perfusion changes in the kidneys of rats with intrauterine growth restriction(IUGR).Methods An IUGR rat model was established through a low-protein diet during pregnancy.Offspring from pregnant rats on a low-protein diet were randomly divided into an IUGR 8-week group and an IUGR 12-week group,while offspring from pregnant rats on a normal diet were divided into a normal 8-week group and a normal 12-week group(n=8 for each group).The apparent diffusion coefficient(ADC),true diffusion coefficient(Dt),pseudo-diffusion coefficient(D*),perfusion fraction(f),T1 value,and T2 value of the renal cortex and medulla were compared,along with serum creatinine and blood urea nitrogen levels among the groups.Results The Dt value in the renal medulla was higher in the IUGR 12-week group than in the IUGR 8-week group,and the D* value in the renal medulla was lower in the IUGR 12-week group than in both the normal 12-week group and the IUGR 8-week group(P＜0.05).The T1 value in the renal medulla was higher than in the cortex in the IUGR 8-week group,and the T1 value in the renal medulla was higher in the IUGR 12-week group than in both the IUGR 8-week group and the normal 12-week group,with the cortical T1 value in the IUGR 12-week group also being higher than that in the normal 12-week group(P＜0.05).The T2 values in the renal medulla were higher than those in the cortex across all groups(P＜0.05).There were no significant differences in the T2 values of either the cortex or medulla among the groups(P＞0.05).There were no significant differences in serum creatinine and blood urea nitrogen levels among the groups(P＞0.05).Glomerular hyperplasia and hypertrophy without significant fibrotic changes were observed in the IUGR 8-week group,whereas glomerular atrophy,cystic stenosis,and interstitial inflammatory infiltration and fibrosis were seen in the IUGR 12-week group.Conclusions IVIM MRI can be used to assess and dynamically observe the microstructural and perfusion damage in the kidneys of IUGR rats.MRI T1 mapping can be used to evaluate kidney damage in IUGR rats,and the combination of MRI T1 mapping and T2 mapping can further differentiate renal fibrosis in IUGR rats.[Chinese Journal of Contemporary Pediatrics,2024,26(3):289-296]

The present study aimed to investigate the protective role of Shaofu Zhuyu Decoction(SFZY) against endometriosis fibrosis in mice, and decipher the underlying mechanism through the phosphatase and tensin homolog deleted on chromosome ten(PTEN)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) pathway. Eighty-five BALB/c female mice were randomly assigned into a blank group, a model group, high-, medium, and low-dose SFZY(SFZY-H, SFZY-M, and SFZY-L, respectively) groups, and a gestrinone suspension(YT) group. The model of endometriosis was induced by intraperitoneal injection of uterine fragments. The mice in different groups were administrated with corresponding groups by gavage 14 days after modeling, and the blank group and model group with equal volume of distilled water by gavage. The treatment lasted for 14 days. The body weight, paw withdrawal latency caused by heat stimuli, and total weight of dissected ectopic focus were compared between different groups. The pathological changes of the ectopic tissue were observed via hematoxylin-eosin(HE) and Masson staining. Real-time PCR was employed to measure the mRNA levels of α-smooth muscle actin(α-SMA) and collagen type Ⅰ(collagen-Ⅰ) in the ectopic tissue. The protein levels of PTEN, Akt, mTOR, p-Akt, and p-mTOR in the ectopic tissue were determined by Western blot. Compared with the blank group, the modeling first decreased and then increased the body weight of mice, increased the total weight of ectopic focus, and shortened the paw withdrawal latency. Compared with the model group, SFZY and YT increased the body weight, prolonged the paw withdrawal latency, and decreased the weight of ectopic focus. Furthermore, the drug administration, especially SFZY-H and YT(P<0.01), recovered the pathological and reduced the area of collagen deposition. Compared with the blank group, the modeling up-regulated the mRNA levels of α-SMA and collagen-Ⅰ in the ectopic focus, and such up-regulation was attenuated after drug intervention, especially in the SFZY-H and YT groups(P<0.05,P<0.01). Compared with the blank group, the modeling down-regulated the protein level of PTEN and up-regulated the protein levels of Akt, mTOR, p-Akt, and p-mTOR(P<0.01, P<0.001). Drug administration, especially SFZY-H and YT, restored such changes(P<0.01). SFZY may significantly attenuate the focal fibrosis in the mouse model of endometriosis by regulating the PTEN/Akt/mTOR signaling pathway.
Female ; Animals ; Mice ; Humans ; Proto-Oncogene Proteins c-akt/genetics* ; Choristoma ; Endometriosis/genetics* ; TOR Serine-Threonine Kinases/genetics* ; RNA, Messenger ; Signal Transduction ; Body Weight ; Mammals ; PTEN Phosphohydrolase/genetics*

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m² group (P_interaction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.
Humans ; Male ; Arsenic/urine* ; Creatinine ; East Asian People ; Testosterone/blood* ; Urinalysis ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged

During the coronavirus disease (COVID-19) epidemic, there have been concerns about the impact of vaccines on people's fertility, including the fertility of those who are currently preparing for pregnancy and those who might become pregnant in future. However, there is still a lack of research on the effect of the COVID-19 vaccine on male fertility, and it is not surprising that couples and donors have concerns regarding vaccination. In this study, a retrospective cohort study was conducted to examine semen quality before and after receipt of the inactivated COVID-19 vaccine. There were no statistically significant changes in semen parameters (volume, sperm concentration, progressive motility, and total progressive motile count) after two doses of vaccine (all P > 0.05). In summary, our study updates the most recent studies on the effects of the COVID-19 vaccine on male fertility, and the information from this study could be used to guide fertility recommendations for assisted reproductive technology (ART) patients and donors.
COVID-19 ; COVID-19 Vaccines ; Female ; Humans ; Male ; Pregnancy ; Retrospective Studies ; Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa ; Vaccination ; Vaccines, Inactivated

OBJECTIVE: To explore and design a novel bi-specific chimeric antigen receptor (CAR) structure. To obtain the corresponding CAR-T cells and verify killing effects on tumor cells in vitro and in vivo. METHODS: Five kinds of bi-specific CAR structures including humanized CD19 scFv and CD79b scFv, CD8 hinge & TM-4-1BB-CD3ζ and/or CD3ε chain intracellular regions were constructed and prepared. CAR-19-79b cells were obtained. Five kinds of CAR-T cells were co-incubated with the 3M-CD19-CD79b-Luc target cells. Luciferase assay and ELISA were used to detecte the killing ability of these five groups of CAR-T cells and the secretion of cytokines and compared. The optimal structure of CAR-T cells was used to treat the leukemia mouse model constructed by Daudi-Luc cells. And the treatment efficacy was evaluated. At the same time, other targets were used in this structure. With the same methods, the stability and effectiveness of the structure were verified. RESULTS: CAR-19-79b-T cells were cultured for 7 days, the expression rates of CAR-19 and CAR-79b were 21.6%-36.3% and 21.7%-37.8%, respectively. The killing rates of 5 kinds of CAR-19-79b-T cells prepared by T cells from 3 healthy donors on 3M-CD19-CD79b-Luc cells were significantly higher than those of the T cell control group at the effect-target ratio of 10∶1. Among them, the killing rates of CAR-19-79b-T cells with No. III and No. IV structures were the strongest. After co-incubation with 3M-CD19-CD79b-Luc target cells, the amount of IFN-γ and TNF-α secreted by CAR-T cells with CAR IV and CARV structures was the lowest. And there was no significance between the two groups (P>0.05). CAR IV cells with remarkable killing effect and low secretion factor had obvious therapeutic effect on Daudi-Luc leukemia mice, extending the survival period of mice to 64 days. And all mice in the T cell control group died at 41.0±2.4 days. The CAR-19-BCMA-T and CAR-19-22-T with the same structure showed significant killing ability and low cytokine expression levels. CONCLUSION A novel bi-specific CAR structures was successfully designed, which could efficiently kill the corresponding tumor cells and secrete less cytokines (such as TNF-α, IFN-γ). Moreover, it shows obvious therapeutic effect on Daudi lymphoma mouse model. The bi-specific CAR structure shows good killing specificity and safety.
Animals ; Mice ; Leukemia ; Receptors, Chimeric Antigen ; T-Lymphocytes ; Tumor Necrosis Factor-alpha