Objective:To provide a scoping review of domestic and international studies on the influencing factors of frailty in stroke inpatients, and to provide guidance for interventional studies on debility in stroke inpatients in China.Methods:A systematic search of domestic and international literature databases, including China National Knowledge Infrastructure, WanFang, VIP, China Biomedical Literature Database, PubMed, Web of Science, Embase, Cochrane Library, CINAHL was conducted about the status and its influencing factors of frailty in stroke inpatients. The retrieval time limit was from database establishment to November 23, 2023. The included literature was extracted, analyzed, and summarized according to the reporting specifications of the scope review guidelines.Results:Thirty-six articles were included, all of the 36 papers reported the prevalence of frailty in patients with stroke. The top three countries with the highest prevalence were China (15.3%-86.9%), the United Kingdom (28%-78%), and Italy (31.37%). The risk factors of stroke frailty were categorized mainly into 4 themes: social demographic factors, physical health factors, disease-related factors, and psychological and social background factors.Conclusions:The confidence of frailty in stroke patients of a higher level at home and abroad, and the risk factors involved are complex and diverse. It is suggested that future studies need to conduct large-sample, multicenter longitudinal studies to clarify the causal relationship, strengthen the exploration of controversial factors of stroke debility, and carry out more targeted intervention studies, so as to reduce the incidence of frailty and improve the recovery process of patients.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To explore the molecular mechanism of miR-4508 regulating the inflammatory response of human bronchial epithelial cells induced by representative chrysotile asbestos.Methods:The chrysotile asbestos was ground into ultrafine dust using a horizontal planetary instrument, and human bronchial epithelium (16HBE) cells were taken as the object of infection. Cell survival rate was detected by cell counting kit-8 method, cytotoxicity was detected by lactate dehydrogenase (LDH) kit. The released of inflammatory factor IL-6 was detected by electrochemical luminescence. The released inflammatory factor IL-8 was detected by enzyme-linked immunosorbent assay. The expression level of miR-4508 was screened and verified by reverse transcription-quantitative real-time polymerase chain reaction. After 16HBE cells were treated with AKT inhibitor MK2206, the phosphorylation levels of AKT and PTEN were detected by western blot. The expression levels of AKT and PTEN and the contents of IL-6 and IL-8 were detected in miR-4508 overexpression and interference experiments.Results:With the increase of chrysotile asbestos exposure concentration, the cell survival rate decreased in a concentration-dependent manner, and the LDH content gradually increased. The secretion of IL-6 and IL-8 in chrysotile 25, 50 and 75 μg/ml groups were (325.92±8.61) pg/ml, (331.51±4.96) pg/ml, (378.74±13.77) pg/ml, and (94.95±3.11) pg/ml, (357.60±1.80) pg/ml, (537.19±3.11) pg/ml, respectively, while the group with 0 μg/ml chrysotile was (95.85±1.20) pg/ml and (7.81±0.00) pg/ml ( P＜0.05). In addition, chrysotile asbestos exposure to 16HBE could induce the high expression of miR-4508 . After pretreatment with MK2206, the phosphorylation levels of AKT and PTEN were decreased, the contents of IL-6 and IL-8 were significantly decreased, and the expression level of miR-4508 was significantly reduced. Overexpression of miR-4508 significantly increased the expressions of AKT and PTEN, and the contents of IL-6 and IL-8 ( P＜0.01). After interfering with miR-4508, the expressions of AKT and PTEN were significantly decreased, and the contents of IL-6 and IL-8 were significantly decreased ( P＜0.01). Conclusions:Chrysotile asbestos can induce the inflammatory response of 16HBE cells and up-regulate the expression level of miR-4508. The up-regulation of miR-4508 promotes the 16HBE inflammatory response induced by chrysotile asbestos through the PI3K/AKT pathway.

The objective of this study was to evaluate the toxicity and safety of novel Mycobacterium tuberculosis fusion strain protein derivatives,referred to as B/R strain active proteins.In cellular experiments,RAW264.7 cells were treated with each vaccine preparation,and apoptosis rates were measured.In subsequent animal experiments,C57BL/6 mice were immunized via subcutaneous injection,and their survival and body weight changes were monitored and recorded at 2,4,8,12,and 16 weeks.The lungs and spleens were harvested to calculate organ coefficients,and pathological examinations were conducted.At the eighth week of immunization,the mice were infected with high concentrations of BCG,and pathological changes in the lungs and spleens were observed 4 weeks post-infection.The apoptosis rate at 6 hours was significantly higher in the experimental group than the PBS group(P<0.05).At 12 and 24 hours,the apoptosis rate in the experimental group remained higher than that in the PBS group,although this difference was not statistically significant.After immunization,mice in all four groups exhibited normal growth patterns,as indicated by stable body weight changes.At 4 and 12 weeks post-immunization,the lung coefficients in the protein group were significantly higher than those in the PBS group at the same time points.Additionally,the lung coefficients in the BCG group were significantly elevated across all time periods(P<0.05).The spleen coefficients in the protein and BCG groups were significantly higher than those in the PBS group at 2,4,8,12,and 16 weeks,whereas the ICD B/R group showed higher spleen coefficients than the PBS group only at week 8(P<0.05).Pathological examination revealed normal lung and spleen tissues in the PBS group.However,during the 2-8 weeks immunization period,lung and spleen tissues in all experimental groups exhibited varying degrees of damage,which gradually diminished by 12-16 weeks.Notably,no tuberculosis nodules were observed in any experimental group.After infection with high concentrations of BCG,no overt pathological changes were observed on the surfaces of the lungs and spleens in any group.Microscopic examination revealed less severe pathological changes in the lungs and spleens of mice in the experimental groups than the PBS group.Furthermore,no statistically significant differences were observed between the protein group and the BCG group.Our findings suggested that the B/R strain active proteins'toxicity and safety profiles were comparable to those of BCG,and showed immunoprotective effects.This study provides an experimental foundation for the development of a novel tuberculosis vaccine.

Objective:The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation.Methods:A male proband who presented with bilateral sensorineural hearing loss at Henan Children′s Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family.Results:In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion:The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.

A deep learning based microwave imaging model which can directly map the scattered electric field to the dielectric property distribution image of the target object is developed,and its potential for medical applications is explored.The two-dimensional time-domain finite difference method is used for numerical simulation to obtain a dataset of scattered electric fields;a deep convolutional autoencoder based imaging model is constructed to perform imaging studies on two types of target objects;the imaging results are quantitatively evaluated using relative error,and the model's ability to distinguish different types of strokes is also analyzed.The results show that the imaging network based on deep convolutional autoencoder exhibits excellent imaging performance when processing both numerical models.For simple objects,the model can accurately locate and preliminarily reconstruct the shape of the object,with an average relative error of 0.3012,while for the stroke models,it can effectively reconstruct the location and shape of the stroke area,and preliminarily reconstruct other brain tissues,with an average relative error of 0.077 8.The microwave imaging network based on deep convolutional autoencoder has great promise for fast and accurate image reconstruction,and the numerical example of stroke detection demonstrates its significant application potential in biomedical imaging.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective To investigate the impact of different cell digestion methods on the binding of a humanized monoclonal antibody targeting CD3L1(designated as 5H)to tumor cells.Methods Trypsin solution and a collagenase/neutral protease cocktail,combined with two digestion temperatures(room temperature and 37℃),were used to dissociate,passage,and collect various adherent tumor cell lines.Flow cytometry and confocal microscopy were then employed to compare differences in 5H antibody binding under different cell digestion conditions.Results Cells dissociated and passaged with trypsin solution at room temperature exhibited only weak binding to the 5H antibody,whereas those treated with the collagenase/neutral protease cocktail at room temperature showed significantly stronger binding.There were notable differences in the binding signal and the proportion of antibody-stained positive cells between the two groups(P<0.01).Additionally,cells treated with the collagenase/neutral protease cocktail exhibited antibody binding signals that were dependent on the concentration of the 5H antibody,enabling receptor occupancy analysis.Compared to digestion at room temperature,treatment at 37℃ resulted in a slight reduction in the binding of target cells to the 5H antibody,however,this difference was not statistically significant.Conclusion Trypsin digestion significantly reduces the binding of the anti-CD3L1 antibody to tumor cells,whereas the collagenase/neutral protease cocktail effectively preserves it.With an appropriate choice of digestion enzymes,the impact of digestion temperature is relatively minor.These findings suggest that optimized cell digestion protocols should be employed when studying interactions between antibody drugs and cell surface antigens.

Background Previous studies have demonstrated that the vagus nerve stimulation improves upper limb function in patients with stroke sequelae(six month-two years).This study aimed to investigate whether the auricular intradermal acupuncture(AIA)acted on the auricular branch of the vagus nerve can facilitate the recovery of upper limb motor function and expedite the effects and characteristics of rehabilitation processes in flaccid phase after stroke in Phase Brunnstrom Ⅰ.Methods This study utilized a randomized controlled single-blinded clinical design.Patients with ischemic stroke in Phase Brunnstrom Ⅰ were randomly assigned to the auricular intradermal acupuncture(AIA)group(AIA,standard rehabilitation,conventional acupuncture)or the sham auricular intradermal acupuncture(sham AIA)group(the sham AIA,standard rehabilitation,conventional acupuncture)for 6 days of 1 week(6 times).Primary outcome measures:Brunnstrom(Ueda Assessment),Fugl-Meyer assessment of the upper extremity(FMA-UE)and its subtype score(FMA-UEFS,FMA-UEES),Wolf motor function test scale(WMFT).Secondary outcome measures:Upper limb active range of joint motion(AROM),manual muscle test(MMT)of upper limb muscles,Barthel index(BI).Results Of the 332 patients who were screened,70 patients met the criteria and were recruited.There were 35 patients in the AIA group,1 patient was fall off,34 patients were actually completed;35 patients in the sham AIA group had no falling off case.Primary outcome measures:The upper Ueda assessment of the AIA group were better than those of the sham AIA group after treatment on days 3 and 6(P<0.05,P<0.001,respectively).The FMA-UEFS score on days 6 of the AIA group were significantly better than those of the sham AIA group(P<0.05).FMA-UEES of the AIA group was more associated with FMA-UE than FMA-UEFS with FMA-UE after treatment on day 6(FMA-UEFS:r=0.728,P<0.001;FMA-UEES:r=0.744,P<0.001).After 3 days and 6 days of treatment,the AIA group of the WMFT were significantly improved in the sham AIA group(P<0.05,P<0.001,respectively).Secondary outcome measures:AROM:After 6 days of treatment,the AIA group of shoulder abduction were more improved than in the sham AIA group(P<0.05).MMT:The muscle strength of elbow flexion,and elbow extension muscle improved more in the AIA group than in the sham AIA group(P<0.05).Barthel index(BI):After 6 days of treatment,there was a significant improvement in the group compared with before treatment(P<0.05),but no difference compared with the group(P>0.05).Conclusions AIA combined with conventional rehabilitation and acupuncture,can effectively improve the upper limb motor function of patients with post-ischemic stroke flaccid hemiplegia and accelerates the rehabilitation process of upper limb motor function.Clinical Trial Registration The study protocol is registered withhttp://www.chictr.org.cn(accession number:ChiCTR2200058141).

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.