ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

Objective: The cross sectional study aimed to identify predominant co-occurrence patterns among six common mental health issues in college students, so as to provide empirical basis for designing targeted interventions. Methods: From October 2024, a total of 9 837 students from 4 universities in Xiangtan City, Hunan Province, participated in the current study by multistage random cluster sampling method. Participants completed self report measures, including the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7 item Scale (GAD-7), Young s Internet Addiction Diagnostic Questionnaire, the Adolescent Insomnia Symptom Self rating Scale, the Ottawa Self injury Inventory, and the Brief Community Assessment of Psychic Experiences Questionnaire. Demographic and co-occurrence characteristics were first compared using Chi square or trend Chi-square tests, followed by application of the Apriori algorithm to mine association rules for primary co-occurrence patterns. Results: The detection rate of co-occuring the common mental health issues was 46.44%. The detection rate was significantly higher in female than in male students (50.42%, 43.61%; χ 2=44.46) and in students from rural versus urban areas (47.22%, 44.60%; χ 2=5.67) (both P <0.05). Significant differences were observed among freshmen, sophomores, juniors, and seniors (46.63%, 48.35%, 45.05% , 43.66%, respectively; χ 2=9.22, P <0.05), although no statistically significant trend was detected ( χ 2 trend =3.75, P = 0.05 ). Association rule mining identified “anxiety + depression” “anxiety + psychotic experiences + depression” and “anxiety + sleep disorder + depression” as the combinations with the highest support. In addition, “anxiety+depression+Internet addiction+psychotic experiences =>sleep disorder (>= refered to the occurrence of the latter item under the condition that the former item occurs)” and “anxiety + depression+Internet addiction=>sleep disorder” were combinations with relatively high confidence. Conclusions Co-occurrence of these mental health issues among college students is high and exhibits diverse patterns. Strategies to address this burden should prioritize integrated interventions that target these specific combinations of factors.

ObjectiveTo address the limitations of the current quality standard for Polygalae Radix（PR）， which relies on a single component for quality assessment and struggles to holistically control its intrinsic quality， by constructing a comprehensive quality evaluation system integrating "macro-characterization of chemical profile， synchronous quantification of multiple index components， and quantitative analysis of multi-components by single marker（QAMS） for key component groups". This study aims to facilitate the scientific revision of the quality standard for PR. MethodsHigh performance liquid chromatography（HPLC） characteristic chromatograms were established for 11 batches of PR medicinal materials（YZ）， 10 batches of PR decoction pieces（YP）， and 10 batches of licorice-processed PR decoction pieces（ZYZ）， followed by similarity evaluation and identification of common peaks. HPLC-QAMS was developed for xanthones（sibiricaxanthone B， polygalaxanthone Ⅺ， polygalaxanthone Ⅲ） in the characteristic chromatograms. Simultaneously， the external standard method（ESM） was used to determine the contents of the corresponding xanthones and 3，6'-disinapoyl sucrose in YZ， YP， and ZYZ， followed by multivariate statistical analysis and Spearman correlation analysis. ResultsThe similarity between the characteristic chromatograms of 31 batches of PR samples and the reference chromatogram was>0.9. A total of 13 common peaks were identified， and 10 of these peaks were characterized through reference standard comparison. The successfully constructed QAMS method showed that the relative correction factors（RCFs） of sibiricaxanthone B and polygalaxanthone Ⅺ to polygalaxanthone Ⅲ were 0.76 and 0.88， and their relative retention times（RRTs） were 0.85 and 0.97， respectively. The results calculated by the QAMS method showed no significant difference from those obtained by the ESM. According to the limit standard for polygalaxanthone Ⅲ in the 2020 edition of the Pharmacopoeia of the People's Republic of China（hereinafter referred to as the Chinese Pharmacopoeia）， the pass rate of 31 batches of samples was only 19.35%. Multivariate statistical analysis indicated certain compositional differences between different batches of YZ and YP， as well as between YP and ZYZ， with 3，6'-disinapoyl sucrose identified as the main differentiating component. Furthermore， correlation analysis revealed that the content of polygalaxanthone Ⅲ was positively correlated with the contents of sibiricaxanthone B and polygalaxanthone Ⅺ， but showed no association with the content of 3，6'-disinapoyl sucrose. ConclusionIt is recommended that the content limit for polygalaxanthone Ⅲ in YZ，YP and ZYZ be revised to not less than 0.07%， or the total content of polygalaxanthone Ⅲ， sibiricaxanthone B and polygalaxanthone Ⅺ be not less than 0.18%. The newly established triple quality control model of "holistic control via characteristic chromatograms， precise quantification of oligosaccharide esters， and efficient detection of xanthones by QAMS" provides a systematic and precise solution for quality evaluation of PR and similar Chinese herbal medicines.

Objective To observe the depressive behavior and neuronal damage induced by different doses of corticosterone(CORT)in mice,and to explore the optimal dose for a corticosterone-induced depression model in mice.Methods Forty male C57BL/6J mice were divided randomly into four groups:control group and low,medium,and high CORT groups(20,40,and 60 mg/kg,respectively),treated with the corresponding drug dose by subcutaneous injection for 4 weeks.Behavioral c hanges in mice after corticosterone administration for 3 and 4 weeks were detected by sugar water preference,forced swimming,tail suspension,and open field tests.Morphological changes in neurons in the hippocampal CA1 area and forebrain cortex area were observed by hematoxylin-eosin(HE)and Nissl staining.Serum levels of 5-hydroxytryptamine(5-HT)were detected by enzyme-linked immunosorbent assay.Depression-related behavioral changes induced by different doses of corticosterone were compared.Results The bodyweights of mice in all three CORT groups(20,40,and 60 mg/kg)decreased(P＜0.05)and the preference for sucrose solution decreased(P＜0.01)compared with the findings in the control group.The immobility time in the forced swimming test was prolonged in the CORT 20 and 40 mg/kg groups(P＜0.01)and the immobility time of mice in the tail suspension test was prolonged in the CORT 40 mg/kg group(P＜0.05).The total distance,the length of time spent in the peripheral area was prolonged and the time entering the central area in the open-field experiment were decreased in the CORT 40 and 60 mg/kg groups(P＜0.05),and average speed were decreased in the CORT 40 mg/kg group(P＜0.05).In addition,CORT injection result ed in abnormal neuronal cell morphology,cell deformation,and nuclear condensation in the hippocampal CA1 and forebrain cortex areas,to different degrees.Serum 5-hydroxytryptamine levels were reduced in the CORT 40 and 60 mg/kg groups(P＜0.05).Conclusions CORT 20,40,and 60 mg/kg can induce depression-like behavioral changes and neuronal damage in mice to varying degrees,with the most notable effect at 40 mg/kg.Under experimental conditions,we consider that 40 mg/kg is the best dose for replicating corticosterone-induced depression in model mice.

Objective:To explore the significance of any correlation between the cost of the rehabilitation provided to stroke survivors during their hospitalization and the functional levels attained, and to analyze factors influencing that correlation.Methods:The International Classification of Functioning, Disability and Health Rehabilitation Set (ICF-RS) was used to evaluate the functioning of 304 stroke survivors on their days of hospital admission and discharge, as well as on their 10th day in hospital. The cost of their rehabilitation was computed, and demographic and clinical data were collected. A generalized estimation equation was used to analyze the changes in dysfunction with time and its risk factors. The relationship between functional levels and rehabilitation cost and its influencing factors were analyzed.Results:Length of stay, age≥60 and hemorrhagic stroke were significant risk factors for greater dysfunction among the stroke survivors. On the 10th day in hospital and the day before discharge (the 18th day), the frequency of severe dysfunction had decreased. The significant predictors of increased cost were severe or moderate dysfunction, the stage of stroke (sub-acute stage), and non-first rehabilitation.Conclusion:Functional level is a useful predictor of rehabilitation cost. It is influenced by the stage of stroke and non-first rehabilitation.

Objective To analyze the antiviral effect of molnupiravir against influenza virus in vitro and in vivo.Methods The antiviral ability of molnupiravir against influenza virus strain H1N1 PR8 was detected in vitro and in vivo.H uman non-small cell lung cancer cell line(A549 cells)was used as an in vitro model of PR8 infection.The antiviral effects of molnupiravir on virus replication,protein synthesis,and viral particle formation were analyzed using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR),Western blot(WB)assay,and plaque assay.PR8 nose-dripping infected C57BL/6 female mice were used as an in vivo infection model.The antivi-ral ability of molnupiravir was evaluated by detecting viral load,pathological changes,and immunohistochemistry in the control group,administration group,inoculation group,and inoculation-administration group.Results In vitro test results showed that molnupiravir had no significant inhibitory effect on influenza virus replication,protein syn-thesis,and virus particle formation(all P＞0.05).In vivo test results showed that compared with mice infected with H1N1 alone,the viral load in the lung tissue of mice treated with molnupiravir declined significantly,and the extent of pathological changes was milder.Immunohistochemical detection showed a significant weakening in nuclear protein(NP)antigen signal,and the expression levels of interferon(IFN)-α,interleukin(IL)-4,and IL-6 in the lungs were lower(all P＜0.01).Conclusion As a precursor with antiviral activity,molnupiravir can not exert anti-viral activity in lung-derived cells cultured in vitro,but can be transformed into an active form in the host,which significantly decreases the ability of H1N1 influenza virus to proliferate in the lungs and thereby alleviates the da-mage of virus to lung tissue.

Objective:To explore the significance of any correlation between the cost of the rehabilitation provided to stroke survivors during their hospitalization and the functional levels attained, and to analyze factors influencing that correlation.Methods:The International Classification of Functioning, Disability and Health Rehabilitation Set (ICF-RS) was used to evaluate the functioning of 304 stroke survivors on their days of hospital admission and discharge, as well as on their 10th day in hospital. The cost of their rehabilitation was computed, and demographic and clinical data were collected. A generalized estimation equation was used to analyze the changes in dysfunction with time and its risk factors. The relationship between functional levels and rehabilitation cost and its influencing factors were analyzed.Results:Length of stay, age≥60 and hemorrhagic stroke were significant risk factors for greater dysfunction among the stroke survivors. On the 10th day in hospital and the day before discharge (the 18th day), the frequency of severe dysfunction had decreased. The significant predictors of increased cost were severe or moderate dysfunction, the stage of stroke (sub-acute stage), and non-first rehabilitation.Conclusion:Functional level is a useful predictor of rehabilitation cost. It is influenced by the stage of stroke and non-first rehabilitation.

Objective To analyze the antiviral effect of molnupiravir against influenza virus in vitro and in vivo.Methods The antiviral ability of molnupiravir against influenza virus strain H1N1 PR8 was detected in vitro and in vivo.H uman non-small cell lung cancer cell line(A549 cells)was used as an in vitro model of PR8 infection.The antiviral effects of molnupiravir on virus replication,protein synthesis,and viral particle formation were analyzed using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR),Western blot(WB)assay,and plaque assay.PR8 nose-dripping infected C57BL/6 female mice were used as an in vivo infection model.The antivi-ral ability of molnupiravir was evaluated by detecting viral load,pathological changes,and immunohistochemistry in the control group,administration group,inoculation group,and inoculation-administration group.Results In vitro test results showed that molnupiravir had no significant inhibitory effect on influenza virus replication,protein syn-thesis,and virus particle formation(all P＞0.05).In vivo test results showed that compared with mice infected with H1N1 alone,the viral load in the lung tissue of mice treated with molnupiravir declined significantly,and the extent of pathological changes was milder.Immunohistochemical detection showed a significant weakening in nuclear protein(NP)antigen signal,and the expression levels of interferon(IFN)-α,interleukin(IL)-4,and IL-6 in the lungs were lower(all P＜0.01).Conclusion As a precursor with antiviral activity,molnupiravir can not exert anti-viral activity in lung-derived cells cultured in vitro,but can be transformed into an active form in the host,which significantly decreases the ability of H1N1 influenza virus to proliferate in the lungs and thereby alleviates the da-mage of virus to lung tissue.

Objective To design a custom 3D printed monoblock acetabular implant for reconstructing PaproskyⅢA acetabular bone defects and to analyze the stress distribution,displacement,and clinical reliability of the implant and surrounding bone using finite element analysis(FEA).Methods Bilateral hip computed tomography(CT)data of a patient with PaproskyⅢA acetabular bone defects were collected.Models were developed and analyzed using Mimics Medical 21.0,Geomagic Wrap 2021,Solidworks 2023,and ANSYS Workbench 2022 R1 softwares.The biomechanical performance of the custom 3D printed monoblock acetabular implant was simulated under a single-leg stance condition.Results The peak von Mises stress of the hip components was observed at the femoral stem,measuring 67.318 MPa.For the custom 3D printeded monoblock acetabular implant,the peak stress was located at the anterosuperior contact area between the implant and acetabular bone,measuring 6.935 MPa.The femoral stem exhibited a peak stress of 67.318 MPa at its junction with the femoral head.The liner's peak stress was 1.333 MPa near the fixation of screw 9 at the superior part of the acetabular cup.The screws showed a peak stress of 2.215 MPa at the junction with the implant.For the cortical bone,the peak stress was 9.844 MPa at the distal femur,while the cancellous bone exhibited a peak stress of 0.701 MPa at its distal connection with the femoral stem.The pelvic bone's peak stress was 8.002 MPa at the anterior transition zone between the normal acetabulum and the defect.The peak micromotion of the custom 3D printed monoblock acetabular implant at its posterosuperior area,measuring 0.114 mm.The femoral stem and head exhibited a peak micromotion of 0.132 mm at the contact interface with the acetabular liner.The micromotion range at the implant-acetabular bone interface was 0.098 mm to 0.131 mm.Conclusion Under a simulated single-leg stance condition,the stress distribution in all components and the acetabular bone surface remains below their respective yield strengths.The micromotion threshold between the acetabular cup and acetabular bone is within acceptable limits.Biomechanical analysis indicates that the patient can perform early weight-bearing rehabilitation postoperatively.However,walking or jogging rehabilitation should be approached with caution.