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:To investigate the effect of infusing different doses of graft cells on viral infections and survival after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 99 patients with hematological diseases who underwent allo-HSCT in Shanxi Bethune Hospital were retrospectively analysed.The proportion of mononuclear cells(MNC)was counted microscopically,the proportions and absolute counts of CD34+cells and lymphocyte subsets(including CD3+T,CD4+T,CD8+T,CD4+CD8+T,B,and NK cells)were detected by flow cytometry,and the infusion dose of each cell types was calculated.The patients were divided into high-dose group and low-dose group based on the median value of the infused cell dose.The effects of different doses of various graft cells on post-transplant viral infections(CMV,EBV,BKV)and survival were analyzed.Results:The low-dose MNC(＜7.97 × 108/kg)and high-dose CD4+CD8+T cell(≥3.02 × 106/kg)groups had a higher Epstein-Barr virus(EBV)infection rate(P=0.031;P=0.020).The high-dose CD34+cell group and low-dose CD3+T,CD8+T and natural killer(NK)cell groups showed a trend toward higher EBV infection rates,but the differences were not statitsically significant(P＞0.05).There was no significant difference in the rates of EBV infection between the high-dose and low-dose groups of CD4+T and B cells(P＞0.05).Multivariate analysis revealed that the doses of MNC and CD4+CD8+T cells in the graft were independent factors influencing EBV infection(P=0.023;P=0.016).The doses of cells in the graft showed no significant impact on CMV and BKV infection,or patient survival(P＞0.05).Conclusion:Infusing a lower dose of MNC and a higher dose of CD4+CD8+T cells increases the risk of EBV infection,but does not affect the survival outcome.

Objective:To explore the construction of clinical competence index system for general practitioners based on CIPP(context evaluation, input evaluation, process evaluation, product evaluation) evaluation model.Methods:Based on the CIPP evaluation model, a research team was established to conduct a literature review. Research articles were retrieved, screened, and analyzed to formulate the primary clinical competence index system for general practitioners based on CIPP evaluation model and the expert consultation questionnaire. The Delphi method was employed to finalize the clinical competence index system for general practitioners based on CIPP evaluation model.Results:A total of 24 experts from grade A tertiary hospitals in several provinces and cities in China participated in two rounds of consultation. The effective recovery rate for both rounds was 100.00%. The authority coefficients were 0.905 and 0.912, respectively. After the consultations, the coefficients of variation of indexes at all levels were <0.25. The Kendall's W of all indexes ranged between 0.769 and 0.814 in the first round and between 0.867 and 0.905 in the second round of expert consultation ( P<0.001). The final clinical competence index system for general practitioners based on CIPP evaluation model included 4 first-level indexes, 12 second-level indexes, and 42 third-level indicators. Conclusions:The clinical competence index system for general practitioners based on CIPP evaluation model established in this study has reference significance for further research on the training assessment and evaluation index system of clinical competence for general practitioners in China, and has important practical significance for the evaluation tool of clinical work performance of general practitioners.

Objective To analyze the relationship between apolipoprotein E(APOE)genotype and cognitive impairment among individuals aged 40 and above in rural Xi'an and to explore the potential influence of education on this relationship.Methods All permanent residents aged 40 and above from two villages in Huyi District,Xi'an City,were selected as research subjects,employing a cross-sectional survey approach.The Mini-Mental State Examination(MMSE)was utilized to assess overall cognitive function,with MMSE scores below the threshold values(illiterate ≤17,primary school ≤20,junior high and above ≤24)considered as cognitive impairment.Fasting elbow venous blood was drawn in the morning,and the APOE genotype was determined.The population was divided into low-education(LE,≤9 years)and high-education(HE,＞9 years)groups based on educational level.Univariate and multivariate analyses were applied to explore the association between APOE genotype and cognitive impairment,as well as MMSE scores in both the total and stratified populations.Results Out of the 1 692 participants,there were 263 APOE ε4 allele carriers(E2/4,E3/4,E4/4)(15.3％),and 205 individuals met the criteria for cognitive impairment(12.1％).Multivariate Logistic regression and linear regression analyses revealed that in both the total population and the LE population,compared to APOE ε4 allele non-carriers(E2/2,E2/3,E3/3),APOE ε4 allele carriers exhibited a higher risk of cognitive impairments(total population:OR=1.509,95％CI:1.030-2.211,P=0.035;LE:OR=1.604,95％CI:1.080-2.381,P=0.019),and their MMSE scores were lower(total population:β=-0.053,95％CI:-0.983--0.162,P=0.006;LE:β=-0.052,95％CI:-1.052--0.124,P=0.013).However,in the HE population,there was no statistically significant difference in the prevalence of cognitive impairment(OR=1.883,95％CI:0.254-13.980,P=0.536)and MMSE scores(β=0.001,95％CI:-0.635-0.642,P=0.992)between APOE ε4 allele carriers and non-carriers.Conclusion The APOE ε4 allele was associated with an increased risk of cognitive impairment in individuals aged 40 and above in rural areas of Xi'an,while HE attainment may offer protective effects against cognitive impairment in APOE ε4 allele carriers.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective To evaluate the cost-effectiveness of inclisiran injection treatment in patients with atherosclerotic heart disease(ASCVD)in China.Methods From the perspective of China's health system,according to the Markov model,patients with ASCVD were divided into inclisilan injection group and placebo group,and both groups were treated with convention-al lipid-lowering drugs.The study period was 25 years.The rate parameters,cost parameters,and effectiveness parameters were de-rived from the ORION-18 trial and other literature.Effects were expressed as quality-adjusted life-years(QALYs).The incremental cost-effectiveness ratio(ICER)was used to evaluate the economy of inclisilan injection.One-way sensitivity analysis and probabil-ity sensitivity analysis were used to verify the reliability of the results.Results The treatment effect of the inclisilan injection group was higher(10.02 QALYs),and the cost of the placebo group was lower(255 179 yuan).The ICER of the two groups was 137 850 yuan per QALY gained,and using 257 094 yuan per capita by 2022 as the threshold,the treatment would be economically advantageous.Sensitivity analysis supported this result.Conclusion At present,the additional use of inclisilan injection can get a better treatment effect,and it has economic advantages under the threshold of three times GDP per capita in China.

Objective:To investigate the correlation between the types and quantities of immune cells in the graft and early immune reconstitution after allogeneic hematopoietic stem cell transplantation(allo-HSCT)and their influence on clinical prognosis.Methods:The clinical data of 83 patients with hematological diseases who received allo-HSCT in Shanxi Bethune Hospital from September 2020 to June 2023 were retrospectively analyzed.The number of mononuclear cells(MNC),CD34+cells and lymphocyte subsets(including CD3+T,CD3+CD4+T(Th),CD3+CD8+T(Ts),NK cells and B cells)infused into the recipients was counted,and the peripheral blood lymphocytes were detected before conditioning and on days 14,30,60 and 100 post-HSCT.Results:Multivariate analysis showed that the number of MNC in the graft affected the recovery of CD4+T lymphocytes after HSCT,and the number of CD4+T lymphocytes in the graft affected the recovery of NK cells and B cells after HSCT.The patient age,donor sex,stem cell source,degree of HLA matching,use of ATG before HSCT,the occurrence of acute graft-versus-host disease(aGVHD)after HSCT,and viral infection all affect the early cellular immune reconstitution post-HSCT.The number of infused cells had no significant impact on the median engraftment time for neutrophils and platelets after HSCT.Patients with lower numbers of CD3+T,CD4+T and B cells in the graft were more prone to viral infection after HSCT.However,the cells in the graft had no significant effect on disease recurrence or mortality.Conclusion:The recovery rate of lymphocyte count after allo-HSCT varies.The numbers of MNC and CD4+T cells in the graft may be related to the cellular immune reconstitution after HSCT,while the numbers of CD34+,CD3+T,CD8+T,NK and B cells have no significant effect on the cellular immune reconstruction.The numbers of CD3+T,CD4+T and B cells in the graft were negatively correlated with viral infection after HSCT,but the cellular components of the graft have no obvious influence on hematopoietic reconstitution,disease recurrence,death,recurrence-free survival(RFS)and overall survival(OS)after HSCT.

Objective:To investigate the effect of infusing different doses of graft cells on viral infections and survival after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 99 patients with hematological diseases who underwent allo-HSCT in Shanxi Bethune Hospital were retrospectively analysed.The proportion of mononuclear cells(MNC)was counted microscopically,the proportions and absolute counts of CD34+cells and lymphocyte subsets(including CD3+T,CD4+T,CD8+T,CD4+CD8+T,B,and NK cells)were detected by flow cytometry,and the infusion dose of each cell types was calculated.The patients were divided into high-dose group and low-dose group based on the median value of the infused cell dose.The effects of different doses of various graft cells on post-transplant viral infections(CMV,EBV,BKV)and survival were analyzed.Results:The low-dose MNC(＜7.97 × 108/kg)and high-dose CD4+CD8+T cell(≥3.02 × 106/kg)groups had a higher Epstein-Barr virus(EBV)infection rate(P=0.031;P=0.020).The high-dose CD34+cell group and low-dose CD3+T,CD8+T and natural killer(NK)cell groups showed a trend toward higher EBV infection rates,but the differences were not statitsically significant(P＞0.05).There was no significant difference in the rates of EBV infection between the high-dose and low-dose groups of CD4+T and B cells(P＞0.05).Multivariate analysis revealed that the doses of MNC and CD4+CD8+T cells in the graft were independent factors influencing EBV infection(P=0.023;P=0.016).The doses of cells in the graft showed no significant impact on CMV and BKV infection,or patient survival(P＞0.05).Conclusion:Infusing a lower dose of MNC and a higher dose of CD4+CD8+T cells increases the risk of EBV infection,but does not affect the survival outcome.

Objective:To explore the construction of clinical competence index system for general practitioners based on CIPP(context evaluation, input evaluation, process evaluation, product evaluation) evaluation model.Methods:Based on the CIPP evaluation model, a research team was established to conduct a literature review. Research articles were retrieved, screened, and analyzed to formulate the primary clinical competence index system for general practitioners based on CIPP evaluation model and the expert consultation questionnaire. The Delphi method was employed to finalize the clinical competence index system for general practitioners based on CIPP evaluation model.Results:A total of 24 experts from grade A tertiary hospitals in several provinces and cities in China participated in two rounds of consultation. The effective recovery rate for both rounds was 100.00%. The authority coefficients were 0.905 and 0.912, respectively. After the consultations, the coefficients of variation of indexes at all levels were <0.25. The Kendall's W of all indexes ranged between 0.769 and 0.814 in the first round and between 0.867 and 0.905 in the second round of expert consultation ( P<0.001). The final clinical competence index system for general practitioners based on CIPP evaluation model included 4 first-level indexes, 12 second-level indexes, and 42 third-level indicators. Conclusions:The clinical competence index system for general practitioners based on CIPP evaluation model established in this study has reference significance for further research on the training assessment and evaluation index system of clinical competence for general practitioners in China, and has important practical significance for the evaluation tool of clinical work performance of general practitioners.

Objective To analyze the relationship between apolipoprotein E(APOE)genotype and cognitive impairment among individuals aged 40 and above in rural Xi'an and to explore the potential influence of education on this relationship.Methods All permanent residents aged 40 and above from two villages in Huyi District,Xi'an City,were selected as research subjects,employing a cross-sectional survey approach.The Mini-Mental State Examination(MMSE)was utilized to assess overall cognitive function,with MMSE scores below the threshold values(illiterate ≤17,primary school ≤20,junior high and above ≤24)considered as cognitive impairment.Fasting elbow venous blood was drawn in the morning,and the APOE genotype was determined.The population was divided into low-education(LE,≤9 years)and high-education(HE,＞9 years)groups based on educational level.Univariate and multivariate analyses were applied to explore the association between APOE genotype and cognitive impairment,as well as MMSE scores in both the total and stratified populations.Results Out of the 1 692 participants,there were 263 APOE ε4 allele carriers(E2/4,E3/4,E4/4)(15.3％),and 205 individuals met the criteria for cognitive impairment(12.1％).Multivariate Logistic regression and linear regression analyses revealed that in both the total population and the LE population,compared to APOE ε4 allele non-carriers(E2/2,E2/3,E3/3),APOE ε4 allele carriers exhibited a higher risk of cognitive impairments(total population:OR=1.509,95％CI:1.030-2.211,P=0.035;LE:OR=1.604,95％CI:1.080-2.381,P=0.019),and their MMSE scores were lower(total population:β=-0.053,95％CI:-0.983--0.162,P=0.006;LE:β=-0.052,95％CI:-1.052--0.124,P=0.013).However,in the HE population,there was no statistically significant difference in the prevalence of cognitive impairment(OR=1.883,95％CI:0.254-13.980,P=0.536)and MMSE scores(β=0.001,95％CI:-0.635-0.642,P=0.992)between APOE ε4 allele carriers and non-carriers.Conclusion The APOE ε4 allele was associated with an increased risk of cognitive impairment in individuals aged 40 and above in rural areas of Xi'an,while HE attainment may offer protective effects against cognitive impairment in APOE ε4 allele carriers.