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 analyze the clinical characteristics, treatment, and prognosis of seven pediatric patients with Acute myeloid leukemia (AML) positive for the t(16;21)(p11;q22) FUS::ERG fusion gene. METHODS: A retrospective analysis was carried out on the clinical data, treatment, and prognosis of seven AML patients with t(16;21)(p11;q22) FUS::ERG fusion gene admitted to Henan Children's Hospital between June 2015 and November 2024. Relevant literature was also reviewed. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-102-001). RESULTS: Among 297 pediatric patients with AML, 7 cases (2.36%) were positive for the t(16;21)(p11;q22) FUS::ERG fusion gene, including 3 males and 4 females, with a median age of 11 years (range: 3 ~ 12 years). According to the FAB classification, these included 1 case of M2, 3 cases of M5, and 3 cases of AML-not otherwise specified (non-M3). All 7 patients were found to harbor the t(16;21)(p11;q22) translocation, with 3 cases showing additional chromosomal abnormalities. Immunophenotyping revealed universal expression of CD13, CD33, CD34, and CD117, with partial expression of CD56, CD4, CD64, CD123, CD15, CD38, CD11b, HLA-DR, cMPO, and CD16. One patient achieved complete remission (CR) after the first course of DAE (cytarabine + daunorubicin + etoposide) induction chemotherapy but relapsed and discontinued the treatment. Six patients received DAH (cytarabine + daunorubicin + homoharringtonine) induction therapy, of whom 2 achieved CR after two courses and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), resulting in an overall CR rate of 42.86%. Five children did not receive allo-HSCT and had a median overall survival of 9 months (range: 6 ~ 18 months). Two children who underwent transplantation achieved bone marrow morphological and molecular biological relapse at 6 and 9 months post-transplantation, respectively. After receiving combined chemotherapy and donor lymphocyte infusion, one child failed to achieve remission and died at 22 months post-transplantation, while the other has been followed up to date with positive fusion gene status. Their overall survival was 25 months and 30 months, respectively. CONCLUSION The t(16;21)(p11;q22) FUS::ERG fusion gene is rare in pediatric AML and associated with poor prognosis. Allo-HSCT may mitigate the adverse prognostic impact of the FUS::ERG fusion gene and contribute to prolonged survival.
Humans ; Male ; Child ; Female ; Leukemia, Myeloid, Acute/drug therapy* ; Oncogene Proteins, Fusion/genetics* ; Translocation, Genetic ; Retrospective Studies ; RNA-Binding Protein FUS/genetics* ; Chromosomes, Human, Pair 16/genetics* ; Adolescent ; Child, Preschool ; Chromosomes, Human, Pair 21/genetics* ; Prognosis ; Treatment Outcome

Objective To investigate the influence of high copper load on neurobehavior in rats and its possible mechanism of action based on the deacetylase sirtuin 3 （SIRT3）/peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） signaling pathway. Methods A total of 50 adult Sprague-Dawley rats were randomly divided into model group and blank group， with 25 rats in each group. The rats in the model group were fed with 1 g/kg high-copper diet and 0.185% copper sulfate solution （prepared using deionized water） to establish a rat model of high copper load， and after 12 weeks， the shuttle box test and the pole-climbing test were used to observe neurobehavioral changes， while Western blotting and immunofluorescent staining were used to measure the protein expression levels of SIRT3 and PGC-1α in hippocampal tissue. Results The shuttle box test showed that compared with the blank group， the model group had a significant reduction in the number of times of active avoidance reaction after stimulation （P<0.01） and significant increases in the times of active avoidance reaction and passive avoidance reaction （P<0.01）；the pole-climbing test showed that compared with the blank group， the model group had a significant increase in pole-climbing time（P<0.01）. Western blotting and immunofluorescent staining showed that compared with the blank group， the model group had significant reductions in the protein expression levels of SIRT3 and PGC-1α in hippocampal tissue （P<0.05）. Conclusion High copper load has a marked influence on the neurobehavior of rats， possibly by regulating the expression of the SIRT3/PGC-1α signal pathway in hippocampal neurons.

By reviewing modern research and integrating clinical practice， this paper interprets the correlation between "deep heat， deep syncope" and the "macrocirculation-microcirculation" uncoupling in sepsis， alongside its clinical applications in sepsis prevention and treatment. It is considered that "deep heat" corresponds to peripheral vasodilation and the hypermetabolic state at the macrocirculation level， whereas "deep syncope" manifests as hypoperfusion and impaired oxygen utilization at the microcirculation level. These two states interact detrimentally， forming the core contradiction of macrocirculation-microcirculation uncoupling in sepsis. Based on the traditional Chinese medicine （TCM） connotations of "deep heat， deep syncope" and modern medical research， this paper elucidates the systemic pathological evolution of sepsis from the inflammatory cascade to impaired oxygen utilization. Accordingly， the following therapeutic principles are proposed. In the early stage， it is suggested to clear heat and drain fire to vent the constrained yang. In the progressive stage， the focus is put on unblocking the lower jiao （焦） and expelling stasis to dredge the vessels and collaterals. In the recovery stage， the method of regulating and harmonizing yin and yang can be used to smooth the flow of qi and blood.

Objective By comparing the prevalence and mortality of dementia among rural people in Xi'an in 1997 and 2014 to clarify the epidemiological changes of dementia among rural people in the city over 17 years.Methods In 1997 and 2014,people aged 55 and above in villages in Xi'an were selected by random cluster sampling method,and face-to-face questionnaire survey was conducted by combining centralized and home visits.Dementia and its subtypes were diagnosed by"the three-step method";the changes of dementia prevalence and mortality were compared between the two surveys.Results The prevalence of dementia among rural residents aged 55 and above in Xi'an was 3.49％in 1997,with age-gender standardized prevalence of 2.08％.In 2014,the prevalence of dementia was 4.25％,with age-gender standardized prevalence of 2.78％.Over the 17 years,the prevalence of dementia increased by 1.79 times(OR=1.79,95％CI:1.20-2.65,P=0.004),with a 1.9-fold increase in females and a 1.67-fold increase in males.The mortality of dementia patients was 61.76‰ and age-gender standardized mortality was 60.20‰ in 1997,while the mortality was 35.71‰ and age-gender standardized mortality was 34.18‰ in 2014.The mortality of dementia decreased by 33％over the 17 years(HR=0.33,95％CI:0.15-0.74,P=0.007).Conclusion The prevalence of dementia in rural areas of Xi'an increased significantly over the 17 years,but the mortality rate decreased,and this trend was more obvious in women.

Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2％)were free of T2DM,158(11.7％)already had T2DM at baseline,and 96(7.1％)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0％of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7％vs.20.9％vs.26.0％,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95％CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95％CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.

Objective To explore the relationship between carotid atherosclerosis(CAS)and cognitive impairment in the stroke high-risk population aged 40 years and above in the rural area of Xi'an City and determine whether CAS is a risk factor for cognitive impairment.Methods In this study,stroke high-risk population found in the Community and Rural Population Stroke High-risk Group Screening and Intervention Project carried out in Huyi District,Xi'an City,from October 2014 to March 2015 were selected as the research subjects.Color Doppler ultrasound was used to evaluate CAS,and CAS was defined as:carotid intima-media thickness(CIMT)≥1.0 mm,or carotid arteries(including common carotid artery,carotid sinus,internal carotid artery,and external carotid artery)have atherosclerotic plaques,or carotid stenosis.Mini-Mental State Examination(MMSE)was used to assess cognitive function.The MMSE score lower than the cut-off value(illiteracy ≤17,primary school ≤ 20 points,and junior high school and above education level ≤24 points)is defined as cognitive impairment.The study population was grouped according to the presence of CAS or cognitive impairment;univariate difference test and bivariate logistic regression were used to analyze the relationship between CAS and cognitive impairment.Results A total of 451 subjects were included in the analysis.The average age of the subjects was(58.7±9.83)years old,and 44.3％were female.Among them,329 cases(72.9％)had CAS and 57 cases(12.6％)met the diagnostic criteria for cognitive impairment.The prevalence of cognitive impairment in CAS group was significantly higher than that in non-CAS group(14.6％vs.7.4％,P=0.041).Multivariate logistic regression analysis showed that cognitive impairment was significantly correlated with age(OR=1.121,95％CI:1.056-1.189,P＜0.001),but not with CAS(OR=1.008,95％CI:0.202-5.170,P=0.992).Conclusion No significant association between CAS and cognitive impairment was found in high stroke risk group aged 40 and above in rural areas of Xi'an.

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.

Objective To develop a risk predictive model of cognitive decline in a prospective cohort study in rural area of Xi'an and compare the predictive performance with that of the classical CAIDE model.Methods The cohort was established between October 2014 and March 2015 in two selected villages in rural Xi'an.Mini-Mental State Examination(MMSE)was applied to assess global cognition at baseline and 4-year follow-up,and cognitive decline was defined as a drop of ≥4 points in MMSE after 4-year follow-up.Participants were randomly split into training set and validation set in a ratio of 7∶3.The Logistic regression analysis was used to develop the predictive model,and the area under the receiver operating characteristic(ROC)curve was applied to assess the performance of the risk model.Results Occurrence of cognitive decline after 4-year follow-up was 4.15％.Future cognitive decline was significantly predicted by age,low education and stroke(AUC in training set=0.73,95％CI:0.63-0.79;AUC in valid data=0.77,95％CI:0.67-0.87),while the classical CAIDE model did not predict the risk of cognitive decline well(AUC=0.68,95％CI:0.61-0.75).The results differed after stratification by APOE genotype,and showed a better predictive value of both our model(AUC=0.87,95％CI:0.78-0.96)and CAIDE model(AUC=0.89,95％CI:0.81-0.98)in APOE ε4 carriers.Conclusion The predictive model was developed based on age,educational level and stroke,and it predicted relatively well 4-year cognitive decline as compared with traditional CAIDE model,especially in APOE ε4 carriers.However,the model should be validated after longer follow-up and further improved to increase its predictive value.

Objective To explore the preoperative assessment of the differentiation degree of hepatocellular carcinoma(HCC),based on the imaging features observed on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI HCC.Methods A retrospective analysis was conducted on the data of 198 patients with HCC confirmed by surgery or biopsy pathology,all of whom underwent Gd-EOB-DTPA enhanced examination before operation.According to pathological results,HCC patients were divided into poorly-differentiated group(group A,69 cases),moderately-differentiated group(group B,97 cases)and well-differentiated group(group C,32 cases).The signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),relative intensity ratio(RIR,,RIR2),and enhancement ratio(ER)of hepatobiliary phase HCC were calculated and analyzed.Results The CNR was the high-est in the group A and the lowest in the group C.Conversely,the SIHCC unenhanced,SIHCC hepatobiliary phase,and RIR1,RIR2 all were the highest in the group C and the lowest in the group A.There were statistically significant differences between the group C and the group B,as well as the group C and the group A(P＜0.05).Regarding signal characteristics during the hepatobiliary phase,the group A had the highest proportion of low/slightly low signal,while the group C had the lowest proportion.A statistically significant difference was observed between the group C and the group A(P＜0.05).Conclusion The Gd-EOB-DTPA enhanced MRI is helpful to preoperative assessment the differentiation degree of HCC.The higher the signal in the hepatobiliary phase,the smaller the CNR,the larger val-ues for the SIHCCunenhanced,SIHCC hepatobiliaryphase and RIR1,RIR2 are associated with the better the differentiation degree of HCC.