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.

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

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:To analyze the relationship between microRNA-21(miR-21)expression and the risk of very early relapse post-induction chemotherapy in children with acute lymphoblastic leukemia(ALL).Methods:A total of 110 newly diagnosed children with ALL admitted to Huanggang Central Hospital from March 2020 to September 2022 were included.All patients received induction chemotherapy according to the CCLG-2008 protocol.The patients who achieved complete response(CR)after induction chemotherapy were followed up for 18 months,with very early relapse as the endpoint event.Then the patients were divided into a relapse group and a non-relapse group.Cox regression was used to analyze the influencing factors of very early relapse after induction chemotherapy in children with ALL.ROC curve and decision curve were used to evaluate the predictive value of peripheral blood miR-21 for very early relapse after induction chemotherapy in children with ALL.Restricted cubic splines were used to analyze the dose-response relationship between peripheral blood miR-21 and very early relapse after induction chemotherapy in children with ALL.Results:A total of 102 children with ALL achieved CR after induction chemotherapy,among whom 24 cases(23.53％)experienced very early relapse,with a median relapse time of 14 months.The proportions of patients with high-risk stratification at initial diagnosis,extramedullary infiltration,and minimal residual disease(MRD)positivity were significantly higher in the relapse group than those in the non-relapse group;The absolute lymphocyte count(ALC)in peripheral blood was significantly lower,while the expression levels of miR-21 and lactate dehydrogenase(LDH)were significantly higher in the relapse group compared with the non-relapse group(all P＜0.05).Cox regression analysis showed that very early relapse after induction chemotherapy in children with ALL was associated with medium risk and high risk at initial diagnosis,extramedullary infiltration,decreased ALC in peripheral blood,MRD positivity,as well as high expression levels of miR-21 and LDH(all P＜0.05).ROC curve analysis indicated that the area under the curve(AUC)of peripheral blood miR-21 for predicting very early relapse after induction chemotherapy in children with ALL was 0.800,with an optimal cutoff value of 4.830.Restricted cubic spline analysis revealed that there was a non-linear dose-response relationship between peripheral blood miR-21 and the risk of very early relapse after induction chemotherapy in children with ALL.When the expression level of peripheral blood miR-21 exceeded 4.830,the risk of very early relapse increased with the elevation of miR-21 expression.Decision curve analysis demonstrated that combining peripheral blood miR-21 with other risk factors enhanced the predictive performance for the risk of very early relapse after induction chemotherapy in children with ALL.Conclusion:Very early relapse after induction chemotherapy in children with ALL is associated with elevated expression of miR-21 in peripheral blood,and high expression of miR-21 may increase the risk of very early relapse.Detecting miR-21 before induction chemotherapy has predictive significance for very early relapse in children with ALL,and combining it with other risk factors can improve the predictive efficacy.

Objective To investigate the effect of early closed reduction and percutaneous Kirschner wire pinning for Gartland type Ⅱ and Ⅲ pediatric supracondylar humerus fractures.Methods Clinical data of 123 children with Gartland type Ⅱ and Ⅲsupracondylar humerus fractures admitted to our hospital from January 2021 to December 2022 were retrospectively analyzed.According to the time from injury to operation,they were divided into early group(≤ 24 h)and delayed group(＞24 h).The perioperative conditions,postoperative complications,fracture healing,and elbow joint functional recovery were compared between the two groups.Results Compared to the delayed group,the early group had less operation time[(22.9±11.3)min vs.(40.3±17.5)min,t=-6.116,P=0.000],less number of intraoperative fluoroscopy[(10.6±4.5)times vs.(17.4±5.5)times,t=-7.471,P=0.000],shorter hospital stay[(3.3±1.0)d vs.(4.2±1.3)d,t=-3.866,P=0.000],and less hospitalization cost[(10 555.0±971.2)yuan vs.(10 972.4±938.9)yuan,t=-2.345,P=0.021].The rate of anatomical reduction in the early group was higher than that in the delayed group[79.0％(60/76)vs.59.6％(28/47),x2=5.354,P=0.021].No serious complications such as vascular and nerve injury,compartment syndrome,ischemic myosclerosis,myositis ossificans,or cubitus varus and valgus occurred in both group after surgery.The incidences of tension blisters[6.6％(5/76)vs.23.4％(11/47),x2=7.265,P=0.007],plaster loosening[22.4％(17/76)vs.40.4％(19/47),x2=4.574,P=0.032],and pin tract infection[2.6％(2/76)vs.14.9％(7/47),x2=4.757,P=0.029]in the early group were lower than those in the delayed group.The fracture union time,and the time to start active and full weight-bearing activities in the early group were earlier than those in the delayed group(P＜0.05).The Flynn elbow joint scores at 3 and 6 months after surgery in the early group were better than those in the delayed group(Z=-3.469,P=0.001;Z=-2.961,P=0.003).Conclusion Early closed reduction and percutaneous Kirschner wire pinning is effective in the treatment of pediatric supracondylar humerus fractures,which can shorten the operation time and hospital stay,reduce the hospitalization cost,lower the incidence of complications,and restore elbow joint function in early stage.

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 analyze the expression of monocyte surface antigen-presenting factors CD86+and HLA-DR in the subacute phase of burn injury,and the molecular mechanism of monocytes contributing to persistent inflammation.Methods The mice were divided into the sham group and the burn group,and a mouse model of 30％body surface burn was estab-lished.Spleens were collected from mice on the 8th day after burn injury,and monocytes were isolated for transcriptomic analy-sis.A mouse model of Notch1 lentiviral transfection was constructed,and models of sham burn+blank control(sham-NC),burn+blank control(burn-NC),sham burn+Notch1 shRNA(sham-sh),and burn+Notch1 shRNA(burn-sh)were estab-lished.The qRT-PCR and Western blot were used to detect the expressions of monocyte surface antigens CD86+and HLA-DR.Immunofluorescence was performed to analyze the expression of CD86+and HLA-DR in splenic monocytes.ELISA was used to analyze serum levels of IL-10 and CRP.Results On the 8th day after burn injury,compared with the sham burn group,the expressions of monocyte surface antigens CD86+and HLA-DR were decreased,while serum levels of IL-10 and CRP were increased in the burn group.Contents of IL-10 and CRP showed significant negative correlations with CD86+and HLA-DR,re-spectively.Transcriptomic analysis revealed 258 significantly upregulated genes and 360 significantly downregulated genes in splenic monocytes from the burn group.The differentially expressed genes primarily enriched in the Notch signaling path-way.Western blot results showed a significant upregulation of Notch1 expression.After lentiviral inhibition of Notch1 signaling invivo,compared with the burn-NC group,expressions of CD86+and HLA-DR on monocyte surfaces were increased,and ser-um levels of IL-10 and CRP were decreased in the burn-sh group.Conclusion The functional inhibition of splenic monocytes is mediated by Notch1 signaling pathway in the subacute phase of burn injury.Inhibition of Notch1 signaling in vivo improves the antigen-presenting capacity of monocytes after burn injury and inhibits the secretion of inflammatory factors.

Objective:To explore the effect of anterior traction orthodontic treatment in adolescents with bone type Ⅲ malocclusion of different bone ages.Methods:Two hundred patients with bony class Ⅲ malocclusion admitted to the Department of Stomatology of the Zhangjiakou First Hospital were prospectively selected as the research subjects; An experienced physician divided the research subjects into the Cvs1 stage group ( n=54), the Cvs2 stage group ( n=56), the Cvs3 stage group ( n=47), and the Cvs4 stage group ( n=43) based on the morphological changes of the second, third, and fourth cervical vertebrae in the modified cervical spine analysis method. Before and after orthodontic treatment, X-ray lateral cranial films were taken respectively to compare the indicators of the upper airway and the structural indicators of the temporomandibular joint. Results:The nasopharyngeal volume (NPvolume), nasopharyngeal minimum cross-sectional area (NParea), and nasopharyngeal minimum cross-sectional sagittal diameter (NPsag) of the four groups of adolescents after treatment all increased significantly compared with those before treatment (all P<0.05), especially the increase was the most obvious in the Cvs3 stage group ( P<0.05). In the Cvs1 stage group, Cvs2 stage group, and Cvs3 stage group, except for the Y-axis to Mandibular first molar (Y-Mn6), Overbite, and the ratio of the Angle between the Posterior maxillary vertical to Occlusal plane angle (PMV/OP), there was no statistically significant difference before and after treatment (all P>0.05). The differences in other items before and after treatment were statistically significant (all P<0.05). Conclusions:Anterior traction orthodontic treatment has a significant effect on adolescents of different bone ages with skeletal class Ⅲ malocclusion, and can improve the maxillofacial structure and the position of the temporomandibular joint. There are differences in therapeutic effects among different bone age groups, and the effect of the Cvs3 stage group is the most obvious. These results provide important reference basis for clinical treatment decisions.

Background and purpose:Gastric cancer,as one of the most common malignant tumors,requires early diagnosis and treatment to improve patient prognosis.This study,based on serum quantitative proteomics research of early-stage gastric cancer patients and non-gastric cancer patients,aims to identify potential diagnostic biomarkers for early gastric cancer.Methods:Serum samples from primary gastric cancer patients and healthy control individuals were collected from Lanzhou University Second Hospital between June and December 2023,following inclusion and exclusion criteria.A protein spectral library was established using Data-Dependent Acquisition(DDA)mode,and each sample was analyzed using Data-Independent Acquisition(DIA)mode.The STRING database was used to analyze protein-protein interactions of upregulated proteins in gastric cancer serum.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)were used to analyze the pathways and functional annotations of the corresponding genes.Gene expression levels in gastric cancer and non-gastric cancer tissues were analyzed using GEPIA 2,and overall survival of each gene in gastric cancer was analyzed using Kaplan-Meier Plotter.Differential gene expression in clinical gastric cancer and adjacent tissues was validated by quantitative reverse transcription polymerase chain reaction(qRT-PCR)This study was approved by the Ethics Committee of Lanzhou University Second Hospital(Ethical No.:2023A-459)and was exempt from the informed consent.Results:Finally,serum samples from 30 primary gastric cancer patients,29 healthy control individuals,along with the para-cancerous tissues from 8 patients were collected.A total of 666 intersecting proteins were identified through serum quantitative proteomics.Among them,16 proteins showed upregulated expression and 22 proteins showed downregulated expression in the gastric cancer group(P＜0.05,|FC|≥1.5).STRING database analysis showed that 10 upregulated proteins were involved in interaction networks.KEGG and GO analysis indicated that these genes were closely related to the biological processes of cancer occurrence and development.GEPIA 2 and Kaplan-Meier Plotter analysis showed that 6 genes,B2M,TAGLN2,CTSD,HSP90AB1,SH3BGRL3,and CFL1,which were highly expressed in the gastric cancer group(P＜0.05)and associated with poor prognosis.Clinical verification by qRT-PCR confirmed that TAGLN2,CTSD,SH3BGRL3,CFL1 and HSP90AB1 were highly expressed in gastric cancer tissues(P＜0.05).Conclusion:TAGLN2,CTSD,SH3BGRL3,CFL1,and HSP90AB1 have the potential to serve as clinical early gastric cancer diagnostic serum biomarkers,which may facilitate early diagnosis and treatment of gastric cancer.