ObjectiveTo explore the mechanism by which the ethanol extract of Epimedium brevicornu （EEBM） intervenes in mesenchymal adipose-derived stem cells （ADSCs） to delay aging in castrated rats. MethodsForty-five 3-month-old SPF female SD rats were ovariectomized and randomly divided into model group， ADSCs treatment group， and ADSCs groups treated with low， medium， and high concentrations of EEBM （1， 50， 100 μg·L^-1）， referred to as the AE low， medium， and high concentration groups， with 9 rats in each group. After tail vein injection of 200 μL of the corresponding stem cell suspension， aging-related indicators including cyclin-dependent kinase inhibitor （p21）， tumor suppressor gene （p53）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， superoxide dismutase （SOD）， malondialdehyde （MDA）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cysteine-aspartic acid protease-3 （Caspase-3）， and lipofuscin were measured using enzyme-linked immunosorbent assay （ELISA） and Western blot. ResultsCompared with the model group， the IL-6 content in the AE low， medium， and high concentration groups was significantly decreased （P<0.05）. Lipofuscin， MDA， and IL-8 levels in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.01）， while SOD content was significantly increased （P<0.05， P<0.01）. Compared with the ADSCs treatment group， lipofuscin and IL-8 levels in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）. The MDA content was significantly decreased in the AE medium concentration group （P<0.01）. Compared with the model group， protein levels of p21， p53， Bax， and Caspase-3 in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， while the Bcl-2 protein level was significantly increased （P<0.01）. Compared with the ADSCs treatment group， protein levels of p21， p53， Bax， and Caspase-3 in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， and the Bcl-2 protein level in the AE low concentration group was significantly increased （P<0.01）. ConclusionThe results of this experiment show that EEBM-treated ADSCs or ADSCs may delay aging in castrated rats by inhibiting cell apoptosis， reducing cell cycle inhibitors and pro-inflammatory factors， enhancing antioxidant capacity， and reducing oxidative reactions. Moreover， EEBM-treated ADSCs demonstrate stronger anti-aging effects than ADSCs alone. This study provides experimental evidence supporting the clinical use of EEBM to intervene in ADSCs and delay aging.

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To study the correlation between miR-122 and early HBV infection and analyze its application value in early infection of voluntary blood donors. METHODS: A total of 150 samples from voluntary blood donors in Fujian Blood Center from May 2021 to July 2022 were collected and divided into group N (normal group), group E (ELISA single positive group), and group D (both ELISA and nucleic acid positive group), and the general information of the three groups of blood donors was collected. Total RNA was extracted from the three groups of samples, and the expression level of miR-122 was detected by qRT-PCR. The expression differences of miR-122 among the three groups of samples were statistically analyzed, and the correlation between the expression level of miR-122 in group D and its HBV DNA copy number was analyzed. The miRNA database was used to predict the potential target genes of miRNA and perform bioinformatics analysis. RESULTS: There was no statistical difference in gender, education level, and occupation distribution among the three groups, but the age distribution and number of blood donations among different groups were statistically significant. Compared with group N, the relative expression levels of miR-122 in the plasma of group E and group D were significantly downregulated (P < 0.05); the relative expression level of miR-122 in group D was more significantly downregulated than that in group E (P < 0.001). Pearson correlation analysis showed that the expression level of miR-122 in group D was negatively correlated with the HBV-DNA copy number (R ²=-0.804,P < 0.01). Two potential target genes were screened using the miRNA database: ALDOA(aldolase A) and PKM (pyruvate kinase). GO analysis results showed that the potential target genes of miRNA mainly involved in biological processes including cell homeostasis and regulation of transcriptional processes. CONCLUSION Downregulation of miR-122 expression is closely related to early HBV infection and replication activity.
Humans ; MicroRNAs ; Blood Donors ; Hepatitis B/diagnosis* ; Hepatitis B virus ; DNA, Viral/blood* ; Male ; Female ; Early Diagnosis ; Adult

OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

Network Meta-analysis was conducted to evaluate the efficacy and safety of different traditional Chinese medicine injections combined with conventional western medicine in treatment of cerebral small vessel disease(CSVD). Computerized searches were conducted in PubMed, Cochrane Library, Web of Science, EMbase, CNKI, Wanfang, VIP, and SinoMed for randomized controlled trial(RCT) published in Chinese or English using traditional Chinese medicine injections to treat CSVD. The search time is from the inception to July 15, 2024. Literature screening and statistical analysis were conducted with NoteExpress 3.0.3, RevMan 5.3.5, and Stata 15.1.6. A total of 45 articles were included, involving 3 717 patients, with 1 944 patients in the treatment group and 1 773 patients in the control group. A total of 15 kinds of traditional Chinese medicine injections were involved. Network Meta-analysis indicated that,(1) in terms of improving clinical total effective rate, the best intervention in SUCRA was Ciwujia Injection + conventional western medicine.(2) In terms of reducing NIHSS scores, the best intervention in SUCRA was Xueshuantong Injection + conventional western medicine.(3) In terms of improving ADL scores, the best intervention in SUCRA was Danshen Injection + conventional western medicine.(4) In terms of improving MMSE scores, the best intervention in SUCRA was Xueshauntong Injection + conventional western medicine.(5) In terms of improving MoCA scores, the best intervention in SUCRA was Salvianolate Injection + conventional western medicine.(6) In terms of reducing plasma viscosity(PV), the best intervention in SUCRA was Danhong Injection + conventional western medicine.(7) In terms of reducing the hematocrit, the best intervention in SUCRA was Xuesaitong Injection + conventional western medicine.(8) In terms of reducing fibrinogen, the best intervention in SUCRA was Xuesaitong Injection + conventional western medicine.(9) In terms of reducing erythrocyte sedimentation rate(ESR), the best intervention in SUCRA was Danshen Injection + conventional western medicine.(10) In terms of reducing total cholesterol(TC), triglycerides(TG), and low-density lipoprotein(LDL), the best intervention in SUCRA was Danshen Injection + conventional western medicine. The radar chart results indicated that the advantage of Salvianolate Injection lies in improving cognitive function, while the advantage of Xueshuantong Injection lies in improving neurological function. The advantage of Xuesaitong Injection lies in improving hemodynamic parameters, and the advantage of Danshen Injection lies in improving behavioral ability, hemodynamics, and blood lipid levels. In terms of safety, there was no significant difference in the incidence of adverse reactions between the traditional Chinese medicine injection treatment group and the conventional western medicine group, and no serious adverse reactions occurred. The results showed that the combination of traditional Chinese medicine injections and conventional western medicine can effectively improve the clinical total effective rate, the neurological and cognitive functions, hemodynamic parameters, and blood lipid levels of patients suffering from CSVD. In addition, more double-blind, multi-center, large-sample RCT is needed to verify these findings and to provide more high-quality evidence on the efficacy and safety of traditional Chinese medicine injections for CSVD.
Humans ; Cerebral Small Vessel Diseases/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Injections ; Randomized Controlled Trials as Topic

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization