Acori Tatarinowii Rhizoma is the dried rhizome of Acorus tatarinowii in the family of Tennantiaceae, which has the efficacy of opening up the orifices and expelling phlegm, awakening the mind and wisdom, and resolving dampness and opening up the stomach. Modern studies have shown that volatile oil is the main active ingredient of Acori Tatarinowii Rhizoma, and α-asarone and β-asarone have been proved to be the active ingredients in the volatile oil of Acori Tatarinowii Rhizoma, with pharmacological effects such as anti-Alzheimer's disease, antiepileptic, anti-Parkinson's disease, antidepressant, anticerebral ischemia/reperfusion injury, anti-thrombosis, lipid-lowering, and antitumor. By summarising and outlining the pharmacological effects of α-asarone and β-asarone and elucidating the possible mechanisms of their pharmacological effects, we can provide theoretical basis for the further research and clinical application of Acori Tatarinowii Rhizoma.
Allylbenzene Derivatives ; Acorus/chemistry* ; Anisoles/chemistry* ; Rhizome/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Humans ; Animals

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

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

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Objective:To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS).Methods:An adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was enrolled as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X).Results:Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c. 206+ 2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the patients mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion:The heterozygous splice site variant c. 206+ 2T>G of the SMAD3 gene probably underlay the disease of this patient. The discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.

Objective:To investigate the clinical characteristics and risk factors of airway mucus plugging in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:This was a retrospective cross-sectional study. A total of 322 hospitalized AECOPD patients admitted to the First Affiliated Hospital of Anhui Medical University from February 2023 to February 2025 were enrolled. Based on chest high-resolution computed tomography (HRCT) findings of airway mucus plugging, patients were classified into mucus plugging and non-mucus plugging groups. General and clinical data were collected, including age, sex, disease duration, smoking and alcohol history, comorbidities, number of acute exacerbations in the past year, routine blood tests, biochemical indices, pulmonary function, and pathogen detection. The incidence of airway mucus plugging in AECOPD patients was calculated, and differences in baseline characteristics, laboratory parameters, and pulmonary function between the two groups were compared. Logistic regression was used to identify independent risk factors for mucus plugging, and receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of relevant indicators.Results:Of the 322 enrolled patients, 87(27.02%) were found to have airway mucus plugging. Univariate analysis revealed statistically significant differences between the mucus plug group and the non-plug group in the following parameters (all P<0.05): body mass index (BMI), disease duration, smoking status, Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, modified British Medical Research Council (mMRC) dyspnea scale, COPD Assessment Test (CAT) score, frequency of acute exacerbations, neutrophil percentage, absolute lymphocyte count, lymphocyte percentage, albumin, C-reactive protein (CRP), activated partial thromboplastin time, fibrinogen, fibrin(ogen) degradation products, D-dimer, Aspergillus infection rate, percentage of forced expiratory volume in 1 second to predicted value (FEV 1%pred), ratio of FEV 1 to forced vital capacity (FEV 1/FVC), and percentage of maximal mid-expiratory flow to predicted value (MMEF 75/25%pred). Multivariate logistic regression analysis identified the following as independent risk factors for airway mucus plugs (all P<0.05): elevated CRP ( OR=1.022, 95% CI: 1.013-1.036), decreased albumin ( OR=0.891, 95% CI: 0.825-0.959), Aspergillus infection ( OR=1.774, 95% CI: 1.366-2.317), and reduced MMEF 75/25%pred value ( OR=0.978, 95% CI: 0.964-0.990). ROC curve analysis showed that the combined predictive model incorporating CRP, albumin, Aspergillus infection, and MMEF 75/25%pred had an area under the ROC curve (AUC) of 0.776(95% CI: 0.714-0.838), which was superior to each individual indicator alone, with AUCs of 0.721 for CRP, 0.687 for albumin, 0.579 for Aspergillus infection, and 0.631 for MMEF 75/25%pred. Conclusions:AECOPD patients with airway mucus plugging exhibit higher inflammatory markers, poorer nutritional status, a higher likelihood of Aspergillus infection, worse pulmonary function, and poorer prognosis. Aspergillus infection, elevated CRP, decreased albumin, and reduced MMEF 75/25%pred are independent risk factors for mucus plugs in AECOPD.

Objective In response to the practical issues of pilot ground simulation ejection training relying on subjective evaluation,which requires high professionalism and lacks objectivity and systematicity,an objective evaluation system and method for ejection training based on pressure detection has been designed.Methods According to the rules of ejection training about posture,maneuver and time,and utilizing technologies such as pressure detection,infrared detection,and time-triggered detection,this paper designed separate modules for ejection posture detection,ejection timing detection,and comprehensive analysis and evaluation.These modules are closely integrated with the ejection training process,achieving objective evaluation of the ejection training.Results This system and method can provide a scientific and real-time objective evaluation of the posture,movements,and time in ejection training without affecting the normal organization and process.Conclusion The objective evaluation system can provide a new approach that is highly objective and easy to operate for comprehensively evaluating and enhancing the effectiveness of ejection training,as well as for scientifically conducting ejection training and assessment.

[摘 要] 目的：回顾性分析树突状细胞-细胞因子诱导的杀伤细胞（DC-CIK）不同抗原负载后在治疗恶性黑色素瘤（MM）中的临床疗效与安全性。方法：采集2012年10月至2024年12月期间东部战区总医院秦淮医疗区收治的42例晚期MM患者的外周血单个核细胞，经实验室体外诱导培养成DC和CIK。根据患者HLA-A2的表达将患者分为多肽组和细胞组，多肽组负载混合多肽，细胞组负载肿瘤细胞A375裂解物。DC与CIK培养成熟后再回输给患者。比较两组患者的客观临床反应及生存期，检测治疗前后两组患者外周血淋巴细胞亚群，观察患者回输后的不良反应。结果：42例MM患者中，0例达CR，0例PR，31例SD，11例PD；其中，多肽组18例SD，6例PD，细胞组13例SD，5例PD。多肽组疾病控制率为75.0%，细胞组为72.2%；42例患者中死亡12例，其中细胞组4例，多肽组8例。1年OS率多肽组为76.6%，细胞组为66.7%；2年OS率多肽组为43.8%，细胞组为66.7%；3年OS率多肽组为43.8%，细胞组为33.3%，多肽组3年OS率略高于细胞组，但两组之间无统计学差异（P = 0.445）。两组MM患者治疗前后淋巴细胞亚群无显著差异（均P > 0.05），两组患者均未出现严重不良反应。结论：细胞负载DC-CIK与混合多肽负载DC-CIK治疗MM患者是安全的，能使患者临床获益，但两组的近期疗效和长期生存有差异以及免疫反应均无显著性差异。