In this study, the pharmacodynamic components and potential pharmacological functions of Danzhi Xiaoyao Formula in treating nervous system diseases were investigated by hippocampal component characterization and network pharmacology. After rats were administrated with Danzhi Xiaoyao Formula by gavage, high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) was employed to explore the components in the hippocampus of rats. Fifty-seven components were identified in the hippocampus of rats by comparing the extract of Danzhi Xiaoyao Formula, herbal components in the hippocampus after administration, and blank samples. KEGG and GO analyses predicted 74 core targets including GSK3B, MAPK1, AKT, IL6. These targets were involved in PI3K/Akt, NF-κB, MAPK, JAK/STAT, Wnt, and other signaling pathways. The results indicated that Danzhi Xiaoyao Formula may ameliorate other nervous system diseases enriched in DO, such as neurodegenerative diseases, cerebrovascular diseases, and mental and emotional disorders by mediating target pathways, inhibiting inflammation, reducing neuronal damage, and alleviating hippocampal atrophy. The relevant activities exhibited by this formula in nervous system diseases such as Alzheimer's disease, Parkinson's disease, and diabetic neuropathy have extremely high development value and are worthy of further in-depth research. This study provides a theoretical basis and practical guidance for expanding the application of Danzhi Xiaoyao Formula in the treatment of nervous system diseases.
Drugs, Chinese Herbal/administration & dosage* ; Animals ; Rats ; Hippocampus/metabolism* ; Network Pharmacology ; Chromatography, High Pressure Liquid ; Tandem Mass Spectrometry ; Rats, Sprague-Dawley ; Male ; Nervous System Diseases/genetics* ; Humans ; Signal Transduction/drug effects*

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 explore the clinical significance of 26 circulating tumor DNA (ctDNA) associated with multiple myeloma (MM) in peripheral blood of new diagnosed patients. METHODS: We conducted a study to detect 26 ctDNA mutations in the peripheral blood of 31 newly diagnosed multiple myeloma (NDMM) patients. RESULTS: Among the 31 NDMM patients, the ctDNA detection rate was 93.55%, significantly higher than that of FISH and chromosome screening methods. The most frequently mutated genes in NDMM were ACTG1 and GNAS. Notably, ACTG1 mutations were exclusive to NDMM patients, furthermore, resulted from the missense mutation of the exon 4. ACTG1 was the gene most frequently co-mutated with others. All patients with ACTG1 mutations were surviving, and there was a positive correlation between ACTG1 mutation and the survival of patients. GNAS mutations were confined to exon 1. CONCLUSION The detection rate of ctDNA sequencing in peripheral blood of NDMM patients was higher than that in bone marrow. ACTG1 and GNAS genes have a guiding role in the prognosis of newly diagnosed patients.
Humans ; Multiple Myeloma/blood* ; Circulating Tumor DNA/genetics* ; Mutation ; Prognosis ; GTP-Binding Protein alpha Subunits, Gs/genetics* ; Chromogranins ; Male ; Female ; Middle Aged

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

Objective To explore the safety and management mode of hysteroscopy in three different modes:outpatient,daily and inpatient.Methods The quality control data of patients who underwent hysteroscopic surgery in Hysterscopy Centre,Obstetrics and Gynecology Hospital,Fudan University from Jan 2019 to Dec 2021 were collected through the electronic information system of the hospital and the monthly quality control report of hysteroscopy center.The amount of surgery,the proportion of grade Ⅳsurgery,the analysis of operation types,the indicator including complications,and unanticipated secondary surgery were retrospectively analyzed.Results From 2019 to 2021,5 162 outpatient hysteroscopic patients,15 331 daily hysteroscopic patients and 5 942 inpatient hysteroscopic patients were admitted in our hospital.The age of inpatient hysteroscopic patients was significantly older than those of outpatient and daily patients(P<0.001).In the past three years,the proportion of daily hysteroscopy gradually increased,and the proportion of inpatient hysteroscopy gradually decreased(P<0.001).The total percentage of grade Ⅳ hysteroscopic surgery was 12.9%,in which inpatient was higher than daily,and daily was higher than outpatient(P<0.001).The incidence of complications and accidents during hysteroscopy was 0.117%(31/26 435),including 17 cases of uterine perforation,7 cases of hysteroscopy failure,3 cases of excessive intraoperative bleeding,2 cases of fluid overload,1 case of intestinal injury,and 1 case of anesthesia accident.The incidence of hysteroscopy in outpatient,daily and inpatient were 0.020%(1/5 162),0.137%(21/15 331)and 0.151%(9/5 942)respectively.Conclusion Hysteroscopy in outpatient,daily and inpatient are all safe and reliable.Outpatient and daily hysteroscopy can improve the efficiency of medical services,which has gradually become a trend.

Pogostemon cablin is a famous southern medicine.As the important raw material for modern medicine and industry,Pogostemon cablin becomes required with a large marketing demand.However,due to the serious continuous cropping obstacles in the growth process of Pogostemon cablin,the aggravation of diseases of Pogostemon cablin and the degradation of its quality arose.This paper outlined the ecological factors such as climate factors,soil factors and topographic factors suitable for the growth of Pogostemon cablin,analyzed the continuous cropping obstacles and diseases arising in the cultivation,reviewed the current ecological planting mode of Pogostemon cablin such as crop rotation,intercropping,relay-cropping and under-forest planting,and also made a comprehensive evaluation of the economic benefits,ecological benefits and social benefits of the ecological planting mode of Pogostemon cablin,aiming to provide a theoretical basis and a reference for the promotion of the ecological planting mode of Pogostemon cablin.

Objective:To explore the influencing factors of atrial fibrillation(AF)in patients with heart failure(HF)and the effects of family empowerment mode strategy.Methods:A total of 220 HF patients who were trea-ted in First Affiliated Hospital of Chinese PLA Air Force Military Medical University between April 2020 and March 2021 were selected.According to presence of AF or not,they were divided into AF group(n=80)and no AF group(n=140);patients in AF group received family empowerment mode strategy management for 3 months.Scores of self-care behavior scale and quality of life scale were compared between before and after intervention in AF group.Multivariate Logistic regression was used to analyze influencing factors of AF in HF patients,receiver operating characteristic(ROC)curve was used to analyze diagnostic value of above risk factors for AF in HF patients.Results:Compared with no AF group,patients in AF group had significant higher level of brain natriuretic peptide(BNP),left ventricular diameter and number of implanted stents(P＜0.001 all).Multivariate Logistic regression indicated that BNP＞400pg/ml,left ventricular diamcter＞40mm and number of implanted stents＞2 were independent risk factors for AF in HF patients(OR=1.349～2.501,P＜0.01 all).ROC curve indicated that AUC of BNP,left ven-tricular diameter and number of implanted stents predicting AF in HF patients was 0.819,0.812 and 0.745 respec-tively,all of them had good diagnostic value.Compared with before intervention,there were significant rise in di-mensional scores of self-care maintenance,self-care management and self-care confidence of HF patient self-care behavior scale,and significant reductions in scores of physical domain,emotional domain and other domain of HF quality of life scale in AF group after 3-month intervention(P＜0.001 all).Conclusion:BNP,left ventricular diameter and number of implanted stents are risk factors for atrial fibrillation in patients with heart failure.Self-management and quality of life significantly improve after family empowerment mode management in these patients.

Extracellular vesicles(EVs)are nano-sized membranous vesicles secreted and released by cells into the extracellular matrix.They carry bioactive molecules derived from parent cells and are regarded as media for intercellular communication and material transfer.Compared to synthetic nanocarriers,EVs possess lower immunogenicity,better biocompatibility,and enhanced ability to traverse biological barriers,making them ideal carriers for nucleic acid drug delivery.This article reviewed the loading technologies of EVs as carriers for nucleic acid drugs,with an in-depth analysis and discussion of the performance and application progress of endogenous and exogenous loading methods,strategies for evaluating nucleic acid loading quality,and the application of EV-mediated nucleic acid delivery in cancer therapy.Finally,the advantages and existing challenges of EVs as nucleic acid delivery vehicles in cancer treatment were summarized and their future development prospects in clinical applications was anticipated.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To analyze the clinical and ultrasonographic characteristics of ductal carcinoma in situ(DCIS)and intraductal papilloma(IDP),and to construct a nomogram predictive model for DCIS and IDP.Methods:We selected data from 156 cases(212 nodules)of DCIS and 158 cases(238 nodules)of IDP confirmed by pathology.Through univariate and multivariate analy-ses,we evaluated the influencing factors of ultrasonic diagnosis of DCIS and established a diagnos-tic model to clarify the value of each ultrasonographic sign in diagnosis.Results:The univariate analysis showed statistically significant differences between the two groups in terms of age,medi-cal history,nodule long diameter,volume,margin,posterior echo,calcification,color Doppler flow imaging(CDFI),and resistance index(R/)(P＜0.05).The multivariate logistic regression analysis showed that the absence of abnormal ducts around the nodule,posterior echo attenuation,pres-ence of microcalcifications,and RI≥0.70,tend to indicate DCIS,while simple dilation or lack of blood supply of the duct around the nodule tend to indicate IDP.These indicators were included in the nomogram model,which showed high predictive performance,calibration,and clinical value in both the training and validation sets.Conclusion:The nomogram model based on sonographic fea-tures can easily distinguish DCIS from IDP.The presence of abnormal ducts around the nodule,posterior echo attenuation,presence of microcalcifications,and RI＞0.70 should raise suspicion for DCIS.