Objective To explore the effects of CYP2C19, CYP2C9 and CYP3A5 genotypes on the plasma concentration of voriconazole in children. Methods Collected blood samples from 50 hospitalized children with invasive fungal infections who received intravenous voriconazole from January 2020 to December 2020. High performance liquid chromatography was used to detect the blood trough concentration of voriconazole, and the time-of-flight mass spectrometry detection system was used to detect the genotypes of CYP2C19, CYP2C9 and CYP3A5, and the effects of children’s genotyping on the plasma concentration, efficacy and adverse reactions of voriconazole were analyzed. Results The total effective rate of 50 children with IFI was 84% （42/50 cases） after voriconazole treatment. The incidence of adverse reactions was 20% （10/50 cases）. The measured plasma concentration of voriconazole ranged from 0.56~7.62 μg/ml. Combined with the different mutation types of CYP2C19 gene loci, three metabolic activities were produced: fast, medium and slow, and the test results showed that there were 16 cases of fast metabolism, 27 cases of intermediate metabolism and 7 cases of slow metabolism. There was a significant difference in plasma concentrations among the three groups （F=15.359, P<0.001）, and the drug concentrations in the fast metabolic group were significantly lower than those in the intermediate metabolic and slow metabolic groups. The mutations of CYP2C9 and CYP3A5 had no significant effect on the plasma concentrations of the drugs, which were （F=2.213, P=0.086 and F=0.757, P=0.475）. Conclusion Voriconazole had significant efficacy in the treatment of invasive fungal infections in children, and the adverse reactions were mild. CYP2C19 genotype was significantly related to the rate of drug metabolism and was an important factor affecting blood drug concentration, the detection of drug concentration and genotype of voriconazole was helpful to adjust the effective drug dose clinically and would achieve more scientific and individualized treatment.

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

OBJECTIVES: Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells and remains incurable. Patients with primary refractory multiple myeloma (PRMM) show poor response to initial induction therapy. This study aims to develop a machine learning-based model to predict treatment response in newly diagnosed multiple myeloma (NDMM) patients, in order to optimize therapeutic strategies. METHODS: NDMM and post-treatment MM patients hospitalized in the Department of Hematology, Third Xiangya Hospital, Central South University, between August 2022 and July 2023 were enrolled. Post-treatment MM patients were categorized into PRMM patients and treatment-responsive MM (TRMM) patients based on therapeutic efficacy. Serum metabolites were detected and analyzed via metabolomics. Based on the metabolomics analysis results and combined with transcriptomic sequencing data of NDMM patients from databases, differentially expressed amino acid metabolism-related genes (AAMGs) among post-treatment NDMM patients with varying therapeutic outcomes were screened. Using bioinformatics analyses and machine learning algorithms, a predictive model for treatment response in NDMM was constructed and used to identify patients at risk for PRMM. RESULTS: A total of 61 patients were included: 22 NDMM, 23 TRMM, and 16 PRMM patients. Significant differences in metabolite levels were observed among the 3 groups, with differential metabolites mainly enriched in amino acid metabolism pathways. Follow-up data were available for 16 of the 22 NDMM patients, including 12 treatment responders (ND_TR group) and 4 with PRMM (ND_PR group). A total of 23 differential metabolites were identified between these 2 groups: 6 metabolites (e.g., tryptophan) were upregulated and 17 (e.g., citric acid) were downregulated in the ND_TR group. Transcriptomic data from 108 TRMM and 77 PRMM patients were analyzed to identify differentially expressed AAMGs, which were then used to construct a prediction model. The area under the receiver operating characteristic curve (AUC) for the model exceeded 0.8, and AUC values in 3 external validation cohorts were all above 0.7. CONCLUSIONS This study delineated the metabolic alterations in MM patients with different treatment response, suggesting that dysregulated amino acid metabolism may be associated with poor treatment response in PRMM. By integrating metabolomics and transcriptomics, a machine learning-based predictive model was successfully established to forecast treatment response in NDMM patients.
Humans ; Multiple Myeloma/drug therapy* ; Machine Learning ; Male ; Female ; Metabolomics/methods* ; Middle Aged ; Aged ; Treatment Outcome ; Transcriptome ; Computational Biology ; Adult ; Multiomics

Objective To investigate the epidemiological characteristics and influencing factors of Femoral Artery Compression-Related Skin Complications Around the Puncture Site(FACR-SCAPS)in patients with primary hepatocellular carcinoma(HCC)undergoing transarterial chemoembolization(TACE).Methods A multicenter cross-sectional study was conducted using convenience sampling.A total of 1 573 HCC patients who underwent TACE between April 2023 and October 2024 were recruited from interventional radiology departments,oncology units,and specialized centers across 10 hospitals in Beijing,Tianjin,Shandong,Hebei,Qinghai,and Inner Mongolia.Descriptive statistics,univariate analysis,and multivariate logistic regression were used to explore the epidemiological characteristics and influencing factors of FACR-SCAPS in this population.Results Among the 1 573 primary HCC patients undergoing TACE interventional therapy,FACR-SCAPS occurred in 28.99％(456/1 573),with a total of 476 complication instances recorded(30.26 per 100 patients).Patients with a single complication accounted for 96.93％,whereas those with multiple complications constituted 3.07％.The most prevalent types of complications were skin erythema,skin ecchymosis,and hard lumps formation,collectively accounting for 96.49％of all complications.Hematoma,blisters,and rupture complications collectively accounted for only 4.61％.Logistic regression analysis revealed that peak diastolic blood pressure during compression(OR=1.024,95％CI:1.013-1.035,P＜0.001),use of rotary compression hemostasis devices(OR=3.220,95％CI:2.120-4.891,P＜0.001),elevated PT-INR(OR=19.630,95％CI:6.039-63.810,P＜0.001),and anticoagulant use within the last three months(OR=1.909,95％CI:1.064-3.427,P=0.030)were significant influencing factors associated with FACR-SCAPS post-TACE.Conclusion FACR-SCAPS is commonly seen among primary HCC patients after TACE,its risk factors include peak diastolic blood pressure during compression,use of rotary compression devices,elevated PT-INR,and recent anticoagulant use.

Objective To study the pathogenic bacteria infection in hospitalized diabetic foot patients in the Third People's Hospital of Yunnan Province and its correlation with different Wagner grades,to understand the the characteristics of pathogenic bacteria and related risk factors in hospitalized diabetic foot patients in the Third People's Hospital of Yunnan Province,and to further provide theoretical guidance for anti-infection treatment of these patients.Methods A retrospective analysis was conducted on the demographic data,severity of foot ulcers,and related laboratory test results of 536 patients with diabetic foot who were detected to have bacterial infection in the Third People's Hospital of Yunnan Province from January 2019 to January 2023.Results Among the 536 diabetic foot patients,pathogenic bacteria were cultured from 268 cases(50.0%)of Gram-positive bacterial infections,214 cases(39.9%)of gram-negative bacterial infections,2 cases(0.4%)of fungal infections,and 52 cases(9.7%)of mixed bacterial infections.The main pathogens among gram-positive bacteria were Staphylococcus aureus,Staphylococcus epidermidis and Enterococcus faecalis.for Gram-negative bacteria,the main pathogens were Escherichia coli,Enterobacter cloacae and Klebsiella pneumoniae.There were 31 cases of multi-drug resistant bacteria,and the multi-drug resistance rate was(5.78%).Among Gram-positive bacteria,all multidrug-resistant strains were Staphylococcus aureus,while among Gram-negative bacteria,the multi-drug resistant strains included Acinetobacter baumannii(1 case),Klebsiella pneumoniae(2 cases),Proteus common(2 cases),Pseudomonas aeruginosa(5 cases),Proteus mirabilis(1 case)and Enterobacter cloacae(1 case).The 536 patients were divided into Wagner grade 1 and 2 groups(78 cases),Wagner grade 3 group(274 cases),and Wagner grade 4 and 5 groups(184 cases).There were 73 cases of single bacterial infections and 5 cases of mixed bacterial infections in Wagner grade 1 and 2 group,including 51 cases(65.4%)of gram-positive bacteria,21 cases(26.9%)of gram-negative bacteria and 1 case(1.3%)of fungi.There were 248 cases of single bacterial infections and 26 cases of mixed bacterial infections in Wagner3 group,with 144 cases(52.6%)of gram-positive bacteria,103 cases(37.6%)of gram-negative bacteria,and 1 case(0.4%)with fungi.In the Wagner grade 4 and 5 groups,there were 163 cases of single bacterial infections and 21 cases of mixed bacterial infection,with 73 strains(39.7%)of gram-positive bacteria,90 strains(48.9%)of gram-negative bacteria and 0 strain(0%)of fungi.The predominant infectious pathogens in Wagner grades 1,2 and 3 were gram-positive bacteria,while those in Wagner grades 4 and 5 patients were mainly gram-negative bacteria.There were statistically significant differences in white blood cell counts,neutrophil percentage,bacterial classification,length of hospital stay,erythrocyte sedimentation rate and albumin levels among diabetic foot patients with different Wagner grades(P<0.01).With the increase of Wagner grade,patients had higher white blood cell counts and hypersensitive C-reactive protein levels,longer hospital stays,and lower albumin levels;however,there were no statistically significant differences in age,sex,duration of diabetes,smoking history,alcohol consumption history and history of hypertension(P>0.05).Conclusion The bacterial infection situation in patients with diabetic foot ulcers is related to different Wagner grades.The higher the Wagner grades,the greater the likelihood of infection with gram-negative bacteria.Antibiotics can be reasonably selected according to the Wagner grades of patients upon admission,actively controlling infection,while also enhancing,shortening hospital stays,and reducing amputation rates,thereby improving the prognosis of diabetic foot patients.

Objective To analyze the bacterial distribution characteristics,drug resistance characteristics and related risk factors of multidrug-resistant organisms(MDRO)in patients with diabetic foot infection(DFI)in some areas of Yunnan Province to provide empirical reference for clinical treatment.Methods Clinical data of 300 DFI patients admitted to the Department of Endocrinology of the Third People's Hospital of Yunnan Province from January 2019 to December 2023 were collected.Based on the results of drug sensitivity tests and matching of basic data,patients were divided into the MDRO group(n=60)and the non-MDRO group(n=240).A retrospective analysis was conducted on the distribution of pathogenic bacteria,drug resistance characteristics of MDRO and risk factors for MDRO infection in DFI patients.Results In 60 patients with MDRO infections,62 strains of MDRO were cultured,with 58 strains from single MDRO infections and 4 strains from mixed MDRO infections.Of the 60 patients,2 were cultured for 2 types of MDRO.Among the strains,there were 45 gram-positive bacteria(72.58％)which were all Staphylococcus aureus,17 strains of gram-negative bacteria(27.42％)mainly including Pseudomonas aeruginosa,Enterobacter cloacae and Klebsiella pneumoniae.Among common MDRO,Staphylococcus aureus showed complete resistance to penicillin G and oxacillin(100％),with high resistance to erythromycin and clindamycin(＞80％),but no resistance to tigacycline vancomycin was observed.The resistance of Klebsiella pneumoniae and Enterobacter cloacae to cephalosporin antibiotics was obvious,and the resistance rate to imipenem and amikacin was low.Pseudomonas aeruginosa was 100％resistant to ticacillin/clavulanate potassium,imipenem,tigacycline and cotrimoxazole,but showed no resistance to cefepime,ciprofloxacin,gentamicin and amikacin.There were statistically significant differences between the two groups in regional distribution,duration of diabetic foot,lower extremity arterial disease,venous plasma glucose levels and glycosylated hemoglobin(P＜0.05).Binary Logistic regression analysis showed that region and duration of diabetic foot disease were independent risk factors for MDRO infection in DFI patients(P＜0.05).Conclusion In some areas of Yunnan Province,the distribution of MDRO in DFI patients is mainly gram-positive bacteria,with varying antibiotic sensitivities among different pathogens.Multiple factors lead to MDRO infections in DFI patients,which assists clinical practitioners in early identification of high-risk DFI patients with MDRO infections and provide empirical reference for clinical treatment.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Taste is an important aspect that affects the application and development of oral liquid preparations of tradi-tional Chinese medicine,and bitterness is the main adverse taste of such preparations.In January 2024,the Chinese Society of Tra-ditional Chinese Medicine released the social organization standard"Technical Specification for Sensory Evaluation of Bitterness of Oral Liquid Preparation of Traditional Chinese Medicine"(standard number:T/CACM 1574-2024),led by the Chinese Medi-cine Preparation Branch of the Chinese Society of Traditional Chinese Medicine,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,and Beijing University of Traditional Chinese Medicine,with the participation of 22 units nation-wide.It provided scientific guidance and good tools for the evaluation of bitterness of such preparations and lays a technical foun-dation for the subsequent implementation of taste improvement.This article provided a detailed introduction to the background and significance,formulation process,and main content of the standard development,which is beneficial for traditional Chinese medi-cine pharmacists to understand the standard better,apply,promote,and improve the group's standard,thereby promoting the im-provement of the taste quality and patient acceptance of such preparations,and promoting the development of the modernization of traditional Chinese medicine.

AIM To evaluate the quality of Gegen Formula Granules.METHODS Linear calibration with two reference substances(LCTRS)was adopted in the predicting of retention time with puerarin and daidzein as internal standards.UPLC characteristic chromatograms were established.The contents of 3'-hydroxy puerarin,puerarin(internal standard),3'-methoxy puerarin,puerarin 6"-O-xyloside,puerarin apioside and daidzin were determined by quantitative determination analysis multi-components by a single marker(QAMS),after which their transfer rates were calculated.RESULTS Compared with relative retention time method,LCTRS demonstrated higher positional accuracy for characteristic peaks and wider application range for columns.There were 9 characteristic peaks in the characteristic chromatograms for 14 batches of formula granules and 15 batches of standard decoctions with the similarities of more than 0.95.The contents and transfer rates of various constituents in formula granules and standard decoctions were basically consistent.CONCLUSION The chemical constituents in formula granules and their standard decoctions of Puerariae lobatae Radix display good consistency,reliable preparation process is observable in the former.