OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

This paper aimed to use non-targeted urine metabolomics to reveal the potential biomarkers of toxicity in rats with hepatic injury induced by aqueous extracts of Dictamni Cortex(ADC). Forty-eight SD rats were randomly assigned to a blank group and high-dose, medium-dose, and low-dose ADC groups, with 12 rats in each group(half male and half female), and they were administered orally for four weeks. The hepatic injury in SD rats was assessed by body weight, liver weight/index, biochemical index, L-glutathione(GSH), malondialdehyde(MDA), and pathological alterations. The qPCR was utilized to determine the expression of metabolic enzymes in the liver and inflammatory factors. Differential metabolites were screened using principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA), followed by a metabolic pathway analysis. The Mantel test was performed to assess differential metabolites and abnormally expressed biochemical indexes, obtaining potential biomarkers. The high-dose ADC group showed a decrease in body weight and an increase in liver weight and index, resulting in hepatic inflammatory cell infiltration and hepatic steatosis. In addition, this group showed elevated levels of MDA, cytochrome P450(CYP) 3A1, interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α), as well as lower levels of alanine transaminase(ALT) and GSH. A total of 76 differential metabolites were screened from the blank and high-dose ADC groups, which were mainly involved in the pentose phosphate pathway, tryptophan metabolism, purine metabolism, pentose and glucuronic acid interconversion, galactose metabolism, glutathione metabolism, and other pathways. The Mantel test identified biomarkers of hepatotoxicity induced by ADC in SD rats, including glycineamideribotide, dIDP, and galactosylglycerol. In summary, ADC induced hepatotoxicity by disrupting glucose metabolism, ferroptosis, purine metabolism, and other pathways in rats, and glycineamideribotide, dIDP, and galactosylglycerol could be employed as the biomarkers of its toxicity.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Biomarkers/metabolism* ; Liver/metabolism* ; Drugs, Chinese Herbal/adverse effects* ; Female ; Chemical and Drug Induced Liver Injury/metabolism* ; Glutathione/metabolism* ; Humans

Brasilicardin A, a diterpene glycoside isolated from pathogenic actinomycete Nocardia brasiliensis IFM 0406, has become a novel immunosuppressant candidate due to its significant immunosuppressive activity, low toxicity and unique mechanism of action. However, brasilicardin A and its analogues have become a research hotspot to the development of this promising immunosuppressant because of the low-yield production in the natural pathogenic producer and the synthetically challenging skeleton. According to the reported biosynthetic pathway of brasilicardin A, the function of involved diterpene synthase was analyzed by bioinformatics. Then the genes bra1-5 that synthesize the brasilicardin A skeleton were directionally amplified from the pathogenic strain N. brasiliensis IFM 0406, and heterologous expression was achieved successfully in Streptomyces albus R1. The compounds were isolated and purified by using various column chromatographies including silica gel column chromatography and semi-preparative HPLC. Six new brasilicardins were established and named brasilicardin H-M. The activity of brasilicardins was screened using lipopolysaccharide (LPS)-activated mouse primary macrophage inflammation model. Brasilicardin H-M exhibited good inhibitory activity on nitric oxide (NO) release with IC₅₀ values of 28.24 ± 3.70, 37.44 ± 2.00, 39.85 ± 4.02, 26.77 ± 4.40, 65.25 ± 1.48 and 15.24 ± 2.72 μmol·L^-1, respectively (indomethacin as the positive control with IC₅₀ value of 34.28 ± 4.10 μmol·L^-1). The results indicated that six compounds had potential anti-inflammatory activity. This study laid a foundation for the elucidation of the brasilicardin A biosynthetic pathway and evaluation of the structure-activity relationship as well as new drug developments.

Purpose: This systematic review aimed to scrutinize the progression of symptom cluster research in adult cancer patients who received primary or adjuvant chemotherapy between 2001 and 2023, providing a comprehensive understanding of clinical practice and future research. Methods: PubMed, Ovid MEDLINE, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Web of Science databases were searched for theme words and free words related to symptom clusters, cancer, and chemotherapy. Eligible studies were published between January 1, 2001, and May 30, 2023; adults who were diagnosed with cancer and received primary or adjuvant chemotherapy were evaluated. Results: Twenty-eight studies were included in this review. The Memorial Symptom Assessment Scale emerged as the predominant instrument and exploratory factor analysis was the most frequently employed statistical method to identify symptom clusters. Psychological, gastrointestinal, and physical image symptom clusters were the most commonly delineated. Furthermore, the temporal stability of the symptom clusters showed varying dynamics, with psychological symptom clusters displaying relative consistency over time. Conclusion Interventions are needed for the most common and stable symptoms in patients with cancer undergoing chemotherapy. Future endeavors may necessitate more longitudinal studies to delve deeper into the temporal stability and dynamic variations of symptom clusters. Such investigations hold promise for advancing symptom cluster research, elucidating the underlying mechanisms, and fostering the development of targeted interventions, thereby enriching the symptom management paradigm in oncological care.

Purpose: This systematic review aimed to scrutinize the progression of symptom cluster research in adult cancer patients who received primary or adjuvant chemotherapy between 2001 and 2023, providing a comprehensive understanding of clinical practice and future research. Methods: PubMed, Ovid MEDLINE, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Web of Science databases were searched for theme words and free words related to symptom clusters, cancer, and chemotherapy. Eligible studies were published between January 1, 2001, and May 30, 2023; adults who were diagnosed with cancer and received primary or adjuvant chemotherapy were evaluated. Results: Twenty-eight studies were included in this review. The Memorial Symptom Assessment Scale emerged as the predominant instrument and exploratory factor analysis was the most frequently employed statistical method to identify symptom clusters. Psychological, gastrointestinal, and physical image symptom clusters were the most commonly delineated. Furthermore, the temporal stability of the symptom clusters showed varying dynamics, with psychological symptom clusters displaying relative consistency over time. Conclusion Interventions are needed for the most common and stable symptoms in patients with cancer undergoing chemotherapy. Future endeavors may necessitate more longitudinal studies to delve deeper into the temporal stability and dynamic variations of symptom clusters. Such investigations hold promise for advancing symptom cluster research, elucidating the underlying mechanisms, and fostering the development of targeted interventions, thereby enriching the symptom management paradigm in oncological care.

Purpose: This systematic review aimed to scrutinize the progression of symptom cluster research in adult cancer patients who received primary or adjuvant chemotherapy between 2001 and 2023, providing a comprehensive understanding of clinical practice and future research. Methods: PubMed, Ovid MEDLINE, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Web of Science databases were searched for theme words and free words related to symptom clusters, cancer, and chemotherapy. Eligible studies were published between January 1, 2001, and May 30, 2023; adults who were diagnosed with cancer and received primary or adjuvant chemotherapy were evaluated. Results: Twenty-eight studies were included in this review. The Memorial Symptom Assessment Scale emerged as the predominant instrument and exploratory factor analysis was the most frequently employed statistical method to identify symptom clusters. Psychological, gastrointestinal, and physical image symptom clusters were the most commonly delineated. Furthermore, the temporal stability of the symptom clusters showed varying dynamics, with psychological symptom clusters displaying relative consistency over time. Conclusion Interventions are needed for the most common and stable symptoms in patients with cancer undergoing chemotherapy. Future endeavors may necessitate more longitudinal studies to delve deeper into the temporal stability and dynamic variations of symptom clusters. Such investigations hold promise for advancing symptom cluster research, elucidating the underlying mechanisms, and fostering the development of targeted interventions, thereby enriching the symptom management paradigm in oncological care.

Purpose: This systematic review aimed to scrutinize the progression of symptom cluster research in adult cancer patients who received primary or adjuvant chemotherapy between 2001 and 2023, providing a comprehensive understanding of clinical practice and future research. Methods: PubMed, Ovid MEDLINE, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Web of Science databases were searched for theme words and free words related to symptom clusters, cancer, and chemotherapy. Eligible studies were published between January 1, 2001, and May 30, 2023; adults who were diagnosed with cancer and received primary or adjuvant chemotherapy were evaluated. Results: Twenty-eight studies were included in this review. The Memorial Symptom Assessment Scale emerged as the predominant instrument and exploratory factor analysis was the most frequently employed statistical method to identify symptom clusters. Psychological, gastrointestinal, and physical image symptom clusters were the most commonly delineated. Furthermore, the temporal stability of the symptom clusters showed varying dynamics, with psychological symptom clusters displaying relative consistency over time. Conclusion Interventions are needed for the most common and stable symptoms in patients with cancer undergoing chemotherapy. Future endeavors may necessitate more longitudinal studies to delve deeper into the temporal stability and dynamic variations of symptom clusters. Such investigations hold promise for advancing symptom cluster research, elucidating the underlying mechanisms, and fostering the development of targeted interventions, thereby enriching the symptom management paradigm in oncological care.

Objective: Single-cell RNA sequencing (scRNA-seq) was used to analyze the developing mouse molars, in order to construct a spatiotemporal development atlas of pulp cells, and further to reveal the developmental process and regulatory mechanism of tooth development. Methods: Ten mandibular first molars from C57BL/6 mice in postnatal day (PN) 0 and 3 were respectively dissected and digested to obtain single-cell suspensions. scRNA-seq was performed on 10× Genomics platform. PN 7 mouse molar scRNA-seq data were obtained from our previous study. PN 0, 3, and 7 scRNA-seq data were integrated for following analysis. The initial quality control, mapping and single cell expression matrix construction were performed by Cell Ranger. Quality control, standardization, dimensional reduction and cluster analysis were performed by using Seurat. Monocle was used to generate the pseudotime trajectory. Scillus was used to perform gene ontology analysis. In order to detect the spatiotemporal change of different population of pulp cells, the marker genes of each cluster were demonstrated by RNAscope in situ hybridization. Results: There were twenty-six cell clusters within mouse molars, which were identified as eight different cell types, including dental pulp cells, dental follicle cells, epithelial cells, immune cells, endothelial cells, perivascular cells, glial cells and erythrocytes. We further re-clustered and analyzed dental pulp cells. Cluster 0 were mature pulp cells, which located at the upper portion of crown. The main functions of cluster 0 were osteogenesis and extracellular structure organization. Cluster 1 were apical papilla cells, which located at the apical part of roots, whose main functions were extracellular structure organization and organ development. Cluster 2 were cycling cells, which were actively proliferated, resided in the lower portion of the crown. Cluster 3 and 4 were preodontoblasts and odontoblasts, respectively. Their functions were closely related to biomineralization. The proportion of mature pulp cells increased with the development process, while the proportion of cycling cells and odontoblast lineage decreased. According to the expression pattern of marker genes of each cluster, we constructed a cell atlas of dental pulp. Pseudotime trajectory analysis found there were two development trajectories within dental pulp. They both started from SPARC related modular calcium binding 2 (Smoc2)+ dental papilla cells, then went through DNA topoisomerase Ⅱ alpha (Top2a)+ cycling cells, and finally divided into coxsackie virus and adenovirus receptor (Cxadr)+ mature pulp cells or dentin sialophosphoprotein (Dspp)+ odontoblasts two lineages. Conclusions: scRNA-seq could fully discover the intercellular heterogeneity of cells on transcriptome level, which provides a powerful tool to study the process and regulatory mechanism of organ development.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

This study was aimed to understand the current status of the antimicrobial resistance and molecular distribution of Campylobacter in various poultry in Jiaodong area,to provide a basis for effective prevention and control of the Campy-lobacter risk to poultry products and human health.Campylobacter was isolated and identified from 565 cloacal samples collect-ed in the Jiaodong area from August to October 2021 through conventional bacterial isolation and culture,mass spectrometry,microbroth dilution and multilocus sequence typing(MLST).The drug resistance and molecular typing of 131 representative strains(67 Campylobacter jejuni and 64 Campylobacter coli)were studied separately.Antimicrobial resistance analysis indica-ted that 131 isolates were highly resistant to ciprofloxacin,nalixic acid and tetracycline,with resistance rates of 96.21％,96.21％and 95.45％,respectively.Except for 2 strains,62 strains of C.coli were completely resistant to these three drugs(100％).A total of 65 strains of 131 strains were multidrug re-sistant,and the overall multidrug resistance rate was 49.62％,among which 11 strains(16.42％)of C.jejuni were resistance to 3-5 antibiotics,and 54 strains(84.38％)of C.coli were re-sistance to 3-6 antibiotics.Among the isolates from different poultry sources,waterfowl isolates were the most resistant,fol-lowed by broiler isolates.The MLST typing results revealed 72 alleles and 35 sequence types obtained from 67 strains of C.je-juni,and the distribution was relatively dispersed,without a dominant ST type and homologous complex.A total of 27 alleles and 19 sequence types were obtained from 64 strains of C.coli.Moreover,59.38％(38/64)strains were homologous complex CC-828,in which the ST-1586 sequence type was most frequent,followed by ST-825.ST-1586,ST-9944 and ST-3735 were the main sources of C.coli in broilers,and ST-825 and ST-1586 were the main sources of C.coli in waterfowl.Differences in C.jejuni and C.coli carriage were observed among poultry in the Jiaodong area.Carriage of the two bacteria was more common in laying hens than in broilers and waterfowl.C.jejuni from poultry in the Jiaodong area was highly resistant to ciprofloxacin,nalixic acid and tetracycline,but had good sensitivity to other drugs.C.coli was highly resistant to a variety of antibiotics,and multiple drug resistance was common.St-type dispersal of C.jejuni showed high genetic diversity.C.coli was cloned and transmitted mainly by ST-1586 in broiler chickens and waterfowl.Poultry carry C.jejuni,which can cause serious diseases in humans.Therefore,dynamic monitoring of Campylobacter from poultry should be strengthened.