Objective To evaluate the predictive value of different machine learning models constructed in a multicenter environment for potential organ donors and verify their clinical application feasibility. Methods The study included 2 000 inpatients admitted to five domestic tertiary hospitals from January 2020 to December 2023, who met the criteria for potential organ donation assessment. They were randomly divided into a training set and an internal validation set (7∶3). Another 300 similar patients admitted to the First Affiliated Hospital of Harbin Medical University from January 2024 to April 2025 were included as an external validation set. The area under the curve (AUC), sensitivity, specificity, accuracy and F1-score of three models were compared, and the consistency of the potential organ donor determination process was tested. Multivariate logistic regression analysis was used to identify predictive factors of potential organ donors. Decision curve analysis (DCA) was employed to verify the resource efficiency of each model, and the threshold interval and intervention balance point were assessed. Results Apart from age, there were no significant differences in other basic characteristics among the centers (all P>0.05). The consistency of the potential organ donor determination process among researchers in each center was good [all 95% confidence interval (CI) lower limits >0]. In the internal validation set, the XGBoost model had the best predictive performance (AUC=0.92, 95% CI 0.89-0.94) and the best calibration (P=0.441, Brier score 0.099). In the external validation set, the XGBoost model also had the best predictive performance (AUC=0.91, 95% CI 0.88-0.94), outperforming logistic regression and random forest models. Multivariate logistic regression showed that mechanical ventilation had the greatest impact (odds ratio=2.06, 95% CI 1.54-2.76, P<0.001). DCA indicated that the XGBoost model had the highest net benefit in the threshold interval of 0.2-0.6. The “treat all” strategy only had a slight advantage at extremely low thresholds. The recommended threshold interval, which balances intervention costs and clinical benefits, considers ≥50% positive predictive value (PPV) and ≤50 referrals per 100 high-risk patients. Conclusions The XGBoost model established in a multicenter environment is accurate and well-calibrated in predicting potential organ donors. Combined with DCA, it may effectively guide the timing of clinical interventions and resource allocation, providing new ideas for the assessment and management of organ donation after brain death.

The randomized controlled trials (RCTs) regarding acupuncture direction published from January 1st, 2013, to November 7th, 2023 were searched in China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP Chinese Journal Database. As a result, 21 RCTs were included. The problems identified included conceptual misunderstandings regarding acupuncture direction, incomplete selection strategies, confounding research factors, and inaccuracies in reporting. Based on the findings, four strategic approaches for enhancing therapeutic efficacy through acupuncture direction were summarized: aligning needle direction with the meridian pathway, directing the needle toward the lesion site, orienting the needle toward adjacent acupoints, and targeting special anatomical structures. Two additional strategies were proposed for optimizing the procedure: simplifying acupuncture operations and directing the needle toward safe anatomical sites. Recommendations were made to improve the rationality of research factor settings and the completeness of acupuncture operation reporting. Furthermore, three methods for reporting acupuncture direction were discussed: reporting the tip-pointed position, reporting the insertion angle and orientation, and reporting azimuth and polar angles, aiming to promote greater standardization and completeness in acupuncture practice and reporting.
Acupuncture Therapy/standards* ; Humans ; Acupuncture Points ; Randomized Controlled Trials as Topic ; Meridians

Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation* ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal/chemistry* ; Models, Theoretical

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

Objective: To investigate the basic situation of pre-analytical quality management in blood station laboratories in North China, and to provide baseline data for promoting the homogenization and standardization of these pre-analytical processes in each blood station laboratory. Methods: A cross-sectional status survey was designed based on the quality management regulations of blood stations, ISO15189 standards and relevant quality management requirements. This survey covering various aspects including laboratory general situation, sample collection and temporary storage, transportation, reception, and quality continuous improvement situations. Data analysis was performed on the survey results of each laboratory. Results: All the 38 blood station laboratories in North China had established a pre-analytical quality management system framework and implemented basic pre-analytical quality control activities; however, there were differences in implementation. 1) Among the 12 basic quality items, 3 items were monitored by all the investigated laboratories (100%), 6 items were monitored by the vast majority of laboratories (about 90%), and 3 items were monitored by a portion of laboratories (about 60%). There were no significant differences in the monitoring index among the three regions and among different types of laboratories (P>0.05). 2) Among the total of 26 items in the three key processes before testing (sample collection and storage, transportation, reception and processing), 12 items were monitored by all laboratories (100%), 11 items were monitored by the vast majority of laboratories (about 90%), and 3 items were monitored by a portion of laboratories (about 75%). There were no significant differences in monitoring index among different regions and types of laboratories (P>0.05). Conclusion: This survey provides a reference and basis for the gap analysis of the pre-analytical process quality management in 38 blood station laboratories across North China. It facilitates laboratories in identifying pre-analytical quality problems, resolving problems, preventing errors, and ensuring that the quality of blood samples before testing meets the established requirements. It lays a foundation for the homogenization of pre-analytical quality management in regional blood stations.

Objective: To determine the frequency and main reasons of unqualified samples by analyzing the quality of pre-analytical samples in blood stations in North China, thereby providing a reference and basis for gap analysis in the implementation of pre-analytical process quality management for participating laboratories and ensuring that only high-standard and high-quality blood samples proceed to testing. Methods: Data on the quality of pre-analytical samples from blood station laboratories in North China was collected via questionnaire. Statistical analysis were performed on: 1) the basic information of samples quality monitoring in the laboratories; 2) the distribution of the overall pre-analytical unqualified rate of samples and the pre-analytical unqualified rate of samples in each laboratory; 3) the distribution of reasons for sample disqualification. Results: 1) The overall pre-analytical unqualified rate of samples in blood station laboratories in North China was 4.55, with a total sigma level of 5.39σ. The 25th, 50th and 75th percentiles (P25, P50, P75) for the total unqualified rate were 0.00, 1.10 and 5.96, respectively. The corresponding percentiles for the Sigma level were 5.34σ, 5.71σ, and 6.00σ, respectively. The pre-analytical unqualified rate of serological and nucleic acid samples (4.89 vs 4.22) showed a significant difference (χ =9.575, P<0.05). 2) The average unqualified rate of samples in region A, B and C was 1.71, 9.50 and 12.64 (χ =1 590.721, P<0.05), and the sigma level was 5.66σ, 5.21σ and 5.16σ, respectively. 3) The main reasons for unqualified serological samples were chylous blood (72.65%), hemolysis (17.39%), abnormal hematocrit (5.80%), and insufficient volume (3.50%). The main reasons for the unqualified nucleic acid samples were chylous blood (78.26%), hemolysis (8.84%), failure to centrifuge as required (5.01%), abnormal hematocrit (4.66%), and insufficient volume (1.92%). Conclusion: In North China, the quality indicators for the pre-analytical processes in blood station laboratories are generally well-managed. Laboratories in region A outperformed the national average in pre-analytical specimen quality control. However, participating laboratories exhibit gaps in implementing pre-analytical quality management. Through effective analysis of pre-analytical process quality metrics and inter-laboratory comparisons, laboratories can identify discrepancies and address shortcomings. By establishing clear quality objectives, they can achieve continuous improvement and ensure the validity of test results.

Objective: To investigate the assessment criteria and subsequent handling practices of hemolytic and lipemic blood samples before testing in blood screening laboratories in North China, and to provide data to support the standardization of their management in blood station laboratories. Methods: Data on the preanalytical management of hemolytic and lipemic samples from 38 laboratories were collected. The details of management on the criteria and verificatioon for assessment, the assessment methods, and subsequent handling procedures of hemolytic and lipemic samples in blood station laboratories were analyzed. Results: 1) All 38 blood station laboratories monitored serological and nucleic acid samples for hemolysis and lipemia in pre-analytical phase. 2) The criteria and methods for assessing hemolytic and lipemic samples varied among the laboratories of the 38 blood stations. 15 laboratories (39.47%) followed manufacturer's instructions, 9 laboratories (23.68%) formulated their own criteria, and 14 laboratories (36.84%) referred to the criteria of other laboratories. 16 laboratories (42.11%) verified the criteria for assessing hemolytic and lipemic samples, with significant variations in verification rate across laboratories from different regions (P<0.05). For the assessment methods, visual inspection was used by 28 laboratories (73.68%) for hemolytic samples and by 27 laboratories (71.05%) for lipemic samples; the colorimetric card method was used by 10 laboratories (26.32%) for assessing both hemolytic and lipemic samples; the instrumental method was used by 1 laboratory (2.63%) for assessing lipemic samples.3) The handling procedures for hemolytic and lipemic samples varied significantly and followed a gradient distribution pattern among 38 laboratories (including accepting samples for testing, accepting samples for concession testing, re-collecting samples, and rejecting samples and halting testing). With increasing severity of hemolysis and lipemia, more laboratories halted testing, and relatively fewer laboratories accepted samples for normal testing. 5 laboratories (13.16%) applied different handling procedures on serological and nucleic acid samples. Conclusion: This survey provides a reference and basis for analyzing gaps in the management of hemolytic and lipemic samples during the preanalyical phase in blood station laboratories in North China. It enables laboratories to identify the problems and deficiencies in the management of hemolytic and lipemic samples, to ensure preanalytical samples quality meets the established requirements, and to lay a foundation for promoting the homogenization and standardization of the regional sample quality management mode.

Objective:To analyze and identify the expression profiles of oxidative stress-related genes and circular RNAs(circRNAs)in ricin toxin(RT)-induced pyroptosis of mouse mononuclear macrophages(RAW264.7)using transcriptome sequencing and bioinformatics technology,and to preliminarily analyze their potential functions.Methods:The macrophages(RAW264.7 cells)were treated with RT to establish a cell pyroptosis model and divided into control group,40 μg·L-1 RT group,and 80 ng/mL RT group.Transmission electron microscope(TEM)was used to observe the morphology of the RAW264.7 cells in various groups;Western blotting method was used to detect the expression levels of the pyroptosis pathway-related proteins in the cells in various groups;80 μg·L-1 RT was selected for subsequent experiments.Transcriptome sequencing(RNA-Seq)was performed to obtain the circRNA and mRNA expression profiles in the RAW264.7 cells in control group and RT-treated group,followed by bioinformatics analysis.Results:Compared with control group,the cells in 40 and 80 μg·L-1 RT groups underwent morphological changes;the cells in RT groups showed obvious pyroptosis-like morphological changes,characterized by significant swelling of dying cells and the appearance of characteristic large bubbles on the plasma membrane.Compared with control group,the expression level of gasdermin DN-terminal fragment(GSDMD-N)protein in 40 and 80 μg·L-1 RT groups was increased(P<0.05);compared with 40 μg·L-1 RT group,the expression level of GSDMD-N protein in the cells in 80 μg·L-1 RT group was increased(P<0.05);therefore,the subsequent experiments used the RT concentration of 80 μg·L-1.A total of 2930 differentially expressed messenger RNAs(mRNAs)and 24 differentially expressed circRNAs were identified.The constructed circRNA-microRNA(miRNA)-mRNA competing endogenous RNA(ceRNA)regulatory network consisted of 7 circRNAs,12 miRNAs and 13 mRNAs.Gene Ontology(GO)functional enrichment analysis showed that in biological process(BP),the functions regulated by differentially expressed genes mainly included immune response and oxidative stress response;in cellular component(CC),differentially expressed genes were mainly localized to the external side of plasma membrane and cell leading edge;in molecular function(MF),they were mainly involved in transporter transmembrane activity and hormone receptor binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis showed that differentially expressed genes were mainly enriched in Toll-like receptor signaling pathway,Forkhead box O(FoxO)signaling pathway and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway.In the protein-protein interaction(PPI)network,the top 10 hub genes with the highest connectivity were screened by CytoHubba,including matrix metalloproteinase 9(MMP9),superoxide dismutase 2(SOD2),and v-src sarcoma viral oncogene homolog(Src).Conclusion:The expression profiles of oxidative stress-related genes and circRNAs in RAW264.7 cells are altered after RT treatment.The screened differentially expressed circRNAs and mRNAs may serve as potential targets to regulate RT-induced pyroptosis in RAW264.7 cells through oxidative stress pathways.

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

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