ObjectiveThis study aimed to evaluate the effectiveness of various statistical methods based on the complementary sensitivity analysis framework recommended by the European Medicines Agency (EMA) in Alzheimer’s disease clinical trials, providing a reference for statistical practice that meets international regulatory standards for similar studies. MethodsBased on longitudinal data from a phase Ⅲ clinical trial for the treatment of Alzheimer’s disease, the change from baseline in Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score from baseline at week 26 (with a decrease indicating cognitive improvement) was used as the primary outcome measure. This study employed a mixed-effects model with repeated measures (MMRM) under the assumption of missing at random (MAR) as the primary analysis, while using critical point analysis, rank-based analysis, and slope-based analysis for sensitivity verification. A systematic comparison of the efficacy estimation results from the four analytical methods was conducted to compare the consistency and robustness differences in research conclusions across different analytical strategies. ResultsThe primary analysis results from the MMRM showed that the improvement in ADAS-Cog score from baseline at week 26 in the treatment group was superior to that in the placebo group (LSMD=-3.22, 95%CI: -4.55 to -1.88, P<0.001). Both rank-based analyses and slope-based analyses indicated significant differences between groups (both P<0.001). Critical point analyses revealed that the treatment effect was negative under most reasonable missing hypothesis scenarios, with the effect value only potentially turning positive in extreme non-random missing scenarios. There was no overall reversal of the efficacy conclusion. ConclusionThe combination of MMRM, critical point analysis, rank-based analysis, and slope-based analysis can effectively address the challenge of missing data in clinical trials for progressive diseases. This strategy fully complies with international regulatory standards, verifies efficacy conclusions from multiple perspectives, and enhances the credibility and scientific validity of clinical trial results. It can provide a practical reference for statistical analysis of missing data in similar clinical trials for progressive diseases.

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.

In this work,with tris(4-aminophenyl)amine(TAPA)and 1,3,5-tris(4-formylphenyl)benzene(TFPB)as monomers,an imine-type porous organic polymer,TAPA-TFPB,was synthesized using a simple method under the catalysis of acetic acid.The material TAPA-TFPB was used as solid-phase extraction adsorbent and combined with ultra-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry(UHPLC-QTOF-MS)to establish a detection method for four kinds of nitrofuran metabolites(NFMs)residues in meat samples.The parameters of the adsorbent dosage,the pH value and volume of sample,and the type and volume of washing and eluent solvents were optimized,respectively.Under the optimal extraction conditions,low detection limits(0.11-1.60 μg/kg)were achieved for four kinds of NFMs.At three different spiked levels,the intra-day and inter-day precisions(Relative standard deviations)were 2.8% -10.9% and 4.3% -16.2%,respectively,and the spiked recoveries were 72.0% -107.2%.The results showed that the method chould be used for efficient extraction and analysis of trace NFMs residues in meat samples,indicating that TAPA-TFPB was a kind of promising SPE adsorbent.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Objective:To explore the specific mechanism of Baijiesan on microangiogenesis of wound after perianal abscess in rats by regulating RAS signal pathway.Methods:A total of 72 SD rats were divided into control group,model group,Baijiesan group and Baijiesan+farnesylthiosalicylic acid(FTS)group,with 18 rats in each group.Cut off the whole layer of skin on the back of rats.The model group,Baijiesan group and Baijiesan+FTS group were treated with fecal supernatant,while the control group was treated with normal saline.After the successful establishment of the model,Baijiesan+FTS group were treated with Baijiesan and received in-traperitoneal injection of FTS,while Baijiesan group were treated with Baijiesan only.The back wound images of rats were taken after successful modeling(day 0),4 days,8 days and 12 days after treatment,and the wound healing rate was calculated.After 4 days,8 days and 12 days of treatment,6 rats in each group were randomly selected and killed,the new wound healing tissue was removed,and the blood of abdominal aorta of rats after treatment for 12 days was collected.Histopathological morphology of wound tissue was observed by HE and Masson staining.Immunohistochemistry was used to detect the number of microvessels.ELISA was used to detect serum inflammatory markers.RAS signal pathway and angiogenesis-related molecules were detected by qRT-PCR and Western blot.Results:Compared with control group,the wound healing rate of model group,Baijiesan group and Baijiesan+FTS group decreased at each time point(P<0.05),while the number of microvessels,the levels of TNF-α,IL-1β,IL-6,RAS and Raf-1,VEGF,VEGFR2 mRNA and protein,ERK1,ERK2 mRNA,p-MEK1/2,p-ERK1/2 protein expressions were increased(P<0.05).Compared with model group and Baijiesan+FTS group,the wound healing rate,the number of microvessels,RAS,Raf-1,VEGF,VEGFR2 mRNA and protein,ERK1,ERK2 mRNA,p-MEK1/2,p-ERK1/2 protein expressions were further increased in Baijiesan group(P<0.05),while the levels of TNF-α,IL-1β and IL-6 were decreased(P<0.05).Conclusion:Baijiesan can reduce the level of wound inflamma-tion after operation of perianal abscess,and may enhance the ability of wound angiogenesis and wound healing by promoting RAS signal pathway.

Objective:To explore the configurational characteristics of conditions influencing HPV vaccination coverage across countries,identify typical models for achieving high vaccination coverage under different developmental contexts,and provide references for the formulation of HPV vaccination policies in China.Methods:Using 110 WHO member states as the analytical sample,this study employed fuzzy-set qualitative comparative analysis(fsQCA).Seven conditions were selected from two dimensions—macrosocial factors and policy elements—to examine their effects on improving HPV vaccination coverage.Results:No single antecedent condition constituted a necessary condition for promoting HPV vaccination coverage.The solution yielded five main condition configurations,which were further categorized into three representative patterns:"Resource-Saving""Economy-Driven"and"Target-Focused."Conclusion:The configurational conditions for improving HPV vaccination coverage exhibit multiple concurrent characteristics.School-based vaccination models play a generally facilitating role,while reducing the number of doses and adjusting target population restrictions are key driving factors under resource-limited conditions.Different patterns reflect the synergistic effects between socioeconomic environments and policy design,providing theoretical and practical references for optimizing HPV vaccination policies across diverse contexts.

Objective:To establish a core competence evaluation index system for pediatric internal medicine nurses.Methods:On the basis of literature review, theoretical analysis, and clinical practice of the research group, the evaluation index system of the core competence of nurses in pediatric internal medicine was preliminarily formulated after the discussion of the research group. The Delphi method was employed for two rounds of expert consultation, involving a total of 18 experts. Finally, the evaluation index system of the core competence of nurses in pediatric internal medicine was established, and the weights of indicators at all levels were calculated.Results:The effective recovery rates of the first and second rounds of expert consultation were 100.00%. In the first and second rounds of expert consultation, the authority coefficients were 0.896 and 0.890, the judgment coefficients were 0.901 and 0.889, and the familiarity coefficients were 0.847 and 0.891, with authority coefficients >0.70 in both rounds. The coefficients of variation of the two rounds of expert correspondence were 0.041-0.227 and 0.002-0.126, respectively, and the coefficients of variation of indicators at all levels were <0.25. In the first round of expert consultation, Kendall's coordination coefficients of primary, secondary, and tertiary indicators were 0.305, 0.362, and 0.364, respectively, with P values <0.001. In the second round of expert consultation, Kendall's coordination coefficients of primary, secondary, and tertiary indicators were 0.371, 0.352, and 0.380, respectively, with P values <0.001. Finally, the core competence evaluation index system of pediatric internal medicine nurses was established, including 3 first-level indicators, 14 second-level indicators, and 57 third-level indicators. Conclusions:The evaluation index system of the core competence of pediatric internal medicine nurses has scientificity, reliability, specialty-specific characteristics, and reference value, which can provide a reference for the training and evaluation of pediatric internal medicine nurses in China.

Sepsis is a systemic inflammatory response triggered by infection and often leads to acute kidney injury(AKI).The pathogenesis of sepsis-associated AKI is complex,involving multiple factors such as renal ischemia,inflammation and oxidative stress.In recent years,pyroptosis,a pro-inflammatory form of programmed cell death,has gradually attracted the attention of researchers.Pyroptosis is activated by inflammasomes(e.g.,the NOD-like receptor pyrin domain-related protein 3 inflammasome,NLRP3 inflammasome),accompanied by Gas-dermin D(GSDMD)-mediated formation of cell membrane pores and release of cellular contents,which leads to exacerbation of local and systemic inflammatory responses.The mechanism of pyroptosis in sepsis-associated AKI has not been fully elucidated,but AKI is directly involved in the process of renal functional impairment by indu-cing the death of renal tubular epithelial cells and exacerbating the local inflammatory response.Blockade of key molecules in the pyroptosis pathway,such as GSDMD or NLRP3 inflammasome,can significantly alleviate renal injury,suggesting that the pyroptosis pathway may be a potential therapeutic target for sepsis-associated AKI.This review summarizes the recent research progress on pyroptosis in sepsis-associated AKI,and discuss its cen-tral role in the pathogenesis,particularly focusing on the inflammasome and GSDMD pathways.Additionally,this paper analyzes the potential of focal death inhibition as a therapeutic strategy and proposes future research direc-tions with the expectation of providing references for the treatment of sepsis-related AKI.