ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

[摘 要] 目的：探讨麻疹-流行性腮腺炎-风疹联合减毒活疫苗（MMR）通过诱导免疫原性细胞死亡（ICD）对三阴性乳腺癌（TNBC）的免疫调节机制。方法：体外实验采用CCK-8法检测MMR对TNBC细胞4T1和MDA-MB-231存活率的影响，免疫荧光法检测MDA-MB-231细胞中钙网蛋白（CALR）表达，磷钼酸比色法检测MDA-MB-231细胞内ATP的含量，ELISA检测细胞上清液中高迁移率族蛋白B1（HMGB1）的表达水平，通过GEPIA网站分析CALR和HMGB1对乳腺癌患者生存期的影响。体内实验中经皮下注射4T1-Luc细胞于雌性BALB/c小鼠乳腺脂肪垫构建TNBC小鼠模型。设Control组、盐酸阿霉素（Dox）组、MMR组，按照分组每两天静脉给药1次，连续给药3次。动物活体成像系统观察肿瘤体积变化；记录小鼠体质量及各器官指数初步评估疫苗安全性；H-E染色观察肿瘤病理变化；免疫组化和Western blotting检测肿瘤中CALR和HMGB1蛋白的表达。流式细胞术分析小鼠脾T淋巴细胞亚群及肿瘤树突状细胞和巨噬细胞比例；免疫组化检测肿瘤CD8+ T淋巴细胞浸润；ELISA检测血清中促炎细胞因子IL-6和TNF-α含量。结果：MMR对4T1细胞的活性抑制作用较弱；MMR对MDA-MB-231细胞抑制率达90.39%（P < 0.001）。与Control组相比，MMR组MDA-MB-231细胞中ICD相关蛋白（CALR、ATP、HMGB1）表达上调（P < 0.001）。GEPIA网站分析表明，CALR和HMGB1高表达的患者总生存期有所延长。MMR延缓了荷瘤小鼠肿瘤体积增长（P < 0.001），延长小鼠的生存期，且28 d内MMR组荷瘤小鼠体重与Control组无显著性差异（P > 0.05）；H-E染色显示，与Control组相比，MMR组小鼠肿瘤组织坏死区域扩大且有免疫细胞浸润；MMR上调肿瘤ICD相关蛋白CALR、HMGB1的表达水平；MMR组脾CD4+、CD8+ T淋巴细胞及肿瘤树突状细胞和M1型巨噬细胞的比例增加（P < 0.05），CD8+ T淋巴细胞在肿瘤组织中的浸润增加（P < 0.001），且促炎细胞因子IL-6和TNF-α水平升高（P < 0.01）。结论：MMR减毒活疫苗对TNBC的抗肿瘤作用可能与诱导肿瘤发生ICD进而激活抗肿瘤免疫相关。

OBJECTIVE To evaluate the influence of pharmaceutical quality control on the efficiency and outcomes of standardized medication therapy management （MTM） services for patients with coronary heart disease by using Economic， Clinical and Humanistic Outcomes （ECHO） model. METHODS This study collected case data of coronary heart disease patients who received MTM services during January-March 2023 （pre-quality control implementation group， n＝96） and June-August 2023 （post-quality control implementation group， n＝164）. Using propensity score matching analysis， 80 patients were selected from each group. The study subsequently compared the economic， clinical， and humanistic outcome indicators of pharmaceutical services between the two matched groups. RESULTS There were no statistically significant differences in baseline data between the two groups after matching （P＞0.05）. Compared with pre-quality control implementation group， the daily treatment cost （16.26 yuan vs. 24.40 yuan， P＜0.001）， cost-effectiveness ratio [23.12 yuan/quality-adjusted life year （QALY） vs. 32.32 yuan/QALY， P＜0.001]， and the incidence of general adverse drug reactions （2.50% vs. 10.00%， P＝0.049） of post-quality control implementation group were decreased significantly； the utility value of the EuroQol Five-Dimensional Questionnaire （0.74± 0.06 vs. 0.71±0.07， P＝0.003）， the reduction in the number of medication related problems （1.0 vs. 0.5， P＜0.001）， the medication adherence score （[ 6.32±0.48） points vs. （6.10±0.37） points， P＝0.001]， and the satisfaction score （[ 92.56±1.52） points vs. （91.95±1.56） points， P＝0.013] all showed significant improvements. Neither group experienced serious adverse drug reactions. There was no statistically significant difference in the incidence of new adverse reactions between the two groups （1.25% vs. 3.75%， P＝0.310）. CONCLUSIONS Pharmaceutical quality control can improve the quality of pharmaceutical care， and the ECHO model can quantitatively evaluate the effect of MTM services， making pharmaceutical care better priced and more adaptable to social needs， thus being worthy of promotion.

ObjectiveTo establish the multi-technique characteristic profiles of Alumen by X-ray diffraction（XRD）， Fourier-transform infrared spectroscopy（FTIR） and thermogravimetric-differential thermal analysis（TG-DTA）， and to explore the spectral characteristics for rapid identification of Alumen and its potential adulterant， Ammonium alum. MethodsA total of 27 batches of Alumen samples from 8 production regions were collected for preliminary identification based on visual characteristics. The PDF standard cards of XRD were used to differentiate Alumen from A. alum， and the XRD characteristic profiles of Alumen were established， and then the common peaks were screened. Based on hierarchical clustering analysis（HCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， the characteristic information that could be used for identification of Alumen was selected with variable importance in the projection（VIP） value>1. FTIR characteristic profiles of Alumen were established， and key wavenumbers for identification were screened by HCA and OPLS-DA with VIP value>1. Meanwhile， the thermogravimetric differences between Alumen and A. alum were analyzed by TG-DTA， and the thermogravimetric traits that could be used for identification were screened. ResultsAlumen and A. alum could not be effectively distinguished by traits alone. However， by comparing the PDF standard cards of XRD， 15 batches of Alumen and 12 batches of A. alum could be distinguished. In the XRD profiles， 10 characteristic peaks were confirmed， corresponding to diffraction angles of 14.560°， 24.316°， 12.620°， 32.122°， 17.898°， 34.642°， 27.496°， 46.048°， 40.697° and 21.973°. In the FTIR profiles， 4 wavenumber ranges（399.193-403.050， 1 186.010-1 471.420， 1 801.190-2 620.790， 3 612.020-3 997.710 cm^-1） and 12 characteristic wavenumbers（1 428.994， 1 430.922， 1 432.851， 1 434.779， 1 436.708， 1 438.636， 1 440.565， 1 442.493， 1 444.422， 1 446.350， 1 448.279， 1 450.207 cm^-1） were identified. In the TG-DTA profiles， there were characteristic decomposition peaks of ammonium ion and mass reduction features near 555.34 ℃ for A. alum. These characteristics could serve as important criteria for distinguishing the authenticity of Alumen. ConclusionXRD， FTIR and TG-DTA can be used to rapidly detect Alumen and A. alum， and combined with the discriminant features selected through chemometrics， the rapid and accurate identification of Alumen and A. alum can be achieved. The research findings provide new approaches for the rapid identification of Alumen.

Objective:To explore the application effect of integrated root cause analysis (RCA) in the analysis of approximate administration error events, and to provide reference for the management of clinical approximate administration error events.Methods:A non-synchronous pre-and post-control study was conducted. The data of 3 cases of approximate error events of drug administration in the Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University from January to September 2021 were retrospectively analyzed. The integrated RCA was used to find out the proximal causes, and the system diagram and problem tree analysis were used to determine the root causes. The improvement measures were formulated through barrier analysis, including improving the safety barrier of hospital information system (HIS), updating the database of drug instructions in the Department of Cardiology, standardizing the barrier of nurses′ treatment and examination of medical orders, and visual management barrier. The integrated RCA improvement measures were applied to the management of approximate error events of drug administration. The improvement effect was evaluated by comparing the number of adverse events of medication errors before improvement (January to September 2021) and after improvement (September 2023 to May 2024), the error rate of HIS drug orders, the number of drug interceptions in pharmacies, the processing time of doctors′ HIS orders, and the qualified rate of medical staff 's drug knowledge assessment.Results:There were 32 medical staff in the department of cardiology before improvement, including 6 males and 26 females, aged (31.03 ± 4.29) years old. After improvement, 30 medical staff, 6 males and 24 females, aged (31.20 ± 4.37) years old. After the implementation of integrated RCA improvement, the number of adverse events of medication errors decreased from 3 cases before improvement to 0 cases after improvement. The error rate of HIS drug orders decreased from 11.83%(11/93) before improvement to 2.74%(2/73) after improvement. Improve the pre-audit system without pharmacy drug delivery interception function, improve the pre-application drug information 6 990, the number of drug interception was 0; after improvement, 7 782 pieces of drug information were claimed, and the number of drug interceptions was 78. The difference before and after improvement was statistically significant ( χ2=68.54, P<0.05). After the improvement, the doctor′s HIS doctor′s order processing time including admission, discharge, preoperative, postoperative, examination and medication, and temporary doctor′s order processing time were (1.14 ± 0.41), (1.37 ± 0.30), (0.43 ± 0.11), (0.51 ± 0.11), (0.40 ± 0.10) and (0.51 ± 0.14) min, respectively. They were lower than (4.07 ± 0.70), (3.69 ± 0.60), (1.44 ± 0.24), (2.10 ± 0.45), (1.41 ± 0.28) and (1.44 ± 0.29) min before improvement, and the differences were statistically significant ( t values were 15.21-21.42, all P<0.05). The qualified rate of drug knowledge examination of medical staff increased from 81.25%(26/32) before improvement to 100.00%(30/30) after improvement, and the difference was statistically significant ( P<0.05). Conclusions:The application of integrated RCA to analyze the approximate error events of drug administration is helpful to identify the system defects in the workflow of electronic medical order administration more comprehensively, improve work efficiency and ensure the quality and safety of medical care.

Objective:To extract and evaluate the relevant evidence to improve the family discharge preparation of premature infants with bronchopulmonary dysplasia, so as to provide evidence-based basis for clinical formulation of scientific and effective discharge plans.Methods:All the evidence on the family discharge readiness of premature infants with bronchopulmonary dysplasia was collected from Chinese and English databases or websites, and the quality of various studies was evaluated. JBI′s evidence grading and recommendation level system (2014 edition) was used to extract and summarize the evidence.Results:A total of 21 articles were included, and 24 pieces of evidence were summarized, which were divided into seven themes: pre-discharge planning, environmental preparedness, parent education and training, support systems, feeding and nutrition, respiratory management, and discharge follow-up.Conclusions:For preterm infants with bronchopulmonary dysplasia, discharge readiness should be improved in terms of standardizing discharge criteria and implementing a discharge plan; improving family care preparation to ensure discharge support; strengthening health management and implementing a personalized plan; and continuing high-quality follow-up to ensure long-term health.

Objective To investigate the clinical significance and potential mechanism of NAT10 in hepatocellular carcinoma.Meth-ods A total of 50 normal and 374 tumor samples were obtained based on The Cancer Genome Atlas(TCGA),and the data were pro-cessed by R 4.2.1.Results The expression of NAT10 in tumor samples was significantly higher than that in normal samples(P＜0.001).Compared with patients with low expression of NAT10,patients with high expression of NAT10had worse prognosis(P＜0.001).Logistic regression analysis showed that high NAT10 expression was associated with adverse clinical prognostic factors,and pa-tients with high NAT10 expression were more likely to progress to the advanced stage.Gene set enrichment analysis(GSEA)results showed that the genes related to heterobiotic metabolism,blood coagulation and fatty acid metabolism were differentially enriched in the samples with high expression of NAT10.The protein interaction analysis results showed that NAT10may interact with genes such as IGF2,SST,MUC2,CHGA,AGR2,etc.Conclusion NAT10 is highly expressed in hepatocellular carcinoma,and the expression level is cor-related with the clinical characteristics and survival rate of patients with hepatocellular carcinoma.NAT10may be a potential molecular bio-marker for hepatocellular carcinoma prognosis.

A 36-year-old male developed unconsciousness and no response to voice stimuli after taking approximately 2 050 mg felodipine (the specific time was unknown). Two hours later, he was sent to the department of emergency by his family and admitted to the hospital. His vital signs showed body temperature 35.1 ℃, pulse 148 times/min, respiration 32 times/min, and blood pressure 65/34 mmHg. Acute drug poisoning, acute toxic cardiomyopathy, acute toxic shock, acute type Ⅱ respiratory failure, acute toxic encephalopathy, and acute renal failure were diagnosed based on the patient′s clinical manifestations combined with laboratory tests results, cardiac ultrasound, chest and abdominal CT scans. Endotracheal intubation connected to a ventilator for invasive assisted ventilation, pressure boosting, and fluid resuscitation were given. At the same time, repeated gastric lavage and enema were performed to remove toxins. Blood perfusion was intermittently and repeatedly administered, and continuous renal replacement therapy was used. The blood concentration of felodipine was 1 298 μg/L at 2 hours after admission, and cardiac arrest occurred at 4 hours. Venous-arterial extracorporeal membrane oxygenation (V-A ECMO) treatment was administered immediately. After 48 hours of ECMO operation, sedatives were discontinued and the patient′s consciousness was improved after 4 hours. On the 5th day of ECMO treatment, his heart rate was 72 beats per minute, and blood pressure was 127/65 mmHg. The blood concentration of felodipine decreased to 2 μg/L. The patient′s vital signs were significantly improved and ECMO supportive treatment was withdrawn. After 26 days of hospitalization, the patient recovered and was discharged.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.