Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

ObjectiveTo develop the Evidence Grading Scale for Ancient classical prescriptions in Traditional Chinese medicine， assess its reliability and validity， and apply it in practice to provide multi-source evidence for clinical practice guidelines development. MethodsLiterature retrieval was conducted to extract and screen existing evaluation dimensions， then the initial items were summarized using thematic analysis. Experts in the clinical medicine， medical history and literature participated in the Delphi questionnaire survey to evaluate and refine the items. An expert consensus meeting was conducted to finalize the included items， refine the method for items evaluation and evidence grading. The evidence quality rating scale for ancient classical traditional Chinese medicine （TCM） prescriptions was then established and tested for reliability and validity. ResultsThrough literature review， extraction， screening and summarization， a total of 3 dimensions and 12 initial items were formed. Questionnaires were sent to 69 experts to evaluate the initial items， with a questionnaire response rate of 100% and an expert authority coefficient of 0.92. All 12 items were retained for they had importance scores above 4. The Evidence Grading Scale on Ancient classical prescriptions in Traditional Chinese medicine includes 3 dimensions with 12 items. The 3 dimensions includes ancient evidence， inheritance status， and modern application. Each dimension contains 4 items， and each item has a full score of 5 points. The evidence was rated as high-level， moderate-level， and low-level according to the final scores. The content validity index （CVI） of the 12 items was ＞0.9， the average CVI of the scale was 0.98， and the intraclass correlation coefficient （ICC） was 0.90. ConclusionThe Evidence Grading Scale on Ancient classical prescriptions in Traditional Chinese medicine has good reliability and validity， which is practical for use in the development of TCM clinical guidelines and can better support clinical decision-making.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

ObjectiveTo understand the process and influencing factors affecting the utilization of influenza vaccination services and vaccination decision-making among the elderly in Shanghai, to explore the delivery of influenza vaccination services and the difficulties faced by the health service system, and to provide guidance for optimizing immunization strategies. MethodsBased on the vaccine hesitancy determinants matrix, semi-structured personal interviews were conducted with stakeholders involved in influenza vaccination services in Shanghai from January to February 2024, using a purposive sampling method. Participants were included until thematic saturation was achieved. Interview data were audio-recorded, transcribed, coded, and organized using NVivo 20 software, and analyzed using the thematic framework method. ResultsA total of 25 interviewees were included, including 9 medical staff, 12 elderly people aged 60 and above, and 4 family members. The study found that Shanghai had a well-managed and standardized influenza vaccination service. However, the promotion of vaccine-related information at the grassroots level was passive and limited. Out-of-pocket payment of the vaccine and cultural beliefs of the elderly negatively impacted vaccination rates. Meanwhile, recommendations from family, friends, and medical staff facilitated vaccination, although the impact varied depending on the type of medical staff. Neighborhood committees in townships and streets played a crucial role in delivering vaccination information to the target population. Additionally, the internet, social media, and the COVID-19 vaccine had both positive and negative impacts on influenza vaccination. Strategic optimization of vaccination should prioritize price concessions, enhance publicity strategies, and improve awareness, professionalism, and willingness among medical and healthcare workers to recommend vaccination. ConclusionThe influenza vaccination service in Shanghai is well-managed and standardized. However, it is essential to consider the influence of family and other support systems on the elderly. It is also necessary to enhance the professionalism, service awareness, and willingness to recommend among the medical staff. Furthermore, systematic interventions and publicity efforts should be effectively integrated with social media and the functions of neighborhood committees.

Objective To analyze the detection efficiency of p16INK4a protein combined with human papillomavirus and liquid-based cytology(LCT)in the screening of cervical precancerous lesions,and to provide a basis for cervical cancer preven-tion and treatment.Methods The results of p16INK4a staining of cervical epithelial cells,human papillomavirus testing and cer-vical cytology were analyzed in 139 inpatients at Guangzhou Women's and Children's Medical Center between January 2019 and December 2020.Of them,there were 111 patients with cervical intraepithelial neoplasia(CIN)and 28 cases of cervical inflam-matory disease.The efficacy of the three methods alone and in combination to screen for CIN lesions was compared.Results In the detection of CIN patients,the sensitivity of p16INK4a,microfluidic microarray and cervical cytology for detecting CIN and a-bove lesions was 91.89% ,94.59% and82.88% ,with specificity of 57.14% ,17.86% and46.43% ,and AUC of 0.75,0.56 and 0.65,respectively;while the sensitivity of"p16INK4a+LCT","p16INK4a+hrHPV","LCT+hrHPV"and their sen-sitivity were 96.40% ,97.30% ,94.59% and 99.10% ,their specificity was 85.71% ,92.86% ,89.29% and 92.86% ,and the AUC was 0.91,0.95,0.92 and 0.96,respectively.Conclusion The combined p16INK4a and hrHPV test helps to improve diagnostic accuracy and early detection,thus allowing for earlier intervention or treatment.This combined application allows for more accurate identification of low-grade and high-grade cervical intraepithelial neoplasia,providing more information for indi-vidualized patient management.

Objective To analyze the differences in serum amino acid levels between preeclampsia(PE)and normal pregnant women in Urumqi,and to explore the correlation between amino acids with statistically significant differences and PE severity,as well as their diagnostic value for PE patients.Methods A total of 49 normal pregnant women who visited Urumqi Maternal and Child Health Hospital from June 2021 to June 2023 were selected as the control group and 55 PE pregnant women were selected as the PE group,and the PE group was further divided into mild PE group(25 cases)and severe PE group(30 cases).Liquid chromatogra-phy-tandem mass spectrometry technology was used to determine the levels of 25 metabolites in pregnant women's serum.Spearman correlation analysis was used to analyze the correlation between the amino acid lev-els and PE severity.Logistic regression was used to correct for potential confounding factors,and receiver op-erating characteristic curve was used to analyze the diagnostic efficacy of amino acids with significant differ-ences in PE.Results There were statistically significant differences in the body mass index(BMI)and deliv-ery method between the PE group and the control group(P＜0.05).The serum levels of histidine,threonine,glutamine,ethanolamine,methylhistidine,and canine uric acid in the PE group were higher than those in the control group(P＜0.05).The serum levels of threonine,glutamine,methylhistidine,and canine uric acid in the severe PE group were higher than those in the mild PE group and control group(P＜0.05).The serum ethanolamine levels in the mild group and severe PE group were higher than those in the control group(P＜0.05).The serum histidine levels in the severe PE group were higher than those in the control group(P＜0.05).Correlation analysis showed that serum glutamine,ethanolamine,methylhistidine,and canine uric acid were positively correlated with the severity of PE(P＜0.05).After adjusting for BMI,there were still statisti-cally significant differences in the levels of threonine,glutamine,and methylhistidine between the PE group and the control group(P＜0.05).The area under the curve of the combined detection of serum threonine,glu-tamine,and methylhistidine for diagnosing PE was 0.734.Conclusion There is a certain correlation between serum levels of threonine,glutamine,and methylhistidine and the severity of PE,and the combined detection has high diagnostic value for patients with PE.

Objective To investigate the effects of lipopolysaccharide (LPS) on human pulmonary vascular endothelial cells (HPVECs) cytoskeleton and perform biological analysis of the microRNA (miRNA) spectrum. Methods The morphology of HPVECs was observed by microscope, the cytoskeleton by FITC-phalloidin staining, and the expression of VE-cadherin was detected by immunofluorescence cytochemical staining; the tube formation assay was conducted to examine the angiogenesis, along with cell migration test to detect the migration, and JC-1 mitochondrial membrane potential to detect the apoptosis. Illumina small-RNA sequencing was used to identify differentially expressed miRNAs in NC and LPS group. The target genes of differentially expressed miRNAs were predicted by miRanda and TargetScan, and the functional and pathway enrichment analysis was performed on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Further biological analysis of related miRNAs was carried out. Results After the LPS got induced, the cells became round and the integrity of cytoskeleton was destroyed. The decreased expression of VE-cadherin was also observed, along with the decreased ability of angiogenesis and migration, and increased apoptosis. Sequencing results showed a total of 229 differential miRNAs, of which 84 miRNA were up-regulated and 145 miRNA were down-regulated. The target gene prediction and functional enrichment analysis of these differential miRNA showed that they were mainly concentrated in pathways related to cell connection and cytoskeleton regulation, cell adhesion process and inflammation. Conclusion In vitro model of lung injury, multiple miRNAs are involved in the process of HPVECs cytoskeleton remodeling, the reduction of barrier function, angiogenesis, migration and apoptosis.
Humans ; Lipopolysaccharides/pharmacology* ; Endothelial Cells/metabolism* ; MicroRNAs/metabolism* ; Lung/metabolism* ; Cytoskeleton ; Gene Expression Profiling

A large number of data show that the prevalence rate of alcoholic liver injury （ALI） is increasing year by year， and it has become one of the main causes of death due to chronic liver diseases such as liver cancer and liver cirrhosis. Quitting drinking is the main method for the prevention of ALI in modern medicine， and the main treatment methods include Western medicine with antioxidant and anti－fibrotic effects and nutritional support. However， Western medicine tends to have an unsatisfactory treatment effect and can only alleviate initial symptoms， and severe ALI still requires surgical treatment. Studies have shown that the monomers extracted from natural drugs and foods have obvious preventive and therapeutic effects on ALI， with high safety and easy access. Therefore， this article systematically summarizes the main natural drug and food monomers used for the prevention and treatment of ALI and proposes the idea of the combination of drug and food for the prevention and treatment of ALI from the perspective of paying attention to the whole process of health， in order to explore more effective prevention， health care， and treatment methods and provide ideas for research on the prevention and control of ALI.

Objective To determine the impact of uric acid changes on kidney function in middle-aged and elderly women with normal renal function.Methods Serum uric acid and estimated glomerular filtration rate(eGFR) were studied by prospective cohort analysis in 1152 middle-aged and elderly Dalian women with serum uric acid<7 mg/dl, estimated glomerular filtration rate(eGFR)≥90 ml·min-1·(1.73 m2)-1, and age>45 years old.Results The analysis of variance (ANOVA) of clinical indices between baseline and follow-up data showed that an eGFR was decreased after three years in both middle-aged and elderly women even with normal serum uric acid.Compared with those in the lowest guartile subgroup, a significant drop of eGFR to less than 90 ml·min-1·(1.73 m2)-1 was seen in those with the highest guartile of baseline serum uric acid group (OR=1.707, 95%CI 1.192-2.443, P=0.003).Furthermore, there were positive correlations between changes in the levels of serum uric acid and eGFR, and linear regression analysis showed that, as the change level of serum uric acid increased, the change level of eGFR declined(β=1.562, 95%CI 1.050-2.075, P<0.01], and the changing degree of uric acid increase is independent risk factors refor eGFR reductions.Conclusion Reduction in eGFR level is inversely related to serum uric acid in perimenopausal and postmenopausal women.However, our study showed that, women with serum uric acid level ranging from normal, slight increase, and relatively high levels, the increasing degrees of uric acid are independent risk factors responsible for the changing degree of eGFR reduction.