ObjectiveTo investigate the therapeutic mechanism of Xuefu Zhuyutang （XFZYT） for metabolic-associated fatty liver disease （MAFLD） through integrated network pharmacology and animal experiments. MethodsNetwork pharmacology was utilized to predict the core components， key therapeutic targets， and signaling pathways of XFZYT in the treatment of MAFLD. For animal experiments， a rat model of MAFLD was established by feeding a high-cholesterol diet for 4 weeks. Intervention was then administered with low-dose （2 g·kg^-1） and high-dose （4 g·kg^-1） XFZYT for 2 weeks. Biochemical assays were performed to measure the serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. In addition， the activities of superoxide dismutase （SOD） and catalase （CAT） and levels of malondialdehyde （MDA） and glutathione （GSH） in the serum were measured. The same way was adopted to measure the levels of TC and TG in the liver tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the serum levels of interleukin （IL）-6， IL-1β， and tumor necrosis factor-alpha （TNF-α）. Histopathological evaluations included hematoxylin and eosin （HE） staining for liver tissue morphology， Oil Red O staining for lipid deposition， and dihydroethidium （DHE） probe staining for reactive oxygen species （ROS） levels. Western blot analysis was conducted to assess the protein levels of AMP-activated protein kinase （AMPK）， phosphorylated （p）-AMPK， nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， nuclear factor-kappa B （NF-κB）， and p-NF-κB in the liver tissue. Untargeted metabolomics analysis of the serum was performed by liquid chromatography-tandem mass spectrometry （LC-MS/MS）. ResultsNetwork pharmacology analysis predicted 155 potential targets of XFZYT for MAFLD treatment， with core targets including signal transducer and activator of transcription 3 （STAT3）， protein kinase B1 （Akt1）， TNF， and IL-6. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment primarily implicated the AMPK signaling pathway. Animal experiments demonstrated that compared with the normal group， the model group exhibited dyslipidemia， hepatic function impairment， pronounced hepatic lipid deposition， and inflammatory manifestations， with elevated serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， reduced HDL and GSH levels plus decreased SOD and CAT activities （P<0.05）， downregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and upregulated protein level of p-NF-κB （P<0.05） in the liver tissue. Compared with the model group， XFZYT intervention groups showed significant amelioration of dyslipidemia and hepatic function impairment， markedly reduced hepatic lipid deposition and inflammatory cell infiltration， decreased serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， increased HDL and GSH levels plus enhanced SOD and CAT activities （P<0.05）， upregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and downregulated protein level of p-NF-κB （P<0.05）. Serum metabolomics revealed 511 differentially expressed metabolites （231 upregulated and 280 downregulated） between normal and model groups， while XFZYT groups versus model group showed 94 differential metabolites （51 upregulated and 43 downregulated）. Among them， 11 metabolites displayed the most significant alterations， with enriched pathways including glycerolipid metabolism， cholesterol metabolism， and insulin resistance， multiple of which demonstrated AMPK association. ConclusionXFZYT alleviates MAFLD by regulating the AMPK signaling pathway and associated metabolic networks.

As a key treatment method for end-stage liver diseases, long-term efficacy of liver transplantation is limited by rejection and serious complications such as liver and kidney toxicity, infection risks and tumor recurrence caused by immunosuppressive drugs. In recent years, nanotechnology, with its targeted delivery capabilities and spatio-temporal controlled release characteristics, has demonstrated great potential in precisely regulating immune responses. This article systematically reviews the multi-level application strategies and mechanisms of nanomedicine in the immunoreprogramming of liver transplantation, covering innate immunoreprogramming (phenotypic transformation of Kupffer cells or macrophages, inhibition of inflammasomes and mitochondrial repair), adaptive immune remodeling (targeted regulation of dendritic cells, gene silencing vectors and reprogramming of T cell functions), and elaborates on the strategies for coordinated regulation of the microenvironment. The article also focuses on the targeted application of liver sinusoidal endothelial cells. In response to clinical translation bottlenecks, innovative solutions such as the design of degradable polymer carriers, the construction of intelligent response systems and the optimization of large-scale production pathways are proposed, providing theoretical support and practical directions for achieving the paradigm shift from "global immunosuppression" to "precise immune tolerance".

BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.

There is a complex biological mechanism in the phosphatidylinositol-3-kinase(PI3K)/protein kinase B(PKB/Akt)/mammalian target of rapamycin(mTOR)signaling pathway,which plays a key role in the development and development of lymphoma.In this review,the relevant literature of PI3K inhibitor research in the past five years summarized and analyzed,and found that the research and development,application,efficacy,and adverse reactions of PI3K inhibitors are the current research hotspots,and the positive results of PI3K inhibitors in clinical trials and basic research have strongly demonstrated the potential of PI3K inhibitors in personalized treatment of lymphoma.In order to maximize the clinical benefits,a variety of strategies need to be explored,including novel drugs with better selectivity and safety,and related combination therapies.

Objective:To explore the training experiences of palliative care nurses participating in a prognosis disclosure workshop based on Kolb's experiential learning model, and to provide references for future educational programs in palliative care nursing.Methods:Using purposive sampling, 11 nurses were recruited who had participated in the "Palliative Care Competency Training Program for Nurses" in Shanghai between March and May 2025 and selected the Third Affiliated Hospital of Naval Medical University as their clinical training site. Semi-structured interviews were conducted, and data were analyzed using Colaizzi's seven-step method.Results:A total of three major themes emerged: a sense of benefit from enhanced competencies; complex emotional experiences; recommendations for course optimisation.Conclusions:Workshops based on Kolb's experiential learning model offer positive value in palliative care education. They effectively improve core competencies such as communication and empathy. However, the emotional experiences of nurses must also be considered, and multifaceted optimizations to the training design are recommended to further enhance training outcomes.

Objective:To investigate the effect of circular RNA (circRNA)_005987 on contrast-associated acute kidney injury (CA-AKI) and its mechanism, and provide new ideas for the prevention and treatment of CA-AKI.Methods:CA-AKI rat models and HK-2 cell injury models were established using iopromide, and CA-AKI-related circRNA_005987 was screened based on circRNA expression chip and real-time quantitative PCR (RT-qPCR). Knockdown and overexpression of circRNA_005987 were performed in HK-2 cell model, respectively. Cell counting kit-8 (CCK-8) and Edu staining assays were used to evaluate cell proliferation. Western blotting was used to detect the protein expression of autophagy-related protein microtubule-associated protein 1 light chain 3B (LC3B), P62, beclin-1 and autophagy-related gene 14 (ATG14). Immunofluorescence staining was used to detect protein expression of LC3B. Electron microscope was used to observe the autophagosome formation. Autophagy activator rapamycin and autophagy inhibitor 3-methyladenine were used for in vitro rescue experiments to observe the changes of the above indicators. Mechanistically, bioinformatics analysis was applied to analyze the binding site among circRNA_005987, miR-129-5p and ATG14, and dual luciferase reporter assay was used to verify their interactions. CircRNA_005987 was knocked down and overexpressed in HK-2 cell model, and RT-qPCR was used to detect the expression of miR-129-5p. HK-2 cells were treated with miR-129-5p inhibitor and mimic, Western blotting was used to detect the protein expression of ATG14, and CCK8 and Edu staining assays were used to evaluate cell proliferation. Results:CircRNA_005987 expression was up-regulated in vitro and vivo CA-AKI models (both P<0.05). Overexpression of circRNA_005987 inhibited cell proliferation and promoted cell autophagy, while knockdown of circRNA_005987 had opposite effects (all P<0.05). In vitro rescue experiments confirmed that circRNA_005987 inhibited cell proliferation by activating autophagy ( P<0.05). The dual luciferase reporter assay suggested that there was an interaction between circRNA_005987, miR-129-5p and ATG14. Knockdown of circRNA_005987 increased miR-129-5p expression, while overexpression of circRNA_005987 inhibited miR-129-5p expression (both P<0.05). Knockdown of miR-129-5p inhibited cell proliferation, while overexpression of miR-129-5p reversed the effect (both P<0.05). Conclusion:CircRNA_005987 promotes CA-AKI through activating autophagy via sponging miR-129-5p, suggesting that circRNA_005987 plays an important role in the pathological process of CA-AKI.

Objective:To analyze the serological and molecular characteristics of rare A el and B el subtypes in the ABO blood group system, and to explore their genotype-phenotype correlation and the potential clinical significance. Methods:From January 1st, 2021, to January 1st, 2025, 289, 815 samples subjected to ABO blood grouping in Henan Provincial People′s Hospital were selected. Samples demonstrating discrepancies between forward and reverse typing, or consistent typing but with abnormal agglutination degree were included. Those affected by underlying diseases, transplantation, age-related and other interferences were excluded. A total of 169 suspected ABO subgroup samples were identified. Sanger sequencing of exons 1-7 and relevant regulatory regions of the ABO gene was performed. Protein structure modeling and mutation effect analysis for two'el′ subtype glycosyltransferases (GTs) were conducted using SWISS-MODEL and PyMOL.Results:A total of 12 Ael, 6 B el, and 2 AB el subtypes were identified. Serological analysis revealed that all 18 A el/B el samples exhibited O phenotype in forward typing. Among them, A el subtypes showed weaker agglutination in reverse typing with A 1c than with Bc (>2+), while the opposite pattern was observed in B el subtypes. The two AB el samples were typed as A in forward typing, with agglutination ranging from 0-1+with Bc in reverse typing. Genetic analysis indicated that AEL.02 (c.646T>A, p.Phe216Ile) was the predominant allele in A el samples accounting for 7 cases. Also, we found an AEL.02-like variant (lacking c.681G>A), AEL.10 (c.963insC), and carrying a compound variant of c.322C>T (p.Gln108Ter) and c.296C>T (p.Thr99Ile). Among B el samples, BEL.03 (c.502C>T, p.Arg168Trp) accounted for 4 cases, one of which lacked the c.297A>G mutation, and novel mutations such as c.145_146dupCG were detected. Structural simulation demonstrated that AEL.02 and BEL.03 disrupted the hydrogen-bonding network within the active centers of GTA and GTB, respectively, and these mutations probably significantly impaired the structural stability of the corresponding GTs. Additionally, the c.296C>T mutation also markedly affected GTA structural stability. Conclusion:A el/B el subtypes are prone to mis-identify routine blood types. Their molecular mechanisms involved a variety of functional variantions, and integrating molecular detection is crucial for achieving accurate sub-typing and transfusion safety.

Objective:To evaluate the screening efficacy and clinical management strategies of cell-free fetal DNA (cffDNA) for copy number variations (CNVs) at 16p13.11-p12.3.Methods:Clinical data of 35 fetuses with high-risk indications for 16p13.11-p12.3 variations identified by non-invasive prenatal test (NIPT) at the First Affiliated Hospital of Zhengzhou University between September 2018 and December 2023 were retrospectively analyzed. Amniocentesis was performed to obtain fetal samples, followed by validation through chromosomal karyotyping and CNV-sequencing. The variant size, genetic origin, and pregnancy outcomes were systematically assessed. Statistical analysis was conducted using Pearson's Chi-square test or Fisher's exact test. Results:(1) Screening efficacy: The overall positive predictive value (PPV) of cffDNA was 45.8% (11/24), with a PPV of 4/8 for deletions and 7/16 for duplications. The false-positive rate was 54.2% (13/24), including one case complicated by a Robertsonian translocation [45,XY,rob(21;22)]. (2) Genetic characteristics: Among confirmed variants, 8/11 were inherited (six maternal duplications, one paternal deletion), while 3/11 were de novo (one deletion and two of undetermined origin). (3) Clinical outcomes: Among live births, 3/9 confirmed cases exhibited abnormal manifestations, including conductive hearing loss (one case with maternal duplication), language developmental delay (one case with 16p13.11 tetrasomy combined with trisomy), and hypotonia (one case with de novo deletion). Follow-up of false-negative or undiagnosed fetuses (22 cases) and 6/9 of confirmed cases showed no abnormalities. Conclusion:CNVs at 16p13.11-p12.3 demonstrate significant incomplete penetrance. Invasive diagnosis combined with familial analysis is recommended for cffDNA-positive cases. Genetic counseling should emphasize variant size and parental origin, and long-term neurodevelopmental follow-up mechanisms should be established for confirmed fetuses.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.