Objective: To prepare the erythrocyte-liposome drug delivery system to enhance the therapeutic effect of drugs on tumors and inhibit tumor metastasis. Methods: This study prepared and characterized paclitaxel (PTX)-plerixafor (AMD3100) liposomes (Lips), developed the erythrocyte-liposome drug delivery system, and evaluated its targeting efficiency and therapeutic efficacy through a series of in vitro cellular and in vivo animal experiments. Results: The particle size of PTX-AMD-Lips was (186.4±0.83) nm. Drug encapsulation efficiency of PTX-AMD-Lips was (75.50±5.27)% for PTX and (88.31±2.45)% for AMD. The Binding efficiency between RBC and liposomes in the drug delivery system was (69.93±2.55)%. Vitro cellular experiments revealed that PTX-AMD-Lips significantly inhibited tumor cell migration. In vivo animal experiments, the erythrocyte-liposome drug delivery system significantly increased drug accumulation in the lungs. At the experimental endpoint, the quantitative fluorescence signal of tumor size measured (4.04±0.44)×10 for the PTX-Lips group, and (5.14±3.40)×10 for the RBC-PTX-AMD-Lips group. Conclusion: The erythrocyte-liposome drug delivery system could enhance the lung-specific targeting capability of liposomes, kill tumor cells and suppress further metastasis effectively.

Objective: To verify the inhibitory effect of a carbon monoxide hemoglobin-based oxygen carrier (CO-HBOC) on the fibrotic process in mice with idiopathic pulmonary fibrosis (IPF), clarify its efficacy difference compared with hemoglobin-based oxygen carriers (HBOCs), and elucidate its mechanism of action via proteomic analysis. Methods: CO-HBOC was prepared using gas loading technology. An IPF mouse model was established and the mice were randomly divided into a normal saline control group, an HBOC treatment group, and a CO-HBOC treatment group. The fibrotic area percentage was analyzed using Micro-CT; the degree of inflammatory infiltration and fibrosis in lung tissue was assessed by pathological section staining (e.g., HE and Masson staining); and differentially expressed proteins in lung tissue of IPF mice after CO-HBOC treatment were screened using proteomic technology. Results: Micro-CT results showed that the mean fibrotic area percentage in the CO-HBOC treatment group on day 21 was (8.89±0.98)%, which was better than that of the HBOC group (16.5±1.732)% and the normal saline group (30.75±6.45)% (P<0.05). HE and Masson staining results showed that the CO-HBOC group had reduced inflammatory cell infiltration and significantly decreased collagen fiber deposition in lung tissue, with a mean pathological score of 3.33±0.58, which was lower than that of the normal saline control group (8.33±1.53)(P<0.05); the mean collagen-positive area percentage was (3.33±1.53)%, significantly lower than that of the normal saline control group (14.00±3.61)% (P<0.05). Proteomic analysis identified 330 differentially expressed proteins, which were mainly enriched in inflammatory response regulatory pathways (such as the complement and coagulation cascades), and the expression changes of complement proteins may be the core target of CO-HBOC's anti-fibrotic effects. Conclusion: CO-HBOC can inhibit inflammatory responses and regulate fibrosis-related signaling pathways, there-by effectively inhibiting the fibrotic process in IPF mice, with superior efficacy to HBOC. Its mechanism of action involves the regulation of complement cascade-related signaling pathways and complement protein expression, providing an experimental and theoretical basis for targeted therapy of IPF.

Objective: To enhance the ability of nanoparticles to target and bind tumor cells by constructing a neutrophil hitchhiking system based on hyaluronic acid (HA)-modified dual-drug loaded lipid nanoparticles. Methods: Lipid nanoparticles (LNPs) were prepared using microfluidic technology, and the nitrogen/phosphate (N/P) ratio, flow rate ratio, and drug-to-lipid ratio were optimized. HA-modified LNPs (HA-LNPs) were prepared and characterized. The interaction between the nanoparticles and tumor cells was evaluated through in vitro cell experiments. Results: The optimal preparation conditions for LNPs are N/P=8, flow rate ratio=5, and drug-to-lipid ratio=1∶30 (w∶w). HA-LNPs has a particle size of (177.28±2.41) nm, a polydispersity index (PDI) of 0.198±0.10, and an siRNA encapsulation efficiency of (91.37±0.47)%. The optimal binding rate with neutrophils was (98.64±2.34)%. Conclusion: An HA-modified dual-drug loaded lipid nanoparticle-neutrophil hitchhiking system was successfully constructed, enhancing the synergistic anti-tumor activity of the nanomedicine and the uptake of nanoparticles by tumor cells, providing a novel delivery strategy for targeted therapy of bone marrow tumors.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

AIM:To compare the degree of disease simulation between the two mouse models of acute exacer-bation of chronic obstructive pulmonary disease(AECOPD)using intranasal instillation of lipopolysaccharide(LPS)and fine particulate matter(PM2.5)for 3 d based on exposure to cigarette smoke(CS)for 90 d.METHODS:Thirty-two male C57BL/6 mice were randomly divided into 4 groups:control group(n=8),CS group(n=8),CS+PM2.5 group(n=8)and CS+LPS group(n=8).The AECOPD models in CS+PM2.5 and CS+LPS groups were established by CS exposure combined with intranasal PM2.5 and LPS instillation.Lung function,lung pathology and airway goblet cell hyperplasia using histologi-cal staining were measured.To evaluate the degree of lung inflammation and mucus secretion in mice,the prorein levels of mucin 5AC(MUC5AC),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the bronchoalveolar lavage fluid(BALF)were detected by ELISA and total white blood cell(WBC)counts and the BALF differential cell counts(neutro-phils,macrophages,lymphocytes)were detected by Giemsa staining.RESULTS:In CS group,lung function decreased(P<0.05),and bronchial inflammation index increased(P<0.01),airway goblet cell hyperplasia and airway collagen de-position were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05),compared with control group.Compared with CS group,lung function decreased(P<0.05),the bronchial inflammation index increased(P<0.01),airway goblet cell hyperplasia and airway collagen deposition were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),and MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05)in CS+PM2.5 and CS+LPS groups.Compared with CS+PM2.5 group,lung function decreased(P<0.05),the bronchial inflamma-tion index increased(P<0.01),airway goblet cell hyperplasia and airway collagen deposition were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),and MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05)in CS+LPS group.CONCLUSION:Exposure to CS combined with both intrana-sal PM2.5 and LPS instillation allowed for establishing AECOPD models in mice,and CS exposure combined with intrana-sal LPS instillation better simulated AECOPD characteristics.

In recent years,the Ross procedure has been increasingly applied in the treatment of aortic valve disease in children and young patients.However,right ventricular outflow tract(RVOT)reconstruction in this procedure often relies on allogeneic or artificial materials,which may lead to complications such as calcification and valve dysfunction.This article reports a case of protective Ross procedure using completely autologous tissue to construct a right ventricular-pulmonary artery(RV-PA)conduit.The patient was an 11-year-old male who presented with severe aortic stenosis combined with regurgitation.During the operation,his dilated ascending aortic wall and fresh pericardium were used to construct an autologous valved conduit for RV-PA reconstruction.This innovative technique achieves RV-PA reconstruction without allogeneic tissue,provides a new technical approach for the Ross procedure.Short-term results are satisfactory and the medium-and long-term outcomes require further follow-up verification.

AIM:To investigate the effects of nebulized sodium tanshinone ⅡA sulfonate(STS)in a mouse model of pulmonary hypertension associated with chronic obstructive pulmonary disease(COPD-PH).METHODS:A to-tal of 32 healthy SPF-grade male C57BL/6 mice were randomly divided into 4 groups:control(CTL,n=8)group,COPD-PH(CS+LPS,n=8)group,STS-treated COPD-PH(CS+LPS+STS,n=8)group,and STS(n=8)group.The COPD-PH model was established through whole-body exposure to cigarette smoke(CS)combined with lipopolysaccharide(LPS)in-halation.Mice were subjected to cigarette smoke exposure in a chamber(9 cigarettes/h,2 h/session,2 sessions/d,6 d/week)for 60 d,except on days of LPS inhalation.On days 1 and 14,COPD-PH model mice received LPS(7.5 μg/mouse in 50 μL saline)via intranasal inhalation,while the CTL and STS groups received an equivalent volume of saline.STS was administered via nebulized inhalation(5 mg/kg,30 min per session,twice daily)immediately before CS exposure.At the end of the modeling period,lung function and right heart pressure were assessed.Bronchoalveolar lavage fluid(BALF)was collected for inflammatory cell counting.Levels of interleukin-6(IL-6)in BALF supernatants and plasma were measured using ELISA.Pathological changes in the airway and lung tissues were evaluated.RESULTS:(1)Com-pared to CTL mice,those exposed to CS and LPS exhibited lesions characteristic of COPD-PH,including emphysema,lung inflammation,decreased lung function,and increased right ventricular systolic pressure(RVSP)and right ventricu-lar hypertrophy index(RVHI)(P<0.05);(2)COPD-PH mice showed significantly elevated IL-6 levels in both BALF and plasma(P<0.05);(3)STS treatment alleviated emphysema and lung inflammation,improved lung function,prevent-ed increases in RVSP and the RV/(LV+S)ratio,and reduced IL-6 levels in both BALF and plasma(P<0.05).CON-CLUSION:The results indicate that nebulized inhalation of STS significantly slows the progression of COPD-PH,likely due to its ability to inhibit lung inflammation and reduce IL-6 expression in the lungs.

Objective To build a hospital data service portal system based on central authentication service(CAS)to solve the problems of dispersed user identity data and low management efficiency caused by independent operation of multiple systems.Methods The CAS-based hospital data service portal system was designed with B/S architecture and developed with Spring MVC framework,which implemented unified authentication with CAS technology and achieved standardized access protocols for integrated access,centralized management and service consolidation across various application systems.There were five functional modules involved in the system for homepage,workflow management,system administration,log management and message management.Results The system significantly enhanced user accessibility and data extraction efficiency,effectively reduced the complexity of system integration and operational maintenance burdens and ensured user privacy and data security.Conclusion The portal system provides users with an easy-to-use,secure and reliable data service portal,laying the foundation for building an efficient,intelligent and safe hospital data service system.

Objective:To investigate the clinical application effect of Zishen Yutai Pill in patients with repeated implantation failure (RIF) undergoing frozen-thawed embryo transfer (FET) cycles.Methods:A retrospective case-control study was conducted, selecting 744 cycles of patients with RIF at the Department of Female Reproductive Medicine,State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University from October 2017 to April 2023. The patients were divided into experimental group (treated with Zishen Yutai Pill, n=279) and control group (treated without Zishen Yutai Pill, n=465) based on whether Zishen Yutai Pill was added to luteal support. The pregnancy outcomes between the two groups were compared. Based on the different endometrial preparation protocols in the FET cycles, the patients were used down-regulation protocol ( n=271) or non-down-regulation protocol ( n=473). The pregnancy outcomes of the two groups in each protocol were compared. Results:There were no statistically significant differences between the two groups in terms of biochemical pregnancy rate, clinical pregnancy rate, embryo implantation rate, early miscarriage rate, late miscarriage rate, and live birth rate (all P>0.05). However, the biochemical pregnancy rate [69.0% (58/84)], clinical pregnancy rate [59.5% (50/84)], and embryo implantation rate [59.4% (57/96)] in the experimental group of the down-regulated protocol were significantly higher than those in control group [56.1% (105/187), P=0.045; 46.5% (87/187), P=0.048; 44.9% (92/205), P=0.019], with statistically significant differences. In the non-down-regulated protocol, there were no statistically significant differences in pregnancy outcomes between the two groups (all P>0.05). Conclusion:In the FET down-regulated protocol, Zishen Yutai Pill can significantly improve the clinical pregnancy rate and the embryo implantation rate in patients with RIF, thereby improving pregnancy outcomes.

Objective To compare the accuracy and clinical application value of contrast-induced fractional flow reserve(cFFR),resting full-cycle ratio(RFR),and quantitative flow ratio(QFR)in evaluating coronary artery borderline lesions,using fractional flow reserve(FFR)as the gold standard.Methods A retrospective study was conducted including 143 patients with 143 lesions who underwent coronary angiography(CAG)and were tested for cFFR,RFR,QFR,and FFR at Peking University Third Hospital from September 2020 to January 2022.Clinical data,CAG lesion anatomical data,and target vessel cFFR,RFR,QFR,and FFR measurements were collected.The correlation and diagnostic concordance of cFFR,RFR,QFR,and FFR were analyzed.Results The mean age of the 143 patients was 66(58,71)years,with 90(62.9％)being male.Among them,60(42.0％)patients were diagnosed with unstable angina,and 115(80.4％)target lesions were located in the left anterior descending artery.Correlation analysis showed that RFR,QFR,and cFFR were all significantly correlated with FFR(r=0.956,r=0.861,r=0.751,P＜0.001).Bland-Altman analysis demonstrated high agreement between cFFR,RFR,QFR,and FFR.Receiver operating characteristics(ROC)curve analysis showed that the area under the curve(AUC)for RFR corresponding to FFR ≤0.80 was 0.92(95％CI 0.87-0.96),for QFR was 0.89(95％CI 0.83-0.95),and for cFFR was 0.96(95％CI 0.94-0.99).Conclusions cFFR,RFR,and QFR show high concordance with FFR,with similar diagnostic consistency between the three methods and FFR.