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.

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.

ObjectiveTo investigate whether modified Taohe Chengqitang （JTCT） treats liver fibrosis by inhibiting hepatic sinusoidal capillarization， and to verify whether its specific mechanism is related to the Homologous genes responsible for the notches along the edges of Drosophila wings（Notch） signaling pathway and endothelial nitric oxide synthase （eNOS） signaling pathway. MethodsFifty C57BL/6 mice were randomized into 5 groups： Control， model （5 mL·kg^-1·3 d^-1）， low-dose JTCT， medium-dose JTCT， and high-dose JTCT （JTCT-L，JTCT-M，JTCT-H）. Except the control group， the other groups were intraperitoneally injected with 20% carbon tetrachloride （CCl₄） olive oil solution every 3 days for 4 weeks to induce liver fibrosis. Meanwhile， JTCT-L， JTCT-M， and JTCT-H groups were administrated with JTCT by gavage at doses of 16.6， 33.3， and 66.6 g·kg^-1·d^-1， respectively， for 4 consecutive weeks （the control and model groups received equal volumes of normal saline by gavage）. Primary liver sinusoidal endothelial cells （LSECs） were isolated from rat livers through in situ perfusion of collagenase， Percoll density gradient centrifugation， and selective removal of Kupffer cells. After verification of cell phenotype， LSECs were used for experiments. For cells at the logarithmic growth phase， the small interfering RNA（siRNA） kit was used to knock down the expression of soluble guanylate cyclase （sGC） through transient transfection. Subsequently， the Notch agonist Jagged-1 was applied. Cell counting kit-8 （CCK-8） was used to examine the cytotoxicity of JTCT on LSECs. Real-time PCR and Western blot were employed to measure the expression of molecules in the Notch and eNOS signaling pathways at mRNA and protein levels， respectively. Intracellular Ca²⁺ was labeled with the fluorescent probe Fluo-4 acetoxymethyl ester（Fluo-4/AM）. ResultsThe animal experiment showed that compared with the control group， the model group exhibited hepatic steatosis， inflammatory cell infiltration， hepatocyte degeneration and necrosis， lobular structural disorder， and fibrous tissue hyperplasia in the mouse liver tissue， significantly elevated serum levels of hydroxyproline （Hyp）， alanine transaminase （ALT）， and aspartate transaminase （AST） （P<0.01）， significantly upregulated expression levels of Notch1， Hes family bHLH transcription factor 1（Hes1）， Cluster of Differentiation 31（CD31）， and von Willebrand factor（vWF） （P<0.01）， and significantly downregulated phosphorylate（p）-eNOS/eNOS ratio and sGC expression （P<0.01）. Compared with the model group， all the JTCT groups showed significantly reduced serum Hyp， ALT， and AST levels （P<0.01）， downregulated expression of Notch1， Hes1， CD31， and vWF （P<0.05， P<0.01）， and upregulated p-eNOS/eNOS ratio and sGC expression （P<0.05， P<0.01） in the liver tissue， with the JTCT-H group showing the most significant changes （P<0.01）. The cell experiment showed that compared with the LSEC-1day group， the LSEC-5day group exhibited significantly increased expression of Notch1， Hes1， CD31， and vWF （P<0.01）， significantly decreased p-eNOS/eNOS ratio and sGC expression （P<0.01）， and elevated intracellular Ca²⁺ concentration （P<0.01）. Compared with the LSEC-5day group， the JTCT group showed decreased expression of Notch1， Hes1， CD31， and vWF （P<0.01）， significantly increased p-eNOS/eNOS ratio （P<0.01）， and significantly reduced intracellular Ca²⁺ concentration （P<0.01）. No significant differences were observed in the expression of Notch1， Hes1， eNOS， p-eNOS， CD31， vWF， sGC， or intracellular Ca²⁺ concentration between the Jagged1 group and the Jagged1+JTCT group. Compared with the LSEC-5day group， the sGC knockout group （sGC-KO） showed significantly increased expression of CD31 and vWF （P<0.01）. There was no significant difference in CD31 or vWF expression between the sGC-KO group and the sGC-KO+JTCT group. ConclusionJTCT inhibits the activation of the Notch signaling pathway and restores the activity of the eNOS signaling pathway to suppress sinusoidal capillarization of LSECs， thereby treating liver fibrosis.

Objective To develop a postoperative precision nursing program for children with obstructive sleep apnea-hypopnea syndrome(OSAHS),so as to provide references for the improvement of nursing quality for children with OSAHS.Methods Literature in precision nursing for children with OSAHS was systematically reviewed and summarised based on precision nursing theory and a postoperative precision nursing program was drafted.Using the Delphi's Method,two rounds of expert consultation were conducted and the postoperative precision nursing program for children with OSAHS was revised and finalised.Results The response rates of the two rounds of expert consultation were 100.00%with the expert authority coefficient of 0.875.The Kendall coefficient of concordance(W)of levels 1,2 and 3 indices in the second round of expert consultation were 0.289,0.203,0.187,respectively(all P<0.01).The importance score of each inclicator ranged from 4.50～4.94.The coefficient of variations for the three-level indices ranged from 0.05 to 0.21.The finalised program composed 8 level-1 indices(postoperative position assessment,intervention,prevention and care of bleeding,maintaining postoperative airway patency,postoperative nausea and vomiting care,postoperative pain assessment and care,dietary care,complication prevention and care,discharge guidance),16 level-2 indices,and 22 level-3 indices.Conclusion The postoperative precision nursing program for the children with OSAHS is scientific,innovative and applicable.It provides clinical references for nursing of the children with OSAHS.

Objective:To explore the feasibility and efficacy of left ventricular decompression in pediatric patients supported by extracorporeal membrane oxygenation（ECMO）.Methods:The clinical data of 15 children who underwent left ventricular decompression during ECMO in the cardiac intensive care unit（CICU）of Guangzhou Women and Children's Medical Center from February 2021 to August 2023 were retrospectively analyzed.Results:Among the 15 patients，there were 8 males and 7 females,with a median age of 1.1 years old（20 days to 15 years old）and a median weight of 8.5（3.1 to 38.0）kg. Cardiac pathologies varied，including hypertrophic obstructive cardiomyopathy(1 case),left coronary artery abnormalities originating from the pulmonary artery（3 cases），aortic coarctation with ventricular septal defect（1 case），complete transposition of great arteries with ventricular septal defect（1 case），ventricular septal defect with severe mitral valve insufficiency（1 case），fulminant myocarditis（5 cases），tetralogy of Fallot（1 case），ascending aortic aneurysm with aortic valve insufficiency（1 case），and Kawasaki disease complicated with giant aneurysm（1 case）. The venous-arterial ECMO mode was used in all 15 children,9 cases were intubated centrally and 6 cases were intubated peripherally. The reasons for ECMO：low cardiac output（8 cases），cardiogenic shock（5 cases），and frequent ventricular tachycardia and ventricular fibrillation（2 cases）. Extracorporeal cardiopulmonary resuscitation was performed in 3 cases. The median duration of mechanical ventilation was 248 (142-590) h,the median CICU stay was 18 (7-26) d,and the median hospital stay was 28 (7-37) d. Of the 15 children,7 cases underwent emergency left ventricular decompression through a small sternal incision,with a mean decompression time of ECMO-assisted 12.2(9-22) h，and 8 cases underwent selective left ventricular decompression through a median sternal incision. Left ventricular systolic function improved significantly after decompression in all 15 patients，of whom 12 cases were successfully withdrew off ECMO and 10 cases of them survived.Conclusion:Left ventricular decompression can improve the cardiac dysfunction in children with ECMO，reduce the occurrence of complications，and increase the success rate and survival rate of ECMO.

Objective:To evaluate the effect of baicalein on acute myocardial injury in rats with high-level spinal cord injury (SCI) and the role of nuclear factor E2-related factor 2 (Nrf2).Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (Sham group), SCI group, SCI+ baicalein group (SCI+ Bai group) and SCI+ baicalein+ ML385 group (SCI+ Bai+ ML385 group). The high-level SCI rat model was established by the modified Allens method. In Sham group, the 7th cervical vertebra (C 7) was only exposed, but the spinal cord was not hit. In SCI group, C 7 was exposed and the spinal cord was hit. In SCI+ Bai group, baicalein 50 mg/kg was intraperitoneally injected immediately after SCI. In SCI+ Bai+ ML385 group, Nrf2 inhibitor ML385 30 mg/kg was intraperitoneally injected at 1 h before SCI, and baicalein 50 mg/kg was intraperitoneally injected immediately after SCI. The rats were anesthetized at 24 h after SCI and sacrificed after the blood samples from the abdominal aorta were collected and the hearts were taken for microscopic examination of the pathological changes (by HE staining) which were scored and the ultrastructure of cells (with a transmission electron microscope) and for determination of the serum cardiac troponin I (cTnI) concentrations (by enzyme-linked immunosorbent assay), content of ferrous ion (Fe 2+ ) in myocardial tissues (by colorimetry), contents of malondialdehyde(MDA) and glutathione (GSH) and activity of superoxide dismutase(SOD) in myocardial tissues (by biochemical method) and expression of glutathione peroxidase 4 (GPX4), acyl CoA synthase long chain family member 4 (ACSl4) and Nrf2 protein and mRNA in myocardial tissues (by Western blot and fluorescent quantitative polymerase chain reaction). The mitochondrial Flameng score was assessed and recorded. Results:Compared with Sham group, the pathological score, mitochondrial Flameng score and serum cTnI concentrations were significantly increased, the contents of Fe 2+ and MDA in myocardial tissues were increased, the content of GSH and SOD activity were decreased, the expression of GPX4 was down-regulated, and the expression of ACSL4 and Nrf2 was up-regulated in SCI group ( P<0.05). Compared with SCI group, the pathological score, mitochondrial Flameng score and serum cTnI concentration were significantly decreased, the contents of Fe 2+ and MDA in myocardial tissues were decreased, the contents of GSH and SOD activity were increased, the expression of GPX4 and Nrf2 was up-regulated, and the expression of ACSL4 was down-regulated in SCI+ Bai group ( P<0.05). Compared with SCI+ Bai group, the pathological score, mitochondrial Flameng score and serum cTnI concentrations were significantly increased, the contents of Fe 2+ and MDA in myocardial tissues were increased, the content of GSH and SOD activity were decreased, the expression of GPX4 and Nrf2 was down-regulated, and the expression of ACSL4 was up-regulated in SCI+ Bai+ ML385 group ( P<0.05). Conclusions:Baicalein can alleviate acute myocardial injury in rats with high-level SCI, and Nrf2 is involved in this process.

Objective:To evaluate the effect of baicalein on acute myocardial injury in rats with high-level spinal cord injury (SCI) and the role of nuclear factor E2-related factor 2 (Nrf2).Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (Sham group), SCI group, SCI+ baicalein group (SCI+ Bai group) and SCI+ baicalein+ ML385 group (SCI+ Bai+ ML385 group). The high-level SCI rat model was established by the modified Allens method. In Sham group, the 7th cervical vertebra (C 7) was only exposed, but the spinal cord was not hit. In SCI group, C 7 was exposed and the spinal cord was hit. In SCI+ Bai group, baicalein 50 mg/kg was intraperitoneally injected immediately after SCI. In SCI+ Bai+ ML385 group, Nrf2 inhibitor ML385 30 mg/kg was intraperitoneally injected at 1 h before SCI, and baicalein 50 mg/kg was intraperitoneally injected immediately after SCI. The rats were anesthetized at 24 h after SCI and sacrificed after the blood samples from the abdominal aorta were collected and the hearts were taken for microscopic examination of the pathological changes (by HE staining) which were scored and the ultrastructure of cells (with a transmission electron microscope) and for determination of the serum cardiac troponin I (cTnI) concentrations (by enzyme-linked immunosorbent assay), content of ferrous ion (Fe 2+ ) in myocardial tissues (by colorimetry), contents of malondialdehyde(MDA) and glutathione (GSH) and activity of superoxide dismutase(SOD) in myocardial tissues (by biochemical method) and expression of glutathione peroxidase 4 (GPX4), acyl CoA synthase long chain family member 4 (ACSl4) and Nrf2 protein and mRNA in myocardial tissues (by Western blot and fluorescent quantitative polymerase chain reaction). The mitochondrial Flameng score was assessed and recorded. Results:Compared with Sham group, the pathological score, mitochondrial Flameng score and serum cTnI concentrations were significantly increased, the contents of Fe 2+ and MDA in myocardial tissues were increased, the content of GSH and SOD activity were decreased, the expression of GPX4 was down-regulated, and the expression of ACSL4 and Nrf2 was up-regulated in SCI group ( P<0.05). Compared with SCI group, the pathological score, mitochondrial Flameng score and serum cTnI concentration were significantly decreased, the contents of Fe 2+ and MDA in myocardial tissues were decreased, the contents of GSH and SOD activity were increased, the expression of GPX4 and Nrf2 was up-regulated, and the expression of ACSL4 was down-regulated in SCI+ Bai group ( P<0.05). Compared with SCI+ Bai group, the pathological score, mitochondrial Flameng score and serum cTnI concentrations were significantly increased, the contents of Fe 2+ and MDA in myocardial tissues were increased, the content of GSH and SOD activity were decreased, the expression of GPX4 and Nrf2 was down-regulated, and the expression of ACSL4 was up-regulated in SCI+ Bai+ ML385 group ( P<0.05). Conclusions:Baicalein can alleviate acute myocardial injury in rats with high-level SCI, and Nrf2 is involved in this process.

[Objective] To investigate the effect of Shenmai injection on the preservation quality of suspended red blood cells of high hemoglobin population in Xizang plateau. [Methods] Whole blood (400 mL, n=8) collected by the Xizang Autonomous Region Blood Center was centrifuged at 3 000 g for 10 minutes to remove most of the plasma, followed by the addition of 100 mL of MAP preservation solution to obtain plateau suspended red blood cells, which were then divided into three equal portions. One portion was the control group, and another part had 15 mL of MAP preservation solution added, which was the dosage group. The third portion involved diluting Shenmai injection with MAP, followed by addition of 15 mL of MAP preservation solution containing Shenmai to the red blood cells, resulting in a final concentration of Shenmai injection of 1%, which was the Shenmai group. Blood routine, pH value, electrolytes, glucose, lactate, free Hb, adenosine triphosphate (ATP), P50, phosphatidylserine (PS) and other indicators were detected at day 1, 21 and 35, respectively. [Results] The Hb concentration and Hct of the dosage group and the Shenmai group were significantly lower than those of the control group, with values of (179.3±17.8) vs (181.0±17.1) vs (199.1±19.5) g/L for Hb concentration and (53.2±2.6)% vs (53.3±2.5)% vs (58.4±3.1)% for Hct. The three groups maintained this pattern until the end of storage. In the middle and late stages of preservation, the glucose and Na⁺ contents in the dosage group and the Shenmai group were higher than those in the control group, while the lactate and K⁺ contents were lower than those in the control group. At the end of storage, the glucose and Na⁺ content of the Shenmai group was higher than that of the dosage group, while the lactate and K⁺ content were lower than that of the dosage group. From day 1 to day 35 of storage, the hemolysis rate of the Shenmai group was significantly lower than that of the control group and the dosage group. On day 21 and 35 of storage, the PS expression rate in the Shenmai group was significantly lower than that in the control group and the dosage group, which were (6.52±0.40)% vs (7.24±0.91)% vs (8.27±0.93)% and (7.29±0.53)% vs (9.37±0.82)% vs (8.39±0.76)%, respectively. [Conclusion] The hemolysis rate and PS of suspended red blood cells of Xizang high altitude prepared by adding Shenmai injection were significantly lower than those in the control group and the dosage group, which was conducive to reducing hemolysis and slowing down the aging of red blood cells, and had a certain improvement on the preservation quality of suspended red blood cells in Xizang plateau people.

[Objective] To use Chitosan Methacryloyl (CSMA) loaded with artificial platelet-derived exosomes (aPexos) as the needle body material, and gelatin and carboxymethyl chitosan (CMCS) loaded with Epigallocatechin gallate(EGCG) as the backing material to prepare microneedles, aims to investigate the therapeutic effect and mechanism of aPexos-EGCG microneedles in the treatment of burn wound healing. [Methods] First, aPexos were extracted using ultrasound and gradient ultracentrifugation. The concentration, morphology, and growth factor content (TGF-β1, PDGF-BB, VEGF) of the exosomes were assessed using NTA, transmission electron microscopy, and ELISA kits. The aPexos and EGCG were then dissolved in the needle body and backing materials, respectively. The aPexos and EGCG were loaded into the needle body and backing layer, respectively. The morphology, mechanical properties, and puncture performance of the microneedles were examined, and the preparation conditions for the microneedles loaded with aPexos-EGCG were optimized. Finally, animal experiments and tissue staining were conducted to assess the efficacy of the aPexos-EGCG microneedles in promoting burn wound healing in rats. [Results] The size distribution of aPexos was mainly in the range of 50-150 nm, with an average diameter of 132.7±3.8 nm and an average concentration of approximately 2.88×10¹³±3.62×10¹² particles/mL. The concentrations of TGF-β1, PDGF-BB, and VEGF were approximately 1 363±135.9 ng/mL, 63.5±14.8 ng/mL, and 1 606.0±77.5 pg/mL, respectively. Mechanical property testing of the microneedles indicated that, compared with the blank microneedles, the drug-loaded microneedles had sufficient piercing ability to penetrate the stratum corneum of the skin. The results of the rat burn wound healing experiment showed that the wound healing rates of the d 3, d 7, aPexos-EGCG microneedle group compared to the control group showed significant differences, with respective values of (47.64±12.5)% vs (18.11±6.40)%, (87.45±5.57)% vs (79.85±5.03)%(P<0.05). Hematoxylin-eosin (HE) staining revealed more intact epidermal layers in the aPexos-EGCG microneedle group. Masson staining showed that the collagen deposition percentage in the aPexos-EGCG microneedle group was higher than in the control group. Immunofluorescence staining results indicated that the aPexos-EGCG microneedle group had a reduced content of M1-type macrophages and an increased content of M2-type macrophages. Additionally, the vascular markers CD31 and α-SMA showed elevated expression in this group, with significant differences compared to the other groups (P<0.05). [Conclusion] The aPexos-EGCG microneedle developed in this study exhibits good mechanical properties, capable of successfully penetrating the skin's stratum corneum and delivering aPexos and EGCG. aPexos promotes wound repair, while EGCG regulates the ratio of M1 and M2 macrophages at the wound site and suppresses the inflammatory response. This microneedle can effectively promote wound healing in rats with burn injuries, offering a novel approach for tissue repair.