Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

AIM: To explore the effect of dihydroquercetin on visual function in mice with form deprivation myopia based on the NOD-like receptor thermoprotein domain-related protein 3(NLRP3)inflammasome pathway.METHODS: The C57BL/6 mice were randomly divided into control group and form deprivation myopia model group, and the form deprivation myopia model group was constructed by covering the right eye with a translucent eye patch. After successful modeling, the mice in the model group of form deprivation myopia were randomly divided into model group, low-, medium- and high-dose dihydroquercetin groups, and high-dose dihydroquercetin + NLRP3 agonist group. The diopter and axial length of mice in each group were detected. The kit was used to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in retinal tissue. RT-qPCR was used to detect the mRNA expressions of NLRP3, apoptosis-associated spot-like protein(ASC), Caspase-1, IL-1β and IL-18 in retinal tissues. Western blot was used to detect the expression of NLRP3, ASC, cleaved Caspase-1, IL-1β and IL-18 proteins in retinal tissues. TUNEL staining was used to detect apoptosis in retinal tissue.RESULTS: Compared with the control group, the diopter of the mice in the model group decreased, and axial length increased, and the SOD decreased whereas MDA, NLRP3, ASC, Caspase-1, IL-1β, IL-18 increased, and the rate of apoptosis in retinal tissue increased(all P<0.05). Compared with the model group, the diopter of mice in the low-, medium- and high-dose dihydroquercetin groups increased, axial length shortened, the SOD increased, whereas MDA, NLRP3, ASC, Caspase-1, IL-1β, IL-18 decreased, and the rate of apoptosis in retinal tissue decreased(all P<0.05). Compared with the high-dose dihydroquercetin group, the high-dose dihydroquercetin+NLRP3 agonist group had reduced diopter, increased axial length, decreased SOD levels, elevated MDA, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 levels, as well as increased apoptosis rate in retinal tissue(all P<0.05).CONCLUSION: Dihydroquercetin can improve visual function in mice with form deprivation myopia by inhibiting pyroptosis and oxidative stress responses, which may be related to the suppression of NLRP3 inflammasome. NLRP3 agonists can partially mitigate the effects of high-dose dihydroquercetin on form deprivation myopia in mice.

AIM: To compare the clinical efficacy of goniosynechialysis versus trabeculectomy combined with cataract phacoemulsification in treating glaucoma complicated with cataract.METHODS:From January 2019 to January 2024, patients with glaucoma complicated with cataract diagnosed in our hospital were included as the study subjects. They were assigned into trabeculectomy group and goniosynechialysis group based on different surgical methods. The trabeculectomy group was treated with cataract phacoemulsification combined with trabeculectomy, while the goniosynechialysis group was treated with cataract phacoemulsification combined with goniosynechialysis. The improvement of visual acuity, anterior chamber depth, chamber angle width, intraocular pressure, whole en face vessel density within the optic disc head and in the peripapillary region, and complications were compared between two groups.RESULTS: A total of 120 patients(120 eyes)with glaucoma combined with cataract were included in this study, among which 60 eyes were in the trabeculectomy group and 60 eyes in the goniosynechialysis group. The age of the trabeculectomy group was 60.72±6.16 years, including 28 males and 32 females. The age of the goniosynechialysis group was 61.04±6.24 years, including 31 males and 29 females. At 3 mo after surgery, the visual acuity of patients in both groups improved significantly, and the improvement of visual acuity in the goniosynechialysis group was significantly better than that in the trabeculectomy group(all P<0.01). At 3 mo after surgery, the anterior chamber depth and chamber angle width of patients in both groups were higher than those before surgery, and with the goniosynechialysis group being higher than the trabeculectomy group(all P<0.01), while the intraocular pressure was lower than that before surgery, and with the goniosynechialysis group being lower than the trabeculectomy group(all P<0.01). Before surgery, there was no significant difference in the whole en face vessel density within the optic disc head between the two groups(P>0.05), however, the whole en face vessel density within the optic disc head in both groups on 1 d after surgery were significantly lower than before surgery(all P<0.05); and compared with 1 d after surgery, there was a significant increase at 1 wk, 1, and 3 mo after surgery(all P<0.05); the whole en face vessel density within the optic disc head in the goniosynechialysis group was significantly higher than that in the trabeculectomy group at various time points after surgery(all P<0.05). However, there was no significant difference in the whole en face vessel density in the peripapillary region between the two groups before surgery and various time points after surgery(all P>0.05). Within 3 mo after surgery, the incidence of complications in the goniosynechialysis group(8.3%)was significantly lower than that in the trabeculectomy group(21.7%; P<0.05).CONCLUSION:Goniosynechialysis combined with phacoemulsification is more effective than trabeculectomy combined with phacoemulsification in the treatment of patients with glaucoma complicated with cataract in improving the visual acuity and whole en face vessel density within the optic disc head of patients, increasing the anterior chamber depth and chamber angle width, reducing intraocular pressure and the risk of complications. It has high safety and ideal short-term efficacy.

[摘 要] 目的：探讨高良姜素（Gal）调控AMPK/mTOR/ULK1信号通路对胃癌细胞凋亡和自噬的影响及其机制。方法：将胃癌NCI-N87细胞分为对照组、多索吗啡（DM）组、Gal低剂量（Gal-L）组、Gal高剂量（Gal-H）组、Gal-H + DM组。采用MTT法、流式细胞术、划痕愈合实验和Transwell实验分别检测各组细胞的增殖、凋亡、迁移和侵袭能力，WB法检测PCNA、C-caspase-3、免疫逃逸相关蛋白（B7H1）、EMT和AMPK/mTOR/ULK1信号通路蛋白的表达水平。建立裸鼠NCI-N87细胞移植瘤模型，观察Gal和5-FU对移植瘤的抑制效果。结果：与对照组比较，DM组NCI-N87细胞增殖活性、划痕愈合率和侵袭细胞数、N-cadherin、vimentin、PCNA、B7H1、p62和p-mTOR/mTOR蛋白表达均显著升高（均P < 0.05），细胞凋亡率、C-caspase-3、E-cadherin、LC3Ⅱ/LC3Ⅰ、p-AMPK/AMPK和p-ULK1/ULK1蛋白表达均显著降低（均P < 0.05）；Gal-L组和Gal-H组NCI-N87细胞的增殖活性、划痕愈合率和侵袭细胞数、N-cadherin、vimentin、PCNA、B7H1、p62和p-mTOR/mTOR蛋白表达均显著降低（均P < 0.05），细胞凋亡率、C-caspase-3、E-cadherin、LC3Ⅱ/LC3Ⅰ、p-AMPK/AMPK和p-ULK1/ULK1蛋白表达均显著升高（均P < 0.05）；DM可部分逆转Gal对NCI-N87细胞恶性生物学行为的抑制作用（P < 0.05）；与对照组比较，Gal组和5-FU组裸鼠移植瘤体积和质量均显著降低，肿瘤组织细胞凋亡率显著升高（P < 0.05）。结论：Gal可促进胃癌NCI-N87细胞自噬和凋亡，抑制其增殖、迁移和侵袭，可能与激活AMPK/mTOR/ULK1信号通路有关。

ObjectiveTo investigate the effects of exogenous nitric oxide （NO） on the accumulation and quality formation mechanism of flavonoids in Scutellariae Radix. MethodsFresh roots of Scutellaria baicalensis were treated with sodium nitroprusside （SNP） solutions at concentrations of 0.0， 7.5， and 20 mmol·L^-1， respectively. Kits and supporting reaction systems were used to determine the following indicators of samples in each group， including （1） reactive oxygen species： changes in the content of nitric oxide （NO）， superoxide anion （O2-·）， and hydrogen peroxide （H₂O₂）， （2） lipid oxidation products： changes in the content of malondialdehyde （MDA）， （3） antioxidant enzymes： changes in the activity of superoxide dismutase （SOD）， catalase （CAT）， and peroxidase （POD）， and （4） metabolic key enzymes and metabolic intermediates： Changes in the activity of phenylalanine ammonia-lyase （PAL） and the content of 1，3-diphosphoglycerate （1，3-DPG）. High-performance liquid chromatography （HPLC） was used to determine the changes in the content of secondary metabolites in flavonoids such as baicalin， wogonoside， baicalein， and wogonin in each group. ResultsCompared with that on day 0， during the treatment with 20 mmol·L^-1 SNP solution， the content of NO， O2-·， H₂O₂， and MDA in fresh roots of Scutellaria baicalensis increased significantly （P<0.01）， by 138.7%， 75.7%， 292.9%， and 140.3% respectively. The activity of SOD， CAT， and POD increased by 100.7%， 41.4%， and 70.4% respectively （P<0.01）， and that of PAL increased by 111.1% （P<0.01）. The content of the secondary metabolites baicalin and wogonoside remained basically unchanged， while that of baicalein and wogonin increased by 401.3% and 457.9% respectively （P<0.01）. The content of 1，3-DPG increased by 165.0% （P<0.01）. In the 7.5 mmol·L^-1 SNP solution treatment group， the stress degree was relatively mild. Compared with that on day 0， the content of NO， O2-·， H₂O₂， and MDA increased by 76.2%， 57.7%， 221.4%， and 99.7% respectively （P<0.01）. The activity of antioxidant enzymes SOD， CAT， and POD increased by 79.5%， 55.6%， and 51.9% respectively （P<0.01）， and that of PAL increased by 69.0% （P<0.01）. The content of baicalein and wogonin increased by 204.7% and 272.2% respectively （P<0.01）， and that of 1，3-DPG increased by 128.0% （P<0.01）. The 20 mmol·L^-1 SNP group showed better performance than the 7.5 mmol·L^-1 SNP group. ConclusionSNP can simulate the physiological state of Scutellaria baicalensis under stress conditions， activate the antioxidant protection mechanism， promote the biosynthesis of flavonoids in Scutellariae Radix， and significantly improve the quality of medicinal materials in Scutellariae Radix.

Natural products have shown great potential in the research and development of antitumor drugs. However， their clinical application is severely limited by inherent drawbacks such as poor water solubility， low stability， and low bioavailability. Cell membrane biomimetic nanoparticles， as a novel drug delivery system， have provided new strategies to overcome this bottleneck. This review systematically summarizes the preparation methods （e.g.， membrane extrusion， ultrasonic fusion， and microfluidic electroporation） and characterization techniques （e.g.， particle size， Zeta potential， and membrane surface protein detection） of cell membrane biomimetic nanoparticles， with a focus on the application of these derived from various sources in delivering antitumor natural products. Cell membrane biomimetic nanoparticles are endowed with unique biological functions， including low immunogenicity conferred by stem cell membranes， prolonged systemic circulation enabled by red blood cell membranes， and homologous targeting facilitated by tumor cell membranes. Despite these advancements， the technology still faces challenges such as difficulties in large-scale production， high costs， and limited characterization methods. Future research needs to further optimize the relevant processes to promote the clinical translation of cell membrane-biomimetic nanoparticles， thereby offering an efficient and safe novel delivery approach for antitumor therapy using natural products.

ObjectiveTo explore the effects of serine hydroxymethyltransferase 1 （SHMT1） rs1979277 polymorphisms on pharmacokinetic characteristics and clinical prognosis of methotrexate （MTX） in children with acute lymphoblastic leukemia （ALL）. MethodsMatrix-assisted laser desorption/ionization time of flight mass spectrometry was used for SHMT1 rs1979277 genotyping in children with ALL . Clinical data including serum MTX concentrations， incidences of adverse events， and ALL relapse after chemotherapy with MTX were collected. The associations of SHMT1 rs1979277 G>A genotypes with dose-adjusted serum concentrations （C/D ratios）， adverse events of MTX， and relapse were analyzed. The associations between rs1979277 genotypes and SHMT1 expression were explored based on Bioinformatics methods. ResultsAmong the 146 children with ALL included， the rs1979277 GG homozygous genotype accounted for 85.62% （125/146）， while the GA heterozygous genotype accounted for 14.38% （21/146）. The frequency of the G allele was 92.81% （271/292）， while the A allele was only 7.19% （21/292）. Children with the GG homozygous genotype had higher median C/D ratios of MTX in 24 h ［12.06 （μmol·m²）/（L·g）］ and higher relapse rates （12.80%） than those in GA heterozygous genotype carriers ［10.96 （μmol·m²）/（L·g）， and 9.52%， respectively］. However， none of the above differences were statistically significant （all P>0.05）. The incidences of respiratory （19.05%） and liver disorders （33.33%） in children with the GA heterozygous genotype were significantly higher than those in GG homozygous genotype carriers （4.00% and 12.00%， respectively， P<0.05）. There were no statistically significant differences in the incidences of other adverse events. Bioinformatics analysis showed that the rs1979277 A allele was significantly associated with higher SHMT1 expression in multiple tissues， such as the tibial artery， pancreas， and adrenal gland （P<0.05）. ConclusionSHMT1 rs1979277 GA genotype may be a risk factor for respiratory and liver disorders in ALL children treated with MTX.

Objective To construct an index system for assessment of schistosomiasis transmission risk following natural disasters such as rainstorms, floods, earthquakes, mudslides, and landslides, so as to provide insights into rapid identification of schistosomiasis transmission risk post-disasters and formulation of targeted schistosomiasis control strategies. Methods An initial framework for the index system for assessment of schistosomiasis transmission risk following natural disasters was drafted through literature review, brainstorming, and focus group discussions. Two rounds of expert correspondence consultations were conducted using the Delphi method to refine and finalize the system, and the degrees of expert activeness, authority and endorse ment, and consensus were evaluated. In addition, the weights of each index were calculated using the analytic hierarchy process. Results A total of 18 experts participated in the consultation. The expert positive coefficients were 100.00% and 94.44% for two rounds of consultations, with authority coefficients of 0.92 and 0.94, respectively. The coefficients of coordination on the index importance, rationality and operability were 0.209, 0.185, 0.222 and 0.407, 0.214, 0.257 for two rounds of consultations, respectively, and all consistency tests were statistically significant (χ² = 246.771 to 505.278, all P values < 0.001). Following two rounds of expert consultations, an index system consisting of 6 first-level indicators, 15 second-level indicators, and 49 third-level indicators was ultimately constructed. In terms of first-level indicators, “disaster situation”, “previous epidemics”, “healthcare guarantee”, “response capacity” and “emergency recovery” had the highest weights, each at 18.18%. Regarding second-level indicators, “Schistosoma japonicum infections in animals”, “S. japonicum infections in snails” and “medical treatment” had the highest weights, each at 7.35%. In terms of third-level indicators, ten items had the highest weights, including “identification of schistosomiasis cases”, “detection of S. japonicum infections in wild feces”, “detection of S. japonicum infections in snails”, “reserves of schistosomiasis diagnostic/testing reagents and consumables”, “reserves of chemotherapy agents for human and animal schistosomiasis”, “reserves of cercariacides”, “periodical surveillance on schistosomiasis”, “identification of schistosomiasis transmission risk and timely response”, “normal provision of diagnosis and treatment services” and “post-disaster schistosomiasis surveillance”, each at 2.40%. Conclusion A scientific, systematic, and practical index system has been constructed for assessment of schistosomiasis transmission risk following natural disasters, which may provide insights into rapid post-disaster identification of schistosomiasis transmission risk, formulation of targeted schistosomiasis control strategies and optimization of resource allocation.

ObjectiveTo analyze the characteristics of 150 patients with spinal cord injury complicated with spasticity. MethodsA cross-sectional survey was conducted on 150 patients with spinal cord injury accompanied by spasticity from September, 2019 to December, 2024. Their age, gender, cause of injury, injury site, severity of injury, spasticity severity and other indicators were recorded. The relationships between different characteristics were analyzed, and a correlation analysis of disease duration, spasticity grade, injury level, injury severity and age were conducted. ResultsThere was no significant difference in age distribution between patients with tetraplegia and paraplegia (Z = 0.806, P = 0.420). The proportions of trauma (χ² = 3.982, P = 0.046) and tetraplegia (χ² = 10.559, P = 0.010) were higher in males than in females. Trauma was the main cause of injury in both tetraplegia and paraplegia patients; the proportion of tetraplegia was higher than paraplegia in trauma patients, while paraplegia was higher than tetraplegia in non-trauma patients (χ² = 11.885, P < 0.001). Patients with tetraplegia was dominated by incomplete injury, whereas patients with paraplegia was dominated by complete injury (χ² = 10.885, P = 0.012). Grade A injury was predominant in trauma patients (P = 0.003). Spasticity grade showed a very weak positive correlation with disease duration (r = 0.175, P = 0.032) and age (r = 0.168, P = 0.040). Injury severity showed a very weak positive correlation with age (r = 0.183, P = 0.025). ConclusionCharacteristics of patients with spinal cord injury complicated with spasticity is different with gender, cause of injury, injury level, injury severity.

ObjectiveProtein-protein interactions (PPIs) are fundamental to the execution of biological functions within living cells. However, traditional biochemical methods, such as co-immunoprecipitation (Co-IP), often fail to capture transient, weak, or membrane-associated interactions due to the stringent detergent requirements for cell lysis. Proximity labeling (PL) has emerged in recent years as a transformative technology for mapping the proteomes of specific subcellular compartments and identifying dynamic interactomes in situ. Golgi protein 73 (GP73, also known as GOLPH2), a resident type II Golgi transmembrane protein, is a well-recognized clinical biomarker for liver diseases, including hepatocellular carcinoma (HCC). Despite its clinical significance, the comprehensive physiological and pathological functions of GP73 remain partially understood. This study aims to establish an APEX2-mediated proximity labeling system specifically targeting GP73 to map its interactome in a living cellular environment, thereby providing new insights into its molecular roles and regulatory mechanisms. MethodsTo achieve spatial specificity, we first constructed a stable cell line expressing a fusion protein consisting of GP73 and the engineered soybean peroxidase APEX2. The localization of the GP73-APEX2 fusion protein was validated to ensure it correctly targeted the Golgi apparatus. The proximity labeling reaction was initiated by incubating the cells with biotin-phenol (BP) for 30 min, followed by a brief (1 min) treatment with1 mmol/L hydrogen peroxide (H₂O₂). This catalytic reaction converts BP into highly reactive, short-lived biotin-phenoxyl radicals that covalently attach to endogenous proteins within a small labeling radius of the GP73-APEX2 enzyme. Subsequently, the cells were quenched, and biotinylated proteins were enriched using high-affinity streptavidin-coated magnetic beads. The captured “neighbor” proteins were subjected to on-bead digestion and analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) for high-throughput identification. Rigorous bioinformatics analysis, including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction network mapping, was performed to interpret the biological significance of the identified candidates. ResultsOur results demonstrate the successful establishment of a robust and sensitive APEX2-based proximity labeling system for GP73. We identified a total of 95 high-confidence interacting proteins that were significantly enriched in the GP73 proximity proteome compared to control groups. Bioinformatics analysis revealed that these interactors were predominantly associated with biological processes such as vesicular transport, protein localization, and, most notably, molecular functions related to “ribosome binding” and “translation regulation”. This suggested an unexpected role for the Golgi-resident GP73 in the cellular translation machinery. To validate these findings, we performed targeted biochemical assays which confirmed a direct interaction between GP73 and the subunits of the eukaryotic translation initiation factor 3 (eIF3) complex, specifically EIF3G and EIF3I. Furthermore, functional validation using the surface sensing of translation (SUnSET) assay—a non-radioactive method to monitor protein synthesis—revealed that the overexpression of GP73 significantly promoted global protein translation levels in the cell, whereas its depletion or inhibition resulted in reduced translation efficiency. ConclusionThis study successfully utilized APEX2-mediated proximity labeling to provide the first systematic map of GP73 interactome in living cells. Our findings uncover a novel, unconventional function of GP73 as a regulator of cellular protein translation, likely mediated through its interaction with the eIF3 complex. This discovery significantly broadens our understanding of the biological roles of GP73 beyond its traditional function in the Golgi apparatus and suggests that it may act as a bridge between Golgi-related trafficking and the protein synthesis machinery. Furthermore, the technical framework established in this study provides a valuable template for investigating other complex organelle-associated protein networks and resolving transient macromolecular interactions in various physiological and pathological contexts.