OBJECTIVE To explore the effect of superoxide dismutase （SOD） administration on the malignant behavior of PLC/PRF/5 liver cancer cells， and analyze the correlation between SOD and alpha-fetoprotein （AFP） expression， to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02， AFP- negative human liver cancer cells HLE， and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP， SOD and activity of SOD in cells before and after changing AFP expression； the effects of different concentrations of SOD [0 （control）， 0.188， 0.375， 0.75， 1.5， 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein （Src） in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group， the expression levels of SOD1 and SOD2， and SOD activity in PLC/PRF/5 cells were significantly reduced （P＜0.05）. After down-regulating AFP expression in PLC/PRF/ 5 cells， compared with PLC/PRF/5 group， the expression levels of SOD1 and SOD2， as well as SOD activity， were significantly increased in the PLC/PRF/5-shAFP group （low-expression） （P＜0.05）. After 48 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups were significantly reduced （P＜0.05）； after 72 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， and 1.5 U/mL SOD groups were significantly reduced （P＜0.05 or P＜0.01）. Compared with control group， proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups （P＜0.05 or P＜0.01）. Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression， the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups （over-expression） after up-regulating SOD1 and SOD2 expression were significantly reduced （P＜0.05）. CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells， and the expression level and activity of SOD are negatively correlated with AFP.

ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

At present,malignant tumor diseases occur frequently and increase year by year.Traditional chemoradiotherapy methods are expensive,have serious toxic and side effects,and are easy to reduce patient tolerance.Natural medicines have advantages of multiple targets,high selectivity and low toxicity and side effects in process of anti-tumor,and are one of important sources of anti-tumor drugs.As a polypeptide substance,lactoferrin has a strong anti-tumor effect and plays a huge role in field of nano-drug delivery.Receptors of lactoferrin are widely expressed on surface of various cancer cells.In addition to its strong anti-tumor effect,it is also widely used to modify nanocarriers.In this paper,anti-tumor mechanism of lactoferrin is reviewed,and the latest research progress of using lactoferrin as an anti-cancer drug delivery carrier is also introduced.

Neuropsychiatric disorders arise from complex interactions between genetic and environmental factors. DNA methylation, a reversible and environmentally responsive epigenetic regulatory mechanism, serves as a crucial bridge linking environmental exposure, gene expression regulation, and neurobehavioral outcomes. During long-duration deep-space missions, astronauts face multiple stressors-including microgravity, cosmic radiation, circadian rhythm disruption, and social isolation, which can induce alterations in DNA methylation and increase the risk of neuropsychiatric disorders. Genome-wide DNA methylation research can be divided into 3 major methodological stages: Study design, sample preparation and detection, and data analysis, each of which can be applied to astronaut neuropsychiatric health monitoring. Systematic comparison of the Illumina MethylationEPIC array and whole-genome bisulfite sequencing reveals their complementary strengths in terms of genomic coverage, resolution, cost, and application scenarios: the array method is cost-effective and suitable for large-scale population studies and longitudinal monitoring, whereas sequencing provides higher resolution and coverage and is more suitable for constructing detailed methylation maps and characterizing individual variation. Furthermore, emerging technologies such as single-cell methylation sequencing, nanopore long-read sequencing, and machine-learning-based multi-omics integration are expected to greatly enhance the precision and interpretability of epigenetic studies. These methodological advances provide key support for establishing DNA-methylation-based monitoring systems for neuropsychiatric risk in astronauts and lay an epigenetic foundation for safeguarding neuropsychiatric health during future long-term deep-space missions.
DNA Methylation ; Humans ; Space Flight ; Mental Disorders/genetics* ; Epigenesis, Genetic ; Astronauts/psychology* ; Weightlessness/adverse effects* ; Epigenomics

Medical professional spirit is an indispensable and important component in the modern medical system.It not only plays a key role in the harmonious development of doctor-patient relationships,but also is of great significance for the im-provement of medical quality and medical services.This article will start from the problems faced by the medical environment in the broader context,and take the cultivation of the"Guangdong Doctor"spirit,namely"cherishing life,respecting science,be-ing willing to contribute,and being united and enterprising",as an example to explore the importance of reshaping the medical professional spirit.Through specific measures such as strengthening professional spirit education,setting up role models,promo-ting the advanced,improving systems,strengthening supervision,and creating a good working environment,which aims to en-hance the professional quality and ethics of doctors,with the expectation of providing useful references for promoting harmonious doctor-patient relations and improving the quality of medical services.

Objective To explore the mechanism of TubA in the treatment of ulcerative colitis in mice,and to lay a foundation for the treatment strategy of ulcerative colitis.Methods Twenty C57BL/6 mice aged 6-8 weeks were randomly divided into 4 groups(n=5):the control group drank pure water every day,the model group and the treatment groups drank 3％dextran sulfate sodium(DSS)every day,and the treatment groups were injected with 10 mg/kg TubA and 20 mg/kg TubA every day from the third day,respectively.The weight changes of mice in all groups were recorded.Nine days later,the serum of mice was collected,and the expression levels of inflammatory factors IL-1β,IL-6 and IL-10 in serum were detected by ELISA.HE staining was used to observe the pathological changes of the mouse colon.The expression of myeloperoxidase(MPO)was detected by immunohistochemistry,the mRNA levels of inflammatory factors IL-1β,IL-6 and IL-10 were detected by RT-qPCR,and the expressions of GPX4 and FTH were detected by immunohistochemistry.The mRNA and protein expression levels of GPX4,GCLM,FTH,Nrf2,Keap1 and HO-1 in colon tissues were detected by RT-qPCR and Western blotting.Results Compared with the control group,the body weight and colon length of the model group decreased significantly.HE staining showed that inflammatory cells infiltrated the mucosa and submucosa of colon tissue,goblet cells were lost and crypt structure disordered and disappeared.Immunohistochemistry showed that the expression of MPO and FTH proteins were significantly increased,while the expression of GPX4 protein was significantly decreased(P＜0.05).The mRNA and protein expression levels of IL-1β and IL-6 were significantly increased,while the mRNA and protein expression levels of IL-10 were significantly decreased(P＜0.05).The mRNA and protein expression levels of FTH,Nrf2 and HO-1 were significantly increased,while the mRNA and protein expression levels of GPX4,GCLM and Keap1 were significantly decreased(P＜0.05).After TubA treatment,compared with the model group,all these changes mentioned above suppressed(P＜0.05).Conclusion TubA may reduce ulcerative colitis symptoms by inhibiting ferroptosis,providing new ideas for the treatment of ulcerative colitis.

Objective:To investigate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of BCR::ABL-negative chronic neutrophilic leukemia (CNL) and MDS/MPN with neutrophilia.Methods:This study retrospectively analyzed 12 cases of CNL and MDS/MPN with neutrophilia that underwent allo-HSCT from March 2017 to June 2024, comprising 7 males and 5 females with a median age of 48 ( IQR: 28, 59) years. The 2-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and transplantation-related mortality (TRM) rates were analyzed. Complications were also assessed. Results:Of the 12 patients, 6 received matched sibling HSCT and 6 received haploidentical HSCT. All patients had successful engraftment, and the median times of neutrophil and platelet engraftment were 17 ( IQR: 11, 24) days and 15 ( IQR: 9, 28) days, respectively. Grade Ⅱ–Ⅳ acute graft versus host disease (GVHD) and chronic GVHD occurred in 2 and 4 cases, respectively. The 2-year OS, DFS, CIR, and TRM rates were (65.6 ± 16.4) %, (41.7 ± 16.6) %, (47.2 ±18.2) %, and (11.1 ± 11.4) %, respectively, after a median follow-up time of 637 ( IQR: 330, 943) days. One patient died from treatment-related complications due to respiratory failure caused by coronavirus disease 2019. Two patients died due to relapse. Conclusion:Allo-HSCT can be applied as a safe and effective approach to treat CNL and MDS/MPN with neutrophilia.

Objective:To investigate the underlying mechanism behind the significant reduction in intracellular virus loads after respiratory syncytial virus (RSV) and influenza viruses infect respiratory epithelial cells overexpressing the chemokine (C-C motif) receptor 1 (CCR1).Methods:A549 cells were infected with respiratory syncytial virus (RSV), influenza A viruses (H1N1, H3N2), or influenza B virus (FluB), and the expression of chemokine (C-C motif) ligand 5 (CCL5) and CCR1 were detected by qRT-PCR, ELISA, and Western blot. After overexpressing or knocking down CCR1 in A549 cells, these cells were infected with RSV, H1N1, H3N2, or FluB, and the expression of CCR1, heat shock protein 90 (HSP90), cyclin-dependent kinase 1 (CDK1), and viral proteins were detected by qRT-PCR and Western blot. After stimulating CCR1-overexpressed A549 cells with CCL5, Western blot was used to detect the expression of HSP90 and CDK1, and co-immunoprecipitation was used to detect the interaction between HSP90 and CCR1. CCR1 -/- mice were infected with RSV, H1N1, or H3N2 to observe the changes in the expression of HSP90, CDK1, and viral proteins with Western blot, and the inflammation in lung tissues with HE staining. One-way analysis of variance and t test were used for statistical analysis. Results:RSV, H1N1, H3N2, and FluB infections induced high expression of CCL5 in A549 cells ( P<0.05), but the expression of CCR1 showed an overall downward trend. After activating its receptor CCR1, CCL5 inhibited the replication of RSV and influenza viruses by suppressing the activity of HSP90 ( P<0.05). The experiments conducted on CCR1 -/- mice confirmed that the enhanced activity of HSP90 facilitated the replication of RSV and influenza viruses. Conclusion:RSV and influenza viruses may reduce the binding of CCL5 to CCR1 by downregulating the expression of CCR1 in respiratory epithelial cells, thereby weakening the inhibitory effect of CCR1 on HSP90 activity, which enables them to evade host immune defense.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Objective To explore the mechanism of TubA in the treatment of ulcerative colitis in mice,and to lay a foundation for the treatment strategy of ulcerative colitis.Methods Twenty C57BL/6 mice aged 6-8 weeks were randomly divided into 4 groups(n=5):the control group drank pure water every day,the model group and the treatment groups drank 3％dextran sulfate sodium(DSS)every day,and the treatment groups were injected with 10 mg/kg TubA and 20 mg/kg TubA every day from the third day,respectively.The weight changes of mice in all groups were recorded.Nine days later,the serum of mice was collected,and the expression levels of inflammatory factors IL-1β,IL-6 and IL-10 in serum were detected by ELISA.HE staining was used to observe the pathological changes of the mouse colon.The expression of myeloperoxidase(MPO)was detected by immunohistochemistry,the mRNA levels of inflammatory factors IL-1β,IL-6 and IL-10 were detected by RT-qPCR,and the expressions of GPX4 and FTH were detected by immunohistochemistry.The mRNA and protein expression levels of GPX4,GCLM,FTH,Nrf2,Keap1 and HO-1 in colon tissues were detected by RT-qPCR and Western blotting.Results Compared with the control group,the body weight and colon length of the model group decreased significantly.HE staining showed that inflammatory cells infiltrated the mucosa and submucosa of colon tissue,goblet cells were lost and crypt structure disordered and disappeared.Immunohistochemistry showed that the expression of MPO and FTH proteins were significantly increased,while the expression of GPX4 protein was significantly decreased(P＜0.05).The mRNA and protein expression levels of IL-1β and IL-6 were significantly increased,while the mRNA and protein expression levels of IL-10 were significantly decreased(P＜0.05).The mRNA and protein expression levels of FTH,Nrf2 and HO-1 were significantly increased,while the mRNA and protein expression levels of GPX4,GCLM and Keap1 were significantly decreased(P＜0.05).After TubA treatment,compared with the model group,all these changes mentioned above suppressed(P＜0.05).Conclusion TubA may reduce ulcerative colitis symptoms by inhibiting ferroptosis,providing new ideas for the treatment of ulcerative colitis.