ObjectiveTo investigate the impact of melanoma-associated antigen D4 （MAGED4） on the malignant biological behavior of hepatocellular carcinoma （HCC）， providing experimental evidence for its evaluation as a potential therapeutic target in HCC. MethodsGenes positively correlated with MAGED4 expression in HCC were screened using the LinkedOmics database， followed by GO functional and KEGG pathway enrichment analyses. Endogenously low-expressing SMMC-7721 and Huh7 cells were selected， with normal hepatic LO2 cells serving as controls. Stable overexpression cell lines were established via lentiviral infection （MAGED4 overexpression group）， with RT-PCR and Western blot validating overexpression efficiency. The effects of MAGED4 overexpression on cell proliferation， cell cycle distribution， migration， and adhesion were systematically analyzed using CCK-8 assays， flow cytometry， scratch healing assays， Transwell migration assays， and cell adhesion assays. ResultsBioinformatics analysis indicated that MAGED4 co-expressed genes were significantly enriched in biological processes closely associated with tumor proliferation and metastasis， including cell-cell adhesion， extracellular matrix organization， and the PI3K-Akt signaling pathway. A stable MAGED4 overexpression cell model was successfully established. In vitro functional assays demonstrated that MAGED4-overexpressing SMMC-7721 and Huh7 cells exhibited a mesenchymal-like morphology， whereas LO2 cells maintained an epithelial-like morphology. Compared with the empty-virus control groups， the MAGED4-overexpressing groups showed significantly increased proliferative activity （48 h： t=3.887， 22.070， 8.866， all P<0.05； 72 h： t=3.231， 23.840， 9.848， all P<0.05； 96 h： t=5.123， 49.800， 5.909， P<0.05， P<0.01， P<0.05）， wound healing rates （12 h： F=40.90， 44.00， 200.50， all P<0.001； 24 h： F=112.00， 34.89， 249.20， all P<0.001）， and numbers of migrated cells （F=239.20， 59.79， 132.80， all P<0.001）， along with significantly decreased numbers of adherent cells （F=73.65， 85.91， 138.00， all P<0.001）， while no significant differences were observed in cell cycle phase distribution in all three cell lines. ConclusionMAGED4 enhances proliferation and migration while suppressing adhesion in both HCC and normal hepatocytes， however， induces mesenchymal-like morphological changes exclusively in HCC cells， suggesting that MAGED4 is capable of driving HCC progression and may serve as a potential therapeutic target for HCC.

Objective To explore the predictive value of growth differentiation factor 15(GDF-15)for atrial fibrillation(AF)in patients with coronary heart disease(CHD).Methods A prospective observation cohort of 1261 elderly CHD patients was randomly sampled from the First Medical Center of Chinese PLA General Hospital from January 2012 to December 2015.ELISA was used to detect GDF-15 level in all the subjects,and their baseline data were collected.Until March 2023,93 patients were lost during the follow-up period,and finally 1168 patients completed the follow-up,with a median time of 9.4 years.According to AF occurred or not during the period,the eligible patients were divided into an AF group(197 cases)and a non-AF group(971 cases),and based on their medical history,also assigned into a stable angina pectoris(SAP,n=304)and an acute coronary syndrome group(ACS,n=864).Logistic regression analysis was used to determine whether GDF-15 is a risk factor for AF in elderly CHD patients.ROC curve was plotted to assess the predictive value of GDF-15,guideline recommended CHARGE-AF scoring model,and their combination for AF events in the patients.Results The AF group had significantly advanced age,larger proportions of smoking history,type 2 diabetes,hypertension,old myocardial infarction,stroke,ACS and administration of statins,higher ratio of angiotensin converting enzyme inhibi-tor/angiotensin receptor blocker,and elevated levels of GDF-15 and N-terminal pro-B-type natri-uretic peptide,and lower left ventricular ejection fraction,SAP incidence,and low-density lipopro-tein cholesterol,total cholesterol and triglycerides levels when compared with the non-AF group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that GDF-15 was not a risk factor for AF in elderly CHD patients(OR=0.92,95％CI:0.74-1.16,P=0.489),but was a risk factor for AF in SAP patients(OR=1.38,95％CI:1.07-2.79,P=0.015),and in ACS patients,still not a risk factor for AF(OR=0.81,95％CI:0.63-1.05,P=0.814).ROC curve analysis showed that the AUC value of GDF-15 combined with the CHARGE-AF scoring model in predic-ting AF was 0.682 in the elderly CHD patients,0.746 in the SAP patients,and 0.680 in the ACS patients.Conclusion Elevated GDF-15 level is an independent risk factor and predictor of AF in elderly SAP patients.In SAP patients,the combination of GDF-15 and CHARGE-AF scoring model further improves the predictive performance of AF occurrence.

Objective To evaluate the effectiveness of different tip positions applied to midline catheters(MC)and provide evidence-based evidence for venous catheter tip positioning in clinical practice.Methods Computerized searches of PubMed,Web of Science,Embase,Cochrane Library,CINAHL,CNKI,Wanfang Database,VIP,and CBM for studies on the effectiveness of applying MC with different tip positions were performed from the time of database construction to July 2024.Meta-analysis was performed using Rev Man 5.3 software after 2 investigators independently screened the studies,extracted the information and evaluated the quality of the included studies.Results A total of 9 studies with 2 302 hospitalized patients were included.The quality evaluation results of the included studies are all B-level.Meta-analysis showed that when the tip of the MC was located in the subclavian vein compared with the tip of the MC in the axillary vein,the rate of total catheter-related complications,phlebitis,blood leakage,infiltration,catheter occlusion,catheter dislocation,and catheter-associated thrombosis were lower,with a statistically significant difference(P＜0.05).When the tip of the MC was located in the subclavian vein compared with the tip of the MC in the axillary vein,the catheter retention time was longer,with a statistically significant difference(P=0.007).The descriptive analysis showed a lower rate of extubation due to complications when the tip of the MC was located in the subclavian vein compared with when the tip was located in the axillary vein(P＜0.05).Conclusion When the tip of the MC is located in the subclavian vein compared to when it is located in the axillary vein,the incidence of total catheter-related complications,phlebitis,blood leakage,infiltration,catheter occlusion,catheter dislocation,catheter-associated thrombosis,and the rate of catheter extractions due to complications were lower,and the catheter was left in place for a longer period of time.Due to the limitations of the quantity and quality of the included studies,more large-sample,high-quality studies are needed to further validate the effectiveness of different tip positions of MC.

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To evaluate the effectiveness of different tip positions applied to midline catheters(MC)and provide evidence-based evidence for venous catheter tip positioning in clinical practice.Methods Computerized searches of PubMed,Web of Science,Embase,Cochrane Library,CINAHL,CNKI,Wanfang Database,VIP,and CBM for studies on the effectiveness of applying MC with different tip positions were performed from the time of database construction to July 2024.Meta-analysis was performed using Rev Man 5.3 software after 2 investigators independently screened the studies,extracted the information and evaluated the quality of the included studies.Results A total of 9 studies with 2 302 hospitalized patients were included.The quality evaluation results of the included studies are all B-level.Meta-analysis showed that when the tip of the MC was located in the subclavian vein compared with the tip of the MC in the axillary vein,the rate of total catheter-related complications,phlebitis,blood leakage,infiltration,catheter occlusion,catheter dislocation,and catheter-associated thrombosis were lower,with a statistically significant difference(P＜0.05).When the tip of the MC was located in the subclavian vein compared with the tip of the MC in the axillary vein,the catheter retention time was longer,with a statistically significant difference(P=0.007).The descriptive analysis showed a lower rate of extubation due to complications when the tip of the MC was located in the subclavian vein compared with when the tip was located in the axillary vein(P＜0.05).Conclusion When the tip of the MC is located in the subclavian vein compared to when it is located in the axillary vein,the incidence of total catheter-related complications,phlebitis,blood leakage,infiltration,catheter occlusion,catheter dislocation,catheter-associated thrombosis,and the rate of catheter extractions due to complications were lower,and the catheter was left in place for a longer period of time.Due to the limitations of the quantity and quality of the included studies,more large-sample,high-quality studies are needed to further validate the effectiveness of different tip positions of MC.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To explore the predictive value of growth differentiation factor 15(GDF-15)for atrial fibrillation(AF)in patients with coronary heart disease(CHD).Methods A prospective observation cohort of 1261 elderly CHD patients was randomly sampled from the First Medical Center of Chinese PLA General Hospital from January 2012 to December 2015.ELISA was used to detect GDF-15 level in all the subjects,and their baseline data were collected.Until March 2023,93 patients were lost during the follow-up period,and finally 1168 patients completed the follow-up,with a median time of 9.4 years.According to AF occurred or not during the period,the eligible patients were divided into an AF group(197 cases)and a non-AF group(971 cases),and based on their medical history,also assigned into a stable angina pectoris(SAP,n=304)and an acute coronary syndrome group(ACS,n=864).Logistic regression analysis was used to determine whether GDF-15 is a risk factor for AF in elderly CHD patients.ROC curve was plotted to assess the predictive value of GDF-15,guideline recommended CHARGE-AF scoring model,and their combination for AF events in the patients.Results The AF group had significantly advanced age,larger proportions of smoking history,type 2 diabetes,hypertension,old myocardial infarction,stroke,ACS and administration of statins,higher ratio of angiotensin converting enzyme inhibi-tor/angiotensin receptor blocker,and elevated levels of GDF-15 and N-terminal pro-B-type natri-uretic peptide,and lower left ventricular ejection fraction,SAP incidence,and low-density lipopro-tein cholesterol,total cholesterol and triglycerides levels when compared with the non-AF group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that GDF-15 was not a risk factor for AF in elderly CHD patients(OR=0.92,95％CI:0.74-1.16,P=0.489),but was a risk factor for AF in SAP patients(OR=1.38,95％CI:1.07-2.79,P=0.015),and in ACS patients,still not a risk factor for AF(OR=0.81,95％CI:0.63-1.05,P=0.814).ROC curve analysis showed that the AUC value of GDF-15 combined with the CHARGE-AF scoring model in predic-ting AF was 0.682 in the elderly CHD patients,0.746 in the SAP patients,and 0.680 in the ACS patients.Conclusion Elevated GDF-15 level is an independent risk factor and predictor of AF in elderly SAP patients.In SAP patients,the combination of GDF-15 and CHARGE-AF scoring model further improves the predictive performance of AF occurrence.

Rhamnose synthase (RHM) is a key enzyme in the biosynthesis of uridine diphosphate rhamnose (UDP-Rha), reversibly converting uridine diphosphate-glucose (UDP-Glc) into UDP-Rha in the presence of NADH or NADPH. In this research, yeast extract (YE) was used to stimulate Sorbus aucuparia suspension cells. Based on a previous study of the transcriptome database of S. aucuparia suspension cells, two RHMs were cloned from S. aucuparia and named SaRHM1 (GenBank No.: MK213340) and SaRHM2 (GenBank No.: MK213341). The SaRHM1 gene contained a 2 007 bp open reading frame (ORF) encoding a polypeptide of 668 amino acids with a molecular weight of 75.25 kD, and a theoretical isoelectric point (pI) of 7.24. The SaRHM2 gene contained a 2 040 bp ORF encoding a polypeptide of 679 amino acids with a molecular weight of 76.26 kD and pI of 6.41. Bioinformatic analysis indicated that SaRHM1 and SaRHM2 contained two special sequences of GxxGxxG/A and YxxxK. Multiple sequence alignments and phylogenetic trees show that SaRHM1 and SaRHM2 have high sequence similarity with other plant species of RHMs. The results of enzyme activity assays in vitro revealed that both recombinant SaRHM1 and SaRHM2 are able to convert UDP-Glc into UDP-Rha. SaRHMs displayed maximum activity at 40 ℃ and a pH of 8 and 9, respectively. The K_m values of SaRHM1 and SaRHM2 for UDP-Glc were 212.4 ± 56.70 and 361.0 ± 63.74 μmol·L^-1, respectively, with V_max values of 235.5 ± 18.98 and 516.5 ± 22.30 nmol·min^-1·μg^-1, respectively. This study reports the cloning and sequencing of RHMs from S. aucuparia and verifies their function, which likely provide rhamnose donors for the subsequent biosynthesis of rhamnosides.

Natural products have been a major source of leading compounds in drug discovery. How to effectively screen active compounds from complex matrix remains an interesting topic. In this review, we comprehensively summarized advanced liquid chromatography based approaches in natural products screening, including pre-column, on-column and post-column screening methods. Their advantages, disadvantages and prospect are also discussed.