Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Ferroptosis is a programmed cell death depends on iron and lipid peroxidation,which has been recognized as the key pathogenic factor for the occurrence of various diseases in recent years,especially playing a significant role in neurodegenerative diseases.Ferroptosis triggers lipid peroxidation and oxidative stress in neuronal cells,leading to neuronal damage and death,thereby accelerating disease progression.Hydrogen sulfide,as an endogenous gaseous signaling molecule,exhibits multiple protective effects,including anti-inflammatory,antioxidant,and anti-ferroptosis properties.Hydrogen sulfide can effectively inhibit the occurrence of ferroptosis through various mechanisms,such as regulating iron metabolism,inhibiting lipid peroxidation,and enhancing the activity of antioxidant enzymes,thereby slowing down the progression of neurodegenerative diseases.This article reviews the related research progress on hydrogen sulfide and ferroptosis and ferroptosis-mediated neurodegenerative diseases,and analyzes the underlying mechanisms,aims to provide new insights and theoretical foundations for the treatment of neurodegenerative diseases.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Objective To observe the clinical effect of doing Huatuo five-animal play treating blood-stasis-type silent myocardial ischemia(SMI)and its influence on coronary hemodynamics.Methods Ninety patients diagnosed as silent myocardial ischemia were randomly divided into a five-animal play group(n=45,age:51.56±11.00 years,24 males and 21 females)and a regular exercise group(n=45,age:52.44±7.19 years old,24 males and 21 females)according to a random number table.The five-animal play group practised the traditional five-animal play,while the regular exercise group con-ducted daily 30-minute moderate-intensity treadmill aerobic exercise,five times a week,for 4 weeks.The changes in the number of abnormal ST-T segment occurrences,myocardial oxygen consumption(CMO),coronary ischemia threshold(CIT),and blood smoothness index(BSD)within 24-hour ambu-latory electrocardiogram before and after the intervention were observed in both groups,with the thera-peutic effect and hemodynamic characteristics of both groups evaluated.Results The average number of ST-T segment abnormalities decreased after intervention in both groups(P<0.001),with significantly greater improvement in the five-animal play group than the regular exercise group(P<0.001).More-over,the average CMO decreased significantly,while the average CMR and BSD increased significant-ly in both groups after intervention(P<0.05),with significantly greater improvement in the five-ani-mal play group than the other group.Meanwhile,the total effective rate in the five-animal play group was significantly higher than the regular exercise group(P<0.01).Conclusion Undergoing the five-ani-mal play and moderate intensity treadmill aerobic exercise both are effective in treating silent myocardi-al ischemia.However,the former therapy is superior to the latter in bettering CMO,CIT and BSD.

BACKGROUND:Mesoporous bioactive glass has great application potential in bone repair due to its excellent biocompatibility and osteoinductive activity.Incorporating therapeutic ions into mesoporous bioactive glass particles can give the material more ideal biological properties.OBJECTIVE:To synthesize copper-doped mesoporous bioactive glass and investigate its in vitro angiogenesis and osteogenic differentiation properties.METHODS:Mesoporous bioactive glass and copper-doped mesoporous bioactive glass were synthesized by microemulsion-assisted sol-gel method.The morphology,structure,composition,and ion release performance of the materials were characterized by scanning electron microscopy,transmission electron microscopy,energy dispersive spectroscopy,and X-ray diffraction.The extracts of mesoporous bioactive glass and copper-doped mesoporous bioactive glass were co-cultured with mouse fibroblasts L929.Biocompatibility of the materials was evaluated by live/dead staining and CCK-8 assay.The extracts of the two materials were co-cultured with human umbilical vein endothelial cells.The angiogenesis-promoting properties of the materials were evaluated by Transwell assay,scratch assay,and CD31 immunofluorescence staining.The extracts of the two materials were co-cultured with mouse bone marrow mesenchymal stem cells.The osteogenic properties of the materials were evaluated by alkaline phosphatase staining(without osteogenic induction solution)and Alizarin red staining(with osteogenic induction solution).RESULTS AND CONCLUSION:(1)The characterization results exhibited that both mesoporous bioactive glass and copper-doped mesoporous bioactive glass presented a tightly packed granular morphology with similar internal mesoporous structures,and copper-doped mesoporous bioactive glass could continuously release copper ions.(2)The live/dead staining and CCK-8 assay results showed that compared with mesoporous bioactive glass,copper-doped mesoporous bioactive glass could promote the proliferation of L929 cells and had good biocompatibility.(3)The results of Transwell assay,scratch assay,and CD31 immunofluorescence staining exhibited that compared with mesoporous bioactive glass,copper-doped mesoporous bioactive glass could promote the migration of human umbilical vein endothelial cells and the expression of CD31 protein,and promote angiogenesis.(4)The results of alkaline phosphatase staining and alizarin red staining demonstrated that the osteogenic performance of copper-doped mesoporous bioactive glass was stronger than that of mesoporous bioactive glass.The results indicate that copper-doped mesoporous bioactive glass has excellent biocompatibility and the potential to promote angiogenesis and bone regeneration.

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.

Ferroptosis is a programmed cell death depends on iron and lipid peroxidation,which has been recognized as the key pathogenic factor for the occurrence of various diseases in recent years,especially playing a significant role in neurodegenerative diseases.Ferroptosis triggers lipid peroxidation and oxidative stress in neuronal cells,leading to neuronal damage and death,thereby accelerating disease progression.Hydrogen sulfide,as an endogenous gaseous signaling molecule,exhibits multiple protective effects,including anti-inflammatory,antioxidant,and anti-ferroptosis properties.Hydrogen sulfide can effectively inhibit the occurrence of ferroptosis through various mechanisms,such as regulating iron metabolism,inhibiting lipid peroxidation,and enhancing the activity of antioxidant enzymes,thereby slowing down the progression of neurodegenerative diseases.This article reviews the related research progress on hydrogen sulfide and ferroptosis and ferroptosis-mediated neurodegenerative diseases,and analyzes the underlying mechanisms,aims to provide new insights and theoretical foundations for the treatment of neurodegenerative diseases.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

BACKGROUND:Mesoporous bioactive glass has great application potential in bone repair due to its excellent biocompatibility and osteoinductive activity.Incorporating therapeutic ions into mesoporous bioactive glass particles can give the material more ideal biological properties.OBJECTIVE:To synthesize copper-doped mesoporous bioactive glass and investigate its in vitro angiogenesis and osteogenic differentiation properties.METHODS:Mesoporous bioactive glass and copper-doped mesoporous bioactive glass were synthesized by microemulsion-assisted sol-gel method.The morphology,structure,composition,and ion release performance of the materials were characterized by scanning electron microscopy,transmission electron microscopy,energy dispersive spectroscopy,and X-ray diffraction.The extracts of mesoporous bioactive glass and copper-doped mesoporous bioactive glass were co-cultured with mouse fibroblasts L929.Biocompatibility of the materials was evaluated by live/dead staining and CCK-8 assay.The extracts of the two materials were co-cultured with human umbilical vein endothelial cells.The angiogenesis-promoting properties of the materials were evaluated by Transwell assay,scratch assay,and CD31 immunofluorescence staining.The extracts of the two materials were co-cultured with mouse bone marrow mesenchymal stem cells.The osteogenic properties of the materials were evaluated by alkaline phosphatase staining(without osteogenic induction solution)and Alizarin red staining(with osteogenic induction solution).RESULTS AND CONCLUSION:(1)The characterization results exhibited that both mesoporous bioactive glass and copper-doped mesoporous bioactive glass presented a tightly packed granular morphology with similar internal mesoporous structures,and copper-doped mesoporous bioactive glass could continuously release copper ions.(2)The live/dead staining and CCK-8 assay results showed that compared with mesoporous bioactive glass,copper-doped mesoporous bioactive glass could promote the proliferation of L929 cells and had good biocompatibility.(3)The results of Transwell assay,scratch assay,and CD31 immunofluorescence staining exhibited that compared with mesoporous bioactive glass,copper-doped mesoporous bioactive glass could promote the migration of human umbilical vein endothelial cells and the expression of CD31 protein,and promote angiogenesis.(4)The results of alkaline phosphatase staining and alizarin red staining demonstrated that the osteogenic performance of copper-doped mesoporous bioactive glass was stronger than that of mesoporous bioactive glass.The results indicate that copper-doped mesoporous bioactive glass has excellent biocompatibility and the potential to promote angiogenesis and bone regeneration.