OBJECTIVE To investigate the protective effect of 2-dodecyl-6-methoxy-2，5-diene-1，4-cyclohexanedione （DMDD）， an active component from Averrhoa carambola root， on myocardial injury in diabetic mice based on the nuclear receptor coactivator 4/ferritin heavy chain 1/autophagy-related protein 8 （NCOA4/FTH1/ATG8） axis. METHODS The successfully modeled diabetic mice were randomly divided into model group and DMDD low-， medium-， and high-dose （12.5， 25， 50 mg/kg） groups， while an additional non-modeled control group was established， with 6 mice in each group. Each group received the corresponding drug solution or an equal volume of normal saline intragastically once daily for 21 consecutive days. After the administration， the levels of fasting blood glucose （FBG）， serum lactate dehydrogenase （LDH）， and creatine kinase isoenzyme MB （CK-MB） were measured. Myocardial pathological changes， degree of fibrosis， and myocardial cell ultrastructure were observed. Myocardial cell death index and NCOA4 protein positive index were detected. The protein expression levels of NCOA4， FTH1， ATG8， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in cardiac tissue were measured. RESULTS Compared with model group， each DMDD group showed significant alleviation of cardiac pathological injury and varying degrees of improvement in the myocardial cell ultrastructure. The FBG and serum LDH and CK-MB levels， the myocardial cell death index and NCOA4 protein positive index，the protein expression levels of NCOA4， FTH1， and ATG8 in cardiac tissue were significantly decreased （ P ＜0.001）， while the protein expression levels of SLC7A11 and GPX4 were significantly increased （ P ＜0.001）. CONCLUSIONS DMDD can reduce blood glucose levels， alleviate myocardial histopathological injury， and inhibit cell death in diabetic mice. The mechanism is associated with inhibiting excessive activation of the NCOA4/FTH1/ATG8 axis and reducing ferritinophagy.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Objective To investigate the dynamic functional connectivity differences between insomnia patients and healthy controls in triple brain networks[the significant network(SN),the default mode network(DMN),and the executive control network(ECN)]using functional magnetic resonance imaging,and uncover their associations with cognitive ability.Methods Dynamic functional connectivity analysis was performed on functional magnetic resonance imaging data from 40 insomnia patients and 40 healthy controls.The changes in dynamic functional connectivity values were studied for SN,DMN,ECN[including the left executive control network(LECN)and the right executive control network(RECN)];the similarities and differences in time characteristic indicators such as time score,average dwell time,and conversion rate were explored;and their associations with clinical information were analyzed.Results The SN-LECN and DMN-RECN dynamic functional connectivity was significantly higher in insomnia patients than in healthy controls(P=0.013,0.047),while the RECN-LECN and RECN internal functional connectivity strength was lower in insomnia patients than in healthy controls(P<0.001).Additionally,the fractional time in state 2 in insomnia group was significantly higher than that in healthy controls(P<0.001),and it was positively correlated with the Pittsburgh sleep quality index(r=0.524,P=0.001).Conclusion Insomnia patients exhibit significant abnormalities in triple brain network dynamic functional connectivity,which may be related to abnormalities in cognitive control and sensory processing in insomnia patients.These findings provide a new perspective for further research on the neural mechanisms and potential intervention strategies for insomnia.

BACKGROUND:Bone tissue,as a highly mineralized and structurally complex connective tissue,plays a pivotal role in maintaining the form and function of living organisms.Traditional imaging techniques have been insufficient to meet the demands for in-depth observation of bone.The advent of tissue clearing technology has enabled researchers to more clearly observe the intricate structures within bones,such as trabecular bone,bone marrow cavities,and neural and vascular networks interacting with bone tissue.This has opened new perspectives for research and clinical applications in orthopedics.OBJECTIVE:To comprehensively summarize the applications of tissue clearing technology in the field of orthopedics and to explore its potential in the study of bone tissue structure and function,elucidation of disease mechanisms,and innovation in treatment strategies.Additionally,it provides an outlook on innovative directions.METHODS:The review encompassed a search of the CNKI and PubMed databases using search terms"tissue clearing,tissue optical,bone"in English and"tissue clearing,bone,bone defect"in Chinese,combined with Boolean logic to optimize the search strategy.The inclusion criteria were scholarly articles and dissertations directly related to tissue clearing technology and orthopedic research,excluding literature with weak relevance,duplication,or incomplete data.A total of 82 articles were finally analyzed,focusing on the efficacy of clearing techniques,their scope of application,and their contributions to orthopedic research.RESULTS AND CONCLUSION:(1)Tissue clearing technology has demonstrated unique advantages in various domains,including the analysis of bone structure,the study of bone metabolism,the pathological characteristics of bone tumors,the process of fracture healing,the mechanisms of bone infection,and the evaluation of biocompatibility of bone grafts and implant materials.(2)The application of this technology has not only accelerated the progress of basic research in the field of orthopedics but also provides new strategies and methods for clinical treatment,indicating a broad application prospect in orthopedic research.

Acute ischemic stroke (AIS) is a cerebrovascular disease characterized by high morbidity, disability, and mortality, posing a significant threat to human health. Endovascular treatment has now been established as a key method for AIS management, in which stent retrievers that can mechanically remove blood clots play a key role in this technique. In recent years, stent retrievers have evolved in complexity and functionality to improve the ability of clot removing and surgical safety. However, the present instruments still have limitations on treatment efficiency, vascular adaptability, and operational precision, posing an urgent need for innovation in the design of stent retrievers. This paper systematically reviewed the structural features and working principles of AIS stent retrievers from the perspective of efficacy evaluation metrics, historical development, recent advancements in stent retrieval technology, and future prospects.
Humans ; Ischemic Stroke/surgery* ; Stents ; Endovascular Procedures/methods* ; Thrombectomy/methods* ; Device Removal/methods*

Objective To explore the clinical efficacy and safety of intravenous thrombolysis and dual antiplatelet therapy in the treatment of acute mild non-disabling ischemic stroke.Methods A retrospective cohort study was conducted,including 138 patients with acute mild non-disabling ischemic stroke[National Institutes of Health Stroke Scale(NIHSS)score≤5]from January 2022 to March 2024,within 6 h of onset.Patients were divided into an intravenous thrombolysis group(66 cases)and a dual antiplatelet group(72 cases).Propensity score matching was used to match patients 1∶1,resulting in 44 patients in each group after matching.Demographic data,clinical data,clinical outcome indicators,and adverse events were collected.The primary outcome was defined as a good functional outcome[modified Rankin Scale(mRS)score 0-2]at 90 d post-onset.Secondary outcomes included NIHSS scores at 24 h,72 h,and 7 d post-onset;the proportion of early neurological deterioration;intracranial and systemic hemorrhagic events within 90 d post-onset;and death within 90 d.Results ①Before matching,the intravenous thrombolysis group had a lower age and admission mRS score than that of the dual antiplatelet group,with statistically significant differences(all P＜0.05).After matching,there were no statistically significant differences between the two groups in terms of age,gender,hypertension,diabetes,cardiac disease,atrial fibrillation,hyper low density lipoprotein-cholesterol(LDL-C),hyperhomocysteinemia,prior stroke,prior smoking,admission NIHSS score,admission mRS score,location of stroke and TOAST classification(all P＞0.05);②There was no statistically significant difference in the proportion of patients with a good functional outcome at 90 d post-onset and the mRS score at 90 d between the intravenous thrombolysis group and the dual antiplatelet group[88.6％(39/44)vs 93.2％(41/44),P=0.458,P=0.308];③ The intravenous thrombolysis group had significantly lower median NIHSS scores at 24 h and 72 h post-onset compared to the dual antiplatelet group,with statistically significant differences[1 vs 2.5,1 vs 2,P=0.018,0.043].There were no statistically significant differences in the other efficacy and safety outcomes.Conclusions Intravenous thrombolysis therapy can bring significant short-term benefits to patients with acute mild non-disabling ischemic stroke,helping to shorten the time to recovery to a good neurological functional outcome,and does not increase the risk of bleeding and mortality.However,in terms of good functional outcomes at 90 d post-onset,its effects are similar to those of dual antiplatelet therapy.Nevertheless,there is an urgent need for larger sample,higher quality clinical studies to further validate these findings.

Objective To investigate the risk factors for mortality and bleeding complications in extracorporeal membrane oxygenation(ECMO)treated patients and to evaluate the impact of thrombocytopenia severity on the prognosis of ECMO therapy.Methods A total of 153 patients who received ECMO treatment at Peking University Third Hospital between January 2013 and September 2024 were en-rolled in this study.The patients were divided into death group(n=97)and recovery group(n=56)based on their final outcomes.Additionally,the patients were categorized into bleeding group(n=104)and non-bleeding group(n=49)based on the occurrence of bleeding complications during ECMO.Clinical baseline characteristics and extreme laboratory values during ECMO were compared be-tween groups.Logistic regression was used to analyze the risk factors for mortality and bleeding.The patients were further divided,based on the initial platelet(PLT)values on the day of catheter placement and the lowest platelet count during ECMO,into normal group(PLT≥ 100× 109/L),moderate reduction group[PLT=(50～99)× 109/L],and severe reduction group(PLT＜50× 109/L).Kaplan-Meier analysis was used to compare survival rates among these groups.The patients in the moderate and severe reduction groups were further divided into a platelet transfusion group and a non-transfusion group,and the outcomes and complication rates were com-pared.Results The recovery group had a higher proportion of myocarditis,higher minimum values of PLT,Hb,and Fib,and higher initial PLT values,while the maximum values of lactic dehydrogenase(LDH),total bilirubin(T-Bil),prothrombin time(PT),and procalcitonin(PCT)were lower(all P＜0.05)with significant differences.Logistic regression showed that age and maximum PCT were independent risk factors for mortality(OR=1.025 and 1.015 respectively,all P＜0.05).The bleeding group had longer ECMO dura-tions,more plasma transfusions,lower minimum Hb values,and higher maximum values of WBC,neutrophils(Neu),and APTT(all P＜0.05)with statistical differences.The minimum PLT value,maximum WBC value,and maximum APTT value were independent risk factors for bleeding complications(OR=0.986,1.062,and 1.004 respectively,all P＜0.05).Kaplan-Meier analysis showed that the patients in the severe reduction group had lower survival rates,regardless of whether the grouping was based on initial or minimum platelet counts(all P＜0.05).Platelet transfusion improved the mortality in the severe reduction group(P＜0.05)but had no effect on the moderate reduction group.Conclusion Age and peak value of PCT are the risk factors for mortality in ECMO patients,while mini-mum PLT count,peak value of WBC and APTT are the risk factors for bleeding complications.Early intervention for infection and in-flammation during ECMO may improve the outcome of patients.Severe thrombocytopenia during ECMO therapy increased the risk of mortality,and targeted platelet transfusion may improve the survival of these patients.

Objective To investigate the dynamic functional connectivity differences between insomnia patients and healthy controls in triple brain networks[the significant network(SN),the default mode network(DMN),and the executive control network(ECN)]using functional magnetic resonance imaging,and uncover their associations with cognitive ability.Methods Dynamic functional connectivity analysis was performed on functional magnetic resonance imaging data from 40 insomnia patients and 40 healthy controls.The changes in dynamic functional connectivity values were studied for SN,DMN,ECN[including the left executive control network(LECN)and the right executive control network(RECN)];the similarities and differences in time characteristic indicators such as time score,average dwell time,and conversion rate were explored;and their associations with clinical information were analyzed.Results The SN-LECN and DMN-RECN dynamic functional connectivity was significantly higher in insomnia patients than in healthy controls(P=0.013,0.047),while the RECN-LECN and RECN internal functional connectivity strength was lower in insomnia patients than in healthy controls(P<0.001).Additionally,the fractional time in state 2 in insomnia group was significantly higher than that in healthy controls(P<0.001),and it was positively correlated with the Pittsburgh sleep quality index(r=0.524,P=0.001).Conclusion Insomnia patients exhibit significant abnormalities in triple brain network dynamic functional connectivity,which may be related to abnormalities in cognitive control and sensory processing in insomnia patients.These findings provide a new perspective for further research on the neural mechanisms and potential intervention strategies for insomnia.

BACKGROUND:Bone tissue,as a highly mineralized and structurally complex connective tissue,plays a pivotal role in maintaining the form and function of living organisms.Traditional imaging techniques have been insufficient to meet the demands for in-depth observation of bone.The advent of tissue clearing technology has enabled researchers to more clearly observe the intricate structures within bones,such as trabecular bone,bone marrow cavities,and neural and vascular networks interacting with bone tissue.This has opened new perspectives for research and clinical applications in orthopedics.OBJECTIVE:To comprehensively summarize the applications of tissue clearing technology in the field of orthopedics and to explore its potential in the study of bone tissue structure and function,elucidation of disease mechanisms,and innovation in treatment strategies.Additionally,it provides an outlook on innovative directions.METHODS:The review encompassed a search of the CNKI and PubMed databases using search terms"tissue clearing,tissue optical,bone"in English and"tissue clearing,bone,bone defect"in Chinese,combined with Boolean logic to optimize the search strategy.The inclusion criteria were scholarly articles and dissertations directly related to tissue clearing technology and orthopedic research,excluding literature with weak relevance,duplication,or incomplete data.A total of 82 articles were finally analyzed,focusing on the efficacy of clearing techniques,their scope of application,and their contributions to orthopedic research.RESULTS AND CONCLUSION:(1)Tissue clearing technology has demonstrated unique advantages in various domains,including the analysis of bone structure,the study of bone metabolism,the pathological characteristics of bone tumors,the process of fracture healing,the mechanisms of bone infection,and the evaluation of biocompatibility of bone grafts and implant materials.(2)The application of this technology has not only accelerated the progress of basic research in the field of orthopedics but also provides new strategies and methods for clinical treatment,indicating a broad application prospect in orthopedic research.

Objective To investigate the risk factors for mortality and bleeding complications in extracorporeal membrane oxygenation(ECMO)treated patients and to evaluate the impact of thrombocytopenia severity on the prognosis of ECMO therapy.Methods A total of 153 patients who received ECMO treatment at Peking University Third Hospital between January 2013 and September 2024 were en-rolled in this study.The patients were divided into death group(n=97)and recovery group(n=56)based on their final outcomes.Additionally,the patients were categorized into bleeding group(n=104)and non-bleeding group(n=49)based on the occurrence of bleeding complications during ECMO.Clinical baseline characteristics and extreme laboratory values during ECMO were compared be-tween groups.Logistic regression was used to analyze the risk factors for mortality and bleeding.The patients were further divided,based on the initial platelet(PLT)values on the day of catheter placement and the lowest platelet count during ECMO,into normal group(PLT≥ 100× 109/L),moderate reduction group[PLT=(50～99)× 109/L],and severe reduction group(PLT＜50× 109/L).Kaplan-Meier analysis was used to compare survival rates among these groups.The patients in the moderate and severe reduction groups were further divided into a platelet transfusion group and a non-transfusion group,and the outcomes and complication rates were com-pared.Results The recovery group had a higher proportion of myocarditis,higher minimum values of PLT,Hb,and Fib,and higher initial PLT values,while the maximum values of lactic dehydrogenase(LDH),total bilirubin(T-Bil),prothrombin time(PT),and procalcitonin(PCT)were lower(all P＜0.05)with significant differences.Logistic regression showed that age and maximum PCT were independent risk factors for mortality(OR=1.025 and 1.015 respectively,all P＜0.05).The bleeding group had longer ECMO dura-tions,more plasma transfusions,lower minimum Hb values,and higher maximum values of WBC,neutrophils(Neu),and APTT(all P＜0.05)with statistical differences.The minimum PLT value,maximum WBC value,and maximum APTT value were independent risk factors for bleeding complications(OR=0.986,1.062,and 1.004 respectively,all P＜0.05).Kaplan-Meier analysis showed that the patients in the severe reduction group had lower survival rates,regardless of whether the grouping was based on initial or minimum platelet counts(all P＜0.05).Platelet transfusion improved the mortality in the severe reduction group(P＜0.05)but had no effect on the moderate reduction group.Conclusion Age and peak value of PCT are the risk factors for mortality in ECMO patients,while mini-mum PLT count,peak value of WBC and APTT are the risk factors for bleeding complications.Early intervention for infection and in-flammation during ECMO may improve the outcome of patients.Severe thrombocytopenia during ECMO therapy increased the risk of mortality,and targeted platelet transfusion may improve the survival of these patients.