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.

In recent years, research on stem cell therapy in the field of lung transplantation has gradually increased, demonstrating its potential in improving the outcomes of lung transplantation. As a treatment option for end-stage lung diseases, lung transplantation faces challenges such as scarcity of donor organs, postoperative complications and rejection. Stem cells, with their self-renewal and multi-directional differentiation capabilities, have emerged as strong candidates for alternative or adjunctive treatments. Current studies show that embryonic stem cells and umbilical cord mesenchymal stem cells play significant roles in lung tissue regeneration and immune regulation. However, stem cell therapy still needs to overcome issues such as the selection of cell sources, low survival rates after transplantation and unclear long-term efficacy in clinical applications. Future research should focus on exploring new stem cell sources, improving transplantation techniques and establishing efficacy evaluation systems.

Lung transplantation is currently the only recognized effective treatment for end-stage lung disease and has improved the quality of life for patients. However, lung transplantation still faces many challenges, including rejection, infection, post-transplant acute kidney injury, post-transplant diabetes mellitus, ischemia-reperfusion injury and donor shortage, etc. Chinese lung transplantation scholars made a series of important progress in the field of clinical research in 2024, focusing on the study and solution of the above problems, and providing new ideas for lung transplantation surgery. This article systematically reviews the clinical research and technological innovation in the field of lung transplantation in 2024, summarizes the achievements of clinical research in the field of lung transplantation in China in 2024, and aims to providing new directions and strategies for future research.

Lung transplantation is the optimal treatment for end-stage lung diseases and can significantly improve prognosis of the patients. However, postoperative complications such as infection, rejection, ischemia-reperfusion injury, and other challenges (like shortage of donor lungs) , limit the practical application of lung transplantation in clinical practice. Chinese research teams have been making continuous efforts and have achieved breakthroughs in basic research on lung transplantation by integrating emerging technologies and cutting-edge achievements from interdisciplinary fields, which has strongly propelled the development of this field. This article will comprehensively review the academic progress made by Chinese research teams in the field of lung transplantation in 2024, with a focus on the achievements of Chinese teams in basic research on lung transplantation. It aims to provide innovative ideas and strategies for key issues in the basic field of lung transplantation and to help China's lung transplantation cause reach a higher level.

Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

Objective:To evaluate the safety and clinical efficacy of enteral nutrition (EN) initiated within 24 h after heart transplantation in pediatric patients.Methods:A retrospective cohort study was conducted. Clinical data from 16 pediatric heart transplant recipients at the Seventh Medical Center of the Chinese People′s Liberation Army General Hospital between October 2022 and October 2024 were collected, including demographics, anthropometric measurements, biochemical markers, cytokine levels, and clinical outcomes. Based on the timing of EN initiation, the patients were divided into EN-initiated within 24 h and EN-initiated after 24 h 2 groups. Demographic data, preoperative extracorporeal membrane oxygenation (ECMO) support, physical examination indicators, laboratory parameters, and cytokine levels were compared between groups using independent samples t-test, Mann-Whitney U test, Fisher′s exact probability test. Results:The cohort comprised 16 patients (10 males and 6 females) with an age of (12.5±1.9) years. The EN-initiated within 24 h group comprised 6 cases, and the EN-initiated after 24 h group comprised 10 cases. No significant difference was observed between the two groups in age, preoperative body mass index Z-score, preoperative ECMO support, physical examination indicators, laboratory parameters (total protein, albumin, hemoglobin), or cytokine levels (all P>0.05). Compared to the EN-initiated after 24 h group, the EN-initiated within 24 h group exhibited a shorter intensive care unit stay ( t=2.65, P<0.05) and shorter mechanical ventilation duration ( t=2.23, P<0.05) than EN-initiated after 24 h group. Total hospitalization length had no significant difference ( P>0.05). At 72 h post-transplant, the EN-initiated within 24 h group had a lower interleukin-12 P70 ( t=2.46, P<0.05) and interferon-γ levels ( t=2.55, P<0.05) than EN-initiated after 24 h group. Prior to discharge, the EN-initiated within 24 h group has a lower mean skinfold thickness ( t=2.49, P<0.05) and lower mid-upper arm circumference ( t=2.36, P<0.05) compared with the EN-initiated after 24 h group. Conclusions:Initiating EN within 24 h postoperatively is safe and feasible in pediatric heart transplant recipients. Early EN may shorten the length of intensive care unit stay and mechanical ventilation while attenuating postoperative release of inflammatory cytokine.

Objective To explore the changes in trace elements and amino acid profiles in serum of patients with hepatocellular carcinoma(HCC) providing a reference for clinical diagnosis and treatment.Methods A total of 104 patients with HCC who underwent surgical treatment in the Department of Hepatobiliary Surgery of our hospital from January 2024 to April 2024 were selected as the study group, and 139 patients with benign biliary diseases during the same period were selected as the control group. Atomic absorption spectrometry was used to detect the levels of six trace elements (copper, zinc, calcium, magnesium, iron, and lead) in the serum of both groups, and liquid chromatography-tandem mass spectrometry was used to measure the concentrations of 21 amino acids.Results Compared with the control group, the serum copper level in the HCC group was significantly increased (P<0.05), while the levels of zinc and iron were significantly decreased (P<0.05). Amino acid profile analysis revealed that, compared with the control group, the concentrations of tyrosine, methionine, and phenylalanine in the HCC group were increased (P<0.05), while the concentrations of valine, leucine, isoleucine, glutamine, and arginine were decreased (P<0.05). Further analysis of the correlation between trace elements and amino acids with statistical differences between the groups showed that copper was negatively correlated with valine and leucine (P<0.05), while zinc and iron were positively correlated with valine, leucine, and isoleucine (P<0.01).Conclusions Imbalances in trace elements and amino acid metabolism changes are common in patients with HCC, and there may be an intrinsic connection between the two.

Objective To investigate the relationship between intracellular HIV RNA load and plasma HIV RNA load in peripheral blood of human immunodeficiency virus(HIV)-1 patients,and to explore the potential clinical value of intracellular HIV RNA load in antiretroviral therapy(ART).Methods A total of 104 HIV-1 patients admitted to the West China Hospital,Sichuan University from April to June 2021 were enrolled,in-cluding 26 untreated patients and 78 treated patients.Peripheral blood was collected and patients were fol-lowed up.The correlation between intracellular HIV RNA load,plasma HIV RNA load and the number of CD4+T lymphocytes during the same period were analyzed.The differences of intracellular HIV RNA load in patients with different plasma HIV RNA load and in patients with different therapeutic effects were com-pared.Results The intracellular HIV RNA load was positively correlated with the plasma HIV RNA load.Both intracellular HIV RNA load and plasma HIV RNA load were negatively correlated with the number of CD4+T lymphocytes.Intracellular HIV RNA load was positive in all patients,among which plasma HIV RNA was negative or below the detection limit in 1 untreated patient and 35 treated patients.There was a statisti-cally significant difference in intracellular HIV RNA load between patients with different plasma viral loads(P＜0.001).Patients with an intracellular HIV RNA load of 3.816 lg copy/106 cells could best distinguish between patients with plasma viral load above the detection limit and below the detection limit[area under the curve(AUC)was 0.738].There was a statistically significant difference in intracellular HIV RNA load be-tween patients with different therapeutic effects(P＜0.000 1),and the intracellular HIV RNA load(3.987 lg copy/106 cells,AUC was 0.985)rather than the plasma HIV RNA load(1.647 lg copy/mL,AUC was 0.854)could better distinguish between virologically suppressed patients and low-level viremia patients.Con-clusion The intracellular HIV RNA load in peripheral blood can reflect the real virus storage level and im-mune damage in HIV-1 patients,and is a promising index to evaluate the efficacy of ART and prognosis of pa-tients.Especially when the plasma viral load was below the detection limit,the monitoring of intracellular HIV RNA load may be a more accurate method for the evaluation of ART efficacy.

Objective:To explore the effects of mechanical ventilation（MV）at birth transition on lung pathophysiology and pathobiology in a very preterm animal model.Methods:Based on the model of respiratory distress syndrome（RDS）in very preterm rabbits at gestational age 26（term 31）days well established by the research group using perinatal medication and lung-protective ventilation strategies（very low tidal volume 1-3 mL/kg），we conducted a secondary data analysis. The studied rabbits were re-grouped according to the MV length（≤3 h，3-6 h，6-9 h，9-12 h，and >12 h）. The changes in lung mechanics，histopathology，phospholipid biochemistry，and mRNA relative expression of inflammatory/growth factor in lung tissue were evaluated over the time course of MV. The trend of each variable was tested by ANOVA trend test（ F trend）and Jonckheere-Terpstra trend test（ J-T value）with corresponding P value. Results:With the prolonged MV length，there was improved mean dynamic compliance of respiratory system（ F trend=16.722， P trend<0.001），along with decreased mean peak inspiratory pressure（ F trend =42.226， P trend<0.001）. The content of total phospholipids，disaturated phosphatidylcholine（ J-T=1 222，1 197， P trend=0.018，0.034，respectively）and total protein（ J-T=1 247 ，P trend= 0.009）in bronchoalveolar lavage fluid gradually increased. The wet lung weight in the ≤3 h group was significantly higher than in the other groups（ F=6.819， P<0.001）. The lung injury score（total，or hemorrhage，or inflammation）had progressive exacerbation in the ≤3 h，3-6 h and 6-9 h groups. The lung tissue mRNA expression of major proinflammatory cytokines increased modestly over the time groups in contrast to decreased expression of growth factors，of which the change of keratinocyte growth factor reached statistical significance（ J-T=531， P trend =0.034）. Conclusion:In the 26-day very preterm rabbits，with prolonged MV time，the content of surfactant phospholipid in the alveolar increased gradually，the lung compliance and lung fluid clearance gradually improved. Nevertheless，ventilator-induced lung injury remained evolving. The study warrants further study on the pathogenesis and protective strategies of early postnatal acute lung injury and chronic lung disease.