Heart failure （HF） is the end-stage of various cardiovascular diseases， with high morbidity and mortality. The existing “new quadruple” standard treatment can hardly reverse the core pathological process of myocardial remodeling， and long-term medication may pose risks of drug resistance and adverse reactions. Therefore， new therapeutic targets and strategies are urgently needed. Metabolic reprogramming is the upstream core mechanism regulating phenotypic polarization and functional activation of macrophages， which drives the occurrence and development of HF through the core axis of metabolic reprogramming-immune imbalance-ventricular remodeling and has become a cutting-edge potential target for the prevention and treatment of HF. Traditional Chinese medicine （TCM） has a long history in the prevention and treatment of HF. A large number of studies in recent years have confirmed that different therapeutic methods of TCM can correct the polarization imbalance， restore the homeostasis of myocardial immune microenvironment， inhibit myocardial injury， and delay the pathological process of HF by targeting and regulating the metabolic reprogramming of glucose， lipids， mitochondria， and amino acids in macrophages. This paper systematically expounds the core pathological mechanism of metabolic reprogramming of macrophages in HF， sorts out the research progress of TCM in preventing and treating HF by intervening this target， analyzes the regulatory rules， summarizes the limitations of existing research， and puts forward future directions. This review aims to provide a systematic theoretical reference and new research ideas for TCM clinical diagnosis and treatment and new drug development of HF.

Objective:To compare the uncertainty of dose calibration systems between EBT4 and EBT3 films, and to evaluate the effectiveness and accuracy of EBT4 films in radiotherapy dose measurements.Methods:EBT4 and EBT3 films were irradiated with clinical 6 MV photon beams at doses ranging from 0 to 1,600 MU. Films were scanned after resting for 0 and 24 h to establish dose calibration functions based on net optical density. The dose uncertainties introduced by function fitting, dose resolution, film non-uniformity, scan repeatability, and scanner non-uniformity during calibration of the two films were obtained through experimental tests and mathematical calculations. Independent-sample t-tests were used to compare differences in fitting uncertainty and dose resolution between the two films, while homogeneity of variance tests were used to compare differences in film non-uniformity and scan repeatability. The combined total uncertainty was then calculated and compared. Finally, the total combined uncertainty was calculated by integrating all individual sources of uncertainty and compared between the two films. Results:Within the absorbed dose range of 1-12 Gy, EBT4 films exhibited significantly lower dose uncertainties from function fitting and dose resolution than EBT3 films at the same standing time ( P<0.01). No significant differences were observed between the two films in terms of non-uniformity and scan repeatability ( P>0.05). The total dose uncertainties of EBT4 and EBT3 films at 0 h standing were 5.65% and 7.87%, respectively, while the total uncertainties at 24 h standing were 4.73% and 6.33%, respectively. Overall, the dose calibration system of EBT4 films demonstrated consistently lower total uncertainty. Conclusion:Under identical conditions, EBT4 films demonstrate superior and more stable dose uncertainty compared with EBT3 films, thereby meeting the clinical requirements for radiation dose measurements with higher precision.

Objective:To explore the influence of initial high-risk cytogenetic abnormalities on the outcomes of children with acute myeloid leukemia (AML) after post-transplant Cyclophosphamide (PTCy)-based allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective cohort study.AML children who underwent PTCy-based allo-HSCT after the first complete remission at Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology between April 2017 and April 2024 were enrolled.Patients were divided into intermediate-risk and high-risk groups based on their initial cytogenetic features.These patients were further divided into complex karyotype, 11q23 rearrangement, and other karyotype groups.Clinical characteristics and survival outcomes were compared among these groups.Measurement and count data were analyzed using Wilcoxon rank-sum/Kruskal-Wallis and χ2 tests, respectively.Survival and risk factor analyses were performed using Kaplan-Meier and Cox proportional hazards methods, respectively. Results:A total of 51 AML children who underwent allo-HSCT were included in this study.The median age at transplantation was 3.2 years and the median follow-up time was 4.6 years.There were 26 cases in the intermediate-risk group and 25 cases in the high-risk group; 8 cases in the complex karyotype group, 14 cases in the 11q23 rearrangement group, and 29 cases in the other karyotype groups.By the end of the follow-up on November 30, 2024, 11 patients relapsed, 8 patients died, and 13 patients developed grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD).The 3-year overall survival (OS), relapse-free survival (RFS), and grades Ⅱ-Ⅳ acute GVHD-free and relapse-free survival (GRFS) were 84.0% (95% CI: 74.4%-94.8%), 74.5% (95% CI: 63.4%-87.5%), and 58.8% (95% CI: 46.7%-74.0%), respectively.The 3-year OS of the high-risk group was significantly lower than that of the intermediate-risk group (71.8% vs.96.2%, P=0.022), while differences in 3-year RFS and GRFS between the 2 groups were not statistically significant (68.0% vs.80.8%, P=0.400; 52.0% vs.65.4%, P=0.420).The 3-year OS, RFS and GRFS of the complex karyotype group were significantly lower than those of 11q23 rearrangement and other karyotype groups (50.0% vs.85.7%, 93.1%, P=0.009; 37.5% vs.85.7%, 79.3%, P=0.022; 25.0% vs.64.3%, 65.5%, P=0.049).Multivariate analysis showed that a complex karyotype was an independent prognostic factor affecting 3-year OS and GRFS [OS: HR=6.79 (95% CI: 1.13-43.80), P=0.044; GRFS: HR=3.72(95% CI: 1.13-12.20), P=0.030]. Conclusions:High-risk cytogenetic features are significant predictors of survival outcomes in pediatric AML patients undergoing PTCy-based allo-HSCT.

Objective:To explore the influence of initial high-risk cytogenetic abnormalities on the outcomes of children with acute myeloid leukemia (AML) after post-transplant Cyclophosphamide (PTCy)-based allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective cohort study.AML children who underwent PTCy-based allo-HSCT after the first complete remission at Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology between April 2017 and April 2024 were enrolled.Patients were divided into intermediate-risk and high-risk groups based on their initial cytogenetic features.These patients were further divided into complex karyotype, 11q23 rearrangement, and other karyotype groups.Clinical characteristics and survival outcomes were compared among these groups.Measurement and count data were analyzed using Wilcoxon rank-sum/Kruskal-Wallis and χ2 tests, respectively.Survival and risk factor analyses were performed using Kaplan-Meier and Cox proportional hazards methods, respectively. Results:A total of 51 AML children who underwent allo-HSCT were included in this study.The median age at transplantation was 3.2 years and the median follow-up time was 4.6 years.There were 26 cases in the intermediate-risk group and 25 cases in the high-risk group; 8 cases in the complex karyotype group, 14 cases in the 11q23 rearrangement group, and 29 cases in the other karyotype groups.By the end of the follow-up on November 30, 2024, 11 patients relapsed, 8 patients died, and 13 patients developed grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD).The 3-year overall survival (OS), relapse-free survival (RFS), and grades Ⅱ-Ⅳ acute GVHD-free and relapse-free survival (GRFS) were 84.0% (95% CI: 74.4%-94.8%), 74.5% (95% CI: 63.4%-87.5%), and 58.8% (95% CI: 46.7%-74.0%), respectively.The 3-year OS of the high-risk group was significantly lower than that of the intermediate-risk group (71.8% vs.96.2%, P=0.022), while differences in 3-year RFS and GRFS between the 2 groups were not statistically significant (68.0% vs.80.8%, P=0.400; 52.0% vs.65.4%, P=0.420).The 3-year OS, RFS and GRFS of the complex karyotype group were significantly lower than those of 11q23 rearrangement and other karyotype groups (50.0% vs.85.7%, 93.1%, P=0.009; 37.5% vs.85.7%, 79.3%, P=0.022; 25.0% vs.64.3%, 65.5%, P=0.049).Multivariate analysis showed that a complex karyotype was an independent prognostic factor affecting 3-year OS and GRFS [OS: HR=6.79 (95% CI: 1.13-43.80), P=0.044; GRFS: HR=3.72(95% CI: 1.13-12.20), P=0.030]. Conclusions:High-risk cytogenetic features are significant predictors of survival outcomes in pediatric AML patients undergoing PTCy-based allo-HSCT.

Objective:To compare the uncertainty of dose calibration systems between EBT4 and EBT3 films, and to evaluate the effectiveness and accuracy of EBT4 films in radiotherapy dose measurements.Methods:EBT4 and EBT3 films were irradiated with clinical 6 MV photon beams at doses ranging from 0 to 1,600 MU. Films were scanned after resting for 0 and 24 h to establish dose calibration functions based on net optical density. The dose uncertainties introduced by function fitting, dose resolution, film non-uniformity, scan repeatability, and scanner non-uniformity during calibration of the two films were obtained through experimental tests and mathematical calculations. Independent-sample t-tests were used to compare differences in fitting uncertainty and dose resolution between the two films, while homogeneity of variance tests were used to compare differences in film non-uniformity and scan repeatability. The combined total uncertainty was then calculated and compared. Finally, the total combined uncertainty was calculated by integrating all individual sources of uncertainty and compared between the two films. Results:Within the absorbed dose range of 1-12 Gy, EBT4 films exhibited significantly lower dose uncertainties from function fitting and dose resolution than EBT3 films at the same standing time ( P<0.01). No significant differences were observed between the two films in terms of non-uniformity and scan repeatability ( P>0.05). The total dose uncertainties of EBT4 and EBT3 films at 0 h standing were 5.65% and 7.87%, respectively, while the total uncertainties at 24 h standing were 4.73% and 6.33%, respectively. Overall, the dose calibration system of EBT4 films demonstrated consistently lower total uncertainty. Conclusion:Under identical conditions, EBT4 films demonstrate superior and more stable dose uncertainty compared with EBT3 films, thereby meeting the clinical requirements for radiation dose measurements with higher precision.

Objective To evaluate the role and potential mechanism of interleukin (IL)-18/IL-18 binding protein (BP) in mediating the killing effect of natural killer (NK)-92MI cells upon endothelial cells from α-1, 3- galactosyltransferase gene-knockout (GTKO) porcine models. Methods NK-92MI cells were divided into the NK, NK+IL-18, NK+GTKO, IL-18+NK+GTKO and IL-18+IL-18BP+NK+GTKO groups. The messenger ribonucleic acid (mRNA) levels of inflammation-related genes in NK-92MI cells were detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The killing effect of NK-92MI cells on endothelial cells from GTKO porcine models was evaluated by lactate dehydrogenase (LDH) assay. The apoptosis of endothelial cells from GTKO porcine models was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The expression levels of proteins with killing effect and apoptosis-related proteins were determined by Western blot. Results Compared with the NK, NK+IL-18 and NK+GTKO groups, the expression levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-8, IL-3, IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA were up-regulated in NK-92MI cells in the IL-18+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Compared with the IL-18+NK+GTKO group, the expression levels of IFN-γ, TNF-α, IL-8, IL-3, IL-6 and GM-CSF mRNA were down-regulated in NK-92MI cells in the IL-18+IL-18BP+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Compared with the NK+GTKO group, the expression levels of perforin, granzyme B and IFN-γ proteins in NK-92MI cells were up-regulated, the killing rate of NK-92MI cells against endothelial cells from GTKO porcine models was enhanced, the apoptosis rate of endothelial cells from GTKO porcine models was increased, and the ratios of B cell lymphoma-2 (Bcl-2)-associated X protein (Bax)/Bcl-2 and cleaved Caspase-3/Caspase-3 in endothelial cells from GTKO porcine models were elevated in the IL-18+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Compared with the IL-18+NK+GTKO group, the expression levels of perforin, granzyme B and IFN-γ proteins were down-regulated, the killing rate of NK-92MI cells against endothelial cells from GTKO porcine models was decreased, the apoptosis rate of endothelial cells from GTKO porcine models was decreased, and the ratios of Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 in endothelial cells from GTKO porcine models were declined in the IL-18+IL-18BP+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Conclusions IL-18BP may block the expression of inflammation-related genes in NK-92MI cells induced by IL-18 and the killing effect of NK-92MI cells on endothelial cells from GTKO porcine models.

Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.
Biomarkers/metabolism* ; Bipolar Disorder/metabolism* ; Depressive Disorder, Major/diagnosis* ; Early Diagnosis ; Humans ; Oxidative Stress

Objective:To construct a bivalent DNA vaccine against SARS-CoV-2 and influenza A virus H3N2 and to evaluate its immunogenicity in mice.Methods:The coding sequences for spike 1 (S1) protein of SARS-CoV-2 Beta variant and hemagglutinin (HA) of influenza A virus Cambodia (H3N2) strain were codon-optimized and synthesized. The two coding genes were ligated by the self-cleaving 2A peptide using over-lapping PCR to construct S1-2A-HA fragment, which was inserted into pVRC vector to construct the bivalent DNA vaccine, named as pVRC-S1-2A-HA. Indirect immunofluorescence assay (IFA) and Western blot were performed to detect the expression of S1 and HA proteins. BALB/c mice were immunized with pVRC-S1-2A-HA by intramuscular injection and electroporation. The humoral immune responses induced in mice were detected by indirect ELISA, pseudovirus neutralization assay and hemagglutination inhibition assay. Cellular immune responses were detected by IFN-γ ELISPOT, intracellular cytokine staining (ICS) and cytometric bead array (CBA).Results:The bivalent DNA vaccine pVRC-S1-2A-HA could express S1 and HA proteins in vitro. Specific cellular immune responses against S1 protein and specific IgG antibody against HA protein were significantly induced in mice with single-dose immunization. The antigen-specific immunity was significantly enhanced after booster immunization. The geometric mean titer (GMT) of specific IgG antibody increased to 3 251 for S1 protein and 45 407 for HA protein after two-dose immunization. Moreover, the S1-specific T cells increased to 1 238 SFC/10 6 cells. ICS results indicated that the booster vaccination induced CD4 + T and CD8 + T cells to produce IL-2, IFN-γ and TNF-α in mice. The secretion of various cytokines including IL-2, IL- 4, IL-6, IL-10 and IFN-γ in mouse splenocytes was induced after single-dose immunization. Conclusions:A bivalent DNA vaccine against SARS-CoV-2 and influenza A virus H3N2 was constructed and could induce S1- and HA-specific humoral and cellular immune responses in mice, suggesting the great potential of it for further development and application.

Objective:To evaluate the effect of electrical stimulation on lipopolysaccharide (LPS)-induced activation of M1 microglia.Methods:The well-growing BV2 microglia cells were divided into 3 groups ( n=18 each) using a random number table method: control group (group C), group LPS, LPS and electrical stimulation group (group LE). The cells were cultured for 24 h in normal culture atmosphere in group C. In group LPS and group LE, the LPS medium culture 100 ng/ml was added, and the cells were cultured for 24 h. In group LE, cells were stimulated with 100 mV/mm direct current for 4 h before LPS incubation.The levels of tumor necrosis factor-α (TNF-α) and leukocyte interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay.The expression of the M1 microglia surface markers CD32 and inducible nitric oxide synase (iNOS) was detected using immunofluorescent staining.The expression of CD32 and iNOS mRNA was detected using quantitative real-time polymerase chain reaction. Results:Compared with group C, the concentrations of TNF-α and IL-1β were significantly increased, and the expression of CD32 and iNOS protein and mRNA was up-regulated in LPS and LE groups ( P<0.05). Compared with group LPS, the concentrations of TNF-α and IL-1β were significantly decreased, and the expression of CD32 and iNOS protein and mRNA was down-regulated in group LE ( P<0.05). Conclusions:Electrical stimulation can inhibit LPS-induced activation of M1 microglia and thus alleviate the inflammatory responses.

Objective    To summarize the experience of surgical treatment of asphyxiating thoracic dysplasia (Jeune syndrome). Methods    A total of 15 patients with asphyxiating thoracic dysplasia from August 2018 to April 2020 in our hospital were retrospectively included. There were 7 males and 8 females, aged 1-25 (8.87±6.71) years. Special steel bars were used to correct the growth direction of the rib and costal cartilage. Meanwhile, the concave and convex deformities of the chest wall on both sides were corrected to increase the chest volume and correct the thoracic deformity. Results    The contour appearance of the chest wall of all patients changed after the operation. The shape was close to normal, and the symptoms of hypoxia were improved. The operation time was 147.73±59.78 min, intraoperative bleeding volume was 105.67±91.90 mL, ICU stay time was 14.20±13.54 d and hospital stay time was 26.00±17.87 d. Eleven patients were directly extubated after the operation, 4 patients underwent tracheotomy and received assisted respiration, and the assisted respiration time was 19, 13, 22 and 12 days, respectively. The postoperative chest circumference was significantly increased, and the blood oxygen saturation was significantly improved. There were 5 patients with cardiac insufficiency, and 3 of them were improved by cardiotonic therapy, 2 of them died of heart failure on the 2nd and 31st day after the operation, respectively. Abdominal distention occurred in 10 patients after operation, and 5 of them were obstinate and eliminated by comprehensive treatment. All patients were followed up. The appearance of thorax was improved obviously and there was no sign of compression in lungs. One 13-year-old patient developed respiratory discomfort 3 months after the operation, and the symptoms were relieved after self-administration of oxygen. A 25-year-old patient developed cardiac insufficiency half a month after the discharge, and the symptoms disappeared after cardiotonic treatment. Four patients took out the steel bars in 13, 13, 15 and 17 months after the operation, respectively. The appearance of thorax remained well after the operation. The imaging examination showed that the position of bone structure was normal, the lung field was clear, and there was no sign of chronic inflammation. Conclusion    This technique is a safe and simple operation method. It can not only eliminate the deformity of chest wall, but also increase the volume of chest obviously. However, the long-term effect needs to be further evaluated.