Which is the best TACE agent for patients with different NLR hepatocellular carcinomas? A systematic review and network meta-analysis.

Background: Transarterial chemoembolization (TACE) is a common treatment for hepatocellular carcinoma (HCC), but the best therapeutic agent for TACE treatment has not been determined. The neutrophil/lymphocyte ratio (NLR) is a systemic immune system marker; however, the ability of the NLR to predict the prognosis of patients with HCC is unknown, and no studies have been conducted to determine the most appropriate TACE regimen for HCC patients with different NLRs. Methods: The PubMed, Embase, Web of Science, and CNKI databases were searched through May 28, 2023. Comparisons of overall survival (OS) among cohort studies with different NLRs and different TACE treatment regimens were performed with a random effects model. Findings: Thirty-five studies involving 9210 patients were included in this meta-analysis. The results showed that Group 3-4 (NLR<2.5) patients had a significantly longer OS than Group 1-2 (NLR 2.5-5.0). Among the patients, Group 1-3 (NLR 2.0-5.0) patients had the best survival after treatment with adriamycin (lnHR (95 % CI = 0.48 [0.31, 0.75] and lnHR (95 % CI = 0.41 [0.19, 0.91]). Among the Group 4 patients (NLR<2.0), the best outcome was obtained with platinum + adriamycin (lnHR (95 % CI = 0.59 [0.45, 0.78]), followed by adriamycin. A subgroup analysis of TACE combined with other treatments showed that adriamycin combined with sorafenib was the most effective and superior to the other treatment agents. Interpretation: The NLR can be used to predict the prognosis of HCC patients treated with TACE; the higher the NLR is, the worse the prognosis. Adriamycin may be the best therapeutic agent for HCC patients treated with TACE.

Prestrain Guided Yield of Large Single-Crystal Nickel Foils with High-Index Facets.

Single-crystal metal foils with high-index facets are currently being investigated owing to their potential application in the epitaxial growth of high-quality van der Waals film materials, electrochemical catalysis, gas sensing, and other fields. However, the controllable synthesis of large single-crystal metal foils with high-index facets remains a great challenge because high-index facets with high surface energy are not preferentially formed thermodynamically and kinetically. Herein, single-crystal nickel foils with a series of high-index facets are efficiently prepared by applying prestrain energy engineering technique, with the largest single-crystal foil exceeding 5×8 cm2 in size. In terms of thermodynamics, the internal mechanism of prestrain regulation on the formation of high-index facets is proposed. Molecular dynamics simulation is utilized to replicate and explain the phenomenon of multiple crystallographic orientations resulting from prestrain regulation. Additionally, large-sized and high-quality graphite films are successfully fabricated on single-crystal Ni(012) foils. Compared to the polycrystalline nickel, the graphite/single-crystal Ni(012) foil composites show more than five-fold increase in thermal conductivity, thereby showing great potential applications in thermal management. This study hence presents a novel approach for the preparation of single-crystal nickel foils with high-index facets, which is beneficial for the epitaxial growth of certain two-dimensional materials.

Neutrophil and macrophage crosstalk might be a potential target for liver regeneration.

The regenerative capability of the liver is remarkable, but further research is required to understand the role that neutrophils play in this process. In the present study, we reanalyzed single-cell RNA sequencing data from a mouse partial hepatectomy (PH) model to track the transcriptional changes in hepatocytes and non-parenchymal cells. Notably, we unraveled the regenerative capacity of hepatocytes at diverse temporal points after PH, unveiling the contributions of three distinct zones in the liver regeneration process. In addition, we observed that the depletion of neutrophils reduced the survival and liver volume after PH, confirming the important role of neutrophils in liver regeneration. CellChat analysis revealed an intricate crosstalk between neutrophils and macrophages promoting liver regeneration and, using weighted gene correlation network analysis, we identified the most significant genetic module associated with liver regeneration. Our study found that hepatocytes in the periportal zone of the liver are more active than in other zones, suggesting that the crosstalk between neutrophils and macrophages might be a potential target for liver regeneration treatment.

Single-cell analyzing of tumor microenvironment and cell adhesion between early and late-stage lung cancer.

Lung adenocarcinoma (LUAD) is a highly heterogeneous disease that threaten human life with serious incidence and high mortality. High heterogeneity of tumor microenvironment (TME) was reported in multiple studies. However, the factor of controlling the tumor migration progression between eary and late-stage LUAD is still not fully understood. In this study, we conducted a comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data of LUAD obtained from the GEO database. The identification of cell clusters revealed significant expansion of epithelial cells in late-stage patients. Interpretation of the cell-cell communication results between early-stage and late-stage patient samples indicated that early tumor cells may interact with epithelial cells through the TGF-ß pathway to promote tumor progression. The cell cycle analysis demonstrated a significant increase in the number of cells in the G2 and M phases in late-stage lung cancer. Further analysis using Non-negative Matrix Factorization (NMF) revealed early-stage cell-specific gene features involved in cell adhesion-related biological processes. Among these, the Tensin (TNS) gene family, particularly TNS1, showed high expression in epithelial cells and fibroblasts of early-stage samples, specifically associated with cell adhesion. Survival analysis using TCGA database for LUAD demonstrated that patients with high expression of TNS1 exhibited significantly higher overall survival rates compared to those with low expression. Immunofluorescence experiments have demonstrated co-expression of TNS1 with fibroblast and tumor cell markers (α-SMA and EPCAM). Immunohistochemistry experiments further validated the significantly higher expression levels of TNS1 in early-stage LUAD tissues compared to late-stage lung cancer tissues (P<0.05). Pathway experiments have shown that early-stage tumor patients with high expression of TNS1 exhibit stronger phosphorylation levels of Akt and mTOR, indicating a more potent activation of the Akt/mTOR signaling pathway. In conclusion, the results of this study demonstrate that TNS1 is an adhesive molecule in the immune microenvironment of early-stage tumor cells, and it may serve as a novel prognostic marker for lug cancer.

Analysis of Health-Related Quality of Life in Elderly Patients with Stroke Complicated by Hypertension in China Using the EQ-5D-3L Scale.

Purpose: To evaluate the health-related quality of life(HRQoL)status of elderly patients with hypertensive stroke, to understand the factors influencing it, and to provide a basis for the development of health intervention policies. Patients and Methods: This study used the EQ-5D-3L scale to assess the HRQoL among elderly patients who experienced a stroke related to high blood pressure. Various analytical methods were employed to examine the factors that influenced the patient's quality of life. Univariate analysis, Tobit regression, random forest, and XGBoost models were applied to analyze the HRQoL of the patients. Furthermore, to interpret the machine learning results, the SHAP method was utilized. This method involved assessing the importance of each feature, examining the effect of each feature on the prediction result of a single sample, and determining the impact of individual features on the overall prediction. Results: The study found that the median health utility value for elderly patients with hypertensive stroke was 0.427, with an interquartile range of 0.186 to 0.745. The results of the Tobit regression model, Random Forest, and XGBoost model were compared. The results of the model evaluation show that the performance of the machine learning model and the Tobit regression model are not very different. The XGBoost model performs slightly better relative to the random forest model. The factors that strongly influenced the health utility value of patients included BMI, social activities, smoking, education level, alcohol consumption, urban/rural residence, annual income, physical activity level, and hours of sleep at night. Conclusion: Health-related quality of life in hypertensive stroke patients is influenced by a variety of factors. Health-related quality of life can be positively influenced by modifying these factors and making lifestyle adjustments. Maintaining a healthy weight, being socially active, quitting smoking, improving living conditions, increasing physical activity levels and getting enough sleep are recommended. Lifestyle changes need to be developed for each individual on a case-by-case basis and by medical advice.

Nanoassembly-Mediated Exendin-4 Derivatives to Decrease Renal Retention.

An Exendin-4 analogue that was conjugated with 68Ga exhibited an excellent diagnostic effect on insulinoma in clinical practice. On account of its low molecular weight and short hydration radius, 68Ga-Exendin-4 showed high accumulation in kidney tissues. Nanoparticle-mediated strategies have attracted much attention due to polyvalent properties and the size amplification effect. In this study, Exendin-4 derivatives of radionuclide nanodevices were developed and evaluated. The Exendin-4 derivatives consisting of a ternary block recombinant protein were purified by an inverse transition cycle (ITC) and allowed to self-assemble into a nanodevice under physiological conditions. Our results showed that the nanoassemblies of Exendin-4 derivatives formed homogeneous spherical nanoparticles, exhibited outstanding affinity for insulinoma cells, and could be deposited in insulinoma tissues in vivo. The nanoassembly-mediated Exendin-4 derivatives showed fivefold reduced renal retention and exhibited an outstanding tumor-suppression effect.

A Cytochrome P450 Enzyme Catalyses Oxetane Ring Formation in Paclitaxel Biosynthesis.

Oxetane synthase (TmCYP1), a novel cytochrome P450 enzyme from Taxus × media cell cultures, has been functionally characterized to efficiently catalyse the formation of the oxetane ring in tetracyclic taxoids. Transient expression of TmCYP1 in Nicotiana benthamiana using 2α,5α,7ß,9α,10ß,13α-hexaacetoxytaxa-4(20),11(12)-diene (1) as a substrate led to the production of a major oxetane derivative, 1ß-dehydroxybaccatin IV (1a), and a minor 4ß,20-epoxide derivative, baccatin I (1b). However, feeding the substrate decinnamoyltaxinine J (2), a 5-deacetylated derivative of 1, yielded only 5α-deacetylbaccatin I (2b), a 4ß,20-epoxide. A possible reaction mechanism was proposed on the basis of substrate-feeding, 2H and 18O isotope labelling experiments, and density functional theory calculations. This reaction could be an intramolecular oxidation-acetoxyl rearrangement and the construction of the oxetane ring may occur through a concerted process; however, the 4ß,20-epoxide might be a shunt product. In this process, the C5-O-acetyl group in substrate is crucial for the oxetane ring formation but not for the 4(20)-epoxy ring formation by TmCYP1. These findings provide a better understanding of the enzymatic formation of the oxetane ring in paclitaxel biosynthesis.

Changes in the Glucose Concentration Affect the Formation of Humic-like Substances in Polyphenol-Maillard Reactions Involving Gibbsite.

The polyphenol-Maillard reaction is considered one of the important pathways in the formation of humic-like substances (HLSs). Glucose serves as a microbial energy source that drives the humification process. However, the effects of changes in glucose, particularly its concentration, on abiotic pathways remain unclear. Given that the polyphenol-Maillard reaction requires high precursor concentrations and elevated temperatures (which are not present in soil), gibbsite was used as a catalyst to overcome energetic barriers. Catechol and glycine were introduced in fixed concentrations into a phosphate-buffered solution containing gibbsite using the liquid shake-flask incubation method, while the concentration of glucose was controlled in a sterile incubation system. The supernatant fluid and HLS components were dynamically extracted over a period of 360 h for analysis, thus revealing the influence of different glucose concentrations on abiotic humification pathways. The results showed the following: (1) The addition of glucose led to a higher degree of aromatic condensation in the supernatant fluid. In contrast, the supernatant fluid without glucose (Glu0) and the control group without any Maillard precursor (CK control group) exhibited lower degrees of aromatic condensation. Although the total organic C (TOC) content in the supernatant fluid decreased in all treatments during the incubation period, the addition of Maillard precursors effectively mitigated the decreasing trend of TOC content. (2) While the C content of humic-like acid (CHLA) and the CHLA/CFLA ratio (the ratio of humic-like acid to fulvic-like acid) showed varying increases after incubation, the addition of Maillard precursors resulted in a more noticeable increase in CHLA content and the CHLA/CFLA ratio compared to the CK control group. This indicated that more FLA was converted into HLA, which exhibited a higher degree of condensation and humification, thus improving the quality of HLS. The addition of glycine and catechol without glucose or with a glucose concentration of 0.06 mol/L was particularly beneficial in enhancing the degree of HLA humification. Furthermore, the presence of glycine and catechol, as well as higher concentrations of glucose, promoted the production of N-containing compounds in HLA. (3) The presence of Maillard precursors enhanced the stretching vibration of the hydroxyl group (-OH) of HLA. After the polyphenol-Maillard reaction of glycine and catechol with glucose concentrations of 0, 0.03, 0.06, 0.12, or 0.24 mol/L, the aromatic C structure in HLA products increased, while the carboxyl group decreased. The presence of Maillard precursors facilitated the accumulation of polysaccharides in HLA with higher glucose concentrations, ultimately promoting the formation of Al-O bonds. However, the quantities of phenolic groups and phenols in HLA decreased to varying extents.

PAK1 inhibition increases TRIM21-induced PD-L1 degradation and enhances responses to anti-PD-1 therapy in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is a common malignancy with a 5-year survival <10 %. Immunosuppressive tumor microenvironment (TME) plays a critical role in the progression of PDA. In recent years, programmed death-ligand 1 (PD-L1)/programmed cell death protein-1 (PD-1) blockade has emerged as a potent anti-tumor immunotherapy, while is yet to achieve significant clinical benefits for PDA patients. P21-Activated kinase 1 (PAK1) is highly upregulated in PDA and has been reported to be involved in the regulation of anti-tumor immunity. This study aims to investigate the combined effect of PAK1 inhibition and anti-PD-1 therapy on PDA and the underlying mechanisms. We have shown that PAK1 expression positively correlated with PD-L1 in PDA patients, and that inhibition of PAK1 downregulated PD-L1 expression of PDA cells. More importantly, we have demonstrated that PAK1 competed with PD-L1 in binding to tripartite motif-containing protein 21 (TRIM21), a ubiquitin E3 ligase, resulting in less ubiquitination and degradation of PD-L1. Moreover, PAK1 inhibition promoted CD8+ T cells activation and infiltration. In a murine PDA model, the combination of PAK1 inhibition and anti-PD-1 therapy showed significant anti-tumor effects compared with the control or monotherapy. Our results indicated that the combination of PAK1 inhibition and anti-PD-1 therapy would be a more effective treatment for PDA patients.

Electroacupuncture stimulation modulates functional brain connectivity in the treatment of pediatric cerebral palsy: a case report.

Background: Pediatric cerebral palsy (CP) is a non-progressive brain injury syndrome characterized by central motor dysfunction and insufficient brain coordination ability. The etiology of CP is complex and often accompanied by diverse complications such as intellectual disability and language disorders, making clinical treatment difficult. Despite the availability of pharmacological interventions, rehabilitation programs, and spasticity relief surgery as treatment options for CP, their effectiveness is still constrained. Electroacupuncture (EA) stimulation has demonstrated great improvements in motor function, but its comprehensive, objective therapeutic effects on pediatric CP remain to be clarified. Methods: We present a case of a 5-year-old Chinese female child who was diagnosed with CP at the age of 4. The patient exhibited severe impairments in motor, language, social, and cognitive functions. We performed a 3-month period of EA rehabilitation, obtaining resting state functional magnetic resonance imaging (rs-fMRI) of the patient at 0 month, 3 months and 5 months since treatment started, then characterized brain functional connectivity patterns in each phase for comparison. Results: After a 12-month follow-up, notable advancements were observed in the patient's language and social symptoms. Changes of functional connectivity patterns confirmed this therapeutic effect and showed specific benefits for different recovery phase: starting from language functions then modulating social participation and other developmental behaviors. Conclusion: This is a pioneering report demonstrating the longitudinal effect of EA stimulation on functional brain connectivity in CP patients, suggesting EA an effective intervention for developmental disabilities (especially language and social dysfunctions) associated with pediatric CP.

Case report: Light-chain amyloidosis responsive to selinexor in combination with daratumumab and dexamethasone (SDd) therapy.

The outcome of AL amyloidosis remains poor, particularly in patients with advanced organ involvement which takes long time to recovery. We conducted an observational study of two patients with AL amyloidosis treated with SDd regimen. Both patients successfully achieved significant hematological and organ responses without severe adverse events, and the time to organ response was remarkably shorter than previously reported. Notably, an over 15% reduction in interventricular septal thickness (IVST) was observed in patient#2 within 6 months. Up to now, SDd therapy has not been previously reported in AL amyloidosis and may be a promising option for these patients.

A finite element model of human hindfoot and its application in supramalleolar osteotomy.

BACKGROUND: The majority of the ankle osteoarthritis cases are posttraumatic and affect younger patients with a longer projected life span. Hence, joint-preserving surgery, such as supramalleolar osteotomy becomes popular among young patients, especially those with asymmetric arthritis due to alignment deformities. However, there is a lack of biomechanical studies on postoperative evaluation of stress at ankle joints. We aimed to construct a verifiable finite element model of the human hindfoot, and to explore the effect of different osteotomy parameters on the treatment of varus ankle arthritis. METHODS: The bones of the hindfoot are reconstructed using normal CT tomography data from healthy volunteers, while the cartilages and ligaments are determined from the literature. The finite element calculation results are compared with the weight-bearing CT (WBCT) data to validate the model. By setting different model parameters, such as the osteotomy height (L) and the osteotomy distraction distance (h), the effects of different surgical parameters on the contact stress of the ankle joint surface are compared. FINDINGS: The alignment and the deformation of hindfoot bones as determined by the finite element analysis aligns closely with the data obtained from WBCT. The maximum contact stress of the ankle joint surface calculated by this model increases with the increase of the varus angle. The maximum contact stresses as a function of the L and h of the ankle joint surface are determined. INTERPRETATION: The relationship between surgical parameters and stress at the ankle joint in our study could further help guiding the planning of the supramalleolar osteotomy according to the varus/valgus alignment of the patients.

SRS 16-86 promotes diabetic nephropathy recovery by regulating ferroptosis.

Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM), and cell death plays an important role. Ferroptosis is a recently discovered type of iron-dependent cell death and one that is different from other kinds of cell death including apoptosis and necrosis. However, ferroptosis has not been described in the context of DN. This study explored the role of ferroptosis in DN pathophysiology and aimed to confirm the efficacy of the ferroptosis inhibitor SRS 16-86 on DN. Streptozotocin injection was used to establish the DM and DN animal models. To investigate the presence or occurrence of ferroptosis in DN, we assessed the concentrations of iron, reactive oxygen species and specific markers associated with ferroptosis in a rat model of DN. Additionally, we performed haematoxylin-eosin staining, blood biochemistry, urine biochemistry and kidney function analysis to evaluate the efficacy of the ferroptosis inhibitor SRS 16-86 in ameliorating DN. We found that SRS 16-86 could improve the recovery of renal function after DN by upregulating glutathione peroxidase 4, glutathione and system xc -light chain and by downregulating the lipid peroxidation markers and 4-hydroxynonenal. SRS 16-86 treatment could improve renal organization after DN. The inflammatory cytokines interleukin 1ß and tumour necrosis factor α and intercellular adhesion molecule 1 were significantly decreased following SRS 16-86 treatment after DN. The results indicate that there is a strong connection between ferroptosis and the pathological mechanism of DN. The efficacy of the ferroptosis inhibitor SRS 16-86 in DN repair supports its use as a new therapeutic treatment for DN.

TREM2 protects against inflammation by regulating the release of mito-DAMPs from hepatocytes during liver fibrosis.

BACKGROUND: Liver fibrosis typically develops as a result of chronic liver injury, which involves inflammatory and regenerative processes. The triggering receptor expressed on myeloid cells 2 (TREM2), predominantly expressing in hepatic non-parenchymal cells, plays a crucial role in regulating the function of macrophages. However, its mechanism in liver fibrosis remains poorly defined. METHODS: Experimental liver fibrosis models in wild type and TREM2-/- mice, and in vitro studies with AML-12 cells and Raw264.7 cells were conducted. The expression of TREM2 and related molecular mechanism were evaluated by using samples from patients with liver fibrosis. RESULTS: We demonstrated that TREM2 was upregulated in murine model with liver fibrosis. Mice lacking TREM2 exhibited reduced phagocytosis activity in macrophages following carbon tetrachloride (CCl4) intoxication. As a result, there was an increased accumulation of necrotic apoptotic hepatocytes. Additionally, TREM2 knockout aggravated the release of mitochondrial damage-associated molecular patterns (mito-DAMPs) from dead hepatocytes during CCl4 exposure, and further promoted the occurrence of macrophage-mediated M1 polarization. Then, TREM2-/- mice showed more serious fibrosis pathological changes. In vitro, the necrotic apoptosis inhibitor GSK872 effectively alleviated the release of mito-DAMPs in AML-12 cells after CCl4 intoxication, which confirmed that mito-DAMPs originated from dead liver cells. Moreover, direct stimulation of Raw264.7 cells by mito-DAMPs from liver tissue can induce intracellular inflammatory response. More importantly, TREM2 was elevated and inflammatory factors were markedly accumulated surrounding dead cells in the livers of human patients with liver fibrosis. CONCLUSION: Our study highlights that TREM2 serves as a negative regulator of liver fibrosis, suggesting its potential as a novel therapeutic target.

The impact of frailty on clinical outcomes of older patients undergoing enhanced recovery after lumbar fusion surgery: A prospective cohort study.

BACKGROUND: Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. ERAS can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains. MATERIALS AND METHODS: An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged ≥75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP ≥ 3). The preoperative variables, operative data, postoperative outcomes and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay (LOS) after surgery. RESULTS: A total of 245 patients (age of 79.8 ± 3.4 yr) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between non-frail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery. CONCLUSION: Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults.

Reproducibility and reliability of pancreatic pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with an extended Tofts linear (ETL) model for tissue and tumor evaluation has been established, but its effectiveness in evaluating the pancreas remains uncertain. PURPOSE: To understand the pharmacokinetics of normal pancreas and serve as a reference for future studies of pancreatic diseases. MATERIAL AND METHODS: Pancreatic pharmacokinetic parameters of 54 volunteers were calculated using DCE-MRI with the ETL model. First, intra- and inter-observer reliability was assessed through the use of the intra-class correlation coefficient (ICC) and coefficient of variation (CoV). Second, a subgroup analysis of the pancreatic DCE-MRI pharmacokinetic parameters was carried out by dividing the 54 individuals into three groups based on the pancreatic region, three groups based on age, and two groups based on sex. RESULTS: There was excellent agreement and low variability of intra- and inter-observer to pancreatic DCE-MRI pharmacokinetic parameters. The intra- and inter-observer ICCs of Ktrans, kep, ve, and vp were 0.971, 0.952, 0.959, 0.944 and 0.947, 0.911, 0.978, 0.917, respectively. The intra- and inter-observer CoVs of Ktrans, kep, ve, vp were 9.98%, 5.99%, 6.47%, 4.76% and 10.15%, 5.22%, 6.28%, 5.40%, respectively. Only the pancreatic ve of the older group was higher than that of the young and middle-aged groups (P = 0.042, 0.001), and the vp of the pancreatic head was higher than that of the pancreatic body and tail (P = 0.014, 0.043). CONCLUSION: The application of DCE-MRI with an ETL model provides a reliable, robust, and reproducible means of non-invasively quantifying pancreatic pharmacokinetic parameters.

Brain Network Characterization of Preterm Infants With Bronchopulmonary Dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) affects the microstructure of white matter in preterm infants, but its influence on the changes of the brain structural network has not been elaborated. This study aims to investigate the connectivity characteristics of the brain structural network of BPD by using diffusion tensor imaging. METHODS: Thirty-three infants with BPD and 26 infants without BPD were enrolled in this study. Brain structural networks were constructed utilizing automated anatomic labeling mapping by tracing the fibers between each pair of regions in individual space. We calculated network metrics such as global efficiency, local efficiency, clustering coefficients, characteristic path length, and small-worldness. Then we compared the network metrics of these infants with those of 57 healthy term infants of comparable postmenstrual age at magnetic resonance imaging scan. Finally, network-based statistics was used to analyze the differences in brain network connectivity between the groups with and without BPD. RESULTS: Preterm infants with BPD had higher local efficiency and clustering coefficient, lower global efficiency, and longer characteristic path length. Also, preterm infants with BPD had decreased strength of limbic connections mainly in four brain regions: the left lingual gyrus, the left calcarine fissure and surrounding cortex, the right parahippocampal gyrus, and the left precuneus. CONCLUSIONS: Our findings suggest that preterm infants with BPD have lower network integration and higher segregation at term-equivalent age, which may reflect a compensatory mechanism. In addition, BPD affects brain regions involved in visual as well as cognitive functions; these findings provide a new approach to diagnose potential brain damage in preterm infants with BPD.

Regulation of optimized new Shengmai powder on cardiomyocyte apoptosis and ferroptosis in ischemic heart failure rats: The mediating role of phosphatidylinositol-3-kinase/protein kinase B/tumor protein 53 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Optimized New Shengmai Powder (ONSMP) is a sophisticated traditional Chinese medicinal formula renowned for bolstering vital energy, optimizing blood circulation, and mitigating fluid retention. After years of clinical application, ONSMP has shown a significant impact in improving myocardial injury and cardiac function and has a positive effect on treating heart failure. However, many unknowns exist about the molecular biological mechanisms of how ONSMP exerts its therapeutic effects, which require further research and exploration. AIM OF THE STUDY: Exploring the potential molecular biological mechanisms by which ONSMP ameliorates cardiomyocyte apoptosis and ferroptosis in ischemic heart failure (IHF). MATERIALS AND METHODS: First, we constructed a rat model of IHF by inducing acute myocardial infarction through surgery and using echocardiography, organ coefficients, markers of heart failure, antioxidant markers, and histopathological examination to assess the effects of ONSMP on cardiomyocyte apoptosis and ferroptosis in IHF rats. Next, we used bioinformatics analysis techniques to analyze the active components, signaling pathways, and core targets of ONSMP and calculated the interactions between core targets and corresponding elements. Finally, we detected the positive expression of apoptosis and ferroptosis markers and core indicators of signaling pathways by immunohistochemistry; detected the mean fluorescence intensity of core indicators of signaling pathways by immunofluorescence; detected the protein expression of signaling pathways and downstream effector molecules by western blotting; and detected the mRNA levels of p53 and downstream effector molecules by quantitative polymerase chain reaction. RESULTS: ONSMP can activate the Ser83 site of ASK by promoting the phosphorylation of the PI3K/AKT axis, thereby inhibiting the MKK3/6-p38 axis and the MKK4/7-JNK axis signaling to reduce p53 expression, and can also directly target and inhibit the activity of p53, ultimately inhibiting p53-mediated mRNA and protein increases in PUMA, SAT1, PIG3, and TFR1, as well as mRNA and protein decreases in SLC7A11, thereby inhibiting cardiomyocyte apoptosis and ferroptosis, effectively improving cardiac function and ventricular remodeling in IHF rat models. CONCLUSION: ONSMP can inhibit cardiomyocyte apoptosis and ferroptosis through the PI3K/AKT/p53 signaling pathway, delaying the development of IHF.

Decoding ferroptosis: Revealing the hidden assassin behind cardiovascular diseases.

The discovery of regulatory cell death processes has driven innovation in cardiovascular disease (CVD) therapeutic strategies. Over the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been shown to drive the development of multiple CVDs. This review provides insights into the evolution of the concept of ferroptosis, the similarities and differences with traditional modes of programmed cell death (e.g., apoptosis, autophagy, and necrosis), as well as the core regulatory mechanisms of ferroptosis (including cystine/glutamate transporter blockade, imbalance of iron metabolism, and lipid peroxidation). In addition, it provides not only a detailed review of the role of ferroptosis and its therapeutic potential in widely studied CVDs such as coronary atherosclerotic heart disease, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, cardiomyopathy, and aortic aneurysm but also an overview of the phenomenon and therapeutic perspectives of ferroptosis in lesser-addressed CVDs such as cardiac valvulopathy, pulmonary hypertension, and sickle cell disease. This article aims to integrate this knowledge to provide a comprehensive view of ferroptosis in a wide range of CVDs and to drive innovation and progress in therapeutic strategies in this field.