Electrocardiographic abnormalities in patients with microtia.

The main objective of this study was to investigate the incidence and characteristics of electrocardiographic abnormalities in patients with microtia, and to explore cardiac maldevelopment associated with microtia. This retrospective study analyzed a large cohort of microtia patients admitted to Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from September 2017 to August 2022. The routine electrocardiographic reports of these patients were reviewed to assess the incidence and characteristics of abnormalities. The study included a total of 10,151 patients (5598 in the microtia group and 4553 in the control group) who were admitted to the Plastic Surgery Hospital of Peking Union Medical College. The microtia group had a significantly higher incidence of abnormal electrocardiographies compared to the control group (18.3% vs. 13.6%, P < 0.01), even when excluding sinus irregularity (6.1% vs. 4.4%, P < 0.01). Among the 1025 cases of abnormal electrocardiographies in the microtia group, 686 cases were reported with simple sinus irregularity. After excluding sinus irregularity as abnormal, the most prevalent abnormalities was right bundle branch block (37.5%), followed by sinus bradycardia (17.4%), ST-T wave abnormalities (13.3%), atrial rhythm (9.1%), sinus tachycardia (8.3%), and ventricular high voltage (4.7%). Less common ECG abnormalities included atrial tachycardia (2.1%), ventricular premature contraction (2.4%), and ectopic atrial rhythm (1.8%). atrioventricular block and junctional rhythm were present in 1.2% and 0.9% of the cases, respectively. Wolff Parkinson White syndrome and dextrocardia had a lower prevalence, at 0.6% and 0.9%, respectively. The occurrence of electrocardiographic abnormalities in microtia patients was found to be higher compared to the control group. These findings highlight the potential congenital defect in cardiac electrophysiology beyond the presence of congenital heart defect that coincide with microtia.

The impact of national health insurance on the cost of auricular reconstruction with skin expansion for microtia in China: A single-center retrospective study based on 1290 surgeries.

BACKGROUND: Congenital microtia presents challenges that encompass physical disabilities and psychosocial distress. It is reported that people with low income have a higher possibility of giving birth to babies with congenital malformations. At the end of June 2023, auricular reconstruction was partially incorporated into national health insurance in our hospital. METHODS: Briefly, 1290 surgeries, including stage-I and stage-II auricular reconstruction with tissue expansion were performed in 2023, involving 779 patients. Patient data, including age, sex, length of stay, residence, and costs, were retrieved from the electronic medical record system. The final cost before and after health insurance coverage, as well as the medical insurance reimbursement ratio in each province and municipality were statistically analyzed. RESULTS: Following insurance coverage, a significant increase in the number of surgeries was observed (514 [39.84%] vs. 776 [60.16%], χ2 = 45.99, p = 0.000), with notable reductions in out-of-pocket costs for unilateral and bilateral stage-I and -II auricular reconstructions ($3915.01 vs. $6645.28, p < 0.05; $11546.80 vs. $5198.08, p < 0.05). Disparities in reimbursement rates across regions were evident, but showed no correlation to the local GDP per capita. There was a positive correlation between the length of stay and inpatient cost. Patient's age was not related to the inpatient cost, but to the length of stay. CONCLUSION: The health insurance coverage for microtia treatment significantly alleviated financial burdens on the patients' family and increased the number of auricular reconstruction surgeries. These findings underscore the critical role of insurance coverage in enhancing healthcare accessibility and affordability for patients with congenital microtia.

Emerging contaminants: A One Health perspective.

Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.

Biomass Ppower generation: A pathway to carbon neutrality.

In light of the pressing need to reduce carbon emissions, the biomass power generation industry has gained significant attention and has increasingly become a crucial focus in China. However, there are still considerable gaps in the historical background, status, and prospects of biomass power generation. Herein, the historical and current status of biomass power generation in China are systematically reviewed, with a particular emphasis on supportive policies, environmental impacts, and future projections. By 2022, the newly installed capacity for biomass power generation reached 3.34 MW with a total installed capacity of 41 MW. The power produced from biomass power generation is 182.4 billion kWh in China. The total installed capacity and generated power in 2022 were 1652 and 1139 folds higher than in 2006 when the first biomass generation plant was established. However, disparities in the distribution of biomass resources and power generation were observed. Key drivers of the industry development include tax, finance, and subsidy policies. Under the implementation of the 14th Five-Year Plan for renewable energy development and the goal of carbon neutrality, biomass power generation may achieve great success through more targeted policy support and advanced technologies that reduce air pollutant emissions. If combined with Bioenergy with Carbon Capture and Storage (BECCS) technology, biomass power generation will make its contribution to carbon neutrality in China.

AgentLens: Visual Analysis for Agent Behaviors in LLM-based Autonomous Systems.

Recently, Large Language Model based Autonomous System (LLMAS) has gained great popularity for its potential to simulate complicated behaviors of human societies. One of its main challenges is to present and analyze the dynamic events evolution of LLMAS. In this work, we present a visualization approach to explore the detailed statuses and agents' behavior within LLMAS. Our approach outlines a general pipeline that organizes raw execution events from LLMAS into a structured behavior model. We leverage a behavior summarization algorithm to create a hierarchical summary of these behaviors, arranged according to their sequence over time. Additionally, we design a cause trace method to mine the causal relationship between agent behaviors. We then develop AgentLens, a visual analysis system that leverages a hierarchical temporal visualization for illustrating the evolution of LLMAS, and supports users to interactively investigate details and causes of agents' behaviors. Two usage scenarios and a user study demonstrate the effectiveness and usability of our AgentLens.

Vismodegib Potentiates Marine Antimicrobial Peptide Tilapia Piscidin 4-Induced Cytotoxicity in Human Non-Small Cell Lung Cancer Cells.

Non-small cell lung cancer (NSCLC) is a common cancer with several accepted treatments, such as chemotherapy, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, and immune checkpoint inhibitors. Nevertheless, NSCLC cells often become insensitive to these treatments, and therapeutic resistance is a major reason NSCLC still has a high mortality rate. The induction of therapeutic resistance in NSCLC often involves hedgehog, and suppression of hedgehog can increase NSCLC cell sensitivity to several conventional therapies. In our previous work, we demonstrated that the marine antimicrobial peptide tilapia piscidin 4 (TP4) exhibits potent anti-NSCLC activity in both EGFR-WT and EGFR-mutant NSCLC cells. Here, we sought to further explore whether hedgehog might influence the sensitivity of NSCLC cells to TP4. Our results showed that hedgehog was activated by TP4 in both WT and EGFR-mutant NSCLC cells and that pharmacological inhibition of hedgehog by vismodegib, a Food and Drug Administration-approved hedgehog inhibitor, potentiated TP4-induced cytotoxicity. Mechanistically, vismodegib acted by enhancing TP4-mediated increases in mitochondrial membrane potential and intracellular reactive oxygen species (ROS). MitoTempo, a specific mitochondrial ROS scavenger, abolished vismodegib/TP4 cytotoxicity. The combination of vismodegib with TP4 also reduced the levels of the antioxidant proteins catalase and superoxide dismutase, and it diminished the levels of chemoresistance-related proteins, Bcl-2 and p21. Thus, we conclude that hedgehog regulates the cytotoxic sensitivity of NSCLC cells to TP4 by protecting against mitochondrial dysfunction and suppressing oxidative stress. These findings suggest that combined treatment of vismodegib and TP4 may be a promising therapeutic strategy for NSCLC.

Semiconservative transmission of DNA N6-adenine methylation in a unicellular eukaryote.

While DNA N6-adenine methylation (6mA) is best known in prokaryotes, its presence in eukaryotes has generated great interest recently. Biochemical and genetic evidence supports that AMT1, a MT-A70 family methyltransferase (MTase), is crucial for 6mA deposition in unicellular eukaryotes. Nonetheless, 6mA transmission mechanism remains to be elucidated. Taking advantage of Single Molecule Real-Time Circular Consensus Sequencing (SMRT CCS), here we provide definitive evidence for semiconservative transmission of 6mA in Tetrahymena thermophila In wild-type (WT) cells, 6mA occurs at the self-complementary ApT dinucleotide, mostly in full methylation (full-6mApT); after DNA replication, hemi-methylation (hemi-6mApT) is transiently present on the parental strand, opposite to the daughter strand readily labeled by 5-bromo-2'-deoxyuridine (BrdU). In ΔAMT1 cells, 6mA predominantly occurs as hemi-6mApT. Hemi-to-full conversion in WT cells is fast, robust, and processive, while de novo methylation in ΔAMT1 cells is slow and sporadic. In Tetrahymena, regularly spaced 6mA clusters coincide with linker DNA of nucleosomes arrayed in the gene body. Importantly, in vitro methylation of human chromatin by reconstituted AMT1 complex recapitulates preferential targeting of hemi-6mApT sites in linker DNA, supporting AMT1's intrinsic and autonomous role in maintenance methylation. We conclude that 6mA is transmitted by a semiconservative mechanism: full-6mApT is split by DNA replication into hemi-6mApT, which is restored to full-6mApT by AMT1-dependent maintenance methylation. Our study dissects AMT1-dependent maintenance methylation and AMT1-independent de novo methylation, reveals a 6mA transmission pathway with striking similarity to 5-methyl cytosine (5mC) transmission at the CpG dinucleotide, and establishes 6mA as a bona fide eukaryotic epigenetic mark.

Chemotherapy-elicited extracellular vesicle CXCL1 from dying cells promotes triple-negative breast cancer metastasis by activating TAM/PD-L1 signaling.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and chemotherapy still serves as the cornerstone treatment functioning by inducing cytotoxic cell death. Notably, emerging evidence suggests that dying cell-released signals may induce cancer progression and metastasis by modulating the surrounding microenvironment. However, the underlying molecular mechanisms and targeting strategies are yet to be explored. METHODS: Apoptotic TNBC cells induced by paclitaxel or adriamycin treatment were sorted and their released extracellular vesicles (EV-dead) were isolated from the cell supernatants. Chemokine array analysis was conducted to identify the crucial molecules in EV-dead. Zebrafish and mouse xenograft models were used to investigate the effect of EV-dead on TNBC progression in vivo. RESULTS: It was demonstrated that EV-dead were phagocytized by macrophages and induced TNBC metastasis by promoting the infiltration of immunosuppressive PD-L1+ TAMs. Chemokine array identified CXCL1 as a crucial component in EV-dead to activate TAM/PD-L1 signaling. CXCL1 knockdown in EV-dead or macrophage depletion significantly inhibited EV-dead-induced TNBC growth and metastasis. Mechanistic investigations revealed that CXCL1EV-dead enhanced TAM/PD-L1 signaling by transcriptionally activating EED-mediated PD-L1 promoter activity. More importantly, TPCA-1 (2-[(aminocarbonyl) amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide) was screened as a promising inhibitor targeting CXCL1 signals in EVs to enhance paclitaxel chemosensitivity and limit TNBC metastasis without noticeable toxicities. CONCLUSIONS: Our results highlight CXCL1EV-dead as a novel dying cell-released signal and provide TPCA-1 as a targeting candidate to improve TNBC prognosis.

New Method Using Local Affected Cartilage and Flap for the Cleft in Question Mark Ear.

BACKGROUND: As a rare auricular deformity, despite numerous surgical procedures for correcting moderate-to-severe question mark ears described in past studies, there remains a need to explore a more cost-effective approach. The optimal utilization of ear cartilage and surrounding skin while achieving superior outcomes continues to pose a significant challenge. METHODS: From 2018 to 2023, twenty-four patients with unilateral question mark ear were enrolled in this study. Seven of them were severe type deformities (absence of lower part of auricle), and seventeen were moderate (only cleft between helix and lobule). All patients were treated with new method using local cartilage and flap without damage in unaffected area. RESULTS: All patients were satisfied with significant improvement of question mark ear and the overall symmetrical appearance. The surgical scar was not obvious. No complications were observed. The follow-up period revealed that the corrective procedure kept producing the symmetrical and cosmetic results. CONCLUSION: Our new method enables optimal utilization of deformed tissue and surrounding skin, rendering this method effective and reliable for correcting moderate-to-severe question mark ears. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Relocation of polyotia tissue to reconstruct the tragus and fill the preauricular depression.

OBJECTIVES: The present article introduces a lingual composite tissue flap based on the tragus-like structure for correcting polyotia deformity, with the aim of providing a surgical technique that involves relocating polyotia tissue to reconstruct the tragus and fill the preauricular depression. METHODS: The study included a total of 21 patients with polyotia who underwent lingual composite tissue flap reconstruction between January 2020 to December 2022. Patients were retrospectively assessed through a comprehensive review of their medical records and photographic data. Tragus morphology was evaluated based on the measurements of tragus length and width. The Aesthetic Outcomes Scale (AOS), modified Vancouver Scar Scale (mVSS), and Visual Analogue Scale (VAS) were employed for the assessment of surgical outcomes. RESULTS: The follow-up period for all patients ranged from 6 to 15 months. The length and width of the normal tragus were not significantly different from those of the reconstructed tragus. The mean preoperative AOS score was 2.73 ± 0.51, while the mean postoperative AOS score increased to 7.61 ± 0.65. The mVSS yielded an average score of 1.80 ± 1.43, indicating inconspicuous scarring post polyotia surgery. The preoperative VAS satisfaction score was recorded as 1.57 ± 0.67, while the postoperative VAS score significantly increased to 8.33 ± 0.91. The flaps all successfully survived post-operation without any occurrences of flap hematoma, necrosis, infection, or wound dehiscence. CONCLUSION: The reconstruction of the tragus should be given careful consideration when addressing polyotia. The utilization of a lingual composite tissue flap for correction can achieve excellent aesthetic results for the tragus, with high patient satisfaction and minimal complications.

Decreased intranuclear cardiac troponin I impairs cardiac autophagy through FOS/ATG5 in ageing hearts.

In our previous study, intranuclear cardiac troponin I (cTnI) may function as a co-factor of Yin Yang 1(YY1). Here, we aimed to explore the role of intranuclear cTnI in ageing hearts. Nuclear translocation of cTnI was demonstrated using Western blot and immunofluorescence. The potential nuclear localization sequences (NLSs) of cTnI were predicted by a web server and then verified in 293T cells by putative NLS-eGFP-GST and NLS-mutant transfection. The ratio of Nuclear cTnI/ Total cTnI (Nu/T) decreased significantly in ageing hearts, accompanied with ATG5-decline-related impaired cardiac autophagy. RNA sequencing was performed in cTnI knockout hearts. The differential expressed genes (DEGs) were analysed by overlapping with YY1 ChIP-sequencing data. cTnI gain and loss experiments in vitro determined those filtered DEGs' expression levels. A strong correlation was found between expression patterns cTnI and FOS. Using ChIP-q-PCR, we demonstrated that specific binding DNA sequences of cTnI were enriched in the FOS promoter -299 to -157 region. It was further verified that pcDNA3.1 (-)-cTnI could increase the promoter activity of FOS by using luciferase report assay. At last, we found that FOS can regulate the ATG5 (autophagy-related gene 5) gene by using a luciferase report assay. Taken together, our results indicate that decreased intranuclear cTnI in ageing hearts may cause impaired cardiac autophagy through the FOS/ATG5 pathway.

Using Machine Learning to Construct the Blood-Follicle Distribution Models of Various Trace Elements and Explore the Transport-Related Pathways with Multiomics Data.

Permeabilities of various trace elements (TEs) through the blood-follicle barrier (BFB) play an important role in oocyte development. However, it has not been comprehensively described as well as its involved biological pathways. Our study aimed to construct a blood-follicle distribution model of the concerned TEs and explore their related biological pathways. We finally included a total of 168 women from a cohort of in vitro fertilization-embryo transfer conducted in two reproductive centers in Beijing City and Shandong Province, China. The concentrations of 35 TEs in both serum and follicular fluid (FF) samples from the 168 women were measured, as well as the multiomics features of the metabolome, lipidome, and proteome in both plasma and FF samples. Multiomics features associated with the transfer efficiencies of TEs through the BFB were selected by using an elastic net model and further utilized for pathway analysis. Various machine learning (ML) models were built to predict the concentrations of TEs in FF. Overall, there are 21 TEs that exhibited three types of consistent BFB distribution characteristics between Beijing and Shandong centers. Among them, the concentrations of arsenic, manganese, nickel, tin, and bismuth in FF were higher than those in the serum with transfer efficiencies of 1.19-4.38, while a reverse trend was observed for the 15 TEs with transfer efficiencies of 0.076-0.905, e.g., mercury, germanium, selenium, antimony, and titanium. Lastly, cadmium was evenly distributed in the two compartments with transfer efficiencies of 0.998-1.056. Multiomics analysis showed that the enrichment of TEs was associated with the synthesis and action of steroid hormones and the glucose metabolism. Random forest model can provide the most accurate predictions of the concentrations of TEs in FF among the concerned ML models. In conclusion, the selective permeability through the BFB for various TEs may be significantly regulated by the steroid hormones and the glucose metabolism. Also, the concentrations of some TEs in FF can be well predicted by their serum levels with a random forest model.

Retrospective study on unilateral polyotia combined with microtia utilizing the technique of preserving residual ear tissue.

BACKGROUND: The presence of polyotia in individuals with microtia is a rare deformity. Due to the intricate structure of the auricle, uncertain etiology, and challenging corrective techniques, it has always been a focal point in the field of plastic surgery. The present study presents a technique for correcting the combination of polyotia and microtia by utilizing residual ear tissue as graft material. METHODS: The retrospective study included 23 patients with polyotia and microtia from 2018 to 2022. The residual ear tissue was used to rectify auricular deformities in all patients. The patients were instructed to evaluate the satisfaction of the auricle shape using a visual analog scale (VAS) both before and 6 months after the surgical procedure. The esthetic outcomes of auricle subunits were simultaneously assessed by a senior physician pre- and postoperatively. RESULTS: The mean duration of follow-up in this study was 8.73 months. The preoperative VAS satisfaction score was recorded as 2.26 ± 0.86, while the post-operative VAS score significantly increased to 7.86 ± 0.86. The preoperative auricle esthetic outcomes score was recorded as 9.95 ± 1.74, while the post-operative score significantly increased to 24.04 ± 2.16. The follow-up period did not present any cases of flap necrosis, hematoma, infection, or wound dehiscence. CONCLUSION: The study demonstrates that comprehensive utilization of residual auricular tissue can lead to optimal outcomes in correcting polyotia with concha-type microtia. The utilization of residual ear tissue can be maximized to streamline the operation, minimize bodily harm, and enhance patient satisfaction.

Repurposing the diuretic benzamil as an anti-osteosarcoma agent that acts by suppressing integrin/FAK/STAT3 signalling and compromising mitochondrial function.

Aims: Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. Methods: MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry. Results: Benzamil suppressed growth of osteosarcoma cells by inducing apoptosis. Benzamil reduced the expression of cell surface integrins α5, αV, and ß1 in MG63 cells, while it only reduced the expression of αV in U2OS cells. Benzamil suppressed the phosphorylation and activation of FAK and STAT3. In addition, mitochondrial function and ATP production were compromised by benzamil. The levels of anti-apoptotic proteins XIAP, Bcl-2, and Bcl-xL were reduced by benzamil. Correspondingly, benzamil potentiated cisplatin- and methotrexate-induced apoptosis in osteosarcoma cells. Conclusion: Benzamil exerts anti-osteosarcoma activity by inducing apoptosis. In terms of mechanism, benzamil appears to inhibit integrin/FAK/STAT3 signalling, which triggers mitochondrial dysfunction and ATP depletion.

Effects of lianas on forest biogeochemistry during their lives and afterlives.

Climate change and other anthropogenic disturbances are increasing liana abundance and biomass in many tropical and subtropical forests. While the effects of living lianas on species diversity, ecosystem carbon, and nutrient dynamics are receiving increasing attention, the role of dead lianas in forest ecosystems has been little studied and is poorly understood. Trees and lianas coexist as the major woody components of forests worldwide, but they have very different ecological strategies, with lianas relying on trees for mechanical support. Consequently, trees and lianas have evolved highly divergent stem, leaf, and root traits. Here we show that this trait divergence is likely to persist after death, into the afterlives of these organs, leading to divergent effects on forest biogeochemistry. We introduce a conceptual framework combining horizontal, vertical, and time dimensions for the effects of liana proliferation and liana tissue decomposition on ecosystem carbon and nutrient cycling. We propose a series of empirical studies comparing traits between lianas and trees to answer questions concerning the influence of trait afterlives on the decomposability of liana and tree organs. Such studies will increase our understanding of the contribution of lianas to terrestrial biogeochemical cycling, and help predict the effects of their increasing abundance.

Co-culture of RhoA-overexpressed Microtia Chondrocytes and Adipose-Derived Stem Cells in the Construction of Tissue-engineered Ear-shaped Cartilage.

Microtia is a congenital auricle dysplasia with a high incidence and tissue engineering technology provides a promising strategy to reconstruct auricles. We previously described that the engineered cartilage constructed from microtia chondrocytes exhibited inferior levels of biochemical and biomechanical properties, which was proposed to be resulted from the decreased migration ability of microtia chondrocytes. In the current study, we found that Rho GTPase members were deficient in microtia chondrocytes. By overexpressing RhoA, Rac1 and CDC42, respectively, we further demonstrated that RhoA took great responsibility for the decreased migration ability of microtia chondrocytes. Moreover, we constructed PGA/PLA scaffold-based cartilages to verify the chondrogenic ability of RhoA overexpressed microtia chondrocytes, and the results showed that overexpressing RhoA was of limited help to improve the quality of microtia chondrocyte engineered cartilage. However, co-culture of ADSCs significantly improved the biochemical and biomechanical property of engineered cartilage. Especially, co-culture of RhoA overexpressed microtia chondrocytes and ADSCs produced an excellent effect on the wet weight, cartilage-specific extracellular matrix and biomechanical property of engineered cartilage. Furthermore, we presented that co-culture of RhoA overexpressed microtia chondrocytes and ADSCs combined with human ear-shaped PGA/PLA scaffold and titanium alloy stent fabricated by CAD/CAM and 3D printing technology effectively constructed and maintained auricle structure in vivo. Collectively, our results provide evidence for the essential role of RhoA in microtia chondrocytes and a developed strategy for the construction of patient-specific tissue-engineered auricular cartilage.

Diagnostic Performance of 18F-FDG Positron Emission Tomography/Computed Tomography and Blood Test Parameters for Pulmonary Inflammatory Pseudotumor.

PURPOSE: Pulmonary inflammatory pseudotumor (PIP) is an inflammatory proliferative tumor-like lesion that frequently exhibits hypermetabolism on 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography imaging (PET/CT) and is readily misdiagnosed as a malignant tumor. The purpose of this study was to identify PIP by combining PET/computed tomography metabolic and blood test characteristics with machine learning. PATIENTS AND METHODS: We recruited 27 patients with PIP and 28 patients with lung cancer (LC). The PET metabolic and blood test parameters were collected, and the differences between the groups were evaluated. In addition, we combined the support vector machine (SVM) classifier with the indicators that differed between the groups to classify PIP and LC. RESULTS: For PET metabolic parameters, our findings showed that, as compared with the LC group, maximal standardized uptake value (P< 0.001, t = -4.780), Mean standardized uptake value SUVmean, P< 0.001, t = -4.946), and SD40% (P< 0.001, t = -4.893) were considerably reduced in the PIP group, whereas CV40% (P= 0.004, t = 3.012) was significantly greater. For blood test parameters, the total white blood cell count (P< 0.001, t= 6.457) and absolute neutrophil count (P< 0.001, t= 6.992) were substantially higher in the PIP group than in the LC group. Furthermore, the performance of SVM trained solely on PET metabolic parameters (mean area under the curve [AUC] = 0.84) was comparable to that of SVM trained solely on blood test parameters (mean AUC = 0.86). Surprisingly, utilizing the combined parameters increased SVM performance significantly (mean AUC = 0.98). CONCLUSION: PET metabolic and blood test parameters differed significantly between the PIP and LC groups, and the SVM paradigm using these significantly different features has the potential to be used to classify PIP and LC, which has important clinical implications.

Synthesis and pharmacological activity of vinpocetine derivatives.

Vinpocetine and its derivatives were extensively employed in the treatment of ischemic stroke, serving as effective cerebrovascular vasodilators. They could also be utilized for neuroprotection, anti-inflammatory purposes, anti-aging interventions, insomnia treatment, and antidepressant effects. However, due to issues such as hepatic first-pass effect, low bioavailability, and poor patient compliance with multiple dosing, the secondary development of Vinpocetine to address these limitations became a prominent area of research. Five primary methodologies were employed for the synthesis of Vinpocetine derivatives. These included substitution on the A ring to modify the 14-ester group, alteration of the 16-ethyl group, simplification of the D and E rings, and modification of the conformation of Vinpocetine. This paper summarized the current synthesis and activity studies of Vinpocetine and its derivatives, with the aim of providing a reference for the discovery of more potent derivatives of Vinpocetine.

Identification of potential molecular mechanism related to craniofacial dysmorphism caused by FOXI3 deficiency.

BACKGROUND: Hemifacial macrosomia (HFM, OMIM 164210) is a complex and highly heterogeneous disease. FORKHEAD BOX I3 (FOXI3) is a susceptibility gene for HFM, and mice with loss of function of Foxi3 did exhibit a phenotype similar to craniofacial dysmorphism. However, the specific pathogenesis of HFM caused by FOXI3 deficiency remains unclear till now. METHOD: In this study, we first constructed a Foxi3 deficiency (Foxi3-/- ) mouse model to verify the craniofacial phenotype of Foxi3-/- mice, and then used RNAseq data for gene differential expression analysis to screen candidate pathogenic genes, and conducted gene expression verification analysis using quantitative real-time PCR. RESULTS: By observing the phenotype of Foxi3-/- mice, we found that craniofacial dysmorphism was present. The results of comprehensive bioinformatics analysis suggested that the craniofacial dysmorphism caused by Foxi3 deficiency may be involved in the PI3K-Akt signaling pathway. Quantitative real-time PCR results showed that the expression of PI3K-Akt signaling pathway-related gene Akt2 was significantly increased in Foxi3-/- mice. CONCLUSION: The craniofacial dysmorphism caused by the deficiency of Foxi3 may be related to the expression of Akt2 and PI3K-Akt signaling pathway. This study laid a foundation for understanding the function of FOXI3 and the pathogenesis and treatment of related craniofacial dysmorphism caused by FOXI3 dysfunction.

A Hypoxia-Related miRNA-mRNA Signature for Predicting the Response and Prognosis of Transcatheter Arterial Chemoembolization in Hepatocellular Carcinoma.

Purpose: Transcatheter arterial chemoembolization (TACE) is commonly used in the treatment of hepatocellular carcinoma (HCC). However, not all patients respond to this treatment. TACE typically leads to hypoxia in the tumor microenvironment. Therefore, we aimed to construct a prognostic model based on hypoxia-related differentially expressed microRNA (miRNAs) in hepatocellular carcinoma (HCC) and to investigate the potential target mRNAs for predicting TACE response. Methods: The hypoxia-related miRNAs (HRMs) were identified in liver cancer cells, then global test was performed to further select the miRNAs which were associated with recurrence and vascular invasion. A prognostic model was constructed based on multivariate Cox regression analysis; qRT-PCR analysis was used to validate the differentially expressed miRNAs in HCC cell lines under hypoxic condition. We further identified the putative target genes of the miRNAs and investigate the relationship between the target genes and TACE response, immune cells infiltration. Results: We established a HRMs prognostic model for HCC patients, containing two miRNAs (miR-638, miR-501-5p), the patients with high-HRMs score showed worse survival in discovery and validation cohort; qRT-PCR analysis confirmed that these two miRNAs are up-regulated in hepatoma cells under hypoxic condition. Furthermore, four putative target genes of these two miRNAs were identified (ADH1B, CTH, FTCD, RCL1), which were significantly associated with TACE response, immune score, immunosuppressive immune cells infiltration, PDCD1 and CTLA4. Conclusion: The HCC-HRMs signature may be utilized as a promising prognostic factor and may have implications for guiding TACE and immune therapy.