Bioinformatics Analysis of Hub Genes in Craniofacial Microsomia Combined With Congenital Heart Disease.

OBJECTIVE: The primary objective of this study was to investigate potential mechanisms and explore hub genes of craniofacial microsomia (CFM) patients associated with congenital heart defects (CHD). METHODS: Initially, the authors acquired target gene data related to CFM and congenital cardiac anomalies. Subsequently, the authors established a protein-protein interaction (PPI) network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and molecular complex detection were conducted using Metascape. Finally, the authors hub genes were screened by the cytoHubba plugin. RESULTS: A total of 43 CFM genes and 120 optimal CHD candidate genes were selected. The PPI networks for pathogenic genes contained 163 nodes and 1179 edges. Functional enrichment analysis largely focused on tissue formation and development. Five modules were identified from the PPI network, and 7 hub genes were screened out. The genes most relevant to CFM associated with congenital cardiac anomalies pathogenesis included fibroblast growth factor 3, GATA binding protein 3, nuclear factor of activated T cells 1, histone cell cycle regulator, EPAS1, mitogen-activated protein kinase 1, and CRK like proto-oncogene, adaptor protein. CONCLUSIONS: This study identified some significant hub genes, pathways, and modules of CFM associated with CHD by bioinformatics analyses. Our findings indicate that gene subfamilies fibroblast growth factor 3, GATA binding protein 3, nuclear factor of activated T cells 1, histone cell cycle regulator, EPAS1, mitogen-activated protein kinase 1, and CRK like proto-oncogene, adaptor protein may have had significant involvement in both CFM and CHD.

Identification of bioactive ingredients and potential mechanisms of flowers of Hosta Plantaginea in treating pneumonia based on network pharmacology and experimental validation.

Flowers of Hosta plantaginea (H. plantaginea), a widely utilized medicinal herb in Mongolian medicine, holds a significant historical background in terms of its medicinal applications. This herb is renowned for its ability to clear heat and detoxify the body, alleviate cough, and provide relief to the throat. However, the active ingredients and the potential mechanism of action remain ambiguity. The objective of this study was to conduct a comprehensive analysis of the efficacy of H. plantaginea in treating pneumonia, identify its active ingredients and unveil the pharmacological mechanism in the treatment of pneumonia. In vivo experiments demonstrate the plant's anti-pneumonia properties, while mass spectrometry analysis identifies 62 chemicals, with 14 absorbed into the bloodstream. Network pharmacology and Venn analysis reveal 195 targets of 52 active ingredients, with 49 gene targets common to H. plantaginea and pneumonia. Protein-protein interaction (PPI) network construction and enrichment analysis highlight the key targets and pathways such as AKT, EGFR, IL-17. Western blotting confirms downregulation of these pathways, indicating the anti-inflammatory effects of H. plantaginea in treating acute lung injury. Our findings showed that the treatment of ALI with the H. plantaginea exerts its anti-inflammatory effects through multiple components, targets, and pathways. This study established a solid experimental foundation for investigating the various components, targets, and pathways involved in the treatment of pneumonia using H. plantaginea. It offers valuable insights from multiple perspectives and can serve as a reference for the clinical application of this plant in pneumonia treatment.

The first diagnosis of Severe Fever with Thrombocytopenia Syndrome caused by tick-borne Severe Fever with Thrombocytopenia Syndrome virus in Chongqing, China: A case report and literature review.

BACKGROUND: Severe Fever with Thrombocytopenia Syndrome (SFTS) is a tick-borne disease caused by the SFTS virus (SFTSV) which has the potential to become a pandemic and is currently a major public health concern. CASE PRESENTATION: We present the case of a 74-year-old female from an urban area of Chongqing, with leukocytopenia, thrombocytopenia, organ function, inflammatory, blood coagulation, and immune abnormalities. SFTSV infection was confirmed through molecular detection and metagenomic next-generation sequencing (mNGS) analysis, indicating a diagnosis of SFTS due to the patient's history of tick bites. The patient received symptomatic and supportive therapy, including antibiotics, antiviral treatment, and antifungal therapy, and finally discharged from the hospital on day 18. CONCLUSIONS: This study highlights the need for increased awareness, early diagnosis, and prompt treatment for tick-borne SFTS. It also provides a comprehensive understanding of the disease's characteristics, pathogenesis, detection methods, and available treatments.

Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia.

OBJECTIVE: In B-cell acute lymphoblastic leukemia (B-ALL), current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50% of cases, underscoring the urgent need for new therapeutic regimens for this patient population. The present study aimed to determine whether HZX-02-059, a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) and tubulin, is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients. METHODS: Cell proliferation, vacuolization, apoptosis, cell cycle, and in-vivo tumor growth were evaluated. In addition, Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL. RESULTS: HZX-02-059 was found to inhibit cell proliferation, induce vacuolization, promote apoptosis, block the cell cycle, and reduce in-vivo tumor growth. Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase (PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations. CONCLUSION: Overall, these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

Effect of prior lenalidomide or daratumumab exposure on hematopoietic stem cell collection and reconstitution in multiple myeloma.

BACKGROUND: The roles of Lenalidomide (Len) and Daratumumab (Dara) in multiple myeloma treatment are well-established, yet their influences on hematopoietic stem cell harvesting and reconstitution remain disputed. METHODS: We conducted a systematic database review to identify cohort studies or RCTs evaluating the effect of the use of Len or Dara on hematopoietic stem cell collection and peripheral blood count recovery in multiple myeloma patients. Effects on hematopoietic collection or reconstitution were estimated by comparing standardized mean differences (SMD) and mean differences (MD), or median differences. RESULTS: Eighteen relevant studies were identified, summarizing mobilization results. For Len, data from 13 studies were summarized, including total CD34+ cell yield, collection failure rate, and time to neutrophil and platelet engraftment. Results indicated that Len exposure led to decreased stem cell collection [SMD=-0.23, 95% CI (-0.34, -0.12)]. However, collection failure (<2×106) could be mitigated by plerixafor [OR=2.14, 95% CI (0.96, 4.77)]. For Dara, two RCTs and three cohort studies were included, showing that Dara exposure resulted in a reduction in total stem cells even with optimized plerixafor mobilization [SMD=-0.75, 95% CI (-1.26, -0.23)], and delayed platelet engraftment recovery [MD=1.20, 95% CI (0.73, 1.66)]. CONCLUSIONS: Our meta-analysis offers a comprehensive view of Len and Dara's impacts on hematopoietic stem cell collection and reconstitution in multiple myeloma. Len usage could lead to reduced stem cell collection, counteracted by plerixafor mobilization. Dara usage could result in diminished stem cell collection and delayed platelet engraftment.

Sparse Action Tube Detection.

Action tube detection is a challenging task as it requires not only to locate action instances in each frame, but also link them in time. Existing action tube detection methods often employ multi-stage pipelines with complex designs and time-consuming linking procedure. In this paper, we present a simple end-to-end action tube detection method, termed as Sparse Tube Detector (STDet). Unlike those dense action detectors, our core idea is to use a set of learnable tube queries and directly decode them into action tubes (i.e., a set of tracked boxes with action label) from video content. This sparse detection paradigm shares several advantages. First, the large number of hand-crafted anchor candidates in dense action detectors is greatly reduced to a small number of learnable tubes, which results in a more efficient detection framework. Second, our learnable tube queries directly attend the whole video content, which endows our method with the capacity of capturing long-range information for action detection. Finally, our action detector is an end-to-end tube detection without requiring the linking procedure, which directly and explicitly predicts the action boundary instead of depending on the linking strategy. Extensive experiments shows that our STDet outperforms the previous state-of-the-art methods on two challenging untrimmed video action detection datasets of UCF101-24 and MultiSports. We hope our method will be an simple end-to-end tube detection baseline and can inspire new ideas in this direction.

Lactate acid promotes PD-1+ Tregs accumulation in the bone marrow with high tumor burden of Acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) displayed poor response to programmed death-1 (PD-1) blockade therapy. Regulatory T cells (Tregs) was one of major immunosuppressive components in Tumor microenvironment and plays a vital role in the resistance of immunotherapy. Coinhibitory receptors regulate function of regulatory Tregs and are associated with resistance of PD-1 blockade. However, the coinhibitory receptors expression and differentiated status of Tregs in AML patients remain to be unclear. METHODS: Phenotypic determination of Tregs and CD8+ T cells in bone marrow of healthy donors and AML patients was performed by flow cytometry. Coculture experiments of AML and Tregs in vitro were performed and the concentrations of lactate acid (LA) in the supernatant were examined by ELISA. RESULTS: More Tregs differentiated into effector subsets in AML patients. However, PD-1 and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression on Tregs were comparable in healthy donors and AML patients. Further analysis showed that PD-1+ and PD-1+TIGIT+Tregs are more abundant in the bone marrow of patients with higher leukemic load. Moreover, PD-1+ Tregs accumulation was associated with higher level of senescent CD4+ T cells and increased frequencies of exhausted CD4+ as well as CD8+ T cells. Notably, neither Tregs nor their effector subsets were decreased among patients in complete remission. PD-1 expression was significantly downregulated in Tregs after achieving complete remission. Mechanistically, both AML cell line (KG-1α) and primary AML blasts produced high concentration of LA. Blockade of LA by lactate transporter inhibitor abrogated the upregulation of PD-1 by AML cells. CONCLUSION: PD-1+ Tregs accumulation in bone marrow in higher leukemic burden setting was linked to lactate acid secreted by AML blasts and decreased after disease remission. Our findings provided a novel insight into Tregs in AML and possible mechanism for resistance of PD-1 blockade in AML.

The novel miR-873-5p-YWHAE-PI3K/AKT axis is involved in non-small cell lung cancer progression and chemoresistance by mediating autophagy.

Non-small cell lung cancer (NSCLC) encompasses approximately 85% of all lung cancer cases and is the foremost cancer type worldwide; it is prevalent in both sexes and known for its high fatality rate. Expanding scientific inquiry underscores the indispensability of microRNAs in NSCLC. Here, we probed the impact of miR-873-5p on NSCLC development and chemoresistance. qRT‒PCR was used to measure the miR-873-5p level in NSCLC cells with or without chemoresistance. A model of miR-873-5p overexpression was constructed. The proliferation and viability of NSCLC cells were evaluated through CCK8 and colony formation experiments. Cell migration and invasion were monitored via Transwell assays. Western blotting was used to determine the levels of YWHAE, PI3K, AKT, EMT, apoptosis, and autophagy-related proteins. The sensitivity of NSCLC cells to the chemotherapeutic agent gefitinib was assessed. Additionally, the correlation of YWHAE with miR-873-5p was validated via a dual-luciferase reporter assay and RNA immunoprecipitation (RIP). Overexpressed miR-873-5p suppressed migration, proliferation, invasion, and EMT while concurrently stimulating apoptotic processes. miR-873-5p was downregulated in NSCLC cells resistant to gefitinib. Upregulating miR-873-5p reversed gefitinib resistance by inducing autophagy. YWHAE was confirmed to be a downstream target of miR-873-5p. YWHAE overexpression promoted the malignant behaviors of NSCLC cells and boosted tumor growth, while these effects were reversed following miR-873-5p overexpression. Subsequent investigations revealed that overexpressing YWHAE promoted PI3K/AKT pathway activation, with miR-873-5p displaying inhibitory effects on the YWHAE-mediated PI3K/AKT signaling cascade. miR-873-5p affects proliferation, invasion, migration, EMT, autophagy, and chemoresistance in NSCLC by controlling the YWHAE/PI3K/AKT axis.

Gut microbiota alteration and its association with immune function in post-COVID-19 patients.

To reveal the variation of gut microbiota and its association with immune function in cured patients with coronavirus 2019 (COVID-19) disease, gut microbiota of patients discharged from hospital for 20 ~ 23 months and healthy volunteers was analyzed by high throughput 16S rRNA sequencing. The diversity and abundance were compared, and the correlation with immunity factors was investigated, and changes in the content of 6 genera microorganisms with proportion higher than 0.1% were revealed in patients with COVID-19 disease: reduced content of Subdoligranulum, Haemophilus, Coprococcus, Eubacterium vertriosum group, and Lachnospiraceae ND3007 group and increased content of Hungatella. NK cells were negatively correlated to Subdoligranulum, while CD8 cells were positively correlated to Subdoligranulum but negative to Hungatella. IL-8 concentration was negatively correlated to Subdoligranulum, Haemophilus, Coprococcus, Eubacterium vertriosum group, and Lachnospiraceae ND3007 group but positively to Hungatella, while IL-1ß concentration was negatively correlated to Haemophilus and Eubacterium ventriosum group but positively to Hungatella. The variation of probiotics and potential pathogenic bacteria implies a higher risk in diseases and inflammation, and the modulation of the gut microbiota may help the healing of COVID-19 patients.

Small Extracellular Vesicles Laden Oxygen-Releasing Thermosensitive Hydrogel for Enhanced Antibacterial Therapy against Anaerobe-Induced Periodontitis Alveolar Bone Defect.

Periodontitis is a bacterially induced chronic destructive inflammatory disease that leads to irreversible destruction of the tooth supporting structure, including connective tissue destruction, bone resorption, and even tooth loss. Until now, there has been no effective treatment to repair inflammatory bone loss in periodontitis. Recently, small extracellular vesicles (sEVs) emerged as the essential paracrine factors of mesenchymal stem cells (MSCs) that mediated tissue regeneration. However, limitations of antimicrobial activity associated with the use of sEVs have led to the urgency of new alternative strategies. Currently, we investigated the potential of a biocompatible oxygen-releasing thermosensitive hydrogel laded with sEVs secreted by bone marrow MSCs (BMMSCs) for the alveolar bone defect in periodontitis. The hydrogel composed of different polymers such as chitosan (CS), poloxamer 407 (P407), and cross-linked hyaluronic acid (c-HA) conglomerating is a kind of nanoporous structure material. Then, the gel matrix further encapsulated sEVs and calcium peroxide nanoparticles to realize the control of sEVs and oxygen release. Furthermore, ascorbic acid was added to achieve the REDOX equilibrium and acid-base equilibrium. The experiments in vivo and in vitro proved its good biocompatibility and effectively inhibited the growth of the periodontal main anaerobe, relieved periodontal pocket anaerobic infections, and promoted the periodontal defect regeneration. Therefore, this finding demonstrated that it was a promising approach for combating anaerobic pathogens with enhanced and selective properties in periodontal diseases, even in other bacteria-induced infections, for future clinical application.

Modeling the Health Impact and Cost-Effectiveness of a Combined Schoolgirl HPV Vaccination and Cervical Cancer Screening Program in Guangdong Province, China.

Low human papillomavirus (HPV) vaccine uptake is a key barrier to cervical cancer elimination. We aimed to evaluate the health impact and cost-effectiveness of introducing different HPV vaccines into immunization programs and scaling up the screening program in Guangdong. We used a dynamic compartmental model to estimate the impact of intervention strategies during 2023-2100. We implemented the incremental cost-effectiveness ratio (ICER) in costs per averted disability-adjusted life year (DALY) as an indicator to assess the effectiveness of the intervention. We used an age-standardized incidence of 4 cases per 100,000 women as the threshold for the elimination of cervical cancer. Compared with the status quo, scaling up cervical cancer screening coverage alone would prevent 215,000 (95% CI: 205,000 to 227,000) cervical cancer cases and 49,000 (95% CI: 48,000 to 52,000) deaths during 2023-2100. If the coverage of vaccination reached 90%, domestic two-dose 2vHPV vaccination would be more cost-effective than single-dose and two-dose 9vHPV vaccination. If Guangdong introduced domestic two-dose 2vHPV vaccination at 90% coverage for schoolgirls from 2023 and increased the screening coverage, cervical cancer would be eliminated by 2049 (95% CI 2047 to 2051). Introducing two doses of domestic 2vHPV vaccination for schoolgirls and expanding cervical cancer screening is estimated to be highly cost-effective to accelerate the elimination of cervical cancer in Guangdong.

Discovery of bi-4-methoxycarbonyl-2-quinolone and evaluation of its anti-inflammatory and anti-cancer activity in vitro.

A novel alkaloid with a hexa-tetra-hexa-cyclic skeleton, Bi-4-methoxycarbonyl-2-quinolone (1), was discovered during the investigation of Brucea javanica. Additionally, six known alkaloids (2-7) were also found. The chemical structures of these compounds were identified using HRESIMS and 1D and 2D NMR spectroscopic analysis. Additionally, the absolute configuration of the new compound 1 was determined through X-ray single crystal diffraction. Compound 1 exhibited significant anti-inflammatory activity in RAW264.7 cells and demonstrated promising anti-cancer effects in Lewis cells.

Expression profiles of oviductal mRNAs and lncRNAs in the follicular phase and luteal phase of sheep (Ovis aries) with 2 fecundity gene (FecB) genotypes.

FecB (also known as BMPR1B) is a crucial gene in sheep reproduction, which has a mutation (A746G) that was found to increase the ovulation rate and litter size. The FecB mutation is associated with reproductive endocrinology, such mutation can control external estrous characteristics and affect follicle-stimulating hormone during the estrous cycle. Previous researches showed that the FecB mutation can regulate the transcriptomic profiles in the reproductive-related tissues including hypothalamus, pituitary, and ovary during the estrous cycle of small-tailed Han (STH) sheep. However, little research has been reported on the correlation between FecB mutation and the estrous cycle in STH sheep oviduct. To investigate the coding and noncoding transcriptomic profiles involved in the estrous cycle and FecB in the sheep oviduct, RNA sequencing was performed to analyze the transcriptomic profiles of mRNAs and long noncoding RNAs (lncRNAs) in the oviduct during the estrous cycle of STH sheep with mutant (FecBBB) and wild-type (FecB++) genotypes. In total, 21,863 lncRNAs and 43,674 mRNAs were screened, the results showed that mRNAs had significantly higher expression levels than the lncRNAs, and the expression levels of these screened transcripts were lower in the follicular phase than they were in the luteal phase. Among them, the oviductal glycoprotein gene (OVGP1) had the highest expression level. In the comparison between the follicular and luteal phases, 57 differentially expressed (DE) lncRNAs and 637 DE mRNAs were detected, including FSTL5 mRNA and LNC_016628 lncRNA. In the comparison between the FecBBB and FecB++ genotypes, 26 DE lncRNAs and 421 DE mRNAs were detected, including EEF1D mRNA and LNC_006270 lncRNA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis indicated that the DE mRNAs were enriched mainly in terms related to reproduction such as the tight junction, SAGA complex, ATP-binding cassette, nestin, and Hippo signaling pathway. The interaction network between DE lncRNAs and DE mRNAs indicated that LNC_018420 may be the key regulator in sheep oviduct. Together, our results can provide novel insights into the oviductal transcriptomic function against a FecB mutation background in sheep reproduction.

Coherent perfect absorber and laser induced by directional emissions in the non-Hermitian photonic crystals.

In this study, we propose the application of non-Hermitian photonic crystals (PCs) with anisotropic emissions. Unlike the ring of exceptional points (EPs) found in isotropic non-Hermitian PCs, the EPs of anisotropic non-Hermitian PCs appear as symmetrical lines about the Γ point. The formation of EPs is related to the non-Hermitian strength and the real spectrum appears in the ΓY direction. The PCs have been validated as the complex conjugate medium (CCM) by effective medium theory (EMT). Conversely, EMT indicates that the effective refractive index has a large imaginary part along the ΓX direction, which forms an evanescent wave inside the PCs. Consequently, coherent perfect absorption (CPA) and laser can be achieved in the directional emission of the ΓY. The outgoing wave in the ΓX direction is weak, which can significantly reduce the losses and electromagnetic interference. The non-Hermitian PCs enable many fascinating applications such as signal amplification, collimation, and angle sensors.

Expression of interferon regulatory factor family and its prognostic value in acute myeloid leukemia.

Aim: To elucidate the clinicopathological and prognostic values of interferon regulatory factor (IRF) family genes in acute myeloid leukemia (AML). Patients & methods: Differential expression analysis and survival analysis from several reliable databases were conducted and further validated using patients with AML. Results: The expression level of IRF1/2/4/5/7/8/9 in patients with AML was upregulated, while IRF3/6 expression was downregulated. High IRF1/7/9 expression indicated a worse overall survival rate. Conclusion: Overexpression of IRF1/7/9 may be associated with poor survival in patients with AML, suggesting that the IRF family may be a promising therapeutic target.

A foodborne outbreak linked to Bacillus cereus at two middle schools in a rural area of Chongqing, China, 2021.

Bacillus cereus (B. cereus) is a common cause of foodborne illness. An outbreak of acute gastrointestinal illness occurred at two middle schools in a rural region of Chongqing, China, in 2021. This study aimed to elucidate the outbreak's characteristics, identify risk factors, and determine the source of contamination. A retrospective cohort study and an environmental investigation were conducted. Vomit samples, anal swabs, and food samples were collected and tested by RT-PCR for 18 species of bacteria and viruses, including B. cereus. Positive samples of B. cereus underwent biochemical experiments and bacterial quantification. A total of 198 cases were reported in this outbreak, with an attack rate of 24.63%. The main symptoms were vomiting (100%), bellyache (83.33%), and dizziness (62.63%). The retrospective cohort study showed a significant association between the outbreak and rice noodles provided by a nearby food manufacturer (RR = 39.63, p < 0.001). B. cereus was detected in 20 vomit samples, three anal swabs, and seven rice noodles samples, with a count exceeding 103 CFU/g. These findings strongly suggested that the outbreak was linked to B. cereus-contaminated rice noodles. Enhancing food safety surveillance and promoting health measures among schools and food manufacturers in rural areas is crucial to prevent similar incidents in the future in Chongqing, China.

Identification of Tumor Antigens and Immune Subtypes of High-grade Serous Ovarian Cancer for mRNA Vaccine Development.

High-grade serous ovarian cancer (HGSC) is the most common pathology of ovarian cancer and has aggressive characteristics and poor prognosis. mRNA vaccines are a novel tool for cancer immune treatment and may play an important role in HGSC therapy. Our study aimed to explore tumour antigens for vaccine development and identify potential populations amenable to vaccine treatment. Based on transcription data from The Cancer Genome Atlas (TCGA), we identified four tumour-specific antigens for vaccine production: ARPC1B, ELF3, VSTM2L, and IL27RA. In addition to being associated with HGSC patient prognosis, the expression of these antigens was positively correlated with the abundances of antigen-presenting cells (APCs). Furthermore, we stratified HGSC samples into three immune subtypes (IS1-IS3) with different immune characteristics. A corhort from ICGC (International Cancer Genome Consortium) was used to validate. Patients of IS3 had the best prognosis, while patients of IS1 were most likely to benefit from vaccination. There was substantial heterogeneity in immune signatures and immune-associated molecule expression in HGSC. Finally, weighted gene coexpression network analysis (WGCNA) was employed to cluster immune-related genes and explore potential biomarkers related to vaccination. In conclusion, we identified four potential tumour antigens for mRNA vaccine production for HGSC treatment, and the immune subtype could be an important indicator to select suitable HGSC patients to receive vaccination.

The Therapeutic Effects of MUC1-C shRNA@Fe3O4 Magnetic Nanoparticles in Alternating Magnetic Fields on Triple-Negative Breast Cancer.

Purpose: Improving the treatment of triple-negative breast cancer (TNBC) is a serious challenge today. The primary objective of this study was to construct MUC1-C shRNA@ Fe3O4 magnetic nanoparticles (MNPs) and investigate their potential therapeutic benefits in alternating magnetic fields (AMF) on TNBC. Methods: Firstly, we verified the high expression of MUC1 in TNBC and synthesized specific MUC1-C shRNA plasmids (MUC1-C shRNA). Then, we prepared and characterized MUC1-C shRNA@Fe3O4 MNPs and confirmed their MUC1-C gene silencing effect and magneto-thermal conversion ability in AMF. Moreover, the inhibitory effects on TNBC in vitro and in vivo were observed as well as biosafety. Finally, the protein levels of BCL-2-associated X protein (Bax), cleaved-caspase3, glutathione peroxidase inhibitor 4 (GPX4), nuclear factor erythroid 2-related factor 2 (NRF2), and ferritin heavy chain 1 (FTH1) in TNBC cells and tissues were examined, and it was speculated that apoptosis and ferroptosis were involved in the synergistic treatment. Results: MUC1-C shRNA@ Fe3O4 MNPs have a size of ~75 nm, with an encapsulation rate of (29.78±0.63) %, showing excellent gene therapy and magnetic hyperthermia functions. Under a constant AMF (3Kw) and a set concentration (200µg mL-1), the nanoparticles could be rapidly warmed up within 20 minutes and stabilized at about 43 °C. It could be uptaken by TNBC cells through endocytosis and significantly inhibit their proliferation and migration, with a growth inhibition rate of 79.22% for TNBC tumors. After treatment, GPX4, NRF2, and FTH1 expression levels in TNBC cells and tumor tissues were suppressed, while Bax and cleaved-caspase3 were increased. As key therapeutic measures, gene therapy, and magnetic hyperthermia have shown a synergistic effect in this treatment strategy, with a combined index (q index) of 1.23. Conclusion: In conclusion, we developed MUC1-C shRNA@Fe3O4 MNPs with magnetic hyperthermia and gene therapy functions, which have shown satisfactory therapeutic effects on TNBC without significant side effects. This study provides a potential option for the precision treatment of TNBC.

Left epigastric isolated tumor fed by the inferior phrenic artery diagnosed as ectopic hepatocellular carcinoma: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the main cause of cancer-related death worldwide. Ectopic HCC, an extremely rare type of HCC, exhibits a wide range of clinical signs and radiographic features, making preoperative identification challenging. CASE SUMMARY: A 47-year-old man underwent routine abdominal color ultrasonography, which identified an asymptomatic tumor in the left upper abdomen. The patient had no history of hepatitis, did not drink alcohol, and had no family history of cancer. Abdominal contrast-enhanced computed tomography (CT) revealed a heterogeneously enhanced lesion between the spleen and stomach that had invaded the diaphragm, with blood supplied by the left inferior phrenic artery. The patient underwent laparoscopic surgery, and HCC was identified by postoperative pathology. Additionally, specific immunohistochemical staining was performed to assess the molecular biological characteristics of the HCC. The patient underwent two rounds of hepatic arterial interventional chemotherapy after surgery. Abdominal plain and enhanced magnetic resonance imaging and lung CT 3 mo postoperatively revealed no signs of local recurrence or distant metastasis. CONCLUSION: This asymptomatic ectopic HCC case described achieved an excellent result due to early detection, radical resection, and systematic surveillance.

Anemia is associated with long-term exposure to PM2.5 and its components: a large population-based study in Southwest China.

Background: Anemia is linked to PM2.5 (particulate matter with aerodynamic diameters of ⩽2.5 µm) exposure, which can increase the risk of various negative health outcomes. It remains unclear which PM2.5 components are associated with anemia and the respective contribution of each component to this association. Objective: This study aimed at investigating the association between PM2.5 and anemia in the general population and to identify the most critical PM2.5 toxic components in this association. Design: Cross-sectional study. Methods: Our study involved a large cohort of 73,511 individuals aged 30-79 from China's multi-ethnic population. We employed satellite observations and the chemical transport model (GEOS-Chem)to estimate the long-term exposure to PM2.5 and its components. Anemia was defined, according to WHO guidelines, as Hb levels below 130 g/L for men and below 120 g/L for women. Through logistic regression, we investigated the association between PM2.5 components and anemia. By utilizing weighted quantile sum (WQS) analysis, we identified key components and gained insights into their combined impact on anemia. Overall, our study sheds light on the relationship between PM2.5 exposure, its constituents, and the risk of anemia in a large cohort. Results: PM2.5 and three components, nitrate (NIT), organic matter (OM), and soil particles (SOIL), were associated with anemia. Per-standard deviation increase in the 3-year average concentrations of PM2.5 [odds ratio (OR): 1.14, 95% confidence interval (CI): 1.01, 1.28], NIT (1.20, 1.06, 1.35), OM (1.17, 1.04, 1.32), and SOIL (1.22, 1.11, 1.33) were associated with higher odds of anemia. In WQS regression analysis, the WQS index was associated with anemia (OR: 1.29, 95% CI: 1.13, 1.47). SOIL has the highest weight among all PM2.5 components. Conclusions: Long-term exposure to PM2.5 and its constituents is associated with anemia. Moreover, SOIL might be the most critical component of the relationship between PM2.5 and anemia. Our research increases the evidence of the association between PM2.5 and anemia in the general population, and targeted emission control measures should be taken into consideration to mitigate the adverse effects of PM2.5-related anemia.