The effect of thermal treatment on the transformation and transportation of arsenic and cadmium in soil.

Thermal treatment can effectively decontaminate soils but alter their properties. Previous research mainly focused on volatile organic compounds and metals, i.e. Hg, neglecting non-volatile metal(loid)s. This study aimed to investigate Cd and As transformation during aerobic and anaerobic calcination. The results showed that both aerobic and anaerobic calcination increased soil pH by reducing soil organic matter (SOM) content, which also influenced the cation exchange capacity (CEC) and the leaching behavior of Cd and As in the soil. The total concentrations of Cd and As in the calcined soils varied depending on the calcination temperature and atmosphere. When the aerobic calcination temperature exceeded 700 °C, Cd volatilized as CdCl2, while anaerobic calcination at relatively low temperatures (600 °C) involved reductive reactions, resulting in the formation of metallic Cd with a lower boiling point. Similarly, As volatilized at 800 °C aerobically and 600 °C anaerobically. The formation of As-based minerals, particularly Ca3(AsO4)2, hindered its gasification, whereas anaerobic calcination promoted volatilization efficiency through the generation of C-As(III) based gaseous components with lower boiling points. Contrasting trends were observed in the TCLP-extractable Cd and As contents of the calcined soils. Over 70% of TCLP-extractable Cd contents were suppressed after thermal treatment, attributed to the elevated pH and reduced CEC of the soil, as well as volatilization. However, TCLP-extractable As contents increased with elevated temperatures, likely due to the desorption of AsO43- and re-adsorption of gaseous As2O3 during cooling. These findings have implications for assessing the environmental impact of thermal treatment and provide insights for remediation strategies concerning Cd and As-contaminated soils.

Interactions of oleanane pentacyclic triterpenoids with human organic anion transporting polypeptide 1B1 and 1B3.

Oleanane pentacyclic triterpenoids have been widely used in clinical practice. However, studies on their interactions with hepatic transporters remain limited. In this study, we systematically investigated the inhibitory effects of 14 oleanane pentacyclic triterpenoids on organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1 and OATP1B3), two liver-specific uptake transporters. Through fluorescence-based cellular uptake assays, we identified three potent OATP1B1 inhibitors (saikosaponin B1, saikosaponin A and 18ß-glycyrrhetinic acid) and five potent OATP1B3 inhibitors (echinocystic acid, 3-oxo-16α-hydroxy-olean-12-en-28ß-oic acid, chikusetsu saponin IVa, saikosaponin B1 and 18ß-glycyrrhetinic acid). Structural analysis revealed that free oleanane triterpenoids inhibited OATP1B1/1B3 more potently than triterpene glycosides. Despite their similar structures, 18ß-glycyrrhetinic acid exhibited much stronger inhibition on OATP1B1/1B3 than 18α-glycyrrhetinic acid, while both were substrates of OATP1B3. Interestingly, OATP1B3 overexpression significantly increased reactive oxygen species (ROS) levels in HepG2 cells after treatment with 18ß-glycyrrhetinic acid. To conclude, this study highlights the potential interactions of oleanane pentacyclic triterpenoids with OATP1B1/1B3, and provides novel insights into the anti-cancer activity of 18ß-glycyrrhetinic acid.

Liensinine sensitizes colorectal cancer cells to oxaliplatin by targeting HIF-1α to inhibit autophagy.

BACKGROUND: Oxaliplatin is the most common chemotherapeutic agent for patients with colorectal cancer. However, its anti-cancer efficacy is restricted by drug resistance occurring through several mechanisms, including autophagy. Liensinine exerts a considerable anti-tumor effect and can regulate autophagy. Inhibition of autophagy is a strategy to reverse resistance to oxaliplatin. The aim of this study was to check if liensinine can enhance the therapeutic efficacy of oxaliplatin in colorectal cancer and if so, elucidate its mechanism. METHODS: Two colorectal cancer cell lines, HCT116 and LoVo, and one normal intestinal epithelial cell, NCM-460 were used for in vitro experiments. Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry assays were used to evaluate the cytotoxicity of liensinine and oxaliplatin. Network pharmacology analysis and Human XL Oncology Array were used to screen targets of liensinine. Transfections and autophagy regulators were used to confirm these targets. The relationship between the target and clinical effect of oxaliplatin was analyzed. Patient-derived xenograft (PDX) models were used to validate the effects of liensinine and oxaliplatin. RESULTS: CCK-8 and colony formation assays both showed that the combination treatment of liensinine and oxaliplatin exerted synergistic effects. Results of the network pharmacology analysis and Human XL Oncology Array suggested that liensinine can inhibit autophagy by targeting HIF-1α/eNOS. HIF-1α was identified as the key factor modulated by liensinine in autophagy and induces resistance to oxaliplatin. HIF-1α levels in tumor cells and prognosis for FOLFOX were negatively correlated in clinical data. The results from three PDX models with different HIF-1α levels showed their association with intrinsic and acquired resistance to oxaliplatin in these models, which could be reversed by liensinine. CONCLUSIONS: Research on the relationship between HIF-1α levels and the clinical effect of oxaliplatin is lacking, and whether liensinine regulates HIF-1α is unknown. Our findings suggest that liensinine overcomes the resistance of colorectal cancer cells to oxaliplatin by suppressing HIF-1α levels to inhibit autophagy. Our findings can contribute to improving prognosis following colorectal cancer therapy.

Study on the mechanism of Huangqi Guizhi Wuwu Decoction in treating diabetes peripheral neuropathy based on network pharmacology and molecular docking.

This study aimed to explore the effective substances and mechanism network of Huangqi Guizhi Wuwu Decoction in treating diabetes peripheral neuropathy. Based on the TCM systemic pharmacological analysis platform (TCMP) and UniProt database, the database of active Huqarqu Decoction was constructed, and the related targets of diabetic peripheral neuropathy were collected through the OMIM, CTD, DisGeNET, TTD and GeneCards databases. The intersection targets were obtained to construct the network diagram of Huangqi dis Guizhi Wuwu Decoction-Active Through the String database, the interaction between target proteins was analyzed, and molecular docking between active components and potential targets was carried out. Combined with the DAVID v6.8 database, GO function analysis and KEGG pathway analysis were performed on the targets. Guizhi Wuwu Decoction mainly acts on core targets such as IL6, MAPK3, VE GFA, JUN and ESR1 through quercetin, kaempferol and naringin and regulates the TNF signaling pathway, estrogen signaling pathway and MAPK signaling pathway, thus achieving the effect of treating diabetes peripheral neuropathy. Huangqi Guizhi Wu has multiple targets and regulates multiple signaling pathways in neuropathy, which lays a foundation for future pharmacological research.

Developing preclinical dog models for reconstructive severed spinal cord continuity via spinal cord fusion technique.

Background: Spinal cord injury (SCI) is a severe impairment of the central nervous system, leading to motor, sensory, and autonomic dysfunction. The present study investigates the efficacy of the polyethylene glycol (PEG)-mediated spinal cord fusion (SCF) techniques, demonstrating efficacious in various animal models with complete spinal cord transection at the T10 level. This research focuses on a comparative analysis of three SCF treatment models in beagles: spinal cord transection (SCT), vascular pedicle hemisected spinal cord transplantation (vSCT), and vascularized allograft spinal cord transplantation (vASCT) surgical model. Methods: Seven female beagles were included in the SCT surgical model, while four female dogs were enrolled in the vSCT surgical model. Additionally, twelve female dogs underwent vASCT in a paired donor-recipient setup. Three surgical model were evaluated and compared through electrophysiology, imaging and behavioral recovery. Results: The results showed a progressive recovery in the SCT, vSCT and vASCT surgical models, with no statistically significant differences observed in cBBB scores at both 2-month and 6-month post-operation (both P>0.05). Neuroimaging analysis across the SCT, vSCT and vASCT surgical models revealed spinal cord graft survival and fiber regrowth across transection sites at 6 months postoperatively. Also, positive MEP waveforms were recorded in all three surgical models at 6-month post-surgery. Conclusion: The study underscores the clinical relevance of PEG-mediated SCF techniques in promoting nerve fusion, repair, and motor functional recovery in SCI. SCT, vSCT, and vASCT, tailored to specific clinical characteristics, demonstrated similar effective therapeutic outcomes.

Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

Application of"Spinal cord fusion" in spinal cord injury repair and its neurological mechanism.

Spinal cord injury (SCI) is a severely disabling and catastrophic condition that poses significant global clinical challenges. The difficulty of SCI repair results from the distinctive pathophysiological mechanisms, which are characterised by limited regenerative capacity and inadequate neuroplasticity of the spinal cord. Additionally, the formation of cystic cavities and astrocytic scars after SCI further obstructs both the ascending and descending neural conduction pathways. Consequently, the urgent challenge in post-SCI recovery lies in repairing the damaged spinal cord to reconstruct a functional and intact neural conduction circuit. In recent years, significant advancements in biological tissue engineering technology and novel therapies have resulted in a transformative shift in the field of SCI repair. Currently, SCI treatment primarily involves drug therapy, stem cell therapy, the use of biological materials, growth factors, and other approaches. This paper comprehensively reviews the progress in SCI research over the years, with a particular focus on the concept of "Spinal Cord Fusion" as a promising technique for SCI reconstruction. By discussing this important research progress and the neurological mechanisms involved, our aim is to help solve the problem of SCI repair as soon as possible and to bring new breakthroughs in the treatment of paraplegia after SCI.

Clinical Presentation, Management, and Diagnostic Performance of 2021 Criteria for Paraneoplastic Neurologic Syndromes in Childhood.

BACKGROUND AND OBJECTIVES: Paraneoplastic neurologic syndromes (PNSs) are remote neurologic immune-related effects of tumors. The clinical characteristics of pediatric PNSs remain unclear. We retrospectively examined the clinical characteristics of cases of pediatric PNSs and assessed the performance of the 2021 diagnostic criteria in children. METHODS: Patients hospitalized in the Beijing Children's Hospital between June 2015 and June 2023 and fulfilling the description of definite by 2004 diagnostic criteria of PNSs were included. A retrospective analysis of clinical characteristics was conducted, and the 2021 diagnostic criteria were applied to rediagnostic stratification. RESULTS: Among the 42 patients included, the most common neurologic syndrome was opsoclonus-myoclonus syndrome (OMS) (62%), followed by rapidly progressive cerebellar syndrome (26%). Most tumors were neuroblastomas (88%), with few being ovarian teratomas (10%). Approximately 71% (30/42) of patients were classified as definite and 24% (10/42) as probable according to the 2021 criteria. All cases judged as probable exhibited rapidly progressive cerebellar ataxia with neuroblastoma. For OMS, chemotherapy was administered based on the tumor's risk stage, accompanied by regular infusion of IV gamma globulin and oral steroids following tumor diagnosis. Twenty-one patients underwent regular follow-ups over 4.92 (0.58-7.58) years. The initial hospitalization recorded a median score of 12 (7-14) on the Mitchell and Pike OMS rating scale, decreasing to 0 (0-5) at the final follow-up. In cases of rapidly progressive cerebellar syndrome, a similar therapeutic regimen was used. Nine patients underwent regular follow-ups over 4.42 (1.17-7.50) years. The mean modified Rankin scale score at first hospitalization was 4 (3-4), reducing to 1 (0-4) at the final follow-up. Only 17% (5/30) of patients across both groups exhibited poor response to this regimen. Among these 5 patients, 4 belonged to the low-risk group (without chemotherapy). DISCUSSION: OMS followed by rapidly progressive cerebellar ataxia are the most common forms of PNSs in children and are associated with neuroblastoma. An aggressive approach with multiple immunotherapies may improve the prognosis of neuroblastoma-associated PNSs. The 2021 criteria perform well in pediatric PNSs. However, we propose upgrading the classification of antibody-negative rapidly progressive cerebellar ataxia with neuroblastoma to definite diagnosis. This adjustment aims to further improve the diagnostic efficacy of this diagnostic criterion in childhood.

SF3B3-regulated mTOR alternative splicing promotes colorectal cancer progression and metastasis.

BACKGROUND: Aberrant alternative splicing (AS) is a pervasive event during colorectal cancer (CRC) development. SF3B3 is a splicing factor component of U2 small nuclear ribonucleoproteins which are crucial for early stages of spliceosome assembly. The role of SF3B3 in CRC remains unknown. METHODS: SF3B3 expression in human CRCs was analyzed using publicly available CRC datasets, immunohistochemistry, qRT-PCR, and western blot. RNA-seq, RNA immunoprecipitation, and lipidomics were performed in SF3B3 knockdown or overexpressing CRC cell lines. CRC cell xenografts, patient-derived xenografts, patient-derived organoids, and orthotopic metastasis mouse models were utilized to determine the in vivo role of SF3B3 in CRC progression and metastasis. RESULTS: SF3B3 was upregulated in CRC samples and associated with poor survival. Inhibition of SF3B3 by RNA silencing suppressed the proliferation and metastasis of CRC cells in vitro and in vivo, characterized by mitochondria injury, increased reactive oxygen species (ROS), and apoptosis. Mechanistically, silencing of SF3B3 increased mTOR exon-skipped splicing, leading to the suppression of lipogenesis via mTOR-SREBF1-FASN signaling. The combination of SF3B3 shRNAs and mTOR inhibitors showed synergistic antitumor activity in patient-derived CRC organoids and xenografts. Importantly, we identified SF3B3 as a critical regulator of mTOR splicing and autophagy in multiple cancers. CONCLUSIONS: Our findings revealed that SF3B3 promoted CRC progression and metastasis by regulating mTOR alternative splicing and SREBF1-FASN-mediated lipogenesis, providing strong evidence to support SF3B3 as a druggable target for CRC therapy.

Wireless Gold/Boron-Nitrogen-Codoped Graphene-Based Antenna Immunosensor for the Rapid Detection of Neuron-Specific Enolase.

Tumor-marker immunosensors for rapid on-site detection have not yet been developed because of immunoreaction bottlenecks, such as shortening the reaction time and facilitating incubation. In this study, a gold-boron-nitrogen-codoped graphene (Au-BNG)-based immunosensor antenna was constructed for the rapid detection of neuron-specific enolase (NSE). A Au-BNG radiation electrode with dual functions of antibody protein fixation and signal transmission was developed for the first time. A radiation sample cell was constructed by embedding a radiation electrode into the groove of a poly(dimethylsiloxane) dielectric substrate. The constructed sense antenna achieves accurate detection of NSE with a range from 50 fg mL-1 to 40,000 pg mL-1 and a limit of detection of 10.99 fg mL-1, demonstrating excellent selectivity, stability, and reliability. The tumor-marker detection meter can provide NSE detection results as rapidly as within 2 min by using the new strategy of the microwave self-incubation of tumor markers. This antenna immunosensor is suitable for rapid detection in outpatient clinics and can be developed into household tumor-marker detectors, which would be significant in the early detection, long-term monitoring, and efficacy evaluation of tumors.

Effects of Different Volumes of Ropivacaine for Pericapsular Nerve Group Block on Incidence of Quadriceps Weakness and Analgesic Efficacy Following Hip Arthroplasty: A Randomized Controlled Trial.

INTRODUCTION: The pericapsular nerve group (PENG) block has been shown to be an effective approach to alleviating pain and reducing the need for opioids among older adults following hip surgery, with possible motor-sparing effects. No reports to date, however, have described appropriate ropivacaine volumes for use in the context of PENG block. The present prospective randomized controlled study was thus developed to assess the quadriceps muscle strength and analgesic efficacy associated with PENG block performed using three different volumes of 0.33% ropivacaine following general anesthesia in older adults undergoing hip arthroplasty. METHODS: In this prospective randomized double-blind controlled clinical study, 60 patients were assigned at random to undergo ultrasound-guided PENG block for hip arthroplasty using different volumes of ropivacaine. Specifically, these patients were administered 10 ml (Group A, n = 20), 20 ml (Group B, n = 20), or 30 ml (Group C, n = 20) of 0.33% ropivacaine. Quadriceps muscle strength was evaluated at 6 h post-surgery. Visual analog scale (VAS) scores at rest and with movement were assessed at 4, 6, 12, and 24 h post-surgery. Block duration, adverse event incidence, and patient satisfaction were evaluated at 24 h post-surgery. RESULTS: Quadriceps motor block incidence rates at 6 h post-surgery in the 10 ml, 20 ml, and 30 ml groups were 5%, 20%, and 75%, respectively. Quadriceps muscle weakness at 6 h post-surgery was significantly more common in the 30 ml group relative to the others (p < 0.001). Patients administered 10 ml 0.33% ropivacaine exhibited significantly higher VAS pain scores at rest and with movement relative to those patients in the 20 ml and 30 ml treatment groups at all time points (p < 0.05). No apparent differences in analgesic efficacy were observed when comparing the 20 ml and 30 ml groups at 4, 6, 12, and 24 h post-surgery. No significant differences in block duration, satisfaction, or adverse event incidence were observed among groups. CONCLUSIONS: The preservation of motor function in the 20 ml 0.33% ropivacaine group was superior to that in the 30 ml 0.33% ropivacaine group. Relative to the group that received 10 ml 0.33% ropivacaine during PENG block, those elderly patients administered 20 ml and 30 ml volumes of 0.33% ropivacaine experienced superior postoperative pain relief following hip arthroplasty.

Hydrogen sulfide improves endothelial barrier function by modulating the ubiquitination degradation of KLF4 through TRAF7 S-sulfhydration in diabetic aorta.

Anomalous vascular endothelium significantly contributes to various cardiovascular diseases. VE-cadherin plays a vital role in governing the endothelial barrier. Krüppel-like factor 4(KLF4), as a transcription factor, which binds the VE-cadherin promoter and enhances its transcription. Tumor necrosis factor receptor-associated factor 7 (TRAF7) is an E3 ubiquitin ligase that has been shown to modulate the degradation of KLF4. H2S can covalently modify cysteine residues on proteins through S-sulfhydration, thereby influencing the structure and functionality of the target protein. However, the role of S-sulfhydration on endothelial barrier integrity remains to be comprehensively elucidated. This study aims to investigate whether protein S-sulfhydration in the endothelium regulates endothelial integrity and its underlying mechanism. In this study, we observed that protein S-sulfhydration was reduced in the endothelium during diabetes and TRAF7 was the main target. Overexpression of TRAF7-Cys327 mutant could mitigate the endothelial barrier damage by weakening TRAF7 interaction with KLF4 and reducing ubiquitination degradation of KLF4. In conclusion, our research demonstrates that H2S plays a pivotal role in regulating S-sulfhydration of TRAF7 at Cys327. This regulation effectively inhibits the ubiquitin-mediated degradation of KLF4, resulting in an upregulation of VE-cadherin levels. This molecular mechanism contributes to the prevention of endothelial barrier damage.

Design, Synthesis, Antifungal Activity, and 3D-QASR of Novel Oxime Ether-Containing Coumarin Derivatives as Potential Fungicides.

Structural modification of natural products is an effective approach for improving antifungal activity and has, therefore, been used extensively in the development of new agrochemical products. In this work, a series of novel coumarin derivatives containing oxime ether structures were designed, synthesized, and evaluated for antifungal activity. Some of the designed compounds exhibited promising antifungal activities against tested fungi, and compounds 4a, 4c, 5a, and 6b had EC50 values equivalent to those of commercial fungicides. Compound 6b was the most promising candidate fungicide against Rhizoctonia solani (EC50 = 0.46 µg/mL). In vivo antifungal bioassays suggested that compounds 5a and 6b could serve as novel agricultural antifungals. Furthermore, microscopy demonstrated that compound 6b induced the sprawling growth of hyphae, distorted the outline of cell walls, and reduced mitochondrial numbers. Additionally, the effects of the substituent steric, electrostatic, hydrophobic, and hydrogen-bond fields were elucidated using an accurate and reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) model. The results presented here will guide the discovery of potential novel fungicides for plant disease control in agriculture.

BET bromodomain inhibitors PFI-1 and CPI-203 suppress the development of follicular lymphoma via regulating Wnt/ß-catenin signaling.

Objective: Follicular lymphoma (FL) is an indolent B-cell lymphoproliferative disorder, characterized by a lymphoid follicular pattern of growth. PFI-1 or CPI-203 has been known to effectively promote the inhibition of primary effusion lymphoma progression. This study aimed at investigating the anti-tumor properties of PFI-1 and CPI-203 on FL cells and uncover the underlying mechanism of action. Methods: FL cells were treated with PFI-1 and CPI-203, and the treated cells were evaluated for their cell viability, cell cycle and apoptosis using CCK8, flow cytometry, and Western blot assays. A xenograft mouse model was used for assessing the in vivo effects of CPI-203 on tumorigenesis. Results: PFI-1 or CPI-203 showed potential inhibitory effects on the cell viability of DOHH2 and RL cells in a dose-response-dependent manner. Furthermore, PFI-1 and CPI-203 inhibited cell growth, induced apoptosis of FL cells in vitro, and facilitated the translocation of ß-catenin into cytoplasm both in vitro and in vivo. After engrafted with FL cells, CPI-203-treated mice got a longer duration of survival and a smaller tumor size than control mice. Mechanistically, PFI-1 and CPI-203 impede the activity of ß-catenin and its downstream molecules by regulating the DVL2/GSK3ß axis. Conclusion: In conclusion, PFI-1 and CPI-203 may serve as potential anti-tumor inhibitors for the therapy of FL.

Comparison of the Efficacy Among Nilotinib, Dasatinib, Flumatinib and Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients: A Real-World Multi-Center Retrospective Study.

BACKGROUND: There are limited data comprehensively comparing therapy responses and outcomes among nilotinib, dasatinib, flumatinib and imatinib for newly diagnosed chronic-phase chronic myeloid leukemia in a real-world setting. PATIENTS AND METHODS: Data from patients with chronic-phase CML receiving initial a second-generation tyrosine-kinase inhibitor (2G-TKI, nilotinib, dasatinib or flumatinib) or imatinib therapy from 77 Chinese centers were retrospectively interrogated. Propensity-score matching (PSM) analyses were performed to to compare therapy responses and outcomes among these 4 TKIs. RESULTS: 2,496 patients receiving initial nilotinib (n = 512), dasatinib (n = 134), flumatinib (n = 411) or imatinib (n = 1,439) therapy were retrospectively interrogated in this study. PSM analyses indicated that patients receiving initial nilotinib, dasatinib or flumatinib therapy had comparable cytogenetic and molecular responses (p = .28-.91) and survival outcomes including failure-free survival (FFS, p = .28-.43), progression-free survival (PFS, p = .19-.93) and overall survival (OS) (p values = .76-.78) but had significantly higher cumulative incidences of cytogenetic and molecular responses (all p values < .001) and higher probabilities of FFS (p < .001-.01) than those receiving imatinib therapy, despite comparable PFS (p = .18-.89) and OS (p = .23-.30). CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.

Locoregional therapies for hepatocellular carcinoma: The current status and future perspectives.

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related mortality. Locoregional therapies (LRTs) play a crucial role in HCC management and are selectively adopted in real-world practice across various stages. Choosing the best form of LRTs depends on technical aspects, patient clinical status and tumour characteristics. Previous studies have consistently highlighted the efficacy of combining LRTs with molecular targeted agents in HCC treatment. Recent studies propose that integrating LRTs with immune checkpoint inhibitors and molecular targeted agents could provide substantial therapeutic benefits, a notion underpinned by both basic and clinical evidence. This review summarised the current landscape of LRTs in HCC and discussed the anticipated outcomes of combinations with immunotherapy regimens.

Pulmonary arterial sarcoma: A case report.

RATIONALE: Pulmonary artery sarcoma (PAS) is a rare malignant tumor primarily originating from the pulmonary artery's intima or subintima. Approximately one-third of cases are classified as undifferentiated type. Its clinical manifestations lack specificity, dyspnea is the main symptom but can also present with chest pain, cough, hemoptysis, and other discomforts, making it prone to misdiagnosis as pulmonary embolism (PE). PATIENT CONCERNS: A 50-year-old woman was admitted to the hospital with "dyspnea for more than 3 months, aggravated for 2 days," and computed tomography pulmonary angiography suggesting "bilateral multiple pulmonary embolisms." DIAGNOSES: The patient was initially misdiagnosed as PE, and was later definitively diagnosed as undifferentiated pleomorphic sarcoma of the pulmonary artery by pathologic biopsy. INTERVENTIONS AND OUTCOMES: The patient was initially treated with anticoagulant therapy, but her dyspnea was not relieved. After that, she underwent positron emission computed tomography (PET-CT) and other investigations, which suggested the possibility of PAS, and then she underwent pulmonary endarterectomy to remove the lesion, which relieved her symptoms and was advised to seek further medical attention from the Department of Oncology and Department of Radiotherapy. LESSONS: PAS can be easily misdiagnosed as PE. If a diagnosis of PE is made, but anticoagulation or even thrombolytic therapy proves ineffective, and there is no presence of PE causative factors such as deep vein thrombosis in the lower extremities, or D-dimer levels are not high, one should be cautious and consider the possibility of PAS.

A novel ferroptosis-related gene signature for overall survival prediction in patients with gastric cancer.

The global diagnosis rate and mortality of gastric cancer (GC) are among the highest. Ferroptosis and iron-metabolism have a profound impact on tumor development and are closely linked to cancer treatment and patient's prognosis. In this study, we identified six PRDEGs (prognostic ferroptosis- and iron metabolism-related differentially expressed genes) using LASSO-penalized Cox regression analysis. The TCGA cohort was used to establish a prognostic risk model, which allowed us to categorize GC patients into the high- and the low-risk groups based on the median value of the risk scores. Our study demonstrated that patients in the low-risk group had a higher probability of survival compared to those in the high-risk group. Furthermore, the low-risk group exhibited a higher tumor mutation burden (TMB) and a longer 5-year survival period when compared to the high-risk group. In summary, the prognostic risk model, based on the six genes associated with ferroptosis and iron-metabolism, performs well in predicting the prognosis of GC patients.

Identification of differentially expressed miRNAs in plasma exosomes from patients with early-onset pre-eclampsia using next generation sequencing.

Pre-eclampsia (PE), a major cause of perinatal morbidity and mortality, accounts for up to 14 % mortality of maternal and 18 % of fetal or infant mortalities. However, the pathogenesis process of PE remains unclear. The aim of this study was to identify differentially expressed microRNAs (miRNAs) in the peripheral blood exosomes of early-onset PE patients versus healthy pregnant women using high-throughput sequencing, and to find candidate miRNAs as molecular markers. Methods: Peripheral blood samples were collected from five preeclamptic patients and five healthy women. Exosomal miRNAs were sequenced using the Illumina HiSeq4000 sequencing platform. The target gene prediction, biological function enrichment, and signaling pathway prediction of the miRNAs with significant differences were carried out using the Starbase database software, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. Our results showed 65 significantly differentially expressed miRNAs in the exosomes of early-onset PE patients compared to control group, with 17 up-regulated and 48 down-regulated (P < 0.05). A total of 2231 target genes were predicted for all differentially expressed miRNAs. Biological functions enriched by these target genes were mainly associated with Ras protein signal transduction, GTPase-mediated signal transduction regulation, histone modification, and ß-transforming growth factor regulatory process. Key regulatory signaling pathways included TGF-ß signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, tumor necrosis factor signaling pathway and EGFR tyrosine kinase inhibition signaling pathways. QPCR validation in 40 independent samples for 10 miRNAs, identified three miRNAs were confirmed in the second population. MIR7151 was a most significant differentially expressed miRNAs, and predicted its downstream regulatory gene, KCNQ10T1, using Starbase software. There were significant differences in miRNA expression profiles between peripheral blood exosomes of early-onset PE patients and normal pregnant women, suggesting that these miRNAs may contribute to the pathophysiology of early-onset PE by regulating various biological functions and signaling pathways.