Remediation mechanism of high concentrations of multiple heavy metals in contaminated soil by Sedum alfredii and native microorganisms.

Pollution accident of nonferrous metallurgy industry often lead to serious heavy metal pollution of the surrounding soil. Phytoremediation of contaminated soil is an environmental and sustainable technology, and soil native microorganisms in the process of phytoremediation also participate in the remediation of heavy metals. However, the effects of high concentrations of multiple heavy metals (HCMHMs) on plants and native soil microorganisms remain uncertain. Thus, further clarification of the mechanism of phytoremediation of HCMHMs soil by plants and native soil microorganisms is required. Using the plant Sedum alfredii (S. alfredii) to restore HCMHM-contaminated soil, we further explored the mechanism of S. alfredii and native soil microorganisms in the remediation of HCMHM soils. The results showed that (i) S. alfredii can promote heavy metals from non-rhizosphere soil to rhizosphere soil, which is conducive to the effect of plants on heavy metals. In addition, it can also enrich the absorbed heavy metals in its roots and leaves; (ii) native soil bacteria can increase the abundance of signal molecule-synthesizing enzymes, such as trpE, trpG, bjaI, rpfF, ACSL, and yidC, and promote the expression of the pathway that converts serine to cysteine, then synthesize substances to chelate heavy metals. In addition, we speculated that genes such as K19703, K07891, K09711, K19703, K07891, and K09711 in native bacteria may be involved in the stabilization or absorption of heavy metals. The results provide scientific basis for S. alfredii to remediate heavy metals contaminated soils, and confirm the potential of phytoremediation of HCMHM contaminated soil.

Targeting the serum marker interleukin 9 improves the underlying characterization and immune homeostasis in rheumatoid arthritis.

Introduction: Rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) are serological markers used for diagnosing rheumatoid arthritis (RA), an autoimmune disease characterized by inflammatory joint damage. However, there is a subset of RA patients who test negative for both RF and ACPA, known as seronegative rheumatoid arthritis (SNRA). Material and methods: The levels of serum markers were examined in both clinical samples and a rat model of type II collagen-induced RA (CIA). The effect of interleukin 9 (IL-9) on RA was investigated using recombinant rat IL-9 (rrIL-9), anti-rat IL-9 neutralizing monoclonal antibody (mAb), and control IgG antibody in the CIA rat. The severity of arthritis was assessed. Treg and Th17 cells, M1 and M2 macrophages, and inflammatory cytokine levels were analyzed. Results: We observed higher levels of IL-9 in clinical samples from SNRA patients compared to the normal group. Rat models of CIA exhibit increased arthritis scores, weight loss, paw swelling, and severe joint damage. IL-9 was the most sensitive serum marker for the diagnosis of RA in serum assays of CIA rats. IL-9 increased arthritis scores and cartilage damage, whereas treatment with IL-9 inhibitors produced the opposite effect. IL-9 inhibitors promoted Treg/Th17 homeostasis, decreased M1 macrophages, increased M2 macrophages, and decreased levels of inflammatory cytokines in joint tissues. Conclusions: These results suggest that IL-9 has potential as a diagnostic marker for SNRA. Inhibition of IL-9 could reduce the severity of arthritis in CIA rats by ameliorating inflammation and modulating the Treg/Th17 immune balance, M2 and M1 macrophage activation.

CRISPR/Cas-mediated "one to more" lighting-up nucleic acid detection using aggregation-induced emission luminogens.

CRISPR diagnostics are effective but suffer from low signal transduction efficiency, limited sensitivity, and poor stability due to their reliance on the trans-cleavage of single-stranded nucleic acid fluorescent reporters. Here, we present CrisprAIE, which integrates CRISPR/Cas reactions with "one to more" aggregation-induced emission luminogen (AIEgen) lighting-up fluorescence generated by the trans-cleavage of Cas proteins to AIEgen-incorporated double-stranded DNA labeled with single-stranded nucleic acid linkers and Black Hole Quencher groups at both ends (Q-dsDNA/AIEgens-Q). CrisprAIE demonstrates superior performance in the clinical nucleic acid detection of norovirus and SARS-CoV-2 regardless of amplification. Moreover, the diagnostic potential of CrisprAIE is further enhanced by integrating it with spherical nucleic acid-modified AIEgens (SNA/AIEgens) and a portable cellphone-based readout device. The improved CrisprAIE system, utilizing Q-dsDNA/AIEgen-Q and SNA/AIEgen reporters, exhibits approximately 80- and 270-fold improvements in sensitivity, respectively, compared to conventional CRISPR-based diagnostics. We believe CrisprAIE can be readily extended as a universal signal generation strategy to significantly enhance the detection efficiency of almost all existing CRISPR-based diagnostics.

Metabolomic biomarkers and altered phenylalanine metabolic pathway in preschool children with atopic dermatitis - A pilot study.

Background Atopic dermatitis (AD) has high prevalence in children. Current AD diagnosis and management focuses only on clinical phenotypes, but do not explore the endophenotypes, which are more important because they are a series of biomarkers linking clinical phenotype and genotype Aims Metabolomics can qualitatively and quantitatively capture real-time dynamic changes in a wide range of small molecule metabolites. This pilot study evaluated metabolomics biomarkers and altered metabolic pathways in preschool children with AD, aiming to explore the underlying molecular mechanisms and signalling pathways of the disease. Methods Blood samples of 23 preschool children with AD and 23 healthy children without AD or any other skin disease were collected. The untargeted metabolomic measurements were performed on a SCIEX-AD ultraperformance liquid chromatography system coupled with an AB SCIEX X500B QTOF system. Characteristics of small molecules in AD children were assessed and their associations with AD clinical index were evaluated. Altered metabolic pathways in AD children were also analysed using a comprehensive metabolomics platform. Results A total of 1,969 metabolites were identified, of which AD children exhibited 377 significantly altered metabolites. Multivariate statistical analysis demonstrated that the AD group and the control group could be clearly separated. Volcano plot analysis illustrated that 144 metabolites were up-regulated and 233 metabolites were down-regulated in AD children. The Severity Scoring of Atopic Dermatitis (SCORAD index) showed a moderate-to-strong association with estrogens, carotenes, leukotrienes, flavonols and keto acids in AD children (|r|=0.440-0.557). Several pathways, including the phenylalanine metabolism, were identified as altered in AD children. Limitations A small group of children was included in the study; the results need to be validated in larger sample sizes. Conclusion Results of this study illustrate potential alterations in metabolites and the phenylalanine metabolic pathway in preschool children with AD. Although this is a pilot study with a limited sample size, it may provide a new perspective for exploring the pathogenesis of AD, and for personalised treatment modalities.

Immunosuppressive effects of triptolide via interleukin-2/receptor signaling.

BACKGROUND: Triptolide (TP) has been confirmed to possess many beneficial functions including anti-inflammation and immunosuppression. OBJECTIVE: The present study aimed to explore the potential involvement of IL-2/IL-2R pathway in the immunosuppressive activities of TP. METHODS: Cultured CTLL-2 cells were utilized to evaluate the potential benefits of TP. Then cell viability was determined by CCK-8 assay, IFN-γ level by ELISA assay, Annexin V-FITC/PI double-staining and CD25 expression by flow cytometry, and protein expression by western blotting. Additionally, rhIL-2-driven lymphocytes following ConA activation were investigated. The interactions of TP with IL-2 and IL-2Rα were investigated by binding assays and molecular dynamics simulations. RESULTS: TP treatment attenuated IFN-γ level and cell viability in both rhIL-2-induced CTLL-2 cells and rhIL-2-driven splenic lymphocytes. TP treatment increased cellular apoptosis/necrosis and cleaved PARP-1 level, while suppressed c-Myc level in rhIL-2-induced CTLL-2 cells. Additionally, TP treatment reduced CD25 expression on CTLL-2 cell surface. Notably, the phosphorylation protein levels in IL-2R signaling pathways were inhibited by TP exposure prior to rhIL-2 stimulation. SPR and BLI assays verified TP that directly bound to rhIL-2 and rmIL-2Rα, respectively. Molecular simulations suggested that TP bound at the interface of IL-2 and IL-2Rα near the hydrophobic patch composed of F62, L92 on IL-2 and L23, I46, V139 on IL-2Rα, resulting in decreased binding free energy between IL-2 and IL-2Rα. CONCLUSIONS: These findings collectively emphasized that TP interfered IL-2/IL-2Rα interactions, down-regulated IL-2Rα expression, and inhibited IL-2R signaling pathways activation, thereby leading to the immune cells being desensitized to rhIL-2 and exhibiting immunosuppressive properties.

Effect of lighting conditions on implantable collamer lens vault: Influence of anterior chamber and lens parameters.

Purpose: To investigate the change in the vault of the implantable collamer lens (ICL) under dark-to-light conditions and its association with anterior chamber and lens parameters in patients undergoing ICL surgery. Methods: In 76 eyes from 40 patients, preoperative anterior chamber volume (ACV), pupil diameter (PD), anterior chamber angle, central corneal thickness (CCT), white-to-white (WTW), lens thickness (LT), axial length (AL), spherical equivalent (SE) and patient's age were collected. Postoperative vault, PD and LT were measured under dark and light conditions using anterior segment optical coherence tomography (CASIA2; TOMEY, Japan), and changes and lens displacement under dark-to-light conditions were calculated. Mixed-effects models were used to analyze the correlation between the vault change and the anterior chamber and lens parameters of all subjects and the high-vault subgroup. Results: The vault under light condition (648.36 ± 304.47 µm) was significantly smaller compared to the vault under dark condition (708.89 ± 316.15 µm). In all patients, vault change increased with the increase of age, lens displacement and PD change; and increased with the decrease of ACV, LT change and baseline vault (under dark condition). In the high-vault subgroup, vault change increased with the increase of CCT, lens displacement and PD change; and increased with the decrease of ACV. Conclusions: ICL vault changes significantly from dark to light, influenced by age, ACV, PD change, LT change, lens displacement, and baseline vault. A higher baseline vault is correlated with a larger LT change, affecting the levels of accommodation under dark-to-light transition.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated encephalitis induced by Mycoplasma pneumoniae infections.

BACKGROUND: This study aims to report the phenomenon of Myelin oligodendrocyte glycoprotein antibody-associated encephalitis induced by Mycoplasma pneumoniae infections and promote the potential benefits of combining early immunotherapy and anti-M-pneumoniae therapy for these patients. METHODS: Three children with MOG-IgG-associated encephalitis due to M. pneumoniae infections who were treated at our hospital from September to November 2023 were included in the study. We investigated and analyzed the background and clinical features of these patients. RESULTS: Three patients developed headaches, seizures, and/or other neurological manifestations, elevated mononuclear cells in cerebrospinal fluid, intracranial lesions on cranial magnetic resonance imaging (MRI), and positive MOG-IgG in serum, within 10-14 days. They were diagnosed with MOG-IgG-associated encephalitis due to M. pneumoniae infections, the treatment consisted of intravenous immunoglobulin, glucocorticoid, and erythromycin, then they were completely recovered. CONCLUSION: Mycoplasma pneumoniae (M. pneumoniae) infections can cause oligodendrocyte glycoprotein (MOG) antibody-associated encephalitis. The recognition of this condition will promote the potential benefits of combining early immunotherapy and anti-M. pneumoniae therapy for patients with MOG-IgG-associated encephalitis.

The evolution and integration of technology in spinal neurosurgery: A scoping review.

Spinal disorders pose a significant global health challenge, affecting nearly 5% of the population and incurring substantial socioeconomic costs. Over time, spinal neurosurgery has evolved from basic 19th-century techniques to today's minimally invasive procedures. The recent integration of technologies such as robotic assistance and advanced imaging has not only improved precision but also reshaped treatment paradigms. This review explores key innovations in imaging, biomaterials, and emerging fields such as AI, examining how they address long-standing challenges in spinal care, including enhancing surgical accuracy and promoting tissue regeneration. Are we at the threshold of a new era in healthcare technology, or are these innovations merely enhancements that may not fundamentally advance clinical care? We aim to answer this question by offering a concise introduction to each technology and discussing in depth its status and challenges, providing readers with a clearer understanding of its actual potential to revolutionize surgical practices.

Non-antibiotic feed additives production by Acremonium terricola solid-fermented Camellia oleifera meal.

The Camellia oleifera meal (COM), a primary byproduct of oil-tea processing, often being discarded or used as a low-grade fertilizer due to its low value. The underutilization has become a significant bottleneck hindering the high-quality development of the oil-tea industry. In this study, the production of antibiotic-free feed additives through the solid-state fermentation of COM by Acremonium terricola was investigated. Our findings revealed that a saponin concentration of 5 mg/mL significantly enhanced the production of cordycepic acid (70.4 mg/g), ergosterol (3.32 mg/g), and chitin (110 mg/g) by A. terricola. This concentration also promoted chitin production and the activities of peroxidase (POD) and Na+/K+-ATPase, thereby maintaining cellular homeostasis and energy balance in A. terricola. Solid-state fermented rice bran (RB), wheat bran (WB), and desaponificated COM (containing 2.6 mg/100 g of tea saponin) were all found to be beneficial for increasing the production of cordycepic acid and ergosterol. The blend of COM, RB, and WB in the ratio of 15:65:20 was particularly advantageous for the production and accumulation of cordycepic acid and ergosterol, yielding 1.54 and 1.43 times, 1.27 and 1.37 times, and 1.98 and 5.52 times more than those produced by WB, RB, and COM alone, respectively.Meantime, the difference in contents of sugar and protein in A. terricola cultures (ATCs) using combination were not significant compared to RB and WB. These results indicated that COM can partially replace foodstuffs or food by-products to prepare antibiotic-free feed additives by A. terricola.

Newman's theory of health as expanding consciousness: an evolutionary concept analysis.

BACKGROUND: The health as expanding consciousness (HEC) theory posits that health and disease are interconnected components of a comprehensive process aimed at expanding consciousness. AIM: The objective of this study is to introduce the concept, research status and applications of HEC and offer a comprehensive understanding of its various key components. DATA SOURCES: Databases including EMBASE, PubMed, ScienceDirect, ProQuest, Wiley, Web of Science, Sinomed, China National Knowledge Infrastructure, Wanfang, and CQVIP, covering the period from 1986 to 2023. METHOD: Employing Rodgers' evolutionary concept analysis approach, this study included and analysed 70 studies. RESULTS: The characteristics of HEC comprise aspects such as movement, time, space, energy, rhythm, and paradigm of health. The antecedents of HEC encompass disease, chaos, binding, centring, and choice point. Consequences associated with HEC include self-transcendence, unbinding, decentring, expanded consciousness, real freedom, pattern recognition, absolute consciousness, and death. CONCLUSION: This study has identified substitute terms, related concepts, attributes, antecedents, consequences, and empirical references associated with HEC. The findings provide valuable information applicable across various domains of nursing, encompassing practice, education, research, and management.

Severe generalized edema in a premature neonate: A case report and literature review.

Key Clinical Message: With no family history, and an atypical phenotype, the clinical diagnosing of Noonan syndrome (NS) can be very difficult. The present case emphasized that generalized edema in neonates may be the potential first symptom of NS. Abstract: Severe generalized edema is a rare pathological condition with high mortality in newborns, in particular the premature infants. It is characterized by the extensive subcutaneous tissue edema and the accumulation of fluid in neonatal body fluid compartments. The etiology and pathogenesis of hydrops in neonates are quite complex. Generally speaking, hydrops can be divided into immune hydrops and non-immune hydrops according to the etiology. It is still challenging in treating severe neonatal edema. In this study, we presented a preterm newborn with severe generalized edema after birth, which was finally diagnosed with Noonan syndrome (NS). The infant clinically manifested as severe generalized edema alone, without the involvement of multiple organ malformation. Generalized edema in neonates was probably the first symptom of NS. Therefore, differential diagnosis of NS is necessary for infants developing generalized edema.

Tumor contour irregularity on preoperative CT predicts prognosis in renal cell carcinoma: a multi-institutional study.

Background: Radiology-based prognostic biomarkers play a crucial role in patient counseling, enhancing surveillance, and designing clinical trials effectively. This study aims to assess the predictive significance of preoperative CT-based tumor contour irregularity in determining clinical outcomes among patients with renal cell carcinoma (RCC). Methods: We conducted a retrospective multi-institutional review involving 2218 patients pathologically diagnosed with RCC. The training and internal validation sets included patients at Zhongshan Hospital between January 2009 and August 2019. The external test set comprised patients from the First Affiliated Hospital, Zhejiang University School of Medicine (January 2016 to January 2018), the Xiamen Branch of Zhongshan Hospital (November 2017 to June 2023), and the Cancer Imaging Archive. The contour irregularity degree (CID), quantified as the ratio of irregular cross-sections to the total tumor cross-sections, was analyzed for its prognostic relevance across different subgroups of RCC patients. A novel CID-based scoring system was developed, and its predictive efficacy was evaluated and compared with existing prognostic models. Findings: The CID exhibited significant discriminatory power in predicting overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS) among patients with RCC tumors measuring 3 cm or larger (all p < 0.001). Multivariate analyses confirmed the CID as an independent prognostic indicator. Notably, the CID augmented prognostic stratification among RCC patients within distinct risk subgroups delineated by SSIGN models and ISUP grades. The CID-based nomogram (C-Model) demonstrated robust predictive performance, with C-index values of 0.88 (95%CI: 0.84-0.92) in the training set, 0.92 (95%CI: 0.88-0.98) in the internal validation set, and 0.86 (95%CI: 0.81-0.90) in the external test set, surpassing existing prognostic models. Interpretation: Routine imaging-based assessment of the CID serves as an independent prognostic factor, offering incremental prognostic value to existing models in RCC patients with tumors measuring 3 cm or larger. Funding: This study was funded by grants from National Natural Science Foundation of China; Shanghai Municipal Health Commission; China National Key R&D Program and Science and Technology Commission of Shanghai Municipality.

Ultrafast near-infrared pyroelectric detector based on inhomogeneous plasmonic metasurface.

Pyroelectric (PE) detection technologies have attracted extensive attention due to the cooling-free, bias-free, and broadband properties. However, the PE signals are generated by the continuous energy conversion processes from light, heat, to electricity, normally leading to very slow response speeds. Herein, we design and fabricate a PE detector which shows extremely fast response in near-infrared (NIR) band by combining with the inhomogeneous plasmonic metasurface. The plasmonic effect dramatically accelerates the light-heat conversion process, unprecedentedly improving the NIR response speed by 2-4 orders of magnitude to 22 µs, faster than any reported infrared (IR) PE detector. We also innovatively introduce the concept of time resolution into the field of PE detection, which represents the detector's ability to distinguish multiple fast-moving targets. Furthermore, the spatially inhomogeneous design overcomes the traditional narrowband constraint of plasmonic systems and thus ensures a wideband response from visible to NIR. This study provides a promising approach to develop next-generation IR PE detectors with ultrafast and broadband responses.

Pharmacological treatments for vascular dementia: a systematic review and Bayesian network meta-analysis.

Background: Vascular dementia (VaD) is one of the most prevalent, burdensome, and costly forms of dementia. Pharmacological treatment is often the first-line choice for clinicians; however, there is a paucity of comparative information regarding the multiple available drug options. Methods and Analysis: A systematic review and network meta-analysis were conducted on randomized trials involving adult patients with VaD, sourced from PubMed, the Cochrane Library, EMBASE, Web of Science, OPENGREY, ClinicalTrials.gov, Wanfang Data, and CNKI. The primary outcomes included changes in Mini-Mental State Examination (MMSE) scores, activities of daily living (ADL) scores, and the incidence of adverse reactions. Efficacy and safety of intervention strategies were comprehensively analyzed using forest plots, cumulative ranking probability curves (SUCRA), and funnel plots, all generated with R software. Results: A total of 194 RCTs comparing 21 different anti-VaD drugs with placebos or no treatment were analysed. Regarding MMSE scores, the five most effective drugs were Butylphthalide, Huperzine A, Edaravone, Rivastigmine, and Memantine. For ADL scores, the top five drugs in efficacy were Huperzine A, Butylphthalide, Tianzhi granule, Nicergoline, and Idebenone. In terms of the incidence of adverse drug reactions, Co-dergocrine Mesylate, Tongxinluo capsule, Butylphthalide, Piracetam, and Oxiracetam demonstrated favourable safety profiles. Conclusion: This study enhances the understanding of the relative benefits and risks associated with various VaD treatments, providing a valuable reference for clinical decision-making. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier registration number.

The impact of depression on platelet activation, cardiocerebral vascular events and arteriovenous fistula dysfunction in patients undergoing haemodialysis.

Depression is a common psychiatric disorder among patients undergoing maintenance haemodialysis (MHD). Depression may reportedly contribute to poor prognosis in several ways, including its effects on platelet function. We hypothesised that depression contributes to the occurrence of cardiocerebral vascular events (CCVE) and dysfunction of arteriovenous fistula (DAVF) in patients undergoing MHD through its effects on platelets. In this prospective cohort study, patients undergoing MHD were recruited and divided into depression and non-depression groups according to their Hamilton Depression Scale (HAMD) scores. The 286 enrolled patients had 103 occurrences of depressive symptoms (prevalence = 36.01%). Compared with the non-depression group, depression group had a significantly higher cumulative prevalence of CCVE and DAVF during follow-up. Cox regression analysis indicated that higher HAMD scores and lower plasma platelet distribution width (PDW) were common risk factors for CCVE and DAVF. Furthermore, HAMD scores were significantly negatively correlated with plasma PDW and was the main variable affecting changes in PDW, as indicated by multiple linear regression analysis. Depression may increase the risk of CCVE and DAVF in patients undergoing MHD by activating platelets. Plasma PDW may be a convenient indicator of platelet activation status and may predict the risk of CCVE and DAVF.

Isolation and characterization of genetic variants of Orthohantavirus hantanense from clinical cases of HFRS in Jiangxi Province, China.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is a severe public health problem in Jiangxi province, China. Previous studies reported genetic variants of Orthohantavirus hantanense (Hantaan virus, HTNV) in rodents in this area. However, the relationship between HTNV variants and human infection needs to be confirmed. This study aimed to identify the HTNV variants in patients and to understand the clinical characteristics of HFRS caused by these variants. METHODS: Samples were collected from hospitalized suspected cases of HFRS during the acute phase. HFRS cases were confirmed using quantitative real-time RT-PCR. Peripheral blood mononuclear cells (PBMC) from patients with HFRS were inoculated into Vero-E6 cells for viral isolation. The genomic sequences of HTNV from patients were obtained by amplicon-based next-generation sequencing. A retrospective analysis was conducted on the clinical characteristics of the patients. RESULTS: HTNV RNA was detected in 53 of 183 suspected HFRS patients. Thirteen HTNVs were isolated from 32 PBMCs of HFRS cases. Whole genome sequences of 14 HTNVs were obtained, including 13 isolates in cell culture from 13 patients, and one from plasma of the fatal case which was not isolated successfully in cell culture. Genetic analysis revealed that the HTNV sequence from the 14 patients showed significant variations in nucleotide and amino acid to the HTNV strains found in other areas. Fever (100%, 53/53), thrombocytopenia (100%, 53/53), increased serum aspartate aminotransferase (100%, 53/53), and increased lactate dehydrogenase (96.2%, 51/53) were the most common characteristics. Severe acute kidney injury was observed in 13.2% (7/53) of cases. Clinical symptoms, such as pain, petechiae, and gastrointestinal or respiratory symptoms were uncommon. CONCLUSION: The HTNV genetic variants cause human infections in Jiangxi. The clinical symptoms of HFRS caused by the HTNV genetic variant during the acute phase are atypical. In addition to renal dysfunction, attention should be paid to the common liver injuries caused by these genetic variants.

Additional Hepatic Arterial Infusion Chemotherapy to Sorafenib Was Cost-Effective for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis.

Purpose: The combination of sorafenib and hepatic arterial infusion chemotherapy (SoHAIC) has shown to enhance overall survival rates in patients with advanced hepatocellular carcinoma and major portal vein tumor thrombosis (HCC-Vp3-4) compared to sorafenib alone. Our objective was to evaluate the cost-effectiveness of SoHAIC versus sorafenib for the treatment of HCC-Vp3-4, taking into account the viewpoint of Chinese healthcare payers. Methods: This pharmacoeconomic study employed a Markov model to assess the cost-effectiveness of treating HCC-Vp3-4 with SoHAIC in comparison to sorafenib. The patient characteristics were drawn from individuals from the trial conducted between June 2017 and November 2019, with cost and health value data sourced from published literature. The primary outcome measure in this research was the incremental cost-effectiveness ratio (ICER), which indicates the additional cost per quality-adjusted life year (QALY). The willingness-to-pay (WTP) threshold per QALY was set at $30,492.00. Furthermore, 1-way sensitivity and probabilistic sensitivity analyses were carried out to validate the consistency of the results. Results: In the baseline scenario, sorafenib resulted in 0.42 QALY at a cost of $10,507.89, while SoHAIC generated 1.66 QALY at a cost of $32,971.56. When comparing SoHAIC to sorafenib, the ICER was $18,237.20 per QALY, which was below the WTP threshold per QALY. Furthermore, the 1-way sensitivity analysis demonstrated that the ICER remained within the WTP threshold despite fluctuations in variables. In the probabilistic sensitivity analysis, SoHAIC had a 98.8% probability of being cost-effective at the WTP threshold, considering a wide range of parameters. Conclusion: In this cost-effectiveness evaluation, SoHAIC demonstrated cost-effectiveness over sorafenib for HCC with major portal vein tumor thrombosis, as observed from the perspective of a Chinese payer.

Tumor perfusion enhancement by microbubbles ultrasonic cavitation reduces tumor glycolysis metabolism and alleviate tumor acidosis.

The tumor microenvironment is increasingly acknowledged as a critical contributor to cancer progression, mediating genetic and epigenetic alterations. Beyond diverse cellular interactions from the microenvironment, physicochemical factors such as tumor acidosis also significantly affect cancer dynamics. Recent research has highlighted that tumor acidosis facilitates invasion, immune escape, metastasis, and resistance to therapies. Thus, noninvasive measurement of tumor acidity and the development of targeted interventions represent promising strategies in oncology. Techniques like contrast-enhanced ultrasound (CEUS) can effectively assess blood perfusion, while ultrasound-stimulated microbubble cavitation (USMC) has proven to enhance tumor blood perfusion. We therefore aimed to determine whether CEUS assesses tumor acidity and whether USMC treatment can modulate tumor acidity. Firstly, we tracked CEUS perfusion parameters in MCF7 tumor models and compared them with in vivo tumor pH recorded by pH microsensors. We found that the peak intensity and area under curve of tumor contrast-enhanced ultrasound correlated well with tumor pH. We further conducted USMC treatment on MCF7 tumor-bearing mice, tracked changes of tumor blood perfusion and tumor pH in different perfusion regions before and after the USMC treatment to assess its impact on tumor acidity and optimize therapeutic ultrasound pressure. We discovered that USMC with 1.0 Mpa significantly improved tumor blood perfusion and tumor pH. Furthermore, tumor vascular pathology and PGI2 assays indicated that improved tumor perfusion was mainly due to vasodilation rather than angiogenesis. More importantly, analysis of glycolysis-related metabolites and enzymes demonstrated USMC treatment can reduce tumor acidity by reducing tumor glycolysis. These findings support that CEUS may serve as a potential biomarker to assess tumor acidity and USMC is a promising therapeutic modality for reducing tumor acidosis.

Dysbiosis promotes recurrence of adenomatous polyps in the distal colorectum.

BACKGROUND: Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled. AIM: To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps. METHODS: Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators. RESULTS: The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella, Plesiomonas, and Cronobacter, was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones. CONCLUSION: These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.