Kidney function-specific cut-off values of high-sensitivity cardiac troponin T for the diagnosis of acute myocardial infarction.

Background: The diagnosis of acute myocardial infarction (AMI) using high-sensitivity cardiac troponin T (hs-cTnT) remains challenging in patients with kidney dysfunction. Methods: In this large, multicenter cohort study, a total of 20 912 adults who underwent coronary angiography were included. Kidney function-specific cut-off values of hs-cTnT were determined to improve the specificity without sacrificing sensitivity, as compared with that using traditional cut-off value (14 ng/L) in the normal kidney function group. The diagnostic accuracy of the novel cut-off values was validated in an independent validation cohort. Results: In the derivation cohort (n = 12 900), 3247 patients had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Even in the absence of AMI, 50.2% of participants with eGFR <60 mL/min/1.73 m2 had a hs-cTnT concentration ≥14 ng/L. Using 14 ng/L as the threshold of hs-cTnT for diagnosing AMI led to a significantly reduced specificity and positive predictive value in patients with kidney dysfunction, as compared with that in patients with normal kidney function. The kidney function-specific cut-off values were determined as 14, 18 and 48 ng/L for patients with eGFR >60, 60-30 and <30 mL/min/1.73 m2, respectively. Using the novel cut-off values, the specificities for diagnosing AMI in participants with different levels of kidney dysfunction were remarkably improved (from 9.1%-52.7% to 52.8-63.0%), without compromising sensitivity (96.6%-97.9%). Similar improvement of diagnostic accuracy was observed in the validation cohort (n = 8012). Conclusions: The kidney function-specific cut-off values of hs-cTnT may help clinicians to accurately diagnose AMI in patients with kidney dysfunction and avoid the potential overtreatment in practice.

The interactions of macrophages, lymphocytes, and mesenchymal stem cells during bone regeneration.

Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes - the main cellular components in BMAC - interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes.

Green synthesis of multifunctional bamboo-based nonwoven fabrics for medical treatment.

Medical nonwovens fabrics are pivotal materials in modern healthcare systems, and find extensively application in surgical gowns, masks, nursing pads, and surgical instrument packaging. As healthcare requirements evolve and medical technology advances, the demand for functional nonwoven medical devices is continuously increasing. In addition, numerous environmental challenges and the need to transition to a sustainable society have increased the popularity of studies on environmentally friendly multifunctional nonwoven materials prepared from biomass fibers. Therefore, in this study, ecofriendly bamboo fibers were used to fabricate multifunctional medical nonwoven materials with superhydrophobic, antibacterial, flame-retardant, and biocompatible properties. Specifically, ZIF-67 was grown in situ on natural bamboo cellulose fibers (BCFs) extracted from natural bamboo and coated with polydimethylsiloxane to construct an environmentally friendly and versatile nonwoven fabric. The treated nonwoven fabric exhibited superhydrophobicity with contact angle of 163° and possess excellent self-cleaning properties. The antibacterial activity of the samples was investigated by the plate-counting method; the results showed that the untreated BCFs did not exhibit antibacterial activity, whereas the treated bamboo nonwoven fabrics demonstrated significant antibacterial activity (p < 0.001), with an antibacterial rate of >99 % against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, and Candida albicans. In addition, when the samples were exposed to different temperatures (-4 and 50 °C) and humidities (0 % and 95 %), they demonstrated an antibacterial activity of >99 % against E. coli (F5,10 = 0.602; p = 0.670) and S. aureus (F4,10 = 0.289; p = 0.879). The heat release rate and smoke production rate of the nonwoven fabric decreased by 54.64 % and 93.18 %, respectively, compared to those of the BCFs, indicating excellent flame retardancy. The nonwoven fabric also exhibited satisfactory biocompatibility and breathability, ensuring user comfortability. This research not only has significant implications for producing low-cost, environmentally friendly, sustainable, and multifunctional medical products and openi up new pathways for the diversified utilization of bamboo, thereby expanding its applicability.

Optimization Design of Submerged-Entry-Nozzle Structure Using NSGA-II Genetic Algorithm in Ultra-Large Beam-Blank Continuous-Casting Molds.

To achieve uniform cooling and effective homogenization control in ultra-large beam-blank molds necessitates the optimization of submerged-entry-nozzle (SEN) structures. This study employed computational fluid dynamic (CFD) modeling to investigate the impact of two-port and three-port SEN configurations on fluid flow characteristics, free-surface velocities, temperature fields, and solidification behaviors. Subsequently, integrating numerical simulations with the non-dominated sorting genetic algorithm II (NSGA-II) and metallurgical quality-control expertise facilitated the multi-objective optimization of a three-port SEN structure suitable for beam-blank molds. The optimized parameters enabled the three-port SEN to deliver molten steel to the meniscus at an appropriate velocity while mitigating harmful effects such as SEN port backflow, excessive surface temperature differences, and shell thickness reduction due to fluid flow. The results indicated that the three-port SEN enhanced the molten-steel flow pattern and mitigated localized shell thinning compared with the two-port SEN. Additionally, the optimized design (op2) of the three-port SEN exhibited reduced boundary layer separation and superior fluid dynamics performance over the initial three-port SEN configuration.

Efficacy evaluation of zirconia crown on primary molars with caries defects.

OBJECTIVES: This study aimed to estimate the therapeutic effects of preformed metal crown (PMC) and prefabricated zirconia crowns (ZC) on decayed primary morals in children, as well as to analyze the possible influencing factors. METHODS: A retrospective cohort study was performed on the data of 192 patients (aged 3 to 8) in the Stomatological Department of Shenzhen Children's Hospital from October 2021 to December 2021. The decayed mandibular first molars were selected and restored by vital-pulp therapy followed by PMC and ZC, including 96 cases (96 caries) in the PMC group and 96 cases (96 caries) in the ZC group. Oral clinical examination was performed at 3 months, 1 year, and 2 years after treatment, overwiewing the clinical therapeutic effects and periodontal status of PMC and ZC groups, as well as recording the crown integrity, gingival index (GI), probing bleeding index (BI), plaque index (PLI) and various prosthetic indices. RESULTS: No significance differences existed in the periodontal status of PMC and ZC groups at 3 months, 1 year, and 2 years after treatment (P>0.05). However, the GI, BI, and PLI in the PMC group were higher than those in the ZC group at 3 months, 1 year, and 2 years after treatment, and the difference was dramatically significant (P<0.05). No significances difference existed in various prosthetic indices (P>0.05), as well as in the GI, BI, and PLI, between the two groups (P>0.05). No significant differences existed in various prosthetic indices between genders after PMC restoration (P>0.05). The scores of girls in various prosthetic indices after ZC restoration were higher than those of boys (P<0.05). Pearson correlation analysis indicated an inverse correlation between age in the PMC group and the GI, BI, PLI, and FDI indices (P<0.01), rather than in the ZC group (P>0.05). CONCLUSIONS: PMC and ZC can be applied to restore deciduous molar caries. The periodontal status of deciduous teeth in ZC group was superior to that in the PMC group. The periodontal status of deciduous teeth in PMC group may be stable with increased age.

Five miRNAs identified in fucosylated extracellular vesicles as non-invasive diagnostic signatures for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer that presents significant challenges for early detection. This study introduces the GlyExo-Capture method for isolating fucosylated extracellular vesicles (Fu-EVs) from serum. We analyze microRNA (miRNA) profiles from Fu-EVs in 88 HCC patients and 179 non-HCC controls using next-generation sequencing (NGS) and identify five miRNAs (hsa-let-7a, hsa-miR-21, hsa-miR-125a, hsa-miR-200a, and hsa-miR-150) as biomarkers for HCC diagnosis. The five-miRNA panel demonstrates exceptional HCC diagnostic performance, with a sensitivity of 0.90 and specificity of 0.92 in a combined cohort of 194 HCC and 412 non-HCC controls, significantly surpassing the performance of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP). Notably, the miRNA model achieves recall rates of 85.7% and 90.8% for stage 0 and stage A early-stage HCC, respectively, identifies 88.1% of AFP-negative HCC cases, and effectively differentiates HCC from other cancers. This study provides a high-throughput, rapid, and non-invasive approach for early HCC detection.

The association between serum cholesterol levels and mild-to-moderate cognitive impairment in the Suita Study and evidence from other epidemiological studies.

BACKGROUND: Serum cholesterols are well-documented markers of cardiovascular diseases; however, their association with cognitive well-being is uncertain. This study investigated the association between serum cholesterol levels and mild-to-moderate cognitive impairment. METHODS: Epidemiological evidence on the role of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), non-HDL-C, and low-density lipoprotein cholesterol (LDL-C) in cognitive impairment was highlighted. Then, data from 6216 Japanese individuals, aged ≥50 years, from the Suita Study were analyzed. Mini-Mental State Examination (MMSE) scores <27 and < 24 were used to define cognitive impairment. Logistic regression was used to calculate the odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for cognitive impairment. RESULTS: Epidemiological studies investigating the association between serum cholesterol and cognitive impairment have shown conflicting findings: elevated risk with certain lipid components in some studies and no association in others. In the Suita Study, HDL-C < 40 mg/dL was associated with cognitive impairment: ORs (95 % CIs) = 1.36 (1.08, 1.72) for MMSE <27 and 1.61 (1.00, 2.60) for MMSE <24. Non-HDL-C ≥ 200 mg/dL was also associated with cognitive impairment: ORs (95 % CIs) = 1.53 (1.02, 2.31) for MMSE <27 and 1.80 (1.16, 2.79) for MMSE <24. No such associations were detected with TC. CONCLUSION: While epidemiological evidence remains inconsistent, the Suita Study showed that decreased HDL-C and increased non-HDL-C, but not increased TC, were associated with mild-to-moderate cognitive impairment. Management of serum cholesterol levels should be considered to prevent cognitive impairment.

The advantages and shortcomings of stem cell therapy for enhanced bone healing.

This review explores the regenerative potential of key progenitor cell types and therapeutic strategies to improve healing of complex fractures and bone defects. We define, summarize, and discuss the differentiation potential of totipotent, pluripotent, and multipotent stem cells, emphasizing the advantages and shortcomings of cell therapy for bone repair and regeneration. The fundamental role of mesenchymal stem cells (MSCs) is highlighted due to their multipotency to differentiate into the key lineage cells including osteoblasts, osteocytes, and chondrocytes, which are crucial for bone formation and remodeling. Hematopoietic stem cells (HSCs) also play a significant role; immune cells such as macrophages and T cells modulate inflammation and tissue repair. Osteoclasts are multi-nucleated cells that are important to bone remodeling. Vascular progenitor cells are critical to oxygen and nutrient supply. The dynamic interplay among these lineages and their microenvironment is essential for effective bone restoration. Therapies involving cells that are more than "minimally manipulated" are controversial and include embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). ESCs, derived from early-stage embryos, possess pluripotent capabilities and have shown promise in preclinical studies for bone healing. iPSCs, reprogrammed from somatic cells, offer personalized medicine applications and can differentiate into various tissue-specific cell lines. Minimally manipulative cell therapy approaches such as the use of concentrated bone marrow aspirate (BMAC), exosomes, and various biomaterials for local delivery are explored for their effectiveness in bone regeneration. BMAC, which contains mostly immune cells but few mesenchymal and vascular progenitors, probably improves bone healing by facilitating paracrine mediated intercellular communication. Exosome isolation harnesses the biological signals and cellular byproducts that are a primary source for cell crosstalk and activation. Safe, efficacious, and cost-effective strategies to enhance bone healing using novel cellular therapies are part of a changing paradigm to modulate the inflammatory, repair and regenerative pathways to achieve earlier more robust tissue healing and improved physical function.

Cysteine sulfenylation contributes to liver fibrosis via the regulation of EphB2-mediated signaling.

Sulfenylation is a reversible oxidative posttranslational modification (PTM) of proteins on cysteine residues. Despite the dissection of various biological functions of cysteine sulfenylation, its roles in hepatic fibrosis remain elusive. Here, we report that EphB2, a receptor tyrosine kinase previously implicated in liver fibrosis, is regulated by cysteine sulfenylation during the fibrotic progression of liver. Specifically, EphB2 is sulfenylated at the residues of Cys636 and Cys862 in activated hepatic stellate cells (HSCs), leading to the elevation of tyrosine kinase activity and protein stability of EphB2 and stronger interactions with focal adhesion kinase for the activation of downstream mitogen-activated protein kinase signaling. The inhibitions of both EphB2 kinase activity and cysteine sulfenylation by idebenone (IDE), a marketed drug with potent antioxidant activity, can markedly suppress the activation of HSCs and ameliorate hepatic injury in two well-recognized mouse models of liver fibrosis. Collectively, this study reveals cysteine sulfenylation as a new type of PTM for EphB2 and sheds a light on the therapeutic potential of IDE for the treatment of liver fibrosis.

Automatic cardiothoracic ratio calculation based on lung fields abstracted from chest X-ray images without heart segmentation.

Introduction: The cardiothoracic ratio (CTR) based on postero-anterior chest X-rays (P-A CXR) images is one of the most commonly used cardiac measurement methods and an indicator for initially evaluating cardiac diseases. However, the hearts are not readily observable on P-A CXR images compared to the lung fields. Therefore, radiologists often manually determine the CTR's right and left heart border points of the adjacent left and right lung fields to the heart based on P-A CXR images. Meanwhile, manual CTR measurement based on the P-A CXR image requires experienced radiologists and is time-consuming and laborious. Methods: Based on the above, this article proposes a novel, fully automatic CTR calculation method based on lung fields abstracted from the P-A CXR images using convolutional neural networks (CNNs), overcoming the limitations to heart segmentation and avoiding errors in heart segmentation. First, the lung field mask images are abstracted from the P-A CXR images based on the pre-trained CNNs. Second, a novel localization method of the heart's right and left border points is proposed based on the two-dimensional projection morphology of the lung field mask images using graphics. Results: The results show that the mean distance errors at the x-axis direction of the CTR's four key points in the test sets T1 (21 × 512 × 512 static P-A CXR images) and T2 (13 × 512 × 512 dynamic P-A CXR images) based on various pre-trained CNNs are 4.1161 and 3.2116 pixels, respectively. In addition, the mean CTR errors on the test sets T1 and T2 based on four proposed models are 0.0208 and 0.0180, respectively. Discussion: Our proposed model achieves the equivalent performance of CTR calculation as the previous CardioNet model, overcomes heart segmentation, and takes less time. Therefore, our proposed method is practical and feasible and may become an effective tool for initially evaluating cardiac diseases.

PTX-RPPR, a conjugate of paclitaxel and NRP-1 peptide inhibitor to prevent tumor growth and metastasis.

Paclitaxel, a potent anti-tumor drug widely recognized for its therapeutic efficacy, has faced limitations in clinical application due to its poor solubility. The use of Cremophor EL (CrEL) as a cosolvent in paclitaxel injections has been associated with hypersensitivity reactions in some patients. To overcome these challenges, we have developed a novel conjugate by linking a neuropilin-1 targeting peptide, RPPR, to paclitaxel, resulting in PTX-RPPR. This innovative approach has significantly enhanced the solubility of paclitaxel, achieving a 3.8 mg/mL concentration, a remarkable 90-fold increase over the native drug. PTX-RPPR has shown potent anti-tumor activity, inhibiting tumor cell proliferation with an IC50 ranging from 0.26 to 1.64 µM and effectively suppressing migration, invasion, and angiogenesis at a concentration of 75 nM. Notably, in a 4T1 mammary carcinoma model, PTX-RPPR administered at a dose of 0.7 µmol/kg exhibited tumor growth inhibition comparable to that of paclitaxel at a higher dose of 3.5 µmol/kg, with superior efficacy in preventing lung metastasis. Furthermore, PTX-RPPR effectively reduced NRP-1 expression in both tumors and lungs post-treatment. In contrast to paclitaxel formulated with CrEL, PTX-RPPR did not induce IL-6 expression, suggesting a safer profile in terms of immunological response. Characterized by a particle size of 200 nm and a zeta potential of +30 mV, the nano-formulation of PTX-RPPR demonstrated remarkable stability over seven days. This study introduced PTX-RPPR as a promising peptide-drug conjugate that addresses the solubility and hypersensitivity issues associated with paclitaxel, offering a safer therapeutic strategy for cancer treatment.

M2 macrophage-derived extracellular vesicles ameliorate Benzalkonium Chloride-induced dry eye.

Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation.

Distinct roles of Kif6 and Kif9 in mammalian ciliary trafficking and motility.

Ciliary beat and intraflagellar transport depend on dynein and kinesin motors. The kinesin-9 family members Kif6 and Kif9 are implicated in motile cilia motilities across protists and mammals. How they function and whether they act redundantly, however, remain unclear. Here, we show that Kif6 and Kif9 play distinct roles in mammals. Kif6 forms puncta that move bidirectionally along axonemes, whereas Kif9 appears to oscillate regionally on the ciliary central apparatus. Consistently, only Kif6 displays microtubule-based motor activity in vitro, and its ciliary localization requires its ATPase activity. Kif6 deficiency in mice disrupts coordinated ciliary beat across ependymal tissues and impairs cerebrospinal fluid flow, resulting in severe hydrocephalus and high mortality. Kif9 deficiency causes mild hydrocephalus without obviously affecting the ciliary beat or the lifespan. Kif6-/- and Kif9-/- males are infertile but exhibit oligozoospermia with poor sperm motility and defective forward motion of sperms, respectively. These results suggest Kif6 as a motor for cargo transport and Kif9 as a central apparatus regulator.

SARS-CoV-2 spike-induced syncytia are senescent and contribute to exacerbated heart failure.

SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.

A novel prediction model for the probability of aggressive behavior in patients with mood disorders: Based on a cohort study.

BACKGROUND: Accurately predicting the probability of aggressive behavior is crucial for guiding early intervention in patients with mood disorders. METHODS: Cox stepwise regression was conducted to identify potential influencing factors. Nomogram prediction models were constructed to predict the probabilities of aggressive behavior in patients with mood disorders, and their performance was assessed using consistency index (C-index) and calibration plots. RESULTS: Research findings on 321 patients with mood disorders indicated that being older (HR = 0.92, 95% CI: 0.86-0.98), single (HR = 0.11, 95% CI: 0.02-0.68), having children (one child, HR = 0.07, 95%CI: 0.01-0.87; more than one child, HR = 0.33, 95%CI: 0.04-2.48), living in dormitory (HR = 0.25, 95%CI: 0.08-0.77), non-student (employee, HR = 0.24, 95% CI: 0.07-0.88; non-employee, HR = 0.09, 95% CI: 0.02-0.35), and higher scores in subjective support (HR = 0.90, 95% CI: 0.82-0.99) were protective factors. On the contrary, minorities (HR = 5.26, 95% CI: 1.23-22.48), living alone (HR = 4.37, 95% CI: 1.60-11.94), having suicide history (HR = 2.51, 95% CI: 1.06-5.95), and having higher scores in EPQ-E (HR = 1.04, 95% CI: 1.00-1.08) and EPQ-P (HR = 1.03, 95% CI: 1.00-1.07) were identified as independent risk factors for aggressive behavior in patients with mood disorders. The nomogram prediction model demonstrated high discrimination and goodness-of-fit. CONCLUSIONS: A novel nomogram prediction model for the probability of aggressive behavior in patients with mood disorders was developed, effective in identifying at-risk populations and offering valuable insights for early intervention and proactive measures.

Determining priority control factors for heavy metal management in urban road dust based on source-oriented probabilistic ecological-health risk assessment: A study in Xi'an during peak pollution season.

Urban road dust (URD) is essential for transporting heavy metals (HMs), which can be a major danger to both the environment and human health. Moreover, URD has the potential to be carried into bodies of water, leading to contamination of the aquatic ecosystem. A study was conducted in Xi'an, a city in northwestern China known for high air pollution levels, during January 2024 - a period characterized by peak pollution due to frequent low wind speeds and temperature inversions. The research investigated the presence of 10 types of HMs (Cu, Zn, Cd, Cr, Pb, As, Ni, Hg, Co, and Mn) in URD. Findings revealed elevated levels of Cu, Zn, Cd, Cr, Pb, As, and Hg in URD compared to background levels. Hg showed the most significant contamination (moderate to heavy), followed by moderate contamination of Cd, and lower levels of As, Zn, and Cu. The main sources of HMs were traffic (58.2%), mixed natural and industrial (30.3%), and industrial (11.5%). The ecological risk in the area was deemed to be very high, primarily because of Hg and Cd. Based on probabilistic health risk assessments, it was determined that non-carcinogenic risks were deemed acceptable for all groups. Nevertheless, the possibility of carcinogenic risks should not be disregarded. Strategies for controlling ecological-health risks prioritize mixed natural and industrial sources, with a focus on Hg, Cd, and As in URD. The results offer a foundation for policymakers to create specific control strategies.

Renin-angiotensin system inhibitors and risk of hepatocellular carcinoma among patients with hepatitis B virus infection.

BACKGROUND: Hepatitis B virus (HBV) infection is a common cause of liver-related morbidity and mortality. Evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) decrease liver fibrosis, an intermediate step between liver injury and hepatocellular carcinoma (HCC). Our aim was to investigate the association between the use of ACEIs and ARBs on incident HCC and liver-related mortality among patients with HBV infection. METHODS: We conducted a population-based study on a new-user cohort of patients seen at 24 hospitals across China. We included adult patients with HBV infection who started ACEIs or ARBs (ACEIs/ARBs), or calcium channel blockers or thiazide diuretics (CCBs/THZs) from January 2012 to December 2022. The primary outcome was incident HCC; secondary outcomes were liver-related mortality and new-onset cirrhosis. We used propensity score matching and Cox proportional hazards regression to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of study outcomes. RESULTS: Among 32 692 eligible patients (median age 58 [interquartile range (IQR) 48-68] yr, and 18 804 male [57.5%]), we matched 9946 pairs of patients starting ACEIs/ARBs or CCBs/THZs. During a mean follow-up of 2.3 years, the incidence rate of HCC per 1000 person-years was 4.11 and 5.94 among patients who started ACEIs/ARBs and CCBs/THZs, respectively, in the matched cohort. Use of ACEIs/ARBs was associated with lower risks of incident HCC (HR 0.66, 95% CI 0.50-0.86), liver-related mortality (HR 0.77, 95% CI 0.64-0.93), and new-onset cirrhosis (HR 0.81, 95% CI 0.70-0.94). INTERPRETATION: In this cohort of patients with HBV infection, new users of ACEIs/ARBs had a lower risk of incident HCC, liver-related mortality, and new-onset cirrhosis than new users of CCBs/THZs.

Design of a Social Justice Curriculum to Expand Critical Consciousness Among Resident Trainees.

BACKGROUND: Health equity curricula emphasizing critical pedagogy and centering perspectives of those with marginalized identities, both in curriculum design and execution, have yet to be described in interdisciplinary graduate medical education settings. AIM: The application of public health critical race praxis (PHCRP) in the redesign and evaluation of a social medicine immersion month (SMIM) curriculum. SETTING: A mandatory, 4-week course within the Residency Program for Social Medicine in the Bronx, NY. PARTICIPANTS: First-year residents in internal medicine, family medicine, pediatrics, and clinical psychology fellows between 2019 and 2020. PROGRAM DESCRIPTION: Residents and faculty underrepresented in medicine employed PHCRP to ground SMIM in critical pedagogy and structural competency with the goals of increasing critical consciousness, sensitizing trainees to structural barriers faced by patients, and promoting meaningful engagement in advocacy. PROGRAM EVALUATION: SMIM was evaluated pre- and post-curriculum using a validated critical consciousness and intersectionality survey, with additional questions to assess competency and behaviors. Participants also provided course feedback. Participants demonstrated significant increases across all domains of the measure (Racism + 1.62 (p < .01), Classism + 1.62 (p < .05), Heterosexism + 1.06 (p < .05)). Participant feedback was positive. DISCUSSION: PHCRP is a valuable model for designing health equity curriculum. SMIM provides insights for incorporating this framework into GME curricula.

Deciphering the Role of Necroptosis-Related Long Non-coding RNAs in Hepatocellular Carcinoma: A Necroptosis-Related lncRNA-Based Signature to Predict the Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, characterized by a high morbidity rate. Long non-coding RNAs (lncRNAs) play an important role in regulating various cellular processes and diseases, including cancer. However, their specific roles and mechanisms in HCC are not fully understood. This study used a multi-cohort design to investigate necroptosis-related lncRNAs (NRLs) in patients with HCC. We curated a list of 1095 NRLs and 838 genes showing differential expression between tumor and normal tissues. Among them, we found 105 NRLs closely associated with the prognosis of HCC patients. The 10 lncRNAs (AC100803.3, AC027237.2, AL158166.1, LINC02870, AC026412.3, LINC02159, AC027097.1, AC139887.4, AC007405.1, AL023583.1) generated by LASSO-Cox regression analysis were used to create a prognostic risk model for HCC and group patients into groups based on risk. The KEGG analysis revealed distinct pathway enrichments in high-risk (H-R) and low-risk (L-R) subgroups. According to GO analysis, this study identified 230 differentially expressed genes (DEGs) that were significantly enriched in specific biological processes. Comparison of immune checkpoint-related genes (MCPGs) between H-R and L-R patients revealed significant differences. Moreover, we established a correlation between the risk scores of patients with liver cancer and their sensitivity to 16 chemotherapeutic agents. Employing protein-protein interaction (PPI) analysis, we identified 10 hub genes that potentially regulate the molecular networks involved in HCC development. This study is a pioneering effort to investigate the roles of NRLs in HCC. It opens a new avenue for potential targeted therapies and provides insights into the molecular mechanisms of HCC.

HS-GC-IMS Analysis of Volatile Organic Compounds in Six Spicy Spices and Their Effects on Ulcerative Colitis.

The volatile organic compounds of six spices, including black pepper, dried ginger, cinnamon, fennel, clove, and zanthoxylum, were analyzed by gas chromatography-ion mobility spectrometry (HS-GC-IMS) combined with principal component analysis (PCA) and Euclidean distance. In further analyses, the effects of volatile oils in six spices on ulcerative colitis were assayed in a zebrafish model induced by 3-nitrobenzenesulfonic acid. A total of 120 kinds of volatile organic compounds were detected and 80 among them were identified, which included 10 common components and 3 to 24 characteristic components belonging to different spices. The major VOCs in six spices were estimated to be terpenes with the contents of 45.02%, 56.87%, 36.68%, 58.19%, 68.68%, and 30.62%, respectively. Meanwhile, the volatile components of fennel, dried ginger, black pepper, and cinnamon are quite similar, but differ from clove and zanthoxylum. The volatile oils in six spices presented efficient activity to improve ulcerative colitis which can decrease the number of neutrophils, restore the structure of intestinal epithelial and the morphology of the epithelial cells. Our study achieved rapid analysis of the volatile organic compounds and flavors in six spices and further revealed the potential health benefits of their volatile oils on ulcerative colitis, especially for clove and zanthoxylum. This study is expected to provide certain data support for the quality evaluation and the potential use in functional foods of six spices.