Long-term outcome of adjuvant radiotherapy upon postoperative relapse of centrally located hepatocellular carcinoma: a real-world study.

Despite that surgical resection is widely regarded as the most effective approach to the treatment of liver cancer, its safety and efficacy upon centrally located hepatocellular carcinoma (HCC) remain unsatisfactory. In consequence, seeking an integrated treatment, like combined with adjuvant radiotherapy, to enhance the prognosis of patients is of critical importance. By recruiting patients undergoing surgical resection for centrally located HCC ranging from June 2015 to 2020, they were divided into liver resection combined with adjuvant radiotherapy (LR + RT) and mere liver resection (LR) groups. The calculation of propensity score and model of Cox proportional hazards regression were utilized. 193 patients were recruited in aggregation, containing 88 ones undergoing LR + RT, while 105 handled with LR. RT was verified to be an independent factor of prognosis for relapse (HR 0.60). In propensity-score analyses, significant association existed between adjuvant radiotherapy and better disease-free survival (DFS) (Matched, HR 0.60; Adjustment of propensity score, HR 0.60; Inverse probability weighting, HR 0.63). The difference of DFS was apparent within two groups (p value = 0.022), and RT significantly down-regulated early relapse (p value < 0.05) in subgroup analysis. The calculation of E-value revealed robustness of unmeasured confounding. The combination of liver surgical resection with RT is safe and effective towards patients with centrally located HCC, which would notably enhance the prognosis and decrease the early relapse of HCC.

Identification of molecular characteristics of hepatocellular carcinoma with microvascular invasion based on deep targeted sequencing.

BACKGROUND: As an indicator of tumor invasiveness, microvascular invasion (MVI) is a crucial risk factor for postoperative relapse, metastasis, and unfavorable prognosis in hepatocellular carcinoma (HCC). Nevertheless, the genetic mechanisms underlying MVI, particularly for Chinese patients, remain mostly uncharted. METHODS: We applied deep targeted sequencing on 66 Chinese HCC samples. Focusing on the telomerase reverse transcriptase (TERT) promoter (TERTp) and TP53 co-mutation (TERTp+/TP53+) group, gene set enrichment analysis (GSEA) was used to explore the potential molecular mechanisms of the TERTp+/TP53+ group on tumor progression and metastasis. Additionally, we evaluated the tumor immune microenvironment of the TERTp+/TP53+ group in HCC using multiplex immunofluorescence (mIF) staining. RESULTS: Among the 66 HCC samples, the mutated genes that mostly appeared were TERT, TP53, and CTNNB1. Of note, we found 10 cases with TERTp+/TP53+, of which nine were MVI-positive and one was MVI-negative, and there was a co-occurrence of TERTp and TP53 (p < 0.05). Survival analysis demonstrated that patients with the TERTp+/TP53+ group had lower the disease-free survival (DFS) (p = 0.028). GSEA results indicated that telomere organization, telomere maintenance, DNA replication, positive regulation of cell cycle, and negative regulation of immune response were significantly enriched in the TERTp+/TP53+ group (all adjusted p-values (p.adj) < 0.05). mIF revealed that the TERTp+/TP53+ group decreased CD8+ T cells infiltration (p = 0.25) and enhanced PDL1 expression (p = 0.55). CONCLUSIONS: TERTp+/TP53+ was significantly enriched in MVI-positive patients, leading to poor prognosis for HCC patients by promoting proliferation of HCC cell and inhibiting infiltration of immune cell surrounding HCC. TERTp+/TP53+ can be utilized as a potential indicator for predicting MVI-positive patients and poor prognosis, laying a preliminary foundation for further exploration of co-mutation in HCC with MVI and clinical treatment.

Telomerase-related advances in hepatocellular carcinoma: A bibliometric and visual analysis.

BACKGROUND: As a critical early event in hepatocellular carcinogenesis, telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma (HCC) patients, and its function in the genesis and treatment of HCC has gained much attention over the past two decades. AIM: To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase. METHODS: The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to "articles" and "reviews" published in English. A total of 873 relevant publications related to HCC and telomerase were identified. We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications, such as the trends in the publications, citation counts, most prolific or influential writers, and most popular journals; to screen for keywords occurring at high frequency; and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences. VOSviewer was utilized to compile and visualize the bibliometric data. RESULTS: A surge of 51 publications on HCC/telomerase research occurred in 2016, the most productive year from 1996 to 2023, accompanied by the peak citation count recorded in 2016. Up to December 2023, 35226 citations were made to all publications, an average of 46.6 citations to each paper. The United States received the most citations (n = 13531), followed by China (n = 7427) and Japan (n = 5754). In terms of national cooperation, China presented the highest centrality, its strongest bonds being to the United States and Japan. Among the 20 academic institutions with the most publications, ten came from China and the rest of Asia, though the University of Paris Cité, Public Assistance-Hospitals of Paris, and the National Institute of Health and Medical Research (INSERM) were the most prolific. As for individual contributions, Hisatomi H, Kaneko S, and Ide T were the three most prolific authors. Kaneko S ranked first by H-index, G-index, and overall publication count, while Zucman-Rossi J ranked first in citation count. The five most popular journals were the World Journal of Gastroenterology, Hepatology, Journal of Hepatology, Oncotarget, and Oncogene, while Nature Genetics, Hepatology, and Nature Reviews Disease Primers had the most citations. We extracted 2293 keywords from the publications, 120 of which appeared more than ten times. The most frequent were HCC, telomerase and human telomerase reverse transcriptase (hTERT). Keywords such as mutational landscape, TERT promoter mutations, landscape, risk, and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years. CONCLUSION: Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.

Genome analysis of a newly isolated Bacillus velezensis-YW01 for biodegrading acetaldehyde.

Acetaldehyde (AL), a primary carcinogen, not only pollutes the environment, but also endangers human health after drinking alcohol. Here a promising bacterial strain was successfully isolated from a white wine cellar pool in the province of Shandong, China, and identified as Bacillus velezensis-YW01 with 16 S rDNA sequence. Using AL as sole carbon source, initial AL of 1 g/L could be completely biodegraded by YW01 within 84 h and the cell-free extracts of YW01 has also been detected to biodegrade the AL, which indicate that YW01 is a high-potential strain for the biodegradation of AL. The optimal culture conditions and the biodegradation of AL of YW01 are at pH 7.0 and 38 °C, respectively. To further analyze the biodegradation mechanism of AL, the whole genome of YW01 was sequenced. Genes ORF1040, ORF1814 and ORF0127 were revealed in KEGG, which encode for acetaldehyde dehydrogenase. Furthermore, ORF0881 and ORF052 encode for ethanol dehydrogenase. This work provides valuable information for exploring metabolic pathway of converting ethanol to AL and subsequently converting AL to carboxylic acid compounds, which opened up potential pathways for the development of microbial catalyst against AL.

Staphylococcus pseudintermedius induces pyroptosis of canine corneal epithelial cells by activating the ROS-NLRP3 signalling pathway.

Staphylococcus pseudintermedius (S. pseudintermedius) is a common pathogen that causes canine corneal ulcers. However, the pathogenesis remained unclear. In this study, it has been demonstrated that S. pseudintermedius invaded canine corneal epithelial cells (CCECs) intracellularly, mediating oxidative damage and pyroptosis by promoting the accumulation of intracellular reactive oxygen species (ROS) and activating the NLRP3 inflammasome. The canine corneal stroma was infected with S. pseudintermedius to establish the canine corneal ulcer model in vivo. The intracellular infectious model in CCECs was established in vitro to explore the mechanism of the ROS - NLRP3 signalling pathway during the S. pseudintermedius infection by adding NAC or MCC950. Results showed that the expression of NLRP3 and gasdermin D (GSDMD) proteins increased significantly in the infected corneas (p < 0.01). The intracellular infection of S. pseudintermedius was confirmed by transmission electron microscopy and immunofluorescent 3D imaging. Flow cytometry analysis revealed that ROS and pyroptosis rates increased in the experimental group in contrast to the control group (p < 0.01). Furthermore, NAC or MCC950 inhibited activation of the ROS - NLRP3 signalling pathway and pyroptosis rate significantly, by suppressing pro-IL-1ß, cleaved-IL-1ß, pro-caspase-1, cleaved-caspase-1, NLRP3, GSDMD, GSDMD-N, and HMGB1 proteins. Thus, the research confirmed that oxidative damage and pyroptosis were involved in the process of CCECs infected with S. pseudintermedius intracellularly by the ROS - NLRP3 signalling pathway. The results enrich the understanding of the mechanisms of canine corneal ulcers and facilitate the development of new medicines and prevention measures.

Molecular classification reveals the sensitivity of lung adenocarcinoma to radiotherapy and immunotherapy: multi-omics clustering based on similarity network fusion.

BACKGROUND: Due to individual differences in tumors and immune systems, the response rate to immunotherapy is low in lung adenocarcinoma (LUAD) patients. Combinations with other therapeutic strategies improve the efficacy of immunotherapy in LUAD patients. Although radioimmunotherapy has been demonstrated to effectively suppress tumors, the underlying mechanisms still need to be investigated. METHODS: Total RNA from LUAD cells was sequenced before and after radiotherapy to identify differentially expressed radiation-associated genes. The similarity network fusion (SNF) algorithm was applied for molecular classification based on radiation-related genes, immune-related genes, methylation data, and somatic mutation data. The changes in gene expression, prognosis, immune cell infiltration, radiosensitivity, chemosensitivity, and sensitivity to immunotherapy were assessed for each subtype. RESULTS: We used the SNF algorithm and multi-omics data to divide TCGA-LUAD patients into three subtypes. Patients with the CS3 subtype had the best prognosis, while those with the CS1 and CS2 subtypes had poorer prognoses. Among the strains tested, CS2 exhibited the most elevated immune cell infiltration and expression of immune checkpoint genes, while CS1 exhibited the least. Patients in the CS2 subgroup were more likely to respond to PD-1 immunotherapy. The CS2 patients were most sensitive to docetaxel and cisplatin, while the CS1 patients were most sensitive to paclitaxel. Experimental validation of signature genes in the CS2 subtype showed that inhibiting the expression of RHCG and TRPA1 could enhance the sensitivity of lung cancer cells to radiation. CONCLUSIONS: In summary, this study identified a risk classifier based on multi-omics data that can guide treatment selection for LUAD patients.

Effect of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction: a meta-analysis.

Heart failure is the final stage of several cardiovascular diseases, and the key to effectively treating heart failure is to reverse or delay ventricular remodelling. Levosimendan is a novel inotropic and vasodilator agent used in heart failure, whereas the impact of levosimendan on ventricular remodelling is still unclear. This study aims to investigate the impact of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction. Electronic databases were searched to identify eligible studies. A total of 66 randomized controlled trials involving 7968 patients were included. Meta-analysis results showed that levosimendan increased left ventricular ejection fraction [mean difference (MD) = 3.62, 95% confidence interval (CI) (2.88, 4.35), P < 0.00001] and stroke volume [MD = 6.59, 95% CI (3.22, 9.96), P = 0.0001] and significantly reduced left ventricular end-systolic volume [standard mean difference (SMD) = -0.52, 95% CI (-0.67, -0.37), P < 0.00001], left ventricular end-diastolic volume index [SMD = -1.24, 95% CI (-1.61, -0.86), P < 0.00001], and left ventricular end-systolic volume index [SMD = -1.06, 95% CI (-1.43, -0.70), P < 0.00001]. In terms of biomarkers, levosimendan significantly reduced the level of brain natriuretic peptide [SMD = -1.08, 95% CI (-1.60, -0.56), P < 0.0001], N-terminal pro-brain natriuretic peptide [SMD = -0.99, 95% CI (-1.41, -0.56), P < 0.00001], and interleukin-6 [SMD = -0.61, 95% CI (-0.86, -0.35), P < 0.00001]. Meanwhile, levosimendan may increase the incidence of hypotension [risk ratio (RR) = 1.24, 95% CI (1.12, 1.39), P < 0.0001], hypokalaemia [RR = 1.57, 95% CI (1.08, 2.28), P = 0.02], headache [RR = 1.89, 95% CI (1.50, 2.39), P < 0.00001], atrial fibrillation [RR = 1.31, 95% CI (1.12, 1.52), P = 0.0005], and premature ventricular complexes [RR = 1.86, 95% CI (1.27, 2.72), P = 0.001]. In addition, levosimendan reduced all-cause mortality [RR = 0.83, 95% CI (0.74, 0.94), P = 0.002]. In conclusion, our study found that levosimendan might reverse ventricular remodelling when applied in patients with left ventricular systolic dysfunction, especially in patients undergoing cardiac surgery, decompensated heart failure, and septic shock.

Association between the traditional Chinese medicine constitution and metabolic dysfunction-associated fatty liver disease in older people: A cross-sectional study.

Background: Few studies have focused on the relationship between the traditional Chinese medicine constitution (TCMC) and metabolic dysfunction-associated fatty liver disease (MAFLD) in older populations. We sought to investigate the distribution of MAFLD and the TCMC in older people, and provide a theoretical basis for TCMC-based management of MAFLD in this population. Methods: A cross-sectional study was conducted among older (≥65 years) individuals in Zhongshan, China. Information on common sociodemographic characteristics, medical history, anthropometric measurements, and the TCMC was collected. The chi-square test, multivariable logistic regression analysis, subgroup analysis, and inverse probability weighting of the propensity score were used to explore the relationship between MAFLD and the TCMC. Results: Of 7085 participants, 1408 (19.9 %) had MAFLD. The three most common TCMC types in MAFLD patients were "phlegm-dampness", "gentleness", and "yin-deficiency". After adjustment for gender, age, tobacco smoking, alcohol consumption, body mass index, abnormal waist-to-hip ratio, hypertension, diabetes mellitus, and dyslipidemia, MAFLD was positively associated with the phlegm-dampness constitution (PDC) (ORadjusted (95 % CI) = 1.776 (1.496-2.108), P < 0.001), and negatively correlated with the qi-depression constitution (0.643 (0.481-0.860), 0.003). A stronger correlation between the PDC and MAFLD was observed in men compared with women (ORadjusted = 2.04 (95%CI = 1.47-2.84) vs. 1.70 (95%CI = 1.39-2.08), Pinteraction = 0.003) as well as between people who smoked tobacco and non-tobacco-smoking individuals (2.11 (1.39-3.21) vs. 1.75 (1.45-2.12), 0.006). Conclusions: A positive relationship was observed between MAFLD and the PDC in older people living in Zhongshan. Early detection and treatment of the PDC (especially in men and smokers) could prevent the occurrence and development of MAFLD.

Particulate polycyclic aromatic hydrocarbons in rural households burning solid fuels in Xuanwei County, Southwest China: occurrence, size distribution, and health risks.

The study is about the size distribution and health risks of polycyclic aromatic hydrocarbons (PAHs) in indoor environment of Xuanwei, Southwest China particle samples were collected by Anderson 8-stage impactor which was used to gather particle samples to nine size ranges. Size-segregated samples were collected in indoor from a rural village in Xuanwei during the non-heating and heating seasons. The results showed that the total concentrations of the indoor particulate matter (PM) were 757 ± 60 and 990 ± 78 µg/m3 in non-heating and heating seasons, respectively. The total concentration of indoor PAHs reached to 8.42 ± 0.53 µg/m3 in the heating season, which was considerably greater than the concentration in the non-heating season (2.85 ± 1.72 µg/m3). The size distribution of PAHs showed that PAHs were mainly enriched in PMs with the diameter <1.1 µm. The diagnostic ratios (DR) and principal component analysis (PCA) showed that coal and wood for residential heating and cooking were the main sources of indoor PAHs. The results of the health risk showed that the total deposition concentration (DC) in the alveolar region (AR) was 0.25 and 0.68 µg/m3 in the non-heating and heating seasons respectively. Throughout the entire sampling periods, the lifetime cancer risk (R) based on DC of children and adults varied between 3.53 ×10-5 to 1.79 ×10-4. During the heating season, the potential cancer risk of PAHs in adults was significant, exceeding 10-4, with a rate of 96%.

Single-cell multi-omics profiling of human preimplantation embryos identifies cytoskeletal defects during embryonic arrest.

Human in vitro fertilized embryos exhibit low developmental capabilities, and the mechanisms that underlie embryonic arrest remain unclear. Here using a single-cell multi-omics sequencing approach, we simultaneously analysed alterations in the transcriptome, chromatin accessibility and the DNA methylome in human embryonic arrest due to unexplained reasons. Arrested embryos displayed transcriptome disorders, including a distorted microtubule cytoskeleton, increased genomic instability and impaired glycolysis, which were coordinated with multiple epigenetic reprogramming defects. We identified Aurora A kinase (AURKA) repression as a cause of embryonic arrest. Mechanistically, arrested embryos induced through AURKA inhibition resembled the reprogramming abnormalities of natural embryonic arrest in terms of the transcriptome, the DNA methylome, chromatin accessibility and H3K4me3 modifications. Mitosis-independent sequential activation of the zygotic genome in arrested embryos showed that YY1 contributed to human major zygotic genome activation. Collectively, our study decodes the reprogramming abnormalities and mechanisms of human embryonic arrest and the key regulators of zygotic genome activation.

Utility of spectral CT with orthopedic metal artifact reduction algorithms for 125I seeds implantation in mediastinal and hepatic tumors.

Background: Virtual monochromatic image (VMI) combined with orthopedic metal artifact reduction algorithms (VMI + O-MAR) can effectively reduce artifacts caused by metal implants of different types. Nevertheless, so far, no study has systematically evaluated the efficacy of VMI + O-MAR in reducing various types of metal artifacts induced by 125I seeds. The aim of this study was to assess the effectiveness of combining spectral computed tomography (CT) images with O-MAR in reducing metal artifacts and improving the image quality affected by artifacts in patients after 125I radioactive seeds implantation (RSI). Methods: A total of 45 patients who underwent dual-layer detector spectral CT (DLCT; IQon, Philips Healthcare) scanning of mediastinal and hepatic tumors after 125I RSI were retrospectively included. Spectral data were reconstructed into conventional image (CI), VMI, CI combined with O-MAR (CI + O-MAR), and VMI + O-MAR to evaluate the de-artifact effect and image quality improvement. Objective indicators included signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and artifact index (AI) of lesions affected by artifacts. Subjective indicators included assessment of overcorrected artifacts and new artifacts, different morphology of artifacts, and overall image quality. Results: In artifact-affected lesion areas, SNR and CNR in the CI/VMI + O-MAR groups were better than those in CI groups (all P values <0.05). The AI showed a downward trend as VMI keV increased (all P values <0.001). The AI values of the CI/VMI (50-150 keV) group were all higher than the groups of CI/VMI + O-MAR (50-150 keV) (P<0.001). Overcorrection artifacts and new artifacts were concentrated in the VMI50/70 keV groups. In the evaluation of artifact morphology, as the VMI keV increased, the number of near-field banding artifacts in hyperdense artifacts gradually decreased, whereas the number of minimal or no artifacts increased, and the total number of hyperdense artifacts were decreased. The diagnostic and image quality scores of hyperdense artifacts were higher than those of hypodense artifacts as VMI keV increased. Conclusions: High VMI level combined with O-MAR substantially improve objective and subjective image quality, lesion display ability, and diagnostic confidence of CT follow-up after 125I RSI, especially at the VMI + O-MAR 150 keV level.

Connective tissue inspired elastomer-based hydrogel for artificial skin via radiation-indued penetrating polymerization.

Robust hydrogels offer a candidate for artificial skin of bionic robots, yet few hydrogels have a comprehensive performance comparable to real human skin. Here, we present a general method to convert traditional elastomers into tough hydrogels via a unique radiation-induced penetrating polymerization method. The hydrogel is composed of the original hydrophobic crosslinking network from elastomers and grafted hydrophilic chains, which act as elastic collagen fibers and water-rich substances. Therefore, it successfully combines the advantages of both elastomers and hydrogels and provides similar Young's modulus and friction coefficients to human skin, as well as better compression and puncture load capacities than double network and polyampholyte hydrogels. Additionally, responsive abilities can be introduced during the preparation process, granting the hybrid hydrogels shape adaptability. With these unique properties, the hybrid hydrogel can be a candidate for artificial skin, fluid flow controller, wound dressing layer and many other bionic application scenarios.

Optimal postoperative delirium prediction after coronary artery bypass grafting surgery: a prospective cohort study.

Background: Postoperative delirium (POD) presents as a serious neuropsychiatric syndrome in patients undergoing off-pump coronary artery bypass grafting (OPCABG) surgery. This is correlated with higher mortality, cognitive decline, and increased costs. The Age-adjusted Charlson Comorbidity Index (ACCI) is recognized as an independent predictor for mortality and survival rate. The purpose of our study is to estimate the predictive value of the ACCI on the POD in patients undergoing OPCABG surgery. Methods: This prospective cohort study enrolled patients undergoing OPCABG surgery between December 2020 and May 2021 in Qilu Hospital. Patients were divided into the low-ACCI group (score, 0-3) and the high-ACCI group (score ≥4) according to their ACCI scores. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and CAM were used to diagnose POD within 7 days after surgery. The general, laboratory, and clinical data of the patients were recorded and collected. The characteristic ROC curve was applied to further assess the predictive value of the ACCI for POD in patients following OPCABG surgery. Results: A total of 89 patients were enrolled, including 45 patients in the low-ACCI group and 44 patients in the high-ACCI group. The incidence of POD was higher in the high-ACCI group than in the low-ACCI group (45.5% vs. 15.6%, P = 0.003). Multivariate logistic regression analyses showed that the ACCI (OR, 2.433; 95% CI, 1.468-4.032; P = 0.001) was an independent risk factor for POD. The ACCI accurately predicted POD in patients following OPCABG surgery with an AUC of 0.738, and the Hosmer-Lemeshow goodness of fit test yielded X2 = 5.391 (P = 0.145). Conclusion: The high-ACCI group showed a high incidence of POD. The ACCI was an independent factor associated with POD in patients following OPCABG surgery. In addition, the ACCI could accurately predict POD in patients following OPCABG surgery. Clinical Trial Registration: ClinicalTrials.gov, identifier CHiCTR2100052811.

PWSC: a novel clustering method based on polynomial weight-adjusted sparse clustering for sparse biomedical data and its application in cancer subtyping.

BACKGROUND: Clustering analysis is widely used to interpret biomedical data and uncover new knowledge and patterns. However, conventional clustering methods are not effective when dealing with sparse biomedical data. To overcome this limitation, we propose a hierarchical clustering method called polynomial weight-adjusted sparse clustering (PWSC). RESULTS: The PWSC algorithm adjusts feature weights using a polynomial function, redefines the distances between samples, and performs hierarchical clustering analysis based on these adjusted distances. Additionally, we incorporate a consensus clustering approach to determine the optimal number of classifications. This consensus approach utilizes relative change in the cumulative distribution function to identify the best number of clusters, resulting in more stable clustering results. Leveraging the PWSC algorithm, we successfully classified a cohort of gastric cancer patients, enabling categorization of patients carrying different types of altered genes. Further evaluation using Entropy showed a significant improvement (p = 2.905e-05), while using the Calinski-Harabasz index demonstrates a remarkable 100% improvement in the quality of the best classification compared to conventional algorithms. Similarly, significantly increased entropy (p = 0.0336) and comparable CHI, were observed when classifying another colorectal cancer cohort with microbial abundance. The above attempts in cancer subtyping demonstrate that PWSC is highly applicable to different types of biomedical data. To facilitate its application, we have developed a user-friendly tool that implements the PWSC algorithm, which canbe accessed at http://pwsc.aiyimed.com/ . CONCLUSIONS: PWSC addresses the limitations of conventional approaches when clustering sparse biomedical data. By adjusting feature weights and employing consensus clustering, we achieve improved clustering results compared to conventional methods. The PWSC algorithm provides a valuable tool for researchers in the field, enabling more accurate and stable clustering analysis. Its application can enhance our understanding of complex biological systems and contribute to advancements in various biomedical disciplines.

Light-driven micro/nanomotors in biomedical applications.

Nanotechnology brings hope for targeted drug delivery. However, most current drug delivery systems use passive delivery strategies with limited therapeutic efficiency. Over the past two decades, research on micro/nanomotors (MNMs) has flourished in the biomedical field. Compared with other driven methods, light-driven MNMs have the advantages of being reversible, simple to control, clean, and efficient. Under light irradiation, the MNMs can overcome several barriers in the body and show great potential in the treatment of various diseases, such as tumors, and gastrointestinal, cardiovascular and cerebrovascular diseases. Herein, the classification and mechanism of light-driven MNMs are introduced briefly. Subsequently, the applications of light-driven MNMs in overcoming physiological and pathological barriers in the past five years are highlighted. Finally, the future prospects and challenges of light-driven MNMs are discussed as well. This review will provide inspiration and direction for light-driven MNMs to overcome biological barriers in vivo and promote the clinical application of light-driven MNMs in the biomedical field.

Airway Management of an Infant With Giant Neck Macro-Cystic Hygroma Utilizing a High-Flow Nasal Cannula.

BACKGROUND:  Cystic hygroma is a congenital lymphatic malformation. It may present as a huge mass in the neck, jeopardizing airway patency and prolonging intubation time, resulting in hypoventilation and hypoxemia. We used a high-flow nasal cannula to decrease the risk of hypoxemia and provide anesthesiologists sufficient time to perform tracheal intubation in young infants. CASE PRESENTATION: A 33-day-old infant (height, 55 cm; weight, 5.05 kg) was diagnosed with macro-cystic hygroma of the right neck. Considering the progressive enlargement of the macrocystic hygroma and its impact on the airway, urgent intervention becomes imperative. Among the available treatment modalities, percutaneous cyst aspiration and sclerotherapy performed under ultrasound guidance represent the most commonly chosen approach. During the induction of general anesthesia, the otolaryngologists were on standby and prepared for emergency tracheotomy. The anesthesiologists chose total intravenous anesthesia induction while maintaining spontaneous breathing. A high-flow nasal cannula was used to keep the infant oxygenated, and endotracheal intubation was successfully performed using a C-MAC video laryngoscope and fiber-optic bronchoscope. CONCLUSIONS: Airway management is the biggest challenge for anesthesiologists when delivering general anesthesia to infants with neck macro-cystic hygroma. Total intravenous anesthesia could be a choice for induction without considering compromised respiration and the side effects of inhalational anesthetics. A high-flow nasal cannula can be used in young infants to maintain oxygenation and allow anesthesiologists a longer time to perform intubation.

Effects of iron homeostasis on epigenetic age acceleration: a two-sample Mendelian randomization study.

BACKGROUND: Epigenetic clocks constructed from DNA methylation patterns have emerged as excellent predictors of aging and aging-related health outcomes. Iron, a crucial element, is meticulously regulated within organisms, a phenomenon referred as iron homeostasis. Previous researches have demonstrated the sophisticated connection between aging and iron homeostasis. However, their causal relationship remains relatively unexplored. RESULTS: Through two-sample Mendelian randomization (MR) utilizing the random effect inverse variance weighted (IVW) method, each standard deviation (SD) increase in serum iron was associated with increased GrimAge acceleration (GrimAA, BetaIVW = 0.27, P = 8.54E-03 in 2014 datasets; BetaIVW = 0.31, P = 1.25E-02 in 2021 datasets), HannumAge acceleration (HannumAA, BetaIVW = 0.32, P = 4.50E-03 in 2014 datasets; BetaIVW = 0.32, P = 8.03E-03 in 2021 datasets) and Intrinsic epigenetic age acceleration (IEAA, BetaIVW = 0.34, P = 5.33E-04 in 2014 datasets; BetaIVW = 0.49, P = 9.94E-04 in 2021 datasets). Similar results were also observed in transferrin saturation. While transferrin manifested a negative association with epigenetic age accelerations (EAAs) sensitivity analyses. Besides, lack of solid evidence to support a causal relationship from EAAs to iron-related biomarkers. CONCLUSIONS: The results of present investigation unveiled the causality of iron overload on acceleration of epigenetic clocks. Researches are warranted to illuminate the underlying mechanisms and formulate strategies for potential interventions.

High spindle and kinetochore-associated complex subunit-3 expression predicts poor prognosis and correlates with adverse immune infiltration in hepatocellular carcinoma.

BACKGROUND: Spindle and kinetochore-associated complex subunit 3 (SKA3) is a malignancy-associated gene that plays a critical role in the regulation of chromosome separation and cell division. However, the molecular mechanism through which SKA3 regulates tumor cell proliferation in hepatocellular carcinoma (HCC) has not been fully elucidated. AIM: To investigate the molecular mechanisms underlying the role of SKA3 in HCC. METHODS: SKA3 expression, clinicopathological, and survival analyses were performed using multiple public database platforms, and the results were verified by Western blot and immunohistochemistry staining using collected clinical samples. Functional enrichment analyses were performed to evaluate the biological functions and molecular mechanisms of SKA3 in HCC. Furthermore, the Tumor Immune Estimation Resource and single-sample Gene Set Enrichment Analysis (ssGSEA) algorithms were utilized to investigate the abundance of tumor-infiltrating immune cells in HCC. The response to chemotherapeutic drugs was evaluated by the R package "pRRophetic". RESULTS: We found that upregulated SKA3 expression was significantly correlated with poor prognosis in patients with HCC. Multivariable Cox regression analysis indicated that SKA3 was an independent risk factor for survival. GSEA revealed that SKA3 expression may facilitate proliferation and migratory processes by regulating the cell cycle and DNA repair. Moreover, patients with high SKA3 expression had significantly decreased ratios of CD8+ T cells, natural killer cells, and dendritic cells. Drug sensitivity analysis showed that the high SKA3 group was more sensitive to sorafenib, sunitinib, paclitaxel, doxorubicin, gemcitabine, and vx-680. CONCLUSION: High SKA3 expression led to poor prognosis in patients with HCC by enhancing HCC proliferation and repressing immune cell infiltration surrounding HCC. SKA3 may be used as a biomarker for poor prognosis and as a therapeutic target in HCC.

Deep Learning Model to Classify and Monitor Idiopathic Scoliosis in Adolescents Using a Single Smartphone Photograph.

Importance: Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal disorder. Routine physical examinations by trained personnel are critical to diagnose severity and monitor curve progression in AIS. In the presence of concerning malformation, radiographs are necessary for diagnosis or follow-up, guiding further management, such as bracing correction for moderate malformation and spine surgery for severe malformation. If left unattended, progressive deterioration occurs in two-thirds of patients, leading to significant health concerns for growing children. Objective: To assess the ability of an open platform application (app) using a validated deep learning model to classify AIS severity and curve type, as well as identify progression. Design, Setting, and Participants: This diagnostic study was performed with data from radiographs and smartphone photographs of the backs of adolescent patients at spine clinics. The ScolioNets deep learning model was developed and validated in a prospective training cohort, then incorporated and tested in the AlignProCARE open platform app in 2022. Ground truths (GTs) included severity, curve type, and progression as manually annotated by 2 experienced spine specialists based on the radiographic examinations of the participants' spines. The GTs and app results were blindly compared with another 2 spine surgeons' assessments of unclothed back appearance. Data were analyzed from October 2022 to February 2023. Exposure: Acquisitions of unclothed back photographs using a mobile app. Main Outcomes and Measures: Outcomes of interest were classification of AIS severity and progression. Quantitative statistical analyses were performed to assess the performance of the deep learning model in classifying the deformity as well as in distinguishing progression during 6-month follow-up. Results: The training data set consisted of 1780 patients (1295 [72.8%] female; mean [SD] age, 14.3 [3.3] years), and the prospective testing data sets consisted of 378 patients (279 [73.8%] female; mean [SD] age, 14.3 [3.8] years) and 376 follow-ups (294 [78.2%] female; mean [SD] age, 15.6 [2.9] years). The model recommended follow-up with an area under receiver operating characteristic curve (AUC) of 0.839 (95% CI, 0.789-0.882) and considering surgery with an AUC of 0.902 (95% CI, 0.859-0.936), while showing good ability to distinguish among thoracic (AUC, 0.777 [95% CI, 0.745-0.808]), thoracolumbar or lumbar (AUC, 0.760 [95% CI, 0.727-0.791]), or mixed (AUC, 0.860 [95% CI, 0.834-0.887]) curve types. For follow-ups, the model distinguished participants with or without curve progression with an AUC of 0.757 (95% CI, 0.630-0.858). Compared with both surgeons, the model could recognize severities and curve types with a higher sensitivity (eg, sensitivity for recommending follow-up: model, 84.88% [95% CI, 75.54%-91.70%]; senior surgeon, 44.19%; junior surgeon, 62.79%) and negative predictive values (NPVs; eg, NPV for recommending follow-up: model, 89.22% [95% CI, 84.25%-93.70%]; senior surgeon, 71.76%; junior surgeon, 79.35%). For distinguishing curve progression, the sensitivity and NPV were comparable with the senior surgeons (sensitivity, 63.33% [95% CI, 43.86%-80.87%] vs 77.42%; NPV, 68.57% [95% CI, 56.78%-78.37%] vs 72.00%). The junior surgeon reported an inability to identify curve types and progression by observing the unclothed back alone. Conclusions: This diagnostic study of adolescent patients screened for AIS found that the deep learning app had the potential for out-of-hospital accessible and radiation-free management of children with scoliosis, with comparable performance as spine surgeons experienced in AIS management.

Topological properties of individual gray matter morphological networks in identifying the preclinical stages of Alzheimer's disease: a preliminary study.

Background: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are preclinical stages of Alzheimer's disease (AD). Individual biomarkers are essential for evaluating altered neurological outcomes at both SCD and MCI stages for early diagnosis and intervention of AD. In this study, we aimed to investigate the relationships between topological properties of the individual brain morphological network and clinical cognitive performances among healthy controls (HCs) and patients with SCD or MCI. Methods: The topological measurements of individual morphological networks were analyzed using graph theory, and inter-group differences of standard graph topology were correlated and regressed to scores of clinical cognitive functions. Results: Compared with HCs, the topology of the individual morphological networks in SCD and MCI patients was significantly altered. At the global level, altered topology was characterized by lower global efficiency, shorter characteristics path length, and normalized characteristics path length [all P<0.05, false discovery rate (FDR) corrected]. In addition, at the regional level, SCD and MCI patients exhibited abnormal degree centrality in the caudate nucleus and nodal efficiency in the caudate nucleus, right insula, lenticular nucleus, and putamen (all P<0.05, FDR corrected). Conclusions: The topological features of individual gray matter morphological networks may serve as biomarkers to improve disease prognosis and intervention in the early stages of AD, namely SCD and MCI. Moreover, these findings may further elucidate the relationships between brain morphological alterations and cognitive dysfunctions in SCD and MCI.