Nomogram for preoperative estimation of microvascular invasion risk in hepatocellular carcinoma.

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167-7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922-41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374-12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780-10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771-0.894) and 0.821 (95 % CI 0.720-0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.

Successful management of Mycobacterium abscessus pneumonia in a 53-day-old immunocompetent infant.

Pulmonary infection due to Mycobacterium abscessus complex (MABC) usually occurs in children with underlying risk factors including cystic fibrosis (CF), chronic lung disease, and immunocompromised status, but rarely in immunocompetent children without underlying lung disease, especially in infants. We present a case of MABC pulmonary disease (MABC-PD) in an otherwise healthy 53-day-old male infant with one week of cough and respiratory distress. Computed tomography showed multiple masses across both lungs. Isolated mycobacteria from his bronchoalveolar lavage fluid were identified as MABC. We describe our complete evaluation, including immunodeficiency evaluation incorporating whole exome sequencing and our therapeutic process given complicated susceptibility pattern of the M. abscessus isolate, and review literature for MABC-PD in immunocompetent children. The infant was successfully treated through prolonged treatment with parenteral Amikacin, Cefoxitin, Linezolid, and Clarithromycin, combined with inhaled Amikacin.

A Predictive Network-Based Immune Checkpoint Blockade Immunotherapeutic Signature Optimizing Patient Selection and Treatment Strategies.

Immune checkpoint blockade (ICB) therapy has brought significant advancements to the field of oncology. However, the diverse responses among patients highlight the need for more accurate predictive tools. In this study, insights are drawn from tumor-immunology pathways, and a novel network-based ICB immunotherapeutic signature, termed ICBnetIS, is constructed. The signature is derived from advanced biological network-based computational strategies involving co-expression networks and molecular interactions networks. The efficacy of ICBnetIS is established through its association with enhanced patient survival and a robust immune response characterized by diverse immune cell infiltration and active anti-tumor immune pathways. The validation process positions ICBnetIS as an effective tool in predicting responses to ICB therapy, analyzing ICB data from a broad collection of over 700 samples from multiple cancer types of more than 15 datasets. It achieves an aggregated prediction AUC of 0.784, which outperforms the other nine renowned immunotherapeutic signatures, indicating the superior predictive capability of ICBnetIS. To sum up, the findings suggest ICBnetIS as a potent tool in predicting ICB therapy responses, offering significant implications for patient selection and treatment optimization in oncology. The study highlights the role of ICBnetIS in advancing personalized treatment strategies, potentially transforming the clinical landscape of ICB therapy.

The influence of novel coronavirus pneumonia on chronic disease management of asthma-a narrative review.

Background and Objective: The coronavirus disease 2019 (COVID-19) pandemic has taken a huge global toll on all fronts, creating new challenges for the diagnosis and treatment of respiratory diseases. For chronic management of asthma, on the one hand, the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect the asthma disease itself; on the other hand, in order to control the spread of the pandemic, forced isolation, mask-wearing and various disinfection measures also have an impact on the condition and medication of asthma patients. This article reviews the changes in chronic asthma management under the COVID-19 pandemic to provide reference for chronic disease management of asthma after the pandemic and for various public health emergencies in the future. Methods: Online searching of literature was performed. The National Center for Biotechnology Information (NCBI), PubMed, Google Scholar, and EMBASE were searched. Key Content and Findings: COVID-19 has had a huge impact on the world, and has also brought new challenges to the diagnosis and treatment of asthma and chronic disease management. On the one hand, the existence of the 2019 novel coronavirus directly affects the asthma disease itself, on the other hand, due to the particularity of the asthma disease itself, different levels of isolation and controls can cause patients with different degrees of medical difficulties; in addition, the application of various disinfectants in the environment also increases the risk of acute attacks of asthma patients, as well as mask-wearing, vaccination, anxiety about the disease, panic, etc., all of which have posed various degrees of impact on the condition and psychology of asthma patients. Conclusions: The pandemic of COVID-19 has brought many difficulties to the chronic disease management of asthma, and has had a certain impact on the disease control of asthma patients. In the era with overflowing information, internet hospital is the current trend, and there is a long way to go for effectively penetrating medical resources virtually via the internet into chronic disease management of asthma.

Lysimachiadanxiashanensis, a new species of Primulaceae from Guangdong, China.

Lysimachiadanxiashanensis, a new Primulaceae species, endemic to the Danxia landscape in Guangdong Province, China, is described and illustrated. This new species is morphologically similar to L.pseudohenryi, L.phyllocephala, L.congestiflora and L.kwangtungensis, but it differs from the similar species by its purplish-red plants, petiole without wings, calyx with orange glandular and the corolla margin serrated on upper half with orange-red glandular punctates. This new species belongs to Lysimachiasubgen.Lysimachiasect.Nummularia. Phylogenetic analysis confirmed that L.danxiashanensis is a distinct clade, based on the combined data of ITS and rbcL sequences. The conservation status of the new species was evaluated as Endangered (EN) according to IUCN Red List Categories and Criteria.

Ferroptosis Contributes to Microvascular Dysfunction in Diabetic Retinopathy.

Ferroptosis is a new form of cell death characterized by iron-dependent lipid peroxidation. Whether ferroptosis is involved in retinal microvascular dysfunction under diabetic condition is not known. Herein, the expression of ferroptosis-related genes in patients with proliferative diabetic retinopathy and in diabetic mice was determined with quantitative RT-PCR. Reactive oxygen species, iron content, lipid peroxidation products, and ferroptosis-associated proteins in the cultured human retinal microvascular endothelial cells (HRMECs) and in the retina of diabetic mice were examined. The association of ferroptosis with the functions of endothelial cells in vitro was evaluated. After administration of ferroptosis-specific inhibitor, Fer-1, the retinal microvasculature in diabetic mice was assessed. Characteristic changes of ferroptosis-associated markers, including glutathione peroxidase 4, ferritin heavy chain 1, long-chain acyl-CoA synthetase 4, transferrin receptor protein 1, and cyclooxygenase-2, were detected in the retinal fibrovascular membrane of patients with proliferative diabetic retinopathy, cultured HRMECs, and the retina of diabetic mice. Elevated levels of reactive oxygen species, lipid peroxidation, and iron content were found in the retina of diabetic mice and in cultured HRMECs. Ferroptosis was found to be associated with HRMEC dysfunction under high-glucose condition. Inhibition of ferroptosis with specific inhibitor Fer-1 in diabetic mice significantly reduced the severity of retinal microvasculopathy. Ferroptosis contributes to microvascular dysfunction in diabetic retinopathy, and inhibition of ferroptosis might be a promising strategy for the therapy of early-stage diabetic retinopathy.

Optimization of FFPE preparation and identification of gene attributes associated with RNA degradation.

Formalin-fixed paraffin-embedded (FFPE) tissues are widely available specimens for clinical studies. However, RNA degradation in FFPE tissues often restricts their utility. In this study, we determined optimal FFPE preparation conditions, including tissue ischemia at 4°C (<48 h) or 25°C for a short time (0.5 h), 48-h fixation at 25°C and sampling from FFPE scrolls instead of sections. Notably, we observed an increase in intronic reads and a significant change in gene rank based on expression level in the FFPE as opposed to fresh-frozen (FF) samples. Additionally, we found that more reads were mapped to genes associated with chemical stimulus in FFPE samples. Furthermore, we demonstrated that more degraded genes in FFPE samples were enriched in genes with short transcripts and high free energy. Besides, we found 40 housekeeping genes exhibited stable expression in FF and FFPE samples across various tissues. Moreover, our study showed that FFPE samples yielded comparable results to FF samples in dimensionality reduction and pathway analyses between case and control samples. Our study established the optimal conditions for FFPE preparation and identified gene attributes associated with degradation, which would provide useful clues for the utility of FFPE tissues in clinical practice and research.

Ultrasonic features of automated breast volume scanner (ABVS) and handheld ultrasound (HHUS) combined with molecular biomarkers in predicting axillary lymph node metastasis of clinical T1-T2 breast cancer.

Background: In the post-American College of Surgeons Oncology Group Z0011 trial era, clinicians are attempting to preoperatively evaluate axillary lymph node (ALN) status using ultrasound. However, the value of preoperative ultrasound examination remains uncertain. The study aimed to investigate the ultrasonic features of automated breast volume scanner (ABVS) and handheld ultrasound (HHUS), in combination with molecular biomarkers, to predict the risk of ALN metastasis (ALNM) in clinical T1-T2 breast cancer. Methods: A retrospective case-control analysis was conducted on 168 patients with clinical T1-T2 breast cancer at Peking University First Hospital between January 2013 and August 2021. Preoperative ABVS and HHUS examinations were performed. According to the pathology results of the ALN, patients were divided into metastatic and nonmetastatic groups. Logistic regression analyses were used to analyze the ultrasonic characteristics of ABVS and HHUS on clinical T1-T2 breast cancer, and molecular biomarkers were incorporated to predict the risk of ALNM. Results: Of the 168 patients, 88 (52.4%) had ipsilateral ALNM while 80 (47.6%) had no ipsilateral ALNM. The univariate analysis showed that shorter tumor-skin distance (P=0.011), the Adler blood flow grade of II-III (P=0.014), and larger tumor size on ABVS (P<0.001) were associated with ALNM. The multivariate logistic analysis showed that these three risk factors, including the tumor-skin distance [odds ratio (OR) =0.279; P=0.024], the Adler blood flow grade (OR =2.164; P=0.046), and the tumor size on ABVS (OR =1.033; P=0.002), were independent predictive parameters. Conclusions: The tumor-skin distance, tumor size on ABVS, and Adler blood flow grade have diagnostic value for ALNM in clinical T1-T2 breast cancer.

Integrative Analysis of miRNA and circRNA Expression Profiles and Interaction Network in HSV-1-Infected Primary Corneal Epithelial Cells.

PURPOSE: Circular RNAs (circRNAs) are products of alternative splicing with roles as competitive endogenous RNAs or microRNA sponges, regulating gene expression and biological processes. However, the involvement of circRNAs in herpes simplex keratitis remains largely unexplored. METHODS: This study examines circRNA and miRNA expression profiles in primary human corneal epithelial cells infected with HSV-1, compared to uninfected controls, using microarray analysis. Bioinformatic analysis predicted the potential function of the dysregulated circRNAs and microRNA response elements (MREs) in these circRNAs, forming an interaction network between dysregulated circRNAs and miRNAs. RESULTS: A total of 332 circRNAs and 16 miRNAs were upregulated, while 80 circRNAs and six miRNAs were downregulated (fold change ≥2.0 and p < 0.05). Gene ontology (GO) and KEGG pathway analyses were performed on parental genes of dysregulated circRNAs to uncover potential functions in HSV-1 infection. Notably, miR-181b-5p, miR-338-3p, miR-635, and miR-222-3p emerged as pivotal miRNAs interacting with multiple dysregulated circRNAs. CONCLUSIONS: This comprehensive study offers insights into differentially expressed circRNAs and miRNAs during HSV-1 infection in corneal epithelial cells, shedding light on circRNA-miRNA interactions' potential role in herpes simplex keratitis pathogenesis.

Efficacy and Safety of Chinese Medicine Resuscitation Pack for Enhanced Recovery after Bronchoscopy: A Randomized, Single-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS: Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).

Minor protopanaxadiol type sapogenins from the alkali hydrolysate of stems-leaves of Panax notoginseng.

Two new protopanaxadiol type sapogenins, (3ß,12ß)-3,12,20-trihydroxydammar-24-en-26-al (1) and (3ß,12ß)-3,12,20-trihydroxydammar-24-en-26-oic acid (2), were isolated from the alkali hydrolysate of stems-leaves of Panax notoginseng, along with seven known analogues (3-9). Their structures were elucidated by spectroscopic analyses and single-crystal X-ray diffraction. Compound 2 and the known sapogenins 5-8 displayed weak to moderate inhibition of NO production in LPS-induced RAW264.7 macrophages with IC50 values from 44.5 to 143.6 µM, respectively.

Matrix in River Water, Sediments, and Biofilms Mitigates Mercury Toxicity to Medaka (Oryzias Latipes).

Impacts of an environmental matrix on mercury (Hg) bioavailability and toxicity to medaka (Oryzias latipes) were investigated in matrix-free controls and treatments with a stepwise increased environmental matrix of river water, sediments, and biofilms. Generally, river water enhanced but the presence of sediments and biofilms reduced Hg bioavailability to medaka up to 105 times, so that Hgtotal concentrations/amounts among different environmental media cannot mirror Hg availability and toxicity to medaka. On average, 12.9 and 12.4% of Hg in medaka was, respectively, methylated to methylmercury (MeHg) in matrix-free and -containing treatments, indicating no influence of the environmental matrix on Hg methylation in medaka. All oxidative stress, inflammatory injury, and malformation parameters correlated strongly and significantly with Hgtotal and MeHg concentrations in medaka, notably with steeper slopes in matrix-free controls than in matrix-containing treatments, highlighting that the environmental matrix mitigated Hg and MeHg toxicity to medaka. Moreover, oxidative stress was more strongly mitigated than inflammatory injury according to the stronger decreases of the regression line slopes from matrix-free to -containing treatments. Here, we have newly identified that the potential of the environmental matrix to decrease Hg bioavailability and mitigate Hg toxicity to fish together could buffer Hg ecotoxicity in the aquatic environment.

Investigating Temporal Features of Carotid Intima-Media Thickness from Ultrasound Imaging with Recurrent Neural Networks.

Measuring carotid intima-media thickness (cIMT) of the Common Carotid Artery (CCA) via B-mode ultrasound imaging is a non-invasive yet effective way to monitor and assess cardiovascular risk. Recent studies using Convolutional Neural Networks (CNNs) to automate the process have mainly focused on the detection of regions of interest (ROI) in single frame images collected at fixed time points and have not exploited the temporal information captured in ultrasound imaging. This paper presents a novel framework to investigate the temporal features of cIMT, in which Recurrent Neural Networks (RNN) were deployed for ROI detection using consecutive frames from ultrasound imaging. The cIMT time series can be formed from estimates of cIMT in each frame of an ultrasound scan, from which additional information (such as min, max, mean, and frequency) on cIMT time series can be extracted. Results from evaluation show the best performance for ROI detection improved 4.75% by RNN compared to CNN-based methods. Furthermore, the heart rate estimated from the cIMT time series for seven patients was highly correlated with the patient's clinical records, which suggests the potential application of the cIMT time series and related features for clinical studies in the future.Clinical relevance- The temporal features extracted from cIMT time series provide additional information that can be potentially beneficial for clinical studies.

KDF1 Promoted Proliferation, Migration and Invasion of Lung Adenocarcinoma Cells through Activating STAT3 and AKT Pathway.

KDF1 has been reported to be correlated with carcinogenesis. However, its role and mechanism are far from clear. To explore the possible role and underlying mechanism of KDF1 in lung adenocarcinoma (LUAD), we investigated KDF1 expression in LUAD tissues and the influence of KDF1 in the phenotype of LUAD cells (A549 and PC-9) as well as the underlying mechanism. Compared to non-tumor lung epithelial cells, KDF1 was upregulated in the cancer cells of the majority of LUAD patients, and its expression was correlated with tumor size. Patients with enhanced KDF1 in cancer cells (compared with paired adjacent non-neoplastic lung epithelial cells) had shorter overall survival than patients with no increased KDF1 in cancer cells. Knockdown of KDF1 inhibited the migration, proliferation and invasion of LUAD cells in vitro. And overexpression of KDF1 increased the growth of the subcutaneous tumors in mice. In terms of molecular mechanisms, overexpression of KDF1 induced the expression of AKT, p-AKT and p-STAT3. In KDF1-overexpressing A549 cells, inhibition of the STAT3 pathway decreased the level of AKT and p-AKT, whereas inhibition of the AKT pathway had no effect on the activation of STAT3. Inhibition of STAT3 or AKT pathways reversed the promoting effects of KDF1 overexpression on the LUAD cell phenotype and STAT3 inhibition appeared to have a better effect. Finally, in the cancer cells of LUAD tumor samples, the KDF1 level was observed to correlate positively with the level of p-STAT3. All these findings suggest that KDF1, which activates STAT3 and the downstream AKT pathway in LUAD, acts as a tumor-promoting factor and may represent a therapeutic target.

Predictive analysis of effects of water stress on strawberry seedlings using fluorescent image channel components.

To investigate the effect of water stress on strawberry seedlings, a chlorophyll-fluorescence-image-acquisition system was developed. Strawberry seedlings of uniform growth were selected for grouped water-stress incubation experiments; the collected chlorophyll-fluorescence images of leaves were converted to red-green-blue (RGB), hue-saturation-value (HSV), and hue-saturation-intensity (HSI) color spaces and analyzed for water and chlorophyll contents measured at the same time for 14 consecutive days. The results indicate that the analysis and prediction of plant stress conditions can be effectively conducted using the channel components of the color-space model and the channel component ratios, which provide a reference for promoting agricultural development.

Liver transplantation for advanced-stage primary hepatic yolk sac tumor: A case report and literature review.

RATIONALE: Primary hepatic yolk sac tumors (YSTs) are rare in adults. Liver resection is an acknowledged treatment modality for primary hepatic YST. Liver transplantation may offer a possible cure for unresectable cases. PATIENT CONCERNS: We present a case of a 31-year-old woman with an abdominal mass who had abnormally elevated alpha-fetoprotein (AFP) levels (31,132 ng/mL; normal: 0-7 ng/mL). Contrast-enhanced computed tomography (CT) revealed large tumors located in both lobes of the liver, with arterial enhancement and venous washout. Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT indicated increased 18F-FDG uptake (maximum standardized uptake value, 24.4) in the liver tumors and left middle intra-abdominal nodule. DIAGNOSES: The diagnosis was primary hepatic YST with metastasis to the greater omentum. INTERVENTIONS: The patient underwent orthotopic liver transplantation and intra-abdominal nodule resection after transarterial chemoembolization (TACE) as a bridge. Intraoperatively, an intra-abdominal nodule was confirmed in the greater omentum. Histopathological examination of the liver tumors revealed Schiller-Duval bodies. The tropomyosin receptor kinase (TRK) inhibitor larotrectinib was administered, followed by four cycles of chemotherapy with bleomycin, etoposide, and cisplatin based on the next-generation sequencing results. OUTCOMES: The AFP level decreased to within the normal range. No evidence of tumor collapse was observed during the 34-month follow-up period. LESSONS: This case suggests that multimodal therapy dominated by liver transplantation, including preoperative TACE, postoperative adjuvant chemotherapy, and TRK inhibitors, is an effective treatment modality for unresectable primary hepatic YST.

Investigating the diet source influence on freshwater fish mercury bioaccumulation and fatty acids-Experiences from Swedish lakes and Chinese reservoirs.

Dietary uptake is key for transferring potentially toxic contaminants, such as mercury (Hg) and essential dietary nutrients, such as polyunsaturated fatty acids (PUFA), to consumers at higher trophic levels of aquatic food webs. We evaluated the role of diet sources for Hg bioaccumulation and PUFA retention in fish across lake food webs in seven Swedish lakes and two Chinese reservoirs. Fish total Hg (THg) and methyl-Hg (MeHg) differed greatly between the two countries: the Chinese fish contained less than 300 ng g-1 dry weight (d.w.) THg with less than 50% as MeHg, versus the Swedish fishes which contained approximately 2000 ng g-1 d.w. THg and nearly 100% as MeHg. Fatty acids enrichment of linoleic acids (LIN) were more prevalent in the Chinese fishes regardless of size (p < 0.05). Here we examined food web length, fish growth rates, and fatty acids patterns in relation to the quality of fish as a food source for both Hg and FA. Contrary to the expectation that biodilution of Hg throughout the food chain would explain these differences, a more complex picture emerged with high levels of Hg at the base of the food web in the Chinese reservoirs, a decoupling of fatty acid and Hg bioaccumulation, and a major role for both fish stocking and fish feed. It is hoped that this work will provide a nuanced picture of fish quality as a food source in different ecosystems.

Molecular Dynamics Simulation and Viscosity Analysis of Red Mud-Steel Slag Glass-Ceramics.

The preparation of glass-ceramics with red mud and steel slag can not only solve the pollution problem caused by industrial waste slag but also produce economic benefits. It is difficult to analyze the high-temperature melt with the existing test methods, so the simulation experiment with molecular dynamics calculation becomes an important research method. The effects of steel slag content on the microstructure of red mud glass-ceramics were studied by molecular dynamics method. The results show that the binding ability of Si-O, Al-O, and Fe-O decreases with the increase in steel slag content. The number of Si-O-Si bridge oxygen increased gradually, while the number of Al-O-Al, Al-O-Fe, and Fe-O-Fe bridge oxygen decreased significantly. The number of tetrahedrons [SiO4] increased, the number of tetrahedrons [FeO4] and [AlO4] decreased, and the total number of three tetrahedrons decreased. The mean square displacement value of Si4+ and O2- increases first and then decreases, resulting in the viscosity of the system decreasing first and then increasing. The molecular dynamics method is used to analyze the structure of red mud-steel slag glass-ceramics on the microscopic scale, which can better understand the role of steel slag and has guiding significance for the experiment of this kind of glass-ceramics.