Neolignans in Magnolia officinalis as natural anti-Alzheimer's disease agents: A systematic review.

BACKGROUND: Magnolia officinalis, a traditional herbal medicine widely used in clinical practice, exerts antibacterial, anti-tumor, anti-inflammatory, antioxidant, and anti-aging activities. Neolignans are the main active ingredients of M. officinalis and exert a wide range of pharmacological effects, including anti-Alzheimer's disease (AD) activity. OBJECTIVE: To summarize the published data on the therapeutic effect and mechanism of neolignans on AD in vivo and in vitro. METHODS: PubMed, Web of Science, Google Scholar, and Scopus were systematically reviewed (up to March 1, 2024) for pre-clinical studies. RESULTS: M. officinalis-derived neolignans (honokiol, magnolol, 4-O-methylhonokiol, and obovatol) alleviated behavioral abnormalities, including learning and cognitive impairments, in AD animal models. Mechanistically, neolignans inhibited Aß generation or aggregation, neuroinflammation, and acetylcholinesterase activity; promoted microglial phagocytosis and anti-oxidative stress; alleviated mitochondrial dysfunction and energy metabolism, as well as anti-cholinergic deficiency; and regulated intestinal flora. Furthermore, neolignans may achieve neuroprotection by regulating different molecular pathways, including the NF-κB, ERK, AMPK/mTOR/ULK1, and cAMP/PKA/CREB pathways. CONCLUSIONS: Neolignans exert anti-AD effects through multiple mechanisms and pathways. However, the exact targets, pharmacokinetics, safety, and clinical efficacy in patients with AD need further investigation in multi-center clinical case-control studies.

Lactylation: The emerging frontier in post-translational modification.

Lactate, a metabolic byproduct, has gained recognition as a highly influential signaling molecule. Lactylation, an emerging form of post-translational modification derived from lactate, plays a crucial role in numerous cellular processes such as inflammation, embryonic development, tumor proliferation, and metabolism. However, the precise molecular mechanisms through which lactylation governs these biological functions in both physiological and pathological contexts remain elusive. Hence, it is imperative to provide a comprehensive overview of lactylation in order to elucidate its significance in biological processes and establish a foundation for forthcoming investigations. This review aims to succinctly outline the process of lactylation modification and the characterization of protein lactylation across diverse organisms. Additionally, A summary of the regulatory mechanisms of lactylation in cellular processes and specific diseases is presented. Finally, this review concludes by delineating existing research gaps in lactylation and proposing primary directions for future investigations.

Dysregulated serum lipid profile is associated with inflammation and disease activity in primary Sjögren's syndrome: a retrospective study in China.

PURPOSE: To investigate the relationship between the lipid profiles of patients with primary Sjögren's syndrome (pSS) and other clinical characteristics, laboratory examination, disease activity, and inflammatory factors. In addition, the risk factors for hyperlipidemia-related complications of pSS and the effect of hydroxychloroquine (HCQ) usage on the lipid profile were incorporated into this study. METHODS: This is a single-center, retrospective study that included 367 patients who were diagnosed with pSS at Tongji Hospital, School of Medicine, Tongji University, China from January 2010 to March 2022. Initially, demographic information, clinical characteristics, medication records, and complications of the patients were gathered. A case-control analysis compared the 12 systems involvement (ESSDAI domain), clinical symptoms, and laboratory tests between pSS patients with and without dyslipidemia. A simple linear regression model was employed to investigate the relationship between serum lipid profile and inflammatory factors. Logistics regression analysis was performed to assess variables for hyperlipidemia-related complications of pSS. The paired t-test was then used to evaluate the improvement in lipid profile among pSS patients. RESULTS: 48.7 % of all pSS patients had dyslipidemia, and alterations in lipid levels were related to gender, age, and smoking status but not body mass index (BMI). Dyslipidemia is more prevalent in pSS patients who exhibit heightened autoimmunity and elevated levels of inflammation. Higher concentrations of multiple highly inflammatory factors correlate with a more severe form of dyslipidemia. Non-traditional cardiovascular risk factors may contribute to hyperlipidemia-related complications of pSS, such as increased, low complement 3 (C3) and low C4. According to our study, HCQ usage may protect against lipid-related disease in pSS. CONCLUSION: Attention should be paid to the dyslipidemia of pSS. This research aims to clarify the population portrait of pSS patients with abnormal lipid profiles and provides insights into the correlation between metabolism and inflammation in individuals with pSS and the potential role they play in the advancement of the disease. These findings provide novel avenues for further understanding the underlying mechanisms of pSS pathogenesis.

A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy.

BACKGROUND: Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranostics. Herein, we propose a proof-of-concept strategy aiming to address the profound differences in the specific requirements of the diagnosis and treatment of radiotheranostics. RESULTS: To validate the concept, we designed an s-tetrazine (Tz) conjugated prostate-specific membrane antigen (PSMA) ligand (DOTA-PSMA-Tz) for 68Ga or 177Lu radiolabeling and tumor radiotheranostics, a trans-cyclooctene (TCO) modified Pd@Au nanoplates (Pd@Au-PEG-TCO) for signal amplification, respectively. We then demonstrated this radiotheranostic strategy in the tumor-bearing mice with the following three-step procedures: (1) i.v. injection of the [68Ga]Ga-PSMA-Tz for diagnosis; (2) i.v. injection of the signal amplification module Pd@Au-PEG-TCO; (3) i.v. injection of the [177Lu]Lu-PSMA-Tz for therapy. Firstly, this strategy was demonstrated in 22Rv1 tumor-bearing mice via positron emission tomography (PET) imaging with [68Ga]Ga-PSMA-Tz. We observed significantly higher tumor uptake (11.5 ± 0.8%ID/g) with the injection of Pd@Au-PEG-TCO than with the injection [68Ga]Ga-PSMA-Tz alone (5.5 ± 0.9%ID/g). Furthermore, we validated this strategy through biodistribution studies of [177Lu]Lu-PSMA-Tz, with the injection of the signal amplification module, approximately five-fold higher tumor uptake of [177Lu]Lu-PSMA-Tz (24.33 ± 2.53% ID/g) was obtained when compared to [177Lu]Lu-PSMA-Tz alone (5.19 ± 0.26%ID/g) at 48 h post-injection. CONCLUSION: In summary, the proposed strategy has the potential to expand the toolbox of pretargeted radiotherapy in the field of theranostics.

Development of small-molecular-based radiotracers for PET imaging of PD-L1 expression and guiding the PD-L1 therapeutics.

PURPOSE: Programmed cell death protein ligand 1 (PD-L1) is a crucial biomarker for immunotherapy. However, nearly 70% of patients do not respond to PD-L1 immune checkpoint therapy. Accurate monitoring of PD-L1 expression and quantification of target binding during treatment are essential. In this study, a series of small-molecule radiotracers were developed to assess PD-L1 expression and direct immunotherapy. METHODS: Radiotracers of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were designed based on a 2-methyl-3-biphenyl methanol scaffold and successfully synthesized. Cellular experiments and molecular docking assays were performed to determine their specificity for PD-L1. PD-L1 status was investigated via positron emission tomography (PET) imaging in MC38 tumor models. PET imaging of [68Ga]Ga-D-pep-PMED was performed to noninvasively quantify PD-L1 blocking using an anti-mouse PD-L1 antibody (PD-L1 mAb). RESULTS: The radiosyntheses of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were achieved with radiochemical yields of 87 ± 6%, 82 ± 4%, and 79 ± 9%, respectively. In vitro competition assays demonstrated their high affinities (the IC50 values of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were 90.66 ± 1.24, 160.8 ± 1.35, and 51.6 ± 1.32 nM, respectively). At 120 min postinjection (p.i.) of the radiotracers, MC38 tumors displayed optimized tumor-to-muscle ratios for all radioligands. Owing to its hydrophilic modification, [68Ga]Ga-D-pep-PMED had the highest target-to-nontarget (T/NT) ratio of approximately 6.2 ± 1.2. Interestingly, the tumor/liver ratio was hardly affected by different concentrations of the inhibitor BMS202. We then evaluated the impacts of dose and time on accessible PD-L1 levels in the tumor during anti-mouse PD-L1 antibody treatment. The tumor uptake of [68Ga]Ga-D-pep-PMED significantly decreased with increasing PD-L1 mAb dose. Moreover, after 8 days of treatment with a single antibody, the uptake of [68Ga]Ga-D-pep-PMED in the tumor significantly increased but remained lower than that in the saline group. CONCLUSION: PET imaging with [68Ga]Ga-D-pep-PMED, a small-molecule radiotracer, is a promising tool for evaluating PD-L1 expression and quantifying the target blockade of PD-L1 to assist in the development of effective therapeutic regimens.

Chiral cysteine-copper ion-based assemblies for improved phototherapy.

Phototherapy, encompassing photothermal therapy and photodynamic therapy, is gaining attention as an appealing cancer treatment modality. To enhance its clinical implementation, a comprehensive exploration of the pivotal factors influencing phototherapy is warranted. In this study, the L/d-cysteine (Cys)-copper ion (Cu2+) chiral nanoparticles, through the assembly of L/d-Cys-Cu2+ coordination complexes, were constructed. We found that these nanoparticles interacted with chiral liposomes in a chirality-dependent manner, with d-Cys-Cu2+ nanoparticles exhibiting more than three times stronger binding affinity than l-Cys-Cu2+ nanoparticles. Furthermore, we demonstrated that the d-Cys-Cu2+ nanoparticles were more efficiently internalized by Hela cells in contrast with l-Cys-Cu2+. On this basis, indocyanine green (ICG), acting as both photothermal and photodynamic agent, was encapsulated into L/d-Cys-Cu2+ nanoparticles. Experimental results showed that the l-Cys-Cu2+-ICG and d-Cys-Cu2+-ICG nanoparticles displayed almost identical photothermal performance and singlet oxygen (1O2) generation capability in aqueous solution. However, upon laser irradiation, the d-Cys-Cu2+-ICG nanoparticles achieved enhanced anti-tumor effects compared to l-Cys-Cu2+-ICG due to their chirality-promoted higher cellular uptake efficiency. These findings highlight the crucial role of chirality in phototherapy and provide new perspectives for engineering cancer therapeutic agents.

Pulmonary contusion: automated deep learning-based quantitative visualization.

PURPOSE: Rapid automated CT volumetry of pulmonary contusion may predict progression to Acute Respiratory Distress Syndrome (ARDS) and help guide early clinical management in at-risk trauma patients. This study aims to train and validate state-of-the-art deep learning models to quantify pulmonary contusion as a percentage of total lung volume (Lung Contusion Index, or auto-LCI) and assess the relationship between auto-LCI and relevant clinical outcomes. METHODS: 302 adult patients (age ≥ 18) with pulmonary contusion were retrospectively identified from reports between 2016 and 2021. nnU-Net was trained on manual contusion and whole-lung segmentations. Point-of-care candidate variables for multivariate regression included oxygen saturation, heart rate, and systolic blood pressure on admission. Logistic regression was used to assess ARDS risk, and Cox proportional hazards models were used to determine differences in ICU length of stay and mechanical ventilation time. RESULTS: Mean Volume Similarity Index and mean Dice scores were 0.82 and 0.67. Interclass correlation coefficient and Pearson r between ground-truth and predicted volumes were 0.90 and 0.91. 38 (14%) patients developed ARDS. In bivariate analysis, auto-LCI was associated with ARDS (p < 0.001), ICU admission (p < 0.001), and need for mechanical ventilation (p < 0.001). In multivariate analyses, auto-LCI was associated with ARDS (p = 0.04), longer length of stay in the ICU (p = 0.02) and longer time on mechanical ventilation (p = 0.04). AUC of multivariate regression to predict ARDS using auto-LCI and clinical variables was 0.70 while AUC using auto-LCI alone was 0.68. CONCLUSION: Increasing auto-LCI values corresponded with increased risk of ARDS, longer ICU admissions, and longer periods of mechanical ventilation.

Chronic Epstein-Barr virus infection: A potential junction between primary Sjögren's syndrome and lymphoma.

Primary Sjögren's syndrome (pSS) is an autoimmune disease that targets exocrine glands, leading to exocrine dysfunction. Due to its propensity to infect epithelial and B cells, Epstein-Barr virus (EBV) is hypothesized to be related with pSS. Through molecular mimicry, the synthesis of specific antigens, and the release of inflammatory cytokines, EBV contributes to the development of pSS. Lymphoma is the most lethal outcome of EBV infection and the development of pSS. As a population-wide virus, EBV has had a significant role in the development of lymphoma in people with pSS. In the review, we will discuss the possible causes of the disease.

Paravertebral Block Under Direct Vision Versus Local Anesthetic Infiltration for Pediatric Thoracoscopic Surgery.

Background: For children with congenital lung malformations (CLMs), there is insufficient evidence of the efficacy of direct visual paravertebral block (PVB). We aimed to evaluate its effectiveness and safety by comparing it with local anesthetic infiltration (LAI). Materials and Methods: This was a nonrandomized control study of CLMs in children younger than 3 years of age who underwent thoracoscopic surgery in our hospital from January to December 2020. The children were divided into group A (PVB analgesia group) and group B (LAI group). The primary outcome was the incidence of rebound pain within 72 hours. Secondary outcomes included the Face, Legs, Activity, Crying, Consolability (FLACC) pain scores at 0, 6, 12, 24, 36, 48, and 72 hours, side effects, adverse events, the number of rebound pains, and the postoperative family observation scores. Results: The incidence of rebound pain was 10% in group A and 60.5% in group B within 72 hours (P < .001). The PVB was associated with decreased FLACC pain scores at 12, 24, 36, 48, and 72 hours, family observation scores, and the number of rebound pains (P < .001, P = .01, P = .028, P = .005, P = .006, P = .026, and P < .001, respectively). Group B was also associated with a higher rate of side effects and adverse events. There was no difference in the length of hospital stay. Conclusion: The PVB under direct vision analgesia technique is effective and safe for postoperative pain control in pediatric patients with CLMs. It may be an attractive alternative to LAI for pediatric thoracoscopic surgical procedures.

Development of [177Lu]Lu-LNC1003 for radioligand therapy of prostate cancer with a moderate level of PSMA expression.

PURPOSE: Evans blue as an albumin binder has been widely used to improve pharmacokinetics and enhance tumor uptake of radioligands, including prostate-specific membrane antigen (PSMA) targeting agents. The goal of this study is to develop an optimal Evans blue-modified radiotherapeutic agent that could maximize the absolute tumor uptake and tumor absorbed dose thus the therapeutic efficacy to allow treatment of tumors even with moderate level of PSMA expression. METHODS: [177Lu]Lu-LNC1003 was synthesized based on PSMA-targeting agent and Evans blue. Binding affinity and PSMA targeting specificity were verified through cell uptake and competition binding assay in 22Rv1 tumor model that has moderate level of PSMA expression. SPECT/CT imaging and biodistribution studies in 22Rv1 tumor-bearing mice were performed to evaluate the preclinical pharmacokinetics. Radioligand therapy studies were conducted to systematically assess the therapeutic effect of [177Lu]Lu-LNC1003. RESULTS: LNC1003 showed high binding affinity (IC50 = 10.77 nM) to PSMA in vitro, which was comparable with that of PSMA-617 (IC50 = 27.49 nM) and EB-PSMA-617 (IC50 = 7.91 nM). SPECT imaging of [177Lu]Lu-LNC1003 demonstrated significantly improved tumor uptake and retention as compared with [177Lu]Lu-EB-PSMA and [177Lu]Lu-PSMA-617, making it suitable for prostate cancer therapy. Biodistribution studies further confirmed the remarkably higher tumor uptake of [177Lu]Lu-LNC1003 (138.87 ± 26.53%ID/g) over [177Lu]Lu-EB-PSMA-617 (29.89 ± 8.86%ID/g) and [177Lu]Lu-PSMA-617 (4.28 ± 0.25%ID/g) at 24 h post-injection. Targeted radioligand therapy results showed noteworthy inhibition of 22Rv1 tumor growth after administration of a single dose of 18.5 MBq [177Lu]Lu-LNC1003. There was no obvious antitumor effect after [177Lu]Lu-PSMA-617 treatment under the same condition. CONCLUSION: In this study, [177Lu]Lu-LNC1003 was successfully synthesized with high radiochemical purity and stability. High binding affinity and PSMA targeting specificity were identified in vitro and in vivo. With greatly enhanced tumor uptake and retention, [177Lu]Lu-LNC1003 has the potential to improve therapeutic efficacy using significantly lower dosages and less cycles of 177Lu that promises clinical translation to treat prostate cancer with various levels of PSMA expression.

Contribution of Sucrose Metabolism in Phloem to Kiwifruit Bacterial Canker Resistance.

Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. actinidiae (Psa), is a catastrophic disease affecting kiwifruit worldwide. As no effective cure has been developed, planting Psa-resistant cultivars is the best way to avoid bacterial canker in kiwifruit cultivation. However, the differences in the mechanism of resistance between cultivars is poorly understood. In the present study, five local kiwifruit cultivars were used for Psa resistance evaluation and classified into different resistance categories, tolerant (T), susceptible (S), and highly susceptible (HS), based on their various symptoms of lesions on the cane. Susceptible and highly susceptible varieties had a higher sucrose concentration, and a greater decrease in sucrose content was observed after Psa inoculation in phloem than in tolerant varieties. Three invertase activities and their corresponding gene expressions were detected in the phloem with lesions and showed the same trends as the variations in sucrose concentration. Meanwhile, after Psa inoculation, enzyme activities involved in antioxidant defense responses, such as PAL, POD, and CAT, were also altered in the phloem of the lesion position. With no differences among cultivars, PAL and POD activities in phloem first increased and then decreased after Psa inoculation. However, great differences in CAT activities were observed between T and S/HS categories. Our results demonstrate that sucrose content was negatively correlated with the disease resistance of different cultivars and that the increase in immune response enzymes is likely caused by increased sucrose metabolism in the phloem.

Blunt splenic injury in adults: Association between volumetric quantitative CT parameters and intervention.

Several ordinal grading systems are used in deciding whether to perform angioembolization (AE) or splenectomy following blunt splenic injury (BSI). The 2018 American Association for the Surgery of Trauma (AAST) Organ Injury Scale incorporates vascular lesions but not hemoperitoneum, which is considered in the Thompson classifier. Granular and verifiable quantitative measurements of these features may have a future role in facilitating objective decision making. The purpose of this study is to compare performance of computed tomography (CT) volumetry-based quantitative modeling to the 1994 and 2018 AAST Organ Injury Scale and Thompson classifier for the following endpoints: decision to perform splenectomy (SPY), and the composite of SPY or AE. Adult BSI patients (age ≥18 years) scanned with dual-phase CT prior to intervention at a single Level I trauma center from 2017 to 2019 were included in this retrospective study (n = 174). Scoring using 2018 AAST, 1994 AAST, and Thompson systems was performed retrospectively by two radiologists and arbitrated by a third. Endpoints included (1) SPY and (2) the composite of SPY or AE. Logistic regression models were developed from segmented active bleed, contained vascular lesion, splenic parenchymal disruption, and hemoperitoneum volumes. Area under the receiver operating characteristic curve (AUC) for ordinal systems and volumetric models were compared. Forty-seven BSI patients (27%) underwent SPY, and 87 patients (50%) underwent SPY or AE. Quantitative model AUCs (0.85­SPY, 0.82­composite) were not significantly different from 2018 AAST AUCs (0.81, 0.88, p = 0.66, 0.14) for both endpoints and were significantly improved over Thompson scoring (0.76, p = 0.02; 0.77, p = 0.04). Quantitative CT volumetry can be used to model intervention for BSI with accuracy comparable to 2018 AAST scoring and significantly higher than Thompson scoring. Prognostic and Epidemiological; Level IV.

Predictors of poor prognosis in ANCA-associated vasculitis (AAV): a single-center prospective study of inpatients in China.

To identify potential predictors by assessing adverse outcomes in ANCA-associated vasculitis (AAV) patients. Eighty-nine untreated AAV patients were followed up to January 31, 2022, death, or loss of follow-up. Clinical characteristics, laboratory tests, treatment, and progress were collected, and disease activity was evaluated via Birmingham Vasculitis Activity Score (BVAS). We determined risk factors of high-risk events, defined as developing tumors, renal replacement therapy (RRT), and death. Patients and renal survivals were computed by the Kaplan-Meier curve analysis. Cox regression analysis was performed for assessing variables for predicting death. During 267 person-years follow-up, 46 patients occurred high-risk events, including 20 patients receiving RRT, 12 patients developing tumors, and 29 patients who died mostly from organ failure and infection. Decreased estimated glomerular filtration rate (eGFR) (P < 0.001) and complement 3 levels (P = 0.019) were associated with high-risk events. Patients with lower serum potassium tended to develop tumors (P = 0.033); with higher BVAS (HR = 1.290, 95%CI 1.075-1.549, P = 0.006) and lower eGFR (HR = 0.782, 95%CI 0.680-0.901, P = 0.001) were more likely to undergo RRT. Patients with cardio and renal involvement exhibited a lower frequency of renal survival and all-cause mortality. Through multivariate COX analysis, age (HR = 1.016, 95%CI 1.016-1.105, P = 0.006) and eGFR (HR = 0.982, 95%CI 0.968-0.997, P = 0.018) predicted death in AAV, separately. The BVAS and eGFR could be a great prognosticator for RRT, while age and eGFR can independently predict the death. Serum potassium level and immunoglobulins should be focused on their predictor value in development of cancer and renal outcomes in AAV patients.

Determining Protein-Protein Interaction with GFP-Trap Beads.

Protein-protein interactions play a vital role in the cellular physiology of living organisms. Among several available approaches, co-immunoprecipitation (co-IP) has emerged as a reliable method to investigate such interactions. The underlying principle is to retrieve a bait protein from a protein extract using bait-specific antibodies and thereby indirectly capture the interacting partner proteins. However, bait-specific antibodies are not always available, and the genetic fusion of a peptide tag offers an alternative. An extensive range of peptide tags and the tag-specific antibodies are available nowadays. Fluorescent proteins are widely used protein tags for co-IP experiments. In this chapter, we describe a method to co-immunoprecipitate the fluorescently tagged candidate protein with its interacting partners from the crude plant cell extracts using green fluorescent protein (GFP)-trap magnetic beads.

Integrated Plastic Surgery Residency Applicant Perceptions of Virtual Interviews.

PURPOSE: The 2020-2021 interview cycle for integrated plastic surgery applicants was the first to be held virtually because of the COVID-19 pandemic. Here, we detail the largest study on integrated plastic surgery applicant perceptions after the virtual interview cycle. METHODS: A 35-question institutional review board-approved survey was distributed to medical students who had applied to the Johns Hopkins/University of Maryland or University of California San Diego integrated residency programs during the 2020-2021 interview cycle. Survey questions assessed the structure, strengths, and weaknesses of the exclusively virtual interview process. Survey administration and data collection were performed using the Qualtrics platform. RESULTS: Of 318 distributed surveys, 94 were completed. In addition, 91.5% of respondents preferred in-person interviews before the interview season, whereas 54.3% preferred in-person interviews afterward. Applicants who favored virtual interviews did not view being unable to physically meet with program staff as a detriment (P = .001) and felt they could effectively advocate for themselves (P = .002). Overall, the most cited strengths were the ability to complete more interviews (P = .01) and cost benefits (P = .02). Criticisms were directed at the impersonal nature of the exchange (86.2%), lack of physical tour (56.4%), and difficulties at self-advocacy (52.1%). CONCLUSION: Preference for virtual interviews increased from 7.5% to 34.0% after the virtual interview cycle. For several students, the ideal interview structure permits both in-person and virtual interviews to maximize flexibility. Augmenting with virtual city tours and one-on-one interviews may mitigate the impersonal nature of virtual interviews as perceived by some applicants.

Deciphering the Biological Effects of Radiotherapy in Cancer Cells.

Radiotherapy remains an effective conventional method of treatment for patients with cancer. However, the clinical efficacy of radiotherapy is compromised by the development of radioresistance of the tumor cells during the treatment. Consequently, there is need for a comprehensive understanding of the regulatory mechanisms of tumor cells in response to radiation to improve radiotherapy efficacy. The current study aims to highlight new developments that illustrate various forms of cancer cell death after exposure to radiation. A summary of the cellular pathways and important target proteins that are responsible for tumor radioresistance and metastasis is also provided. Further, the study outlines several mechanistic descriptions of the interaction between ionizing radiation and the host immune system. Therefore, the current review provides a reference for future research studies on the biological effects of new radiotherapy technologies, such as ultra-high-dose-rate (FLASH) radiotherapy, proton therapy, and heavy-ion therapy.

A pilot study of deep learning-based CT volumetry for traumatic hemothorax.

PURPOSE: We employ nnU-Net, a state-of-the-art self-configuring deep learning-based semantic segmentation method for quantitative visualization of hemothorax (HTX) in trauma patients, and assess performance using a combination of overlap and volume-based metrics. The accuracy of hemothorax volumes for predicting a composite of hemorrhage-related outcomes - massive transfusion (MT) and in-hospital mortality (IHM) not related to traumatic brain injury - is assessed and compared to subjective expert consensus grading by an experienced chest and emergency radiologist. MATERIALS AND METHODS: The study included manually labeled admission chest CTs from 77 consecutive adult patients with non-negligible (≥ 50 mL) traumatic HTX between 2016 and 2018 from one trauma center. DL results of ensembled nnU-Net were determined from fivefold cross-validation and compared to individual 2D, 3D, and cascaded 3D nnU-Net results using the Dice similarity coefficient (DSC) and volume similarity index. Pearson's r, intraclass correlation coefficient (ICC), and mean bias were also determined for the best performing model. Manual and automated hemothorax volumes and subjective hemothorax volume grades were analyzed as predictors of MT and IHM using AUC comparison. Volume cut-offs yielding sensitivity or specificity ≥ 90% were determined from ROC analysis. RESULTS: Ensembled nnU-Net achieved a mean DSC of 0.75 (SD: ± 0.12), and mean volume similarity of 0.91 (SD: ± 0.10), Pearson r of 0.93, and ICC of 0.92. Mean overmeasurement bias was only 1.7 mL despite a range of manual HTX volumes from 35 to 1503 mL (median: 178 mL). AUC of automated volumes for the composite outcome was 0.74 (95%CI: 0.58-0.91), compared to 0.76 (95%CI: 0.58-0.93) for manual volumes, and 0.76 (95%CI: 0.62-0.90) for consensus expert grading (p = 0.93). Automated volume cut-offs of 77 mL and 334 mL predicted the outcome with 93% sensitivity and 90% specificity respectively. CONCLUSION: Automated HTX volumetry had high method validity, yielded interpretable visual results, and had similar performance for the hemorrhage-related outcomes assessed compared to manual volumes and expert consensus grading. The results suggest promising avenues for automated HTX volumetry in research and clinical care.

Exploring the value of rectal anal canal pressure measurement in the diagnosis of Hirschsprung's disease.

Background: The value of rectal anorectal manometry (ARM) in the diagnosis of Hirschsprung's disease (HD), especially in newborns, has been controversial. This study aims to further explore the value of ARM in the diagnosis of HD. Methods: This study prospectively collected the rectal and anal canal pressure records of children with high suspicion of HD diagnosed by rectal suction biopsy (RSB) from the West China Hospital of Sichuan University from November 2019 to September 2021. With RSB results as the diagnostic gold standard, the value of ARM examination in the diagnosis of HD was explored through age stratification. Results: Among 170 children, the sensitivity of ARM in diagnosing HD was 98%, the specificity was 65%, and the accuracy was 93%. The positive likelihood ratio was 2.83, and the negative likelihood ratio was 0.03. The positive result of ARM is more important to HD. The positive predictive value was 94%, the negative predictive value of the ARM negative result for HD was 85%, the kappa value was 0.680, and the Yuedeng index was 0.63. Through age stratification, it was found that the sensitivity of ARM for HD diagnosis in each age group was relatively close, but the neonatal specificity was only 33%, which was significantly lower than that of children of other age groups. Conclusion: ARM has high sensitivity in HD children of all ages. In neonates, ARM has a high false positive rate in the diagnosis of HD.

Electrochemiluminescent determination of CYFRA21-1 serum levels using Ti-Fe-O nanotubes immunoassay.

Prominent electrochemiluminescence (ECL) in Ti-Fe-O nanotube arrays (Ti-Fe-O NTs) with K2S2O8 as the cathode coreactant is reported for the first time. Compared with pure titanium dioxide nanotubes (TiO2 NTs), this heterojunction could effectively reduce the band gap, facilitate electronic transitions, and move the ECL potential to a positive direction. The ECL performance motivated the development of an ultrasensitive ECL immunosensor for detecting cytokeratin fragment 21-1 (CYFRA21-1). Magnetic beads loaded with conductive carbon black (CCB/MNTs) were used to efficiently quench the ECL signal of a Ti-Fe-O NTs electrode and were combined with an ECL immunoassay to realize sensitive detection of CYFRA21-1. Over a CYFRA21-1 concentration range of 1.0 pg·mL-1 ~ 100 ng·mL-1, the change in the ECL signal was highly linear with the logarithm of the CYFRA21-1 concentration, and the limit of detection (LOD) was 0.114 pg·mL-1. This ECL immunosensor was used to successfully determine the CYFRA21-1 content in serum. The recovery of CYFRA21-1 in actual serum was 88.6 - 104.4%, and the RSD was 1.4 - 3.0%. The coreaction solution used in this work was PBS (0.1 M, pH = 7.4) containing 0.05 M K2S2O8, the scanning range was -1.0 - 0 V, the photomultiplier tube (PMT) was set to 750 V, and the scanning rate was 100 mV·s-1.