ß-Cyclodextrin metal-organic framework as a green carrier to improve the dissolution, bioavailability, and liver protective effect of luteolin.

The incidence of acetaminophen-induced liver injury has increased, but effective prevention methods are limited. Although luteolin has hepatoprotective activity, its low solubility and bioavailability limit its applications. Cyclodextrin metal-organic frameworks (CD-MOFs) possess 3D-network structures and large inner cavities, which make them excellent carriers of poorly soluble drugs. In this study, we used CD-MOFs as carriers to improve the dissolution of luteolin and assessed their antioxidant activity, bioavailability, and hepatoprotective effects. Luteolin was loaded into ß-CD-MOF, γ-CD-MOF, ß-CD, and γ-CD, and characterized by powder X-ray diffractometry (PXRD) and thermogravimetric analysis (TGA). Our results showed that luteolin-ß-CD-MOF was the most stable. The main driving forces were hydrogen bonds and van der Waals forces, as determined by molecular simulation. The loading capacity of luteolin-ß-CD-MOF was 14.67 wt%. Compared to raw luteolin, luteolin-ß-CD-MOF exhibited a 4.50-fold increase in dissolution and increased antioxidant activity in vitro. Luteolin-ß-CD-MOF increased the bioavailability of luteolin by approximately 4.04- and 11.07-fold in healthy rats and liver injured rats induced by acetaminophen in vivo, respectively. As determined by biochemical analysis, luteolin-ß-CD-MOF exhibited a better hepatoprotective effect than raw luteolin in rats with acetaminophen-induced liver injury. This study provides a new approach for preventing acetaminophen-mediated liver damage.

Correction: Paracrine Factors of Mesenchymal Stem Cells Recruit Macrophages and Endothelial Lineage Cells and Enhance Wound Healing.

[This corrects the article DOI: 10.1371/journal.pone.0001886.].

Application of ChatGPT-based blended medical teaching in clinical education of hepatobiliary surgery.

OBJECTIVE: This study evaluates the effectiveness of incorporating the Chat Generative Pre-trained Transformer (ChatGPT) into the clinical teaching of hepatobiliary surgery for undergraduate medical students. MATERIALS AND METHODS: A group of 61 medical undergraduates from the Affiliated Hospital of Guizhou Medical University, undergoing hepatobiliary surgery training, were randomly assigned to either an experimental group (31 students) using ChatGPT-based blended teaching or a control group (30 students) with traditional teaching methods. The evaluation metrics included final exam scores, teaching satisfaction, and teaching effectiveness ratings, analyzed using SPSS 26.0 (SPSS Inc., Chicago, IL) with t-tests and χ2 tests. RESULTS: The experimental group significantly outperformed the control group in final exam theoretical scores (86.44 ± 5.59 vs. 77.86 ± 4.16, p < .001) and clinical skills scores (83.84 ± 6.13 vs. 79.12 ± 4.27, p = .001). Additionally, the experimental group reported higher teaching satisfaction (17.23 ± 1.33) and self-evaluation of teaching effectiveness (9.14 ± 0.54) compared to the control group (15.38 ± 1.5 and 8.46 ± 0.70, respectively, p < .001). CONCLUSIONS: The integration of ChatGPT into hepatobiliary surgery education significantly enhances theoretical knowledge, clinical skills, and overall satisfaction among medical undergraduates, suggesting a beneficial impact on their educational development.

Very Long-Term Functional Outcomes and Dependency in Children With Anti-NMDA Receptor Encephalitis.

OBJECTIVES: To assess the daily function of children with anti-N-methyl-d-aspartate receptor encephalitis (NMDARe) after a minimal follow-up of 5 years. METHODS: Patients 18 years and younger by the time of disease onset, whose serum and CSF were studied in our center between 2013 and 2017, were included in the study. Patients' daily life function was assessed by their physicians using a 15-domain question format (Liverpool Outcome Score). RESULTS: Of 76 patients, 8 (11%) died and 68 were followed for a mean of 7.1 years (SD 1.5 years, range: 5.0-10.1). Three outcome patterns were identified: full recovery (50; 73%); behavioral and school/working deficits (12; 18%); and multidomain deficits (6; 9%) involving self-care ability, behavioral-cognitive impairment, and seizures. Younger age of disease onset was significantly associated with multidomain deficits (OR 1.6, 95% CI 1.02-2.4, p = 0.04), particularly in children younger than 6 years, among whom 8 of 23 (35%) remained sociofamiliar dependent. DISCUSSION: After a minimal follow-up of 5 years, most children with NMDARe had substantial or full functional recovery, but approximately one-fifth remained with behavioral and school/working deficits. The younger the patient at disease onset, the more probable it was to remain with multidomain deficits and dependent on sociofamiliar support.

MOG Antibodies Restricted to CSF in Children With Inflammatory CNS Disorders.

OBJECTIVES: To assess the clinical significance of myelin oligodendrocyte glycoprotein antibodies (MOG-abs) restricted to CSF in children with inflammatory CNS disorders. METHODS: Patients included 760 children (younger than 18 years) from 3 multicenter prospective cohort studies: (A) acquired demyelinating syndromes, including acute disseminated encephalomyelitis (ADEM); (B) non-ADEM encephalitis; and (C) noninflammatory neurologic disorders. For all cases, paired serum/CSF samples were systematically examined using brain immunohistochemistry and live cell-based assays. RESULTS: A total of 109 patients (14%) had MOG-abs in serum or CSF: 79 from cohort A, 30 from B, and none from C. Of these, 63 (58%) had antibodies in both samples, 37 (34%) only in serum, and 9 (8%) only in CSF. Children with MOG-abs only in CSF were older than those with MOG-abs only in serum or in both samples (median 12 vs 6 vs 5 years, p = 0.0002) and were more likely to have CSF oligoclonal bands (86% vs 12% vs 7%, p = 0.0001) and be diagnosed with multiple sclerosis (6/9 [67%] vs 0/37 [0%] vs 1/63 [2%], p < 0.0001). DISCUSSION: Detection of MOG-abs in serum or CSF is associated with CNS inflammatory disorders. Children with MOG-abs restricted to CSF are more likely to have CSF oligoclonal bands and multiple sclerosis than those with MOG-abs detectable in serum.

Enhancing the photodynamic effect of curcumin through modification with TiO2 nanoparticles and cationic polymers.

Curcumin (CUR), a natural compound extracted from turmeric, has shown potential as a photosensitizer in photodynamic therapy (PDT). The aim of this work was to enhance the efficacy of CUR by modifying it using titanium dioxide (TiO2) nanoparticles and a cationic polymer called Sofast to create a nanocomposite TiO2-CUR-Sofast (TCS). Compared to unmodified CUR, TCS exhibited a broadening toward longer wavelength in the absorption wavelength within the 400-550 nm range, leading to improved CUR absorption. Cellular uptake efficiency of TCS was also enhanced, and it demonstrated nearly 4.7-fold higher reactive oxygen species (ROS) generation than CUR. Furthermore, TCS displayed the ability to attach to the cell membrane and enter cells within a 30-min incubation period. Upon irradiation, TCS exhibited remarkable cytotoxicity, resulting in a significant reduction in the viability of various cancer cells. Autofluorescence lifetime imaging of intracellular reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) enzymes indicated that cancer cells treated with TCS and irradiation undergo a metabolic pathway shift from oxidative phosphorylation to glycolysis. These findings highlight the potential of TCS as an effective PDT agent for cancer treatment.

Association of Neonatal Antibiotic Exposure with Long-Term Growth Trajectory Faltering in Preterm-Birth Children.

INTRODUCTION: Preterm neonates often receive a variety of duration of antibiotic exposure during admission. The aim of the study was to evaluate whether neonatal antibiotic exposure is relevant with longitudinal growth problems in preterm-birth children. METHODS: This prospective study enrolled 481 infants who were born <32 weeks of gestation, discharged, and longitudinally followed from corrected age (CA) 6-60 months. After excluding 153 infants with blood culture-confirmed bacteremia, necrotizing enterocolitis, severe cerebral palsy, intestinal ostomy, and congenital anomaly, 328 infants were included for analysis. Covariates included perinatal demographics, neonatal morbidities, extrauterine growth restriction, and antibiotic exposure accumulated by term equivalent age. The primary outcome was the anthropometric trajectories in z-score of bodyweight (zBW), body height (zBH), and body mass index (zBMI) from CA 6-60 months. RESULTS: Antibiotic exposure duration was significantly negatively associated with zBW and zBH at CA 6, 12, and 60 months, and zBMI at CA 60 months. Multivariate generalized estimating equation analyses showed antibiotic exposure duration had significantly faltering z-score increment from CA 6 to 60 months in zBW and zBH (adjusted mean [95% CI]; ΔzBW: -0.021 [-0.041 to -0.001], p = 0.042; ΔzBH: -0.019 [-0.035 to -0.002], p = 0.027) after adjustment. Children with neonatal antibiotic exposure duration >15 days were significantly lower in the mean anthropometric zBW, zBH, and zBMI at CA 6, 12, 24, and 60 months compared with children with neonatal antibiotic exposure ≤15 days (all p < 0.01). CONCLUSIONS: Growth increments were negatively associated with antibiotic exposure duration in preterm neonates implicating that antibiotic stewardship and growth follow-up for preterm neonates are thus warranted.

The Quartile Levels of Thyroid-Stimulating Hormone by Newborn Screening Stratified Risks of Neurodevelopmental Impairment in Extremely Preterm Infants - A Population Cohort Study.

BACKGROUND: To evaluate whether thyroid-stimulating hormone (TSH) by newborn screening (NBS) at birth and at discharge can be surrogate markers for neurodevelopmental impairment (NDI) in extremely preterm infants. METHODS: The population cohort enrolled infants born <29 weeks' gestation in 2008 - 2020 in southern Taiwan. Infants with a maternal history of thyroid disorders and infants who required thyroxine supplementation during hospitalization were excluded. TSH levels by NBS at birth and at term-equivalent age (TEA)/discharge were respectively categorized into the lowest quartile, the interquartile range, and the highest quartile, which were correlated to NDI outcomes. RESULTS: Among 392 patients with paired TSH data, 358 (91%) were prospectively followed until corrected age 24 months. At birth, infants with lowest-quartile TSH had higher NDI risks (OR 2.3, 95% CI 1.3 - 4.1, P = 0.004) compared to infants with interquartile-range TSH. Conversely, by TEA/discharge, infants with highest-quartile TSH had increased NDI (OR 1.9, 1.0 - 3.4, P = 0.03). By paired TSH categories, infants persistently in the lowest TSH quartile (48%, aOR 4.4, 1.4 - 14.5, P = 0.01) and those with a shift from interquartile range to the highest quartile (32%, aOR 2.7, 1.0 - 7.4, P = 0.046) had increased NDI risks compared with the reference with consistent interquartile-range TSH. CONCLUSIONS: Extremely preterm infants persistently in the lowest-quartile TSH level at birth and at discharge had the highest NDI risk. TSH quartile levels by NBS may serve as a population surrogate biomarker for assessing NDI risks in infants born extremely preterm.

Dust detection and cleanliness assessment based on S-YOLOv5s for NPP reactor containment wall-climbing cleaning robot.

NPP reactor containment dust can easily turn into radioactive dust, endangering staff health and the environment. However, the nuclear reactor containment wall-climbing cleaning robot cleans blindly without the ability to clean the dust in a timely and thoroughly. In this paper, ShuffleNetV2-YOLOv5s (S-YOLOv5s) model is proposed to solve the problem of wall-climbing robots unable to detect different categories of dust in time. The use of ShuffleNetV2 in the backbone of the network not only ensures a large number of characterized channels and a large network capacity, but also reduces the complexity of the model; SIoU is chosen for the loss function to improve the model accuracy. Then, planar cleaning index (PCI) is proposed by combining the results of S-YOLOv5s to evaluate whether the wall-climbing cleaning robot cleans thoroughly. Compared to other methods, PCI considers amount and area occupation of different classes of dust. The dust data set is collected to train the designed model, and the model size is reduced to 14 % of the original model, and the FPS is 7.313 higher than the original model. Especially when compared with the state-of-the-art lightweight methods, our model has smaller model size and higher recognition speed. Experimental results have shown that our dust detection and cleanliness assessment method can be used on a wall-climbing cleaning robot to clean dust in time and thoroughly.

Alleviative Effect of Ficus formosana Extract on Peripheral Neuropathy in Ovariectomized Diabetic Mice.

In diabetes mellitus, Ficus formosana has been reported to ameliorate blood sugar levels and inhibit inflammation through its polyphenol and flavonoid contents. However, its effect on diabetic peripheral neuropathy (DPN) remains unknown. This study aimed to investigate the effect of Ficus formosana extract (FFE) on DPN in ovariectomized diabetic mice. Ovariectomized female C57BL/6J mice fed a high-fat diet plus streptozotocin injections to induce type 2 diabetes were orally administered FEE at 20 or 200 mg/kg BW daily, for 6 weeks. To evaluate the pain responses in the paws of the mice, a von Frey filament test and a thermal hyperalgesia test were performed. Additionally, the intraepidermal and sciatic nerve sections were examined, along with an assessment of inflammation- and pain response-related mRNA expression in the paws of the mice. The results showed that the oral administration of both 20 and 200 mg/kg BW FEE significantly alleviated the hypersensitivity of the paw and the abnormal proliferation and rupture of the C fiber, and reduced the mRNA expression of interleukin-1ß, interleukin-6, interferon-γ, cyclooxygenase-2, and voltage-gated sodium channel 1.8 in the sciatic nerve of ovariectomized diabetic mice. We propose that FFE ameliorates peripheral neuropathy by suppressing oxidative damage in ovariectomized diabetic mice.

The combined effect of pit and fissure sealant application and oral health education on oral health status of children aged 6-9 years: a 12-month follow-up study in Northeast China.

BACKGROUND: Children aged 6-9 years are vulnerable to dental caries due to age-related limitations and a lack of adequate knowledge regarding oral health and hygiene practices. This study aimed to establish a cohort of children aged between 6 and 9 years and conducted a 12-month follow-up to examine the combined effect of pit and fissure sealant (PFS) application and oral health education on their oral health status. METHODS: A cohort study with 12-month follow-up was conducted in Liaoning province, China. A multi-stage stratified cluster sampling approach was employed in the study. The enrolled 6- to 9-year-old children were all from the selected primary schools, who had resided in the designated area for at least 6 months. Children who were unable to cooperate with the examiner or without informed consent from their guardians were excluded. Experienced dental professionals examined the oral health status of primary school children aged 6-9 years. All children and their guardians were mandated to complete a questionnaire (qualitative data) at the beginning of the study. In the experiment group, children underwent PFS application and chairside oral health education. Clinical examinations and questionnaire surveys were repeated at the 12-month follow-up. The chi-square test and binary logistic regression were conducted to investigate the potential risk factors associated with dental caries prevalence (dependent variable). Independent variables were items from the questionnaire (such as living place, parents' education level and children' birth weight). The significant variables identified in the chi-square tests were subsequently included in the binary logistic regression analysis. RESULTS: A total of 4,085 children aged 6-9 years were included in the study, with 1805 participants assigned to the experiment group and 2280 to the control group. At baseline, the caries rates of the experimental and control group were 77.95% and 80.35%, respectively without any statistically significant differences. However, at the 12-month follow-up, the caries rate in the experimental group (83.65%) was significantly lower than that in the control group (86.62%) (P < 0.05). The results from the binary logistic regression analysis indicated that parents with a college degree and children in the experimental group exhibited lower caries rates. Conversely, higher caries rates were associated with the consumption of sweet beverages and foods more than once a day and a lack of knowledge regarding the causes of caries (P < 0.05). CONCLUSIONS: In Liaoning, China, children aged 6 to 9 years exhibited a high prevalence of dental caries. Several factors, including the parent's education level, the frequency of consuming sweet beverages and foods, and the children's understanding of the cause of caries, significantly affected the caries prevalence rates. The implementation of PFS application and oral health education effectively reduce the caries rate among the surveyed children.

Attribution of lake eutrophication risk to anthropogenic forcing adjacent to the agriculture areas: a case study of Chagan Lake.

Lake eutrophication, exacerbated by high-intensity anthropogenic forcing, threatens water ecological security and the sustainable development of fisheries. Accurately evaluating lake eutrophication is the basis for effective management of the water environment. This study aimed to study eutrophication and its anthropogenic forcing in Chagan Lake, which is surrounded by agricultural areas with irrigation discharge as the primary water source. The spatiotemporal evolution characteristics of lake eutrophication and the anthropogenic forcing factors were analyzed based on the long-series multi-source data and modified eutrophication index. The results showed that (1) the average trophic state of Chagan Lake was eutrophic according to the modified eutrophication index (TLI = 58.31) and the nutrient level was higher in summer, reaching hypertrophy (TLI 61.49); (2) the maximum pollution footprint affecting the lake reached 34.7 km2, with a maximum buffer zone radius of 1 km; (3) the gross domestic product of primary industry, total sown area, and rice field area were the main anthropogenic factors leading to the lake eutrophication, with contribution rates of 64.43%, 13.09%, and 10.23%, respectively. Multidimensional management strategies for maximum pollution footprint, buffer zone radius, and contribution of anthropogenic factors were used to improve the water quality of the lake. The findings provided scientific support for the management of water environment of Chagan Lake and guided the formulation of "one lake, one policy."

Comparison of the C-TIRADS, ACR-TIRADS, and ATA guidelines in malignancy risk stratification of thyroid nodules.

Background: To compare the diagnostic performance in determining the malignancy of thyroid nodules and the fine needle aspiration (FNA) recommendations of the guidelines set forth by the Superficial Organ and Vascular Ultrasound Group of the Society of Ultrasound in Medicine of the Chinese Medical Association in 2020 [2020 Chinese Thyroid Imaging Reporting and Data System (C-TIRADS)], the American College of Radiology in 2017 (2017 ACR-TIRADS) and the American Thyroid Association in 2015 (2015 ATA guidelines). Methods: From January 2021 to December 2021, 1,228 thyroid nodules with definitive postoperative histopathology and ultrasound (US) examination within 3 months before surgery in Shantou Central Hospital were enrolled in this study. We collected the data in 2022. The participants formed a consecutive series. The clinical and US features of the nodules were retrospectively reviewed and categorized according to the 2020 C-TIRADS, the 2017 ACR-TIRADS and the 2015 ATA guidelines. The diagnostic performance and unnecessary FNA rates of the three guidelines were calculated. Results: The 2017 ACR-TIRADS had the highest diagnostic performance [area under the receiver operating characteristic curve (AUROC) 0.938], followed by the 2020 C-TIRADS (AUROC 0.933) and the 2015 ATA guidelines (AUROC 0.928). The ATA guidelines had the highest specificity (93.38%), accuracy (92.10%) and positive predictive value (PPV) (80.56%) among the three guidelines. There were no significant differences in the sensitivity and negative predictive value (NPV) among the three guidelines. The sensitivity, specificity, PPV, NPV and accuracy of the FNA recommendations based on the C-TIRADS were 84.25%, 58.76%, 38.92%, 92.28% and 64.82%, respectively, which were higher than those of the ACR-TIRADS (57.53%, 42.94%, 23.93%, 76.43% and 46.42%, respectively) and the ATA guidelines (62.67%, 13.25%, 18.39%, 53.22% and 25.00%, respectively). Compared with the ACR-TIRADS (76.07%) and the ATA guidelines (81.61%), the C-TIRADS showed advantages in the unnecessary FNA rate (61.08%), especially in nodules larger than 20 mm. Conclusions: The 2020 C-TIRADS, the 2017 ACR-TIRADS and the 2015 ATA guidelines can effectively predict the malignancy risk of thyroid nodules. Compared with the 2017 ACR-TIRADS and the 2015 ATA guidelines, the 2020 C-TIRADS may offer a meaningful reduction in FNA recommendations with the highest efficacy in distinguishing thyroid carcinoma.

Screening and validation of plasma cell-derived, purinergic, and calcium signalling-related genetic signature to predict prognosis and PD-L1/PD-1 blockade responses in lung adenocarcinoma.

BACKGROUND: This study aims at  screening and validation of prospective genetic signature for lung adenocarcinoma (LUAD) prognosis and treatment. METHODS: The immune-related genes (IRGs) were obtained from The Cancer Genome Atlas (TCGA) dataset where a total of 535 LUAD and 59 control samples were included. A risk model was then developed for the risk stratification of LUAD patients.  The immune cell infiltration, clinical outcomes, and the therapeutic efficacy of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) blockade were compared between high and low-risk groups. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to explore the biological processes and signalling pathways associated with the IRGs. Finally, IRGs mRNA levels were assayed by reverse transcription quantitative real-time PCR (RT-qPCR) in LUAD and relevant cell lines. RESULTS: Two IRGs, P2RX1 (purinergic receptor P2X 1) and PCP4 (Purkinje cell protein 4), were screened from a module that possesses the highest correlation with plasma cells. RT-qPCR verified the expression of the two IRGs in plasmacytoma cell RPMI 8226 but not in LUAD cells. A higher risk score is associated with a lower infiltration of immune cells. Kaplan-Meier and nomogram analysis showed that the high-risk group has a lower survival rate than the low-risk cohort. Furthermore, the high-risk group had a worse response rate to PD-L1/PD-1 blockade. GSVA and GSEA-GO results indicated that a lower risk score is linked to signalling pathways and biological functions promoting immune response and inflammation. In contrast, a higher risk score is associated with signalling cascades promoting tumour growth. CONCLUSION: The immune-related prognostic model based on P2RX1 and PCP4 is conducive to predicting the therapeutic response of PD-L1/PD-1 blockade and clinical outcomes of LUAD.

National Brain Tumour Registry of China (NBTRC) statistical report of primary brain tumours diagnosed in China in years 2019-2020.

Background: The lack of a well-designed brain tumour registry with standardized pathological diagnoses in underdeveloped countries hinders the ability to compare epidemiologic data across the globe. The National Brain Tumour Registry of China (NBTRC), created in January 2018, is the first multi-hospital-based brain tumour registry in China. Patient data reported to the NBTRC in years 2019-2020 were assessed. Methods: Tumour pathology was based on the 2016 World Health Organization (WHO) classification of tumours of the central nervous system and ICD-O-3. The anatomical site was coded per the Surveillance, Epidemiology, and End Results (SEER) solid tumour module (version of July 2019). The cases were tabulated by histology and anatomical site. Categorical variables were reported as numbers (percentages). The distribution of tumours by age (0-14, 15-19, 20-39, 40-64, and 65+ years) was analysed. Findings: There were a total of 25,537 brain tumours, foremost among them meningioma (23.63%), followed by tumours of the pituitary (23.42%), and nerve sheath tumours (9.09%). Glioblastoma, the most common and lethal form of primary brain cancer in adults, represented 8.56% of all cases. Of note, 6.48% of the malignant tumours were located in the brain stem. The percentage of malignant brain tumours decreased with increasing age, 24.08% in adults (40+ years), 30.25% in young adults (20-39 years), 35.27% in adolescents (15-19 years), and 49.83% in children (0-14 years). Among the 2107 paediatric patients, the most common sites were ventricle (17.19%), brainstem (14.03%), pituitary and craniopharyngeal duct (13.4%), and cerebellum (12.3%), a distribution that differed from that of the entire cohort. The histology distribution was also unique in children, with glioblastoma much less incident compared to the whole cohort (3% vs. 8.47%, p < 0.01). 58.80% of all patients chose higher-level neurosurgical hospitals outside of their province of residence. The median in-hospital length of stay (LOS) for the various pathologies ranged from 11 to 19 days. Interpretation: The histological and anatomical site distribution of brain tumours in the NBTRC was statistically different in the subgroup of children (0-14 years). Patient choice of pursuing trans-provincial treatment was common and the in-hospital LOS was longer compared to that reported in similar European and American patient populations, which merits further attention. Funding: The National Key Research and Development Program of China (2015BAI12B04, 2013BAI09B03, 2014BAI04B01, and 2021YFF1201104) and Chinese National Natural Science Foundation of China (81971668).

The pretherapeutic systemic inflammation score is a prognostic predictor for elderly patients with oesophageal cancer: a case control study.

BACKGROUND: The systemic inflammation score (SIS), based on serum albumin (Alb) and lymphocyte-to-monocyte ratio (LMR), is a novel prognostic tool for some tumours. Studies indicate that the SIS can be used as a postoperative prognostic marker. However, its predictive value in elderly oesophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy is unclear. METHODS: In total, 166 elderly ESCC patients who received radiotherapy with or without chemotherapy were included. Based on different combinations of Alb and LMR levels, the SIS was divided into 3 groups, SIS = 0 (n = 79), SIS = 1 (n = 71) and SIS = 2 (n = 16). The Kaplan-Meier method was used for survival analysis. Univariate and multivariate analyses were performed to assess prognosis. Time-dependent receiver operating characteristic (t-ROC) curves were used to compare the prognostic accuracy of the SIS with that of Alb, LMR, neutrophil-to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII). RESULTS: Decreased Alb and LMR were both associated with shorter OS, whereas a lower SIS was significantly associated with better outcomes. The OS of SIS = 0, SIS = 1 and SIS = 2 was 28.0 ± 2.9, 16.0 ± 2.8 and 10.0 ± 7.0 months, respectively (p = 0.000). Similar results were also observed for PFS. Multivariate analysis of the model with SIS revealed that the SIS was a significant independent biomarker for predicting OS and PFS. The nomogram showed that the C-index was improved to 0.677 when the SIS factor was incorporated. Furthermore, the 3-year OS rates for patients in the SIS-high group (SIS = 1 and SIS = 2) undergoing concurrent radiotherapy with a single agent (CCRT-1) and concurrent radiotherapy with two agents (CCRT-2) were 42% and 15%, respectively (p = 0.039). The t-ROC curve showed that the SIS was more sensitive than other prognostic factors for predicting overall survival. CONCLUSION: The SIS may be a useful prognostic marker in elderly patients with ESCC receiving radiotherapy alone or chemoradiotherapy. The SIS showed a better predictive ability for OS than the continuous variable Alb and could stratify patient prognosis in different therapeutic regimens. CCRT-1 may be the best treatment for SIS-high patients.

Associating phthalate exposure during pregnancy with preschooler's FMI, ABSI and BRI trajectories via putative mechanism pathways.

Phthalates are well-known obesogens, but a few studies have explored their impacts on the childhood fat mass index (FMI), body shape index (ABSI) and body roundness index (BRI). Information from 2950 participants recruited in the Ma'anshan Birth Cohort was analyzed. The relationships between six maternal phthalate metabolites and their mixture and childhood FMI, ABSI and BRI were investigated. FMI, ABSI and BRI in children aged 3.5 y, 4.0 y, 4.5 y, 5.0 y, 5.5 y and 6.0 y were calculated. The latent class trajectory modeling categorized the FMI trajectories into "rapidly increasing FMI" (4.71%) and "stable FMI" (95.29%) groups; ABSI trajectories were categorized as "decreasing ABSI" (32.74%), "stable ABSI" (46.55%), "slowly increasing ABSI" (13.26%), "moderately increasing ABSI" (5.27%) and "rapidly increasing ABSI" (2.18%) groups; BRI trajectories were categorized as "increasing BRI" (2.82%), "stable BRI" (19.85%), and "decreasing BRI" (77.34%) groups. Prenatal MEP exposure was associated with repeated measurements of FMI (ß = 0.111, 95% CI = 0.002-0.221), ABSI (ß = 0.145, 95% CI = 0.023-0.268) and BRI (ß = 0.046, 95% CI = -0.005-0.097). Compared with each stable trajectory group, prenatal MEP (OR = 0.650, 95% CI = 0.502-0.844) and MBP (OR = 0.717, 95% CI = 0.984-1.015) were linked to a decreased risk of "decreasing BRI" in children; there was a negative relationship between MBP and the "decreasing ABSI" group (OR = 0.667, 95% CI = 0.487-0.914), and MEP increased the risks of "slowly increasing ABSI" (OR = 1.668, 95% CI = 1.210-2.299) and "rapidly increasing ABSI" (OR = 2.522, 95% CI = 1.266-5.024) in children. Phthalate mixture during pregnancy showed significant relationships with all anthropometric indicator trajectories, with MEP and MBP always being of the largest importance. In conclusion, this study suggested that prenatal phthalate coexposure increased the childhood probability of being in higher ABSI and BRI trajectory groups. That is, children were more likely to be obese when they were exposed to higher levels of some phthalate metabolites and their mixture. The low-molecular weight phthalates, including MEP and MBP, contributed the greatest weights.

Neonicotinoid Imidacloprid Affects the Social Behavior of Adult Zebrafish by Damaging Telencephalon Neurons through Oxidation Stress, Inflammation, and Apoptosis.

The neonicotinoid imidacloprid is a widely used insecticide worldwide. We assessed the effects of acute and chronic imidacloprid exposure on the social behavior of adult zebrafish. We assembled simple apparatus to detect 2D locomotion: a single camera capture system and two specially designed water tanks. We then used the tracking and heat maps of the behavior trajectories of zebrafish subjected to sham and imidacloprid exposure and compared their social behavior. Furthermore, histomorphology and immunohistochemistry of their brain tissue sections were performed to clarify possible neurotoxicity due to imidacloprid exposure in our adult zebrafish. Our results showed that imidacloprid exposure significantly reduced the zebrafish's swimming speed, distance traveled, acceleration, and deceleration. The longer the imidacloprid exposure, the more severe the locomotor behavior disability. Furthermore, imidacloprid exposure significantly reduced heterosexual attractive behavior between the different sexes, as well as defensive alert behavior among males. Our histomorphology and immunohistochemistry evidence showed imidacloprid exposure may lead to neuronal oxidative stress, inflammation, apoptosis, and damage in the telencephalon of adult zebrafish. Thus, we suggested that neonicotinoid imidacloprid exposure can damage the telencephalon neurons of adult zebrafish through oxidative stress, inflammation, and apoptosis and then affect the social behavior of adult zebrafish.