Gut microbiota intervention alleviates pulmonary inflammation in broilers exposed to fine particulate matter from broiler house.

The gut microbiota of poultry is influenced by a variety of factors, including feed, drinking water, airborne dust, and footpads, among others. Gut microbiota can affect the immune reaction and inflammation in the lungs. To investigate the effect of gut microbiota variation on lung inflammation induced by PM2.5 (fine particulate matter) in broilers, 36 Arbor Acres (AA) broilers were randomly assigned to three groups: control group (CON), PM2.5 exposure group (PM), and PM2.5 exposure plus oral antibiotics group (PMA). We used non-absorbable antibiotics (ABX: neomycin and amikacin) to modify the microbiota composition in the PMA group. The intervention was conducted from the 18th to the 28th day of age. Broilers in the PM and PMA groups were exposed to PM by a systemic exposure method from 21 to 28 days old, and the concentration of PM2.5 was controlled at 2 mg/m3. At 28 days old, the lung injury score, relative mRNA expression of inflammatory factors, T-cell differentiation, and dendritic cell function were significantly increased in the PM group compared to the CON group, and those of the PMA group were significantly decreased compared to the PM group. There were significant differences in both α and ß diversity of cecal microbiota among these three groups. Numerous bacterial genera showed significant differences in relative abundance among the three groups. In conclusion, gut microbiota could affect PM2.5-induced lung inflammation in broilers by adjusting the capacity of antigen-presenting cells to activate T-cell differentiation. IMPORTANCE: Gut microbes can influence the development of lung inflammation, and fine particulate matter collected from broiler houses can lead to lung inflammation in broilers. In this study, we explored the effect of gut microbes modified by intestinal non-absorbable antibiotics on particulate matter-induced lung inflammation. The results showed that modification in the composition of gut microbiota could alleviate lung inflammation by attenuating the ability of dendritic cells to stimulate T-cell differentiation, which provides a new way to protect lung health in poultry farms.

Dynamics of antibiotic resistance genes in the sediments of a water-diversion lake and its human exposure risk behaviour.

The dynamics and exposure risk behaviours of antibiotic resistance genes (ARGs) in the sediments of water-diversion lakes remain poorly understood. In this study, spatiotemporal investigations of ARG profiles in sediments targeting non-water (NWDP) and water diversion periods (WDP) were conducted in Luoma Lake, a typical water-diversion lake, and an innovative dynamics-based risk assessment framework was constructed to evaluate ARG exposure risks to local residents. ARGs in sediments were significantly more abundant in the WDP than in the NWDP, but there was no significant variation in their spatial distribution in either period. Moreover, the pattern of ARG dissemination in sediments was unchanged between the WDP and NWDP, with horizontal gene transfer (HGT) and vertical gene transfer (VGT) contributing to ARG dissemination in both periods. However, water diversion altered the pattern in lake water, with HGT and VGT in the NWDP but only HGT in the WDP, which were critical pathways for the dissemination of ARGs. The significantly lower ARG sediment-water partition coefficient in the WDP indicated that water diversion could shift the fate of ARGs and facilitate their aqueous partitioning. Risk assessment showed that all age groups faced a higher human exposure risk of ARGs (HERA) in the WDP than in the NWDP, with the 45-59 age group having the highest risk. Furthermore, HERA increased overall with the bacterial carrying capacity in the local environment and peaked when the carrying capacity reached three (NWDP) or four (WDP) orders of magnitude higher than the observed bacterial population. HGT and VGT promoted, whereas ODF covering gene mutation and loss mainly reduced HERA in the lake. As the carrying capacity increased, the relative contribution of ODF to HERA remained relatively stable, whereas the dominant mechanism of HERA development shifted from HGT to VGT.

MRI-Based Clinical-Imaging-Radiomics Nomogram Model for Discriminating Between Benign and Malignant Solid Pulmonary Nodules or Masses.

RATIONALE AND OBJECTIVES: Pulmonary nodules or masses are highly prevalent worldwide, and differential diagnosis of benign and malignant lesions remains difficult. Magnetic resonance imaging (MRI) can provide functional and metabolic information of pulmonary lesions. This study aimed to establish a nomogram model based on clinical features, imaging features, and multi-sequence MRI radiomics to identify benign and malignant solid pulmonary nodules or masses. MATERIALS AND METHODS: A total of 145 eligible patients (76 male; mean age, 58.4 years ± 13.7 [SD]) with solid pulmonary nodules or masses were retrospectively analyzed. The patients were randomized into two groups (training cohort, n = 102; validation cohort, n = 43). The nomogram was used for predicting malignant pulmonary lesions. The diagnostic performance of different models was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Of these patients, 95 patients were diagnosed with benign lesions and 50 with malignant lesions. Multivariate analysis showed that age, DWI value, LSR value, and ADC value were independent predictors of malignant lesions. Among the radiomics models, the multi-sequence MRI-based model (T1WI+T2WI+ADC) achieved the best diagnosis performance with AUCs of 0.858 (95%CI: 0.775, 0.919) and 0.774 (95%CI: 0.621, 0.887) for the training and validation cohorts, respectively. Combining multi-sequence radiomics, clinical and imaging features, the predictive efficacy of the clinical-imaging-radiomics model was significantly better than the clinical model, imaging model and radiomics model (all P < 0.05). CONCLUSION: The MRI-based clinical-imaging-radiomics model is helpful to differentiate benign and malignant solid pulmonary nodules or masses, and may be useful for precision medicine of pulmonary diseases.

Case report: Efficacy of icotinib treatment in lung adenocarcinoma with esophageal squamous cell carcinoma: a rare case of double primary malignant tumors.

Background: Lung adenocarcinoma with esophageal squamous cell carcinoma is rare and the prognosis is poor, therefore there is an urgent need to improve this situation. The objective of this study was to explore the effect of first-generation tyrosine kinase inhibitors (TKIs) in the patient of the double primary malignant tumors. Case report: We report a case of lung adenocarcinoma with esophageal squamous cell carcinoma treated by icotininb after five-year follow-up. A 71-year-old Chinese woman complaining of swallowing obstruction, heartburn, regurgitation of gastric acid for more than 2 months. An esophageal lesion was found by chest CT scans in T7 vertebral level. The diagnosis by gastroscopic biopsy was squamous cell carcinoma (SCC) with EGFR over-expression. Simultaneously, chest CT showed a 2 cm x 1 cm solitary lesion in the right superior pulmonary. The histological diagnosis by percutaneous lung Biopsy was "adenocarcinoma." Epidermal growth factor receptor (EGFR) gene mutation status was evaluated by Sanger sequencing, and an exon 21 point mutation (L858R) was identified. When the double primary malignant tumors were diagnosed, the patient refused operation and received a tyrosine kinase inhibitor (TKI), icotinib, at the dose of 125 mg, three times per day. All serum tumor biomarkers such as CEA and cancer antigen 125 (CA125) were in the normal range during the treatment period. After five-year follow-up, the patient has no evidence of recurrence or metastasis. The lung cancer was stable, meanwhile the esophageal lesion was almost cured. Conclusion: Icotininb is an effective treatment in the patients of the double primary malignant tumors of lung adenocarcinoma with EGFR gene mutation and esophageal squamous cell carcinoma with EGFR over-expression.

Quantitative measurement of the ureter on three-dimensional magnetic resonance urography images using deep learning.

BACKGROUND: Accurate measurement of ureteral diameters plays a pivotal role in diagnosing and monitoring urinary tract obstruction (UTO). While three-dimensional magnetic resonance urography (3D MRU) represents a significant advancement in imaging, the traditional manual methods for assessing ureteral diameters are characterized by labor-intensive procedures and inherent variability. In the realm of medical image analysis, deep learning has led to a paradigm shift, yet the development of a comprehensive automated tool for the precise segmentation and measurement of ureters in MR images is an unaddressed challenge. PURPOSE: The ureter was quantitatively measured on 3D MRU images using a deep learning model. METHODS: A retrospective cohort of 445 3D MRU scans (443 patients, 52 ± 18 years; 217 female patients) was collected and split into training, validation, and internal testing cohorts. A 3D V-Net model was trained for urinary tract segmentation, and a post-processing algorithm was developed for ureteral measurements. The accuracy of the segmentation was evaluated using the Dice similarity coefficient (DSC) and volume intraclass correlation coefficient (ICC), with ground truth segmentations provided by experienced radiologists. The external cohort comprised 50 scans (50 patients, 55 ± 21 years; 30 female patients), and the model-predicted ureteral diameter measurements were compared with manual measurements to assess system performance. The various diameter parameters of ureter among the different measurement methods (ground truth, auto-segmentation with automatic diameter extraction, and manual segmentation with automatic diameter extraction) were assessed with Friedman tests and post hoc Dunn test. The effectiveness of the UTO diagnosis was assessed by receiver operating characteristic (ROC) curves and their respective areas under the curve (AUC) between different methods. RESULTS: In both the internal test and external cohorts, the mean DSC values for bilateral ureters exceeded 0.70. The ICCs for the bilateral ureter volume obtained by comparing the model and manual segmentation were all greater than 0.96 (p  < â€¯0.05), except for the right ureter in the internal test cohort, for which the ICC was 0.773 (p  < â€¯0.05). The mean DSCs for interobserver and intraobserver reliability were all above 0.97. The maximum diameter of the ureter exhibited no statistically significant differences either in the dilated (p = 0.08) or in the non-dilated (p = 0.32) ureters across the three measurement methods. The AUCs of ground truth, auto-segmentation with automatic diameter extraction, and manual segmentation with automatic diameter extraction in diagnosing UTO were 0.988 (95% CI: 0.934, 1.000), 0.961 (95% CI: 0.893, 0.991), and 0.979 (95% CI: 0.919, 0.998), respectively. There was no statistical difference between AUCs of the different methods (p > 0.05). CONCLUSION: The proposed deep learning model and post-processing algorithm provide an effective means for the quantitative evaluation of urinary diseases using 3D MRU images.

Preparation and performance of solid thermal energy storage materials based on low-grade pyrophyllite minerals.

The new sensible thermal energy storage materials were prepared by the sintering method with low-grade pyrophyllite mineral powders as main raw materials, Suzhou clay as the sintering aid and sulfite liquors as the binder. Further, the performance of sensible thermal energy storage under different size distributions and sintering temperatures was investigated and analyzed. The results show that the optimum particle size distribution is 50:15:35, the bulk density, thermal conductivity, and specific heat capacity are the largest values, which are 1.97 g cm-3, 0.87 W m-1 K-1 and 0.63 kJ kg-1 K-1, respectively. Other properties including porosity, water absorption, flexural and compressive strength and so on are optimal under this size distribution. When the sintering temperature is 1200 °C, the material has a good thermal conductivity of 0.89 W m-1 K-1 and a high bulk density of 2.05 g cm-3. Meanwhile, the sample with the used temperature from 50 to 900 °C has the best thermal energy storage capacity of 306.29 kWh·m-3.

LTX-315 triggers anticancer immunity by inducing MyD88-dependent maturation of dendritic cells.

LTX-315 is a synthetic cationic oncolytic peptide with potent anticancer activity but limited toxicity for non-malignant cells. LTX-315 induces both immunogenic tumor cell death and generation of tumor-specific immune responses in multiple experimental tumor models. Given the central role of dendritic cell (DC) maturation in the induction of antigen-specific immunity, we investigated the effect of LTX-315 treatment on the maturation of tumor-infiltrating DCs (TiDCs) and the generation of anti-melanoma immunity. We found that LTX-315 treatment induces the maturation of DCs, both indirectly through the release of cancer cell-derived damage-associated molecular patterns (DAMPs)/alarmins and nucleic acids (DNA and RNA) capable of triggering distinct Toll-like receptor (TLR) signaling, and, directly by activating TLR7. The latter results in the ignition of multiple intracellular signaling pathways that promotes DC maturation, including NF-κB, mitogen activated protein kinases (MAPKs), and inflammasome signaling, as well as increased type 1 interferon production. Critically, the effects of LTX-315 on DCs the consequent promotion of anti-melanoma immunity depend on the cytosolic signal transducer myeloid differentiation response gene 88 (MyD88). These results cast light on the mechanisms by which LTX-315 induces DC maturation and hence elicits anticancer immunity, with important implications for the use of LTX-315 as an anticancer immunotherapeutic.

Simultaneous Determination of D and L Enantiomers of 2-Hydroxyglutarate by UHPLC-MS/MS Method in Human Biological Fluids and its Clinical Application.

2-hydroxyglutarate has limited abundance in normal tissues but a high level under certain pathologic conditions. To clarify the diagnostic value of two chiral isomers of 2-hydroxyglutarate in plasma and urine of Chinese cancer patients, an ultra-high performance liquid chromatography-tandem mass spectrometric method was developed for simultaneous quantification of D-/L-2-hydroxyglutarate. The selected D-/L-2-hydroxyglutarate-d5 as internal standards were added to samples before the SPE on Waters Oasis® MAX 96-Well plate (30 µm, 60 mg). A derivatization step with (+)-O,O'-diacetyl-L-tartaric anhydride permitted the chromatography separation of D-/L-2-hydroxyglutarate on an ACQUITY UPLC-HSS T3 column (50 × 2.1 mm, i.d. 1.8 µm) with acetonitrile and water (containing 0.1% formic acid and 10 mmol ammonium acetate) as the mobile phase. The calibration curves showed good linearity (R ≥ 0.99) over the concentration ranges of 200-5,000 ng/mL and 500-20,000 ng/mL for analysis of D-/L-2-hydroxyglutarate in plasma and urine samples, respectively. Intra- and inter-run precision were ≤ 12.33%, and the accuracy was within the range of -10.44 to 13.90%. This method was further successfully applied to clinical sample analysis in isocitrate dehydrogenase 1/2 mutated Chinese cancer patients.

Clinical features of non-syndromic late developing supernumerary teeth: a sign of the third dentition?

OBJECTIVES: This study aimed to summarize the clinical features of non-syndromic late developing supernumerary teeth (LDST) and comparisons with common supernumerary teeth (ST) and explore the association between LDST and the third dentition. MATERIALS AND METHODS: This study retrospected cone-beam computed tomography (CBCT) and medical history of 41,903 consecutive patients from January to December 2021. Comparisons between ST and LDST were evaluated by Chi-square test or Fisher exact test. Correlation between chronological age and dental stage age was evaluated by Spearman's rank correlation coefficient. Binary logistic regression analysis was used to explore the features of LDST originating from the third dentition. RESULTS: Sixty patients with 126 non-syndromic LDST and 1602 patients with 1988 non-syndromic ST were identified. The prevalence of ST and LDST was 3.82% and 0.14%, respectively, with a male-female ratio of 1.78:1 and 1.31:1. LDST patients mainly had LDST in multiple (58.33%) and bilaterally (41.67%), with an average of 2.1/patient. Most LDST were normal-shaped (84.13%), vertically oriented (71.43%), located in the mandible (80.16%), and distributed in the premolar region (82.54%). The study also indicated that the development of LDST was correlated with permanent teeth, with LDST developing 6.48 to 10.45 years later. In this study, 72.22% of LDST met the clinical criteria for the third dentition. CONCLUSIONS: LDST manifested different clinical features from common ST. LDST might be closely related to the third dentition. CLINICAL RELEVANCE: This work would help to comprehend LDST from a clinical perspective, and may be complementary to the criteria of the third dentition.

Soil fungal communities varied across aspects of restored grassland in former mining areas of the Qinghai-Tibet Plateau.

To determine whether different aspects lead to a heterogeneous distribution of soil fungi, we investigated artificially established alpine grasslands in the Muli mining area in the Qinghai-Tibet Plateau. Employing high-throughput sequencing techniques, we analyzed the composition, diversity, and function of soil fungal communities across various aspects (flat, East-facing, South-facing, West-facing, North-facing). We also examined their relationships with environmental factors. Soil fungal communities of restored alpine grasslands differed significantly across aspects in terms of the dominant phyla, classes and species level. Compared with No aspect, the Shannon index of fungi respectively decreased by 2.99%, 19.32%, 19.37% and 10.56% for East aspect, South aspect, West aspect and North aspect, respectively, and the Chao1 index of fungi respectively decreased by-2.44%, 35.50%, 42.15% and 3.21%, respectively. A total of 22 different types of fungi were identified in the study area. Predictive analysis, based on PICRUSt2, indicated that the primary functions of the fungal communities across different aspects were aerobic respiration I (cytochrome c) and aerobic respiration II (cytochrome c). Among the environmental variables, total phosphorus (P) and total nitrogen (N) were the principal factors influencing the fungal community composition.In conclusion, aspect plays a significant role in shaping the composition of fungal communities and also affects their overall diversity.

Designed Synthesis of Fe/Zr Bimetallic Organic Framework to Enhance the Selective Conversion of H2S to Sulfur.

The development of stable and effective catalysts to convert toxic H2S into high value-added sulfur is essential for production safety and environmental protection. However, the inherent defects of traditional iron- and zirconium-based catalysts, such as poor activity, high oxygen consumption, and low sulfur selectivity, limit their further developments and applications. Herein, the Fe-Zr bimetallic organic framework FeUIO-66(x) with different cubic morphologies was synthesized via a facile solvothermal method. The results indicate that the introduction of Fe not only increases the specific surface area and weak L-sites of the catalyst without changing its crystal structure, which provides enough reaction space and more active sites for the adsorption and activation of H2S, but also reduces the activation energy of the reaction, significantly promoting the selective oxidation of H2S. As a result, the as-obtained FeUIO-66(1) catalyst exhibits the highest desulfurization activity and superior durability and water resistance stability, and its H2S conversion and sulfur selectivity within 50 h are 100 and 88%, respectively. More importantly, the structure of the catalyst after the desulfurization reaction is consistent with that of the fresh counterpart. The study offers new insights into the development of effective and stable bimetallic catalysts to eliminate H2S and recycle sulfur.

Natural variation in OsMYB8 confers diurnal floret opening time divergence between indica and japonica subspecies.

The inter-subspecific indica-japonica hybrid rice confer potential higher yield than the widely used indica-indica intra-subspecific hybrid rice. Nevertheless, the utilization of this strong heterosis is currently hindered by asynchronous diurnal floret opening time (DFOT) of indica and japonica parental lines. Here, we identify OsMYB8 as a key regulator of rice DFOT. OsMYB8 induces the transcription of JA-Ile synthetase OsJAR1, thereby regulating the expression of genes related to cell osmolality and cell wall remodeling in lodicules to promote floret opening. Natural variations of OsMYB8 promoter contribute to its differential expression, thus differential transcription of OsJAR1 and accumulation of JA-Ile in lodicules of indica and japonica subspecies. Furthermore, introgression of the indica haplotype of OsMYB8 into japonica effectively promotes DFOT in japonica. Our findings reveal an OsMYB8-OsJAR1 module that regulates differential DFOT in indica and japonica, and provide a strategy for breeding early DFOT japonica to facilitate breeding of indica-japonica hybrids.

Gender differences in gastrointestinal, biopsychosocial and healthcare-seeking behaviors in Chinese patients with irritable bowel syndrome predominant with diarrhea.

BACKGROUND: Evidences of comparison of sex difference in Chinese irritable bowel syndrome (IBS) patients were few. We aim to compare gender difference in the biopsychosocial characteristics of Chinese patients of IBS predominant with diarrhea (IBS-D). METHODS: IBS-D patients meeting Rome III criteria were enrolled. We administered IBS symptom questionnaires, evaluation of psychological status (HAMD and HAMA scales) and IBS quality of life (IBS-QOL), dietary habits, healthcare seeking behaviors, and compared biopsychosocial characteristics between male and female patients. RESULTS: Four hundred and ninety patients were enrolled including 299 males and 191 females. More female patients reported abdominal pain associated with defecation (84.3% vs. 74.9%, P = 0.014) while males reported more abdominal discomfort (39.8% vs. 26.7%, P = 0.003). Females had higher IBS symptom score (9.7 ± 1.7 vs. 9.4 ± 1.4, P = 0.025) and more of females had severe abdominal pain/discomfort (17.8% vs. 12.4%, P = 0.013) while there were no significant differences of other bowel symptoms. Females reported higher incidence of comorbid anxiety state (64.9% vs. 52.8%, P = 0.008) and depression state (35.6% vs. 19.7%, P < 0.001) than males. Female patients also had lower IBS-QOL score (70.2 ± 20.4 vs. 75.1 ± 16.8, P = 0.028) and more frequent consultations, as well as less response for dietary modification than males. CONCLUSIONS: Chinese female patients with IBS-D had more prominent psychosocial disorders compared to male patients and their abdominal symptoms had minor differences.

Population pharmacokinetic model for oral ORIN1001 in Chinese patients with advanced solid tumors.

Background: ORIN1001, a first-in-class oral IRE1-α endoribonuclease inhibitor to block the activation of XBP1, is currently in clinical development for inhibiting tumor growth and enhancing the effect of chemical or targeted therapy. Early establishment of a population pharmacokinetic (PopPK) model could characterize the pharmacokinetics (PK) of ORIN1001 and evaluate the effects of individual-specific factors on PK, which will facilitate the future development of this investigational drug. Methods: Non-linear mixed effect model was constructed by Phoenix NLME software, utilizing the information from Chinese patients with advanced solid tumors in a phase I clinical trial (Register No. NCT05154201). Statistically significant PK covariates were screened out by a stepwise process. The final model, after validating by the goodness-of-fit plots, non-parametric bootstrap, visual predictive check and test of normalized prediction distribution errors, was further applied to simulate and evaluate the impact of covariates on ORIN1001 exposure at steady state up to 900 mg per day as a single agent. Results: A two-compartment model with first-order absorption (with lag-time)/elimination was selected as the best structural model. Total bilirubin (TBIL) and lean body weight (LBW) were considered as the statistically significant covariates on clearance (CL/F) of ORIN1001. They were also confirmed to exert clinically significant effects on ORIN1001 steady-state exposure after model simulation. The necessity of dose adjustments based on these two covariates remains to be validated in a larger population. Conclusion: The first PopPK model of ORIN1001 was successfully constructed, which may provide some important references for future research.

Anti-sepsis effect of Xiaochaihu decoction based on the TLR4/MyD88/NF-κB signalling pathway.

The aims of this study were to explore the protective effect of Xiaochaihu decoction in mice with sepsis induced by intraperitoneal injection; to explore its anti-inflammatory effect on the TLR4-MyD88-NF-κB signalling pathway; and to explore the main material basis of the anti-inflammatory effect of Xiaochaihu decoction, with the aim of supplementing and expanding the associated research and providing a scientific foundation for the clinical use of the decoction. The effects of Xiaochaihu decoction on septic mice were analysed by measurements of white blood cells (WBC) and Platelets (PLT); Nitric Oxide (NO) level in serum; IL-6, IL-1ß and TNF-α levels in serum; RT-PCR; Haematoxylin-Eosin (HE) immunohistochemistry; western blotting (WB). The results showed the excellent in vivo anti-inflammatory effects of Xiaochaihu decoction in LPS-induced septic mice, through down regulation of the gene and protein expression of TLR4, MYD88, TRAF6, IKK, IKBα and p65 and the subsequent reduction in the release of inflammatory mediators IL-6, IL-1ß, TNF-α and NO. Moreover, significant anti-septic effect was observed from high and medium doses of Xiaochaihu decoction, but not from the low dose.

An Ultra-Low Modulus of Ductile TiZrHfTa Biomedical High-Entropy Alloys through Deformation Induced Martensitic Transformation/Twinning/Amorphization.

Biomedical alloys are paramount materials in biomedical applications, particularly in crafting biological artificial replacements. In traditional biomedical alloys, a significant challenge is simultaneously achieving an ultra-low Young's modulus, excellent biocompatibility, and acceptable ductility. A multi-component body-centered cubic (BCC) biomedical high-entropy alloy (Bio-HEA), which is composed of non-toxic elements, is noteworthy for its outstanding biocompatibility and compositional tuning capabilities. Nevertheless, the aforementioned challenges still remain. Here, a method to achieve a single phase with the lowest Young's modulus among the constituent phases by precisely tuning the stability of the BCC phase in the Bio-HEA, is proposed. The subtle tuning of the BCC phase stability also enables the induction of stress-induced martensite transformation with extremely low trigger stress. The transformation-induced plasticity and work hardening capacity are achieved via the stress-induced martensite transformation. Additionally, the hierarchical stress-induced martensite twin structure and crystalline-to-amorphous phase transformation provide robust toughening mechanisms in the Bio-HEA. The cytotoxicity test confirms that this Bio-HEA exhibits excellent biocompatibility without cytotoxicity. In conclusion, this study provides new insights into the development of biomedical alloys with a combination of ultra-low Young's modulus, excellent biocompatibility, and decent ductility.

Latent profiles of bullying perpetration and victimization: Gender differences and family variables.

BACKGROUND: School bullying is a prevalent issue that threatens the psychological and social well-being of adolescents. However, little research has investigated how gender and family variables were related to bullying-involvement patterns among adolescents with siblings. OBJECTIVE: This study explored gender differences in the profiles of bullying involvement and the relationship between sibling, parental variables, and these profiles among Chinese adolescents. PARTICIPANTS AND SETTING: Participants (N = 1,060; 46.0 % boys; Mage = 15.53) were recruited from junior and senior high schools in Jiangxi and Guizhou Provinces, China. METHODS: Bullying involvement, sibling warmth and conflict, and parental psychological maltreatment and neglect were assessed by self-report questionnaire. Latent profile analysis was used to identify subgroups with distinct bullying involvement patterns, then multiple logistic regressions were performed to investigate the associations between family variables and bullying-involvement subgroups. RESULTS: We found gender differences in both the latent profiles of bullying involvement and the associations between profiles and family variables. Only boys were identified severe bully-victims (3.39 %), while only girls were categorized as relational bully-victims (20.18 %). Boys and girls were similarly represented among uninvolved students (70.76 % vs. 66.85 %), moderate bully-victims (15.25 % vs. 6.49 %), and victims (10.59 % vs. 6.49 %). Students with more sibling warmth manifested less likelihood of engaging in bullying-related profiles, with more parental psychological maltreatment, and more parental neglect manifested more likelihood of engaging in bullying-related profiles only among girls. While students with more sibling conflict were related to more bullying-related profiles among boys than girls. CONCLUSIONS: The findings emphasize the importance of developing gender-specific bullying intervention strategies that also consider relevant family factors.

The impact of intraarterial, intravenous, and combined tirofiban on endovascular treatment for acute intracranial atherosclerotic occlusion.

Background and purpose: Adjunctive tirofiban administration in patients undergoing endovascular treatment (EVT) for acute large vessel occlusion (LVO) has been investigated in several studies. However, the findings are conflict. This study aimed to compare the effect of different administration pathways of tirofiban on patients undergoing EVT for acute LVO with intracranial atherosclerotic disease (ICAD). Methods: Patients were selected from the ANGEL-ACT Registry (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke: A Prospective Multicenter Registry Study) and divided into four groups: intra-arterial (IA), intravenous (IV), and intra-arterial plus intravenous (IA+IV) and non-tirofiban. The primary outcome was 90-day ordinal modified Rankin Scale (mRS) score, and the secondary outcomes included the rates of mRS 0-1, 0-2, and 0-3 at 90-day, successful recanalization. The safety outcomes were symptomatic intracranial hemorrhage (sICH) and other safety endpoints. The multivariable logistic regression models adjusting for potential baseline confounders were performed to compare the outcomes. A propensity score matching (PSM) with a 1:1:1:1 ratio was conducted among four groups, and the outcomes were then compared in the post-matched population. Results: A total of 502 patients were included, 80 of which were in the IA-tirofiban group, 73 in IV-tirofiban, 181 in (IA+IV)-tirofiban group, and 168 in the non-tirofiban group. The median (IQR) 90-day mRS score in the four groups of IA, IV, IA+IV, and non-tirofiban was, respectively 3(0-5) vs. 1(0-4) vs. 1(0-4) vs. 3(0-5). The adjusted common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.77 (95% CI, 0.45-1.30, P = 0.330), with IV-tirofiban vs. non-tirofiban was 1.36 (95% CI, 0.78-2.36, P = 0.276), and with (IA+IV)-tirofiban vs. non-tirofiban was 1.03 (95% CI, 0.64-1.64, P = 0.912). The adjusted OR for mRS 0-1 and mRS 0-2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.51 (95% CI, 0.27-0.98, P = 0.042) and 0.50 (95% CI, 0.26-0.94, P = 0.033). The other outcomes of each group were similar with non-tirofiban group, all P was >0.05. After PSM, the common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.41 (95% CI, 0.18-0.94, P = 0.036), and the OR for mRS 0-1 and mRS 0-2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.28 (95% CI, 0.11-0.74, P = 0.011) and 0.25 (95% CI, 0.09-0.67, P = 0.006). Conclusions: Intra-arterial administration of tirofiban was associated with worse outcome than non-tirofiban, which suggested that intra-arterial tirofiban had a harmful effect on patients undergoing EVT for ICAD-LVO. Clinical trial registration: http://www.clinicaltrials.gov, Unique identifier: NCT03370939.

Effect of CHRDL1 on angiogenesis and metastasis of colorectal cancer cells via TGF-ß/VEGF pathway.

Colorectal cancer (CRC) is a common digestive tract tumor with the third incidence and death in the world. There is still an urgent need for effective therapeutic targets and prognostic markers for CRC. Herein, we report a novel potential target and marker, Chordin like-1 (CHRDL1). The function of CHRDL1 has been reported in gastric cancer, breast cancer, and oral squamous cell carcinoma. However, the biological effect of CHRDL1 in CRC remains unrevealed. Transwell and tube formation experiments were used to determine the biological function of CHRDL1. Western blot and rescue experiments were used to determine the specific mechanisms of CHRDL1. Results showed CHRDL1 is significantly downregulated in CRC cell lines and tissues. In vitro, experiments confirmed that CHRDL1 can inhibit cell growth, migration, invasion, angiogenesis and reverse epithelial-mesenchymal transformation. In vivo, experiments proved that it can inhibit tumor growth and metastasis. Mechanistically, we newly find that CHRDL1 exerts biological functions through the transforming growth factor-beta (TGF-ß)/vascular endothelial growth factor signaling axis in vitro and in vivo. Therefore, we concluded that CHRDL1 reduces the growth, migration, and angiogenesis of CRC cells by downregulating TGF-ß signaling. Our new findings on CHRDL1 may provide a basis for clinical antiangiogenesis therapy and the prognosis of CRC.