Assessment of causal associations between obesity and peripheral artery disease: a bidirectional Mendelian randomization study.

Background: Several observational studies have documented a potential link between obesity and peripheral artery disease (PAD), although conflicting findings exist. The causal relationship between obesity and PAD continues to be a subject of ongoing debate in the medical community. Objectives: In this study, we employed a bidirectional Mendelian randomization (MR) analysis to explore the potential causal relationship between obesity and the risk of PAD. Methods: To investigate these causal relationships, we conducted bidirectional MR analysis using publicly available genome-wide association study (GWAS) data. Effect estimates were calculated using the random-effects inverse variance-weighted (IVW) method. Results: We identified eight independent single nucleotide polymorphisms (SNPs) associated with obesity in 218,735 samples involving 16,380,465 SNPs, all of which met the genome-wide significance threshold (p < 5 × 10-8). The IVW analysis indicates a significant positive association between genetic obesity and multiple datasets with PAD as the outcome: Queue-1 (GWAS ID: finn-b-I9_PAD) (OR = 1.138, 95% CI: 1.027-1.261, p = 0.013), Queue-2 (GWAS ID: bbj-a-144) (OR = 1.190, 95% CI: 1.019-1.390, p = 0.028), Queue-3 (GWAS ID: ebi-a-GCST90018670) (OR = 1.174, 95% CI: 1.014-1.360, p = 0.032), and Queue-4 (GWAS ID: ebi-a-GCST90018890) (OR = 1.194, 95% CI: 1.099-1.296, p < 0.001). However, we did not observe a significant genetic-level association between obesity and PAD for Queue-5 (GWAS ID: ukb-d-I9_PAD) (OR = 1.001, 95% CI: 1.000-1.002, p = 0.071). Furthermore, we conducted a reverse causal MR analysis to explore the potential reverse causal relationship between obesity and PAD. This comprehensive analysis did not provide evidence of a reverse causal association between these two factors. Conclusions: In summary, our study offers genetic evidence suggesting a possible causal link between obesity and PAD. While we did not find evidence supporting the "obesity paradox", prudent weight management remains crucial, as lower weight does not necessarily guarantee better outcomes. As with any study, caution is required in interpreting the findings. Further research is essential to assess the clinical relevance of weight in preventing PAD, which could inform the development of more precise intervention strategies.

Computer-assisted three-dimensional individualized extreme liver resection for hepatoblastoma in proximity to the major liver vasculature.

BACKGROUND: The management of hepatoblastoma (HB) becomes challenging when the tumor remains in close proximity to the major liver vasculature (PMV) even after a full course of neoadjuvant chemotherapy (NAC). In such cases, extreme liver resection can be considered a potential option. AIM: To explore whether computer-assisted three-dimensional individualized extreme liver resection is safe and feasible for children with HB who still have PMV after a full course of NAC. METHODS: We retrospectively collected data from children with HB who underwent surgical resection at our center from June 2013 to June 2023. We then analyzed the detailed clinical and three-dimensional characteristics of children with HB who still had PMV after a full course of NAC. RESULTS: Sixty-seven children diagnosed with HB underwent surgical resection. The age at diagnosis was 21.4 ± 18.8 months, and 40 boys and 27 girls were included. Fifty-nine (88.1%) patients had a single tumor, 39 (58.2%) of which was located in the right lobe of the liver. A total of 47 patients (70.1%) had PRE-TEXT III or IV. Thirty-nine patients (58.2%) underwent delayed resection. After a full course of NAC, 16 patients still had close PMV (within 1 cm in two patients, touching in 11 patients, compressing in four patients, and showing tumor thrombus in three patients). There were 6 patients of tumors in the middle lobe of the liver, and four of those patients exhibited liver anatomy variations. These 16 children underwent extreme liver resection after comprehensive preoperative evaluation. Intraoperative procedures were performed according to the preoperative plan, and the operations were successfully performed. Currently, the 3-year event-free survival of 67 children with HB is 88%. Among the 16 children who underwent extreme liver resection, three experienced recurrence, and one died due to multiple metastases. CONCLUSION: Extreme liver resection for HB that is still in close PMV after a full course of NAC is both safe and feasible. This approach not only reduces the necessity for liver transplantation but also results in a favorable prognosis. Individualized three-dimensional surgical planning is beneficial for accurate and complete resection of HB, particularly for assessing vascular involvement, remnant liver volume and anatomical variations.

In Situ TEM Tracking of Disconnection Motion and Atomic Cooperative Reorientation in the Oriented Attachment of Pt Nanoparticles.

The oriented attachment (OA) of nanoparticles (NPs) is an important crystal growth mechanism in many materials. However, a comprehensive understanding of the atomic-scale alignment and attachment processes is still lacking. We conducted in situ atomic resolution studies using high-resolution transmission electron microscopy to reveal how two Pt NPs coalesce into a single particle via OA, which involves the formation of atomic-scale links and a grain boundary (GB) between the NPs, as well as GB migration. Density functional theory calculations showed that the system energy changes as a function of the number of disconnections during the coalescence process. Additionally, the formation and annihilation processes of disconnection are always accompanied by the cooperative reorientation motion of atoms. These results further elucidate the growth mechanism of OA at the atomic scale, providing microscopic insights into OA dynamics and a framework for the development of processing strategies for nanocrystalline materials.

Influence of health-related behaviors patterns on obesity among primary and secondary school students: A latent profile analysis.

OBJECTIVE: To analyze the co-existing patterns of health-related behaviors among children and adolescents at different education stages and the association with obesity. DESIGN: Cross-sectional study. SAMPLE: A total of 5651 primary and secondary school students were drawn from the National Student Physical Health Survey in 2014 with an average age of 13.53 ± 2.87 years. MEASUREMENTS: Physical measurements and questionnaires were completed, which concluded height, weight, and health-related behaviors (sleep, physical activity, dietary, and screen behavior et al.). Latent profile analysis (LPA) was conducted using Mplus 8.3 and SPSS 26.0 was used for other statistical analysis. RESULTS: Three latent classes of health-related behaviors were fitted for each of the education stages. After adjustment for age, gender, and region, the high-screen behavior group were 2.217 (95%CI = 1.030-4.772, p = .042) times more likely to be obesity than the health-behavior group in primary school, and the poor-diet group and poor-diet and high-screen behavior group were 2.101 (95%CI = 1.396-3.396, p < .001) and 1.788 (95%CI = 1.003-3.190, p = .049) times more likely to be overweight than the health-behavior group in junior middle school respectively. CONCLUSION: Obesity is mainly influenced by screen behavior and dietary patterns among children and adolescents. Health-related behavior patterns should be accurately identified and comprehensive joint interventions should be carried out to prevent obesity.

Associations of maternal sleep trajectories during pregnancy and adverse perinatal outcomes: a prospective cohort study.

OBJECTIVE: Sleep problems are common in pregnant women and sleep is altered during pregnancy. However, the associations between sleep trajectory patterns and adverse maternal and neonatal outcomes are unclear. The current study aims to identify sleep trajectory patterns and explore their associations with adverse perinatal outcomes in a prospective cohort study. METHODS: Pregnant women (N = 232) completed the Pittsburgh Sleep Quality Index each trimester during pregnancy in Tianjin, China. Perinatal outcomes were extracted from the hospital delivery records. Latent class growth analysis (LCGA) described the trajectories of sleep timing, duration, and efficiency. Multivariable linear regression and multivariable logistic regression were employed to evaluate associations between sleep trajectory patterns and perinatal outcomes. RESULTS: Trajectories were identified for bedtime (early, 49.1%; delaying, 50.9%), wake-up time (early, 82.8% of the sample; late, 17.2%), duration (short, 5.2%; adequate 78.0%; excessive, 16.8%), and efficiency (high, 88.4%; decreasing, 11.6%). Compared with women in more optimal sleep groups, those in the late wake-up, excessive duration, and decreasing efficiency groups had babies with shorter birth lengths (ß range, -0.50 to -0.28, p < 0.05). Moreover, women in the decreasing efficiency group had babies with lower birth weight (ß, -0.44; p < 0.05). Women in the delaying bedtime group had greater odds of preterm delivery (OR, 4.57; p < 0.05), while those in the decreasing efficiency group had greater odds of cesarean section (OR, 3.12; p < 0.05). CONCLUSIONS: Less optimal sleep trajectory patterns during pregnancy are associated with perinatal outcomes. Therefore, early assessment of maternal sleep during pregnancy is significant for identifying at-risk women and initiating interventions to reduce perinatal outcomes.

A cluster-randomized controlled trial of a nurse-led artificial intelligence assisted prevention and management for delirium (AI-AntiDelirium) on delirium in intensive care unit: Study protocol.

BACKGROUND: Delirium is a common complication among intensive care unit (ICU) patients that is linked to negative clinical outcomes. However, adherence to the Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (PADIS guidelines), which recommend the use of the ABCDEF bundle, is sub-optimal in routine clinical care. To address this issue, AI-AntiDelirium, a nurse-led artificial intelligence-assisted prevention and management tool for delirium, was developed by our research team. Our pilot study yielded positive findings regarding the use of AI-AntiDelirium in preventing patient ICU delirium and improving activities of daily living and increasing intervention adherence by health care staff. METHODS: The proposed large-scale pragmatic, open-label, parallel-group, cluster randomized controlled study will assess the impact of AI-AntiDelirium on the incidence of ICU delirium and delirium-related outcomes. Six ICUs in two tertiary hospitals in China will be randomized in a 1:1 ratio to an AI-AntiDelirium or a PADIS guidelines group. A target sample size of 1,452 ICU patients aged 50 years and older treated in the ICU for at least 24 hours will be included. The primary outcome evaluated will be the incidence of ICU delirium and the secondary outcomes will be the duration of ICU delirium, length of ICU and hospital stay, ICU and in-hospital mortality rates, patient cognitive function, patient activities of daily living, and ICU nurse adherence to the ABCDEF bundle. DISCUSSION: If this large-scale trial provides evidence of the effectiveness of AI-AntiDelirium, an artificial intelligence-assisted system tool, in decreasing the incidence of ICU delirium, length of ICU and hospital stay, ICU and in-hospital mortality rates, patient cognitive function, and patient activities of daily living while increasing ICU nurse adherence to the ABCDEF bundle, it will have a profound impact on the management of ICU delirium in both research and clinical practice. CLINICAL TRIAL REGISTRATION: ChiCTR1900023711 (Chinese Clinical Trial Registry).

Pd-Catalyzed Cascade Cyclization/Thiocarbonylation with Thioformates: Synthesis of Thioester-Functionalized Oxindoles.

A Pd-catalyzed thiocarbonylative cyclization of N-(o-iodoaryl)acrylamides with easily accessible thioformates has been developed. The reaction has a wide substrate scope with good yields and represents a powerful route to the synthesis of thioester-functionalized oxindoles. Both S-aryl and alkyl thioformates as the thioester sources were well tolerated. The active Pd-CO intermediate may play an important role in the transformation process.

Study of stress-strain loops on cardiotoxicity related to immune checkpoint inhibitors.

OBJECTIVE: To evaluate the effect of immune checkpoint inhibitors (ICIs) on left ventricular myocardial work by pressure-strain loop (PSL). METHODS: Forty-three immunotherapy patients were enrolled in the case group, and another 43 healthy volunteers were enrolled in the control group. They were examined by echocardiography before immunotherapy (T0 phase), after three cycles of treatment (T3 phase) and after six cycles of treatment (T6 phase). Conventional echocardiographic parameters, left ventricular global longitudinal strain (GLS), and myocardial work indices, including global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE), were collected for analysis to compare the results of the different immunotherapy cycles. RESULTS: There were no statistically significant differences of baseline characteristics, conventional echocardiographic parameters, left ventricular strain, and myocardial work indices between T0 phase and control group (all p > .05). There were no statistically significant differences in LVEF between T0, T3, and T6 phase (all p > .05). GLS, GWI, GCW, and GWE were decreased and GWW was increased in T3 and T6 phase. There were no statistically significant difference between GLS in T3 and T0 phase (q = .9057, p > .05). The difference was statistically significant between GLS in T6 and T0 phase (q = 5.5651, p < .01). The difference was statistically significant between GLS in T3 and T6phase(q = 4.6594, p < .01). There were statistically significant difference in GWI, GCW, GWE, and GWW in the T3 and T6 phase compared with the T0 phase (p < .01). CONCLUSION: PSL can effectively evaluate the effect of ICIs on left ventricular myocardial work, to provide a new method for the early clinical detection of ICIs-related cardiotoxicity.

Characterization of group Ⅰ metabotropic glutamate receptors in rat superior cervical ganglion and their changes following chronic intermittent hypoxia / 解剖学报

Objective To observe the expression and localization of group Ⅰ metabotropic glutamate receptors (mGluR1/ 5) in rat superior cervical ganglion (SCG) and the effect of chronic intermittent hypoxia (CIH) on mGluR1/ 5 protein level. Methods Twelve male SD rats were randomly divided into control group(Ctrl)and CIH group(CIH), 6 rats in each group. After 6 weeks of modeling, the effect of CIH on mGluR1/ 5 protein level was detected by Western blotting, the expression and distribution of mGluR1/ 5 in SCG were detected by immunohistochemistry and double-immunofluorescent staining. Results mGluR1/ 5 was expressed in rat SCG. mGluR1 was distributed in neurons and small intensely fluorescent (SIF) cells, but not in satellite glial cells (SGCs), nerve fibers and blood vessels, whereas mGluR5 was mainly distributed in nerve fibers and a little in neurons, but not in SGCs, SIF cells and blood vessels. CIH increased the protein levels of mGluR1/ 5 (P<0. 01) in rat SCG. Conclusion Both mGluR1 and mGluR5 are expressed in the rat SCG, but their distribution are different, and the increased protein levels of both may be involved in CIH-induced hypertension.

Associations between R.E.N.A.L. nephrometry score and survival outcomes in renal tumours.

OBJECTIVE: The radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score could be used to predict surgical outcomes and renal tumour aggressiveness. We aimed to analyse its associations with survival outcomes. METHODS: We included 1368 patients with sporadic, unilateral and non-metastatic renal tumours who received curative nephrectomy in Zhongshan Hospital from January 2009 to September 2019. Radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores were assigned by three urologists based on preoperative CT/MRI scans. Correlations between parameters or sum of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores, overall survival and recurrence-free survival were analysed by Kaplan-Meier analyses and the multivariate Cox regression model. We further compared survival outcomes between patients who received partial nephrectomy and patients who received radical nephrectomy. RESULTS: We observed statistically significant associations between all components of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores and oncologic outcomes, including R (radius) (overall survival, P < 0.001; recurrence-free survival , P < 0.001), E (exophytic/endophytic) (overall survival, P = 0.003; recurrence-free survival, P < 0.001), N (nearness) (overall survival, P = 0.063; recurrence-free survival, P < 0.001), A (anterior/posterior) (overall survival, P < 0.001; recurrence-free survival, P = 0.005), L (location) (overall survival, P = 0.008; recurrence-free survival, P < 0.001) and suffix 'h' (overall survival, P = 0.237; recurrence-free survival, P = 0.034). Kaplan-Meier curves of overall survival and recurrence-free survival rates were significantly different when stratified by radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score complexity group (overall survival, P < 0.001; recurrence-free survival, P < 0.001). After adjusting for tumour stage and grade, radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score as continuous variables was an adverse independent risk factor for survival outcomes [P = 0.027, hazard ratio (95% confidence interval) = 1.151 (1.016-1.303)] and recurrence-free survival [P < 0.001, hazard ratio (95% confidence interval) = 1.299 (1.125-1.501)]. For tumours with radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores of 4 and 5, partial nephrectomy showed a survival benefit than radical nephrectomy. CONCLUSION: Both components and complexity groups of the radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score are associated with survival outcomes in renal tumour patients.

Kirschner wire reconstruction of medial and lateral column periosteal hinge in the treatment of multidirectionally unstable supracondylar fracture of the humerus in children.

AIM AND OBJECTIVE: To compare the clinical effect of reconstruction of internal and lateral column periosteal hinge-assisted treatment with Kirschner wire and internal fixation with Kirschner wire in the treatment of multidirectional unstable supracondylar fractures of humerus in children. METHODS: A retrospective cohort study was conducted to analyze the clinical data of 48 patients (31 male, 17 female; mean age: 6.7 ± 2.4 years old) with multidirectionally unstable supracondylar fractures of the humerus treated in our Hospital from August 2020 to August 2022. Twenty-five cases were treated with Kirschner wire reconstruction of the internal and lateral column periosteal hinge assisted by closed reduction and Kirschner wire internal fixation (study group). Twenty-three cases were treated with closed reduction and Kirschner wire internal fixation (control group). The operation time, intraoperative fluoroscopy times, percentage of patients who underwent open reduction after failure of closed reduction, fracture healing time, Baumann angle (BA), shaft-condylar angle (SCA), range of motion (ROM), and Flynn score of elbow at the last follow-up were compared between two groups. Complications such as infection and irritation of Kirschner wire tail were observed in two groups 2 months after the operation. RESULTS: All patients were followed up for 10-22 months ([13.85 ± 2.89] months). The average operation time of the control group was 82.1 min, which was significantly longer than that of the study group 32.3 min (P < 0.05). The number of intraoperative fluoroscopy (29.4 ± 9.2) in the control group was significantly higher than that in the study group (15.2 ± 6.3) (P < 0.05). The incision rate of the control group was 17% while that of the study group was 0 (P < 0.05). According to Flynn score, the excellent and good rate of the elbow joint in the control group was 86.9% (20/23). The excellent and good rate of the elbow joint in the study group was 92.0% (23/25) (P > 0.05). There was no significant difference in fracture healing time, BA, SCA, and ROM between the two groups (P > 0.05). No infection or Kirschner wire tail irritation occurred in the two groups during the 2-month follow-up. CONCLUSION: Reconstruction of internal and lateral periosteal hinges with Kirscher wire has similar effects to closed reduction and Kirschner wire fixation in the treatment of multidirectionally unstable supracondylar fractures of the humerus in children, but it can shorten the operation time and reduce intraoperative fluoroscopy times and incision rate.

Exposure to phthalates and their alternatives in relation to biomarkers of inflammation and oxidative stress in adults: evidence from NHANES 2017-2018.

Phthalates and their alternatives are considered significant environmental risk factors that potentially influence inflammation and oxidative stress. However, their impact on biomarkers of inflammation and oxidative stress was inconsistent. This study aimed to explore the associations between phthalates and high-sensitivity C-reactive protein (hsCRP), gamma-glutamyl transferase (GGT), and white blood cell (WBC) counts, employing both univariate exposure and multivariate co-exposure models. For this analysis, a total of 1619 individuals aged 18 years and above, sourced from the National Health and Nutrition Examination Survey (NHANES) conducted between 2017 and 2018, were selected as subjects. We explored the associations between hsCRP, GGT, and WBC counts and eighteen different phthalate metabolites. Multiple linear regression analysis revealed significant associations between both MCNP and MEHP and hsCRP. We observed negative correlations of MCOP, MCPP, MHBP, and MONP with GGT. Conversely, MEHHP and MEHHTP exhibited positive correlations with GGT. Furthermore, MECPTP and MEHHTP showed positive correlations with WBC. Notably, we identified a non-linear relationship between phthalates and inflammation and oxidative stress markers. The Bayesian kernel machine regression (BKMR) analysis demonstrated a negative joint effect of the phthalates mixture on GGT, particularly at lower concentrations. The BKMR model also found that MEOHP and MHiBP were negatively associated with GGT. In contrast, MEHHP showed a significant positive association with GGT. Moderating effect analysis suggested that dietary inflammatory index (DII), income-to-poverty ratio (PIR), age, BMI, and physical activity influenced the association between phthalates and inflammation and oxidative stress. These findings contribute to a deeper understanding of the relationships between phthalates and inflammation and oxidative stress.

Clinical Significance of Preoperative Assessment of Intravesical Prostatic Protrusion in Radical Prostatectomy.

Background: Intravesical prostatic protrusion (IPP) is common in prostate-related diseases, whose clinical significance in radical prostatectomy was unknown. Methods: 791 patients underwent robot-assisted or open radical prostatectomy at our institution were enrolled. The transabdominal ultrasound examination of prostate and IPP was carried out preoperatively, by which IPP was classified as no (0-0.5cm, grade 0), slight (0.6-1.0cm, grade 1) and noticeable (>1.0cm, grade 2). Results: 185 (23.4%), 170 (21.5%) and 436 (55.1%) patients had no, slight and noticeable IPP, respectively. Generally, prostate specific antigen (PSA), Gleason score and pT stage increased with IPP grade. In particular, cases with grade 0 IPP had a decreased proportion of seminal vesicles' involvement than those with grade 1 and grade 2 IPP (p=0.035). Reconstruction of the bladder neck (in robot-assisted group), increased surgical bleeding (>200ml), and prolonged postoperative hospital stays (>14 days) happened more in patients with grade 2 IPP. Blood transfusion only happened in patients with noticeable IPP. PSM of bladder neck was only associated with higher IPP grade in open surgery group (p=0.032), not in robot-assisted surgery group. Conclusion: IPP is associated with cancer aggressiveness, surgery difficulty and PSM of bladder neck in prostate cancer. Assessment of it provides more information for operations.

TL-MSE2-Net: Transfer learning based nested model for cerebrovascular segmentation with aneurysms.

Cerebrovascular (i.e., cerebral vessel) segmentation is essential for diagnosing and treating brain diseases. Convolutional neural network models, such as U-Net, are commonly used for this purpose. Unfortunately, such models may not be entirely satisfactory in dealing with cerebrovascular segmentation with tumors due to the following issues: (1) Relatively small number of clinical datasets from patients obtained through different modalities such as computed tomography (CT) and magnetic resonance imaging (MRI), leading to inadequate training and lack of transferability in the modeling; (2) Insufficient feature extraction caused by less attention to both convolution sizes and cerebral vessel edges. Inspired by the existence of similar features on cerebral vessels between normal subjects and patients, we propose a transfer learning strategy based on a pre-trained nested model called TL-MSE2-Net. This model uses one of the publicly available datasets for cerebrovascular segmentation with aneurysms. To address issue (1), our transfer learning strategy leverages a pre-trained model that uses a large number of datasets from normal subjects, providing a potential solution to the lack of sufficient clinical datasets. To tackle issue (2), we structure the pre-trained model based on 3D U-Net, comprising three blocks: ResMul, DeRes, and REAM. The ResMul and DeRes blocks enhance feature extraction by utilizing multiple convolution sizes to capture multiscale features, and the REAM block increases the weight of the voxels on the edges of the given 3D volume. We evaluated the proposed model on one small private clinical dataset and two publicly available datasets. The experimental results demonstrated that our MSE2-Net framework achieved an average Dice score of 70.81 % and 89.08 % on the two publicly available datasets, outperforming other state-of-the-art methods. Ablation studies were also conducted to validate the effectiveness of each block. The proposed TL-MSE2-Net yielded better results than MSE2-Net on a small private clinical dataset, with increases of 5.52 %, 3.37 %, 6.71 %, and 0.85 % for the Dice score, sensitivity, Jaccard index, and precision, respectively.

Rapid Determination of Dapagliflozin in Rat Plasma by UHPLC-Q-Orbitrap MS and Its Application to a Pharmacokinetic Study.

Dapagliflozin (DAPA), sodium-glucose co-transporter 2 (SGLT-2) inhibitor, is used to treat Type 2 diabetes. In this study, a highly sensitive and selective analytical method based on ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was established and validated for the determination of DAPA in rat plasma. The separation of DAPA and internal standard (DAPA-d5) were performed on a reversed-phase ACQUITY UPLC® BEH C18 column (100 × 3.0 mm, 1.7 µm). The mobile phase is composed of 0.1% formic acid in water (solvent A) and methanol (solvent B) in gradient elution. Under the negative ion mode, full MS/dd-MS2 was adopted to collect data via Q-Orbitrap. DAPA was effectively separated from matrix backgrounds within 10 min, and DAPA in plasma showed a good linear relationship in the range of 10-10000 µg/L. The determination coefficient (R2) was 0.9987, and the lower limit of quantification (LLOQ) was 10 µg/L. The precision and accuracy were all less than 10%, and the extraction recovery of DAPA was 86.16-96.06% from plasma. This study offered an efficient separation and quantification method for DAPA. The improved and validated method succeeded in evaluating the pharmacokinetics of DAPA in rat plasma samples after a single oral administration of 1 mg/kg.

Loss and recovery of myocardial mitochondria in mice under different tail suspension time: Apoptosis and mitochondrial fission, fusion and autophagy.

Long-term weightlessness in animals can cause changes in myocardial structure and function, in which mitochondria play an important role. Here, a tail suspension (TS) Kunming mouse (Mus musculus) model was used to simulate the effects of weightlessness on the heart. We investigated the effects of 2 and 4 weeks of TS (TS2 and TS4) on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling. Our study revealed significant changes in the ultrastructural features of cardiomyocytes in response to TS. The results showed: (1) mitochondrial swelling and disruption of cristae in TS2, but mitochondrial recovery and denser cristae in TS4; (2) an increase in the total number of mitochondria and number of sub-mitochondria in TS4; (3) no significant changes in the nuclear ultrastructure or DNA fragmentation among the two TS groups and the control group; (4) an increase in the bax/bcl-2 protein levels in the two TS groups, indicating increased activation of the bax-mediated apoptosis pathway; (5) no change in the phosphorylation ratio of dynamin-related protein 1 in the two TS groups; (6) an increase in the protein levels of optic atrophy 1 and mitofusin 2 in the two TS groups; and (7) in comparison to the TS2 group, an increase in the phosphorylation ratio of parkin and the ratio of LC3II to LC3I in TS4, suggesting an increase in autophagy. Taken together, these findings suggest that mitochondrial autophagy and fusion levels increased after 4 weeks of TS, leading to a restoration of the bax-mediated myocardial apoptosis pathway observed after 2 weeks of TS. NEW FINDINGS: What is the central question of this study? What are the effects of 2 and 4 weeks of tail suspension on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling? What is the main finding and its importance? Increased mitochondrial autophagy and fusion levels after 4 weeks of tail suspension help to reshape the morphology and increase the number of myocardial mitochondria.

Nomogram predicting overall prognosis for invasive micropapillary carcinoma of the breast: a SEER-based population study.

OBJECTIVES: The prognosis of invasive micropapillary carcinoma (IMPC) of the breast is determined by many clinicopathological factors. This study aims to identify prognostic factors and develop reliable nomogram to predict the overall survival (OS) in patients with IMPC. DESIGN: Log-rank test and Cox proportional hazards analysis were used to identify variables and construct a nomogram based on the training cohort. C-index and calibration curves were performed to evaluate the performance of the model in the training cohort and validation cohorts. SETTING: We collected the patient data from the Surveillance, Epidemiology and End Results (SEER) database. This database holds data related to the cancer incidence from 18 population-based cancer registries in the USA. PARTICIPANTS: The SEER database was used to screen 754 eligible patients as the study cohort. The whole cohort was randomly divided into a training cohort (n=377) and a validation cohort (n=377). RESULTS: Age at diagnosis, hormone receptors, number of positive regional lymph nodes and clinical stage were independent prognostic factors for patients with IMPC. The calibration curves presented excellent consistency between the actual and nomogram-predict survival probabilities in the training and validation cohorts. The C-index values of the nomogram were 0.794 and 0.774 for OS in the training and validation cohorts, respectively. CONCLUSIONS: The novel nomogram provides new insights of the risk of each prognostic factor and can assist doctors in predicting the 1-year, 3-year and 5-year OS in patients with IMPC.

Comparison and validation of different risk models for papillary renal cell carcinoma.

BACKGROUND: Several prognostic algorithms were specifically or nonspecifically used for papillary renal cell carcinoma (PRCC). No consensus was reached upon their efficacy of discrimination. We aim to compare the stratifying ability of current models or systems in predicting the risk of recurrence of PRCC. METHODS: A PRCC cohort consisting of 308 patients from our institution and 279 patients from The Cancer Genome Atlas (TCGA) was generated. With ISUP grade, TNM classification, UCLA Integrated Staging System (UISS), STAGE, SIZE, GRADE AND NECROSIS (SSIGN), Leibovich model and VENUSS system, recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) were studied using Kaplan-Meier method and concordance index (c-index) was compared. Differences between risk groups in gene mutation and infiltration of inhibitory immune cells were studied with TCGA database. RESULTS: All the algorithms were able to stratify patients in RFS as well as DSS and OS (all P < 0.001). VENUSS score and risk group generally had the highest and balanced c-index (0.815 and 0.797 for RFS). ISUP grade, TNM stage and Leibovich model had the lowest c-indexes in all analysis. Among the 25 most frequently mutated genes in PRCC, eight had different mutation frequency between VENUSS low- and intermediate-/high-risk patients and mutated KMT2D and PBRM1 resulted in worsened RFS (P = 0.053 and P = 0.007). Increased Treg cells in tumors of intermediate-/high- risk patients were also identified. CONCLUSIONS: VENUSS system showed better predictive accuracy in RFS, DSS and OS compared with SSIGN, UISS and Leibovich risk models. VENUSS intermediate-/high-risk patients had increased frequency of mutation in KMT2D and PBRM1 and increased infiltration of Treg cells.

Surface-strain-enhanced oxygen dissociation on gold catalysts.

The excellent low-temperature oxidation performance and stability of nanogold catalysts have attracted significant interest. However, the main active source of the low-temperature oxidation of gold remains to be determined. In situ electron microscopy and mass spectrometry results show that nitrogen is oxidized, and the catalyst surface undergoes reconstruction during the process. Strain analysis of the catalyst surface and first-principles calculations show that the tensile strain of the catalyst surface affects the oxidation performance of gold catalysts by enhancing the adsorption ability and dissociation of O2. The newly formed active oxygen atoms on the gold surface act as active sites in the nitrogen oxidation reaction, significantly enhancing the oxidation ability of gold catalysts. This study provides evidence for the dissociation mechanism of oxygen on the gold surface and new design concepts for improving the oxidation activity of gold catalysts and nitrogen activation.

Palladium-Catalyzed Allylation of P(O)H Compounds: Access to 2-Fluoroallylic Phosphorus Compounds.

An efficient palladium-catalyzed 2-fluoroallylation of P(O)H compounds with gem-difluorocyclopropanes is presented. The reaction provides a variety of 2-fluoroallylic phosphorus compounds in good yields with high Z selectivity through the sequential C-C bond activation, C-F bond cleavage, and C-P coupling process. Various H-phosphonates, H-phosphinates, and secondary phosphine oxides are all tolerated. In addition, the gram-scale synthesis and the late-stage modification of complex bioactive molecules show practical utilities of the transformation.