Fibroblast activation protein (FAP) has attracted much attention as a pan-cancer target with tumor-specific expression. Successful translation of FAP-targeting radiotherapeutic drugs requires a multidisciplinary approach, in which ideal pharmacokinetic (PK) characteristics are essential. This paper summarizes the PK mechanisms governing systemic clearance, tissue distribution, cellular uptake, and intracellular retention of various ligands (such as organic small molecules, peptide mid-molecules, non-peptide mid-molecules, and antibody macromolecules), analyzes the advantages and disadvantages of FAP-targeting ligands based on non-clinical PK data, and reviews PK alterations following various modification strategies (such as antibody fragmentation, albumin binding, homo- or hetero-polymerization, and click chemistry modifications), as well as the comparison of clinical PK data of different FAP-targeting radiotherapeutic drugs. This review aims to provide references for the development of FAP-targeting radiotherapeutic drugs in the industry.

Fibroblast activation protein (FAP) has attracted much attention as a pan-cancer target with tumor-specific expression. Successful translation of FAP-targeting radiotherapeutic drugs requires a multidisciplinary approach, in which ideal pharmacokinetic (PK) characteristics are essential. This paper summarizes the PK mechanisms governing systemic clearance, tissue distribution, cellular uptake, and intracellular retention of various ligands (such as organic small molecules, peptide mid-molecules, non-peptide mid-molecules, and antibody macromolecules), analyzes the advantages and disadvantages of FAP-targeting ligands based on non-clinical PK data, and reviews PK alterations following various modification strategies (such as antibody fragmentation, albumin binding, homo- or hetero-polymerization, and click chemistry modifications), as well as the comparison of clinical PK data of different FAP-targeting radiotherapeutic drugs. This review aims to provide references for the development of FAP-targeting radiotherapeutic drugs in the industry.

Decreased ovarian reserve (DOR) impairs the physical and mental health of women. It is difficult to obtain the ovary of human for research due to ethical reason. Construction of animal model of DOR may handle the problem. Research on animal model of DOR is useful to explore the pathophysiology and treatment of DOR. There are several mouse models of DOR with its individual characteristics, including drug model (chemotherapeutic drugs, metabolic drugs, immunomodulators), radiation exposure model, genetic engineering model and environmental toxicant exposure model. The better mouse model of DOR is conducted by injection of cyclophosphamide, with the following advantages: simple, economic, efficient, effective, repeatable and controllable. In this paper, the principles and characteristics of commonly used mouse model of DOR were reviewed.

Decreased ovarian reserve (DOR) impairs the physical and mental health of women. It is difficult to obtain the ovary of human for research due to ethical reason. Construction of animal model of DOR may handle the problem. Research on animal model of DOR is useful to explore the pathophysiology and treatment of DOR. There are several mouse models of DOR with its individual characteristics, including drug model (chemotherapeutic drugs, metabolic drugs, immunomodulators), radiation exposure model, genetic engineering model and environmental toxicant exposure model. The better mouse model of DOR is conducted by injection of cyclophosphamide, with the following advantages: simple, economic, efficient, effective, repeatable and controllable. In this paper, the principles and characteristics of commonly used mouse model of DOR were reviewed.

Atrial fibrillation (AF) is a common arrhythmia, which can lead to thrombosis and increase the risk of a stroke or even death. In order to meet the need for a low false-negative rate (FNR) of the screening test in clinical application, a convolutional neural network with a low false-negative rate (LFNR-CNN) was proposed. Regularization coefficients were added to the cross-entropy loss function which could make the cost of positive and negative samples different, and the penalty for false negatives could be increased during network training. The inter-patient clinical database of 21 077 patients (CD-21077) collected from the large general hospital was used to verify the effectiveness of the proposed method. For the convolutional neural network (CNN) with the same structure, the improved loss function could reduce the FNR from 2.22% to 0.97% compared with the traditional cross-entropy loss function. The selected regularization coefficient could increase the sensitivity (SE) from 97.78% to 98.35%, and the accuracy (ACC) was 96.62%, which was an increase from 96.49%. The proposed algorithm can reduce the FNR without losing ACC, and reduce the possibility of missed diagnosis to avoid missing the best treatment period. Meanwhile, it provides a universal loss function for the clinical auxiliary diagnosis of other diseases.
Algorithms ; Atrial Fibrillation/diagnosis* ; Electrocardiography ; Humans ; Neural Networks, Computer ; Stroke

Objective:To explore the eye movement characteristics of social cognitive processing in schizophrenia patients across different stages and its association with clinical symptoms.Methods:Fifteen patients with first-episode schizophrenia, forty-six patients with chronic inpatient schizophrenia, thirty-six patients with psychiatric clinical high-risk syndrome, and twenty-six healthy controls were recorded using eye tracking technology when viewing social interaction pictures. Covariance analysis and partial correlation analysis were conducted by SPSS17.0.Results:When watching the pictures of person communication, there were statistically significant differences in the average fixation duration of the four groups of subjects ((294.6±36.7)ms in control group, (280.0±54.0)ms in clinical high-risk group, (268.5±34.9)ms in first-episode group, and (315.7±75.7) ms in chronic group, respectively, F=3.18, P=0.027). When viewing the pictures of no person landscape, the average saccade amplitude of the four groups of subjects was significantly different (5.3±1.1) ° in control group, (4.7±1.1) ° in clinical high-risk group, (5.2±1.0) ° in first-episode group, and (4.4±1.2) ° in chronic group, respectively, F=3.37, P=0.021). The average fixation duration of chronic patients when observing person communication pictures was positively correlated with the total score of PANSS (partial correlation coefficient=0.313, P=0.039). The average fixation duration of chronic patients when observing the other two types of pictures were also positively correlated with the total score of PANSS (partial correlation coefficient=0.320, P=0.034, no person communication pictures; partial correlation coefficient=0.372, P=0.013, no person landscape pictures) . The average fixation duration of chronic patients when observing pictures of no person landscape was positively correlated with the PANSS positive symptom score (partial correlation coefficient=0.321, P=0.034). The average fixation duration of chronic patients when observing any type of picture was positively correlated with the PANSS general symptom score (person communication pictures: partial correlation coefficient=0.385, P=0.010; no person communication pictures: partial correlation coefficient=0.409, P=0.006; no person landscape pictures: partial correlation coefficient=0.465, P=0.001). In the first-episode patient, the average saccade amplitude when observing no person communication pictures was positively correlated with the PANSS positive symptom score (partial correlation coefficient=0.555, P=0.049). In the clinical high-risk group, the average saccade amplitude when observing person communication pictures was negatively correlated with the SOPS positive symptom score (partial correlation coefficient=-0.373, P=0.030). Conclusion:There are statistically significant differences of eye movement characteristics of social cognitive processing in patients with schizophrenia across different clinical stages.The average saccade amplitude is more sensitive than the average fixation duration in predicting the severity of symptoms in clinical high-risk patients.

Objective: To acknowledge the availability and rates of annual transition of outcomes during the progression and regression stages of colorectal cancer (CRC) and related diseases, by pooling global follow-up studies on the natural history of CRC. Methods: Till March, 2017, data was collected through systematic literature review over multiple databases, including PubMed, Embase, Cochrane and Chinese Biology Medicine (CBM) disc. Information regarding the characteristics, classification system of health states, related outcomes and incidence rates on CRC or high-risk adenoma for the surveillance cohorts of the studies, were extracted and summarized. Both Meta and sensitivity analyses were performed on those outcomes if they appeared in more than 3 studies, using the random effects model. Annual transition rate with 95%CI was used to estimate each of the outcomes, Quality of the studies was assessed, using the Newcastle-Ottawa Scale. Results: A total of 29 cohort studies were included, with the mean follow-up period as 5.7 years. All studies except one, focused on adenoma-carcinoma pathway and reported the outcome parameters of adenomas by different risk, and some reported the findings on different sizes (n=6) of adenomas. These cohorts were divided into three groups (normal status, with low-risk or high-risk adenoma) according to the status of baseline endoscopic pathologic findings. Their available outcome parameters, corresponding number of involved articles, aggregated sample size and pooled annual transition rates were presented. Six parameters were obtained in the normal cohorts, including those from normal to low-risk adenoma (16 articles, 58 235, 0.030: 0.024-0.037), to high-risk adenoma (17 articles, 62 089, 0.003: 0.002-0.004), to diminutive adenoma (<5 mm, 4 articles, 1 277, 0.021: 0.013-0.029), to small adenoma (6-9 mm, 4 articles, 1 277, 0.006: 0.001-0.010), to large adenoma (≥10 mm, 7 articles, 3 531, 0.002: 0.000-0.003) and to CRC (19 articles, 104 836, 0.000 3: 0.000 2-0.000 5). Three parameters were obtained in low-risk adenoma in cohorts with polypectomy findings, including recurrence (9 articles, 4 788, 0.109: 0.062-0.157) from low-risk adenoma after polypectomy to high-risk adenoma (10 articles, 5 736, 0.009: 0.004-0.013) and to CRC (12 articles, 11 347, 0.000 6: 0.000 4-0.000 8). Three parameters were obtained on high-risk adenoma from cohorts with polypectomy findings, including recurrence (12 articles, 7 030, 0.038: 0.028-0.048) from high-risk adenoma after polypectomy to low-risk adenoma (8 articles, 2 489, 0.133: 0.081-0.185) and CRC (14 articles, 14 899, 0.002: 0.001-0.003). Except for normal to low-risk adenomas, results from the sensitivity analysis for the other parameters showed stable. Of the included studies, two presented incidence rates of CRC in different clinical stages and the another two were focusing on the parameters related to serrated pathway. Conclusions Globally, follow-up studies reported data on natural history of colorectal cancer is of paucity. Compared to the "adenoma-carcinoma" pathway, transition parameters of the serrated lesion pathway are more limited. This Meta-analysis provided convincing evidence for optimizing the strategies regarding follow-up program on the disease, using the baseline endoscopic findings from global CRC Screening Program. These results also offered strong data-related support for Chinese population- specific interventional model on colorectal cancer.

Objective To observe the clinical effect of traditional Chinese medicine inflammatory mixture on vascular endothelial cell injury, mcrocirculation disorder and organ dysfunction in sepsis. Methods 73 patients with sepsis were randomly divided into two groups: Anti-inflammatory mixture-treated group (40 cases) and control group (33 cases). Routine medicine therapy was given in both groups.Additionally, in the Anti-inflammatory mixture-treated group, 100 ml Anti-inflammatory mixture was given By oral or nasal feeding, every 12 hours for consecutive 7 days. Vascular endothelial injury index (Soluble thrombomodulin,Vascular endothelial growth factor-2, endothelial specific molecule-1), mcrocirculation disorder index (arterial blood lactate, central venous oxygen saturation, total vessel density, perfused vessel density, proportion of perfused vessels, microcirculatory flow index) of two group patients before and after therapy were observed and the sequential organ failure score (SOFA) was recorded before and after treatment. Results After treatment, the indexes of vascular endothelial injury sTM (12.37 ± 5.08 μg/L vs. 18.77 ± 6.88 μg/L, t=3.448), VEGF-2 [45.6 ng/L (14.3, 112.5) vs. 52.4 ng/L (17.2, 123.6), Z=4.009], ESM-1 (15.54 ± 4.09 ng/ml vs. 17.64 ± 6.79 ng/ml, t=-1.551), Lac (2.6 ± 1.2 mmol/L vs. 3.7 ± 1.8 mmol/L, t=4.115) and SOFA (4.1 ± 1.7 vs. 6.1 ± 3.2, t=-2.118) in anti-inflammatory mixture group decreased significantly than those in the control group. but the ScvO2(0.719 ± 0.243 vs. 0.603 ± 0.201, t=-2.773), PVD (14.8 ± 5.8 mm/mm2 vs. 13.1±5.1 mm/mm2, t=-5.114), PPV (59.1% ± 22.5% vs. 53.9% ± 20.6%, t=1.779), MFI (9.4 ± 4.6 vs. 7.2 ± 2.2, t=4.339) in the anti-inflammatory mixture group were significantly higher than those in the control group. Correlation analysis showed that the sTM and PPV were significantly negatively correlated (r=-0.875, P＜0.01), ESM-1 was significantly negatively correlated with PVD, PPV and MFI (r=-0.877, P＜0.01; r=-0.799, P＜0.01; r=-0.821, P＜0.01) and ESM-1 and SOFA were significantly positively correlated (r=0.840, P＜0.01). Conclusions Anti-inflammatory mixture of Chinese medicine has a certain therapeutic effect on sepsis by protecting vascular endothelial cell function.

Objective:To explore the effect of intervention of E-cadherin (E-cad) and B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) mediated by transcription activator-like effector nuclease (TALEN) on the biological behaviors ofnasopharyngeal carcinoma cells.Methods:Multi-locus gene targeting vectors pUC-DS1-CMV-E-cad-2A-Neo-DS2 and pUC-DS1-Bmi-1 shRNA-Zeo-DS2 were constructed,and the E-cad and Bmi-1 targeting vectors were transferred with TALEN plasmids to CNE-2 cells individually or simultaneously.The integration of target genes were detected by PCR,the expressions of E-cad and Bmi-1 were detected by Western blot.The changes of cell proliferation were detected by cell counting kit-8 (CCK-8) assay.T-he cell cycle and apoptosis were detected by flow cytometry.The cell migration and invasion were detected by Transwell assay.Results:The E-cad and Bmi-1 shRNA expression elements were successfully integrated into the genome of CNE-2 cells,the protein expression level of E-cad was up-regulated,and the protein expression level of Bmi-1 was down-regulated.The intervention of E-cad and Bmi-1 didn't affect the proliferation,cell cycle and apoptosis of CNE-2 cells,but it significantly inhibited the migration and invasion ability of CNE-2 cells.Furthermore,the intervention of E-cad and Bmi-1 together significantly inhibited the migration ability of nasopharyngeal carcinoma cells compared with the intervention of E-cad or Bmi-1 alone (all P＜0.01).Conclusion:The joint intervention of E-cad and Bmi-1 mediated by TALEN can effectively inhibit the migration and invasion of nasopharyngeal carcinoma cells in vitro,which may lay the preliminary experimental basis for gene therapy of human cancer.

Objective To investigate the difference of niacin skin flush response between patients with major depressive disorder (MDD) and healthy controls (HCs), and its sensitivity and specificity for the diagnosis of MDD. Methods Twenty-one untreated patients with MDD and 28 age- and gender-matched HCs were enrolled in this study. The severity of depressive symptoms was assessed mainly by using the 17-item Hamilton Depression Rating Scale (HDRS-17). Methyl Nicotinate (MN) solution at 8 different concentrations (10-5 mol/L, 10-4 mol/L, 10-3.5 mol/L, 10-3 mol/L, 10-2.5 mol/L, 10-2 mol/L, 10-1.5 mol/L, 10-1 mol/L) were applied on subjects' forearms. Signals of blood flow were collected using the Doppler Laser Flowmetry to detect the skin flushing of the test. Results Under the concentrations of 10-2.5 mol/L, 10-2 mol/L, 10-1.5 mol/L and 10-1 mol/L MN solution, the blood flow was significantly higher in depressive patients than in HCs (P<0.01). The MN sensitivity (logEC50) was inversely correlated to the severity of depressive symptoms (r=-0.57, P<0.05). ROC curve analysis implied that the maximum blood flow (MBF) caused by the niacin skin flush response, could efficiently discriminate MDD from HCs (AUC=0.90, P<0.01). Conclusion The presence of enhanced niacin skin flush response may be helpful in the diagnosis of MDD.