[Research progress on biomarkers and detection methods for Alzheimer's disease diagnosis in vitro].

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset, posing a serious threat to human physical and mental health. The cognitive impairments caused by AD are generally diffuse and overlap symptomatically with other neurodegenerative diseases. Moreover, the symptoms of AD are often covert, leading to missed opportunities for optimal treatment after diagnosis. Therefore, early diagnosis of AD is crucial. In vitro diagnostic biomarkers not only contribute to the early clinical diagnosis of AD but also aid in further understanding the disease's pathogenesis, predicting disease progression, and observing the effects of novel candidate therapeutic drugs in clinical trials. Currently, although there are numerous biomarkers associated with AD diagnosis, the complex nature of AD pathogenesis, limitations of individual biomarkers, and constraints of clinical detection methods have hindered the development of efficient, cost-effective, and convenient diagnostic methods and standards. This article provides an overview of the research progress on in vitro diagnostic biomarkers and detection methods related to AD in recent years.

Bifocal 532/1064 nm alternately illuminated photoacoustic microscopy for capturing deep vascular morphology in human skin.

BACKGROUND: As a promising technology, photoacoustic microscopy (PAM) plays a critical role in diagnosis and assessment of dermatological conditions by providing subtle vascular networks non-invasively. However, the established PAMs are insufficient for clinical dermatology when faced with complex structures of human skin instead of animal models owing to high melanin content and superimposed vasculature for Asians, which cannot balance the spatial resolution and the imaging depth. OBJECTIVES: To evaluate the ability of bifocal 532/1064-nm alternately illuminated photoacoustic microscopy (BF-PAM) to non-invasively reveal the morphological structure of human skin for improving the diagnosis and therapeutic efficacy of skin diseases. METHODS: A BF-PAM was developed to capture biopsy-like information of human skin from epidermis to hypodermis. The optical foci of the two excitation beams are staggered in the axial direction to form an extended depth-of-field, which can maintain the lateral resolution and the contrast of PA image. RESULTS: The imaging capability of the BF-PAM was demonstrated by depicting the vascular morphology of multilayered skin with imaging depth of ˜3 mm. Furtherly, vascular malformations in port-wine stains skin were quantitatively assessed without the need for any contrast agent, and the distribution, depth and diameter of the ectatic vessels can determine an optimal treatment protocol for port-wine stains lesions. CONCLUSIONS: The quantitative vascular morphology in the dermis can be used to accurately assess vascular characteristics, in which case it enables clinicians to determine optimum treatment parameters in individual patients. As a non-invasive imaging technique, BF-PAM holds great potential to provide objective assessment to enhance the therapeutic efficacy. ETHICAL STATEMENT: The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200184) and registered with Chinese Clinical Trial Registry (ChiCTR2000034400). Before skin imaging, written informed consent was taken from all individual participants.

[Correlation between heart rate index, SBPpeak-to-SBPrest ratio and peak oxygen consumption in patients with chronic heart failure].

Objective: To investigate the correlation between heart rate index (HRI), systolic blood pressure(SBP) peak-to-SBPrest ratio (SBPR) and peak oxygen consumption (peakVO2) in patients with chronic heart failure (CHF), and discuss the possibility of using HRI and SBPR collected during exercise to assess the exercise tolerance of CHF patients in the absence of gas analysis. Methods: In this cross-sectional study, a total of 547 patients with CHF who underwent cardiopulmonary exercise test(CPET) in Tongji Hospital Heart Rehabilitation Center Affiliated to Tongji University from March 2007 to December 2018 were collected retrospectively, focusing on their clinical data including age, gender, type of heart failure,BMI as well as data collected during their CPETs, such as peakVO2, HRI and SBPR. Spearman univariate correlation analysis was used for statistical analysis, to unveil the correlations between peakVO2 and those parameters, and multiple linear regression analysis was also conducted. Results: A total of 547 CHF patients conducting CPET were included in this research, of which 447 were male, at age of 63(56, 69). Univariate analysis indicates that HRI, SBPR and peakVO2 showed significant positive correlation (r=0.323, 0.263, respectively, all P<0.001); Age and peak VO2 showed significant negative correlation(r=-0.207, P<0.001); Male patients showed peakVO2 higher than female(r=-0.229, P<0.001); PeakVO2 of heart failure with reduced ejection fraction(HFrEF) was lower than heart failure with mid-range ejection fraction(HFmrEF)and heart failure with preserved ejection fraction(HFpEF) (r=0.181, P<0.001). Body mass index (BMI) had no significant correlation with peakVO2 (P>0.05). Multivariate linear regression analysis showed that the HRI, SBPR were positively correlated with peakVO2(t=7.68, 5.08, respectively, all P<0.05), while age and BMI showed negative correlation with peakVO2(t=-5.43, -0.31, respectively, all P<0.05). PeakVO2 of male was higher than female(t=-6.03, P<0.05), and peakVO2 of HFrEF was lower than those of HFmrEF and HFpEF(t=3.17, 4.48, respectively, all P<0.05). A linear equation (F=33.52, adjusted R2=0.29) could be constructed: peakVO2=10.65(male) or 8.53(female)+4.26HRI+3.31SBPR-0.07age-0.13BMI+0(HFrEF) or 1.05 (HFmrEF) or 1.62(HFpEF). Conclusion: HRI and SBPR are positively correlated with peakVO2. In the absence of gas analysis, it is possible to apply HRI and SBPR during exercise to predict exercise tolerance in patients with CHF.

[The role of STAT-6/KLF-4/PPAR-γ activation in alveolar macrophage polarization changes in silica-induced pulmonary fibrosis].

Objective: To observe the effect of silicon dioxide (SiO(2)) on the polarization of alveolar macrophages (AMs) , and to explore the expressions and the significance of signal transducer and activator of transcription-6 (STAT-6) /Krüppel-like factor-4 (KLF-4) /peroxisome proliferators-activated receptors-γ (PPAR-γ) signaling molecules in AMs. Methods: In November 2020, C57BL/6 mice were randomly divided into crystalline SiO(2) group and normal saline (NS) group, and 12 mice in each group. Mice were intratracheally instillated with 100 µl crystalline SiO(2) suspension (20 mg/ml) or 100 µl NS, and were sacrificed after 28 days. Masson staining was used to observe the degree of pulmonary fibrosis of mice and hydroxyproline (HYP) level were assessed. The proportions of M1-typed and M2-typed AMs in bronchoalveolar lavage fluid (BLAF) were analyzed by flow cytometry. The mRNA relative expression levels of inducible nitric oxide synthase (iNOS) , arginidase-1 (Arg-1) , interleukin (IL) -1ß, tumor necrosis factor-α (TNF-α) , IL-6, IL-10, transforming growth factor-ß (TGF-ß) , STAT-6, KLF-4 and PPAR-γ were detected by real-time fluorescence quantitative PCR. Activities of iNOS and Arg-1, as well as contents of IL-1ß, TNF-α, IL-6, IL-10 and TGF-ß were assessed by the enzyme-linked immunosorbent. The protein relative expression levels of phosphorylation-signal transducer and activator of transcription-6 (p-STAT-6) , KLF-4 and PPAR-γ were evaluated by immunofluorescence. Results: After 28 days of treatment, the structure of the lung tissue of the mice was destroyed, and the deposition of collagen was significantly increased in the crystalline SiO(2) group. Compared with NS group, HYP level of lung tissue in crystalline SiO(2) group were increased, the proportion of M2-typed AMs in crystalline SiO(2) group was increased, the proportion of M1-typed AMs in crystalline SiO(2) group was decreased, the mRNA relative expressions and contents of Arg-1, IL-10, TGF-ß in crystalline SiO(2) group were significantly increased, the mRNA relative expressions and contents of iNOS, IL-1ß, TNF-α, IL-6 in crystalline SiO(2) group were significantly decreased, the mRNA of STAT-6, KLF-4, PPAR-γ and the protein relative expression levels of p-STAT-6, KLF-4, PPAR-γ were significantly increased in crystalline SiO(2) group, and the the differences were statistically significant (P<0.05) . Conclusion: Crystalline SiO(2) may mediate the process of pulmonary fibrosis through promote AMs polarization toward M2-typed by activating the STAT-6/KLF-4/PPAR-γ signaling pathway.

[Correlation analysis between blood routine-derived inflammatory markers and respiratory function in pneumoconiosis patients].

Objective: To analyze the correlation between blood routine-derived inflammation indicators and respiratory function in patients with pneumoconiosis. Methods: In January 2021, 492 male pneumoconiosis patients hospitalized in Hefei Institute of Occupational Disease Control and Prevention from 2012 to 2020 were randomly selected as the case group, 492 dust exposed non pneumoconiosis workers who underwent occupational health examination at the same time were taken as the control group. The occupational history and clinical examination data of the two groups of subjects were collected, the correlation between blood routine-derived inflammatory indexes and pulmonary function and blood gas analysis was analyzed retrospectively. Results: Compared with the control group, the lymphocyte monocyte ratio (LMR) in the case group was decreased, and the neutrophil lymphocyte ratio (NLR) was increased, and the difference was statistically significant (P<0.05) . There were significant differences in forced vital capacity as a percentage of the predicted value (FVC) , forced expiratory volume in the first second as a percentage of the predicted value (FEV(1)%) , one second rate (FEV(1)/FVC) , partial pressure of oxygen (PaO(2)) , partial pressure of carbon dioxide (PaCO(2)) , and pH among pneumoconiosis patients at different stages (P<0.05) . FVC%, FEV(1)%, FEV(1)/FVC, and PaO(2) decreased with the increase of the stage, the trend test was statistically significant (tau-b=-0.24, -0.34, -0.37, -0.17, P<0.05) , PaCO(2) and pH increased with the increase of the stage, and the trend test was statistically significant (tau-b=0.10, 0.08, P<0.05) . There were statistically significant differences in LYM, LMR, NLR, platelet lymphocyte ratio (PLR) in patients with pneumoconiosis at different stages (P<0.05) , and LYM and LMR decreased with the increase of stage, trend test showed that there was statistically significant (tau-b=-0.11, -0.13, P<0.05) . There were significant differences in FVC%, FEV(1)%, FEV(1)/FVC, PaO(2), pH, LMR, NLR, PLR among patients with different types of pneumoconiosis (P<0.05) . LMR in pneumoconiosis patients was significantly positively correlated with FVC%, FEV(1)%, FEV(1)/FVC and PaO(2) (r(s)=0.342, 0.324, 0.203, 0.207, P<0.05) , NLR was significantly negatively correlated with FVC%, FEV(1)%, FEV(1)/FVC and PaO(2) (r(s)=-0.193, -0.202, -0.164, -0.177, P<0.05) , PLR was significantly negatively correlated with FVC%, FEV(1)%, FEV(1)/FVC and PaO(2) (r(s)=-0.194, -0.193, -0.106, -0.113, P<0.05) . Multiple linear regression analysis showed that LMR in pneumoconiosis patients was positively related with FVC%, FEV(1)% and PaO(2) (P<0.05) . Conclusion: LMR in patients with pneumoconiosis has a certain correlation with lung function and blood gas analysis, LMR is expected to become a sensitive indicator for evaluating pneumoconiosis.

Structural basis of acquired resistance to selpercatinib and pralsetinib mediated by non-gatekeeper RET mutations.

BACKGROUND: Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are highly potent RET-selective protein tyrosine kinase inhibitors (TKIs) for treating advanced RET-altered thyroid cancers and non-small-cell lung cancer (NSCLC). It is critical to analyze RET mutants resistant to these drugs and unravel the molecular basis to improve patient outcomes. PATIENTS AND METHODS: Cell-free DNAs (cfDNAs) were analyzed in a RET-mutant medullary thyroid cancer (MTC) patient and a CCDC6-RET fusion NSCLC patient who had dramatic response to selpercatinib and later developed resistance. Selpercatinib-resistant RET mutants were identified and cross-profiled with pralsetinib in cell cultures. Crystal structures of RET-selpercatinib and RET-pralsetinib complexes were determined based on high-resolution diffraction data collected with synchrotron radiation. RESULTS: RETG810C/S mutations at the solvent front and RETY806C/N mutation at the hinge region were found in cfDNAs of an MTC patient with RETM918T/V804M/L, who initially responded to selpercatinib and developed resistance. RETG810C mutant was detected in cfDNAs of a CCDC6-RET-fusion NSCLC patient who developed acquired resistance to selpercatinib. Five RET kinase domain mutations at three non-gatekeeper residues were identified from 39 selpercatinib-resistant cell lines. All five selpercatinib-resistant RET mutants were cross-resistant to pralsetinib. X-ray crystal structures of the RET-selpercatinib and RET-pralsetinib complexes reveal that, unlike other TKIs, these two RET TKIs anchor one end in the front cleft and wrap around the gate wall to access the back cleft. CONCLUSIONS: RET mutations at the solvent front and the hinge are resistant to both drugs. Selpercatinib and pralsetinib use an unconventional mode to bind RET that avoids the interference from gatekeeper mutations but is vulnerable to non-gatekeeper mutations.

Differentially expressed proteins identified by TMT proteomics analysis in children with verrucous epidermal naevi.

BACKGROUND: Verrucous epidermal naevi (VEN) are benign skin tumours, considered keratinocytic epidermal naevi, that appear at birth or early childhood. VEN may display a range of appearances, depending on patient age. Although the number of studies regarding VEN is increasing, the exact mechanism of VEN is still unknown. OBJECTIVES: The aim of this study was to analyse the changes in the expression of protein factors in lesions of VEN children by TMT labelling-based quantitative proteomics. METHODS: A total of 8 children with VEN (5 for experiment and 3 for validation) and 8 healthy children (5 for experiment and 3 for validation) presented to the Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Boao Super Hospital, between January 2019 and November 2019. The lesions and lesion-adjacent tissues from children with VEN and naevus-adjacent normal skin tissues from children with pigmented naevi were defined as the VEN group, VENC group and C group, respectively. We performed a proteomics analysis to screen for differentially expressed proteins in the lesions of these individuals. We further performed Western blotting to validate the relative expression levels of nine targeted proteins in the validation group. RESULTS: According to the proteomics results, a total of 4970 proteins were identified, and 4770 proteins were quantified. Among these proteins, 586 proteins were up- or downregulated at least 1.3-fold with a P-value < 0.05 (upregulated: 399, downregulated: 187) in lesions between the VEN group and the C group. These proteins played important roles in multiple biological functions, such as cornification, epidermal cell differentiation and neutrophil activation, and formed a complicated protein-protein interaction network. Of the 586 up- or downregulated proteins, nine were selected for further validation. According to Western blotting analysis results, the relative expression levels of Involucrin, NDUFA4, Loricrin, Keratin type II cytoskeletal 6A (Cytokeratin 6A), BRAF, Filaggrin, S100A7 and Desmocollin-3 were significantly upregulated in VEN children and may be associated with skin barrier dysfunction, epidermal cell overgrowth and differentiation, inflammation and immune and oxidative phosphorylation, which are involved in the pathogenesis of VEN. CONCLUSIONS: According to TMT-based proteomics and Western blotting results, we identified eight noteworthy proteins, Involucrin, NDUFA4, Loricrin, Keratin type II cytoskeletal 6A, BRAF, Filaggrin, S100A7 and Desmocollin-3, that were upregulated in the lesions of VEN children and may be associated with the pathogenesis of VEN. Our findings provide new starting points for identifying precise pathogenic mechanisms or therapeutic targets for VEN.

[Increased risk of cardiovascular disease in elderly population with carotid plaque and low ankle brachial index].

Objective: To investigate whether the co-presence of carotid plaques and low ankle-brachial index (ABI) might increase the risks of ischemic cardiovascular and cerebrovascular event in elderly population. Methods: It was a prospective study. Participants from the elderly cohort of the Kailuan Study, who completed a carotid sonography and ABI examination, were included in this study. Participants underwent physical examinations between 2010 and 2011 and were divided into 3 groups: no carotid plaque and ABI>0.9 group (n=526), carotid plaque and ABI>0.9 group (n=1 067), and carotid plaques and ABI≤0.9 group (n=49). Follow up ended on the 31 December 2016. The incidence of ischemic cardiovascular and cerebrovascular event was compared between the 3 groups, the relationship between carotid plaque and low ABI with ischemic cardiovascular and cerebrovascular event was analyzed. Results: A total of 1 642 participants were included (age, (67.1±6.4) years). There were 1 028 males (62.6%) and 1 028 females(37.4%). The average follow-up time was 5.41 years, the incidence of ischemic cardiovascular and cerebrovascular event in the 3 group was 2.1%(11/526), 5.5%(59/1 067), and 12.2%(6/49),respectively; the incidence of myocardial infarction in the 3 group was 0.2%(1/526), 1.6%(17/1 067), 10.2%(5/49), respectively; the incidence of cerebral infarction in the 3 group was 1.9%(10/526), 3.9%(42/1 067) and 2.0%(1/49), respectively. Multivariate Cox risk proportional regression analysis showed that compared with the group without carotid plaque and ABI>0.9, the HR values (95%CI) of ischemic cardiovascular and cerebrovascular event in the group with carotid plaque and ABI>0.9, carotid plaques and ABI≤0.9 group were 3.52 (1.49-8.35), 7.16(2.11-24.26) respectively, after adjusting for sex,age,systolic blood pressure,fast blood glucose,body mass index,total cholesterol,smoke,alcohol consumption and lipid-lowering medication and antihypertensive medication. Conclusions: Co-presence of carotid plaques and low ankle-brachial index may further increase the risk of ischemic cardiovascular and cerebrovascular event among elderly population in this cohort.

[Abnormalities of white matter differentiate the Parkinson variant of multiple system atrophy from Parkinson's disease].

Objective: To identify objective markers between the Parkinson variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD). Methods: Retrospective analysis was performed on 10 patients with MSA-P, 15 patients with PD, and 15 healthy control group during the period from August 2016 to February 2019 in Baoshan Branch of Shanghai First People's Hospital.We combined the novel tract based spatial statistics (TBSS) and region of interest (ROI) analyses for the first time to investigate three groups with diffusion tensor imaging. By TBSS, we performed pairwise comparisons of mean diffusivity and fractional anisotropy (FA) maps. The clusters with significant differences between MSA-P and PD were used as ROIs for further analyses. Results: FA values in the left anterior thalamic radiation(ATR) (ROI values were 0.371(0.287-0.535), 0.472(0.390-0.594), 0.473(0.388-0.555); P values were 0.008, 0.008) and left superior longitudinal fasciculus (SLF)(ROI values were 0.397(0.291-0.469), 0.456(0.338-0.560), 0.473(0.427-0.530); P values were 0.013,<0.001) were significantly decreased in MSA-P compared with PD or controls, and significantly correlated with clinical data((r =-0.807, P =0.005),(r =-0.455, P =0.022)). Conclusion: Our findings indicate the abnormalities of left ATR and left SLF as specific biomarkers for differential diagnosis.

[Effects of ticagrelor on cardiorespiratory fitness in patients after percutaneous coronary intervention].

Objective: To investigate the effects of ticagrelor on cardiorespiratory fitness in patients with coronary heart disease after percutaneous coronary intervention (PCI). Methods: A total of 1 073 patients, who were diagnosed as coronary heart disease and underwent cardiopulmonary exercise testing (CPET) within 1 year after PCI, were enrolled from September 2017 to September 2019 in Peking University Third Hospital, including 309 patients in ticagrelor group and 764 patients in clopidogrel group. Clinical information, blood test results, echocardiographic parameters, cardiorespiratory fitness related parameters (including peak oxygen uptake (VO(2)), anaerobic threshold VO(2), peak oxygen pulse (VO(2)/HR) and carbon dioxide ventilation equivalent (VE/VCO(2)) slope), coronary lesions and intervention information were obtained. Cardiopulmonary fitness related indexes were compared between the two groups, and the correlation between ticagrelor use and cardiopulmonary fitness related indexes was analyzed by multivariate logistic regression. Patients who underwent CPET within 1 month after PCI were included in the subgroup analysis. Results: In ticagrelor group, the age was (60.3±10.3) years, and 253(81.9%) cases were male. The age of clopidogrel group was (60.6±10.0) years, and there were 608(79.6%) males. No significant differences were observed in peak VO(2), anaerobic threshold VO(2), and peak VO(2)/HR between the two groups (all P>0.05), but the VE/VCO(2) slope was significantly higher in the ticagrelor group than in the clopidogrel group (30.075 (27.207, 33.603) vs. 28.853 (25.970, 32.336), P<0.001). Logistic regression analysis suggested that the peak VO(2), anaerobic threshold VO(2) and peak VO(2)/HR were not significantly correlated with the ticagrelor use (all P>0.05), while the VE/VCO(2) slope was independently correlated with ticagrelor use (OR=1.098, 95%CI 1.032-1.168, P=0.003). Subgroup analysis of patients who underwent CPET within 1 month after PCI also indicated that no significant difference were observed in peak VO(2), anaerobic threshold VO(2), peak VO(2)/HR and VE/VCO(2) slope between the two groups (all P>0.05). Logistic regression analysis suggested that the peak VO(2), anaerobic threshold VO(2) and peak VO(2)/HR were not significantly correlated with ticagrelor use (all P>0.05), while the VE/VCO(2) slope was significantly correlated with ticagrelor use (OR=1.132, 95%CI 1.030-1.244, P=0.010). Conclusion: Among coronary heart disease patients after PCI, treatment with clopidogrel does not result in significant decrease in exercise endurance as compared with patients treated with ticagrelor.

Quercetin and Isoquercitrin Inhibiting Hepatic Gluconeogenesis Through LKB1-AMPKα Pathway.

OBJECTIVE: To observe the impact of quercetin and isoquercitrin on gluconeogenesis in hepatocytes. METHODS: Mouse primary hepatocytes were cultured with lactic acid and pyruvic acid. After treatment with quercetin and isoquercitrin for 24 hours, the glucose concentration in the culture supernatant was determined. RT-PCR was used to detect the mRNAs of PEPCK, G6Pase, LKB1, and AMPKα. Protein levels of LKB1, AMPKα, and Thr172 phosphorylation were evaluated by Western blot. RESULTS: The glucose concentration in the gluconeogenesis group (GN) was significantly higher than in the control group (C), but the glucose concentrations in the high level quercetin(group 80Q) and high level isoquercitrin (group 80I) were significantly lower than in the group GN, P<0.01. In the group 80Q, and group 80I, the mRNA levels of PEPCK and LKB1were significantly lower than in the group GN (P<0.01), and the G6Pase mRNA were significantly lower than in the group GN (P<0.05). The protein levels of LKB1 and the phosphorylation of AMPKα Thr172 in the group 80Q, group 40I, and group 80I were higher than in the group GN. The effects of quercetin and isoquercitrin on LKB1 and AMPKα were similar to those of metformin. CONCLUSIONS: Quercetin and isoquercitrin inhibit gluconeogenesis in hepatocytes, which may be related to the LKB1 upregulation and phosphorylation of AMPKα.

Low frequency, weak MCP-1 secretion and exhausted immune status of peripheral monocytes were associated with progression of severe enterovirus A71-infected hand, foot and mouth disease.

A minority of hand, foot and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) results in severe neural complications. However, whether monocyte-mediated immunity is involved in the disease progression of HFMD remains unknown. One hundred and twenty mild and 103 severe HFMD patients were recruited and enzyme-linked immunosorbent assay (ELISA), flow cytometry and Transwell culture were performed in the study. Peripheral monocyte counts were lower in both absolute counts and frequencies in severe cases compared to mild cases. After screening 10 monocyte-related cytokines by ELISA, only monocyte chemoattractant protein-1 (MCP-1) was found at higher levels in sera of mild cases compared to those with severe symptoms. Monocytes purified from mild cases produced more MCP-1 than the cells from severe patients when stimulated in vitro. We observed that immune exhaustion markers programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) were highly regulated on the surface of monocytes from severe cases compared to mild cases. PD-L1 blockade induced a higher production of MCP-1 in the supernatant of a Transwell system. The production of MCP-1 also increased following PD-L1 blockade of purified monocytes activated by granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with R848 or EV-A71 virus. Our results indicate that absolute count, frequency and levels of MCP-1 secretion of peripheral monocytes, together with their immune status, probably contribute to differential disease prognosis in EV-A71-associated HFMD.

The potential of cadmium ion-immobilized Rhizobium pusense KG2 to prevent soybean root from absorbing cadmium in cadmium-contaminated soil.

AIMS: Because the effect of Cd2+ -immobilized microbe on Cd uptake of plants in Cd-contaminated soil remains underexplored, this study focuses on the effect of Cd2+ -immobilized rhizobia on Cd uptake of soybean. METHODS AND RESULTS: Strain KG2 from soybean nodule was identified as Rhizobium pusense KG2 by phylogenetic analysis. Rhizobium pusense KG2 showed the 120 mg l-1 of minimal lethal concentration for Cd2+ . In 50 and 100 mg l-1 of Cd2+ liquid, approximately 2 × 1010 cells removed 56·71 and 22·11% of Cd2+ , respectively. In pot soil containing 50 and 100 mg kg-1 of Cd2+ , strain KG2 caused a 45·9 and 35·3% decrease in soybean root Cd content, respectively. Meanwhile, KG2 improved the root and shoot length, nitrogen content and biomass of soybean plants and superoxide dismutase activity. CONCLUSIONS: The Cd2+ -immobilized rhizobia could inhibit soybean plants to absorb Cd2+ from soil, promote plant growth and improve plant's tolerance against Cd. This study is the first time to report that R. pusense is an effective nodulating rhizobium of legume. SIGNIFICANCE AND IMPACT OF THE STUDY: Some Cd2+ -immobilized microbe lowering Cd uptake of plant and promoting plant growth should be considered as an effective strategy for producing safety crops in the Cd-contaminated agricultural soil.

High Performance Bi-2212 Round Wires Made with Recent Powders.

Multifilamentary Bi2Sr2CaCu2Ox (Bi-2212) wire made by the powder-in-tube technique is the only high temperature superconductor made in the round shape preferred by magnet builders. The critical current density (J C ) of Bi-2212 round wire was improved significantly by the development of overpressure heat treatment in the past few years. Bi-2212 wire is commercially available in multiple architectures and kilometer-long pieces and a very promising conductor for very high field NMR and accelerator magnets. We studied the effects of precursor powder and heat treatment conditions on the superconducting properties and microstructure of recent Bi-2212 wires. Short samples of recent wire with optimized overpressure processing showed J C (4.2 K, 15 T) = 6640 A/mm2 and J C (4.2 K, 30 T) = 4670 A/mm2, which correspond to engineering critical current densities J E (4.2 K, 15 T) = 1320 A/mm2 and J E (4.2 K, 30 T) = 930 A/mm2.

[The evaluation of training program "resident team leader in the Department of General Internal Medicine" at Peking Union Medical College Hospital].

Objective: To evaluate senior resident training program "resident team leader in the Department of General Internal Medicine" at Peking Union Medical College Hospital. Methods: We surveyed the residents or the fellows who had been selected as resident team leaders and received the training from October 2014 to September 2018 on their comments and suggestions. Results: Twenty-two rotated senior residents who were selected as team leaders in the Department of General Internal Medicine completed the survey. Almost all (21/22, 95.5%) of the respondents reported that they learnt more in general as team leaders by Visual Analog Scale (VAS). The mean VAS scores of clinical skills were 7.23±1.27, 7.86±1.32 in teaching abilities, 8.14±0.89 in leadership evaluation. Scales as chief resident assistants were 8.44±1.26. Sixteen respondents (72.7%) considered that pre-job training by attending doctors was necessary. Another 8 (36.4%) respondents addressed their demands on training of teaching skills. Conclusions: The senior resident training program "resident team leader in the Department of General Internal Medicine" improves the competency of rotated senior residents. It is a valuable pilot study on senior resident training and worthy of further application in other departments and hospitals.

In situ study on surface roughening in radiation-resistant Ag nanowires.

Metallic materials subjected to heavy ion irradiation experience significant radiation damage. Free surface is a type of effective defect sinks to improve the radiation resistance in metallic materials. However, the radiation resistance of metallic nanowires (NWs) is largely unknown. Here we show, via in situ Kr ion irradiations in a transmission electron microscope, Ag NWs exhibited much better radiation resistance than coarse-grained Ag. Irradiation-induced prominent surface roughening in Ag NWs provides direct evidence for interaction between defect clusters and free surface. Diameter dependent variation of the surface roughness in irradiated Ag NWs has also been observed. This study provides insight on mechanisms of enhanced radiation resistance via free surfaces in metallic NWs.

[Application and prospect of artificial intelligence in cancer diagnosis and treatment].

Artificial intelligence is a man-made device that simulates intellectual work such as human thinking and judgment. There are many successful applications of artificial intelligence in the fields of medicine, healthcare, agriculture, education, finance, service, news and machinery. Intelligent computer hospital management systems, intelligent medical diagnostic expert systems and intelligent surgical robots have revolutionized the medical field. Therefore, the attentions which are paid to artificial intelligence in cancer diagnosis and cancer treatment are on the rise. Some breakthroughs have also been made in the application of imaging diagnosis, pathological diagnosis, oncology surgery, oncology radiotherapy, drug development and cancer screening. Artificial intelligence is gradually changing the traditional medical model, which is a future direction and trend of human medical development. Here, we delineate the concept and development of artificial intelligence, and its application and prospect in the diagnosis and treatment of malignant tumors.

[An analysis of residents' self-evaluation and faculty-evaluation in internal medicine standardized residency training program using Milestones evaluation system].

Objective: To assess the value of internal medicine residency training program at Peking Union Medical College Hospital (PUMCH), and the feasibility of applying revised Milestones evaluation system. Methods: Postgraduate-year-one to four (PGY-1 to PGY-4) residents in PUMCH finished the revised Milestones evaluation scales in September 2017. Residents' self-evaluation and faculty-evaluation scores were calculated. Statistical analysis was conducted on the data. Results: A total of 207 residents were enrolled in this cross-sectional study. Both self and faculty scores showed an increasing trend in senior residents. PGY-1 residents were assessed during their first month of residency with scores of 4 points or higher, suggesting that residents have a high starting level. More strikingly, the mean score in PGY-4 was 7 points or higher, proving the career development of residency training program. There was no statistically significant difference between total self- and faculty-evaluation scores. Evaluation scores of learning ability and communication ability were lower in faculty group (t=-2.627, -4.279, all P<0.05). The scores in graduate students were lower than those in standardized training residents. Conclusions: The goal of national standardized residency training is to improve the quality of healthcare and residents' career development. The evaluation results would guide curriculum design and emphasize the importance and necessity of multi-level teaching. Self-evaluation contributes to the understanding of training objectives and personal cognition.

[Relationships between percentage of skeletal muscle mass and cardiorespiratory fitness in elderly patients with coronary heart disease].

Objective: To determine the relative percentage of skeletal muscle mass (SMM) in elderly patients with coronary heart disease, analyse the relationship between percentage of SMM and cardiorespiratory fitness (CRF), predict exercise capacity and cardiac reserve. Methods: Patients aged 65 years and over after PCI, receiving cardiopulmonary exercise testing (CPET) during February 2014 to December 2016 in Department of Cardiology at Peking University Third Hospital were enrolled.All patients' basic data, percentage of SMM and CPET related parameters, including peak oxygen uptake (VO(2)peak), oxygen pulse (VO(2)/HR), oxygen uptake efficiency slope (OUES) and other cardiorespiratory endurance indicators were collected, to do correlation analysis. Results: There were 402 patients enrolled, with average age (71±5) years, including 283 cases of male (70.40%) and 119 cases of female patients (29.60%). There were 62 patients with acute myocardial infarction (15.42%), 113 patients with old myocardial infarction (28.11%), and 227 patients diagnosed with angina pectoris (56.47%). The percentage of SMM was correlated to CRF.The percentage of SMM[97.00 (92.05, 102.10)%] and VO(2)/HR (r=0.231, P<0.001) and OUES (r=0.264, P<0.001) were positively correlated.Body mass index was negatively correlated with VO(2)peak(r=-0.162, P=0.001). Visceral fat area (VFA) was also negatively correlated with VO(2)peak(r=-0.126, P=0.016). Multiple linear regression analysis showed that Body mass index and VFA were negatively correlated with VO(2)peak (r=-0.204, P=0.014; r=-0.031, P=0.013). The percentage of SMM was positively independently correlated with OUES(r=11.020, P<0.001). Conclusions: Muscle content is positively correlated with exercise capacity of patients.The percentage of skeletal muscle mass determines the core index of cardiorespiratory fitness, such as the slope of oxygen pulse and oxygen uptake efficiency.These indexes can be used as an important criterion for predicting and guiding rehabilitation exercise in patients with coronary heart disease.

[EMA/CO regimen for chemotherapy 24 patients with ultra high-risk gestational trophoblastic neoplasia].

Objective: To evaluate etoposide, methotrexate and dactinomycin (EMA) /cyclophosphamide and vincristine (CO) regimen for treatment of ultra high-risk gestational trophoblastic neoplasia (GTN) . Methods: A total of twenty-four ultra high-risk patients who had International Federation of Gynecology and Obstetrics (FIGO) prognostic scores greater or equal to 12 with liver, brain, or extensive metastases did poorly when treated with primary chemotherapy admitted in Women's Hospital, School of Medicine, Zhejiang University from January 2001 to December 2015. All of the patients were treated by EMA/CO regimen and followed up to death or December 2017. The clinical data of patients were analyzed retrospectively and the efficacy and toxicity of EMA/CO were evaluated. Results: All of the cases with ultra high-risk GTN had FIGO prognostic scores ≥12 (ranged 12-18, median 13.0) . Twenty patients (83%, 20/24) received EMA/CO regimen as primary treatment and 4 patients (17%, 4/24) had a history of failed chemotherapy. Seven patients (29%, 7/24) had metastasis of liver or brain and 17 patients (71%, 20/24) had no metastasis of liver and brain. Twenty-four patients received totally 167 courses of EMA/CO regimen (average 7.0 courses) . Sixteen patients achieved complete remission and 8 patients showed drug-resistant. The complete remission rate was 67% (16/24) and the resistance rate was 33% (8/24) . Of the 16 patients who got complete remission, 6 cases were treated with EMA/CO regimen alone, and 10 cases were treated by chemotherapy combined with surgery. For the 8 patients who showed drug-resistant to EMA/CO, 5 cases of them received EMA/etoposide and cisplatin (EP) regimen and 3 cases got remission, 1 case received methotrexate, dactinomycin and cyclophosphamide (MAC) regimen and got remission, 2 cases gave up treatment because of economic factors. The side effects of EMA/CO mainly included Ⅲ-Ⅳ degree neutropenia, anemia and alopecia. The incidence of Ⅲ-Ⅳ degree neutropenia during the treatment of EMA/CO was 21.6% (36/167) , the incidence of anemia was 96.4% (161/167) , and the incidence of alopecia was 60.5% (101/167) . In these 24 ultra high-risk GTN patients, 4 patients died during follow-up. In the 20 patients who got complete remission, no recurrence or secondary tumor by chemotherapy were occurred. Conclusion: EMA/CO is an effective regimen with manageable toxicity for patients with ultra high-risk GTN.