Rational engineering strategies for achieving high-yield, high-quality and high-stability of natural product production in actinomycetes.

Actinomycetes are recognized as excellent producers of microbial natural products, which have a wide range of applications, especially in medicine, agriculture and stockbreeding. The three main indexes of industrialization (titer, purity and stability) must be taken into overall consideration in the manufacturing process of natural products. Over the past decades, synthetic biology techniques have expedited the development of industrially competitive strains with excellent performances. Here, we summarize various rational engineering strategies for upgrading the performance of industrial actinomycetes, which include enhancing the yield of natural products, eliminating the by-products and improving the genetic stability of engineered strains. Furthermore, the current challenges and future perspectives for optimizing the industrial strains more systematically through combinatorial engineering strategies are also discussed.

Comprehensive dissection of dispensable genomic regions in Streptomyces based on comparative analysis approach.

BACKGROUND: Large-scale genome reduction has been performed to significantly improve the performance of microbial chassis. Identification of the essential or dispensable genes is pivotal for genome reduction to avoid synthetic lethality. Here, taking Streptomyces as an example, we developed a combinatorial strategy for systematic identification of large and dispensable genomic regions in Streptomyces based on multi-omics approaches. RESULTS: Phylogenetic tree analysis revealed that the model strains including S. coelicolor A3(2), S. albus J1074 and S. avermitilis MA-4680 were preferred reference for comparative analysis of candidate genomes. Multiple genome alignment suggested that the Streptomyces genomes embodied highly conserved core region and variable sub-telomeric regions, and may present symmetric or asymmetric structure. Pan-genome and functional genome analyses showed that most conserved genes responsible for the fundamental functions of cell viability were concentrated in the core region and the vast majority of abundant genes were dispersed in the sub-telomeric regions. These results suggested that large-scale deletion can be performed in sub-telomeric regions to greatly streamline the Streptomyces genomes for developing versatile chassis. CONCLUSIONS: The integrative approach of comparative genomics, functional genomics and pan-genomics can not only be applied to perform a multi-tiered dissection for Streptomyces genomes, but also work as a universal method for systematic analysis of removable regions in other microbial hosts in order to generate more miscellaneous and versatile chassis with minimized genome for drug discovery.

Remnant lipoproteins play an important role of in-stent restenosis in type 2 diabetes undergoing percutaneous coronary intervention: a single-centre observational cohort study.

BACKGROUND: Increasing evidence has suggested that the presence of remnant lipoproteins is a significant risk factor for atherosclerosis. Remnant lipoproteins are lipoproteins that are rich in triglycerides (TGs), and the main components include very-low-density lipoprotein (VLDL) in the fasting state. Diabetic patients often have hypertriglyceridemia with elevated levels of VLDL cholesterol but normal levels of low-density lipoprotein cholesterol (LDL-C). The aim of the present study was to elucidate the potential role of remnant lipoproteins-induced atherosclerosis in the occurrence and development of in-stent restenosis (ISR) in diabetic patients with coronary artery disease. METHODS: The present study enrolled 2312 patients with type 2 diabetes mellitus who underwent percutaneous coronary intervention from January 2013 to December 2014 and who were followed up by angiography. Patients were divided into two groups based on the presence or absence of ISR, and multivariate Cox's proportional hazards regression modelling showed that remnant-like particle cholesterol (RLP-C) was an independent risk factor for ISR. According to the receiver operating characteristic curve, the optimal cutoff point of the RLP-C was identified, and the patients were further divided into 2 groups. Propensity score matching analysis was performed, and 762 pairs were successfully matched. Log-rank tests were used to compare Kaplan-Meier curves for overall follow-up to assess ISR. RESULTS: The multivariate Cox's proportional hazards regression analysis showed that RLP-C was independently associated with ISR, and the baseline RLP-C level at 0.505 mmol/L was identified as the optimal cutoff point to predict ISR. Patients were divided into 2 groups by RLP levels. After propensity score matching analysis, a total of 762 pairs matched patients were generated. Kaplan-Meier curves showed that the estimated cumulative rate of ISR was significantly higher in patients with RLP-C levels ≥ 0.505 mmol/L (log-rank P < 0.001; HR equal to 4.175, 95% CI = 3.045-5.723, P < 0.001) compared to patients with RLP-C levels < 0.505 mmol/L. CONCLUSIONS: The present study emphasized the importance of remnant-like particle cholesterol in cardiovascular pathology in diabetic patients. Physicians should take measures to control RLP-C below the level of 0.505 mmol/L to better prevent of in-stent restenosis in diabetic patients.

FadR1, a pathway-specific activator of fidaxomicin biosynthesis in Actinoplanes deccanensis Yp-1.

Fidaxomicin, an 18-membered macrolide antibiotic, is highly active against Clostridium difficile, the most common cause of diarrhea in hospitalized patients. Though the biosynthetic mechanism of fidaxomicin has been well studied, little is known about its regulatory mechanism. Here, we reported that FadR1, a LAL family transcriptional regulator in the fidaxomicin cluster of Actinoplanes deccanensis Yp-1, acts as an activator for fidaxomicin biosynthesis. The disruption of fadR1 abolished the ability to synthesize fidaxomicin, and production could be restored by reintegrating a single copy of fadR1. Overexpression of fadR1 resulted in an approximately 400 % improvement in fidaxomicin production. Electrophoretic mobility shift assays indicated that fidaxomicin biosynthesis is under the control of FadR1 through its binding to the promoter regions of fadM, fadA1-fadP2, fadS2-fadC, and fadE-fadF, respectively. And the conserved binding sites of FadR1 within the four promoter regions were determined by footprinting experiment. All results indicated that fadR1 encodes a pathway-specific positive regulator of fidaxomicin biosynthesis and upregulates the transcription levels of most of genes by binding to the four above intergenic regions. In summary, we not only clearly elucidate the regulatory mechanism of FadR1 but also provide strategies for the construction of industrial high-yield strain of fidaxomicin.

Nation wide epidemiological survey of primary palmar hyperhidrosis in the People's Republic of China.

OBJECTIVE: To investigate the prevalence and epidemiological characteristics of primary palmar hyperhidrosis (PPH) among adolescents in PR China. METHODS: A nationwide survey was performed, including all seven geological areas of Mainland China. Stratified cluster sampling was performed, and a cross-sectional epidemiological survey was applied via questionnaire among 10,000 college students in each geological area. RESULTS: The prevalence rate of PPH was 2.08%. The prevalence in female adolescents was slightly higher than the prevalence in male adolescents (2.29 vs. 1.94%). The prevalence of PPH in coastal areas was higher than the prevalence of PPH in inland areas (2.81 vs. 1.53%). The peak age of onset is 7-15 years, accounting for 97.3% of the PPH population. Positive family history was found in 25.40% of PPH cases. In addition to palms, axillae and soles can also be affected. CONCLUSIONS: PPH affects a larger group of individuals than previously reported. More measures should be taken to enhance the recognition, diagnosis, and treatment of PPH.

Development and implementation of a high-fidelity simulation training course for medical and nursing collaboration based on the Fink integrated course design model.

Aim: The purpose of this study is to examine the design and implementation of a high-fidelity simulation training course for medical and nursing collaboration, based on the Fink integrated course design model. Additionally, the study aims to validate the teaching effectiveness of the course. Background: Previous empirical studies have highlighted the effectiveness of collaborative healthcare education in institutional teaching and hospital training. However, the development of healthcare collaborative education in China has been slow to develop in China. In recent years, Chinese nursing educators and researchers have shown interest in utilizing high-fidelity simulators for healthcare collaborative education. These simulators help address the limitations of traditional nursing teaching and healthcare separation simulation. Nevertheless, a standardized simulation interprofessional education curriculum is still lacking. Therefore, nursing educators need to develop a standardized high-fidelity simulation training curriculum for healthcare collaboration, guided by established science curriculum development theories. Methods: A high-fidelity simulation training course on healthcare collaboration was designed based on the Fink integrated curriculum design model. The course was taught to 14 nursing students and 8 clinical medicine students from March to July 2022. To comprehensively evaluate the effectiveness of the healthcare collaboration high-fidelity simulation training course, several assessment tools were used. These included course grades, satisfaction and self-confidence scales, simulation teaching practice scales, healthcare collaboration attitude scales, critical thinking skills scales, and semi-structured interviews. Results: After the course was implemented, students demonstrated high overall scores (79.19 ± 5.12) and reported high satisfaction ratings (4.44 ± 0.37). They also exhibited increased self-confidence (4.16 ± 0.33). Additionally, students evaluated all four dimensions of the course teaching practice scale positively. Furthermore, the study demonstrated significant improvements in various aspects, such as attitudes toward medical and nursing collaboration (t = -7.135, P < 0.01), shared education and teamwork (t = -3.247, P = 0.002), job autonomy for nurses (t = -1.782, P = 0.000), and reduced physician dominance (t = -6.768, P = 0.000). The critical thinking skills of the students showed significant improvement, with higher scores in truth-seeking (t = -3.052, P = 0.004), analytical ability (t = -2.561, P = 0.014), systematic ability (t = -3.491, P = 0.001), self-confidence in critical thinking (t = -4.024, P = 0.000), and curiosity (t = -5.318, P = 0.000) compared to their scores before the course (all P < 0.05). The interviews showed that the course's student-centered approach enabled active learning. Students suggested enhancing teaching cases and allocating more time for reflection and summarization. Conclusion: The study successfully designed a high-fidelity simulation training course for healthcare collaboration by utilizing the Fink integrated curriculum design model. The findings provide valuable insights for the development of standardized curricula and healthcare collaboration education in China. Moreover, the course adheres to best practice principles, fostering improved attitudes toward healthcare collaboration and enhancing students' healthcare collaboration and clinical thinking skills.

Stepwise increase of fidaxomicin in an engineered heterologous host Streptomyces albus through multi-level metabolic engineering.

The anti-Clostridium difficile infection (CDI) drug fidaxomicin is a natural polyketide metabolite mainly produced by Micromonosporaceae, such as Actinoplanes deccanensis, Dactylosporangium aurantiacum, and Micromonospora echinospora. In the present study, we employed a stepwise strategy by combining heterologous expression, chassis construction, promoter engineering, activator and transporters overexpression, and optimization of fermentation media for high-level production of fidaxomicin. The maximum yield of 384 mg/L fidaxomicin was achieved with engineered Streptomyces albus D7-VHb in 5 L-tank bioreactor, and it was approximately 15-fold higher than the native strain Actinoplanes deccanensis YP-1 with higher strain stability and growth rate. This study developed an enhanced chassis strain, and for the first time, achieved the heterologous synthesis of fidaxomicin through a combinatorial metabolic engineering strategy.

[Surgical treatment for correcting abnormal complicated head posture in nystagmus].

OBJECTIVE: To demonstrate the surgical choices for patients with complicated head posture associated with nystagmus. METHODS: It was a retrospective clinical study. Thirty-eight cases of congenital nystagmus with abnormal head posture in all three axes without strabismus were retrospectively analyzed. Twenty-nine(76.32%) cases whose dominant head posture were with face turn, 3 cases (7.89%) with chin up or down , respectively, were performed horizontal null zone shift as well as vertical null zone transposition; 2 cases (5.26%) with head tilt as the dominant position were underwent one tendon width transposition of all four vertical muscles;4 cases (10.53%)basically with the same degree for face turn and chip up or down, 2 cases were preferred with recess a group of horizontal yoke muscles and a group of vertical yoke muscles, the other 2 cases were combined with weaken both synergistic oblique muscles. SPSS 13.0 was used to analyse the difference of them. RESULTS: In 29 patients with horizontal head posture dominanted, 15 cases (68.18%) with 25 °-30 ° in horizontal head posture were corrected completely, 5°-15° was the residue for 7 cases (31.82%) with 35 °- 40 °degree in horizontal before surgery. 15 °-20° was residue for 3 cases larger than 40 ° before operation after modified Parks procedure. Anderson procedure can correct the angle of 15°-20° in 4 cases. The horizontal, vertical and torsional components of 22 cases whose predominant head posture were in horizontal with 25°-40° (3.18° ± 1.01°, 4.32° ± 1.14°, 4.55° ± 1.95°) were significantly reduced (t = 63.13, 3.57, 3.95;P < 0.01) after Parks procedure. Recession a group of vertical muscles 5mm or combined with oblique muscles in 3 patients could correct the 20° of vertical head posture, but the improvement of the other two axes was about 5°-10°.One tendon width transposition of all four vertical muscles in 2 cases could correct the 10° of head tilt and 10°-15°of chip up or down. Recession a group of horizontal and vertical muscles can correct 20°-25° of face turn and 20° of vertical head posture. CONCLUSIONS: When head turn with 25°-40°predominates over the vertical and torsional components, recess the horizontal muscles could be effective way in diminishing the abnormal head position on all three axes.When vertical or torsional head posture predominates for the complicated nystagmus, individual designs should be considered.When necessary, reoperations should be needed.

Transcriptional regulation of the fidaxomicin gene cluster and cellular development in Actinoplanes deccanensis YP-1 by the pleiotropic regulator MtrA.

IMPORTANCE: Cascade regulation networks are almost present in various kinds of microorganisms, but locating and systematically elucidating specific pleiotropic regulators related to a certain gene cluster can be a tricky problem. Here, based on the promoter of the fidaxomicin pathway-specific regulator FadR1, we utilized a "DNA to Proteins" affinity purification method and captured a global regulator MtrA, which positively regulates fidaxomicin biosynthesis. In the mtrA overexpressed strain, the production of fidaxomicin was improved by 37% compared to the native strain. Then, we combined the "Protein to DNAs" affinity purification method (DAP-seq) with the results of RNA-seq and systematically elucidated the primary and secondary metabolic processes in which MtrA directly or indirectly participates. Thus, our work brought up a new way to improve fidaxomicin production from the perspective of global regulation and analyzed the regulatory mechanism of MtrA. Meanwhile, we provided a novel methodology for the research of cascade regulation networks and vital secondary metabolites.

Effect of Alirocumab on Coronary Calcification in Patients With Coronary Artery Disease.

Background: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been documented with significantly reduction in LDL cholesterol levels and cardiovascular events. However, evidence regarding the impact of PCSK9 inhibitors on coronary calcification is limited. Methods: Eligible patients with intermediate coronary lesions and elevated LDL cholesterol values were randomized to either alirocumab 75 mg Q2W plus statin (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) therapy or standard statin therapy. Calcium score based on coronary computed tomographic angiography at baseline and follow up were compared. Results: Compared with baseline levels, LDL cholesterol were significantly decreased in both groups, while the absolute reduction of LDL cholesterol levels were higher in patients treated with alirocumab (1.69 ± 0.52 vs. 0.92 ± 0.60, P < 0.0001). Additionally, patients in alirocumab group demonstrated a significant reduction of Lp(a) levels, whereas it was not observed in the standard statin group. Notably, greater increases in the percentage changes of CAC score (10.6% [6.3-23.3] vs. 2.9% [-6.7-8.3]; P < 0.0001) were observed in the statin group compared to the alirocumab group. Consistently, CAC progression was significantly lower in the alirocumab group than in the standard statin group (0.6 ± 2.2% vs. 2.7 ± 2.3%; P = 0.002). Conclusions: Study indicated that administration of the PCSK9 inhibitors to statins produced significantly lower rate of CAC progression in patients with coronary artery disease. Further studies with CAC progression and their clinical outcomes are needed. Trial Registration: ClinicalTrials.gov, Identifier: NCT04851769.

Control of Behavioral Arousal and Defense by a Glutamatergic Midbrain-Amygdala Pathway in Mice.

In response to external threatening signals, animals evolve a series of defensive behaviors that depend on heightened arousal. It is believed that arousal and defensive behaviors are coordinately regulated by specific neurocircuits in the central nervous system. The ventral tegmental area (VTA) is a key structure located in the ventral midbrain of mice. The activity of VTA glutamatergic neurons has recently been shown to be closely related to sleep-wake behavior. However, the specific role of VTA glutamatergic neurons in sleep-wake regulation, associated physiological functions, and underlying neural circuits remain unclear. In the current study, using an optogenetic approach and synchronous polysomnographic recording, we demonstrated that selective activation of VTA glutamatergic neurons induced immediate transition from sleep to wakefulness and obviously increased the amount of wakefulness in mice. Furthermore, optogenetic activation of VTA glutamatergic neurons induced multiple defensive behaviors, including burrowing, fleeing, avoidance and hiding. Finally, viral-mediated anterograde activation revealed that projections from the VTA to the central nucleus of the amygdala (CeA) mediated the wake- and defense-promoting effects of VTA glutamatergic neurons. Collectively, our results illustrate that the glutamatergic VTA is a key neural substrate regulating wakefulness and defensive behaviors that controls these behaviors through its projection into the CeA. We further discuss the possibility that the glutamatergic VTA-CeA pathway may be involved in psychiatric diseases featuring with excessive defense.

[Retrospective study on clinical characteristics and surgical treatment of bilateral DRS].

OBJECTIVE: To investigate the clinical characteristics and surgical treatment of bilateral Duane retraction syndrome. METHODS: To collect 24 cases with bilateral DRS among 123 cases with DRS from hospital data during 2005.7 to 2009.11. Retrospective study included the clinical types, characteristics, plus diseases and surgical treatments. RESULTS: Fourteen male cases (58.3%) and 10 female cases (41.7%), aging 2 to 23-year-old. 16 cases were type I (66.7%), 1 case was type II (4.2%). 7 cases were type III (29.1%), in which patients with esotropia or exotropia were 3 and 4 cases respectively. 11 cases had up- or down-shoot pre-operation, which disappeared or improved post-operation in 8 cases (73%). 15 cases had abnormal head posture (AHP) and AHP disappeared or improved in all. Seven cases (29%) were associated with other congenital ocular or systemic anomalies. For horizontal deviation, unilateral medial or lateral rectus weakening procedures were performed in 13 cases and bilateral procedures in 11 cases. Post-operation, horizontal deviation was less than ± 10(Δ) in 21 patients (91%), 1 case was under-corrected and 2 cases were overcorrected. Simultaneously, the restriction of ocular motility and global retraction were improved in all the patients. Additional vertical or oblique muscle procedures were performed in 4 patients among 7 with vertical deviation more than 10(Δ) and up- or down-shoot. CONCLUSIONS: Bilateral DRS has more frequency in male, obviously horizontal deviation in primary position and more cases with vertical deviation which is related with up- or down-shoot phenomenon. The key point for successful surgery are forced duction test pre- and during operation to conform to relieve the mechanical factor and estimating abnormal innervation in horizontal and vertical rectus.

Genome-based rational engineering of Actinoplanes deccanensis for improving fidaxomicin production and genetic stability.

Microbial fermentation is currently still the major way to produce structural complicated clinical drugs. Yet, the low productivity and genetic instability of producing strains remain the bottlenecks in microbial pharmaceutical industry. Fidaxomicin is a microbial drug against the Clostridium difficile infection. Here, a genome-based combinatorial engineering strategy was established to improve both fidaxomicin production and the genetic stability of Actinoplanes deccanensis YP-1. Guided by genomic analysis, several genetic instability-associated elements were cumulatively deleted, generating a more genetically stable mutant. Further rational engineering approaches including elimination of a pigment pathway, duplication of the fidaxomicin gene cluster, overexpression of a positive regulator and optimization of the fermentation medium, led to an overall 27-folds improvement in fidaxomicin production. Taken together, the genome-based rational combinatorial engineering strategy was efficient to enhance the fidaxomicin production and ameliorate the genetic stability of YP-1, it can also be widely used in other industrial actinomycetes for strain improvement.

Kinetic Characteristics of Neutralizing Antibody Responses Vary among Patients with COVID-19.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2. RESULTS: NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective. CONCLUSION: We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.

[Recombinant lentivirus-mediated gene transfer of NT4-p53(N15)-Ant inhibits the growth of hepatocellular carcinoma cells in vitro].

OBJECTIVE: To construct a recombinant lentivirus vector containing fusion gene NT4-p53(N15)-Ant and transfer it into HepG2 cancer cells for gene therapy. METHODS: The gene of p53(N15)-Ant was obtained by T-vector method. After restriction enzyme digestion, the interest gene of p53(N15)-Ant was inserted in pBV220/NT4 vector and fusion gene of NT4-p53(N15)-Ant was subcloned into the plasmid of lentivirus and cotransferred into HEK-293 cells with helper plasmid. The recombinant lentivirus was produced by homologous recombination of the above mentioned two plasmids in HEK-293 cells and its titer was measured by plaque-forming. The expression of LV. NT4-p53-Ant in transfected HepG2 cells was finally confirmed by reverse transcription polymerase chain reaction (RT-PCR) procedure. The effect of LV. NT4-p53(N15)-Ant on HepG2 cells was measured by a colorimetric 3-[4,5-dimethyl thiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibition effect on HepG2 cells of LV. NT4-p53(N15)-Ant and its potential mechanism was detected by light microscopy, electron microscopy, MTT, LDH-release assay and annexin V-PI double staining. RESULTS: The gene of p53(N15)-Ant was confirmed by restriction enzyme digestion and DNA sequencing. High titer of the recombinant lentivirus was obtained by homologous recombination in HEK-293 cell lines (1 x 10(11) pfu/ml), and the expression of NT4-p53(N15)-Ant gene in HepG2 cells was confirmed by RT-PCR. The viability of HepG2 cells was decreased to 83.4%, 46.9% and 33.9%, at 24 h, 48 h and 72 h, respectively, after infection by LV. NT4-p53(N15)-Ant. Compared with the LV. EGFP control group, there were significant differences (P < 0.01). The LDH level in HepG2 cells infected by LV. NT4-p53(N15)-Ant at 48 h, 72 h and 96 h after infection was 682 IU/L, 815 IU/L and 979 IU/L, respectively, significantly increased than that in the LV. EGFP group (P < 0.01), indicating the cell membrane destruction. CONCLUSION: The recombinant lentivirus vector encoding gene NT4-p53(N15)-Ant is successfully constructed in this experiment by molecular cloning and recombination in vitro techniques, and the results suggested that this fusion gene has an anti-tumor effect, which provides the basis for further research on recombinant adenovirus for cancer gene therapy.

[Effects of upstream tirofiban versus downstream tirofiban on platelet aggregation and clinical outcomes in patients with high-risk acute coronary syndromes undergoing percutaneous coronary interventions].

OBJECTIVE: To observe the effects of upstream versus downstream application of tirofiban on platelet aggregation and clinical outcomes (major adverse cardiovascular event, MACE) in patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). METHODS: From July 2006 to July 2007, 160 high-risk NSTE-ACS patients undergoing PCI were randomized to receive upstream (4-6 h prior PCI) tirofiban and downstream (immediately prior to PCI) tirofiban. Platelet aggregation inhibition was determined at admission, before coronary angiography and after PCI. Incidences of MACE at 1, 3, 7, 30 and 180 days after PCI were compared. The incidences of bleeding complications and thrombocytopenia during tirofiban treatments were recorded. RESULTS: The extent of platelet aggregation inhibition post tirofiban was significantly greater in upstream tirofiban than that in downstream tirofiban group (8% vs. 42%, P<0.05). The incidences of MACE at various time points were similar between the two groups (all P>0.05). Aging, hypertension and type-2 diabetes were independent risk factors of MACE. The incidences of major and minor bleeding complications as well as mild thrombocytopenia during tirofiban treatments were similar between the two groups (2.5% vs. 1.3%, 1.3% vs. 1.3% and 1.3% vs. 1.3%, respectively; all P>0.05). CONCLUSION: On top of aspirin and clopidogrel, upstream application of tirofiban is associated with increased platelet aggregation inhibition but the incidences of MACE up to 180 days post tirofiban are similar in the upstream and downstream tirofiban treated patients with high-risk NSTE-ACS after PCI. Aging, hypertension and type-2 diabetes were independent risk factors of MACE in these patients.

A sparse deep learning model for privacy attack on remote sensing images.

Deep learning tools have been a new way for privacy attacks on remote sensing images. However, since labeled data of privacy objects in remote sensing images are less, the samples for training are commonly small. Besides, traditional deep neural networks have a huge amount of parameters which leads to over complexity of models and have a great heavy of computation. They are not suitable for small sample image classification task. A sparse method for deep neural network is proposed to reduce the complexity of deep learning model with small samples. A singular value decomposition algorithm is employed to reduce the dimensions of the output feature map of the upper convolution layers, which can alleviate the input burden of the current convolution layer, and decrease a large number of parameters of the deep neural networks, and then restrain the number of redundant or similar feature maps generated by the over-complete schemes in deep learning. Experiments with two remote sensing image data sets UCMLU and WHURS show that the image classification accuracy with our sparse model is better than the plain model,which is improving the accuracy by 3%,besides, its convergence speed is faster.

Diagnostic accuracy of a deep learning approach to calculate FFR from coronary CT angiography.

BACKGROUND: The computational fluid dynamics (CFD) approach has been frequently applied to compute the fractional flow reserve (FFR) using computed tomography angiography (CTA). This technique is efficient. We developed the DEEPVESSEL-FFR platform using the emerging deep learning technique to calculate the FFR value out of CTA images in five minutes. This study is to evaluate the DEEPVESSEL-FFR platform using the emerging deep learning technique to calculate the FFR value from CTA images as an efficient method. METHODS: A single-center, prospective study was conducted and 63 patients were enrolled for the evaluation of the diagnostic performance of DEEPVESSEL-FFR. Automatic quantification method for the three-dimensional coronary arterial geometry and the deep learning based prediction of FFR were developed to assess the ischemic risk of the stenotic coronary arteries. Diagnostic performance of the DEEPVESSEL-FFR was assessed by using wire-based FFR as reference standard. The primary evaluation factor was defined by using the area under receiver-operation characteristics curve (AUC) analysis. RESULTS: For per-patient level, taking the cut-off value ≤ 0.8 referring to the FFR measurement, DEEPVESSEL-FFR presented higher diagnostic performance in determining ischemia-related lesions with area under the curve of 0.928 compare to CTA stenotic severity 0.664. DEEPVESSEL-FFR correlated with FFR (R = 0.686, P < 0.001), with a mean difference of -0.006 ± 0.0091 (P = 0.619). The secondary evaluation factors, indicating per vessel accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 87.3%, 97.14%, 75%, 82.93%, and 95.45%, respectively. CONCLUSION: DEEPVESSEL-FFR is a novel method that allows efficient assessment of the functional significance of coronary stenosis.

A new deep learning model for assisted diagnosis on electrocardiogram.

In order to enhance the accuracy of computer aided electrocardiogram analysis, we propose a deep learning model called CBRNN to assist diagnosis on electrocardiogram for clinical medical service. It combines two sub networks which are convolutional neural network (CNN) and bi-directional recurrent neural network (BRNN). In the model, CNN with one-dimension convolution is employed to extract features for each lead of ECG, and BRNN is used to fuse features of different leads to represent deeper features. In the training step, we use more than 40 thousand training data and more than 19 thousand validation data to obtain the optimal parameters of the model. Besides, by validating our model on more than CCDD 120,000 real data, it achieves an 87.69% accuracy rate, higher than popular deep learning models such as CNN and ResNet. Our model has better accuracy than state-of-the-art models and it is also slightly higher than the average accuracy of human judgement. It can be served for the first round screening of ECG examination clinical diagnosis.

Epidemiological survey of primary palmar hyperhidrosis in adolescent in Fuzhou of People's Republic of China.

OBJECTIVE: To investigate the prevalence and epidemiological characteristics of primary palmar hyperhidrosis (PPH) among adolescents in Fuzhou City of PR China. METHODS: Stratified cluster sampling was carried out and a cross-sectional epidemiological survey by questionnaire was applied among 13,000 college and high school students. RESULTS: The prevalence rate of PPH was 4.59% affecting both sexes equally. The peak age of onset is 6-16 years, accounting for 95.6% of the PPH population. Positive family history was found in 15.3% PPH cases. Besides palms, axillae and soles can be also affected. CONCLUSIONS: PPH affects a larger group of individuals than previously reported. More measures should be taken to enhance the recognition, diagnosis, and treatment of PPH.