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OBJECTIVES: Compare the clinical practice and outcomes in severe community-acquired pneumonia (sCAP) patients to those in non-sCAP patients using guideline-defined criteria for sCAP. DESIGN: Retrospective observational cohort study. SETTING: One hundred seventy-seven U.S. hospitals within the Premier Healthcare Database. PATIENTS: Hospitalized adult (≥ 18 yr old) patients with pneumonia. MEASUREMENTS AND MAIN RESULTS: Adult patients (≥ 18 yr old) with a principal diagnosis of pneumonia or a secondary diagnosis of pneumonia paired with a principal diagnosis of sepsis or respiratory failure were included. Patients with at least one guideline-defined major criterion for severe pneumonia were compared with patients with nonsevere disease. Among 154,799 patients with pneumonia, 21,805 (14.1%) met criteria for sCAP. They had higher organ failure scores (1.9 vs 0.63; p < 0.001) and inpatient mortality (22.0 vs 5.0%; p < 0.001), longer lengths of stay (8 vs 5 d; p < 0.001), and higher costs ($20,046 vs $7,543; p < 0.001) than those with nonsevere disease. Patients with sCAP had twice the rate of positive blood cultures (10.0% vs 4.5%; p < 0.001) and respiratory cultures (34.2 vs 21.1%; p < 0.001) and more often had isolates resistant to first-line community-acquired pneumonia antibiotics (10% of severe vs 3.1% of nonsevere; p < 0.001). Regardless of disease severity, Streptococcus pneumoniae was the most common pathogen recovered from blood cultures and Staphylococcus aureus and Pseudomonas species were the most common pathogens recovered from the respiratory tract. Although few patients with sCAP had cultures positive for a resistant organism, 65% received vancomycin and 42.8% received piperacillin-tazobactam. CONCLUSIONS: sCAP patients had worse outcomes and twice the rate of culture positivity. S. aureus and S. pneumoniae were the most common organisms in respiratory and blood specimens, respectively. Although only recommended for sCAP patients, nearly all pneumonia patients received blood cultures, a quarter of nonsevere patients received sputum cultures, and treatment with broad-spectrum agents was widespread, indicating fertile ground for antimicrobial and diagnostic stewardship programs.

Dental biofilm is the initiating factor of oral diseases, such as periodontitis and caries. Orthodontic treatment could alter the microbiome structure balance, and increase the risk of such diseases. Furthermore, fixed appliances can induce temporary changes in the microbiome community, and the changes that clear aligners bring are smaller by comparison. Temporary anchorage devices (TADs) are skeletal anchorages that are widely used in orthodontic treatment. Microorganisms affect the occurrence and development of inflammation surrounding TADs. At present, existing researches have verified the existence of plaque biofilm on the surface of TADs, but the formation of plaque biofilm and plaque composition under different stable conditions have not been fully understood. The development of high-throughput sequencing, molecular biology experiments, and metabonomics have provided new research ideas to solve this problem. They can become an effective means to explore the microbiome surrounding TADs.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is derived from the bacterial innate immune system and engineered as a robust gene-editing tool. Due to the higher specificity and efficiency of CRISPR/Cas9, it has been widely applied to many genetic and non-genetic disease, including cancers, genetic hemolytic diseases, acquired immunodeficiency syndrome, cardiovascular diseases, ocular diseases, and neurodegenerative diseases, and some X-linked diseases. Furthermore, in terms of the therapeutic strategy of cancers, many researchers used the CRISPR/Cas9 technique to cure or alleviate cancers through different approaches, such as gene therapy and immune therapy.Here, we conclude the recent application and clinical trials of CRISPR/Cas9 in non-cancerous diseases and cancers and pointed out some of the problems to be solved.CRISPR/Cas9, derived from the microbial innate immune system, is developed as a robust gene-editing tool and has been applied widely. Due to its high accuracy and efficiency, CRISPR/Cas9 techniques may provide a great chance to treat some gene-related diseases by disrupting, inserting, correcting, replacing, or blocking genes for clinical application with gene therapy.

The complexity of the tumor microenvironment and the diversity of tumors seriously affect the therapeutic effect, the focus, therefore, has gradually been shifted from monotherapy to combination therapy in clinical research in order to improve the curative effect. The synergistic enhancement interactions among multiple monotherapies majorly contribute to the birth of the multi-mode cooperative therapy, whose effect of the treatment is clearly stronger than that of any single therapy. In addition, the accurate diagnosis of the tumour location is also crucial to the treatment. Bismuth-based nanomaterials (NMs) hold great properties as promising theranostic platforms based on their many unique features that include low toxicity, excellent photothermal conversion efficiency as well as the high ability of X-ray computed tomography imaging and photoacoustic imaging. In this review, we will introduce briefly the main features of the tumor microenvironment first and its effect on the mechanism of nanomedicine actions and present the recent advances of bismuth-based NMs for diagnosis and photothermal therapy-based combined therapies using bismuth-based NMs are presented, which may provide a new way for overcoming drug resistance and hypoxia. In the end, further challenges and outlooks regarding this promising field are discussed accompanied with some design tips for bismuth- based NMs, hoping to provide researchers some inspiration to design safe and effective nanotherapeutic agents for clinical treatments of cancers.

Soft robotic glove with brain computer interfaces (BCI) control has been used for post-stroke hand function rehabilitation. Motor imagery (MI) based BCI with robotic aided devices has been demonstrated as an effective neural rehabilitation tool to improve post-stroke hand function. It is necessary for a user of MI-BCI to receive a long time training, while the user usually suffers unsuccessful and unsatisfying results in the beginning. To propose another non-invasive BCI paradigm rather than MI-BCI, steady-state visually evoked potentials (SSVEP) based BCI was proposed as user intension detection to trigger the soft robotic glove for post-stroke hand function rehabilitation. Thirty post-stroke patients with impaired hand function were randomly and equally divided into three groups to receive conventional, robotic, and BCI-robotic therapy in this randomized control trial (RCT). Clinical assessment of Fugl-Meyer Motor Assessment of Upper Limb (FMA-UL), Wolf Motor Function Test (WMFT) and Modified Ashworth Scale (MAS) were performed at pre-training, post-training and three months follow-up. In comparing to other groups, The BCI-robotic group showed significant improvement after training in FMA full score (10.05 ± 8.03, p = 0.001), FMA shoulder/elbow (6.2 ± 5.94, p = 0.0004) and FMA wrist/hand (4.3 ± 2.83, p = 0.007), and WMFT (5.1 ± 5.53, p = 0.037). The improvement of FMA was significantly correlated with BCI accuracy (r = 0.714, p = 0.032). Recovery of hand function after rehabilitation of SSVEP-BCI controlled soft robotic glove showed better result than solely robotic glove rehabilitation, equivalent efficacy as results from previous reported MI-BCI robotic hand rehabilitation. It proved the feasibility of SSVEP-BCI controlled soft robotic glove in post-stroke hand function rehabilitation.

Background Calcified nodule (CN) is a type of potentially vulnerable plaque. Its formation mechanism remains unknown. This study was to assess serum marker and computed tomography angiography (CTA) characteristics of CN validated by intravascular ultrasound (IVUS). Methods Patients who underwent coronary CTA followed by invasive coronary angiography and IVUS were retrospectively analyzed. Serum levels of alkaline phosphatase (ALP), gamma-glutamyltransferase, and calcium were collected. Results IVUS detected 128 de novo calcified lesions in 79 patients with coronary artery disease (CAD). CNs were identified in 11.4% (9/79) of patients and 9.4% (12/128) of lesions. Compared with patients with non-nodular calcified plaques, CN patients had higher serum level of ALP (82.00 vs 65.00 U/L, P = 0.022) and total plaque volume (673.00 vs 467.50 mm3, P = 0.021). Multivariable analyses revealed that serum ALP level and total plaque volume were independently associated with the prevalence of CN in CAD patients with calcified plaques. At lesion level, the CN group had a higher frequency of moderate to heavy calcification on angiography (75.00% vs 40.52%, P = 0.017). In terms of CTA characteristics, plaques with CN had a more severe diameter stenosis (79.00% vs 63.00%, P = 0.007), higher plaque burden (85.40% vs 77.05%, P = 0.005), total plaque density (398.00 vs 283.50 HU, P = 0.008), but lower lipid percentage (14.65% vs 19.75%, P = 0.010) and fiber percentage (17.90% vs 25.65%, P = 0.011). Mean plaque burden is an independent predictor of the prevalence of CN in calcified plaques (odds ratio = 1.102, 95% confidence interval: 1.025–1.185, P = 0.009). The AUC is 0.753 (95% confidence interval: 0.615–0.890, P = 0.004). When using 84.85% as the best cutoff value, the diagnostic sensitivity and specificity of mean plaque burden for predicting the presence of CN within calcified plaques were 66.7% and 80.2%, respectively. Conclusions CN had different CTA imaging features from non-nodular coronary calcification. The presence of a CN was associated with a higher serum ALP level and plaque burden.

Changes in diastolic blood pressure (DBP) are common in patients with acute myocardial infarction (AMI). The relationship between the dynamic change of DBP and in-hospital mortality among patients with AMI remains unclear. This study aimed to explore the importance of DBP during disease development among patients with AMI. We performed a retrospective cohort study involving patients from the Medical Information Mart for Intensive Care III database, which included40,000 patients admitted to the intensive care unit (ICU). Overall, 3209 adult AMI admissions were identified. We extracted the clinical and laboratory information in the patients with AMI. Cox proportional hazards models were used to evaluate the prognostic values of baseline DBP. We used the generalized additive mixed model (GAMM) to compare trends in DBP over time among survivors and non-survivors, after adjusting for potential confounders. During the ICU stay, 189 patients died (mortality rate, 6.36%). The age of each non-survivor together with the variations in DBP over time from admission to the time of death is of great importance to the scientific community. Cox multivariable regression analysis displayed that after adjusting for confounding factors, ascended baseline DBP was an important hazard factor for hospital deaths (hazard ratio, 1.02; 95% confidence interval, 1.01-1.03; P = .003). Based on GAMM, DBP in the death group was markedly lower than that of the surviving group. Moreover, the difference between the two groups showed an increasing trend within 3 days after ICU admission. After adjusting for various variables, the results were stable. DBP significantly contributed to in-hospital mortality among patients with AMI. There was a nonlinear correlation between baseline DBP and in-hospital mortality among patients with AMI, and the DBP of the non-survivors decreased within the first 3 days after ICU admission. However, the causality cannot be deduced from our data.

Few studies have simultaneously examined the influence of clinical characteristics of patients with pneumonia, the vancomycin pharmacokinetic/pharmacodynamic (PK/PD) index, and the phenotypic and genetic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains. We assessed risk factors for vancomycin failure in patients with MRSA pneumonia by analyzing these influences in a prospective multicenter study.

Each vertebrate species appears to have a unique timing mechanism for forming somites along the vertebral column, and the process in human remains poorly understood at the molecular level due to technical and ethical limitations. Here, we report the reconstitution of human segmentation clock by direct reprogramming. We first reprogrammed human urine epithelial cells to a presomitic mesoderm (PSM) state capable of long-term self-renewal and formation of somitoids with an anterior-to-posterior axis. By inserting the RNA reporter Pepper into HES7 and MESP2 loci of these iPSM cells, we show that both transcripts oscillate in the resulting somitoids at ~5 h/cycle. GFP-tagged endogenous HES7 protein moves along the anterior-to-posterior axis during somitoid formation. The geo-sequencing analysis further confirmed anterior-to-posterior polarity and revealed the localized expression of WNT, BMP, FGF, and RA signaling molecules and HOXA-D family members. Our study demonstrates the direct reconstitution of human segmentation clock from somatic cells, which may allow future dissection of the mechanism and components of such a clock and aid regenerative medicine.

To study the correlation between CT imaging features of acceleration and deceleration brain injury and injury degree.A total of 299 cases with acceleration and deceleration brain injury were collected and divided into acceleration brain injury group and deceleration brain injury group according to the injury mechanism. Subarachnoid hemorrhage (SAH) and Glasgow coma scale (GCS), combined with skull fracture, epidural hematoma (EDH), subdural hematoma (SDH) and brain contusion on the same and opposite sides of the stress point were selected as the screening indexes.EDH on the same side of the stress point, brain contusion on the opposite of the stress point and GCS can be used as key indicators to distinguish acceleration and deceleration injury mechanism. In addition, skull fracture on the same side of the stress point, EDH and SDH on the opposite of the stress point and SAH were relatively weak indicators in distinguishing acceleration and deceleration injury mechanism.

To apply the convolutional neural network (CNN) Inception_v3 model in automatic identification of acceleration and deceleration injury based on CT images of brain, and to explore the application prospect of deep learning technology in forensic brain injury mechanism inference.CT images from 190 cases with acceleration and deceleration brain injury were selected as the experimental group, and CT images from 130 normal brain cases were used as the control group. The above-mentioned 320 imaging data were divided into training validation dataset and testing dataset according to random sampling method. The model classification performance was evaluated by the accuracy rate, precision rate, recall rate,In the training process and validation process, the accuracy rate of the model to classify acceleration injury, deceleration injury and normal brain was 99.00% and 87.21%, which met the requirements. The optimized model was used to test the data of the testing dataset, the result showed that the accuracy rate of the model in the test set was 87.18%, and the precision rate, recall rate,Inception_v3 model has potential application value in distinguishing acceleration and deceleration injury based on brain CT images, and is expected to become an auxiliary tool to infer the mechanism of head injury.

To understand the perceptions of doctors, patients and forensic examiners on the current situation of medical disputes and medical damage identification in China, and to explore the medical damage identification model that is more conducive for the resolution of medical disputes.A questionnaire was designed, and in-service clinicians, forensic examiners and inpatients in Sichuan Province and Chongqing City were randomly selected from April to November 2019. SPSS 22.0 software was used to analyze the data of various survey results.Compared with patients (24.92%), doctors (61.72%) believed that the current doctor-patient relationship was more tense than before; both doctors and patients were more inclined to choose voluntary consultation and people's mediation to resolve medical disputes; forensic examiners have the highest level of cognition of medical and health-related laws and regulations, followed by doctors and patients; 66.72% of doctors and 78.41% of patients believed that medical damage identification was necessary, and they were more inclined to entrust forensic identification institutions; different groups all believed that forensic examiners and doctors should participate in the identification together, 80.94% of doctors believed that the appraisal institutions should be responsible for the forensic opinion, not the appraiser.It is suggested that the Medical Association identification and forensic identification should learn from each other and formulate basic unified rules for the identification of medical damage. It is suggested to standardize the behavior of medical damage forensic identification institutions and appraisers, to improve their own appraisal level, actively invite clinical medical experts for consultation in identification, and promote the standardized, scientization of forensic identification.

Functional complete revascularization (FCR) after percutaneous coronary intervention (PCI) as determined by the residual functional SYNTAX score (rFSS) based on pressure wire fractional flow reserve assessment has been associated with an improved prognosis.This study sought to determine the rates and clinical implications of FCR as assessed by the quantitative flow ratio (QFR), and to determine the outcomes of pre-PCI QFR guidance compared with standard angiography guidance in patients achieving and not achieving FCR after PCI.In the randomized, sham-controlled, blinded, multicenter FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial, QFR-guided PCI reduced the 1-year rate of major adverse cardiac events (MACE) compared with angiography-guided PCI. In the present prespecified substudy, the incidence of MACE was compared according to the presence of post-PCI FCR (rFSS = 0 based on core laboratory-assessed QFR) in the QFR-guided and angiography-guided groups.Among 3,781 patients with available rFSS assessments, 3,221 (85.2%) achieved FCR, including 88.1% after QFR guidance and 82.2% after angiography guidance (P 0.001). Patients with FCR had a markedly lower rate of 1-year MACE compared with those with functional incomplete revascularization (FIR) (rFSS ≥1) (5.1% vs 19.7%; P 0.001). Prognostic models including the rFSS had higher discrimination and reclassification ability than those with the anatomic residual SYNTAX score. The relative risks for 1-year MACE with QFR-guided compared with the angiography-guided lesion selection were consistent in patients achieving FCR (4.1% vs 6.3%; HR: 0.65; 95% CI: 0.47-0.88) and in those with FIR (18.7% vs 20.4%; HR: 0.90; 95% CI: 0.61-1.32) (PIn this large-scale trial, achieving FCR after PCI was associated with markedly lower 1-year rates of MACE. Compared with standard angiography guidance, QFR-guided PCI lesion selection improved the likelihood of achieving FCR and improved 1-year clinical outcomes in patients with both FCR and FIR.

Objective To investigate the radioactivity of 131-iodine (

To explore the application value of virtual autopsy to obtain key evidence information on drowned corpses and its application value of virtual autopsy in the diagnosis of drowning.In this study, 7 corpses were selected as the research objects. The image data of corpses were collected by computed tomography (CT) before conventional autopsy. The characteristics of corpses were observed through image reading, combined with virtual measurement indexes, and compared with 15 non-drowned corpses.The postmortem CT of drowning showed the more fluid in respiratory tract than the non-drowning, and ground-glass opacities in the lung. The statistical volume of fluid in the sinus (maxillary sinus and sphenoid sinus) was (10.24±4.70) mL in drowning cases and (2.02±2.45) mL in non-drowning cases. The average CT value of fluid in the sinus, left atrial blood and gastric contents in drowning cases were (15.91±17.20), (52.57±9.24) and (10.33±12.81) HU, respectively, which were lower than those in non-drowning cases (The comprehensive consideration of multiple characteristic image manifestations and the virtual measurement indexes are helpful to the forensic pathological diagnosis of drowning. Virtual autopsy can be used as an auxiliary method in the forensic diagnosis of drowning.

Guidelines recommend testing hospitalized patients with community-acquired pneumonia (CAP) for Legionella pneumophila only if the infection is severe or risk factors are present. There are no validated models for predicting Legionella.To derive and externally validate a model to predict a positive Legionella test.Diagnostic study of adult inpatients with pneumonia using data from 177 US hospitals in the Premier Healthcare Database (training and hold-out validation sets) and 12 Cleveland Clinic Health System (CCHS) hospitals (external validation set). We used multiple logistic regression to predict positive Legionella tests in the training set, and evaluated performance in both validation sets.The outcome was a positive Legionella test. Potential predictors included demographics and co-morbidities, disease severity indicators, season, region, and presence of a local outbreak.Of 166,689 patients hospitalized for pneumonia, 43,070 were tested for Legionella and 642 (1.5%) tested positive. The strongest predictors of a positive test were a local outbreak (odds ratio [OR], 3.4), June-October occurrence (OR, 3.4), hyponatremia (OR, 3.3), smoking (OR, 2.4), and diarrhea (OR, 2.0); prior admission within 6 months (OR, 0.27) and chronic pulmonary disease (OR, 0.49) were associated with a negative test. Model c-statistics were 0.79 in the Premier and 0.77 in the CCHS validation samples. High-risk patients were only slightly more likely to have been tested than lower-risk patients. Compared to actual practice, the model-based testing strategy detected twice as many cases.Although Legionella is an uncommon cause of pneumonia, patient characteristics can identify individuals at high risk, allowing for more efficient testing.

To compare the clinical effect of wheat grain moxibustion combined with rehabilitation training and simple rehabilitation training on finger spasm after stroke.A total of 80 patients with finger spasm after stroke were randomly divided into an observation group and a control group, 40 cases in each group. The control group was given routine rehabilitation training, once a day, 30 min each time. The observation group was given wheat grain moxibustion at Shixuan (EX-UE 11) on the basis of the control group, 8~10 moxibustion cones at each point, once a day. Both groups were treated for 6 days as one course of treatment for 4 courses. The motor function of the affected hand (Fugl-Meyer assessment [FMA] score) and muscle tension (modified Ashworth scale [MAS] grading), surface EMG indexes (wrist dorsiflexor muscle and flexor carpal metacarpal muscle mean square [RMS] value), hand muscle strength (neurological deficit score [NDS]) and daily living ability (modified Barthel index [MBI] score) were compared between the two groups before and after treatment, and clinical efficacy was evaluated.After treatment, FMA and MBI scores in the 2 groups were increased compared with before treatment (Wheat grain moxibustion at Shixuan (EX-UE 11) combined with rehabilitation training can improve the hand motor function and daily living ability of patients with finger spasm after stroke, improve the degree of spasm and the function of wrist dorsiflexor muscle and flexor carpal metacarpal muscle, the clinical effect is better than simple rehabilitation training.

Hepatic iron overload is a universal phenomenon in patients with myelodysplastic syndromes (MDS) who undergo bone marrow transplantation and may experience the toxicity of peri- and post-bone marrow transplantation. To clarify the mechanisms of iron overload-triggered liver injury, we determined the effects of iron overload on changes in protein phosphorylation in human hepatocyte cell line HH4 in vitro by using a phosphoproteomics approach. The hepatocytes were exposed to high concentrations of ferric ammonium citrate (FAC) to build up an iron overload model in vitro. Changes in protein phosphorylation initiated by iron overloading were studied by 2D-LC/MS. We identified 335 differentially expressed phosphorylated proteins under the condition of excess hepatocyte iron, 11% of which were related to cell cycle progression. The results of phosphoproteomics showed that iron overload induced 10.9 times increase in Thr 14/Tyr 15-phosphorylated Cdk1 in HH4 cells. Flow cytometry analysis revealed that FAC-treated HH4 cells showed significant G2/M phase arrest. Our subsequent RT-PCR and Western blot experiments indicated that FAC-induced G2/M phase arrest was related to the activation of p53-p21-Cdk1, p53-14-3-3 sigma-Cdk1, and 14-3-3 gamma pathway. Our findings demonstrate the first evidence that iron overload causes G2/M arrest in HH4 hepatocytes.

To evaluate the potential of MR elastography (MRE)-based shear strain mapping to noninvasively predict the presence of microvascular invasion (MVI) in hepatocellular carcinoma (HCC).Fifty-nine histopathology-proven HCC patients with conventional 60-Hz MRE examinations (+/-MVI, n = 34/25) were enrolled retrospectively between December 2016 and October 2019, with one subgroup comprising 29/59 patients (+/-MVI, n = 16/13) who also underwent 40- and 30-Hz MRE examinations. Octahedral shear strain (OSS) maps were calculated, and the percentage of peritumoral interface length with low shear strain (i.e., a low-shear-strain length, pLSL, %) was recorded. For OSS-pLSL, differences between the MVI (+) and MVI (-) groups and diagnostic performance at different MRE frequencies were analyzed using the Mann-Whitney test and area under the receiver operating characteristic curve (AUC), respectively.The peritumor OSS-pLSL was significantly higher in the MVI (+) group than in the MVI (-) group at the three frequencies (all p0.01). The AUC of peritumor OSS-pLSL for predicting MVI was good/excellent in all frequency groups (60-Hz: 0.73 (n = 59)/0.80 (n = 29); 40-Hz: 0.84; 30-Hz: 0.90). On further analysis of the 29 cases with all frequencies, the AUCs were not significantly different. As the frequency decreased from 60-Hz, the specificity of OSS increased at 40-Hz (53.8-61.5%) and further increased at 30-Hz (53.8-76.9%), and the sensitivity remained high at lower frequencies (100.0-93.8%) (all p0.05).MRE-based shear strain mapping is a promising technique for noninvasively predicting the presence of MVI in patients with HCC, and the most recommended frequency for OSS is 30-Hz.• MR elastography (MRE)-based shear strain mapping has the potential to predict the presence of microvascular invasion (MVI) in hepatocellular carcinoma preoperatively. • The low interface shear strain identified at tumor-liver boundaries was highly correlated with the presence of MVI.

Nowadays, there is a serious lack of information about the value-added apoptosis of sarcoma cells in China. Especially in clinical medicine, exploring the effect of ibuprofen on the growth and apoptosis of fibrosarcoma cells under the PI3K/Akt/mTOR signaling pathway can not only effectively prevent us in advance, but also be a great way to break through this field. The main purpose of this study was to investigate the effects of ibuprofen on the proliferation, cell cycle and apoptosis of fibrosarcoma cells through the PI3K/Akt/mTOR signaling pathway. We divided the HTl080 cell line into zero control group, control group and experimental group. The withering group was not inoculated with any cells, while the control group was only added with the same amount of culture medium, while the experimental group was added with 5,10,15,20 concentrations respectively. We found that the apoptosis rate of sarcoma cells in the control group increased from 5.66% to 7.12%, while the apoptosis rate of sarcoma cells in the experimental group increased significantly faster than that in the control group, with an overall increase of 7.16%, from 4.56% to 11.72%. Therefore, we can be surer that ibuprofen has a very good inhibitory effect on the proliferation, cell cycle and apoptosis of fibrosarcoma cells under the PI3K/Akt/mTOR signaling pathway. Therefore, when ibuprofen was injected into the body, it could not only observe the sarcoma cells well but also reflect the good inhibitory effect of ibuprofen on other substances in vivo under the PI3K/Akt/mTOR signaling pathway.

Type 2 diabetes mellitus (T2DM) is one of the major public health problems worldwide; both genetic and environmental factors are its risk factors. Arsenic, an environmental pollutant, might be a risk factor for T2DM, but the association of low-to-moderate level arsenic exposure with the risk of T2DM is still inconsistent. Single nucleotide polymorphisms (SNPs) can affect the development of T2DM, but the study on KEAP1 rs11545829 (GA) SNP is few. In this paper, we explored the effect of KEAP1 rs11545829 (GA) SNP and low-to-moderate level arsenic exposure on risk of T2DM in a cross-sectional case-control study conducted in Shanxi, China. Total of 938 participants, including 318 T2DM cases and 618 controls, were enrolled. Blood glycosylated haemoglobin (HbA1c) was detected by Automatic Biochemical Analyzer, and participants with HbA1c≧6.5% were diagnosed as T2DM. Urinary total arsenic (tAs, mg/L), as the indicator of arsenic exposure, was detected by liquid chromatography-atomic fluorescence spectrometry (LC-AFS). Genomic DNA was extracted and the genotypes of KEAP1 rs11545829 SNP were examined by multiplex polymerase chain reaction (PCR). The urinary tAs concentration in recruited participants was 0.075 (0.03-0.15) mg/L, and was associated with an increased risk of T2DM (OR = 8.45, 95% CI 2.63-27.17); rs11545829 mutation homozygote AA genotype had a protective effect on risk of T2DM (OR = 0.42, 95 % CI 0.25-0.73). Although this protective effect of AA genotype was found in participants with higher urinary tAs level (0.032 mg/L) (OR = 0.48, 95% CI 0.26-0.86), there was no interaction effect for arsenic exposure and rs11545829 SNP on risk of T2DM. In addition, BMI modified the association between rs11545829 SNP and the risk of T2DM (RERI = -1.11, 95% CI -2.18-0.04). The present study suggest that low-to-moderate level arsenic exposure may be a risk factor, while KEAP1 rs11545829 SNP mutation homozygote AA genotype may be a protective factor for risk of T2DM, especially for T2DM patients with urinary tAs level0.032 mg/L.

Objective. To explore the effects of systematic diet education combined with multidisciplinary nursing on nutritional status and calcium and phosphorus metabolism in patients with diabetic kidney disease (DKD) in uremic phase after treatment with alogliptin. Methods. A total of 90 DKD patients with uremia admitted to our hospital from January 2020 to January 2021 were selected as the research objects. The subjects were divided into combined group and routine group by random number table method. All patients received alogliptin medication. The combination group received systematic dietary education combined with multidisciplinary nursing after the medication, and the conventional group received conventional intervention. Serum albumin, blood calcium, and other indexes were detected between both groups after intervention. Results. After intervention, compared with the conventional group, all nutritional indexes of the combined group were obviously higher, levels of serum phosphorus and calcium-phosphorus product of the combined group were obviously lower (P

Transposable elements (TEs) are the major sources of lineage-specific genomic innovation and comprise nearly half of the human genome, but most of their functions remain unclear. Here, we identify that a series of endogenous retroviruses (ERVs), a TE subclass, regulate the transcriptome at the definitive endoderm stage with in vitro differentiation model from human embryonic stem cell. Notably, these ERVs perform as enhancers containing binding sites for critical transcription factors for endoderm lineage specification. Genome-wide methylation analysis shows most of these ERVs are derepressed by TET1-mediated DNA demethylation. LTR6B, a representative definitive endoderm activating ERV, contains binding sites for FOXA2 and GATA4 and governs the primate-specific expression of its neighboring developmental genes such as ERBB4 in definitive endoderm. Together, our study proposes evidence that recently evolved ERVs represent potent de novo developmental regulatory elements, which, in turn, fine-tune species-specific transcriptomes during endoderm and embryonic development.

This study aims to develop an automatic classifier based on deep learning for exacerbation frequency in patients with chronic obstructive pulmonary disease (COPD). A three-layer deep belief network (DBN) with two hidden layers and one visible layer was employed to develop classification models and the models' robustness to exacerbation was analyzed. Subjects from the COPDGene cohort were labeled with exacerbation frequency, defined as the number of exacerbation events per year. A total of 10 300 subjects with 361 features each were included in the analysis. After feature selection and parameter optimization, the proposed classification method achieved an accuracy of 91.99%, using a ten-fold cross validation experiment. The analysis of DBN weights showed that there was a good visual spatial relationship between the underlying critical features of different layers. Our findings show that the most sensitive features obtained from the DBN weights are consistent with the consensus showed by clinical rules and standards for COPD diagnostics. We, thus, demonstrate that DBN is a competitive tool for exacerbation risk assessment for patients suffering from COPD.

Biologic therapies have revolutionized the management of moderate-to-severe psoriasis; however, there are a limited number of US real-world studies characterizing patients based on response to these treatments. This study examined characteristics at enrollment and change in outcomes of US patients with moderate-to-severe psoriasis who achieved insufficient responses with ustekinumab.This study included patients enrolled in the Corrona Psoriasis Registry from April 2015 to June 2018 who initiated ustekinumab at enrollment and who were stratified based on achievement of psoriasis body surface area improving to3% or by 75% from enrollment to the 6-month follow-up visit (response vs insufficient response). Patient demographics and disease characteristics were described at enrollment, and changes in outcomes were assessed at 6-month follow-up for ustekinumab responders and insufficient responders.Of the 178 patients who initiated ustekinumab in the Corrona Psoriasis Registry and had ≥1 follow-up visit, 99 (55.6%) were classified as responders at the 6-month follow-up visit. Logistic regression modeling showed that increasing age was significantly associated with a decreased likelihood of achieving a response (OR, 0.981 [95%CI, 0.962-0.999];These findings may help dermatologists characterize patients with moderate-to-severe psoriasis who have inadequate responses to biologic treatments.

Introduction: Impaired cardiac function is one of the most concomitant symptoms in patients with kidney failure after long-term dialysis. In addition, the preservation of adequate perfusion pressure to the graft plays a significant role in the intraoperative management during kidney transplantation, but the use of positive inotropic drugs in kidney transplant patients has been studied less. We investigated the protective effects of renal function by means of cardiac inotropes in kidney transplant patients. Methods: Eighty-nine patients that received kidney transplantation between April 2014 and December 2016 at Qilu Hospital were included and randomly divided into the treatment group receiving levosimendan and a control group. All kidney recipients received ABO-compatible donors. A poor outcome was defined as one of the following: delayed graft function, graft hemorrhage, or nephrectomy. Results: The treatment group had a better composite outcome and the level of neutrophil gelatinase-associated lipocalin was also lower than in the control group. Conclusion: Inotropic drugs may play a protective role in renal function in kidney transplantation.

On account of the biological significance of self-assembling peptides in blocking the cellular mass exchange as well as impeding the formation for actin filaments resulting in program cell death, stimuli-responsive polypeptide nanoparticles have attracted more and more attention. In this work, we successfully fabricated doxorubicin-loaded polyethylene glycol-block-peptide (FFKY)-block-tetraphenylethylene (PEG-Pep-TPE/DOX) nanoparticles, where the aggregation-induced emission luminogens (AIEgen, TPE-CHO) can become a fluorescence resonance energy transfer (FRET) pair with the entrapped antitumor drug DOX to detect the release of drugs dynamically. This is the first successful attempt to detect and quantify the change of FRET signals in A549 cells via three methods to monitor the cellular uptake of nanoprobes and intracellular drug molecule release intuitively. As we proposed here, the combination of free DOX and the self-assembling peptide could achieve the synergistic anticancer efficacy. The multifunctional PEG-Pep-TPE/DOX nanoparticles may provide a new opportunity for combination cancer therapy and real-time detection of the drug release from stimuli-responsive nanomedicine.

Rhizoma Picrorhizae (RP) is a traditional Chinese medicine, which has always been used to treat many diseases like infantile epilepsy and malnutrition. In modern applications, it has been used to treat hepatitis B and various liver injuries with remarkable curative effects. So far, more than 90 chemical components have been reported in RP, mainly including iridoid glycosides, cucurbitacins, phenylethanoid glycosides, and phenolic glycosides. Among these, iridoid glycosides are the most important active ingredients, and about 30 such compounds have been isolated at present. In pharmacology, RP is beneficial to the choleresis, liver protection, anti-inflammation, asthma relief, immune regulation, and protection of heart, brain, kidney, and other organs. There have been many investigations on this medicinal herb in recent years, and it has attracted much attention in the medicine domain. In this paper, through systematically consulting the relevant books and electronic databases, we analyzed, arranged, and summarized the available information on this herb to provide reference for its further research.

Objective: Biologic therapies have dramatically changed the management of moderate to severe psoriasis; however, few US real-world studies characterize the unmet needs of patients who do not respond to biologic therapies. This study examined the characteristics at enrollment of patients with moderate to severe psoriasis who had insufficient responses to anti-tumor necrosis factor therapies (anti-TNFs). Methods: Patients enrolled in the Corrona Psoriasis Registry from April 2015 to June 2018 who initiated an anti-TNF at enrollment were stratified on the basis of body surface area (BSA) improvement to

Recently, deep learning-based denoising methods have been gradually used for PET images denoising and have shown great achievements. Among these methods, one interesting framework is conditional deep image prior (CDIP) which is an unsupervised method that does not need prior training or a large number of training pairs. In this work, we combined CDIP with Logan parametric image estimation to generate high-quality parametric images. In our method, the kinetic model is the Logan reference tissue model that can avoid arterial sampling. The neural network was utilized to represent the images of Logan slope and intercept. The patient's computed tomography (CT) image or magnetic resonance (MR) image was used as the network input to provide anatomical information. The optimization function was constructed and solved by the alternating direction method of multipliers (ADMM) algorithm. Both simulation and clinical patient datasets demonstrated that the proposed method could generate parametric images with more detailed structures. Quantification results showed that the proposed method results had higher contrast-to-noise (CNR) improvement ratios (PET/CT datasets: 62.25%±29.93%; striatum of brain PET datasets : 129.51%±32.13%, thalamus of brain PET datasets: 128.24%±31.18%) than Gaussian filtered results (PET/CT datasets: 23.33%±18.63%; striatum of brain PET datasets: 74.71%±8.71%, thalamus of brain PET datasets: 73.02%±9.34%) and nonlocal mean (NLM) denoised results (PET/CT datasets: 37.55%±26.56%; striatum of brain PET datasets: 100.89%±16.13%, thalamus of brain PET datasets: 103.59%±16.37%).

To explore the genetic basis for a girl with febrile convulsion as the main manifestation.The child was subjected to whole exome sequencing (WES) and copy number variation sequencing(CNV-seq). Fluorescence quantitative PCR was carried out to validate the microdeletion in her family.The 7-year-old girl was diagnosed with febrile convulsion (complex type) for having fever for 3 days, mild cough and low thermal convulsion once. Her father, mother and aunt also had a history of febrile convulsion. A heterozygous deletion with a size of approximately 1.5 Mb was detected in the 16p13.11 region by WES and CNV-seq. The deletion has derived from her father and was confirmed by fluorescence quantitative PCR.16p13.11 microdeletion syndrome has significant clinical heterogeneity. Different from those with epilepsy, mental retardation, autism, multiple malformations, carriers of 16p13.11 deletion may only manifest with febrile convulsion. Deletion of certain gene(s) from the region may be related to febrile convulsion and underlay the symptom of this child.

Parametric imaging based on dynamic positron emission tomography (PET) has wide applications in neurology. Compared to indirect methods, direct reconstruction methods, which reconstruct parametric images directly from the raw PET data, have superior image quality due to better noise modeling and richer information extracted from the PET raw data. For low-dose scenarios, the advantages of direct methods are more obvious. However, the wide adoption of direct reconstruction is inevitably impeded by the excessive computational demand and deficiency of the accessible raw data. In addition, motion modeling inside dynamic PET image reconstruction raises more computational challenges for direct reconstruction methods. In this work, we focused on the 18F-FDG Patlak model, and proposed a data-driven approach which can estimate the motion corrected full-dose direct Patlak images from the dynamic PET reconstruction series, based on a proposed novel temporal non-local convolutional neural network. During network training, direct reconstruction with motion correction based on full-dose dynamic PET sinograms was performed to obtain the training labels. The reconstructed full-dose /low-dose dynamic PET images were supplied as the network input. In addition, a temporal non-local block based on the dynamic PET images was proposed to better recover the structural information and reduce the image noise. During testing, the proposed network can directly output high-quality Patlak parametric images from the full-dose /low-dose dynamic PET images in seconds. Experiments based on 15 full-dose and 15 low-dose 18F-FDG brain datasets were conducted and analyzed to validate the feasibility of the proposed framework. Results show that the proposed framework can generate better image quality than reference methods.

To map the locations of level I axilla (Ax-L1) lymph nodes (LNs), evaluate the clinical target volume (CTV) coverage defined by the Radiation Therapy Oncology Group (RTOG) Breast Cancer Atlas, and assess the optimal techniques for whole-breast and Ax-L1 irradiation (WBI + Ax-L1).We identified 76 patients newly diagnosed with breast cancer with 1 to 4 positive LNs confirmed by axillary dissection. The locations of 116 involved Ax-L1 LNs on diagnostic computed tomography (CT) were mapped onto simulated CT images of a standard patient. Ax-L1 LN coverage by the RTOG atlas was evaluated, and a modified Ax-L1 CTV with better coverage was proposed. Treatment plans were designed for WBI + Ax-L1 with high tangential simplified intensity modulated radiation therapy (HT-sIMRT) and volumetric modulated arc therapy (VMAT) and for WBI + RTOG Ax-L1 with VMAT with a prescription dose of 50 Gy in 25 fractions, respectively. The differences in dosimetric parameters were compared.The RTOG Atlas missed 29.3% of LNs. Modification by extending 1 cm caudal and 0.5 cm anterior to the RTOG-defined CTV borders allowed the modified Ax-L1 CTV to encompass 90.5% of LNs. All plans met the required prescription dose to WBI and Ax-L1. The mean dose and the V20 and V5 (percentage volume receiving 20 Gy and 5 Gy) of the ipsilateral lung were 11.7 Gy, 23.0%, and 38.1% for HT-sIMRT WBI + Ax-L1 and 8.9 Gy, 16.4%, and 32.5% for VMAT WBI + Ax-L1 plans, respectively. The mean heart doses in the left-sided plans were 3.2 Gy and 3.0 Gy, respectively. The V30 of the humeral head and the minimum dose to the axillary-lateral thoracic vessel junction were 2.0% versus 1.8% and 45.5 Gy versus 45.7 Gy for VMAT WBI + Ax-L1 and VMAT WBI + RTOG Ax-L1 plans, respectively.A modified Ax-L1 CTV with expansion of the caudal and anterior borders might provide better coverage. Compared with HT-sIMRT WBI + Ax-L1, VMAT WBI + Ax-L1 provided an adequate dose to the Ax-L1 while decreasing the doses to most normal tissues. Coverage of the modified Ax-L1 did not increase the dose to organs at risk compared with coverage of RTOG Ax-L1.

Objective The aim of this study was to investigate the potential therapeutic effects of a newly discovered osteopontin-derived synthetic peptide "RSKKFRR" in a rat model of ischemic stroke. Methods A total of 24 male SD rats were randomly divided into three groups. The model of ischemic stroke was made up of the middle cerebral artery occlusion (MACO). The rats were divided into sham operation group (Sham), control group (MACO + PBS) and treatment group (MACO + OPNpt9), eight rats in each group. In the control group and the treatment group, PBS or OPNpt9 was injected into the nasal cavity after MACO once a day, and the area of new blood vessels and the recovery of nerve function were observed 14 days later. Whether the proliferation, migration and tube formation of HUVECs were promoted by OPNpt9 was tested. The expression levels of related proangiogenic factors were also detected. Results OPNpt9 was found to contribute to cerebral microvascular remodeling and neurological improvement in ischemic rats while promoting endothelial cell migration, proliferation and tube formation in vitro. These effects were mediated by activation of the p-ERK/MMP-9/VEGF pathway. Conclusion In conclusion, OPNpt9 promotes angiogenesis and neurological recovery after ischemic stroke.

Background To investigate the influence of artificial intelligence (AI) based on deep learning on the diagnostic performance and consistency of inexperienced cardiovascular radiologists. Methods We enrolled 196 patents who had undergone both coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) within 6 months. Four readers with less cardiovascular experience (Reader 1–Reader 4) and two cardiovascular radiologists (level II, Reader 5 and Reader 6) evaluated all images for ≥ 50% coronary artery stenosis, with ICA as the gold standard. Reader 3 and Reader 4 interpreted with AI system assistance, and the other four readers interpreted without the AI system. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy (area under the receiver operating characteristic curve (AUC)) of the six readers were calculated at the patient and vessel levels. Additionally, we evaluated the interobserver consistency between Reader 1 and Reader 2, Reader 3 and Reader 4, and Reader 5 and Reader 6. Results The AI system had 94% and 78% sensitivity at the patient and vessel levels, respectively, which were higher than that of Reader 5 and Reader 6. AI-assisted Reader 3 and Reader 4 had higher sensitivity (range + 7.2–+ 16.6% and + 5.9–+ 16.1%, respectively) and NPVs (range + 3.7–+ 13.4% and + 2.7–+ 4.2%, respectively) than Reader 1 and Reader 2 without AI. Good interobserver consistency was found between Reader 3 and Reader 4 in interpreting ≥ 50% stenosis (Kappa value = 0.75 and 0.80 at the patient and vessel levels, respectively). Only Reader 1 and Reader 2 showed poor interobserver consistency (Kappa value = 0.25 and 0.37). Reader 5 and Reader 6 showed moderate agreement (Kappa value = 0.55 and 0.61). Conclusions Our study showed that using AI could effectively increase the sensitivity of inexperienced readers and significantly improve the consistency of coronary stenosis diagnosis via CCTA. Trial registration Clinical trial registration number: ChiCTR1900021867. Name of registry: Diagnostic performance of artificial intelligence-assisted coronary computed tomography angiography for the assessment of coronary atherosclerotic stenosis.

To explore the value of an artificial intelligence (AI)-based application for identifying plaque-specific stenosis and obstructive coronary artery disease from monoenergetic spectral reconstructions on coronary computed tomography angiography (CTA).This retrospective study enrolled 71 consecutive patients (52 men, 19 women; 63.3 ± 10.7 years) who underwent coronary CTA and invasive coronary angiography for diagnosing coronary artery disease. The conventional 120 kVp images and eight different virtual monoenergetic images (VMIs) (from 40 keV to 140 keV at increment of 10 keV) were reconstructed. An AI system automatically detected plaques from the conventional 120 kVp images and VMIs and calculated the degree of stenosis, which was further compared to invasive coronary angiography. The assessment was performed at a segment, vessel, and patient level.Vessel and segment-based analyses showed comparable diagnostic performance between conventional CTA images and VMIs from 50 keV to 90 keV. For vessel-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of conventional CTA were 74.3% (95% CI: 64.9%-82.0%), 85.6% (95% CI: 77.0%-91.4%), 84.3% (95% CI: 75.2%-90.7%), 76.1% (95% CI: 67.1%-83.3%) and 79.8% (95% CI: 73.7%-84.9%), respectively; the average sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy values of the VMIs ranging from 50 keV to 90 keV were 71.6%, 90.7%, 87.5%, 64.1% and 81.6%, respectively. For plaque-based assessment, diagnostic performance of the average VMIs ranging from 50 keV to 100 keV showed no significant statistical difference in diagnostic accuracy compared to those of conventional CTA images in detecting calcified (91.4% vs. 93.8%, p0.05), noncalcified (92.6% vs. 85.2%, p0.05) or mixed (80.2% vs. 81.2%, p0.05) stenosis, although the specificity was slightly higher (53.4% vs. 40.0%, p0.05) in detecting stenosis caused by mixed plaques. For VMIs above 100 keV, the diagnostic accuracy dropped significantly.Our study showed that the performance of an AI-based application employed to detect significant coronary stenosis in virtual monoenergetic reconstructions ranging from 50 keV to 90 keV was comparable to conventional 120 kVp reconstructions.

OBJECTIVES To evaluate the risk category performance of artificial intelligence-based coronary artery calcium score (AI-CACS) software used in non-gated chest computed tomography (CT) on three types of CT machines, considering the manual method as the standard. METHODS A total of 901 patients who underwent both chest CT and electrocardiogram (ECG)-gated non-contrast-enhanced cardiac CT with the same equipment within a 3-month period were enrolled in the study. AI-CACS software was based on a deep learning algorithm and was trained on multi-vendor, multi-scanner, and multi-hospital anonymized data from the chest CT database. The AI-CACS was automatically obtained from chest CT data by the AI-CACS software, while the manual CACS was obtained from cardiac CT data by the manual method. The correlation of the AI-CACS and manual CACS, concordance rate and kappa value of the risk categories determined by the two methods were calculated. The chi-square test was used to evaluate the differences in risk categories among the three types of CT machines from different manufacturers. The risk category performance of the AI-CACS for dichotomous risk categories bounded by 0, 100 and 400 was assessed. RESULTS The correlation of the AI-CACS with the manual CACS was ρ = 0.893 (p

As the end execution tool of agricultural robots, the manipulator directly determines whether the grasping task can be successfully completed. The human hand can adapt to various objects and achieve stable grasping, which is the highest goal for manipulator design and development. Thus, this study combines a multi-sensor fusion tactile glove to simulate manual grasping, explores the mechanism and characteristics of the human hand, and formulates rational grasping plans. According to the shape and size of fruits and vegetables, the grasping gesture library is summarized to facilitate the matching of optimal grasping gestures. By analyzing inter-finger curvature correlations and inter-joint pressure correlations, we investigated the synergistic motion characteristics of the human hand. In addition, the force data were processed by the wavelet transform algorithms and then the thresholds for sliding detection were set to ensure robust grasping. The acceleration law under the interaction with the external environment during grasping was also discussed, including stable movement, accidental collision, and placement of the target position. Finally, according to the analysis and summary of the manual gripping mechanism, the corresponding pre-gripping planning was designed to provide theoretical guidance and ideas for the gripping of robots.

PURPOSE: To investigate the diagnostic performance of preoperative MR elastography (MRE) in predicting early recurrence (ER) and late recurrence (LR) of HCC after hepatectomy. METHOD: In total, 180 patients (median age, 52 years; interquartile range, 41–50 years; 161 men) who underwent conventional MRI and MRE before hepatectomy between December 2014 and April 2020 were retrospectively recruited. A preoperative clinic-radiologic model and a combined postoperative clinic-pathologic and radiologic model were built using quantitatively MRE-derived stiffnesses, and image features to predict tumor ER and LR after hepatectomy. The Cox proportional hazards model and ROC analyses were used to identify the value of parameters to predict ER and LR. RESULTS: Seventy-three (40.5%) and 16 (8.9%) developed ER and LR after hepatectomy, respectively. For prediction of ER, the preoperative model integrated higher tumor stiffness (TS) (hazard ratio [HR],1.142; p < 0.001) with AFP ≥ 400 ng/mL (HR,1.761; p = 0.022), multifocal tumors (HR,3.229; p < 0.001) and lower ADC (HR,0.998; p = 0.017) variables; and the postoperative model incorporated higher TS, microvascular invasion, multifocal tumors, Child-Pugh class and ADC predictors. The two models provided comparable predictive performance (pre- 0.812 vs. post- 0.834, p = 0.283). Moreover, TS alone had a high sensitivity (90.4%) for predicting ER. Liver stiffness (LS) (HR, 1.757; p < 0.001) was the only independent predictor for LR in multivariate analysis in both the pre- and postoperative models with high specificity (90.0%), and its AUC with an optimal cut-off of 3.62 kPa was 0.860. CONCLUSIONS: Quantitative MRE-based stiffness is a useful biomarker for preoperative prediction of ER and LR of HCC.

Previous studies have shown an independent association between increased red cell distribution width (RDW) and mortality after acute myocardial infarction (AMI). However, evidence regarding the predictive significance of repeated measures of RDW in patients with AMI remains scarce. We aimed to investigate the association between the dynamic profile of RDW and in-hospital mortality in patients with AMI. This was a cross-sectional study. We extracted clinical data from the Medical Information Mart for Intensive Care IIIV1.4 database. Demographic data, vital signs, laboratory test data, and comorbidities were collected from the database. The clinical endpoint was in-hospital mortality. Cox proportional hazards models were used to evaluate the prognostic values of basic RDW, and the Kaplan–Meier method was used to plot survival curves. Subgroup analyses were performed to measure mortality across various subgroups. The repeated-measures data were compared using a generalized additive mixed model. In total, 3101eligible patients were included. In multivariate analysis, adjusted for age, sex, and ethnicity, RDW was a significant risk predictor of in-hospital mortality. Furthermore, after adjusting for more confounding factors, RDW remained a significant predictor of in-hospital mortality (tertile 3 vs tertile 1: hazard ratio 2.3; 95% confidence interval 1.39–4.01; P for trend

The field of functional neuroimaging has substantially advanced as a big data science in the past decade, thanks to international collaborative projects and community efforts. Here we conducted a literature review on functional neuroimaging, with focus on three general challenges in big data tasks: data collection and sharing, data infrastructure construction, and data analysis methods. The review covers a wide range of literature types including perspectives, database descriptions, methodology developments, and technical details. We show how each of the challenges was proposed and addressed, and how these solutions formed the three core foundations for the functional neuroimaging as a big data science and helped to build the current data-rich and data-driven community. Furthermore, based on our review of recent literature on the upcoming challenges and opportunities toward future scientific discoveries, we envisioned that the functional neuroimaging community needs to advance from the current foundations to better data integration infrastructure, methodology development toward improved learning capability, and multi-discipline translational research framework for this new era of big data. Keywords: Big data, Neuroimaging, Machine learning, Health informatics, fMRI

Induced pluripotent stem cells (iPSCs) show huge variations in their differentiation potential, even in the same condition. However, methods for predicting these differentiation tendencies, especially in the early stage of differentiation, are still scarce. This study aimed to establish a simple and practical system to predict the differentiation tendency of iPSC lines using embryoid bodies (EBs) with identified parameters in the early stage. We compared four human iPSC lines in terms of the morphology and maintenance of EBs and their gene expression levels of specific markers for three germ-layers. Furthermore, the differentiation potentials of these iPSC lines into melanocytes, which are ectoderm-derived cells, were also compared and correlated with the above parameters. The results showed that iPSC lines forming regular, smooth, and not cystic EBs, which could be maintained in culture for a relatively longer time, also expressed higher levels of ectoderm-specific markers and lower levels of mesoderm/endoderm markers. Additionally, these iPSC lines showed greater potential in melanocyte differentiation using EB-based protocol, and the induced melanocytes expressed melanocytic markers and presented characteristics that were similar to those of normal human melanocytes. By contrast, iPSC lines that formed cystic EBs with bright or dark cavities and expressed relatively lower levels of ectoderm-specific markers failed in the melanocyte differentiation. Collectively, the differentiation tendency of human iPSC lines may be predicted by specific parameters in the EB stage. The formation and maintenance of optimal EBs and the expression of germ layer-specific markers are particularly important and practical for the prediction assay in the early stage.

Shuxuening injection (SXNI), one of the traditional Chinese medicine injections (TCMI), is widely used for the treatment of cardiovascular diseases in the clinic. However, its allergic reactions have impeded the clinical applications of SXNI, such adverse reactions have not been well understood due to the lack of methods for detecting haptens. In this study, a high-performance liquid chromatography-diode–array detector–multi-stage mass spectrometry–human serum albumin–fluorescence detector (HPLC–DAD–MSn–HSA–FLD) system was established to identify and screen haptens for the first time. Flavones, flavonols and their glycosides in SXNI showed strong HSA binding ability in different degrees. Fifteen of these compounds were used to study the association of HSA binding ability and sensitizability using isothermal titration calorimetry (ITC) and fluorescence techniques, furthermore, RBL-2H3 cell experiments were conducted to verify the results. It was found that ginkgolides showed no sensitizability, while flavones and flavonol aglycones showed stronger sensitizability than their glycosides. The system was proven to be precise, stable and reproducible, which lays a foundation for screening haptens in SXNI and relevant samples.

Objective: This study was aimed to develop DOX-TPP loaded acetal-PEG-PCCL micelles to improve the clinical efficacy of drug resistance tumor.Significance: Chemotherapy is one of the main tr...

Background: The pathogenesis of the development of IgA nephropathy has not been clear up to now. At present, some studies revealed that the mTOR pathway may participate in IgA nephropathy; however, the mechanism has not been systematically studied. In this study, we established an IgAN rat model to investigate the protective effects of rapamycin as a new type of immunosuppressant, as well as its therapeutic mechanisms. Methods: After the establishment of IgA nephropathy model, rats were treated with different concentrations of rapamycin, and the protective effect of different concentrations of rapamycin on renal function of the rats was observed. The deposition of IgA was observed by immunofluorescence. The kidney expression of Akt and p70S6k proteins in mTOR pathway was examined using the western blot assay after rapamycin treatment. Results: Morphology and immunofluorescence confirmed that the rat model of IgA nephropathy was successfully established. In particular, the level of proteinuria decreased with the increase of the dose of rapamycin, as well as the deposition of IgA in glomeruli. Moreover, the western blot analysis indicated that the expression of p70S6K in the downstream of mTOR pathway decreased and the upstream protein AKT of the mTOR pathway was overexpressed in the rats model. Conclusion: We found that rapamycin has protective effects in the IgA nephropathy rat model in a dose-dependent manner. In addition, the result of western blot assay suggested that rapamycin may display its therapeutic effects through interfering the AKT-mTOR-p70S6K signaling pathway.

Children with normal intelligence may experience varying degrees of mathematics learning disabilities (MD). This study aims to conduct training to improve the brain's cognitive ability for mathematics learning by focusing on two important mathematical cognitive abilities. This was a prospective study of 70 children in grades 2-5 from two primary schools in Changzhou and with MD enrolled from June 2015 to February 2017. The children were randomized 1:1 to the training and control groups. A training cycle included 40 sessions (5/weeks) (30 min each session). The efficacy of learning was assessed by assessing number learning and graph reasoning, and by using the Raven standard reasoning test score. In the training group, backward number memory (from 6.1 ± 1.8 to 6.7 ± 1.3

Perivascular fat attenuation index is considered a sensitive biomarker of vulnerable coronary plaques. However, its application in studying the carotid artery are unknown.This study aimed to explore the association between cerebrovascular symptoms and carotid attenuation density of perivascular adipose tissue (PVAT) on computed tomography angiography (CTA).A total of 206 participants (mean age, 63.9 ± 7.9 years, 145 men) who underwent CTA were retrospectively analyzed. Perivascular fat density (PFD) was evaluated via CTA. The association between PFD and the occurrence of cerebrovascular symptoms was examined via generalized estimating equations and receiver operating characteristic analysis.Among the 206 subjects, 49.5% (plaques were observed in 102 patients) presented cerebrovascular symptoms. Plaques with symptoms (-55.0 ± 10.0 Hounsfield units [HU]) had a higher PFD than those without symptoms (-68.0 ± 10.3 HU) (p 0.001). After adjusting for hyperlipidemia, statin use, antiplatelet use, calcification, degree of luminal stenosis, maximum plaque thickness, and ulceration, PFD was found to be strongly associated with cerebrovascular symptoms (OR, 1.13; 95% CI, 1.07-1.19; p 0.001). Receiver operating characteristic analysis revealed an area under the curve of 0.81 by using PFD measurements to discriminate between symptomatic and asymptomatic plaques with a sensitivity of 87.3% and a specificity of 60.6%.An increase in attenuation density of PVAT on CTA was found to be related to an increase in the risks of cerebrovascular symptoms. PFD might serve as an imaging marker of symptomatic carotid plaques.

Current evidence indicates that carotid atherosclerosis is an independent risk factor for cognitive impairment. Serum metabolomic analysis holds significant promise for uncovering the relationship between carotid atherosclerosis and cognitive impairment. In this study, we aimed to evaluate the profiling of serum carbonyl compounds in subclinical carotid atherosclerosis (SCA) patients and to explore the relationship between serum carbonyl compounds and cognitive performance. We enrolled 51 SCA patients and 45 healthy control individuals using carotid ultrasound assessment. All the participants were subjected to a neuropsychological assessment and their fasting serum samples were collected for untargeted stable isotope-labeling strategy combined with liquid chromatography-double precursor ion scan-mass spectrometry analysis. Compared with the control, the SCA group showed lower scores in global cognition, immediate memory, verbal fluency, executive function, and visual attention. For the isotope-labeling strategy combined with liquid chromatography-double precursor ion scan-mass spectrometry analysis, 149 potential carbonyl candidates were discovered in the pooled serum. In the SCA serum, 41 carbonyl compounds showed significantly increased levels and 14 carbonyl compounds showed significantly decreased levels. In addition, six carbonyl compounds involved in the oxidation of polyunsaturated fatty acids and vitamin E were correlated with cognitive performance. A negative correlation was observed between cognitive performance and the levels of octanal, nonanal, α-tocopherolquinone, and heptanal, respectively. A positive correlation was observed between cognitive performance and the levels of acetophenone and 1-(3-aminopropyl)-4-aminobutanal, respectively. In summary, the SCA individuals have poor cognitive performance, which may be reflected by aberrant serum carbonyl compound profiles.

Objective Presently, interesting research related to induced pluripotent stem cells (iPSCs) is emerging. However, the development of new therapies and techniques for treatment of refractory diseases is still required in dermatology. We are exploring novel methods to provide stem cell therapy and elucidate research mechanisms underlying troublesome diseases by reprogramming iPSCs from the fibroblasts of keloid lesions from patients in vitro. Method Here, we identified the expression of fibroblastic genes in the fibroblast derived from diseased individuals. Corresponding iPSCs were then produced by transfecting patient fibroblasts with non-modified RNA cocktails, expressing OCT4, SOX2, KLF4, cMYC, NANOG, and LIN28 reprogramming factors. The pluripotency of these patient-derived iPSCs was identified by immunocytochemistry, real-time quantitative polymerase chain reaction, and teratoma formation in vivo in non-obese diabetic/severe combined immunodeficiency mice. Results All iPSCs derived from patients significantly expressed the pluripotent transcription factors and could be expanded in vitro. Furthermore, induction of terminal differentiation in long-term culture and the capability of forming embryonic bodies to differentiate into all 3 germ layers in vivo were confirmed in immune-deficient mice. Conclusion Fibroblasts from a keloid patient were successfully reprogrammed to iPSCs in vitro. This reprogramming may provide a basis for the production of individualized modified artificial skin to prevent rejections after xenogeneic skin transplantation and trauma through autologous skin transplantation. These cells can also offer a new platform for research on mechanisms underlying skin diseases and personal medical applications.