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ADHD in children is one of the most common neurodevelopmental disorders. It is manifested as inattention, hyperactivity, impulsiveness, and other symptoms that are inconsistent with the developmental level in different occasions, accompanied by functional impairment in social, academic, and occupational aspects. At present, the treatment for children with ADHD is mainly based on psychological nursing intervention combined with drug therapy. Therefore, the actual efficacy evaluation of this treatment regimen is very important. Neural networks are widely used in smart medical care. This work combines artificial intelligence with the evaluation of clinical treatment effects of ADHD children and designs an intelligent model based on neural networks for evaluating the clinical efficacy of psychological nursing intervention combined with drug treatment of children with ADHD. The main research is that, for the evaluation of clinical treatment effect of ADHD in children, this paper proposes a 1D Parallel Multichannel Network (1DPMN), which is a convolutional neural network. The results show that network models can extract different data features through different channels and can achieve high accuracy evaluation of clinical efficacy of ADHD in children. On the basis of the model, performance is improved through the study of Adam optimizer to speed up the model convergence, adopts batch normalization algorithm to improve stability, and uses Dropout to improve the generalization ability of the network. Aiming at the problem of too many parameters, the 1DPMN is optimized through the principle of local sparseness, and the model parameters are greatly reduced.

Objective Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist and can act synergistically to drive adverse outcomes of one another. This study aimed to unravel the metabolomic changes in patients with NAFLD and T2DM, to identify potential noninvasive biomarkers, and to provide insights for understanding the link between NAFLD and T2DM. Methods Three hundred participants aged 35 to 70 years who were diagnosed with NAFLD (n = 100), T2DM (n = 100), or a comorbidity of NAFLD and T2DM (n = 100) were included in this study. Anthropometrics and routine blood chemistry were assessed after overnight fast. The global serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers. Results A set of serum biomarkers that could effectively separate NAFLD from NAFLD + T2DM and T2DM from NAFLD + T2DM were identified. We found that patients with coexisting NAFLD and T2DM had significantly higher levels of total protein (TP), triglycerides (TG), glucose in urine, and gamma-hydroxybutyric acid than those with NAFLD and had significant increased levels of TP, albumin, alanine aminotransferase, aspartate aminotransferase, total cholesterol, cholinesterase, TG, low-density lipoprotein, and apolipoprotein A when compared to patients with T2DM. Conclusion The metabolomics results provide evidence that the comorbidity of NAFLD and T2DM considerably altered patients’ metabolomics patterns compared to those of patients with only NAFLD or T2DM.

Background Previous reports about risk factors for linezolid-induced thrombocytopenia have been insufficient, often due to the variability in study design and population, and some factors have not yet been studied. Aim The aims of this study are to determine potential risk factors for linezolid-induced thrombocytopenia, and to analyze the influencing factors of different thrombocytopenia definitions. Method This retrospective study involved patients who were administered intravenous linezolid for ≥ 1 day between January 1, 2015 and January 1, 2021. Their demographic and clinical data were extracted from electronic medical records. Thrombocytopenia was defined as: ①thrombocytopenia with platelet count

Objective To investigate the correlation between the triglyceride-glucose (TyG) index and rheumatoid factor levels and the existence of cardiovascular disease in patients in the rheumatoid arthritis population and to analyze their potential value in predicting the risk of cardiovascular disease. Methods Patients with rheumatoid arthritis treated by the Traditional Chinese Medicine Department of Rheumatism of the China-Japan Friendship Hospital from 2019–01 to 2021–12 were included in this retrospective study. Regression analysis was performed with multifactor-corrected multimodal logistic models to observe the correlation between the TyG index and rheumatoid factor and cardiovascular disease risk, construct predictive models and assess the potential predictive value of the variables on cardiovascular disease risk with receiver operating characteristic curves. The results were further corrected by sensitivity analysis and trend tests. Results A total of 418 patients with rheumatoid arthritis were included in the study. In the rheumatoid arthritis population, high rheumatoid factor (OR = 1.002, 95% CI = 1.001–1.002, P P = 0.022), advanced age (OR = 1.080, 95% CI = 1.050–1.112, P P = 0.018) were independent risk factors for the existence of cardiovascular disease in patients. The combined coefficient calculated on the basis of the TyG index and rheumatoid factor was used to plot the receiver operating characteristic curve with an area under the curve of 0.791, which can be used to predict the potential risk of cardiovascular disease in patients with rheumatoid arthritis. Further sensitivity analysis found that the marker of focus remained associated with cardiovascular disease risk in a high-physical activity population with rheumatoid arthritis. The final trend test found a linear trend between the TyG index, rheumatoid factor levels and the risk of cardiovascular disease. Conclusion In the rheumatoid arthritis population, the TyG index and rheumatoid factor have some potential predictive value in determining the risk of cardiovascular disease, and the predictive efficacy is better when the two tests are combined.

AIMS The extent that pre-diabetic fasting plasma glucose (FPG) levels influence the effectiveness of lifestyle interventions in preventing type 2 diabetes (T2DM) is uncertain. We aimed to determine if the outcome of lifestyle intervention in people with impaired glucose tolerance (IGT) differs in those with normal or impaired FPG levels. MATERIALS AND METHODS Data were used from the Da Qing Diabetes Prevention Outcome Study, which was a 30-year follow-up of a 6-year randomized trial of lifestyle intervention in 576 people with IGT. We then conducted a post-hoc analysis to compare the efficacy of intervention to reduce the incidence of T2DM and its complications in those with baseline FPG

The purpose of our study was to investigate the effect of the 15° left operating table tilt on the inferior vena cava (IVC) and the hemodynamics of full-term pregnant women, and to evaluate the efficacy of inferior vena cava collapse index (IVCCI) in predicting hypotension.All parturients planning to perform cesarean section (CS) were randomly divided into supine group and 15° group. Their parameters of IVC were measured by ultrasound and then calculated the IVCCI. Systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) in two positions were recorded from baseline to fetal delivery.The IVCCI in the 15° group was significantly lower when compared with that in the supine group (20.40 [18.84-21.60] vs. 21.82 [20.16-22.79] %, p = 0.012). The incidence of hypotension was observed statistically lower in the 15° group than the supine group (27.5% vs. 50%, p = 0.039). Best cut-off value was 21.69% and area under the receiver operating characteristic (ROC) curve of IVCCI in supine position to predict hypotension was 0.93. Best cut-off value was 21.78% and area under the ROC curve of IVCCI in supine position to predict hypotension was 0.80.The 15° left operating table tilt can relieve the extent of compression of IVC and reduce the incidence of hypotension. IVCCI can predict the occurrence of hypotension.

The characteristic hypoxia of solid tumors and inadequate oxygen supply become a key causation of the resistance to chemotherapy in cancer treatment. Herein, a bimetallic oxygen nanogenerator

Introduction Ankle pump exercise (APE) is an effective method to prevent deep vein thrombosis (DVT) in the lower extremities. However, traditional APE at a frequency of 3 times/min applied in the clinic lacked high compliance, and individuals were found to prefer an APE of 30 times/min. This study aimed to compare the effects of APEs with the above two different frequencies on the venous hemodynamics and fatigue of lower extremities. Methods The study applied a randomized cross-over design, and 307 healthy adults were randomly assigned into two groups, whose left feet performed 5 minutes of traditional APE (3 times/min, after 10 minutes of rest) and 5 minutes of selected APE (30 times/min, after 10 minutes of rest) in different orders. The diameters and blood flow velocities of the external iliac vein, femoral vein, and popliteal vein of the left extremities were recorded with the color doppler ultrasound when participants were at rest and after 5 minutes of traditional or selected APE. The fatigue of lower extremities was assessed with the Rating of Perceived Exertion (RPE) after the participants performed 5 minutes of different APEs. Results After both traditional APE and selected APE, the diameters and blood flow (peak systolic) velocities of the external iliac vein, femoral vein, and popliteal vein increased significantly in the participants (P.05). However, participants reported that traditional APE caused higher fatigue, and 252 (82.1%) participants preferred APE at 30 times/min. Conclusion Both traditional and selected APE could increase venous blood flow in the lower extremity. Despite the equivalent effects, the selected APE of 30 times/min may cause less fatigue than the traditional one of 3 times/min.

Gold nanodendrite (AuND)-based nanotheranostic agents with versatile capabilities were fabricated by optimizing the geometrical configurations (dendrite length and density) of AuND to achieve localized surface plasmon resonance (LSPR) in near-infrared biowindow II (NIR-II), and then subsequently functionalizing with a mitochondria-targeting compound (triphenylphosphonium, TPP), loading with an NIR-photosensitizer (indocyanine green, ICG) and coating with the macrophage cell membrane (MCM) to trap ICG within AuND and selectively interact with MDA-MB-231 cells. The novel AuND-TPP-ICG@MCM system enabled the integration of multimodal fluorescence/photoacoustic/surface-enhanced Raman imaging with synergistic therapies of NIR-II photothermal therapy and NIR-I photodynamic therapy for cancer treatment. Enhanced hyperthermia and elevated production of reactive oxygen species within the tumors via MCM coating and mitochondria targeting afforded a synergistic efficacy for tumor eradication with limited side effects. The demonstrated biocompatibility, multi-imaging capability, and high therapeutic efficiency under NIR laser irradiation indicate the potentials of this multifunctional nanotheranostic platform for clinical utility in cancer therapy.

We aimed to determine associations of regression to normal glucose tolerance (NGT), maintaining impaired glucose tolerance (IGT) or progression to diabetes with subsequent risks of CVD and microvascular disease among Chinese adults with IGT. We conducted an observational study among 540 participants in the Da Qing Diabetes Prevention Study, a 6 year lifestyle intervention trial in people with IGT, defined by 1985 WHO criteria as fasting plasma glucose

ObjectiveThe clinical features of interstitial lung disease (ILD) in patients with dermatomyositis (DM) and negative myositis autoantibodies had not been exactly demonstrated previously. This study aimed to describe and expand the phenotype of interstitial lung disease (ILD) in this cohort of patients.MethodsA total of 1125 consecutive Chinese patients with idiopathic inflammatory myopathies (IIM) between 2006 and 2020 were screened retrospectively. All proven cases of isolated ILD with both negative myositis-specific autoantibodies (MSA) and negative myositis-associated autoantibodies (MAA) were selected for inclusion. The clinical features and outcome among this group, MDA5+DM (DM patients with positive anti-MDA5 antibody) and ASS (patients with positive anti-aminoacyl tRNA synthetases antibodies were recorded and compared.ResultsOf 1125 IIM patients with an average follow-up of 6 years, 154 DM patients with negative MSA and MAA (MSA/MAA) were identified, with an ILD incidence of 46.8%. DM-ILD Patients with negative MSA/MAA presented younger age at onset (p+DM and ASS.The estimated high-resolution computed tomography patterns of ILD showed non-specific interstitial pneumonia (66.6%), followed by organizing pneumonia in patients with negative MSA/MAA. OP pattern was more common in patients with MDA5+DM (69.7%), and the ratios of the OP (48.7%) and NSIP (51.3%) patterns were almost equal in patients with ASS. Of these DM-ILD patients with negative MSA/MAA, 25% developed rapidly progressive interstitial lung disease (RP-ILD). Patients with RP-ILD had a shorter disease duration (p=0.002), higher percentage of positive ANA(p=0.01) and organizing pneumonia patterns (p=0.04), elevated CYFRA211(p=0.04) and decreased FiO2/PaO2 (p+ DM (75%) and ASS (89%) (p=0.006). The cumulative 5- and 10-year survival rates in the DM-ILD patients with negative MSA/MAA were 91% and 88%, respectively, during the long-term follow-up study. And they had more favorable survival rate compared with ILD patients with MDA5+DM and ASS (pConclusionsThis study indicates DM-ILD patients with negative MSA/MAA had favorable long-term outcomes. Decreased baseline PaO2/FiO2 acted as an independent prognostic factor for this group of patients.

To investigate the association of potential cardiovascular disease (CVD) biomarkers in patients with type 2 diabetes.We enrolled 120 participants (aged 61.5-69.5 years) with type 2 diabetes and 60 (aged 62.5-73.5 years) with normal glucose tolerance in the discovery group from the original Da Qing Diabetes Study. Their diabetes status was confirmed in 1986; then, the participants were followed over 23 years to collect CVD outcome data. Untargeted and targeted metabolomics analyses based on ultra-high-performance liquid chromatography-tandem mass spectrometry were used to identify potential markers. Multivariable regression analysis was used to evaluate the association between metabolites and CVD outcomes. An independent group of 335 patients (aged 67.0-77.0 years) with diabetes was used for biomarker validation.In the discovery group, untargeted metabolomics analysis found 16 lipids and fatty acids metabolites associated with CVD risk in patients with diabetes, with palmitoyl sphingomyelin (PSM) having the strongest association. Plasma PSM concentrations were significantly higher in cases of diabetes with CVD than without (41.68 ± 10.47 vs. 9.69 ± 1.47 μg/mL; P0.0001). The odds ratio (OR) of CVD for 1 µg/mL PSM change was 1.19 (95% CI 1.13-1.25) after adjustment of clinical confounders. The validation study confirmed that PSM was significantly associated with increased CVD risk in diabetes (OR 1.22 [95% CI 1.16-1.30]).Changes in lipid and fatty acid content were significantly associated with CVD risk in the Chinese population with diabetes. PSM is a potential biomarker of increased CVD risk in diabetes.

Background There is evidence that direct oral anticoagulants administered as potentially inappropriate medications increase the risk of bleeding and thromboembolic complications, which represent serious threats to human health. Objective To identify direct oral anticoagulants administered as potentially inappropriate medications for hospitalized patients aged ≥ 65 years in our hospital, and to determine associated factors and the correlation between potentially inappropriate medications and adverse reactions. Setting Xi’an Central Hospital, China. Method A retrospective cross-sectional study of elderly hospitalized patients who received either dabigatran or rivaroxaban at Xi’an Central Hospital between June 1, 2018 and June 1, 2019. The evaluation criteria of direct oral anticoagulants were formulated based on drug labels, disease guidelines and the 2019 American Geriatrics Society Beers Criteria, and any non-compliance with the criteria was considered to be potentially inappropriate medications. The Pearson chi-square test and a binary logistic regression model were used. Main outcome measure Factors associated with potentially inappropriate medications and correlation between potentially inappropriate medications and adverse reactions. Results This study analysed 315 patients aged ≥ 65 years. The application of our evaluation criteria identified 155 (49.2%) instances of potentially inappropriate medications, comprising 5 different types of potentially inappropriate medications. Fifteen adverse drug reactions occurred in the study participants. The Pearson chi-square test revealed significant differences in number of medications (p = 0.021) and creatinine clearance rate (p = 0.002) between potentially inappropriate medications and non-potentially inappropriate medications groups. In the binary logistic regression model, potentially inappropriate medications use was associated with creatinine clearance (creatinine clearance

Atherosclerosis (AS), known as the chronic inflammatory disease, results from the dysfunction of vascular endothelial cells (VECs). Transforming growth factor-β1 (TGF-β1) has been reported to be induced by oxidized low-density lipoprotein (ox-LDL) and contribute to AS-related vascular endothelial cell damage. This work planned to study the mechanism of TGF-β1 in vascular endothelial cell damage. We found that TGF-β1 was activated by ox-LDL in human umbilical vascular endothelial cells (HUVECs). Silence of TGF-β1 reversed the inductive effect of ox-LDL on apoptosis and inflammatory response of HUVECs. Mechanistically, microRNA-4286 (miR-4286) targeted and inhibited TGF-β1 to inhibit Smad3, and Smad3 bound to the promoter of miR-4286 to repress its transcription. Rescue assays indicated that miR-4286 ameliorated the ox-LDL-induced apoptosis and inflammatory response through inhibiting TGF-β1. In conclusion, our study first demonstrated that miR-4286/TGF-β1/Smad3-negative feedback loop ameliorated vascular endothelial cell damage by attenuating apoptosis and inflammatory response, providing new thoughts for promoting the treatment of AS.

ObjectiveA meta-analysis of published studies was performed to determine whether the efficacy of antiseizure drugs in adults with primary generalized tonic-clonic seizures (PGTCS) is comparable with that in the pediatric population (2–12 years of age).MethodsElectronic searches were conducted in EMBASE, Medline, and the Cochrane Central Register of Controlled Trials for clinical trials of PGTCS in adults and children 2–12 years of age. Neurologists used standardized search and study evaluations to select eligible trials. Median percent reduction in seizure frequency from baseline and ≥50% responder rates were used to compare drug efficacy in adults and children.ResultsAmong 7 adjunctive-therapy PGTCS trials in adults and children (2–12 years of age) that met evaluation criteria, effect sizes were consistent between adults and children for lamotrigine and topiramate. The baseline-subtracted median percent seizure reduction in seizure frequency ranged from 50.0% to 79.7% in children and 57.0% to 64.0% in adults. The ≥50% responder rate was similar between children and adults in a topiramate study (50% in children compared with 58% in adults).ConclusionsThis meta-analysis supports the use of drug response from antiseizure drug clinical trials for PGTCS in adults to predict comparable treatment response in children 2–12 years of age with PGTCS.

Rab22a, a member of the proto-oncogene RAS family, belongs to the Rab5 subfamily. It participates in early endosome formation and regulates vesicle trafficking. The relationship between Rab22a and tumorigenesis remains elusive. In non-small cell lung cancer specimens, immunohistochemical staining showed consistently high expression of Rab22a in lung adenocarcinoma, but not in squamous cell carcinoma. In lung adenocarcinoma cell lines, A549 and H1299, transfection with Rab22a significantly promoted cell proliferation, migration, and invasion, whereas interference with Rab22a specific siRNA significantly inhibited the above capacities. Transfection with Rab22a also up-regulated the phosphorylation levels of core effector proteins on the PI3K/Akt/mTOR pathway. The Co-IP assay further confirmed the interaction between Rab22a and PI3Kp85α, the core regulatory subunit of PI3K. Application of rapamycin, the mTOR inhibitor, significantly reduced the upregulation of the proliferation, migration, and invasion abilities of lung adenocarcinoma cells transfected with Rab22a. These results suggest that Rab22a can promote the malignant phenotype of lung adenocarcinoma by upregulating the PI3K/Akt/mTOR signaling pathway, and may function as a potential anti-tumor therapeutic target.

IgG4-related lung disease (IgG4-RLD) is an unusual disease, with various clinical manifestations and various chest imaging findings. The patients may have no respiratory symptoms. Therefore, diagnosis is challenging. This can easily cause misdiagnosis and mistreatment.A 71-year-old male presented with chest pain, cough, and shortness of breath. Plain chest computed tomography scans showed multi-locus nodes at the center of the hilum.Percutaneous lung biopsy was performed, and IgG4-RLD was diagnosed.Prednisone was orally administered daily.The case's symptoms improved. The patient was discharged from the hospital. After 2 months of reexamination, his symptoms were relieved. Reexamination of the chest computed tomography showed that multi-locus nodes of the lung were obviously absorbed compared with those before.IgG4-RLD is a rare respiratory disease. It has atypical clinical manifestations and chest images. We report the first case of IgG4-RLD showing multi-locus nodes centered on the hilar, hypertrophic mucosa; as well as a narrow and even occluded lumen.

To investigate the relationship between circulating growth differentiation factor (GDF-15) levels and the risk of cardiovascular disease and cancer in people with diabetes.Totally, 510 participants with type 2 diabetes were enrolled from the long-term follow-up of the Da Qing Impaired Glucose Tolerance (IGT) and Diabetes Study (2006-2009). Plasma GDF-15 levels were assessed. Outcomes of cardiovascular events, cancer, and related death were followed up until 2016.Over a 7.5-year follow-up period, 143 (28.0%) of the participants died, and 155 and 56 experienced cardiovascular events and cancer respectively. Multivariable Cox analysis showed that higher circulating GDF-15 levels were significantly associated with the increased risk of cardiovascular and cancer death. The HRs after adjustment of traditional confounders were 1.90 (95%CI 1.31-2.74) and 2.50 (95%CI 1.34-4.67) respectively for an increase in one unit of logElevated circulating levels of GDF-15 predicted a significant increase in the dual risk of cancer and cardiovascular diseases in Chinese people with type 2 diabetes. Thus, it may be a potential predictor of these outcomes in people with diabetes.

To examine the long-term influence of metabolic syndrome (MetS) on death and vascular complications.Altogether, 1419 individuals with different levels of glycemia and MetS were recruited for this study. The participants were followed up for 30 years to assess outcomes.Compared with the non_MetS, individuals with impaired glucose tolerance (IGT) plus MetS had a higher incidence (per 1000 person-years) of all-cause death (20.98 vs 11.70, hazard ratio [HR] = 1.84), macrovascular events (29.25 vs 15.94, HR = 1.36), and microvascular complications (10.66 vs 3.57, HR = 1.96). The incidence of these outcomes was even higher in participants with type 2 diabetes mellitus (T2DM) plus MetS. The T2DM without MetS shared a comparable risk profile of the outcomes with the T2DM plus MetS group (HRs were 3.45 vs 3.15, 2.21 vs 2.65, and 6.91 vs 7.41, respectively).The degree of hyperglycemia in MetS is associated with the severity of death and both micro- and macrovascular complications. T2DM was associated with a comparable risk for all outcomes as T2DM plus MetS. The findings highlight the need of early prevention of diabetes in individuals with IGT plus MetS, while the justification to redefine a subgroup of patients with T2DM as having MetS remains to be clarified.

Background We aimed to explore if hyperglycaemia and hyperinsulinemia in the diabetes and prediabetes population were associated with increased risk of cancer occurence. Methods Overall, 1700 participants with different glycaemic statuses were screened from the 110,660 residents of Da-Qing, China, in 1985. They were followed up to 30 years to access cancer outcomes. Results Cancer was identified in 15.2% (259/1700) of the participants. The incidence of cancer in the normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes groups was 6.06, 6.77, and 7.18 per 1000 person-years, respectively (P = 0.02). In the Fine-Gray model with all cause death as competing risk, compared with the NGT controls, both IGT and diabetes groups demonstrated significantly higher risk of cancer (for the IGT group, adjusted hazard ratio (aHR) = 1.77, 95% CI 1.38–2.27, P P P = 0.008) and insulin-area under the curve at baseline (for 1 SD increase, aHR = 1.39, P = 0.02) were also associated with the risk of cancer after adjustment of covariables. Conclusions Hyperglycaemia in patients with diabetes, hyperinsulinemia, and progression to diabetes in people with IGT is significantly associated with the long-term increased risk of cancer occurrence.

Background The adverse drug reactions (ADRs) related to clonazepam are mild, and only two cases of myotoxicity induced by clonazepam have been reported, with both patients recovering well. We present a unique case of a serious ADR outcome after taking clonazepam. Case presentation A 24-year-old woman with a long-standing history of polio and a 2-year history of epilepsy developed a serious ADR after repeated exposure to oral clonazepam combined with sodium valproate that manifested as myotoxicity and elevated levels of creatine phosphokinase. The patient is currently bedridden and unable to take care of herself. Conclusion Clinicians should be vigilant of the possibility of myotoxicity induced by clonazepam, especially in specific populations such as polio patients or when clonazepam is used in combination therapies.

Paying attention to the rising popularity of virtual assistants (VAs) that offer unique user experiences through voice-centered interaction, this study examined the effects of modality, device, and task differences on perceived human likeness of, and attitudes toward, voice-activated VAs. To do so, a 2 (modality: voice vs. text) × 2 (device: mobile vs. laptop) × 2 (task type: hedonic vs. utilitarian) mixed factorial experimental design was employed. Findings suggest that voice (vs. text) interaction leads to more positive attitudes toward the VA system mediated by heightened perceived human likeness of the VA, but only with utilitarian (vs. hedonic) tasks. Interestingly, laptop (vs. mobile phone) interaction also enhanced perceived human likeness of the VA. This study offers theoretical and practical implications for VA research by exploring the combinational effects of modality, device, and task differences on user perceptions through human-like interactions.

Background Both of the modern medicine and the traditional Chinese medicine classify depressive disorder (DD) and chronic fatigue syndrome (CFS) to one type of disease. Unveiling the association between depressive and the fatigue diseases provides a great opportunity to bridge the modern medicine with the traditional Chinese medicine. Methods In this work, 295 general participants were recruited to complete Zung Self-Rating Depression Scales and Chalder Fatigue Scales, and meanwhile, to donate plasma and urine samples for 1H NMR-metabolic profiling. Artificial intelligence methods was used to analysis the underlying association between DD and CFS. Principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to analyze the metabolic profiles with respect to gender and age. Variable importance in projection and t-test were employed in conjunction with the PLS-DA models to identify the metabolite biomarkers. Considering the asymmetry and complexity of the data, convolutional neural networks (CNN) model, an artificial intelligence method, was built to analyze the data characteristics between each groups. Results The results showed the gender- and age-related differences for the candidate biomarkers of the DD and the CFS diseases, and indicated the same and different biomarkers of the two diseases. PCA analysis for the data characteristics reflected that DD and CFS was separated completely in plasma metabolite. However, DD and CFS was merged into one group. Limitation Lack of transcriptomic analysis limits the understanding of the association of the DD and the CFS diseases on gene level. Conclusion The unmasked candidate biomarkers provide reliable evidence to explore the commonality and differences of the depressive and the fatigue diseases, and thereby, bridge over the traditional Chinese medicine with the modern medicine.

This study aimed to investigate premature mortality and the risk of cardiovascular disease (CVD) in Chinese adults with diabetes diagnosed before the age of 45 years. A total of 519 participants with normal glucose tolerance (NGT) and 630 with newly diagnosed diabetes mellitus (DM) were recruited in 1986 in the Da Qing Diabetes Study. In 2009, the participants were followed up to assess mortality and CVD events. The subjects were stratified into four subgroups according to age and diabetes status: age

Hypertension is more prevalent in subjects with impaired glucose tolerance (IGT), but whether higher blood pressure per se or the mild hyperglycemia in combination with the hypertension enhanced the risk of cardiovascular disease (CVD) remains unclear.Five hundred and sixty-eight participants with IGT in the original Daqing diabetes prevention study, 297 with hypertension (HBP) and 271 without hypertension (NBP), were enrolled in 1986 and the intervention phase lasted for 6 years. In 2009, they were followed up to assess the outcomes of cardiovascular events (including stroke and myocardial infarction) and incidence of diabetes.Over 23 years, the incidence of diabetes was 93.9/1000 person-years in HBP and 72.2/1000 person-years in the NBP group, with an age- and sex-adjusted hazard ratio of 1.26 (95% confidence interval [CI], 1.04-1.54, P = 0.02). The yearly incidence of CVD events was 27.7/1000 person-years and 16.6/1000 person-years, indicating a 35% higher risk in HBP than in the NBP group (95% CI, 1.01-1.81; P = 0.04). Cox proportional hazard analysis showed that a 10-mm Hg increase of the baseline systolic blood pressure was associated with 9% increased risk of the development of diabetes (P = 0.02), together with a 7% higher risk of the CVD events (P = 0.02).Hypertension predicted diabetes and enhances long-term risk of CVD events in patients with IGT. An individualized strategy that targets hypertension as well as hyperglycemia is needed for diabetes and its cardiovascular complications.背景: 高血压在糖耐量受损(impaired glucose tolerance，IGT)人群中更为普遍。而它对心血管疾病(CVD)的影响是来自高血压本身还是轻度高血糖与血压的共同作用尚不清楚。 方法: 1986年大庆糖尿病预防研究初始纳入IGT患者568例，分为IGT伴高血压组297例，IGT不伴高血压组271例。对IGT患者进行6年生活方式干预。随访至2009年评估两组的新发糖尿病和心血管事件(包括脑卒中和急性心肌梗死)发生率。 结果: 随访23年中，IGT伴高血压组和不伴高血压组的2型糖尿病发生率分别为93.9/千人/年和72.2/千人/年。校正年龄和性别影响后，IGT伴高血压组的糖尿病发病风险为非高血压组1.26倍[95%可信区间(CI)，1.04-1.54，P = 0.02]。心血管事件的发生率在IGT伴高血压组为27.7/千人/年，不伴高血压组为16.6/千人/年，与不伴高血压组相比，IGT伴高血压组的发病风险增加35%(95% CI，1.01-1.81，P = 0.04]。COX比例风险分析显示基线收缩压每升高10 mmHg，糖尿病的发生风险增加9.0%(P = 0.02)，同时心血管事件的发生风险增加7%(P = 0.02)。 结论: 在糖耐量受损人群中，高血压预测2型糖尿病的发生，并提高长期心血管事件的发生风险。个体化治疗策略应是降糖的同时还兼顾降压，以预防糖尿病及心血管并发症发生。.

An interference-free photoelectrochemical (PEC) immunoassay was developed for cardiac troponin I (cTnI) detection. Covalent linkage of cTnI antibody to carboxymethylated (CM-) dextran pre-immobilized onto a gold nanoparticles (AuNPs)-modified TiO

Online users today are provided with a variety of customization tools to build their own information environment. A growing number of public health messages reach their target audiences via these digital venues. Given the deeply personal and individualized nature of customized environments, do online users show lesser reactance to persuasive health messages? Or, are they more likely to show reactance because they feel intruded upon? We conducted a 2 (Customization: present vs. absent) × 2 (Message threat: high vs. low) experiment (N = 145) to find out. Data showed that interface customization increases the sense of control and sense of identity among users. Sense of control is positively associated with threat to freedom of action, causing more affective reactance. In contrast, a sense of identity is negatively associated with anger toward the persuasive message. Theoretical and practical implications for online health campaigns are discussed.

Background Lecanemab (BAN2401), an IgG1 monoclonal antibody, preferentially targets soluble aggregated amyloid beta (Aβ), with activity across oligomers, protofibrils, and insoluble fibrils. BAN2401-G000-201, a randomized double-blind clinical trial, utilized a Bayesian design with response-adaptive randomization to assess 3 doses across 2 regimens of lecanemab versus placebo in early Alzheimer’s disease, mild cognitive impairment due to Alzheimer’s disease (AD) and mild AD dementia. Methods BAN2401-G000-201 aimed to establish the effective dose 90% (ED90), defined as the simplest dose that achieves ≥90% of the maximum treatment effect. The primary endpoint was Bayesian analysis of 12-month clinical change on the Alzheimer’s Disease Composite Score (ADCOMS) for the ED90 dose, which required an 80% probability of ≥25% clinical reduction in decline versus placebo. Key secondary endpoints included 18-month Bayesian and frequentist analyses of brain amyloid reduction using positron emission tomography; clinical decline on ADCOMS, Clinical Dementia Rating-Sum-of-Boxes (CDR-SB), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14); changes in CSF core biomarkers; and total hippocampal volume (HV) using volumetric magnetic resonance imaging. Results A total of 854 randomized subjects were treated (lecanemab, 609; placebo, 245). At 12 months, the 10-mg/kg biweekly ED90 dose showed a 64% probability to be better than placebo by 25% on ADCOMS, which missed the 80% threshold for the primary outcome. At 18 months, 10-mg/kg biweekly lecanemab reduced brain amyloid (−0.306 SUVr units) while showing a drug-placebo difference in favor of active treatment by 27% and 30% on ADCOMS, 56% and 47% on ADAS-Cog14, and 33% and 26% on CDR-SB versus placebo according to Bayesian and frequentist analyses, respectively. CSF biomarkers were supportive of a treatment effect. Lecanemab was well-tolerated with 9.9% incidence of amyloid-related imaging abnormalities-edema/effusion at 10 mg/kg biweekly. Conclusions BAN2401-G000-201 did not meet the 12-month primary endpoint. However, prespecified 18-month Bayesian and frequentist analyses demonstrated reduction in brain amyloid accompanied by a consistent reduction of clinical decline across several clinical and biomarker endpoints. A phase 3 study (Clarity AD) in early Alzheimer’s disease is underway. Trial registration Clinical Trials.govNCT01767311.

Objectives: To evaluate the effect of Yugengtongyu granules on reducing the incidence of adverse cardiovascular events and improving quality of life (QOL) in patients with stable coronary artery di...

The simple and scalable synthesis of poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC)-coated conducting polymer (CP) nanocomposites is described. These functional nanocomposites exhibit tunable absorption in the near-infrared region with relatively high photothermal efficiencies. More importantly, their potential for bio-imaging and therapeutic treatment is proven by cellular uptake and cytotoxicity studies.

In treatment of hypoxic tumors, oxygen-dependent photodynamic therapy (PDT) is considerably limited. Herein, a new bimetallic and biphasic Rh-based core–shell nanosystem (Au@Rh-ICG-CM) is developed to address tumor hypoxia while achieving high PDT efficacy. Such porous Au@Rh core–shell nanostructures are expected to exhibit catalase-like activity to efficiently catalyze oxygen generation from endogenous hydrogen peroxide in tumors. Coating Au@Rh nanostructures with tumor cell membrane (CM) enables tumor targeting via homologous binding. As a result of the large pores of Rh shells and the trapping ability of CM, the photosensitizer indocyanine green (ICG) is successfully loaded and retained in the cavity of Au@Rh-CM. Au@Rh-ICG-CM shows good biocompatibility, high tumor accumulation, and superior fluorescence and photoacoustic imaging properties. Both in vitro and in vivo results demonstrate that Au@Rh-ICG-CM is able to effectively convert endogenous hydrogen peroxide into oxygen and then elevate the production of tumor-toxic singlet oxygen to significantly enhance PDT. As noted, the mild photothermal effect of Au@Rh-ICG-CM also improves PDT efficacy. By integrating the superiorities of hypoxia regulation function, tumor accumulation capacity, bimodal imaging, and moderate photothermal effect into a single nanosystem, Au@Rh-ICG-CM can readily serve as a promising nanoplatform for enhanced cancer PDT.

Recently, ultrasmall gadolinium oxide (Gd2O3) nanoparticles with high longitudinal relaxation rate have received enormous attention. However, it can't be concentrated in tumor site through intravenous administration due to its ultrasmall size. In this project, we coated ultrasmall Gd2O3 nanoparticles with a near-infrared (NIR) light-absorbing polymer polypyrrole (PPy), modifying with hyaluronic acid (HA) and loaded aluminum phthalocyanine (AlPc), the Gd2O3@PPy/AlPc-HA nanoparticles could be used for fluorescence (FL)/magnetic resonance (MR)/photoacoustic (PA) imaging guided as well as remotely controlled PTT/PDT combined anti-tumor therapy. Polymerized PPy with high photothermal conversion efficiency was introduced to assemble the ultrasmall Gd2O3 nanoparticles which have high longitudinal relaxation rate and signal-to-noise ratio, thus obtaining Gd2O3@PPy nanoparticles which possess a larger particle size and can be more suitable for tumor targeting based on the EPR effect. HA and AlPc were adsorbed on PPy for HA-mediated tumor targeting and photodynamic therapy respectively. The in vivo triple-modal imaging revealed that Gd2O3@PPy/AlPc-HA nanoparticles possess enhanced tumor uptake effect after intravenous injection. More importantly, the nanoparticles exhibited an obvious photothermal effect, which can trigger the release and de-quench of AlPc. The anti-tumor efficiency further corroborated that the combined therapy achieved an excellent tumor inhibition therapeutic effect which was much better than any other mono-therapy. Consequently, our work encouraged further exploration of polymer-based multifunctional theranostic nanoparticles for cancer combination therapy under remote near-infrared (NIR) light controls.

For integrating therapy and diagnosis into a single nanoparticle for higher antitumor efficiency and lower toxicity, our group designed a smart theranostic nanoplatform based on a hyaluronic acid-doped polypyrrole-coated bismuth selenide loading with a zinc phthalocyanine nanodish complex (Bi2Se3@HA-doped PPy/ZnPc) for multimodal imaging-guided combined phototherapy. Moreover, we expect that the HA-doped PPy smart shell for the surface functionalization will also be applied to a variety of 2D nanomaterials sharing a similar structure with Bi2Se3 to broaden their applications in biomedicine. The Bi2Se3 hexagon nanodish was synthesized via a simple and safe solution-based method compared to the commonly adopted ones. A one-pot synthesis of the naoncomplex was carried out by adding HA during the polypyrrole coating on the Bi2Se3 process, and then it was further loaded with ZnPc. Besides the good ability for infrared thermal, photoacoustic, fluorescence, and X-ray computed tomography imaging, the nanodish com...

Chimeric antigen receptor modified T cells against CD19 (CART19s) have potent anti-leukemia activities in patients with refractory/relapsed acute lymphoblastic leukemia (R/R ALL). This study was designed to investigate the correlation between safety/efficacy and therapeutic modalities including chemotherapy and CART19 therapy. Total 23 and 69 patients were enrolled in the CART19 group and in the chemotherapy group, respectively. The safety and efficacy profiles of 66 and 22 patients in the 2 groups were evaluated. The complete remission (CR) rate was higher in the CART19 group than that in the chemotherapy group (90.9 vs 37.9%, P = 0.000). For patients relapsed after allo-HSCT and chemotherapy, CR rates were 100% (8/8) vs 48.0% (12/25) (P = 0.009) and 85.7% (12/14) vs 31.7% (13/41) (P = 0.000), respectively. Moreover, a higher percentage in the CART19 group had results below the threshold for minimal residual disease (100 vs 7.58%, P = 0.000). In survival analysis, the overall survival rate at 12 months was higher in the CART19 group than that in the chemotherapy group (60.9 vs 10.1%, P = 0.000). For post-transplant patients achieving CR, 25.0% (2/8) and 75.0% (9/12) complicated with GVHD (P = 0.04) in the CART19 group and chemotherapy group, respectively. For all CR patients, the median duration of absolute neutrophil count less than 500/μL and platelet count less than 20,000/μL were longer in the CART19 group than in the chemotherapy group (p = 0.0047 and 0.0003, respectively). Our data demonstrated that patients with CART19s therapy acquired higher rates of remission and longer survival, confirming the encouraging application of CART19 therapy in R/R ALL.

Blood-based protein biomarkers have recently shown as simpler diagnostic modalities for colorectal cancer, while their association with clinical pathological characteristics is largely unknown. In this study, we not only examined the sensitivity and reliability of single/multiple serum markers for diagnosis, but also assessed their connection with pathological parameters from a total of 279 colorectal cancer patients. Our study shown that glycoprotein carcinoembryonic antigen (CEA) owns the highest sensitivity among single marker in the order of CEA > cancer antigen 72-4 (CA72-4) > cancer antigen 19-9 9 (CA19-9) > ferritin > cancer antigen 125 (CA125), while the most sensitive combined-markers for two to five were: CEA + CA72-4; CEA + CA72-4 + CA125; CEA + CA19-9 + CA72-4 + CA125; and CEA + CA19-9 + CA72-4 + CA125 + ferritin, respectively. We also demonstrated that patients who had positive preoperative serum CEA, CA19-9, or CA72-4 were more likely with lymph node invasion, positive CA125 were prone to have vascular invasion, and positive CEA or CA125 were correlated with perineural invasion. In addition, positive CA19-9, CA72-4, or CA125 was associated with poorly differentiated tumor, while CEA, CA19-9, CA72-4, CA125 levels were positively correlated with pathological tumor-node-metastasis stages. We here conclude that combined serum markers can be used to not only diagnose colorectal cancer, but also appraise the tumor status for guiding treatment, evaluation of curative effect, and prognosis of patients.

Mesoporous silica nanoparticles (MSNs) have long since been investigated to provide a versatile drug-delivery platform due to their multitudinous merits. Presently, gadolinium (Gd), a T1 magnetic resonance imaging (MRI) contrast agent, was doped into MSNs as a newly emerging theranostic nanocomposite, which has received much research attention. However, it is still concerned about the dispersibility and drug leakage of MSNs. Hence, in this project, we constructed an near-infrared (NIR) irradiation-triggered, triple-modal imaging-guided nanoplatform based on doxorubicin (DOX)@Gd-doped MSNs, conjugating with indocyanine green (ICG)-loaded thermosensitive liposomes (designated as DOX@GdMSNs-ICG-TSLs). In this platform, ICG could contribute to both photodynamic therapy and photothermal therapy effects; meanwhile, it could also give play to near-infrared fluorescence imaging (NIRFI) as well as photoacoustic imaging (PAI). Consequently, NIRFI and PAI from ICG combined with the MRI function of Gd, devoted to triple-modal imaging with success. At the same time, folic acid-modified thermosensitive liposomes were explored to be coated onto the surface of DOX@GdMSNs, to solve the DOX leakage as well as improve cellular uptake. Under NIR irradiation, ICG could generate heat, thus leading to the rupture of ICG-TSLs and the release of DOX. Accordingly, the multifunctional nanocomposite appeared to be a promising meritorious theranostic nanoplatform to pave a way for treating cancer.

Background and study aims For bowel preparation, using a reduced volume of polyethylene glycol (PEG) solution without influencing its effectiveness would be preferable. While simethicone shows great potential as an adjunctive agent, data on its use are limited. We aimed to clarify whether simethicone added to low-volume PEG solution improved bowel cleansing. Patients and methods Consecutive adult patients registered for colonoscopy were recruited from seven medical centers in South China between 15 April and 15 July 2015 and prospectively randomized into two groups: 2 L PEG (conventional group) and 2 L PEG plus simethicone (simethicone group). The primary endpoint was the effectiveness of bowel cleansing according to the Boston Bowel Preparation Scale (BBPS). Secondary endpoints included cecal intubation time, adenoma detection rate (ADR), patient safety and compliance, and adverse events. Results We included 290 and 289 patients in the conventional and simethicone groups, respectively, for analysis. The proportion with acceptable bowel cleansing (BBPS ≥ 6) was significantly higher in the simethicone group than in the conventional group (88.2 % vs. 76.6 %; P Conclusions Simethicone added to low-volume PEG solution improves bowel-cleansing efficacy, with similar safety and compliance, shorter cecal intubation time, and higher ADR.

Purpose: Patients with relapsed/refractory acute lymphocytic leukemia (R/R ALL) have a poor prognosis. Chimeric antigen receptor–modified T cells against CD19 (CART19) have displayed anti-leukemia activities. However, data from systemic trials in Chinese patients are limited. Experimental Design: T cells transduced with CD19-directed CAR lentiviral vectors were infused in patients with R/R ALL under fludarabine- and cyclophosphamide-based lymphodepletion. The postinfusion responses, toxicities, expansion, and persistence of CART19s in enrolled patients were observed and monitored. Results: We enrolled 15 patients with R/R ALL. The median transduction efficiency of CART19s was 33%. In vitro cytotoxicity assays were conducted and showed prominent antileukemia activities with CART19s. The patients received CART19s infusion at doses of 1.1 × 106/kg to 9.8 × 106/kg. Twelve patients achieved complete remission 1 month after CART19s infusion. CART19s expanded and persisted in peripheral blood and bone marrow. At 150 days, the overall survival rate and leukemia-free survival rate were 65.5% and 37.8%, respectively. The cumulative incidence of relapse and the nonrelapse mortality rate were 54.5% and 7.7%, respectively. Four patients underwent subsequent haploidentical hematopoietic stem cell transplantation. In this trial, 10 patients experienced cytokine release syndrome (CRS). Grade 3 CRS developed in 40% of patients and was associated with a higher disease burden on day −1 and a higher number of previous relapses. Conclusions: This trial demonstrated potent antileukemia activities of CART19s in Chinese patients with R/R ALL. Disease relapse remained the main obstacle. However, patients with a high risk of relapse after CART19s might benefit from subsequent haploidentical hematopoietic stem cell transplantation. Clin Cancer Res; 23(13); 3297–306. ©2016 AACR.

OBJECTIVE: To describe the characteristics of nystagmus in patients with Light Cupulopathy and to investigate its therapeutic effect. METHOD: The Supine roll test in our hospital's otology clinic showed persistent DCPN in 26 patients, who received Supine roll test, null-point position test, and prone-supine test. All patients were treated with barbecue maneuver. The immediate, short-term and long-term effects of treatment were investigated. RESULT: Null-point position on one side was present in 26 patients. The angles ranged from 15-45°, with an average of (26.34±8.78)°. Spontaneous nystagmus was observed in 30.8% (8/26) patients. The nystagmus was directed to the affected side in prone position and to the healthy side in supine position. Seventy-three percent of the patients had strong nystagmus and 26.9% had weak nystagmus in the Supine roll test. All patients received Barbecue maneuver, and the recovery rates were 0, 42.3% and 88.5% immediately, 1 week and 1 month after treatment respectively. There was a statistical difference in the recovery rate among immediate, one week and one month later (P < 0.01). CONCLUSION: The nystagmus performance of patients with persistent DCPN conforms to the light cupula hypothesis. The lesion side can be determined according to the null-point position and prone-supine test. The lesion side cannot be determined by the intensity of nystagmus in the Supine roll test in some cases. Repositioning maneuver is ineffective in treating light cupulopathy, but the disease is self-limited.

Dual-emission carbon dots were synthesized by one-pot hydrothermal pyrolysis of citric acid and polyethyleneimine in the presence of rhodamine B at 160 °C for 5 h. The carbon dots have an average diameter of 2.51 nm with rhodamine moiety on their surface. Two emission bands centered at 447 and 581 nm are exhibited in their fluorescence spectra excited at 360 nm, and the former is sensitive while the latter is insensitive to Hg

The patterning of nanoparticles, which are promising photothermal agents, is of great importance to selectively and precisely ablate tissues by thermal effects. In this paper, we demonstrated that nano-sized gold particles (gold nanocages, AuNCS) with a hollow structure could be used to generate various wavefront patterns of surface acoustic waves (SAWs) and the aligned AuNC lines facilitated the destruction of cancer cells by the thermal effect with high spatial resolution. The hollow structure improved the acoustic sensitivity of AuNCs, making them more sensitive to the acoustic radiation force. Moreover, the multi-scale patterning of AuNCs could be achieved by the interference of multiple acoustic beams. Given the photothermal characteristics of AuNCs, selective temperature elevation within a micrometer-sized region could be realized when the patterned AuNCs were irradiated by a laser. The cancer cells where the patterned AuNCs were located were eliminated by thermal ablation, while other cells remained alive. In particular, the acoustic frequency used in this study was as low as 11. 35 MHz and was in the range of diagnostic ultrasound (less than 12 MHz), offering a potential to serve as a powerful tool in clinical applications.

A highly selective lysosome-targeting NIR fluorescent probe (Lyso-SiR-2S) for HOCl was constructed based on Si-rhodamine B spirodithiolactone. This probe was very effectively employed to sense HOCl produced in various living cells and to visualize fluctuations of endogenous HOCl resulting from GEN-induced acute kidney injury in vivo for the first time.

Background Limited information is available on the long-term risk of cardiovascular disease (CVD) associated with hypertriglyceridaemia (HTG) in the Chinese population. We estimated this risk over a 23-year period in participants recruited from among those included in the Da Qing Diabetes Study. Methods A total of 833 Chinese adults including 379 with normal glucose levels and 454 with hyperglycaemia were identified by their oral glucose tolerance in 1986 in Da Qing, China. CVD outcomes were monitored until 2009. Thirty-four percent (280/833) of the participants had HTG, which was defined as a fasting plasma triglyceride (TG) level ≥ 1.7 mmol/L, at the baseline time point. Results Over the 23-yearfollow-up period, 149 subjects in the HTG group and 190 subjects in the non-HTG group (NTG group) experienced their first CVD event, including fatal or nonfatal myocardial infarction (MI) and stroke. The age and sex-adjusted annual incidence of the first CVD event per 1000 person-years was 30.23 for the HTG group vs 18.68 for the NTG group. The corresponding rates for MI and stroke were 7.71 vs 3.89 and 19.55 vs 13.98, respectively. After adjusting for confounders, the HTG group had a 28% higher risk of the first CVD event than the NTG group. This association was significant among only the subjects with a serum cholesterol level > 5.7 mmol/L and those with diabetes or impaired glucose tolerance (IGT). Conclusion HGT predicted a substantially higher subsequent long-term risk of the first CVD event in Chinese adults, especially in those with hypercholesterolaemia and hyperglycaemia.

Unstable angina pectoris (UA) is one of the most dangerous clinical symptoms of acute coronary syndrome due to the risk of myocardial ischemia, which can lead to high morbidity and mortality worldwide. Though there are many advantages in understanding the pathophysiology of UA, the identification of biomarkers for the diagnosis, prognosis, and treatment of UA remains a challenge in the clinic. A global metabolomics research based on ultra-performance liquid chromatography (UPLC) combined with Q-TOF/MS was performed to discover the metabolic profile of health controls, UA patients, and UA patients with diabetes mellitus (DM), and screen for potential biomarkers. Twenty-seven potential biomarkers were determined using pattern recognition. These biomarkers, which include free fatty acids, amino acids, lysoPE and lysoPC species, and organic acids, can benefit the clinical diagnosis of UA. Pathway analysis indicated that arginine and proline metabolism, glycerophospholipid metabolism, and purine metabolism were affected in the UA patients, uniquely. Additionally, alterations in the metabolic signatures between UA and UA-complicated DM were also explored. As a result, six differential metabolites with an area under the curve (AUC) of more than 0.85 were identified as biomarkers for the diagnosis of UA and UA complicated with DM. Pathway analysis implied tryptophan metabolism was a key metabolic pathway in UA patients with DM, which provides new insights into the pathological study and drug discovery of UA.

We report an efficient and highly diastereoselective protocol for the rapid construction of 3-nitro substituted 4-chromanones by an intramolecular Michael-type cyclization of α-nitro aryl ketones bearing unsaturated ester units. A catalytic amount of KOtBu was found to be crucial for the high diastereoselective control of this transformation. With this protocol, a series of 3,3-disubstituted 3-nitro-4-chromanones were synthesized in good to excellent yields with high diastereoselectivities and showed moderate to good in vitro antitumor activities, representing promising antitumor hits for further drug discovery.

Rod-shape nanoplatform have received tremendous attention owing to their enhanced ability for cell internalization and high capacity for drug loading. MoS2, widely used in electronic devices, electrocatalysis, sensor and energy-storage, has been studied as photothermal agents over the years. However, the efficacy of rod-shape MoS2 based photothermal agents for photothermal therapy has not been studied before. Here, a near-infrared (NIR) light-absorbing MoS2 nanosheets coated mesoporous silica nanorods with human serum albumin (HSA) modifying and Ce6 loading (MSNR@MoS2-HSA/Ce6) were constructed for combined photothermal and photodynamic therapy. Methods: The near-infrared (NIR) light was used to trigger the synergistic anti-tumor therapy. In addition, breast cancer cell line was applied to evaluate the in vitro anti-tumor activity. The multi-modal imaging capacity and tumor-killing efficiency of the designed nanocomposites in vivo was also demonstrated with the 4T1 tumor-bearing mouse model. Results: These nanocomposites could not only perform NIR light triggered photodynamic therapy (PDT) and photothermal therapy (PTT), but also achieve in vivo fluorescence (FL) /multispectral optical tomography (MSOT)/X-ray computed tomography (CT) triple-model bioimaging. What's more, the rod-shape nanoplatform could be endowed with better anti-tumor ability based on the EPR effect and HSA-mediated active tumor targeting. At the same time, the hyperthermia generated by MoS2 could synergistically improve the PDT effect with the acceleration of the blood flow, leading to the increase of the oxygen level in tumor tissue. Conclusion: MSNR@MoS2-HSA/Ce6 proves to be a promising multi-functional nanoplatform for effective treatment of tumor.

To examine whether high-sensitivity C-reactive protein (hs-CRP) can predict all-cause death in Chinese adults with hyperglycemia.All the 237 diabetes and 49 prediabetes recruited in the study were evolved from the participants with impaired glucose tolerance in the original Da Qing Diabetes Study. Blood hs-CRP level was measured at 2006. Ten-year outcome of death was traced from 2006 to 2016. Cox model was used to analyse the association between hs-CRP level and the risk of all-cause death occurred over the subsequent 10 years.During the follow-up, death occurred in 36 (37.9%) subjects in the highest hs-CRP tertile group (hs-CRP 2.16 mg/L) and 19 (20.0%) in the lowest hs-CRP tertile group (hs-CRP 0.82 mg/L, p 0.05). The corresponding incidence of all-cause death (per 1,000 person-years) was 44.7 (95% CI 30.1-59.3) and 21.6 (95% CI 11.9-31.3) in the two groups respectively (p 0.0001). The highest hs-CRP tertile was associated with the increased risk of all-cause death significantly (hazard ratio 1.88, 95% CI 1.07-3.32) after controlling for traditional risk factors.Serum hs-CRP was predictive of 10-year all-cause death in Chinese adults with hyperglycemia, suggesting the impact of low-grade inflammation on mortality deserves more attention.

OBJECTIVE People with impaired glucose tolerance (IGT) have increased risk of mortality and a high risk of progression to diabetes, but the extent that the excess mortality is associated with IGT per se or is the result of subsequent diabetes is unclear. RESEARCH DESIGN AND METHODS We compared mortality before and after the development of diabetes among 542 persons with IGT initially who participated in a 6-year lifestyle diabetes prevention trial and were followed-up from 1986 to 2009. RESULTS During the 23-year follow-up, 174 (32.1%) died, with an overall death rate of 15.9/1,000 person-years. The majority of deaths (74.7%; 130 of 174) occurred after progression to type 2 diabetes, with age-adjusted death rates of 11.1/1,000 person-years (95% CI 8.2–12.0) before and 19.4/1,000 person-years (95% CI 11.9–23.3) after the development of type 2 diabetes. The cumulative mortality was 37.8% (95% CI 33.1–42.2%) in participants who developed type 2 diabetes during first 10 years of follow-up, 28.6% (95% CI 21.6–35.0%) in those who progressed to type 2 diabetes in 10–20 years, and 13.9% (95% CI 7.0–20.3%) in those who did not develop to type 2 diabetes within 20 years. Time-dependent multivariate Cox proportional hazards analyses, with adjustment for baseline age, sex, intervention, and other potential confounding risk factors, showed that the development of type 2 diabetes was associated with a 73% higher risk of death (hazard ratio 1.73 [95% CI 1.18–2.52]). CONCLUSIONS As elsewhere, IGT is associated with increased risk of mortality in China, but much of this excess risk is attributable to the development of type 2 diabetes.

Photodynamic therapy (PDT) is commonly restricted by inefficient tumor selectivity during clinical study. Hence, a mitochondria-targeting multifunctional nanocarrier "theranosome (TNS)" was developed for near-infrared fluorescent (NIRF) imaging and photoacoustic (PA) imaging. What's more, the TNS can also enhance PDT efficacy. In this work, chlorin e6 (Ce6) undertakes reactive oxygen generation and fluorescence emission. Ce6 was quenched when being encapsulated into TNS together with IR780 iodide. When exposed under 808 nm NIR light, IR780 from the TNS can be photobleached; thus, the phototoxicity of Ce6 can be activated. The IR780 induced hyperthermia damaged tumor cells to perform photothermal therapy (PTT) effect. Then lysosomes disruption under PTT facilitated PDT effect induced by Ce6 through enhanced cytoplasmic delivery. Moreover, in vitro subcellular uptake experiments showed that triphenylphosphonium (TPP) group attached to the IR780/Ce6 TNS (ICT) could promote mitochondria targeting capacity. It can lead to PDT induced oxidizing damage to the mitochondria by mitochondrial membrane potential decreasing and cell apoptosis eventually. In in vivo antitumor studies, the TPP/IR780/Ce6 TNS (TICT) substantially repressed tumor growth in nude mice. Besides, we did not find any obvious side effects to normal tissues and organs. The results suggested the TICT conjugate provided a dual NIRF/PA tumor imaging modalities with spatial resolution and superior imaging contrast. This study offered an improved phototherapy for potential theranostic application.