A Systematic Review and Meta-Analysis of the Predictive Power of China-PAR Against Cardiovascular Disease.

Background and Purpose: To evaluate the predictive power of the China-PAR model for cardiovascular disease (CVD).Methods: Dominate databases, including PubMed, Web of Science, CNKI, Wanfang Data Knowledge Service Platform, Chinese Biomedical Literature Service System, and VIP self-built database, were searched from January 1, 2016 to February 22, 2022. The primary outcome included observed events and predicted events by China-PAR. Meta-analysis was performed using RevMan 5.3 software. Stroke, arteriosclerotic cardiovascular disease (ASCVD), male, and female were divided into subgroup analyses. Funnel plots were used to assess publication bias.Results: A total of nine studies, which included 221,918 participants, were analyzed. Meta-analysis showed the combined observed incidence of CVD was 3.97%, and the combined predicted incidence was 9.59% by China-PAR. There was no significant difference between the observed and the predicted events. Subgroup analysis showed there was no statistical significance between the observed and the predicted events for stroke or for ASCVD. The difference between the observed and the predicted events by China-PAR was not statistically significant in either males or females.Conclusions: China-PAR model has important public health significance to further improve the primary prevention strategy of CVD.

Changes in brain function and heart sound in acute sleep deprivation individuals.

AIMS: Sleep deprivation (SD) has become a health problem in modern society due to its adverse effects on different aspects. However, the relationship between sleep and cardiovascular system function remains unclear. Here we explored the changes occurring in the brain and the heart sounds after SD. METHODS: Ninety healthy adult men were recruited and subjected to 36 h of Sleep Deprivation (SD). They participated in a number of tests, including measurements of the heart sound, blood oxygen, and heart rate every 2 h. By using of principal component analysis to reduced the dimensionality of heart sound data. While the ALFF and ReHo indexes were measured via fMRI before and after SD. Correlation and regression analyses were used to reveal the relationship between fMRI and heart sound changes due to SD. RESULTS: In this study, there were no abnormal values in the heart rate and blood oxygen during 36 h of SD, whereas the intensity of heart sounds fluctuated significantly increased and decreased. The ALFF was increased in bilateral pericalcarine(Calcarine), left anterior cuneus, (Precuneus_L), right superior temporal gyrus(Temporal_Sup_R), left supplementary motor area (Supp_Motor_Area_L); However, it was reduced in the right medial superior frontal gyrus (Frontal_Sup_Medial_R), right dorsolateral superior frontal gyrus (Frontal_Sup_R) and left medial frontal gyrus (Frontal_Mid_L). The regression analysis uncovered that the intensity of the heart sound in the systole, s1, and s2 phase could be explained by Calcarine_L changes. CONCLUSION: Acute sleep deprivation affects cardiac-brain axis and the specific brain regions. Calcarine_L changes during sleep deprivation are involved in regulating heart contractions.

The Effect of Transcranial Electrical Stimulation on the Recovery of Sleep Quality after Sleep Deprivation Based on an EEG Analysis.

Acute sleep deprivation can reduce the cognitive ability and change the emotional state in humans. However, little is known about how brain EEGs and facial expressions change during acute sleep deprivation (SD). Herein, we employed 34 healthy adult male subjects to undergo acute SD for 36 h, during which, their emotional states and brain EEG power were measured. The subjects were divided randomly into electronic stimulation and control groups. We performed TDCS on the left dorsolateral prefrontal cortex for 2 mA and 30 min in the TDCS group. These results indicated that the proportion of disgusted expressions in the electrical stimulation group was significantly less than the controls after 36 h post-acute SD, while the proportion of neutral expressions was increased post-restorative sleep. Furthermore, the electrical stimulation group presented a more significant impact on slow wave power (theta and delta) than the controls. These findings indicated that emotional changes occurred in the subjects after 36 h post-acute SD, while electrical stimulation could effectively regulate the cortical excitability and excitation inhibition balance after acute SD.

Accuracy of Raman spectroscopy in the diagnosis of Alzheimer's disease.

Objective: To systematically evaluate the accuracy of Raman spectroscopy in the diagnosis of Alzheimer's disease. Methods: Databases including Web of Science, PubMed, The Cochrane Library, EMbase, CBM, CNKI, Wan Fang Data, and VIP were electronically searched for studies on Raman spectroscopy in diagnosis of Alzheimer's disease from inception to November 2022. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. Then, meta-analysis was performed using Meta-Disc1.4 and Stata 16.0 software. Results: A total of eight studies were finally included. The pooled sensitivity of Raman spectroscopy was 0.86 [95% CI (0.80-0.91)], specificity was 0.87 [95% CI (0.79-0.92)], positive likelihood ratio was 5.50 [95% CI (3.55-8.51)], negative likelihood ratio was 0.17 [95% CI (0.09-0.34)], diagnosis odds ratio and area under the curve of SROC were 42.44 [95% CI (19.80-90.97)] and 0.931, respectively. Sensitivity analysis was carried out after each study was excluded one by one, and the results showed that pooled sensitivity and specificity had no significant change, indicating that the stability of the meta-analysis results was great. Conclusions: Our findings indicated that Raman spectroscopy had high accuracy in the diagnosis of AD, though it still did not rule out the possibility of misdiagnosis and missed diagnosis. Limited by the quantity and quality of the included studies, the above conclusions need to be verified by more high-quality studies.

Endothelial function and arterial stiffness indexes in subjects with carotid plaque and carotid plaque length: A subgroup analysis showing the relationship with hypertension and diabetes.

BACKGROUND: Stroke is a leading cause of death and disability globally. A large proportion of ischemic strokes are caused by carotid atherosclerotic plaques. However, the relationship between vascular health status (arterial stiffness and endothelial dysfunction) and carotid plaque remains unclear. OUR STRATEGY: Here, we recruited 991 subjects with carotid plaques and 1170 subjects without carotid plaques to measure arterial stiffness and endothelial dysfunction, using a logistic regression model and multiple linear regression models to predict the relationship between them and carotid plaques. MAIN RESULTS: The data revealed that patients with carotid plaques presented a significantly higher mean of cf-PWV and lower mean RHI values. Age, male gender, diabetes, hypertension, and smoking contributed to plaque formation. Carotid plaques and their lengths were negatively associated with RHI values and positively associated with cf-PWV values; diabetes combined with hypertension showed a cumulative effect on arteriosclerosis. CONCLUSION: RHI combined with cf-PWV could improve the efficacy of predicting the presence of carotid plaques and their lengths.

Vigilant Attention, Cerebral Blood Flow and Grey Matter Volume Change after 36 h of Acute Sleep Deprivation in Healthy Male Adults: A Pilot Study.

It is commonly believed that alertness and attention decrease after sleep deprivation (SD). However, there are not enough studies on the changes in psychomotor vigilance testing (PVT) during SD and the corresponding changes in brain function and brain structure after SD. Therefore, we recruited 30 healthy adult men to perform a 36 h acute SD experiment, including the measurement of five indicators of PVT every 2 h, and analysis of cerebral blood flow (CBF) and grey matter volume (GMV) changes, before and after SD by magnetic resonance imaging (MRI). The PVT measurement found that the mean reaction time (RT), fastest 10% RT, minor lapses, and false starts all increased progressively within 20 h of SD, except for major lapses. Subsequently, all indexes showed a significant lengthening or increasing trend, and the peak value was in the range of 24 h-32 h and decreased at 36 h, in which the number of major lapses returned to normal. MRI showed that CBF decreased in the left orbital part of the superior frontal gyrus, the left of the rolandic operculum, the left triangular part, and the right opercular part of the inferior frontal gyrus, and CBF increased in the left lingual gyrus and the right superior gyrus after 36 h SD. The left lingual gyrus was negatively correlated with the major lapses, and both the inferior frontal gyrus and the superior frontal gyrus were positively correlated with the false starts. Still, there was no significant change in GMV. Therefore, we believe that 36 h of acute SD causes alterations in brain function and reduces alert attention, whereas short-term acute SD does not cause changes in brain structure.

Precision Targeted Therapy with BLU-667 for RET-Driven Cancers.

The receptor tyrosine kinase rearranged during transfection (RET) is an oncogenic driver activated in multiple cancers, including non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and papillary thyroid cancer. No approved therapies have been designed to target RET; treatment has been limited to multikinase inhibitors (MKI), which can have significant off-target toxicities and limited efficacy. BLU-667 is a highly potent and selective RET inhibitor designed to overcome these limitations. In vitro, BLU-667 demonstrated ≥10-fold increased potency over approved MKIs against oncogenic RET variants and resistance mutants. In vivo, BLU-667 potently inhibited growth of NSCLC and thyroid cancer xenografts driven by various RET mutations and fusions without inhibiting VEGFR2. In first-in-human testing, BLU-667 significantly inhibited RET signaling and induced durable clinical responses in patients with RET-altered NSCLC and MTC without notable off-target toxicity, providing clinical validation for selective RET targeting.Significance: Patients with RET-driven cancers derive limited benefit from available MKIs. BLU-667 is a potent and selective RET inhibitor that induces tumor regression in cancer models with RET mutations and fusions. BLU-667 attenuated RET signaling and produced durable clinical responses in patients with RET-altered tumors, clinically validating selective RET targeting. Cancer Discov; 8(7); 836-49. ©2018 AACR.See related commentary by Iams and Lovly, p. 797This article is highlighted in the In This Issue feature, p. 781.

Assessment of the translational value of mouse lupus models using clinically relevant biomarkers.

Lupus is an autoimmune disease with a poorly understood etiology that manifests with a diverse pathology. This heterogeneity has been a challenge to clinical drug development efforts. A related difficulty is the uncertain translational power of animal models used for evaluating potential drug targets and candidate therapeutics, because it is unlikely that any 1 preclinical model will recapitulate the spectrum of human disease. Therefore, multiple models, along with an understanding of the immune mechanisms that drive them, are necessary if we are to use them to identify valid drug targets and evaluate candidate therapies successfully. To this end, we have characterized several different mouse lupus models and report their differences with respect to biomarkers and symptoms that are representative of the human disease. We compared the pristane-induced mouse lupus disease model using 3 different strains (DBA/1, SJL, BALB/c), and the spontaneous NZB x NZW F1(NZB/W) mouse model. We show that the models differ significantly in their autoantibody profiles, disease manifestations such as nephritis and arthritis, and expression of type I interferon-regulated genes. Similar to the NZB/W model, pristane-induced disease in SJL mice manifests with nephritis and proteinuria, whereas the pristane-treated DBA/1 mice develop arthritis and an interferon-driven gene signature that closely resembles that in human patients. The elucidation of each model's strengths and the identification of translatable biomarkers yields insight for basic lupus research and drug development, and should assist in the proper selection of models for evaluating candidate targets and therapeutic strategies.

Clonal analysis of the differentiation potential of human adipose-derived adult stem cells.

Pools of human adipose-derived adult stem (hADAS) cells can exhibit multiple differentiated phenotypes under appropriate in vitro culture conditions. Because adipose tissue is abundant and easily accessible, hADAS cells offer a promising source of cells for tissue engineering and other cell-based therapies. However, it is unclear whether individual hADAS cells can give rise to multiple differentiated phenotypes or whether each phenotype arises from a subset of committed progenitor cells that exists within a heterogeneous population. The goal of this study was to test the hypothesis that single hADAS are multipotent at a clonal level. hADAS cells were isolated from liposuction waste, and ring cloning was performed to select cells derived from a single progenitor cell. Forty-five clones were expanded through four passages and then induced for adipogenesis, osteogenesis, chondrogenesis, and neurogenesis using lineage-specific differentiation media. Quantitative differentiation criteria for each lineage were determined using histological and biochemical analyses. Eighty one percent of the hADAS cell clones differentiated into at least one of the lineages. In addition, 52% of the hADAS cell clones differentiated into two or more of the lineages. More clones expressed phenotypes of osteoblasts (48%), chondrocytes (43%), and neuron-like cells (52%) than of adipocytes (12%), possibly due to the loss of adipogenic ability after repeated subcultures. The findings are consistent with the hypothesis that hADAS cells are a type of multipotent adult stem cell and not solely a mixed population of unipotent progenitor cells. However, it is important to exercise caution in interpreting these results until they are validated using functional in vivo assays.

Altered expression of genes involved in hepatic morphogenesis and fibrogenesis are identified by cDNA microarray analysis in biliary atresia.

Biliary atresia (BA) is characterized by a progressive, sclerosing, inflammatory process that leads to cirrhosis in infancy. Although it is the most common indication for liver transplantation in early childhood, little is known about its etiopathogenesis. To elucidate factors involved in this process, we performed comprehensive genome-wide gene expression analysis using complementary DNA (cDNA) microarrays. We compared messenger RNA expression levels of approximately 18,000 human genes from normal, diseased control, and end-stage BA livers. Reverse-transcription polymerase chain reaction (RT-PCR) and Northern blot analysis were performed to confirm changes in gene expression. Cluster and principal component analysis showed that all BA samples clustered together, forming a distinct group well separated from normal and diseased controls. We further identified 35 genes and ESTs whose expression differentiated BA from normal and diseased controls. Most of these genes are known to be associated with cell signaling, transcription regulation, hepatic development, morphogenesis, and fibrogenesis. In conclusion, this study serves to delineate processes that are involved in the pathogenesis of BA.