Nucleated red blood cell distribution in critically ill patients with acute pancreatitis: a retrospective cohort study.

OBJECTIVES: This study examined the potential association between nucleated red blood cell (NRBC) levels and mortality in critically ill patients with acute pancreatitis (AP) in the intensive care unit, due to limited existing research on this correlation. METHODS: This retrospective cohort study utilized data from the MIMIC-IV v2.0 and MIMIC-III v1.4 databases to investigate the potential relationship between NRBC levels and patient outcomes. The study employed restricted cubic splines (RCS) regression analysis to explore non-linear associations. The impact of NRBC on prognosis was assessed using a generalized linear model (GLM) with a logit link, adjusted for potential confounders. Furthermore, four machine learning models, including Gradient Boosting Classifier (GBC), Random Forest, Gaussian Naive Bayes, and Decision Tree Classifier model, were constructed using NRBC data to generate risk scores and evaluate the potential of NRBC in predicting patient prognosis. RESULTS: A total of 354 patients were enrolled in the study, with 162 (45.8%) individuals aged 60 years or older and 204 (57.6%) males. RCS regression analysis demonstrated a non-linear relationship between NRBC levels and 90-day mortality. Receiver Operating Characteristic (ROC) analysis identified a 1.7% NRBC cutoff to distinguish survivor from non-survivor patients for 90-day mortality, yielding an Area Under the Curve (AUC) of 0.599, with a sensitivity of 0.475 and specificity of 0.711. Elevated NRBC levels were associated with increased risks of 90-day mortality in both unadjusted and adjusted models (all Odds Ratios > 1, P < 0.05). Assessment of various machine learning models with nine variables, including NRBC, Sex, Age, Simplified Acute Physiology Score II, Acute Physiology Score III, Congestive Heart Failure, Vasopressin, Norepinephrine, and Mean Arterial Pressure, indicated that the GBC model displayed the highest predictive accuracy for 90-day mortality, with an AUC of 0.982 (95% CI 0.970-0.994). Post hoc power analysis showed a statistical power of 0.880 in the study. CONCLUSIONS: Elevated levels of NRBC are linked to an increased mortality risk in critically ill patients with AP, suggesting its potential for predicting mortality.

Skeletal muscle index based on CT at the 12th thoracic spine level can predict osteoporosis and fracture risk: a propensity score-matched cohort study.

Background: Multiple studies have shown that skeletal muscle index (SMI) measured on abdominal computed tomography (CT) is strongly associated with bone mineral density (BMD) and fracture risk as estimated by the fracture risk assessment tool (FRAX). Although some studies have reported that SMI at the level of the 12th thoracic vertebra (T12) measured on chest CT images can be used to diagnose sarcopenia, it is regrettable that no studies have investigated the relationship between SMI at T12 level and BMD or fracture risk. Therefore, we further investigated the relationship between SMI at T12 level and FRAX-estimated BMD and fracture risk in this study. Methods: A total of 349 subjects were included in this study. After 1∶1 propensity score matching (PSM) on height, weight, hypertension, diabetes, hyperlipidemia, hyperuricemia, body mass index (BMI), age, and gender, 162 subjects were finally included. The SMI, BMD, and FRAX score of the 162 participants were obtained. The correlation between SMI and BMD, as well as SMI and FRAX, was assessed using Spearman rank correlation. Additionally, the effectiveness of each index in predicting osteoporosis was evaluated through the receiver operating characteristic (ROC) curve analysis. Results: The BMD of the lumbar spine (L1-4) demonstrated a strong correlation with SMI (r = 0.416, p < 0.001), while the BMD of the femoral neck (FN) also exhibited a correlation with SMI (r = 0.307, p < 0.001). SMI was significantly correlated with FRAX, both without and with BMD at the FN, for major osteoporotic fractures (r = -0.416, p < 0.001, and r = -0.431, p < 0.001, respectively) and hip fractures (r = -0.357, p < 0.001, and r = -0.311, p < 0.001, respectively). Moreover, the SMI of the non-osteoporosis group was significantly higher than that of the osteoporosis group (p < 0.001). SMI effectively predicts osteoporosis, with an area under the curve of 0.834 (95% confidence interval 0.771-0.897, p < 0.001). Conclusion: SMI based on CT images of the 12th thoracic vertebrae can effectively diagnose osteoporosis and predict fracture risk. Therefore, SMI can make secondary use of chest CT to screen people who are prone to osteoporosis and fracture, and carry out timely medical intervention.

HGCTNet: Handcrafted Feature-Guided CNN and Transformer Network for Wearable Cuffless Blood Pressure Measurement.

Biosignals collected by wearable devices, such as electrocardiogram and photoplethysmogram, exhibit redundancy and global temporal dependencies, posing a challenge in extracting discriminative features for blood pressure (BP) estimation. To address this challenge, we propose HGCTNet, a handcrafted feature-guided CNN and transformer network for cuffless BP measurement based on wearable devices. By leveraging convolutional operations and self-attention mechanisms, we design a CNN-Transformer hybrid architecture to learn features from biosignals that capture both local information and global temporal dependencies. Then, we introduce a handcrafted feature-guided attention module that utilizes handcrafted features extracted from biosignals as query vectors to eliminate redundant information within the learned features. Finally, we design a feature fusion module that integrates the learned features, handcrafted features, and demographics to enhance model performance. We validate our approach using two large wearable BP datasets: the CAS-BP dataset and the Aurora-BP dataset. Experimental results demonstrate that HGCTNet achieves an estimation error of 0.9 ± 6.5 mmHg for diastolic BP (DBP) and 0.7 ± 8.3 mmHg for systolic BP (SBP) on the CAS-BP dataset. On the Aurora-BP dataset, the corresponding errors are -0.4 ± 7.0 mmHg for DBP and -0.4 ± 8.6 mmHg for SBP. Compared to the current state-of-the-art approaches, HGCTNet reduces the mean absolute error of SBP estimation by 10.68% on the CAS-BP dataset and 9.84% on the Aurora-BP dataset. These results highlight the potential of HGCTNet in improving the performance of wearable cuffless BP measurements.

Size and fixation options of dorsoulnar fragments in distal radius fractures.

PURPOSE: This study aimed to investigate the influence of size and fixation options of dorsoulnar fragments on the clinical outcomes of distal radius fractures (DRFs). METHODS: This retrospective analysis was performed on 94 patients with DFR accompanied by dorsoulnar fragments, spanning the period from October 2018 to November 2022. Mean follow-up was 15.5 (range, 12-20) months. Patients were divided into small- (<5 %, n = 28), middle- (5-15 %, n = 50), and large- (>15 %, n = 16) sized groups according to articular involvement of dorsoulnar fragments determined by three-dimensional (3D) computed tomography (CT) modeling. Subdivision also took place for the presence of postoperative fragment displacement (>2 mm) and fixation methods including volar locking plate (VLP), VLP combined with dorsal hollow compression screw (VDS), and VLP combined with dorsal low-profile mini plate (VDP). The radiographic parameters (volar tilt, radial inclination, and radial height) and functional outcome measures of wrist range of motion, wrist function (DASH, PRWE), and wrist pain (VAS) were evaluated and compared between groups. RESULTS: Fracture healing was observed in all patients at final follow-up. No instances of dorsoulnar fragment displacement were observed in patients undergoing VDS and VDP treatment and the incidence of the dorsoulnar fragment displacement was 35 % (n = 8) in small-sized group, 21 % (n = 7) in middle-sized group, and 7 % (n = 1) in large-sized group when patients were treated with VLP. In small-sized group, no significant differences were found between patients with and without dorsoulnar fragment displacement in dorsiflexion restriction (10.6 ± 2.8°, 9.1 ± 2.3°, P = 0.159), pronosupination restriction (9.6 ± 2.1°, 8.6 ± 1.7°, P = 0.188), DASH (11.5 ± 4.1, 10.7 ± 3.2, P = 0.562), PRWE (11.9 ± 4.2, 10.6 ± 3.6, P = 0.425), and VAS (1.1 ± 1.1, 0.9 ± 1.0, P = 0.528). In middle-sized combined with large-sized group, the functional outcome measures of dorsiflexion restriction (12.5 ± 3.7°, 9.8 ± 2.9°, P = 0.022), DASH (14.6 ± 5.2, 11.4 ± 3.7, P = 0.030), and PRWE (15.0 ± 4.5, 11.3 ± 3.9, P = 0.016) were superior in patients without dorsoulnar fragment displacement. In patients treated with VLPs, no significant differences were found in dorsiflexion restriction (9.8 ± 2.5°, 10.8 ± 3.5°, 9.4 ± 2.5°, P = 0.299), pronosupination restriction (9.2 ± 1.9°, 10.1 ± 2.8°, 8.9 ± 1.5°, P = 0.200), DASH (11.1 ± 3.5, 12.9 ± 4.3, 11.1 ± 3.6, P = 0.162), PRWE (11.1 ± 3.9, 12.8 ± 4.2, 10.8 ± 3.9, P = 0.188), and VAS (1.0 ± 1.0, 1.4 ± 1.1, 0.9 ± 0.9, P = 0.151) between small-sized, middle-sized, and large-sized groups. In middle-sized group, no significant differences were found in dorsiflexion restriction (10.8 ± 3.5°, 9.4 ± 2.2°, 9.4 ± 2.4°, P = 0.316); pronosupination restriction (10.1 ± 2.8°, 8.8 ± 1.9°, 9.0 ± 2.5°, P = 0.314), DASH (12.9 ± 4.3, 10.3 ± 3.7, 10.5 ± 3.7, P = 0.133), PRWE (12.8 ± 4.2, 10.4 ± 3.8, 10.6 ± 4.1, P = 0.199), and VAS (1.4 ± 1.1, 0.8 ± 0.7, 1.0 ± 1.1, P = 0.201) between subgroups of VLP, VDS, and VDP. No significant differences were found in radiographic parameters between all groups compared. CONCLUSION: This study indicated that the strict reduction and fixation of a dorsoulnar fragment might be not essential when its articular involvement was less than 5 %. The volar locking plate (VLP) fixation was commonly effective in treating distal radius fractures accompanied by a dorsoulnar fragment involving over 15 % of the articular surface. Additionally, the use of an additional dorsal hollow compression screw or a dorsal low-profile mini plate can get good wrist function in the early-term follow-up when the dorsoulnar fragment involve 5-15 % of the articular surface.

Review of the Protective Mechanism of Curcumin on Cardiovascular Disease.

Cardiovascular diseases (CVDs) are the most common cause of death worldwide and has been the focus of research in the medical community. Curcumin is a polyphenolic compound extracted from the root of turmeric. Curcumin has been shown to have a variety of pharmacological properties over the past decades. Curcumin can significantly protect cardiomyocyte injury after ischemia and hypoxia, inhibit myocardial hypertrophy and fibrosis, improve ventricular remodeling, reduce drug-induced myocardial injury, improve diabetic cardiomyopathy(DCM), alleviate vascular endothelial dysfunction, inhibit foam cell formation, and reduce vascular smooth muscle cells(VSMCs) proliferation. Clinical studies have shown that curcumin has a protective effect on blood vessels. Toxicological studies have shown that curcumin is safe. But high doses of curcumin also have some side effects, such as liver damage and defects in embryonic heart development. This article reviews the mechanism of curcumin intervention on CVDs in recent years, in order to provide reference for the development of new drugs in the future.

Identification of Key Genes and Related Drugs of Adrenocortical Carcinoma by Integrated Bioinformatics Analysis.

Adrenocortical carcinoma (ACC) is a malignant carcinoma with an extremely poor prognosis, and its pathogenesis remains to be understood to date, necessitating further investigation. This study aims to discover biomarkers and potential therapeutic agents for ACC through bioinformatics, enhancing clinical diagnosis and treatment strategies. Differentially expressed genes (DEGs) between ACC and normal adrenal cortex were screened out from the GSE19750 and GSE90713 datasets available in the GEO database. An online Venn diagram tool was utilized to identify the common DEGs between the two datasets. The identified DEGs were subjected to functional assessment, pathway enrichment, and identification of hub genes by performing the protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The differences in the expressions of hub genes between ACC and normal adrenal cortex were validated at the GEPIA2 website, and the association of these genes with the overall patient survival was also assessed. Finally, on the QuartataWeb website, drugs related to the identified hub genes were determined. A total of 114 DEGs, 10 hub genes, and 69 known drugs that could interact with these genes were identified. The GO and KEGG analyses revealed a close association of the identified DEGs with cellular signal transduction. The 10 hub genes identified were overexpressed in ACC, in addition to being significantly associated with adverse prognosis in ACC. Three genes and the associated known drugs were identified as potential targets for ACC treatment.

Automatic synthesis of 18F-AV-45 and its clinical application in Alzheimer's disease.

OBJECTIVE: To investigate the automatic synthesis of ß-amyloid (Aß) positron emission tomography (PET) imaging agent (E) -4- (2- (6- (2- (2-18F fluoroethoxy) ethoxy) ethoxy) pyridine-3-yl) vinyl) - N-methylaniline (18F-AV-45) for the diagnosis of Alzheimer's disease (AD) and its clinical application in AD patients. MATERIALS AND METHODS: Fluorine-18-AV-45 was synthesized with AV-105 as the precursor, and the factors affecting the synthesis efficiency, such as the amount of precursor, nucleophilic reaction temperature were studied. At the same time, 18F-AV-45 PET/computed tomography (CT) brain scanning was performed in 15 patients with dementia to determine whether AD was the cause of the dementia. RESULTS: After optimizing the parameters, it was discovered that the highest synthesis efficiency was achieved with a AV-105 dosage of 2mg, a reaction temperature of 130oC, and 1mL of DMSO. The radiochemical yield (RCP) was greater than 98, and the uncorrected synthesis efficiency was about 31.0%±2.8%. Ten of the 15 patients with dementia showed positive Aß protein deposition, and the main deposition site of the imaging agent was the gray matter area of the brain, which was consistent with AD diagnosis, while the other 5 patients showed negative Aß protein deposition, suggesting non-AD dementia. CONCLUSION: ß-amyloid protein 18F-AV-45 imaging agent can be easily and quickly prepared by the All in One radiochemical synthesis module. Our preliminary results offer hope that it can effectively detect ß-amyloid deposition in the brain of AD patients in order to determine the etiology of dementia.

Severe congenital neutropenia and liver abscess: Surgical treatment breaks the vicious cycle.

Here, we present a case with genetically confirmed SCN. The main symptom of the child was recurring fever. The combination of antibiotics combined with G-CSF injection was proved to be insufficient, and the patient developed "solid" liver abscess. After undergoing surgical anatomical hepatic lobectomy, the child's infection symptoms showed improvement. The postoperative culture of the purulent material from the liver infection lesion revealed an infection with Staphylococcus aureus. Our case raises the possibility of pathogen sources and routes of infection, clinical characteristics, and effective treatment for SCN patients with concomitant liver abscess.

Review of the Protective Mechanism of Paeonol on Cardiovascular Disease.

Cardiovascular disease (CVD) is one of the leading causes of death in the world. Paeonol(Pae) is a phenolic component extracted from peony bark, peony root and Xu Changqing. Studies have shown that Pae can protect cardiomyocytes by inhibiting oxidative stress, promoting mitochondrial fusion, regulating mitochondrial autophagy and inhibiting inflammation. In addition, Pae improves ventricular remodeling by inhibiting myocardial apoptosis, hypertrophy and fibrosis. Pae also has a good protective effect on blood vessels by inhibiting vascular inflammation, reducing the expression of adhesion molecules, inhibiting vascular proliferation, and inhibiting oxidative stress and endoplasmic reticulum stress(ERS). Pae also has the effect of anti-endothelial cell senescence, promoting thrombus recanalization and vasodilating. In conclusion, the molecular targets of Pae are very complex, and the relationship between different targets and signaling pathways cannot be clearly explained, which requires us to use systems biology methods to further study specific molecular targets of Pae. It has to be mentioned that the bioavailability of Pae is poor, and some nanotechnology-assisted drug delivery systems improve the therapeutic effect of Pae. We reviewed the protective mechanism of paeonol on the cardiovascular system, hoping to provide help for drug development in the treatment of CVD.

Review on the protective mechanism of astragaloside IV against cardiovascular diseases.

Cardiovascular disease is a global health problem. Astragaloside IV (AS-IV) is a saponin compound extracted from the roots of the Chinese herb Astragalus. Over the past few decades, AS-IV has been shown to possess various pharmacological properties. It can protect the myocardium through antioxidative stress, anti-inflammatory effects, regulation of calcium homeostasis, improvement of myocardial energy metabolism, anti-apoptosis, anti-cardiomyocyte hypertrophy, anti-myocardial fibrosis, regulation of myocardial autophagy, and improvement of myocardial microcirculation. AS-IV exerts protective effects on blood vessels. For example, it can protect vascular endothelial cells through antioxidative stress and anti-inflammatory pathways, relax blood vessels, stabilize atherosclerotic plaques, and inhibit the proliferation and migration of vascular smooth muscle cells. Thus, the bioavailability of AS-IV is low. Toxicology indicates that AS-IV is safe, but should be used cautiously in pregnant women. In this paper, we review the mechanisms of AS-IV prevention and treatment of cardiovascular diseases in recent years to provide a reference for future research and drug development.

Cuffless Blood Pressure Measurement Using Smartwatches: A Large-Scale Validation Study.

This study aimed to evaluate the performance of cuffless blood pressure (BP) measurement techniques in a large and diverse cohort of participants. We enrolled 3077 participants (aged 18-75, 65.16% women, 35.91% hypertensive participants) and conducted followed-up for approximately 1 month. Electrocardiogram, pulse pressure wave, and multiwavelength photoplethysmogram signals were simultaneously recorded using smartwatches; dual-observer auscultation systolic BP (SBP) and diastolic BP (DBP) reference measurements were also obtained. Pulse transit time, traditional machine learning (TML), and deep learning (DL) models were evaluated with calibration and calibration-free strategy. TML models were developed using ridge regression, support vector machine, adaptive boosting, and random forest; while DL models using convolutional and recurrent neural networks. The best-performing calibration-based model yielded estimation errors of 1.33 ± 6.43 mmHg for DBP and 2.31 ± 9.57 mmHg for SBP in the overall population, with reduced SBP estimation errors in normotensive (1.97 ± 7.85 mmHg) and young (0.24 ± 6.61 mmHg) subpopulations. The best-performing calibration-free model had estimation errors of -0.29 ± 8.78 mmHg for DBP and -0.71 ± 13.04 mmHg for SBP. We conclude that smartwatches are effective for measuring DBP for all participants and SBP for normotensive and younger participants with calibration; performance degrades significantly for heterogeneous populations including older and hypertensive participants. The availability of cuffless BP measurement without calibration is limited in routine settings. Our study provides a large-scale benchmark for emerging investigations on cuffless BP measurement, highlighting the need to explore additional signals or principles to enhance the accuracy in large-scale heterogeneous populations.

[Protective mechanism of tetramethylpyrazine on cardiovascular system].

Tetramethylpyrazine is the main component of Ligusticum chuanxiong. Studies have found that tetramethylpyrazine has a good protective effect against cardiovascular diseases. In the heart, tetramethylpyrazine can reduce myocardial ischemia/reperfusion injury by inhibiting oxidative stress, regulating autophagy, and inhibiting cardiomyocyte apoptosis. Tetramethylpyrazine can also reduce the damage of cardiomyocytes caused by inflammation, relieve the fibrosis and hypertrophy of cardiomyocytes in infarcted myocardium, and inhibit the expansion of the cardiac cavity after myocardial infarction. In addition, tetramethylpyrazine also has a protective effect on the improvement of familial dilated cardiomyopathy. Besides, the mechanisms of tetramethylpyrazine on blood vessels are more abundant. It can inhibit endothelial cell apoptosis by reducing oxidative stress, maintain vascular endothelial function and homeostasis by inhibiting inflammation and glycocalyx degradation, and protect vascular endothelial cells by reducing iron overload. Tetramethylpyrazine also has a certain inhibitory effect on thrombosis. It can play an anti-thrombotic effect by reducing inflammatory factors and adhesion molecules, inhibiting platelet aggregation, and suppressing the expression of fibrinogen and von Willebrand factor. In addition, tetramethylpyrazine can also reduce the level of blood lipid in apolipoprotein E-deficient mice, inhibit the subcutaneous deposition of lipids, inhibit the transformation of macrophages into foam cells, and inhibit the proliferation and migration of vascular smooth muscle cells, thereby reducing the formation of atherosclerotic plaque. In combination with network pharmacology, the protective mechanism of tetramethylpyrazine on the cardiovascular system may be mainly achieved through the regulation of phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt), hypoxia-inducible factor 1(HIF-1), and mitogen-activated protein kinase(MAPK) pathways. Tetramethylpyrazine hydrochloride and sodium chloride injection has been approved for clinical application, but some adverse reactions have been found in clinical application, which need to be paid attention to.

Diagnosis, treatment, and prevention of monkeypox in children: an experts' consensus statement.

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment,  and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

Plasma Core Alzheimer's Disease Biomarkers Predict Amyloid Deposition Burden by Positron Emission Tomography in Chinese Individuals with Cognitive Decline.

Blood-based biomarkers have been considered as a promising method for the diagnosis of Alzheimer's disease (AD). The reliability and accuracy of plasma core AD biomarkers, including phosphorylated tau (P-tau181), total tau (T-tau), Aß42, and Aß40, have also been confirmed in diagnosing AD and predicting cerebral ß-amyloid (Aß) deposition in Western populations, while fewer research studies have ever been conducted in China's Han population. In this study, we investigated the capability of plasma core AD biomarkers in predicting cerebral Aß deposition burden among the China Aging and Neurodegenerative Disorder Initiative (CANDI) cohort consisting of cognitively normal (CN), mild cognitive impairment (MCI), AD dementia, and non-Alzheimer's dementia disease (Non-ADD). Body fluid (plasma and CSF) AD core biomarkers were measured via single-molecule array (Simoa) immunoassay. The global standard uptake value ratio (SUVR) was then calculated by 18F-florbetapir PET, which was divided into positive (+) and negative (-). The most significant correlation between plasma and CSF was plasma P-tau181 (r = 0.526, P < 0.0001). Plasma P-tau181 and P-tau181/T-tau ratio were positively correlated with global SUVR (r = 0.257, P < 0.0001; r = 0.263, P < 0.0001, respectively), while Aß42 and Aß42/Aß40 ratio were negatively correlated with global SUVR (r = -0.346, P < 0.0001; r = -0.407, P < 0.0001, respectively). Interestingly, voxel-wise analysis showed that plasma P-tau181 and P-tau181/T-tau ratio were negatively related to 18F-florbetapir PET in the hippocampus and parahippocampal cortex. The optimal predictive capability in distinguishing all Aß+ participants from Aß- participants and MCI+ from MCI- subgroups was the plasma P-tau181/T-tau ratio (AUC = 0.825 and 0.834, respectively). Our study suggested that plasma P-tau181 and P-tau181/T-tau ratio possessed better diagnostic and predictive values than plasma Aß42 and Aß42/Aß40 in this cohort, a finding that may be useful in clinical practices and trials in China.

Contribution of cyclooxygenase-2 overexpression to enhancement in tonically active glutamatergic inputs to the rostral ventrolateral medulla in hypertension.

OBJECTIVE: Cyclooxygenase (COX) is critical in regulating cardiovascular function, but its role involved in the central control of blood pressure (BP) is uncovered. The tonic glutamatergic inputs to the rostral ventrolateral medulla (RVLM) are enhanced in hypertension. Here, the present study was designed to investigate the effect and mechanism of central COX on tonic glutamatergic inputs to the RVLM and BP regulation. METHODS: Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs) received RVLM microinjection of adeno-associated viral vectors to promote or inhibit the COX2 expression were subjected to subsequent experiments. Glutamate level and glutaminase expression were detected by ELISA and western blot, respectively. The function of tonic glutamatergic inputs was assessed by BP response to microinjection of the glutamate receptor antagonist into the RVLM. PC12 cells were used to detect the underlying signal pathway. RESULTS: The RVLM COX2 expression and prostaglandin E2 level were significant higher in SHRs than in WKY rats. Overexpression of COX2 in the RVLM produced an increase in basal BP, RVLM glutamate level, and glutaminase expression in WKY rats, while they were significantly reduced by interfering with COX2 expression in SHRs. Microinjections of the glutamate receptor antagonist into the RVLM produced a significant BP decrease in WKY rats with COX2 overexpression pretreatment. Furthermore, the increased levels of BP, glutamate content, and glutaminase activity in the RVLM evoked by central infusion of angiotensin II were attenuated in COX2 knockout mice. It was also found that prostaglandin E2 increased supernatant glutamate level and phosphorylation of signal transducer and activator of transcription 3 in PC12 cells. CONCLUSION: Our findings suggest that upregulated COX2 expression enhances the tonically active glutamatergic inputs to the RVLM, which is associated with cardiovascular regulation in hypertension.

Invasive Salmonella Infections Among Children in Shenzhen, China: A Five-year Retrospective Review.

BACKGROUND: Invasive Salmonella infections are highly prevalent worldwide. Clinical data of childhood invasive Salmonella infections from China are limited. METHODS: Data of hospitalized children <18 years old with invasive Salmonella infections from 2016 to 2020 in Shenzhen Children's Hospital in Shenzhen were retrospectively collected. Serotypes and antimicrobial susceptibility tests of the invasive Salmonella isolates were performed. RESULTS: Sixty-three cases were enrolled during the 5-year study period including 8 in 2016, 11 in 2017, 16 in 2018, 6 in 2019 and 22 in 2020. The median age was 15 months (interquartile range, 11-22 months), and 79.4% (50 cases) were <2 years of age. Underlying diseases were found in 28.6% (18 cases) of the patients with a great variety, but no cases of malaria or HIV infection were identified. Most of the invasive Salmonella cases were bloodstream infections (84.1%), followed by osteoarthritis (11.1%) and meningitis (4.8%). Gastroenteritis (49.2%) and pneumonia (28.6%) were found to be the major manifestations among the patients. Furthermore, invasive Salmonella infections resulted in the death of 3 children (4.8%). Salmonella enteritis (12 cases; 15.9%) and Salmonella typhimurium (9 cases; 19.0%) as the most common serovars were identified. The resistance rates of Salmonella strains to ceftriaxone, ceftazidime and cefepime were also measured to be 17.5%, 17.5% and 9.5%, respectively. CONCLUSIONS: An increasing number of childhood invasive Salmonella infections with a broad range of serotypes was observed in Shenzhen, China. It is critical to pay attention to the antimicrobial resistance of the isolates taken from children with invasive Salmonella infections.

Correlation between Cerebrospinal Fluid Core Alzheimer's Disease Biomarkers and ß-Amyloid PET in Chinese Dementia Population.

The current diagnoses of Alzheimer's disease (AD) mainly rely on such measures as amyloid-ß (Aß) and tau neuropathology biomarkers in vivo via cerebrospinal fluid (CSF) and positron emission tomography (PET) imaging, which had been systematically studied in Caucasian individuals, whereas diagnostic performances of these approaches in Chinese dementia population still remain unclear. This study investigated the associations between the levels of CSF core AD biomarkers, including phosphorylated tau (p-Tau181), total tau (t-Tau), Aß42, and Aß40 measured by the single-molecule array (Simoa) and cerebral Aß deposition status assessed by 18F-Florbetapir PET (Aß PET), and evaluated the predictive values of CSF core AD biomarkers in discriminating Aß PET status in a clinical dementia cohort of the Chinese population, which consisted of patients with mild cognitive impairment (MCI), AD dementia, and non-Alzheimer's dementia disease (Non-ADD). Global standard uptake value ratios (SUVRs) were calculated by Aß PET, which was divided into positive (Aß+) and negative (Aß-) through visual analysis. CSF p-Tau181 and p-Tau181/t-Tau ratio were positively correlated with the global SUVR, while CSF Aß42 and Aß42/Aß40 ratio were negatively correlated with the global SUVR. CSF Aß40 has the highest predictive value in discriminating the MCI group from the AD group, while CSF p-Tau181 was applied to discriminate the AD group from the non-ADD group. CSF Aß42/Aß40 ratio, as the optimal predictive factor, was combined with APOE ε4 status rather than age and education, which could improve the predictive ability in differentiating the Aß+ group from the Aß- group. The results reveal the universal applicability of CSF core AD biomarkers and Aß PET imaging in Chinese dementia population, which is helpful in clinical practice and drug trials in China.

Efficient and automatic synthesis of TSPO PET ligand [18F]-GE-180 and its application in rheumatoid arthritis model.

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic synovial inflammation, which ultimately leads to joint deformity and dysfunction. [18F]-GE-180 is a specific PET tracer of the 18 kDa translocator protein (TSPO), which is overexpressed on activated macrophages, and proposed as a biomarker of inflammation. Our study addresses the need to streamline the automatic synthesis of [18F]-GE-180 to make it more accessible for routine production and widespread clinical evaluation and application. The nucleophilic radiofluorination was performed on an AllinOne synthesis module by SPE purification method, and the formulated [18F]-GE-180 was obtained in non-decay corrected radiochemical yields of 69 ± 1.8% in 32 min. PET/CT imaging in animal model showed that [18F]-GE-180 highly concentrated in joints from RA rats. This methodology facilitates efficient synthesis of [18F]-GE-180 in a commercially available synthesis module and shows potential diagnosis performance in RA models.

[Value of 18F-FDG PET/CT Imaging in Secondary Extramedullary Infiltration of Multiple Myeloma].

OBJECTIVE: To investigate the characteristics of 18F-FDG PET/CT images of multiple myeloma secondary extramedullary infiltration in order to improve recognition. METHODS: Twenty-one patients with multiple myeloma secondary extramedullary infiltration confirmed by pathology or follow-up from January 2012 to October 2020 in the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed. All the patients underwent 18F-FDG PET/CT imaging before treatment, and the PET/CT characteristics of extramedullary infiltration and bone marrow were analyzed. RESULTS: Twenty-one patients included 12 males and 9 females, aged from 41 to 77 years old, with an average of 58.3±10.0; 9 cases of extramedullary infiltration involving lymph nodes; lung, stomach, spleen, and kidney were involved respectively in 2 cases; retroperitoneal, right auricle, subcutaneous nodule, and spinal meninges involvement were reported in each one case respectively. The maximum SUVmax value of extra-medullary lesions was 21.2, the minimum value was 2.1, and mean was 7.7±5.3. The maximum SUVmax value of bone marrow was 33.5, the minimum was 2.4, and mean was 6.6±3.6. There was no statistically significant difference in SUVmax value between extra-medullary lesions and bone marrow (Z=-1.195, P=0.232). CONCLUSION: 18F-FDG PET/CT not only has a good diagnostic value for multiple myeloma, but also a good evaluation value for secondary extramedullary infiltration, which provides reference for clinical treatment and prognosis.