Association of procalcitonin with voriconazole concentrations: a retrospective cohort study.

Inflammation is a potential risk factor of voriconazole (VCZ) overdose, procalcitonin (PCT) is reported to act as a diagnostic marker for bacterial infections. However, the association of PCT with VCZ trough serum concentrations (VCZ-Cmin) is not fully clear. Our study aims to investigate the associations between PCT and VCZ-Cmin. In this retrospective cohort study, we collected the clinical data of 147 patients who received VCZ and monitored the VCZ concentration of them in our hospital from August 2017 to August 2021. All patients underwent routine clinical examinations on the day or the day before VCZ administration. General information and clinical symptoms of these patients were recorded. Multivariate liner analysis showed that PCT was significantly associated with VCZ-Cmin (p < 0.001). Overall, it was shown that VCZ-Cmin was significantly increased by 0.32 µg/mL for each fold increment in PCT in crude model. In the minor adjusted model (Model 1, adjustment for sex, age, albumin, direct bi1irubin, WBC) and fully adjusted model (Model 2, adjustment for sex, age, albumin, direct bilirubin, WBC, AST and ALT), VCZ-Cmin was significantly increased by 0.23 µg/mL and 0.21 µg/mL, respectively, for each fold increment in PCT. In conclusion, this research reveals the correlation between PCT and VCZ-Cmin, indicating that PCT has the potential to serve as a valuable biomarker for drug monitoring in the treatment of VCZ.

[High-throughput screening of 54 alternative plasticizers in sesame oil using gas chromatography-quadrupole time-of-flight mass spectrometry].

Restrictions on the use of phthalates have led to the wide use of alternative plasticizers (APs) such as organophosphate, adipate, citrate, and sebacate. However, because plasticizers combine with polymers in plastic products via unstable noncovalent bonds, they can easily migrate out of these products, causing environmental pollution. In particular, their migration out of food packaging, containers, and other food-contact materials and into food has raised great concerns. Toxicological studies have shown that APs contain potentially toxic substances that can affect endocrine functions and cause neurotoxicity, genotoxicity, and other adverse effects. Thus, their potential risks to food should not be underestimated. Sesame oil is a necessity in daily cooking. The results of risk monitoring in recent years have indicated that sesame oil often contains phthalates in excess of the standard limits. However, the potential risks of APs in sesame oil have not yet been reported. Some common detection methods for APs include gas chromatography-mass spectrometry, gas chromatography-triple quadrupole mass spectrometry, and liquid chromatography-triple quadrupole mass spectrometry. Unfortunately, these methods use low-resolution mass spectrometry and are limited by the resolution, scan rate, and analysis mode. Gas chromatography-quadrupole time-of-flight mass spectrometry (GC-Q-TOF/MS) has the advantages of high resolution, sensitivity, and analysis speed. In full-scan mode, GC-Q-TOF/MS can accurately collect the full-spectrum mass number of target compounds with low content levels in complex substrates, thereby realizing efficient screening and quantitative analysis. It shows outstanding advantages in the trace analysis of pesticide residues and pollutants. Furthermore, it features strong qualitative and high screening abilities. Establishment of a personal compound database and library (PCDL) addresses limitations in the number of compounds that can be measured and enables the rapid identification of targets without the use of standard products. In addition, increasing the number of targets for synchronous screening enables the retrospective analysis of new targets. In this study, a method based on GC-Q-TOF/MS was developed for the determination of 54 APs in sesame oil. The samples were extracted with acetonitrile and purified using a PSA/silica solid-phase extraction column. The mass-spectral information of the samples was then collected by GC-Q-TOF/MS in full-scan mode, and the 54 APs were searched using an established high-resolution mass-spectrum database to simultaneously achieve the broad-spectrum screening, qualitative identification, and quantitative analysis of multiple targets. The effects of different extraction solvents and purification methods on sample extraction and purification were compared. The accuracy of the screening results was improved by optimizing the GC-separation conditions, quality-extraction window, retention-time deviation, and other screening parameters. The screening detection limits (SDLs) of the 54 APs ranged from 0.01 to 0.02 mg/kg; specifically, the SDL of 41 compounds was 0.01 mg/kg and that of 13 compounds were 0.02 mg/kg. The limits of quantification were in the range of 0.02-0.04 mg/kg. A total of 80 sesame-oil samples were rapidly screened using this method under optimal conditions. Five APs were identified from the 80 sesame-oil samples and quantitatively analyzed using the matrix-matched external-standard method. The results of this quantitative methodology showed that the five APs had good linear relationships in the range of 0.01-0.2 mg/L, with all correlation coefficients greater than 0.99. The accuracy and precision of the method were verified using a standard recovery test with blank sesame-oil samples. Under the three standard levels of 0.04, 0.08, and 0.2 mg/kg, the recoveries of the five APs ranged from 71.3% to 97.8%, and the relative standard deviations (RSDs) ranged from 0.4% to 6.1%(n=6). The developed method is fast, accurate, sensitive, and has high throughput. Thus, it can realize the efficient screening, qualitative identification, and quantitative analysis of the 54 APs in sesame oil and provides a potential solution for the monitoring of other contaminants in food.

Generation of Human Blood Vessel and Vascularized Cerebral Organoids.

Brain organoids have been widely used to study diseases and the development of the nervous system. Many reports have investigated the application of brain organoids, but most of these models lack vascular structures, which play essential roles in brain development and neurological diseases. The brain and blood vessels originate from two different germ layers, making it difficult to induce vascularized brain organoids in vitro. We developed this protocol to generate brain-specific blood vessel and cerebral organoids and then fused them at a specific developmental time point. The fused cerebral organoids exhibited robust vascular network-like structures, which allows simulating the in vivo developmental processes of the brain for further applications in various neurological diseases. Key Features • Culturing vascularized brain organoids using human embryonic stem cells (hESCs). • The new approach generates not only neural cells and vessel-like networks but also brain-resident microglia immune cells in a single organoid.

Heel bone mineral density and various oral diseases: a bidirectional Mendelian randomization.

INTRODUCTION: Observational studies demonstrated that the relationship between bone mineral density and oral diseases is mixed. To access the association between heel bone mineral density and various oral diseases, we conducted the Mendelian randomization analysis to explore the association. MATERIALS AND METHODS: Two-sample bidirectional Mendelian analysis was used to explore the relationship between heel bone mineral density and various oral diseases. The inverse-variance weighted (IVW) was used as the primary effect estimate, and various methods were applied to test the reliability and stability of the results, namely MR-Egger, weighted median, simple mode, and weighted mode. RESULTS: This study showed that there was a negative relationship between heel BMD and periodontitis when heel BMD was used as an exposure factor and periodontitis as an outcome factor (IVW OR = 0.85; 95% CI, 0.75-0.95; p = 0.005). Bidirectional Mendelian randomization showed that there was no statistically significant association between periodontitis and heel bone mineral density when chronic periodontitis was the exposure factor (p > 0.05). And there was no significant relationship between heel bone mineral density and other oral diseases (dental caries, diseases of pulp and periapical tissues, impacted teeth, cleft lip, and cleft palate, oral and oropharyngeal cancer) (p > 0.05). CONCLUSION: This study showed that there was a negative relationship between heel bone density and periodontitis, and the decrease in heel bone density could promote the occurrence of periodontitis. In addition, there was no statistically significant relationship between heel bone density and other oral diseases.

HOXD-AS2-STAT3 feedback loop attenuates sensitivity to temozolomide in glioblastoma.

AIMS: Glioblastoma multiforme (GBM) is the deadliest glioma and its resistance to temozolomide (TMZ) remains intractable. Long non-coding RNAs (lncRNAs) play crucial roles in that and this study aimed to investigate underlying mechanism of HOXD-AS2-affected temozolomide sensitivity in glioblastoma. METHODS: We analyzed and validated the aberrant HOXD-AS2 expression in glioma specimens. Then we explored the function of HOXD-AS2 in vivo and in vitro and a clinical case was also reviewed to examine our findings. We further performed mechanistic experiments to investigate the mechanism of HOXD-AS2 in regulating TMZ sensitivity. RESULTS: Elevated HOXD-AS2 expression promoted progression and negatively correlated with prognosis of glioma; HOXD-AS2 attenuated temozolomide sensitivity in vitro and in vivo; The clinical case also showed that lower HOXD-AS2 sensitized glioblastoma to temozolomide; STAT3-induced HOXD-AS2 could interact with IGF2BP2 protein to form a complex and sequentially upregulate STAT3 signaling, thus forming a positive feedback loop regulating TMZ sensitivity in glioblastoma. CONCLUSION: Our study elucidated the crucial role of the HOXD-AS2-STAT3 positive feedback loop in regulating TMZ sensitivity, suggesting that this could be provided as a potential therapeutic candidate of glioblastoma.

[High-throughput screening of multi-pesticide residues in animal-derived foods by QuEChERS-online gel permeation chromatography-gas chromatography-tandem mass spectrometry].

Improvements in living standards have led to an increase in the consumption of animal-derived foods. Pesticides may be used illegally during animal breeding as well as meat production and processing for pest control and preservation. Pesticides applied to crops may also be enriched in animal tissues through the food chain, thereby increasing the risk of pesticide residue accumulation in muscles and visceral tissues and endangering human health. China has stipulated maximum residue limits for pesticide residues in livestock and poultry meat and their viscera. Many other major developed countries and organizations, including the European Union, Codex Alimentarius Commission, and Japan, have also set maximum residue limits for these residues (0.005-10, 0.004-10, and 0.001-10 mg/kg, respectively). Research on pretreatment technologies for pesticide residue detection in plant-derived foods is widely available, but insufficient attention has been paid to animal-derived foods. Thus, high-throughput detection technologies for pesticide residues in animal-derived foods are limited. The impurities that can interfere with the detection process for plant-derived foods mainly include organic acids, polar pigments, and other small molecular compounds; by contrast, the matrix of animal-derived foods is much more complex. Macromolecular proteins, fats, small molecular amino acids, organic acids, and phospholipids can interfere with the detection of pesticide residues in animal-derived foods. Thus, selecting the appropriate pretreatment and purification technology is of great importance. In this study, the QuEChERS technique was combined with online gel permeation chromatography-gas chromatography-tandem mass spectrometry (GPC-GC-MS/MS) to determine 196 pesticide residues in animal-derived foods. The samples were extracted with acetonitrile, purified using the QuEChERS technique coupled with online GPC, detected by GC-MS/MS, determined in multiple reaction monitoring mode (MRM), and quantified using the external standard method. The effects of the extraction solvent and purification agent type on the extraction efficiency and matrix removal of the method were optimized. The purification effect of online GPC on the sample solution was investigated. The optimal distillate receiving time was obtained by studying the recoveries of the target substances and matrix effects over different distillate receiving periods to achieve the effective introduction of target substances and efficient matrix removal. Further, the advantages of the QuEChERS technique combined with online GPC were evaluated. The matrix effects of 196 pesticides were assessed; ten pesticide residues showed moderate matrix effects, while four pesticide residues showed strong matrix effects. A matrix-matched standard solution was used for quantification. The 196 pesticides showed good linearity in the range of 0.005-0.2 mg/L, with correlation coefficients greater than 0.996. The limits of detection and quantification were 0.002 and 0.005 mg/kg, respectively. The recoveries of 196 pesticides at spiked levels of 0.01, 0.05, and 0.20 mg/kg were 65.3%-126.2%, with relative standard deviations (RSDs) of 0.7%-5.7%. The proposed method is rapid, accurate, and sensitive; thus, it is suitable for the high-throughput screening and detection of multiple pesticide residues in animal-derived foods.

Deep learning-based automatic sella turcica segmentation and morphology measurement in X-ray images.

BACKGROUND: Although the morphological changes of sella turcica have been drawing increasing attention, the acquirement of linear parameters of sella turcica relies on manual measurement. Manual measurement is laborious, time-consuming, and may introduce subjective bias. This paper aims to develop and evaluate a deep learning-based model for automatic segmentation and measurement of sella turcica in cephalometric radiographs. METHODS: 1129 images were used to develop a deep learning-based segmentation network for automatic sella turcica segmentation. Besides, 50 images were used to test the generalization ability of the model. The performance of the segmented network was evaluated by the dice coefficient. Images in the test datasets were segmented by the trained segmentation network, and the segmentation results were saved in binary images. Then the extremum points and corner points were detected by calling the function in the OpenCV library to obtain the coordinates of the four landmarks of the sella turcica. Finally, the length, diameter, and depth of the sella turcica can be obtained by calculating the distance between the two points and the distance from the point to the straight line. Meanwhile, images were measured manually using Digimizer. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to analyze the consistency between automatic and manual measurements to evaluate the reliability of the proposed methodology. RESULTS: The dice coefficient of the segmentation network is 92.84%. For the measurement of sella turcica, there is excellent agreement between the automatic measurement and the manual measurement. In Test1, the ICCs of length, diameter and depth are 0.954, 0.953, and 0.912, respectively. In Test2, ICCs of length, diameter and depth are 0.906, 0.921, and 0.915, respectively. In addition, Bland-Altman plots showed the excellent reliability of the automated measurement method, with the majority measurements differences falling within ± 1.96 SDs intervals around the mean difference and no bias was apparent. CONCLUSIONS: Our experimental results indicated that the proposed methodology could complete the automatic segmentation of the sella turcica efficiently, and reliably predict the length, diameter, and depth of the sella turcica. Moreover, the proposed method has generalization ability according to its excellent performance on Test2.

Alterations of Spontaneous Cortical and Subcortical Activity in Type 2 Diabetes Mellitus with and without Depression.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) patients with depression have a higher risk of complications and mortality than T2DM without depression. However, the exact neuropathophysiological mechanism remains unclear. Consequently, the current study aimed to investigate the alteration of cortical and subcortical spontaneous neural activity in T2DM patients with and without depression. METHODS: The demographic data, clinical variables, neuropsychological tests, and functional and anatomical magnetic resonance imaging of depressed T2DM (n = 47) of non-depressed T2DM (n = 59) and healthy controls (n = 41) were collected and evaluated. The correlation analysis, stepwise multiple linear regression, and receiver operating characteristic curve were performed for further analysis. RESULTS: Abnormal neural activities in the bilateral posterior cingulate cortex (PCC) and hippocampus were observed in depressed and non-depressed T2DM and the right putamen of the depressed T2DM. Interestingly, the subcortical degree centrality (DC) of the right hippocampus and putamen were higher in depressed than non-depressed T2DM. Furthermore, the cortical amplitude of low-frequency fluctuation (ALFF) in PCC, subcortical DC in the putamen of depressed T2DM, and hippocampus of non-depressed T2DM was correlated with cognitive scores. In contrast, the cortical fractional ALFF in PCC of non-depressed T2DM was correlated with depression scores. CONCLUSIONS: The abnormalities of spontaneous cortical activity in PCC and subcortical activity in the hippocampus might represent the neurobiological feature of cerebral dysfunction in T2DM. Notably, the altered subcortical activity in the right putamen might mainly associate with negative emotion in T2DM, which could be a promising biomarker for recognizing early cerebral dysfunction in depressed T2DM. This study provided a novel insight into the neuropathophysiological mechanism of brain dysfunction in T2DM with and without depression.

Relationship of family function and pre-hospital delay among Chinese patients with recurrent ischaemic stroke and the mediation effect of stigma.

AIMS: Pre-hospital delay refers to the time span from the onset of symptoms to arrival at a hospital ≥ 3 h and is the main limitation of stroke reperfusion therapies. Family factors and stroke-related stigma may influence pre-hospital delay. However, few studies have confirmed the influence of stigma on pre-hospital delay or explored the relationships between family function, stigma, and pre-hospital delay among patients with recurrent stroke. This study aimed to explore the relationship between family function and pre-hospital delay among patients with recurrent stroke and examine the mediation role of stigma in this relationship. METHODS AND RESULTS: A cross-sectional study was performed at the neurology departments of two hospitals in Guangzhou, China between July 2021 and April 2022. A total of 115 patients with recurrent stroke completed questionnaires and were included in the analysis. Data were collected using the Short Form Family Assessment Device, the Stroke Stigma Scale, and the Stroke Knowledge Questionnaire. Spearman's correlation and a structural equation model were used for data analysis. Family function directly influenced pre-hospital delay [ß=0.27, P = 0.033, 95%CI = (0.02-0.51)] and indirectly influenced pre-hospital delay [ß=0.17, P = 0.038, 95%CI = (0.02-0.34)] through stigma. Moreover, stigma partially mediated the effect of family function on pre-hospital delay. CONCLUSION: Family function and stigma directly and indirectly influenced pre-hospital delay among patients with recurrent stroke. Future health education and interventions need to focus on strengthening and improving emotional support from family members to improve family function and reduce stigma, thereby reducing pre-hospital delay among patients with recurrent stroke.

Correlation between carotid atherosclerosis stenotic severity and myocardial infarction size assessed by carotid color ultrasonography / 心血管康复医学杂志

Objective:To study correlation between carotid atherosclerosis(AS)stenotic severity and myocardial infarction(MI)size assessed by carotid color ultrasonography.Methods:According to infarction size,a total of 180 MI patients trea-ted in our hospital were divided into focal necrosis group(n=92),small-medium size infarction group(n=45)and large size infarction group(n=43).Carotid artery stenosis,peak systolic flow velocity(PSV),end diastolic flow velocity(EDV),number of AS plaques and MI location were compared among all group.And correlation between carotid AS ste-notic severity and MI size was analyzed.Results:Compared with focal necrosis group,there were significant reductions in PSV[(101.43±23.16)cm/s vs.(154.35±65.73)cm/s vs.(325.19±105.27)cm/s]and EDV[(34.19±19.36)cm/s vs.(77.13±20.61)cm/s vs.(138.41±84.93)cm/s]in small-medium size infarction group and large size infarction group,and above indexes of large size infarction group were significantly higher than those of small-medium size infarction group(P=0.001 all).Compared with focal necrosis group and small-medium size infarction group,there were significant rise in percentages of severe carotid stenosis(4.35%,11.11%vs.37.27%),occlusion(1.09%,4.44%vs.27.91%),number of atherosclerotic plaque＞2(38.04%,40.00%vs.65.12%)and anterior infarction(32.61%,35.56%vs.69.77%),and significant reduction in percentage of posterior infarction(48.91%,44.44%vs.23.26%)in large size infarction group(P＜0.05 or＜0.01).Spearman correlation analysis indicated that carotid AS stenotic severity was significant positively cor-related with MI size(r=0.733,P=0.001).Conclusion:Incidence rates of severe carotid stenosis and occlusion are higher in patients with large size myocardial infarction.Carotid AS stenotic severity is significant positively correlated with myo-cardial infarction size,which possesses certain application value in detecting myocardial infarction.

One new glycoside naphthopyranone from the Yiling cave-derived Metarhizium anisopliae NHC-M3-2 / 药学学报

Seven compounds were isolated from fermentation extract of cave-derived Metarhizium anisopliae NHC-M3-2 by silica gel, semi-preparative HPLC and other chromatographic methods. Their structures were elucidated by UV, IR, MS and NMR methods as 2,3-dehydroindigotide G (1), (-)-regiolone (2), naphtho-γ-pyrone (3), indigotide G (4), indigotide B (5) destruxin A (6) and destruxin B (7). Compound 1 is a new glycoside naphthopyranone compound. The anti-hepatitis B virus (HBV) activity of these compounds was evaluated. The EC50 and CC50 of compound 3 against HBV were 4.5 μmol·L-1 and 92.3 μmol·L-1, respectively. This is the first report of the antiviral activity of compound 3.

Neurovascular coupling and central nervous system diseases / 中国药理学通报

Neurovascular coupling is the function of regulating blood flow of the central nervous system at the level of neurovascular units. The central nervous system diseases related to neurovascular coupling mainly include cerebrovascular diseases such as chronic cerebral ischemia and neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease and Lewy body dementia. The main mechanism of neurovascular coupling dysfunction leading to the above diseases is cerebrovascular dysfunction or loss,which leads to serious damage to neuronal ischemia and affects its function. Therefore,this paper reviews the research status of neurovascular coupling and its related central nervous system diseases,in order to guide the follow-up research. The purpose of this paper is to provide a basis for the prevention,relief and treatment of central nervous system diseases related to neurovascular coupling through the mechanism of neurovascular coupling.

Influence of Heat Stress on Intestinal Epithelial Barrier Function, Tight Junction Protein, and Immune and Reproductive Physiology.

The potential threat of global warming in the 21st century is on the ecosystem through many aspects, including the negative impact of rising global temperature on the health of humans and animals, especially domestic animals. The damage caused by heat stress to animals has been more and more significant as the worldwide climate continues to rise, along with the breeding industry's expanding scale and stocking density, and it has become the most important stress-causing factor in southern China. In this review, we described the effects of heat stress on animal immune organs and immune system. The much-debated topic is how hyperthermia affects the tight junction barrier. Heat stress also induces inflammation in the body of animals causing low body weight and loss of appetite. This review also discussed that heat stress leads to hepatic disorder, and it also damages the intestine. The small intestine experiences ischemia, and the permeability of the intestine increases. Furthermore, the oxidative stress and mitogen-activated protein kinase (MAPK) pathways have a significant role in stress-induced cellular and organ injury. The study has shown that MAPK activity in the small intestine was increased by heat stress. Heat stress caused extreme small intestine damage, enhanced oxidative stress, and activated MAPK signaling pathways.

Translation and validation of M.D. Anderson Symptom Inventory-Thyroid Cancer module in Chinese thyroid cancer patients: a cross-sectional and methodological study.

AIM: To translate and validate the Chinese version of the MDASI-THY among thyroid cancer patients. BACKGROUND: The M.D. Anderson Symptom Inventory-Thyroid Cancer module (MDASI-THY) is one of well-validated instruments for thyroid-specific symptom assessment. To date, the instrument has not been used in China. METHODS: After standard forward- and back-translation procedures, two instruments, the Chinese version of MDASI-THY and the European Organization for Research and Treatment of Cancer QLQ C30, were answered by 309 thyroid patients. The content, convergent discriminant validity and reliability of the MDASI-THY were evaluated. RESULTS: The scale of content validity index (S-CVI) and the item of content validity index (I-CVI) of the instrument were over 0.80. There were significant relationships between MDASI-THY and EORTC QLQ-C30 (r range, 0.139 ~ 0.766, -0.759 ~ -0.461, p < 0.001). Symptoms were severer for patients underwent surgical treatment (Z = -9.999, p < 0.001). The Cronbach's alpha was 0.966 (between 0.954 and 0.827 for subscales). Most symptom items had moderate to high interitem correlations (r range, 0.297 ~ 0.773). CONCLUSIONS: The Chinese version of MDASI-THY demonstrated favorable validity and reliability. It can be used in development of symptom management program in thyroid cancer patients in China. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers can apply this instrument to assess Chinese thyroid cancer patients to increase the understanding of their symptom experience, resulting in a better symptom management.

The intestinal absorption mechanism of chicoric acid and its bioavailability improvement with chitosan.

Chicoric acid (CA), an active phenolic acid of Echinacea purpurea (Linn.) Moench, has been demonstrated to exhibit antioxidative, antiviral and immunological activities. A prior study showed that CA is a water-soluble compound with low bioavailability. The current study was performed to study the intestinal absorption mechanism of CA and improve its bioavailability using natural biodegradable chitosan. A Caco-2 monolayer cell model was established to characterise the mechanisms involved in the intestinal absorption of CA. The bioavailability improvement of CA was studied in Sprague-Dawley rats after oral (20 mg/kg) administration of 0.5% chitosan. In vitro, the results showed that the absorption transport of CA was fairly poor, with Papp values of 8.2 × 10-8 to 2.1 × 10-7 cm/s in the absorption direction and 1.5 × 10-7 to 2.6 × 10-7 cm/s in the secretory direction. The permeability was increased by EDTA and chitosan in both directions. Moreover, the transport through the intestinal monolayer was H+ dependent, and P-glycoprotein and OATP2B1 transporters were involved in the intestinal transport of CA. In vivo, the absorption of CA was increased and accelerated with chitosan in rats because the bioavailability was 1.74-fold that of the prototype drug. The above mentioned results indicated that CA was a poor absorption drug and that paracellular and carrier-mediated trancellular transport both participated in its transport route. Chitosan is an excellent absorption enhancer for CA. The transport characteristics uncovered in this study lay the groundwork for further studies directed toward the development and utilisation of its new formulations.

Generation of vascularized brain organoids to study neurovascular interactions.

Brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis and brain disorders, limits the utility of brain organoids. In this study, we induced vessel and brain organoids, respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood-brain barrier-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids and showed ability of engulfing synapses. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, particularly the vasculature and microglia niche.

Understanding how the organs form and how their cells behave is essential to finding the causes and treatment for developmental disorders, as well as understanding certain diseases. However, studying most organs in live animals or humans is technically difficult, expensive and invasive. To address this issue, scientists have developed models called 'organoids' that recapitulate the development of organs using stem cells in the lab. These models are easier to study and manipulate than the live organs. Brain organoids have been used to recapitulate brain formation as well as developmental, degenerative and psychiatric brain conditions such as microcephaly, autism and Alzheimer's disease. However, these brain organoids lack the vasculature (the network of blood vessels) that supplies a live brain with nutrients and regulates its development, and which has important roles in brain disorders. Partly due to this lack of blood vessels, brain organoids also do not develop a blood brain barrier, the structure that prevents certain contents of the blood, including pathogens, toxins and even certain drugs from entering the brain. These characteristics limit the utility of existing brain organoids. To overcome these limitations, Sun, Ju et al. developed brain organoids and blood vessel organoids independently, and then fused them together to obtain vascularized brain organoids. These fusion organoids developed a robust network of blood vessels that was well integrated with the brain cells, and produced more neural cell precursors than brain organoids that had not been fused. This result is consistent with the idea that blood vessels can regulate brain development. Analyzing the fusion organoids revealed that they contain structures similar to the blood-brain barrier, as well as microglial cells (immune cells specific to the brain). When exposed to lipopolysaccharide ­ a component of the cell wall of certain bacteria ­ these cells responded by initiating an immune response in the fusion organoids. Notably, the microglial cells were also able to engulf connections between brain cells, a process necessary for the brain to develop the correct structures and work normally. Sun, Ju et al. have developed a new organoid system that will be of broad interest to researchers studying interactions between the brain and the circulatory system. The development of brain-blood-barrier-like structures in the fusion organoids could also facilitate the development of drugs that can cross this barrier, making it easier to treat certain conditions that affect the brain. Refining this model to allow the fusion organoids to grow for longer times in the lab, and adding blood flow to the system will be the next steps to establish this system.

The L-shaped association between superoxide dismutase levels and blood pressure in older Chinese adults: community-based, cross-sectional study.

BACKGROUND: As an antioxidant, serum superoxide dismutase (SOD) have been found to be associated with hypertension. METHODS: The data were derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a prospective cohort study in China. We explored the association between serum SOD and blood pressure (BP) using multivariable correction analysis in an older Chinese population. RESULTS: We observed a significantly gradual downward trend in the association between serum SOD levels and diastolic BP (DBP) in participants with lower serum SOD levels (< 58 IU/mL), while no associations were observed between serum SOD levels and DBP in participants with higher serum SOD levels (> 58 IU/mL). Similar results showed a significant gradual downward trend in associations between serum SOD levels and the risk of diastolic hypertension only at SOD < 58 IU/mL. Multiple linear regression analysis suggested that serum SOD was negatively correlated with DBP (Sß = -0.088,P < 0.001) but not with SBP (Sß = 0.013, P = 0.607). Multiple logistic regression analysis suggested that serum SOD was independently associated with the risk of diastolic hypertension (OR = 0.984, 95% CI: 0.973-0.996, P = 0.010) but not with the risk of systolic hypertension (OR = 1.001, 95% CI: 0.990-1.012,P = 0.836)) after adjusting for relevant confounding factors. Serum SOD levels (< 58 IU/mL, > 58 IU/mL) were an effect modifier of the association between serum SOD and DBP (interactionP = 0.0038) or the risk of diastolic hypertension (interaction P = 0.0050). CONCLUSIONS: Our study indicated for the first time that there was an L-shaped association between serum SOD levels and the risk of diastolic hypertension in the older Chinese population.

A Decade-long Comparison of Prestroke Health Behaviors Among Hypertensive Stroke Patients in Mainland China.

ABSTRACT: BACKGROUND: Patients with hypertension are at a high risk for stroke, but a healthy lifestyle can greatly reduce the risk of stroke. However, there has been no research on the change in prestroke health behaviors in Chinese patients with hypertensive stroke over a decade. OBJECTIVES: The aims of this study were to determine whether prestroke health behaviors of patients with hypertensive stroke changed over a decade and to explore the predictors of prestroke health behaviors over a decade. METHODS: This study used data from 2 cross-sectional studies conducted in the neurology departments of 3 hospitals in Guangzhou, China. In total, 110 hypertensive stroke patients were recruited in stage I (2008-2009), and 119 hypertensive stroke patients were recruited in stage II (2018-2019). Patients' stroke knowledge was measured by the Stroke Knowledge Questionnaire. Patients' prestroke health behavior was measured by the Health Behavior Scale for Stroke Patients. RESULTS: The total score of prestroke health behaviors significantly increased over the decade (P < .001), but the scores of the subcategories of low-fat diet, low-sugar diet, and blood pressure checkups decreased over the decade (P < .05). Stroke knowledge was a significant predictor of prestroke health behaviors in stage I (P < .05). Besides stroke knowledge, sex and age were significant predictors of prestroke health behaviors in stage II (P < .05). CONCLUSIONS: Prestroke health behaviors of hypertensive stroke patients significantly improved over the decade. Moreover, prestroke health behaviors were significantly influenced by stroke-related knowledge over the decade. Healthcare providers should focus in particular on assisting patients who are male, young, and middle-aged, and lack stroke-related knowledge to improve their prestroke health behaviors, especially in terms of adherence to a low-fat/low-sugar diet and regular blood pressure checks.