CYP1B1 affects the integrity of the blood-brain barrier and oxidative stress in the striatum: An investigation of manganese-induced neurotoxicity.

AIMS: Excessive influx of manganese (Mn) into the brain across the blood-brain barrier induces neurodegeneration. CYP1B1 is involved in the metabolism of arachidonic acid (AA) that affects vascular homeostasis. We aimed to investigate the effect of brain CYP1B1 on Mn-induced neurotoxicity. METHOD: Brain Mn concentrations and α-synuclein accumulation were measured in wild-type and CYP1B1 knockout mice treated with MnCl2 (30 mg/kg) and biotin (0.2 g/kg) for 21 continuous days. Tight junctions and oxidative stress were analyzed in hCMEC/D3 and SH-SY5Y cells after the treatment with MnCl2 (200 µM) and CYP1B1-derived AA metabolites (HETEs and EETs). RESULTS: Mn exposure inhibited brain CYP1B1, and CYP1B1 deficiency increased brain Mn concentrations and accelerated α-synuclein deposition in the striatum. CYP1B1 deficiency disrupted the integrity of the blood-brain barrier (BBB) and increased the ratio of 3, 4-dihydroxyphenylacetic acid (DOPAC) to dopamine in the striatum. HETEs attenuated Mn-induced inhibition of tight junctions by activating PPARγ in endothelial cells. Additionally, EETs attenuated Mn-induced up-regulation of the KLF/MAO-B axis and down-regulation of NRF2 in neuronal cells. Biotin up-regulated brain CYP1B1 and reduced Mn-induced neurotoxicity in mice. CONCLUSIONS: Brain CYP1B1 plays a critical role in both cerebrovascular and dopamine homeostasis, which might serve as a novel therapeutic target for the prevention of Mn-induced neurotoxicity.

SCANeXt: Enhancing 3D medical image segmentation with dual attention network and depth-wise convolution.

Existing approaches to 3D medical image segmentation can be generally categorized into convolution-based or transformer-based methods. While convolutional neural networks (CNNs) demonstrate proficiency in extracting local features, they encounter challenges in capturing global representations. In contrast, the consecutive self-attention modules present in vision transformers excel at capturing long-range dependencies and achieving an expanded receptive field. In this paper, we propose a novel approach, termed SCANeXt, for 3D medical image segmentation. Our method combines the strengths of dual attention (Spatial and Channel Attention) and ConvNeXt to enhance representation learning for 3D medical images. In particular, we propose a novel self-attention mechanism crafted to encompass spatial and channel relationships throughout the entire feature dimension. To further extract multiscale features, we introduce a depth-wise convolution block inspired by ConvNeXt after the dual attention block. Extensive evaluations on three benchmark datasets, namely Synapse, BraTS, and ACDC, demonstrate the effectiveness of our proposed method in terms of accuracy. Our SCANeXt model achieves a state-of-the-art result with a Dice Similarity Score of 95.18% on the ACDC dataset, significantly outperforming current methods.

The association of dietary patterns with latent tuberculosis infection among young adults: A case-control study in Shanghai.

INTRODUCTION: In developing and underdeveloped countries, undernutrition plays a major role in subverting the immune system, leading to an increase in TB infections; this study investigated the associations between dietary patterns and latent tuberculosis infection risk among young adults in Shanghai. METHODOLOGY: In a case-control study, 96 cases of latent tuberculosis infection and 192 healthy controls were studied among contacts of students in clusters of tuberculosis epidemics in colleges from January 2021 to March 2023. A standardized questionnaire assessing sociodemographic, lifestyle, and dietary characteristics was applied. Food intake was estimated using a 95-item semiquantitative Food Frequency Questionnaire. Using the principal component analysis to extract dietary patterns from food groups intake. Logistic regression models were applied. RESULTS: Four dietary patterns were identified: "traditional balanced" pattern, "unsaturated fatty acid" pattern, "snack" pattern, and "protein and fruit" pattern. Four components explaining 64.52% of the total variation in consumption were derived. In a conditional logistic regression analysis, three models were created. After adjusting for various confounders, compared to "snack" pattern, the risk of latent TB infection was 91% lower in the "traditional balanced" pattern (OR 0.05, 95% CI 0.01, 0.38, p = 0.004). CONCLUSIONS: To prevent TB infection among young adults living in high TB burden areas, a balanced dietary pattern rather than a "snack" pattern should be promoted in school settings. Future research should explore the risk of developing active tuberculosis in Mtb-infected people with different dietary patterns and the prevention of this risk by healthy dietary patterns.

Association of Fat Mass and Skeletal Muscle Mass with Cardiometabolic Risk Varied in Distinct PCOS Subtypes: A Propensity Score-Matched Case-Control Study.

(1) Background: polycystic ovarian syndrome (PCOS) is a heterogeneous syndrome with a constellation of cardiometabolic risk factors. We aimed to investigate if the association of body fat mass (BFM) and skeletal muscle mass (SMM) with cardiometabolic risk differed in PCOS subtypes. (2) Methods: 401 participants (245 PCOS and 156 controls) were assessed for anthropometric measurements, glucose-lipid profiles, reproductive hormones and body composition with propensity score-matched (PSM) analysis. The association of the cardiometabolic risk score (z score, calculated based on levels of obesity and gluco-lipid measurements) with BFM (estimated by trunk BFM/Height2) and SMM (estimated by SMM/Height2) was calculated. (3) Results: Trunk BFM/Height2 and SMM/Height2 were both positively associated with cardiometabolic risk in PCOS (trunk BFM/Height2, OR 2.33, 95% CI 1.49-3.65; SMM/Height2, OR 2.05, 95% CI 1.12-3.76). SMM/Height2 associated with increased cardiometabolic risk in obese PCOS (BMI ≥ 28 kg/m2, OR 2.27, 95% CI 1.15-4.47). For those with lower BMI (<28 kg/m2), trunk BFM/Height2 showed a higher OR in both groups (PCOS, OR 2.12, 95% CI 1.06-4.24; control 2.04, 95% CI 1.04-4.02). Moreover, distinct associations among BMI-stratified groups were validated in hierarchical clustering identifying metabolic and reproductive clusters. (4) Conclusions: BFM and SMM are synergistically associated with higher cardiometabolic risk in PCOS women. Although BFM contributes to increased cardiometabolic risk, SMM also plays a primary role in obese PCOS. Our results highlight the importance of body composition in the management of PCOS.

Thigh muscle fat fraction is independently associated with impaired glucose metabolism in individuals with obesity.

Background: The aim of this study was to address the intramuscular adipose tissue (IMAT) accumulation in the lower extremities and further detect the relationship between adipose tissue (AT) distribution in the muscle and glucose metabolism in subjects with obesity. Methods: We conducted a cross-sectional study in 120 Chinese obese adults (80 male and 40 female) with BMI ≥ 28 kg/m2. MRI was applied to access the IMAT content in lower extremities. The oral glucose tolerance test was used to evaluate the glucose metabolism and insulin secretion in all individuals. The correlations between glucose metabolism and the fat content of the lower extremities were further assessed. Results: Among 120 included subjects, 54 were classified as subjects with normal glucose tolerance (NGT) and 66 with impaired glucose regulation (IGR). We presented that those with IGR had higher fat accumulation in semitendinosus, adductor magnus, gracilis and sartorius than those with NGT (all P < 0.05). In sex-specific analyses, females have higher IMAT in adductor magnus than males (P < 0.001). Males with IGR had higher fat fraction of semitendinosus and sartorius than those with NGT (P = 0.020, P = 0.014, respectively). Logistic regression analyses revealed that IMAT content in semitendinosus was the independent factor of IGR in individuals with obesity after adjustment for age, gender, triglycerides, creatinine and albumin (odds ratio: 1.13, 95% CI: 1.02-1.26, P = 0.024). Conclusions: Increased adipose tissue accumulation in thigh muscles was associated with glucose dysregulation in patients with obesity. IMAT content in semitendinosus may serve as a possible risk factor for impaired glucose metabolism.

A prediction model of liver fat fraction and presence of non-alcoholic fatty liver disease (NAFLD) among patients with overweight or obesity.

The global prevalence of non-alcoholic fatty liver disease (NAFLD) has attained a level of 25.24%. The prevalence of NAFLD in China has exhibited an upward trajectory in parallel with the increasing incidence of obesity over the preceding decade. In order to comprehensively assess hepatic lipid deposition in individuals with overweight or obesity, we have devised a pioneering prognostic formula that capitalizes on clinical parameters. To this end, we have conducted a cross-sectional cohort study involving 149 overweight or obese subjects. Magnetic resonance imaging proton density fat fraction (MRI-PDFF) has been employed to evaluate the extent of liver fat accumulation. Through univariate analysis, we have identified potential factors, and the definitive elements in the prediction model were selected utilizing the forward stepwise regression algorithm. The Shang Hai Steatosis Index (SHSI) incorporates alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting insulin, and 1-h postload glycaemic levels, thereby furnishing the capability to predict NAFLD with an area under the receiver operator characteristic (AUROC) of 0.87. By establishing a threshold value of 10.96, determined through Youden's index, we have achieved a sensitivity of 69.57% and a specificity of 88.24%. The Spearman correlation coefficient between liver fat fraction ascertained by MRI-PDFF and that predicted by the SHSI equation amounts to 0.74. Consequently, the SHSI equation affords a dependable means of predicting the presence of NAFLD and liver fat accumulation within the overweight and obese population.

Cavitation Erosion Prevention Using Laser Shock Peening: Development of a Predictive Evaluation System.

Marine flow-passing components are susceptible to cavitation erosion (CE), and researchers have worked to find ways to reduce its effects. Laser Shock Peening (LSP), a material strengthening method, has been widely used in aerospace and other cutting-edge fields. In recent years, LSP has been used in cavitation resistance research. However, the current LSP research does not realize a comprehensive predictive assessment of the material's CE resistance. This paper uses m stresses to develop a comprehensive set of strengthening effect prediction models from LSP to CE using finite element analysis (FEA). Results show that the LSP-1 sample (4 mm spot, 10 J energy) introduced a compressive residual stress value of 37.4 MPa, better than that of 16.6 MPa with the LSP-2 sample (6 mm spot, 10 J energy), which is generally consistent with the experimental findings; the model predicts a 16.35% improvement in the resistance of LSP-1 sample to water jet damage, which is comparable to the experimental result of 14.02%; additionally, interactions between micro-jets do not predominate the cavitation erosion process and the final CE effect of the material is mainly due to the accumulation of jet-material interaction.

Myocardial Tissue-Level Characteristics of Adults With Metabolically Healthy Obesity.

BACKGROUND: It remains unclear whether adults with metabolically healthy obesity (MHO) have altered myocardial tissue-level characteristics. OBJECTIVES: This study aims to assess the subclinical myocardial tissue-level characteristics of adults with MHO. METHODS: The EARLY-MYO-OBESITY (EARLY Assessment of MYOcardial Tissue Characteristics in OBESITY; NCT05277779) registry was a prospective, 3-center, cardiac imaging study of obese nondiabetic individuals without cardiac symptoms who underwent cardiac magnetic resonance. Myocardial tissue-level characteristics, including extracellular volume fraction (ECV) and native T2 values, were measured as indicators of myocardial fibrosis and edema. Global longitudinal peak systolic strain and early diastolic longitudinal strain rate were assessed by tissue tracking analysis to detect subclinical systolic and diastolic dysfunction. RESULTS: A total of 120 participants were included: MHO (n = 32; mean age, 38 years; 41% men), metabolically healthy controls without obesity (n = 32; mean age: 37 years; 41% men), and metabolically unhealthy obesity (MUHO) (n = 56; mean age: 37 years; 55% men). The MHO group had higher ECV and native T2 values than healthy controls (both P < 0.001); furthermore, the ECV was higher in the MUHO group than in the MHO group (P = 0.002). The prevalence of myocardial fibrosis was 44% (14 of 32) in the MHO group and 71% (40 of 56) in the MUHO group. Although there was no intergroup difference in left ventricular ejection fraction, the MHO group had reduced global longitudinal peak systolic and early diastolic longitudinal strain rates, indicating subclinical systolic and diastolic dysfunction. Multivariate regression analysis identified increased body mass index to be an independent risk factor for myocardial fibrosis (OR: 6.28 [95% CI: 3.17-12.47]; P < 0.001). CONCLUSIONS: This study provides the first evidence of subclinical myocardial tissue-level remodeling in adults with obesity, regardless of metabolic health. Early identification of cardiac impairment may facilitate preventive strategies against heart failure in the MHO population. (EARLY Assessment of MYOcardial Tissue Characteristics in OBESITY [EARLY-MYO-OBESITY]; NCT05277779).

An intelligent phase transformation system based on lyotropic liquid crystals for sequential biomolecule delivery to enhance bone regeneration.

Endogenous repair of critical bone defects is typically hampered by inadequate vascularization in the early stages and insufficient bone regeneration later on. Therefore, drug delivery systems with the ability to couple angiogenesis and osteogenesis in a spatiotemporal manner are highly desirable for vascularized bone formation. Herein, we devoted to develop a liquid crystal formulation system (LCFS) attaining a controlled temporal release of angiogenic and osteoinductive bioactive molecules that could orchestrate the coupling of angiogenesis and osteogenesis in an optimal way. It has been demonstrated that the release kinetics of biomolecules depend on the hydrophobicity of the loaded molecules, making the delivery profile programmable and controllable. The hydrophilic deferoxamine (DFO) could be released rapidly within 5 days to activate angiogenic signaling, while the lipophilic simvastatin (SIM) showed a slow and sustained release for continuous osteogenic induction. Apart from its good biocompatibility with mesenchymal stem cells derived from rat bone marrow (rBMSCs), the DFO/SIM loaded LCFS could stimulate the formation of a vascular morphology in human umbilical vein endothelial cells (HUVECs) and the osteogenic differentiation of rBMSCs in vitro. The in vivo rat femoral defect models have witnessed the prominent angiogenic and osteogenic effects induced by the sequential presentation of DFO and SIM. This study suggests that the sequential release of DFO and SIM from the LCFS results in enhanced bone formation, offering a facile and viable treatment option for bone defects by mimicking the physiological process of bone regeneration.

Research progress on maintaining chloroplast homeostasis under stress conditions: a review.

On a global scale, drought, salinity, extreme temperature, and other abiotic stressors severely limit the quality and yield of crops. Therefore, it is crucial to clarify the adaptation strategies of plants to harsh environments. Chloroplasts are important environmental sensors in plant cells. For plants to thrive in different habitats, chloroplast homeostasis must be strictly regulated, which is necessary to maintain efficient plant photosynthesis and other metabolic reactions under stressful environments. To maintain normal chloroplast physiology, two important biological processes are needed: the import and degradation of chloroplast proteins. The orderly import of chloroplast proteins and the timely degradation of damaged chloroplast components play a key role in adapting plants to their environment. In this review, we briefly describe the mechanism of chloroplast TOC-TIC protein transport. The importance and recent progress of chloroplast protein turnover, retrograde signaling, and chloroplast protein degradation under stress are summarized. Furthermore, the potential of targeted regulation of chloroplast homeostasis is emphasized to improve plant adaptation to environmental stresses.

A novel visceral adiposity index predicts bone loss in female early rheumatoid arthritis patients detected by HR-pQCT.

The purpose of this prospective study is to compare the Chinese visceral adiposity index (CVAI) between early rheumatoid arthritis (ERA) patients and healthy controls; and to assess the relationship between CVAI and the bone microstructure using high-resolution peripheral quantitative computed tomography (HR-pQCT) in ERA patients. 104 female ERA and 100 age-, gender- and BMI-matched healthy controls were recruited for the comparison of CVAI. All ERA patients were prospectively followed for 1 year. HR-pQCT scan of the distal radius, tibia and second metacarpal head were performed at baseline and after one-year. ERA patients were divided into two sub-groups according to the median CVAI value (65.73) (low CVAI and high CVAI groups). CVAI in the ERA group was significantly higher than the controls group (p = 0.01). At baseline, the high CVAI group had a higher ESR level (p = 0.004) while the cortical volumetric bone mineral density (vBMD) was lower (at both the distal radius and tibia, all p < 0.05) compared to the low CVAI group. Linear regression analysis revealed that a higher baseline CVAI was an independent predictor of a lower cortical vBMD at month 12 (distal radius: B = - 0.626, p = 0.022, 95%CI - 1.914 to - 0.153; tibia: B = - 0.394, p = 0.003, 95%CI - 1.366 to - 0.290); and a greater reduction in trabecular vBMD (tibia: B = 0.444, p = 0.001, 95%CI 0.018-0.063; distal radius: B = 0.356, p = 0.008, 95%CI 0.403-0.063). In summary, CVAI is an independent predictor of trabecular bone loss in female patients with ERA, which may be augmented by a chronic inflammatory state in patients with visceral dysfunction of fat metabolism.Trial registration: http://Clinicaltrial.gov no: NCT01768923, 16/01/2013.

Liver fat is superior to visceral and pancreatic fat as a risk biomarker of impaired glucose regulation in overweight/obese subjects.

AIM: To investigate the distribution of abdominal fat, particularly ectopic fat accumulation, in relation to glucose metabolism in overweight/obese patients. MATERIALS AND METHODS: This study included 257 overweight/obese subjects with body mass index ≥23 kg/m2 . All the subjects underwent an oral glucose tolerance test. Magnetic resonance imaging-proton density fat fraction was used to measure fat accumulation in the liver, pancreas and abdomen. Impaired glucose regulation (IGR) was defined as the presence of prediabetes or diabetes. RESULTS: Liver fat content (LFC) and visceral adipose tissue (VAT) were higher in overweight/obese subjects with diabetes than in those with normal glucose tolerance (NGT). No significant differences were observed in the pancreas fat content and subcutaneous fat area between subjects with NGT and IGR. LFC was an independent risk factor of IGR (odds ratio = 1.824 per standard deviation unit, 95% CI 1.242-2.679, p = .002). Compared with the lowest tertile of LFC, the multivariate-adjusted odds ratio for the prevalence of IGR in the highest tertile was 2.842 (95% CI 1.205-6.704). However, no association was observed between the VAT per standard deviation increment and tertiles after adjusting for multiple factors. For discordant visceral and liver fat phenotypes, the high LFC-low VAT and high LFC-high VAT groups had a higher prevalence of IGR than the low LFC-low VAT group. However, there was no difference in the prevalence of IGR between the low LFC-low VAT and low LFC-high VAT groups. CONCLUSION: Compared with visceral and pancreatic fat content, LFC is a superior risk biomarker for IGR in overweight/obese subjects.

Split-Ubiquitin Two-Hybrid Screen for Proteins Interacting with slToc159-1 and slToc159-2, Two Chloroplast Preprotein Import Receptors in Tomato (Solanum lycopersicum).

The post-translational import of nuclear-encoded chloroplast preproteins is critical for chloroplast biogenesis, and the Toc159 family of proteins is the receptor for this process. Our previous work identified and analyzed the Toc GTPase in tomato; however, the tomato-specific transport substrate for Toc159 is still unknown, which limits the study of the function of the TOC receptor in tomato. In this study, we expand the number of preprotein substrates of slToc159 receptor family members using slToc159-1 and slToc159-2 as bait via a split-ubiquitin yeast two-hybrid membrane system. Forty-one specific substrates were identified in tomato for the first time. Using slToc159-1GM and slToc159-2GM as bait, we compared the affinity of the two bait proteins, with and without the A domain, to the precursor protein, which suggested that the A domain endowed the proproteins with subclass specificity. The presence of the A domain enhanced the interaction intensity of slToc159-1 with the photosynthetic preprotein but decreased the interaction intensity of slToc159-2 with the photosynthetic preprotein. Similarly, the presence of the A domain also altered the affinity of slToc159 to non-photosynthetic preproteins. Bimolecular fluorescence complementation (BiFC) analysis showed that A domain had the ability to recognize the preprotein, and the interaction occurred in the chloroplast. Further, the localization of the A domain in Arabidopsis protoplasts showed that the A domain did not contain chloroplast membrane targeting signals. Our data demonstrate the importance of a highly non-conserved A domain, which endows the slToc159 receptor with specificity for different protein types. However, the domain containing the information on targeting the chloroplast needs further study.

[Analysis of PM2.5 Transmission Characteristics in Main Cities of Jinzhong Basin in Winter].

In this study, we analyzed the hourly concentration data of PM10 and PM2.5 in major cities in Jinzhong basin from 2017 to 2019. The main distribution characteristics of aerosols in Jinzhong and Taiyuan were determined, and PM2.5 hourly concentration data and HYSPLIT in Jinzhong basin in winter were discussed. The results showed that the overall level of particulate matter concentration in Taiyuan was higher than that in Jinzhong, and the monthly and seasonal variation characteristics were similar. All showed high concentrations in winter and low concentrations in summer, and the highest concentration value appeared in January. The aerosol pollution caused by the static and stable weather in Jinzhong was more common than that caused by the sand and dust weather in Taiyuan. The distribution of particulate matter showed the characteristics of more intermediate values in Jinzhong and more high and fewer low values in Taiyuan, and winter was the highest incidence season of PM2.5 pollution in Jinzhong basin. PM2.5 transmission passageways in the main cities of Jinzhong basin in winter could be divided into four categories:class 1 was transmitted along the transverse valley of Taihang Mountain, and class 2 was the southeast transmission channel. Class 1 and class 2 were the short-range transmission passageways; air masses carried more moisture, and PM2.5 transmitted along such passageways allowed moisture to be absorbed more easily, increasing levels and aggravating local pollution. Class 3 was the northwest passageway, corresponding to the most serious pollution period of PM2.5 in Jinzhong basin before the arrival of cold air, which also corresponded to the dust transmission passageway. Class 4 was the Fenwei Plain passageway, corresponding to high-concentration PM2.5 pollution. Areas with dense pollution tracks (more than 100 pollution tracks) and areas with slow air flow movement (RTA pollution track end points greater than 50) easily became potential source areas of target cities (PSCF contribution greater than 0.7). The main potential source areas of PM2.5 in winter in Jinzhong (PSCF contributing more than 0.7) were mainly distributed in Linfen, Jincheng, and other places in Shanxi province, as well as in the north of Henan province, the south of Hebei province, and central and south Shaanxi province. The distribution range of main potential source areas of PM2.5 in Taiyuan in winter was wider than that in Jinzhong, including the south of Lvliang, Yangquan, Linfen, and Yuncheng and the south of Jinzhong in Shanxi, as well as most areas in southern Shaanxi, northern Henan province, and southern Hebei province. In addition, the PSCF distribution of high-value centers above 0.9 was wider than that of Jinzhong. When pollution occurs in cities that PSCF contributed more than 0.9, special attention should be paid to the influence of mutual transmission between them and cities in Jinzhong basin. Jinzhong and Taiyuan showed different distribution characteristics corresponding to the surface wind direction when light and higher pollution occur, when the wind direction near the ground in Jinzhong was E, the frequency of light and higher pollution was 8.1%; it was the highest in all wind directions. When the wind direction near the ground in Taiyuan was SSW, the frequency of light to higher polluted weather was the highest in all wind directions (5.1%). In the case of calm wind, the frequency of light to higher pollution in Taiyuan (3.4%) was higher than that in Jinzhong (0.5%).

Magnesium implantation or supplementation ameliorates bone disorder in CFTR-mutant mice through an ATF4-dependent Wnt/ß-catenin signaling.

Magnesium metal and its alloys are being developed as effective orthopedic implants; however, the mechanisms underlying the actions of magnesium on bones remain unclear. Cystic fibrosis, the most common genetic disease in Caucasians caused by the mutation of CFTR, has shown bone disorder as a key clinical manifestation, which currently lacks effective therapeutic options. Here we report that implantation of magnesium-containing implant stimulates bone formation and improves bone fracture healing in CFTR-mutant mice. Wnt/ß-catenin signaling in the bone is enhanced by the magnesium implant, and inhibition of Wnt/ß-catenin by iCRT14 blocks the magnesium implant to improve fracture healing in CFTR-mutant mice. We further demonstrate that magnesium ion enters osteocytes, increases intracellular cAMP level and activates ATF4, a key transcription factor known to regulate Wnt/ß-catenin signaling. In vivo knockdown of ATF4 abolishes the magnesium implant-activated ß-catenin in bones and reverses the improved-fracture healing in CFTR-mutant mice. In addition, oral supplementation of magnesium activates ATF4 and ß-catenin as well as enhances bone volume and density in CFTR-mutant mice. Together, these results show that magnesium implantation or supplementation may serve as a potential anabolic therapy for cystic fibrosis-related bone disease. Activation of ATF4-dependent Wnt/ß-catenin signaling in osteocytes is identified as a previously undefined mechanism underlying the beneficial effect of magnesium on bone formation.

Dyslipidemia Is Related to Mortality in Critical Patients With Coronavirus Disease 2019: A Retrospective Study.

Background: It has been reported that dyslipidemia is related to coronavirus-related diseases. Critical patients with coronavirus disease 2019 (COVID-19) who suffered from multiple organ dysfunctions were treated in the intensive care unit (ICU) in Wuhan, China. Whether the lipids profile was associated with the prognosis of COVID-19 in critical patients remained unclear. Methods: A retrospective study was performed in critical patients (N=48) with coronavirus disease 2019 in Leishenshan hospital between February and April 2020 in Wuhan. The parameters including lipid profiles, liver function, and renal function were collected on admission day, 2-3days after the admission, and the day before the achievement of clinical outcome. Results: Albumin value and creatine kinase (ck) value were statistically decreased at 2-3 days after admission compared with those on admission day (P<0.05). Low density lipoprotein (LDL-c), high density lipoprotein (HDL-c), apolipoprotein A (ApoA), and apolipoprotein A (Apo B) levels were statistically decreased after admission (P<0.05). Logistic regression showed that HDL-c level both on admission day and the day before the achievement of clinical outcome were negatively associated with mortality in critical patients with COVID-19. Total cholesterol (TC) level at 2-3days after admission was related to mortality in critical patients with COVID-19. Conclusions: There were lipid metabolic disorders in the critical patients with COVID-19. Lower levels of HDL-c and TC were related to the progression of critical COVID-19.

Reduced inflammatory responses to SARS-CoV-2 infection in children presenting to hospital with COVID-19 in China.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children is associated with better outcomes than in adults. The inflammatory response to COVID-19 infection in children remains poorly characterised. METHODS: We retrospectively analysed the medical records of 127 laboratory-confirmed COVID-19 patients aged 1 month to 16 years from Wuhan and Jingzhou of Hubei Province. Patients presented between January 25th and March 24th 2020. Information on clinical features, laboratory results, plasma cytokines/chemokines and lymphocyte subsets were analysed. FINDINGS: Children admitted to hospital with COVID-19 were more likely to be male (67.7%) and the median age was 7.3 [IQR 4.9] years. All but one patient with severe disease was aged under 2 and the majority (5/7) had significant co-morbidities. Despite 53% having viral pneumonia on computed tomography (CT) scanning only 2 patients had low lymphocyte counts and no differences were observed in the levels of plasma proinflammatory cytokines, including interleukin (IL)-2, IL-4, IL-6, tumour necrosis factor (TNF)- α , and interferon (IFN)- γ between patients with mild, moderate or severe disease. INTERPRETATIONS: We observed that the immune responses of children to COVID-19 infection is significantly different from that seen in adults. Our evidence suggests that SARS-CoV-2 does not trigger a robust inflammatory response or 'cytokine storm' in children with COVID-19, and this may underlie the generally better outcomes seen in children with this disease.

Broadening the role of osteocalcin in the hypothalamic-pituitary-gonadal axis.

Bone is emerging as a versatile endocrine organ and its interactions with apparently unrelated organs are being more widely recognized. Osteocalcin (OCN), a polypeptide hormone secreted by osteoblasts, has been found to exert multiple endocrine functions through its metabolically active form, uncarboxylated OCN (uOCN). Mounting evidence has shown that following its binding to G-protein coupled receptor 6a (Gprc6a) in the peripheral tissues, uOCN acts on pancreatic ß cells to increase insulin secretion, and on muscle and white adipose tissue to promote glucose and lipid metabolism. More strikingly, researchers have found a surprising role of uOCN in testicular function to facilitating testosterone biosynthesis and regulating male fertility via a pancreas-bone-gonadal axis. However, the detailed functional mechanisms of uOCN on the hypothalamic-pituitary-gonadal axis or the pancreas-bone-gonadal axis are not fully understood. Besides highlighting the regulatory mechanisms of uOCN in the hypothalamus and pituitary, we also discuss its role in male as well as female fertility and its potential clinical implications in some reproductive endocrine diseases and pubertal developmental disorders.

Intervention by clinical pharmacists can improve blood glucose fluctuation in patients with diabetes and acute myocardial infarction: A propensity score-matched analysis.

Acute phase hyperglycemia and exaggerated glucose fluctuation may be associated with poor outcomes in diabetic patients after acute myocardial infarction (AMI). This study aimed to determine whether intervention by clinical pharmacists can mitigate blood glucose and glucose fluctuations in these fragile patients. This retrospective study enrolled patients with diabetes and AMI, from 1 January 2019 to 30 June 2020 in our institution. Blood glucose and glucose fluctuations were calculated before and after the pharmacist's intervention and between patients who underwent intervention and those who did not. Propensity score matching (PSM) was used to reduce the impact of patient characteristics on the results. A total of 170 patients were included in our primary analysis, including 29 patients who received the pharmacist intervention and 141 patients who did not. After the pharmacist's intervention, blood glucose (fasting blood glucose-FBG, from 11.9 to 9.8; postprandial blood glucose-PBG, from 15.3 to 13.2; mean blood glucose-BG, 14.5 to 12.3 mmol/L; p < .001), and glucose fluctuations (standard deviation of blood glucose-SDBG, from 3.8 to 3.0, mmol/L, p = .005) were significantly improved. Before PSM, no clear effects were found in intervention versus nonintervention patients, in terms of blood glucose and glucose fluctuation indicators, except for FBG (9.3 vs. 8.0. mmol/L, p = .005). Further analysis indicated a high incidence of FBG <7.8 mmol/L in nonintervention versus intervention patients (51.5% vs. 27.6%, p = .003). After PSM, a significant reduction in blood glucose fluctuation (SDBG, 3.0 vs. 4.1, p = .031; PBGE, 2.1 vs. 4.1, p = .017; LAGE, 4.7 vs. 7.2, mmol/L, p = .004), and PBG (11.1 vs. 13.0, mmol/L, p = .048) was observed in the intervention group than in the nonintervention group. The clinical pharmacist intervention contributed to improved outcomes, specifically, in reducing blood glucose fluctuations and potential hypoglycemia risk.