Causal Association of Iron Status With Functional Outcome After Ischemic Stroke.

BACKGROUND: Iron status has been associated with functional outcomes after ischemic stroke (IS). Nonetheless, this association may be affected by confounders. We perform Mendelian randomization to clarify the causal association between iron status and functional outcome after IS. METHODS: We obtained summary-level statistics related to iron status biomarkers from a meta-analysis of a gene-wide association study conducted by the Genetics of Iron Status Consortium, which included 11 discovery cohorts and 8 replication cohorts. We also took genetic variants related to 4 biomarkers of iron status from combining gene-wide association study results of Iceland, the United Kingdom, and Denmark to perform a replicate Mendelian randomization analysis. This data set included 4 iron status biomarkers, namely, ferritin, total iron binding capacity, iron, and transferrin saturation (TSAT). The confounders in these data sets have been adjusted to mitigate the collider bias. We acquired summary statistics data sets for functional outcomes following IS from the gene-wide association study meta-analysis conducted by the Genetics of Ischemic Stroke Functional Outcome Consortium. The genetic estimates for functional outcomes at 90 days after IS were evaluated by the modified Rankin Scale score, including 3741 cases with good functional outcomes (modified Rankin Scale score, 0-2) and 2280 subjects with poor functional outcomes poststroke (modified Rankin Scale score, 3-6). Inverse variance weighting was used as the primary method, complemented by sensitivity analyses for pleiotropy and increasing robustness. RESULTS: Reported with odds ratios (ORs) of stroke outcome with per SD unit increase in genetically determined iron status biomarker, TSAT and iron were associated with poor functional outcome after IS (TSAT: OR, 1.36 [95% CI, 1.23-1.50]; P=2.27×10-9; iron: OR, 1.44 [95% CI, 1.13-1.85]; P=0.0033). In replicate Mendelian randomization analysis, the detrimental effects of iron on poor functional outcome after IS remained stable (OR, 1.60 [95% CI, 1.24-2.08]; P=0.0003). In the meta-analysis, iron and TSAT were associated with poor functional outcomes after IS (TSAT: ORmeta, 1.35 [95% CI, 1.23-1.48]; iron: ORmeta, 1.51 [95% CI, 1.27-1.81]). Through sensitivity analyses and reverse Mendelian randomization analyses, we confirmed the robustness of the results. CONCLUSIONS: Our study provides evidence suggesting a potential causal relationship between iron status and poor functional outcomes after IS. Future studies are required to illuminate the underlying mechanism.

Global, Regional, and National Burden of Stroke, 1990-2021: A Systematic Analysis for Global Burden of Disease 2021.

BACKGROUND: This study aims to perform a comprehensive analysis of stroke burden from the Global Burden of Disease 2021. METHODS: We conducted a comprehensive analysis of the burden, including prevalence, incidence, mortality, and disability-adjusted life year rates, for stroke across 204 countries and regions from 1990 to 2021 using data from the Global Burden of Disease 2021. We calculated the estimated annual percentage change (EAPC) and performed a joinpoint regression analysis to identify the trends. We also explored the association between the stroke burden and sociodemographic index. RESULTS: The age-standardized prevalence, incidence, mortality, and disability-adjusted life year rates for stroke were 1099.310, 141.553, 87.454, and 1886.196 per 100 000 persons in 2021, respectively. The general stroke burden trends declined in EAPC analysis (age-standardized prevalence: EAPC, -0.37; age-standardized incidence: EAPC, -0.99; age-standardized mortality: EAPC, -1.81; and disability-adjusted life year: EAPC, -1.76). However, we found an increasing burden of stroke in East Asia and Southern Sub-Saharan Africa (EAPC >0). The global burdens of intracerebral hemorrhage, subarachnoid hemorrhage, and ischemic stroke showed a similar trend. The stroke, intracerebral hemorrhage, and ischemic stroke burdens were heavier in men than in women, except for that of subarachnoid hemorrhage in women. Our joinpoint regression analysis revealed that the age-standardized burden rates of stroke decreased from 1990 to 2021 (average annual percent change <0), whereas an upward trend was observed between 2019 and 2021 (average annual percent change >0). The burden of stroke was inversely proportional to the sociodemographic index (P<0.05), except in the case of subarachnoid hemorrhage. The actual stroke burden showed an increasing trend for stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and ischemic stroke in 2021 (during the coronavirus pandemic). CONCLUSIONS: We found age-standardized rates of stroke burden declining over time, but some areas exhibited a notable increase in the prevalence, incidence, mortality, and disability-adjusted life year rates.

Exploring the heart-brain and brain-heart axes: Insights from a bidirectional Mendelian randomization study on brain cortical structure and cardiovascular disease.

INTRODUCTION: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. METHODS: This study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures. RESULTS: A total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q<0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation. CONCLUSION: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.

Causal association between circulating inflammatory cytokines and intracranial aneurysm and subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The causal association between inflammatory cytokines and the development of intracranial aneurysm (IA), unruptured IA (uIA) and subarachnoid hemorrhage (SAH) lacks clarity. METHODS: The summary-level datasets for inflammatory cytokines were extracted from a genome-wide association study of the Finnish Cardiovascular Risk in Young Adults Study and the FINRISK survey. The summary statistics datasets related to IA, uIA and SAH were obtained from the genome-wide association study meta-analysis of the International Stroke Genetics Consortium and FinnGen Consortium. The primary method employed for analysis was inverse variance weighting (false discovery rate), supplemented by sensitivity analyses to address pleiotropy and enhance robustness. RESULTS: In the International Stroke Genetics Consortium, 10, six and eight inflammatory cytokines exhibited a causal association with IA, uIA and SAH, respectively (false discovery rate, p < 0.05). In FinnGen datasets, macrophage Inflammatory Protein-1 Alpha (MIP_1A), MIP_1A and interferon γ-induced protein 10 (IP_10) were verified for IA, uIA and SAH, respectively. In the reverse Mendelian randomization analysis, the common cytokines altered by uIA and SAH were vascular endothelial growth factor (VEGF), MIP_1A, IL_9, IL_10 and IL_17, respectively. The meta-analysis results show that MIP_1A and IP_10 could be associated with the decreased risk of IA, and MIP_1A and IP_10 were associated with the decreased risk of uIA and SAH, respectively. Notably, the levels of VEGF, MIP_1A, IL_9, IL_10 and TNF_A were increased with uIA. Comprehensive heterogeneity and pleiotropy analyses confirmed the robustness of these results. CONCLUSION: Our study unveils a bidirectional association between inflammatory cytokines and IA, uIA and SAH. Further investigations are essential to validate their relationship and elucidate the underlying mechanisms.

The association of glaucoma with ischemic stroke and functional outcome after ischemic stroke from the perspective of causality.

INTRODUCTION: Glaucoma may be related to ischemic stroke (IS) and poor outcomes after IS in observational studies, while the causal association remains unclear. METHODS: We obtained single nucleotide polymorphisms (SNPs) related to glaucoma from the gene-wide association study (GWAS) conducted by the FinnGen consortium. The GWAS included a total of 13,614 cases and 295,540 controls. The summary-level of datasets regarding IS were collected from the MEGASTROKE consortium, including 34,217 cases and 406,111 controls. Furthermore, we acquired summary statistics datasets for functional outcomes following IS from the GWAS meta-analysis conducted by the GISCOME consortium, which involved 6,021 individuals. The genetic association estimates for functional outcomes at 90 days after IS were evaluated by the modified Rankin Score (mRS), including 3,741 cases with good functional outcomes (mRS=0-2) and 2,280 subjects with poor functional outcomes post-stroke (mRS=3-6). Inverse variance weighting (IVW) was used as the primary method, complemented by sensitivity analyses for pleiotropy and increasing robustness. RESULTS: Genetically, glaucoma is associated with an increased risk of IS (odds ratio [OR]=1.08, 95% confidence interval [CI] = 1.02-1.14, P = 0.0039), as well as poor prognosis after IS with adjustment for severity (OR=1.64; 95% CI=1.27-2.13, P=0.0001) and functional outcome after IS (OR=1.45, 95% CI=1.12-1.87, P=0.0038). Through sensitivity analyses, we confirmed the robustness of the results. In addition, we did not identify any causal association between IS, functional outcome after IS, and glaucoma in reverse analysis. CONCLUSION: Our study provides evidence suggesting a potential genetic causal relationship between glaucoma and an increased risk of IS, as well as a poor functional outcome following IS. Future studies are necessary to confirm these findings.

Regulation of the CB1R/AMPK/PGC-1α signaling pathway in mitochondria of mouse hearts and cardiomyocytes with chronic intermittent hypoxia.

PURPOSE: This study evaluated the effects of chronic intermittent hypoxia (CIH) at different times on the mitochondria of mouse hearts and H9C2 cardiomyocytes to determine the role of the cannabinoid receptor 1 (CB1R)/adenosine 5'-monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) signaling pathway. METHODS: Animal and cellular CIH models were prepared in an intermittent hypoxia chamber at different times. The cardiac function of mice was determined, and heart tissue and ultrastructural changes were observed. Apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential were detected, and MitoTracker™ staining was performed to observe cardiomyocyte mitochondria. Western blot, immunohistochemistry, and cellular immunofluorescence were also performed. RESULTS: In the short-term CIH group, increases in mouse ejection fraction (EF) and heart rate (HR); mitochondrial division; ROS and mitochondrial membrane potential; and the expression levels of CB1R, AMPK, and PGC-1α were observed in vivo and in vitro. In the long-term CIH group, the EF and HR increased, the myocardial injury and mitochondrial damage were more severe, mitochondrial synthesis decreased, the apoptosis percentage and ROS increased, mitochondrial fragmentation increased, membrane potential decreased, CB1R expression increased, and AMPK and PGC-1α expression levels decreased. Targeted blocking of CB1R can increase AMPK and PGC-1α, reduce damage attributed to long-term CIH in mouse hearts and H9C2 cells, and promote mitochondrial synthesis. CONCLUSION: Short-term CIH can directly activate the AMPK/PGC-1α pathway, promote mitochondrial synthesis in cardiomyocytes, and protect cardiac structure and function. Long-term CIH can increase CB1R expression and inhibit the AMPK/PGC-1α pathway, resulting in structural damage, the disturbance of myocardial mitochondria synthesis, and further alterations in the cardiac structure. After targeted blocking of CB1R, levels of AMPK and PGC-1α increased, alleviating damage to the heart and cardiomyocytes caused by long-term CIH.

Timing of decompression in central cord syndrome: a systematic review and meta-analysis.

PURPOSE: This study compared the recovery of motor function and the safety of early and delayed surgical intervention in patients with central cord syndrome (CCS). METHODS: PubMed, Embase, Cochrane Library, and Web of Science were employed to retrieve the targeted studies published from inception to February 19, 2023. Comparative studies of early versus delayed surgical decompression in CCS based on American Spinal Injury Association motor score (AMS) recovery, complication rates, and mortality were selected. The statistical analyses were performed using STATA 16.0 and RevMan 5.4. RESULTS: Our meta-analysis included 13 studies comprising 8424 patients. Results revealed that early surgery improved AMS scores significantly compared with delayed surgery, with an increase in MDs by 7.22 points (95% CI 1.98-12.45; P = 0.007). Additionally, early surgery reduced the complication rates than delayed surgery (OR 0.53, 95% CI 0.42-0.67, P < 0.00001). However, no significant difference was observed in mortality between the two groups (OR 0.97; 95% CI 0.75-1.26; P = 0.84). CONCLUSIONS: Early surgical decompression for CCS can improve motor function and reduce the incidence of complications without affecting the mortality rate in patients. Future research should focus on investigating and analyzing the optimal window period for early CCS surgery. Additionally, the timing of surgery should be determined based on the patient's condition and available medical resources.

Correlation between axial symptoms and cervical sagittal alignment parameters in patients with two-level or three-level cervical spondylotic myelopathy: anterior cervcial discectomy and fusion versus hybird surgery.

OBJECTIVE: To comparatively analyze the correlation between axial symptoms (AS) and cervical sagittal alignment parameters after anterior cervical discectomy and fusion (ACDF) and hybrid surgery (HS). METHODS: From January 2018 to June 2023, 74 patients who underwent ACDF (n = 36) or HS (n = 38) for two-level or three-level cervical spondylotic myelopathy were retrospectively analyzed. The Visual Analogue Scale (VAS), Japanese Orthopedic Association (JOA), Neck Disability Index (NDI) were recorded to assess clinical outcomes. Cervical sagittal alignment parameters (Cobb's angle C2-7, C7 slope [C7S], and C2-7 sagittal vertical axis [C2-7 SVA]) were measured preoperatively, 3 days postoperatively, and at the last follow-up. The range of motion (ROM) of C2-7 and ROM of surgical segment were measured. The occurrence of AS was observed at the last follow-up. Logistic regression was used to analyze the correlation between postoperative AS and cervical sagittal alignment parameters. RESULTS: Both in ACDF group and HS group, VAS, JOA and NDI scores showed significant improvements at 3-day postoperation and at the last follow-up (P < 0.05). However, there was no significant difference between the two groups (P > 0.05). The Cobb's angle C2-7 and C7S were significantly increased at 3 days postoperation compared with pre-operatively in both groups (P < 0.05). C2-7SVA was increased in both groups 3 days after surgery compared with pre-operatively, but there was no significant difference (P > 0.05). At the last follow-up, the ROM of C2-7 in ACDF group was significantly smaller than HS group (P < 0.05). The prevalence of postoperative AS in the ACDF group and HS group was 41.7 and 18.4%, respectively, with statistical difference between the two groups (P < 0.05). When simple Logistic regression analysis was used, the last Cobb's angle C2-7 (ß = -0.088), the last C2-7SVA (ß = 0.099) in ACDF group and the last C2-7SVA (ß = 0.222) in HS group were all correlated with the occurrence of postoperative AS. When multiple Logistic regression analysis was used, only the last C2-7SVA (ß = 0.181) in the HS group was positively correlated with the occurrence of postoperative AS. CONCLUSIONS: Both ACDF and HS can achieve satisfied clinical outcomes. ACDF and HS can improve cervical sagittal balance to a certain extent, and HS is superior to ACDF in maintaining ROM. The decrease of the last Cobb's angle C2-7 and the increase of the last C2-7SVA may be related to the occurrence of AS after ACDF. The increase of the last C2-7SVA was an independent risk factor for the occurrence of AS after HS.

Changes in the centre of rotation and the anterior bone loss of the vertebral body in Mobi-C artificial disc replacement segments after cervical hybrid surgery: a retrospective study.

OBJECTIVE: To examine the short-term efficacy and imaging results of using the Mobi-C in cervical hybrid surgery on 2-level cervical spondylolisthesis. To observe post-operative changes in the flexion-extension centre of rotation (FE-COR) and anterior bone loss (ABL) of the anterior cervical disc replacement (ACDR) segment. METHODS: Forty-two patients (20 males and 22 females, aged 42‒67 years) who underwent cervical hybrid surgery were retrospectively analysed. Their ACDR segment used Mobi-C, and the fusion segment used ROI-C, with a follow-up of 25‒42 months (31.1 ± 4.8 months). The modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI), and visual analogue scale (VAS) were used to assess clinical outcomes. Pre-operative, 6-month post-operative, and final follow-up radiographs were collected to compare total cervical spine curvature (C2-C7), curvature of the operated segments, range of motion (ROM) in the total cervical spine, operated segmental ROM, ACDR segmental ROM, and operated adjacent segmental ROM. The height of the superior articular process (HSAP), the orientation of zygapophyseal joint spaces (OZJS), and the length of the superior articular surface (LSAS) were measured. The FE-COR of the ACDR segment was measured using the mid-plumb line method. The translation distance of the Mobi-C was measured. The degree of disc degeneration in the adjacent segment, bony fusion of the ACDF segment, and ABL of the upper and lower vertebra of the ACDR segment were observed. RESULTS: In our group, all patients have shown improvements in their postoperative mJOA, NDI, and VAS scores. Overall cervical ROM and surgical segmental ROM decreased (P < 0.05). However, there was no significant decrease in ACDR segmental ROM and upper or lower adjacent segmental ROM compared with pre-operatively (P > 0.05). For FE-COR-X, only the last follow-up compared with pre-surgery showed statistical significance (46.74 ± 7.71% vs. 50.74 ± 6.92%, P < 0.05). For FE-COR-Y, the change was statistically significant at both 6 months post-operation and the final follow-up compared to pre-operation (45.37% ± 21.11% vs. 33.82% ± 10.87%, 45. 37% ± 21.11% vs. 27.48% ± 13.58%, P < 0.05). No significant difference in the Mobi-C translation distance was observed (P > 0.05). Moreover, the difference in HSAP was not statistically significant at each node (P > 0.05). The OZJS and LSAS were significantly different at the final follow-up compared to the pre-operative period (P < 0.05). All the ACDF segments were observed in a stable condition at the final follow-up. Furthermore, 9 of the adjacent segments showed imaging ASD (9/82, 10.98%), and all were present at the last follow-up, of which 6 were mild, and 3 were moderate. Twenty of the 42 Mobi-C segments had no significant ABL (grade 0) 6 months post-operatively (47.62%). Sixteen cases (38.10%) showed mild ABL (grade 1), and 6 cases (14.28%) showed moderate ABL (grade 2). No severe ABL occurred. CONCLUSION: The cervical hybrid surgery using Mobi-C artificial cervical discs can achieve satisfactory results. The Mobi-C segmental FE-COR-X shows a slow forward shift trend, and FE-COR-Y drops noticeably within 6 months post-surgery before stabilizing. It's common to see mild to moderate ABL after cervical hybrid surgery using Mobi-C, and significant progression is unlikely in the short term. Furthermore, changes in the FE-COR after hybrid surgery in the Mobi-C segment might not affect clinical outcomes.

Dissipation behaviours, residues, and health risk of six herbicides in sugar beets under field conditions.

This study established a residue detection method based on the QuEChERS pre-treatment method and combined it with high-performance liquid chromatography-tandem mass spectrometry to test six herbicides (metamitron, clopyralid, desmedipham, phenmedipham, ethofumesate, and haloxyfop-p-methyl) in sugar beet plants, soil, and roots. The degradation dynamics and terminal residues of each herbicide in sugar beets were analysed. Finally, the dietary risks of various herbicides in sugar beets were evaluated based on the dietary structure of Chinese people, and the risk quotient values were below 100%. Using this detection method, all reagents exhibited good linearity (0.9724 ≤ R2 ≤ 0.9998), The limit of quantification (LOQ) ranged from 0.01 to 0.05 mg/L, the matrix effect ranged from -1.2% to -50%, the addition recovery rate ranged from 77.00% to 103.48%, and the relative standard deviation ranged from 1.61% to 16.17%; therefore, all indicators of this method met the residue detection standards. Under field conditions, the half-lives (t1/2) ranged about 0.65 ∼ 2.96 d and 0.38 ∼ 27.59 d in sugar beet plants and soil, respectively. All herbicides were easily degraded in sugar beet plants and soil (t1/2 < 30 d). The terminal residue amounts in the beet plants, soil, and roots ranged from < LOQ to 0.243 mg/kg. The dietary risk assessment of each pesticide was conducted based on the residual median of the terminal residues and the highest residual values on the edible part of the beetroot. The chronic exposure risk quotient (RQc) and acute exposure risk quotient (RQa) values were < 100%, indicating that the residue of each pesticide in beetroot posed low risks to consumers in China at the recommended dosage.

Possible sarcopenia and risk of chronic kidney disease: a four-year follow-up study and Mendelian randomization analysis.

INTRODUCTION: Chronic kidney disease (CKD) is a common risk factor for sarcopenia. However, whether sarcopenia increases the risk of CKD remains unclear. To investigate the longitudinal and causal associations between possible sarcopenia and CKD, this study was performed. METHODS: Possible sarcopenia was defined according to the Asian Working Group for Sarcopenia in 2019. Participants aged ≥ 40 years were recruited from the baseline survey of the China Health and Retirement Longitudinal Study and followed up for four years. Binary logistic regression was used to evaluate the cross-sectional and longitudinal associations between possible sarcopenia, low muscle strength, low physical performance and CKD. Propensity score matching was used to balance the intergroup differences. Subgroup and interactive analyses were adopted to identify potential interactive effects. Mendelian Randomization analysis was used to assess the causal association between appendicular lean mass (ALM) and CKD. RESULTS: After data cleansing, a total of 7296 participants were included in the baseline survey. In the cross-sectional analyses, the odds ratios (ORs) of prevalent CKD were 1.50 (95% CI = 1.23-1.84, p < 0.001) for possible sarcopenia, 1.37 (95% CI = 1.10-1.70, p < 0.01) for low muscle strength and 1.42 (95% CI = 1.16-1.74, p < 0.001) for low physical performance in the full models. No significant interaction effects of covariates were detected (all P for interaction > 0.05). After four years of follow-up, an increased risk of incident CKD was also observed in participants with possible sarcopenia (OR = 1.66, 95% CI = 1.13-2.44, p = 0.010) and low physical performance (OR = 1.69, 95% CI = 1.16-2.45, p = 0.006), but not in participants with low muscle strength (OR = 1.19, 95% CI = 0.75-1.88, p = 0.469). In the Mendelian Randomization analysis, the inverse variance weighted estimator showed that a 1-standard deviation increase of genetically predicted ALM was associated with a lower risk of CKD (OR = 0.92, 95% CI = 0.85-0.99, p = 0.035). All the sensitivity analyses supported the main findings. CONCLUSIONS: Possible sarcopenia is an independent risk factor for CKD and may serve as a predictor of CKD for early identification and intervention.

Surgical treatment of osteogenesis imperfecta: a summary of the incidence of femoral implant-related complications in children with Sillence type I, III and IV.

PURPOSE: This study explored the incidence of IRCs used in the procedures of the femur in children with osteogenesis imperfecta (OI) and investigated the independent risk factors of IRCs. METHODS: Three hundred eight-eight cases of surgical data about children with OI were included, who were treated with plate, elastic nail, Kirschner wire and telescopic rod. The choice of different procedures depended on the age of children, the status of femur and the availability of devices. Patient demographics and major IRCs were recorded to compare the outcomes of the four procedures. Then, Cox proportional hazard regression was used to analyse the independent risk factors of IRC, and subgroup analysis was applied to further verify the above results. RESULTS: The total incidence of IRC in the four groups was 90.1% (191/212) for plate, 96.8% (30/31) for Kirschner wire, 87.7% (57/65) for elastic nail and 30.0% (24/80) for telescopic rod. The incidence of IRC in the telescopic rod was lower than that in plate, elastic nail and Kirschner wire (P < 0.001). Cox proportional hazard regression analysis confirmed that procedure was the independent risk factor of IRC (HR, 0.191; 95% CI, 0.126-0.288; P < 0.001), fracture (HR, 0.193; 95% CI, 0.109-0.344; P < 0.001) and deformity (HR, 0.086; 95% CI, 0.027-0.272; P < 0.001). In addition, age of surgery was the independent risk factor of fracture (HR, 0.916; 95% CI, 0.882-0.952; P < 0.001) and deformity (HR, 1.052; 95% CI, 1.008-1.098; P = 0.019). Subgroup analysis confirmed that age of surgery, gender, classification, preoperative state and angle did not affect the effect of telescopic rod on reducing the risk of IRCs. CONCLUSIONS: In our cohort, lower incidence of IRCs was observed in telescopic rod group compared with plate, Kirschner wire and elastic nail. Procedure and age of surgery were independent risk factors of fracture. Likewise, procedure and age of surgery were independent risk factors of deformity, and procedure was independent risk factors of IRC.

Pharmacokinetics of ginkgolide B-lyophilized nanoparticles after intravenous injection in rats using liquid chromatography-tandem mass spectrometry.

RATIONALE: Ginkgolide B (GB) performs diverse pharmacological activities but has poor water solubility. The currently available GB injections have a short half-life and are lethal when injected rapidly. We prepared GB-lyophilized nanoparticles (GB-NPs) using a new nonsurfactant polysaccharide polymer, ZY-010, as its carrier to regulate the release of GB in vivo. Here, the pharmacokinetics (PK) of GB-NPs after intravenous injection in rats was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: The samples were separated on an Agilent Eclipse XDB-C 18 column (2.1 × 50 mm, 1.85 µm) maintained at 30°C. The MS/MS transitions of GB and glibenclamide as the internal standard (IS) were set at m/z 423.1 → 367.1 and m/z 492.1 → 367.0, respectively. The standard curve of GB content was constructed, and the specificity, sensitivity, precision, and extraction recovery of LC-MS/MS analysis were assessed. The main PK parameters were analyzed using DAS (Drug And Statistics for Windows) software, version 2.0. RESULTS: The retention time of GB and IS at elution was 2.77 and 4.75 min, respectively. An excellent linear response across the concentration range of 0.001-100 µg/ml was achieved (r = 0.9997). The relative standard deviation value of precision was less than 10%. The total extraction recovery was above 80.76 ± 2.08%. The main PK parameters for the GB-NPs were as follows: t1/2 = 69.32 h, AUC(0 → ∞) = 188 312.97 ± 143 312.41 µg/L h, CL = 0.03 ± 0.02 L/h/kg, and V = 0.09 ± 0.05 L/kg. The t1/2 of the GB-NPs was significantly longer than that of GB solution, and AUC(0 → ∞) of GB-NPs was about 1.4 times that of GB solution. The PK data demonstrated that the blood concentration of GB in rats conformed to a three-compartment model in both GB solution and GB-NPs. CONCLUSION: A rapid and accurate LC-MS/MS method was established for the determination of GB-NPs in rats. GB-NPs exhibited a sustained-release behavior in vivo compared with GB solution.

Obesity, metabolic dysfunction, and risk of kidney stone disease: a national cross-sectional study.

BACKGROUND: This study aimed to investigate the association between different metabolic syndrome-body mass index (MetS-BMI) phenotypes and the risk of kidney stones. MATERIALS AND METHODS: Participants aged 20-80 years from six consecutive cycles of the NHANES 2007-2018 were included in this study. According to their MetS status and BMI, the included participants were allocated into six mutually exclusive groups: metabolically healthy normal weight (MHN)/overweight (MHOW)/obesity (MHO) and metabolically unhealthy normal weight (MUN)/overweight (MUOW)/obesity (MUO). To explore the association between MetS-BMI phenotypes and the risk of kidney stones, binary logistic regression was used to determine the odds ratios (ORs). RESULTS: A total of 13,589 participants were included. It was revealed that all the phenotypes with obesity displayed higher risks of kidney stones (OR = 1.38, p < 0.01 for MHO & OR = 1.80, p < 0.001 for MUO, in the fully adjusted model). The risk increased significantly when metabolic dysfunction coexisted with overweight and obesity (OR = 1.39, p < 0.05 for MUOW & OR = 1.80, p < 0.001 for MUO, in the fully adjusted model). Of note, the ORs for the MUO and MUOW groups were higher than those for the MHO and MHOW groups, respectively. CONCLUSIONS: Obesity and unhealthy metabolic status can jointly increase the risk of kidney stones. Assessing the metabolic status of all individuals may be beneficial for preventing kidney stones.

Evaluation of a high-sensitivity SARS-CoV-2 antigen test on the fully automated light-initiated chemiluminescent immunoassay platform.

OBJECTIVES: To describe a high-sensitivity SARS-CoV-2 antigen test that is based on the fully automated light-initiated chemiluminescent immunoassay (LiCA®), and to validate its analytical characteristics and clinical agreement on detecting SARS-CoV-2 infection against the reference molecular test. METHODS: Analytical performance was validated and detection limits were determined using different types of nucleocapsid protein samples. 798-pair anterior nasal swab specimens were collected from hospitalized patients and asymptomatic screening individuals. Agreement between LiCA® antigen and real-time reverse transcription polymerase chain reaction (rRT-PCR) was evaluated. RESULTS: Repeatability and within-lab precision were 1.6-2.3%. The C5∼C95 interval was -5.1-4.6% away from C50. Detection limits in average (SD) were 325 (±141) U/mL on the national reference panel, 0.07 (±0.04) TCID50/mL on active viral cultures, 0.27 (±0.09) pg/mL on recombinant nucleocapsid proteins and 1.07 (±1.01) TCID50/mL on inactivated viral suspensions, respectively. LiCA detected a median of 374-fold (IQR 137-643) lower levels of the viral antigen than comparative rapid tests. As reference to the rRT-PCR method, overall sensitivity and specificity were determined to be 97.5% (91.4-99.7%) and 99.9% (99.2-100%), respectively. Total agreement between both methods was 99.6% (98.7-99.9%) with Cohen's kappa 0.98 (0.96-1). A positive detection rate of 100% (95.4-100%) was obtained as Ct≤37.8. CONCLUSIONS: The LiCA® system provides an exceptionally high-sensitivity and fully automated platform for the detection of the SARS-CoV-2 antigen in nasal swabs. The assay may have high potential use for large-scale population screening and surveillance of COVID-19 as an alternative to the rRT-PCR test.

Which is the best femoral implant in children with osteogenesis imperfecta? a retrospective cohort study of 783 procedures.

BACKGROUND: Osteogenesis imperfecta (OI) is a hereditary genetic disorder characterized by bone fragility and extremity deformities. The surgical management for long-bone fractures and deformities in OI remains a challenge. We aimed to compare clinical outcomes after femoral surgery splinted with the telescopic rod, the plate and screws, the elastic nail and the non-elongating rod in setting of OI. METHODS:  A retrospective cohort study included 783 femoral procedures (mean age 6.00 (interquartile range (IQR) 5.00) years, 335 (42.8%) females) was conducted, and individuals were categorized into four groups according to implants. After verifying comparability among the groups, revision rate and implant survival period were compared among the Sillence types and the same comparison were made among four groups within each Sillence type. The incidence of refractures, deformities, and implant-related complications were also compared among the four groups. RESULTS: There were no significant differences in demographic information among the four groups in terms of sex (p = 0.101), laterality (p = 0.587), Sillence type (p = 0.122), and postoperative follow-up period (p = 0.214). In total, children with Sillence type III had the highest revision rate and the shortest implant survival period; children with Sillence type I had the lowest revision rate and the longest implant survival period; and children with Sillence type IV had the revision rate and the implant survival period between those observed in Sillence types I and III. In Sillence types III and IV, the telescopic rod had lower revision rate (III 24.8%; IV 20.9%) compared to the plate (III 97.2%, p<0.001; IV 80.3%, p<0.001), the elastic nail (III 100.0%, p=0.019; IV 73.9%, p<0.001) and the non-elongating rod (III 65.0%, p<0.001; IV46.9%, p<0.001); the median implant survival period of the telescopic rod (III 48.00 (IQR 28.50) months; IV 43.00 (33.00) months) is longer than the plate (III 11.00 (9.00) months, p<0.001; IV 19.00 (20.00) months, p<0.001), the elastic nail (III 45.00 (37.75) months, p=1.000; IV 19.00 (35.00) months, p=0.028) and the non-elongating rod (III 39.00 (31.75) months, p=0.473; IV 38.50 (29.75) months, p=1.000).A similar trend was observed in Sillence type I (p = 0.063, p = 0.003; respectively). In addition, the incidence of refracture (15.5%), deformity (2.8%) and implant-related complications (23.1%) were also statistically lower in the telescopic rod group. CONCLUSION: In our cohort, lower revision rate and longer implant survival period were observed in telescopic rod group. This was mainly due to the significant lower incidence of refracture, deformity and implant-related complications with the use of telescopic rod.

Soyasaponin I alleviates hypertensive intracerebral hemorrhage by inhibiting the renin-angiotensin-aldosterone system.

BACKGROUND: Hypertensive intracerebral hemorrhage (HICH) is a life-threatening disease and lacks effective treatments. Previous studies have confirmed that metabolic profiles altered after ischemic stroke, but how brain metabolism changes after HICH was unclear. This study aimed to explore the metabolic profiles after HICH and the therapeutic effects of soyasaponin I on HICH. METHODS: HICH model was established first. Hematoxylin and eosin staining was used to estimate the pathological changes after HICH. Western blot and Evans blue extravasation assay were applied to determine the integrity of the blood-brain barrier (BBB). Enzyme-linked immunosorbent assay was used to detect the activation of the renin-angiotensin-aldosterone system (RAAS). Next, liquid chromatography-mass spectrometry-untargeted metabolomics was utilized to analyze the metabolic profiles of brain tissues after HICH. Finally, soyasaponin I was administered to HICH rats, and the severity of HICH and activation of the RAAS were further assessed. RESULTS: We successfully constructed HICH model. HICH significantly impaired BBB integrity and activated RAAS. HICH increased PE(14:0/24:1(15Z)), arachidonoyl serinol, PS(18:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, and 19Z)), PS(20:1(11Z)/20:5(5Z, 8Z, 11Z, 14Z, and 17Z)), glucose 1-phosphate, etc., in the brain, whereas decreased creatine, tripamide, D-N-(carboxyacetyl)alanine, N-acetylaspartate, N-acetylaspartylglutamic acid, and so on in the hemorrhagic hemisphere. Cerebral soyasaponin I was found to be downregulated after HICH and supplementation of soyasaponin I inactivated the RAAS and alleviated HICH. CONCLUSION: The metabolic profiles of the brains changed after HICH. Soyasaponin I alleviated HICH via inhibiting the RAAS and may serve as an effective drug for the treatment of HICH in the future.

Genome-wide association study reveals the genetic basis of growth trait in yellow catfish with sexual size dimorphism.

Sexual size dimorphism has been widely observed in a large number of animals including fish species. Genome-wide association study (GWAS) is a powerful tool to dissect the genetic basis of complex traits, whereas the sex-differences in the genomics of animal complex traits have been ignored in the GWAS analysis. Yellow catfish (Pelteobagrus fulvidraco) is an important aquaculture fish in China with significant sexual size dimorphism. In this study, GWAS was conducted to identify candidate SNPs and genes related to body length (BL) and body weight (BW) in 125 female yellow catfish from a breeding population. In total, one BL-related SNP and three BW-related SNPs were identified to be significantly associated with the traits. Besides, one of these SNPs (Chr15:19195072) was shared in both the BW and BL traits in female yellow catfish, which was further validated in 185 male individuals and located on the exon of stat5b gene. Transgenic yellow catfish and zebrafish that expressed yellow catfish stat5b showed increased growth rate and reduction of sexual size dimorphism. These results not only reveal the genetic basis of growth trait and sexual size dimorphism in fish species, but also provide useful information for the marker-assisted breeding in yellow catfish.

A causal effects of gut microbiota in the development of migraine.

BACKGROUND: The causal association between the gut microbiome and the development of migraine and its subtypes remains unclear. METHODS: The single nucleotide polymorphisms concerning gut microbiome were retrieved from the gene-wide association study (GWAS) of the MiBioGen consortium. The summary statistics datasets of migraine, migraine with aura (MA), and migraine without aura (MO) were obtained from the GWAS meta-analysis of the International Headache Genetics Consortium (IHGC) and FinnGen consortium. Inverse variance weighting (IVW) was used as the primary method, complemented by sensitivity analyses for pleiotropy and increasing robustness. RESULTS: In IHGC datasets, ten, five, and nine bacterial taxa were found to have a causal association with migraine, MA, and MO, respectively, (IVW, all P < 0.05). Genus.Coprococcus3 and genus.Anaerotruncus were validated in FinnGen datasets. Nine, twelve, and seven bacterial entities were identified for migraine, MA, and MO, respectively. The causal association still exists in family.Bifidobacteriaceae and order.Bifidobacteriales for migraine and MO after FDR correction. The heterogeneity and pleiotropy analyses confirmed the robustness of IVW results. CONCLUSION: Our study demonstrates that gut microbiomes may exert causal effects on migraine, MA, and MO. We provide novel evidence for the dysfunction of the gut-brain axis on migraine. Future study is required to verify the relationship between gut microbiome and the risk of migraine and its subtypes and illustrate the underlying mechanism between them.

Reduced sleep duration increases the risk of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in middle-aged and elderly males: a national cross-sectional study.

BACKGROUND: The prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) remains high in men. However, whether reduced sleep duration enhances the risk of LUTS/BPH remains unknown. MATERIALS AND METHODS: The 2015 China Health and Retirement Longitudinal Study was used in this study. Binary logistic regression was adopted to test the relationship between sleep duration and LUTS/BPH. Restricted cubic spline (RCS) regression was used to examine the non-linear association. In sensitivity analyses, propensity scores matching was performed to verify the robustness of the results. RESULTS: In this study, 8,920 males aged 40 years above were enrolled. In the fully adjusted logistic model, across the quartiles of sleep duration, the odds ratios of LUTS/BPH were 1.00 (reference), 0.94 (95% CI 0.77-1.15), 0.74 (95% CI 0.58-0.94), 0.54 (0.37-0.75), respectively. The results of RCS indicated a non-linear inverted U-shaped association between sleep duration and LUTS/BPH (p for non-linearity <0.05). In the subgroup analyses, no significant effects of settlements, alcohol and cigarette consumption, depression, and hypertension on the association between sleep duration and prevalent LUTS/BPH were observed (p for interaction >0.05). CONCLUSION: Reduced sleep duration is significantly associated with the increases of the LUTS/BPH risk in Chinese middle-aged and elderly males.