Anterior peri-sacroiliac joint osteotomy in the treatment of malunion and nonunion of complex pelvic ring fracture: techniques and preliminary results.

PURPOSE: To introduce anterior peri-sacroiliac joint osteotomy (APSJO) through the lateral-rectus approach (LRA) for treating pelvic fracture malunion and nonunion, and to evaluate the safety, feasibility, and potential effectiveness. METHODS: Data of 15 patients with pelvic fracture malunion and nonunion who underwent treatment by APSJO were selected and analyzed. The reduction quality was assessed using the Mears and Velyvis criteria, while the pre-operative and post-operative function was revealed by the Majeed scoring system. The British Medical Research Council (BMRC) grading system was recruited for the evaluation of lumbosacral plexus function. RESULTS: The average operative duration was 264.00 ± 86.75 min, while the intra-operative blood loss was 2000 (600, 3000) mL. Anatomical reduction was complete in three cases, satisfactory in ten cases, and unsatisfactory in two cases. Among the seven patients with lumbosacral plexus injury, the pre-operative Majeed grades were good in two cases, fair in two cases, and poor in three cases, while the post-operative Majeed grades were excellent in three cases, good in three cases, and fair in one case. Muscle strength recovered to M5 in two cases, M4 in three cases, and showed no recovery in two cases. The pre-operative Majeed grades were good in five cases, fair in two cases, and poor in one case of the series without lumbosacral plexus injury, while the post-operative Majeed grades were excellent in seven cases and good in one case. CONCLUSION: APSJO through LRA may be a feasible strategy for treating pelvic fracture malunion and nonunion with promising application.

Sirtuin 5-Mediated Lysine Desuccinylation Protects Mitochondrial Metabolism Following Subarachnoid Hemorrhage in Mice.

BACKGROUND AND PURPOSE: Sirt5 (Sirtuin 5) desuccinylates multiple metabolic enzymes and plays an important role in maintaining energy homeostasis. The goal of this study was to determine whether Sirt5-mediated desuccinylation restores the energy metabolism and protects brain against subarachnoid hemorrhage (SAH). METHODS: Male C57BL/6 or Sirt5-/- mice were used. The endovascular perforation SAH model was applied. Protein lysine succinylation in the brain cortex was examined using liquid chromatography-tandem mass spectrometry analysis. The brain metabolism was evaluated by measurement of brain pH as well as ATP and reactive oxygen species level. Neuronal cell death and neurobehavioral deficits were assessed 24 hours after SAH. The expression and desuccinylation activity of Sirt5, lysine succinylation of citrate synthase and ATP synthase subunits were investigated by Western blot, immunohistochemistry, and ELISA in SAH mice and patients. Furthermore, the benefits of resveratrol-mediated Sirt5 activation were investigated. RESULTS: A total of 211 lysine succinylation sites were differentially expressed on 170 proteins in mice brain after SAH. Thirty-nine percent of these succinylated proteins were localized in mitochondria and they are related to energy metabolism. SAH caused a decrease of Sirt5 expression and succinylated citrate synthase as well as the subunits of ATP synthase, subsequently lowered brain pH, reduced ATP and increased reactive oxygen species production, leading to neuronal cell death, and neurological deficits. Knockdown of Sirt5 aggravated SAH-induced effects, mentioned above. Administration of resveratrol resulted in activation of Sirt5. The activation was accompanied both with restoration of the mitochondrial metabolism and alleviation of early brain injury as well as with desuccinylating citrate synthase and ATP synthase. CONCLUSIONS: Protein lysine succinylation is a biochemical hallmark of metabolic crisis after SAH, and disruption of lysine succinylation through activation of Sirt5 might be a promising therapeutic strategy for the treatment of SAH.

Management of Proximal Segment of the Anterior Cerebral Artery Aneurysms.

ABSTRACT: The authors reported 2 cases with proximal anterior cerebral artery (A1) aneurysms, and one was treated with aneurysm clipping, whereas another was treated with coil embolization. The authors suggest both endovascular surgery and aneurysm clipping are good options for A1 aneurysms.

Insight into the soil bacterial community succession of Nicotiana benthamiana in response to Tobacco mosaic virus.

Background: Tobacco mosaic virus (TMV) is one famous plant virus responsible for substantial economic losses worldwide. However, the roles of bacterial communities in response to TMV in the tobacco rhizosphere remain unclear. Methods: We explored the soil physicochemical properties and bacterial community succession of the healthy (YTH) and diseased (YTD) plants with TMV infection by 16S rRNA gene sequencing and bioinformatics analysis. Results: We found that soil pH in the YTD group was significantly lower than in the YTH group, and the soil available nutrients were substantially higher. The bacterial community analysis found that the diversity and structure significantly differed post-TMV disease onset. With TMV inoculated, the alpha diversity of the bacterial community in the YTD was markedly higher than that in the YTH group at the early stage. However, the alpha diversity in the YTD group subsequently decreased to lower than in the YTH group. The early bacterial structure of healthy plants exhibited higher susceptibility to TMV infection, whereas, in the subsequent stages, there was an enrichment of beneficial bacterial (e.g., Ramlibacter, Sphingomonas, Streptomyces, and Niastella) and enhanced energy metabolism and nucleotide metabolism in bacteria. Conclusion: The initial soil bacterial community exhibited susceptibility to TMV infection, which might contribute to strengthening resistance of Tobacco to TMV.

Vertical differences in carbon metabolic diversity and dominant flora of soil bacterial communities in farmlands.

The carbon cycle in soil is significantly influenced by soil microbes. To investigate the vertical distribution of the dominant groups in agricultural soil and the carbon metabolic diversity of soil bacteria, 45 soil samples from the 0 ~ 50 cm soil layer in Hunan tobacco-rice multiple cropping farmland were collected in November 2017, and the carbon diversity of the soil bacterial community, bacterial community composition and soil physical and chemical properties were determined. The results showed that the carbon metabolic capabilities and functional diversity of the soil bacterial community decreased with depth. The three most widely used carbon sources for soil bacteria were carbohydrates, amino acids, and polymers. The dominant bacterial groups in surface soil (such as Chloroflexi, Acidobacteriota, and Bacteroidota) were significantly positively correlated with the carbon metabolism intensity. The alkali-hydrolysable nitrogen content, soil bulk density and carbon-nitrogen ratio were the key soil factors driving the differences in carbon metabolism of the soil bacterial communities in the different soil layers.

Clinical features, angio-architectural phenotypes, and treatment strategy of foramen magnum dural arteriovenous fistulas: a retrospective case series study.

Background: The rarity and complex angioarchitecture of foramen magnum dural arteriovenous fistulas (DAVFs) make its treatment difficult and controversial. We aimed to describe their clinical features, angio-architectural phenotypes, and treatments, through a case series study. Methods: We first retrospectively studied cases of foramen magnum DAVFs treated in our Cerebrovascular Center, and then reviewed the published cases on Pubmed. The clinical characteristics, angioarchitecture, and treatments were analyzed. Results: A total of 55 patients were confirmed with foramen magnum DAVFs, which included 50 men and 5 women, with a mean age of 52.8 years. Most patients presented with subarachnoid hemorrhage (SAH) (21/55) or myelopathy (30/55), depending on the venous drainage pattern. In this group, 21 DAVFs were supplied by only the vertebral artery (VA), three by only the occipital artery (OA), three by only the ascending pharyngeal artery (APA), and the remaining 28 DAVFs were supplied by two or three of these feeding arteries. Most cases (30/55) were treated with only endovascular embolization, 18 cases (18/55) with only surgical disconnection, five cases (5/55) with combined therapy, and two cases rejected treatment. The angiographic outcome of complete obliteration was achieved in most patients (50/55). In addition, two cases of foramen magnum DAVFs were treated by us in a Hybrid Angio-Surgical Suite (HASS) with good outcomes. Conclusions: Foramen magnum DAVFs are rare and their angio-architectural features are complicated. The treatment option (microsurgical disconnection or endovascular embolization) should be weighed carefully, and combined therapy in HASS could be a more feasible and less invasive treatment option.

Microbial interactions and metabolisms in response to bacterial wilt and black shank pathogens in the tobacco rhizosphere.

Background: Tobacco bacterial wilt (TBW) and black shank (TBS) are responsible for substantial economic losses worldwide; however, microbial interactions and metabolisms in response to TBW and TBS pathogens in the tobacco rhizosphere remain unclear. Methods: We explored and compared the response of rhizosphere microbial communities to these two plant diseases with the incidences in moderate and heavy degrees by sequencing of 16S rRNA gene amplicons and bioinformatics analysis. Results and discussions: We found that the structure of rhizosphere soil bacterial communities was significantly (p < 0.05) changed from the incidences of TBW and TBS, which also led to decreased Shannon diversity and Pielou evenness. Compared with the healthy group (CK), the OTUs with significantly (p < 0.05) decreased relative abundances were mostly affiliated with Actinobacteria (e.g., Streptomyces and Arthrobacter) in the diseased groups, and the OTUs with significantly (p < 0.05) increased relative abundances were mainly identified as Proteobacteria and Acidobacteria. Also, molecular ecological network analysis showed that the nodes (<467) and links (<641) were decreased in the diseased groups compared with the control group (572; 1056), suggesting that both TBW and TBS weakened bacterial interactions. In addition, the predictive functional analysis indicated that the relative abundance of genes related to the biosynthesis of antibiotics (e.g., ansamycins and streptomycin) was significantly (p < 0.05) decreased due to incidences of TBW and TBS, and antimicrobial tests showed that some Actinobacteria strains (e.g., Streptomyces) and their secreted antibiotics (e.g., streptomycin) could effectively inhibit the growth of these two pathogens.

Dissecting the HGT network of carbon metabolic genes in soil-borne microbiota.

The microbiota inhabiting soil plays a significant role in essential life-supporting element cycles. Here, we investigated the occurrence of horizontal gene transfer (HGT) and established the HGT network of carbon metabolic genes in 764 soil-borne microbiota genomes. Our study sheds light on the crucial role of HGT components in microbiological diversification that could have far-reaching implications in understanding how these microbial communities adapt to changing environments, ultimately impacting agricultural practices. In the overall HGT network of carbon metabolic genes in soil-borne microbiota, a total of 6,770 nodes and 3,812 edges are present. Among these nodes, phyla Proteobacteria, Actinobacteriota, Bacteroidota, and Firmicutes are predominant. Regarding specific classes, Actinobacteria, Gammaproteobacteria, Alphaproteobacteria, Bacteroidia, Actinomycetia, Betaproteobacteria, and Clostridia are dominant. The Kyoto Encyclopedia of Genes and Genomes (KEGG) functional assignments of glycosyltransferase (18.5%), glycolysis/gluconeogenesis (8.8%), carbohydrate-related transporter (7.9%), fatty acid biosynthesis (6.5%), benzoate degradation (3.1%) and butanoate metabolism (3.0%) are primarily identified. Glycosyltransferase involved in cell wall biosynthesis, glycosylation, and primary/secondary metabolism (with 363 HGT entries), ranks first overwhelmingly in the list of most frequently identified carbon metabolic HGT enzymes, followed by pimeloyl-ACP methyl ester carboxylesterase, alcohol dehydrogenase, and 3-oxoacyl-ACP reductase. Such HGT events mainly occur in the peripheral functions of the carbon metabolic pathway instead of the core section. The inter-microbe HGT genetic traits in soil-borne microbiota genetic sequences that we recognized, as well as their involvement in the metabolism and regulation processes of carbon organic, suggest a pervasive and substantial effect of HGT on the evolution of microbes.

Neurons Release Injured Mitochondria as "Help-Me" Signaling After Ischemic Stroke.

Mitochondrial dysfunction has been regarded as one of the major contributors of ischemic neuronal death after stroke. Recently, intercellular mitochondrial transfer between different cell types has been widely studied and suggested as a potential therapeutic approach. However, whether mitochondria are involved in the neuron-glia cross-talk following ischemic stroke and the underlying mechanisms have not been explored yet. In this study, we demonstrated that under physiological condition, neurons release few mitochondria into the extracellular space, and the mitochondrial release increased when subjected to the challenges of acidosis, hydrogen peroxide (H2O2), N-methyl-D-aspartate (NMDA), or glutamate. Acidosis reduced the mitochondrial basal respiration and lowered the membrane potential in primary-cultured mouse cortical neurons. These defective mitochondria were prone to be expelled to the extracellular space by the injured neurons, and were engulfed by adjacent astrocytes, leading to increased astrocytic expressions of mitochondrial Rho GTPase 1 (Miro 1) and mitochondrial transcription factor A (TFAM) at mRNA level. In mice subjected to transient focal cerebral ischemia, the number of defective mitochondria in the cerebrospinal fluid increased. Our results suggested that the neuron-derived mitochondria may serve as a "help-me" signaling and mediate the neuron-astrocyte cross-talk following ischemic stroke. Promoting the intercellular mitochondrial transfer by accelerating the neuronal releasing or astrocytic engulfing might be a potential and attractive therapeutic strategy for the treatment of ischemic stroke in the future.

Determining the effects of tencha-ro drying on key volatile compounds in tencha (Camellia sinensis) through gas chromatography-mass spectrometry.

Drying is the key process through which the aroma of tencha forms. However, the effects of drying method on volatiles are unknown. We compared tencha-ro drying with regular drying. Volatiles in tencha infusions were extracted using headspace solid-phase microextraction and solvent-assisted flavor evaporation combined with gas chromatography-mass spectrometry. Partial least squares (PLS), odor activity value (OAV), and heat map analyses were performed to identify the optimal drying method for creating a seaweed-like aroma. Changes in the key volatile compounds of the samples were investigated. The tencha infusions contained 125 volatiles with nine chemical structures. According to the sensory evaluation, tencha-ro drying was the optimal method for producing high-quality tencha with an intense and consistent seaweed-like aroma. The PLS model accurately distinguished among the types of tencha. By combining OAVs with screening through multivariate statistical analysis, six volatile compounds were revealed to contribute substantially to tencha's seaweed-like aroma: 2-ethyl-3,5-dimethylpyrazine, 2-ethyl-6-methylpyrazine, 2-ethyl-5-methylpyrazine, dimethyl sulfide, ß-ionone, and 2-formyl-1-methylpyrrole. The findings provide a theoretical basis and technical guidance for the processing of high-quality tencha with a strong seaweed-like aroma. PRACTICAL APPLICATION: This study demonstrated that tencha-ro drying contributes to the formation of a seaweed-like aroma in tencha and provides theoretical guidance for tea factories to use the appropriate drying methods for high-quality tencha.

Identification and characterization of pathogenicity-related genes of Rhizoctonia solani AG3 during tobacco infection.

Tobacco target spot disease is caused by a ubiquitous soil-borne phytopathogen Rhizoctonia solani; the pathogenic mechanisms underlying the effects of R. solani remain unclear. Deeper understanding of the functional responses to R. solani during host plant infection would help identify the molecular mechanisms essential for successful host invasion. In this study, we performed global transcriptional analysis of R. solani during various stages (12, 24, 48, 72, 96, and 120 h) of tobacco infection via an RNA sequencing method, while utilizing the pathosystem model R. solani AG3-tobacco (Nicotiana tabacum L.). After R. solani inoculation, the number of differentially expressed genes of R. solani differed at the various time points. Moreover, several gene ontology and Kyoto encyclopedia of genes and genomes pathways were unique in different infection stages, especially with respect to the genes involved in plant cell wall degradation and catalysis of biotransformation reactions, such as the pectin metabolic process and pectin catabolic process. The overexpressing-PD8 N. benthamiana plants enhanced the susceptibility to R. solani. In addition, we found that large amounts of reactive oxygen species (ROS) were generated in tobacco after infected by R. solani. R. solani encoding FAD/NAD binding oxidoreductase and peroxidase gene family to eliminating ROS and counteract oxidative stress. Moreover, Perox3 was validated that can enhance the ability of scavenging ROS by co-injecting. Overall, our findings show that pectin-degrading enzymes and cytochrome P450 genes are critical for plant infection. These results provide comprehensive insights into R. solani AG3 transcriptome responses during tobacco invasion.

microRNA-455-5p alleviates neuroinflammation in cerebral ischemia/reperfusion injury.

Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion. Downregulation of microRNA (miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia. However, the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated. In this study, mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion. Agomir-455-5p, antagomir-455-5p, and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion (MCAO). The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood. Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue, reduced the cerebral infarct volume, and improved neurological function. Furthermore, primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion. miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels, inhibited microglia activation, and reduced the production of the inflammatory factors tumor necrosis factor-α and interleukin-1ß. These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.

Effects of stem removal on physicochemical properties and sensory quality of tencha beverages (Camellia sinensis; Chuanxiaoye).

Fresh tea leaves (Camellia sinensis; Chuanxiaoye) used to make tencha tea are a combination of the stem and leaf. Tencha made from the leaf alone is considered a high-quality tencha beverage with a seaweed-like aroma, mellow taste, and a green appearance. However, no study has investigated the differences between these two variants. In this study, the effects of stem removal on physicochemical properties and sensory quality of tencha beverage were investigated. The appearance feature, taste, and aroma were evaluated, and the results indicated that stem removal improved the quality of tencha beverages. The water extract, total free amino acids, total catechin, epigallocatechin gallate, caffeine, and chlorophyll were higher in leaf-only tencha (LOT) than in leaf and stem tencha (LST), whereas the crude fiber and phenol ammonia ratios were lower in LOT than in LST. Principal component analysis and hierarchical clustering analysis further discriminated between the tencha beverages with different stem contents. This study provided a theoretical basis for quality control by adopting a stem-leaf separation process in tencha manufacturing. PRACTICAL APPLICATION: This research provides theoretical guidance for improving tencha quality during manufacturing.

Quality chemical analysis of crush-tear-curl (CTC) black tea from different geographical regions based on UHPLC-Orbitrap-MS.

Crush-tear-curl (CTC) black tea is a popular beverage, owing to its unique taste characteristics and health benefits. However, differences in the taste quality and chemical profiles of CTC black tea from different geographical regions remain unclear. In this study, 28 CTC black tea samples were collected from six geographical regions and analyzed using electronic tongue and ultrahigh performance liquid chromatography-Orbitrap-mass spectroscopy. The e-tongue analysis indicated that each region's CTC black tea has its own relatively prominent taste characteristics: Sri Lanka (more umami and astringent), North India (more umami), China (more sweetness and astringent), South India (moderate umami and sweetness), and Kenya (moderate umami and astringent). Based on multivariate statistical analysis, 78 metabolites were tentatively identified and used as potential markers for CTC black tea of different origins, mainly including amino acids, flavone/flavonol glycosides, and pigments. Different metabolites, which contributed to the taste characteristics of CTC black tea, were clarified by partial least squares regression correlation analysis. Our findings may serve as useful references for future studies on origin traceability and quality characteristic determination of CTC black teas. PRACTICAL APPLICATION: This study provides useful references for future studies on the origin traceability and taste characteristic determination of CTC black teas from different geographical regions.

Targeted and nontargeted metabolomics analysis for determining the effect of storage time on the metabolites and taste quality of keemun black tea.

The black tea could be stored for a long time, and subsequently affects the flavor characteristics. In the present study, the effects of storage years (1, 2, 3, 4, 5, 10, 17 and 20 years) on the chemical profiling and taste quality of keemun black tea (KBT) were compared by metabolomics and quantitative sensory evaluation. The main polyphenols were degraded during the storing, especially 10-year storage, but caffeine and theobromine were stable. The intensity of bitterness, astringency, umami was negatively correlated to storage years, with correlation coefficient at -0.95, -0.91 and -0.83 respectively, whereas sweetness had positive correlation coefficient at 0.74. Quinic acid, galloylated catechins, linolenic acid, linoleic acid, malic acid, palamitic acid, and theaflavin-3́-gallate were marker compounds which were responsible for distinguishing short and long time preserved KBT. The contents of fatty acids were positively correlated to storage time and sweet intensity.

Analysis of Chemosensory Genes in Full and Hungry Adults of Arma chinensis (Pentatomidae) Through Antennal Transcriptome.

The predatory insect Arma chinensis (Hemiptera: Pentatomidae) is widely distributed in China, where it is also used to control many agricultural and forest pests. The chemosensory genes expressed in its antennae play crucial roles in food-seeking and mating behaviors. To better understand the olfaction of A. chinensis antennae, we identified the genes related to food-seeking and mating. Sequencing of the antennal transcriptomes of full and hungry male and female A. chinensis revealed 38 odorant-binding proteins (OBPs), 1 chemosensory protein (CSP), 1 Niemann-Pick C2 protein (NPC2), 3 odorant receptors (ORs), 12 ionotropic receptors (IRs), 2 gustatory receptors (GRs), and 3 sensory neuron membrane proteins (SNMPs). These results were used to construct phylogenetic trees. A quantitative real-time PCR (qRT-PCR) analysis showed that the relative transcript levels of AchiGR1, AchiGR2, and AchiOBP28 were higher in female than in male antennae in both full and hungry insects, but that the expression of AchiOBP13 and AchiOBP16 was higher only in full A. chinensis females. Thus, the latter genes may encode proteins involved in oviposition selection behavior. AchiGRs (1 and 2), AchiIR6, and AchiOBPs (6-8, 12, 20-22, 28, and 34) were highly expressed only in the antennae of full males, indicating the participation of these genes in mate-searching or male pheromone recognition. The expression of AchiOBP31 in the antennae of starved males, AchiOBPs (15, 18, and 29) in the antennae of starved females, and AchiOBPs (3, 4, and 24) in the antennae of starved males and females suggested that these genes encode food-seeking functions. Our identification of chemosensory genes in A. chinensis antennae and their differential expression in full and hungry insects provides the basis for further functional studies on the chemoreception system of A. chinensis and the sex hormones of predatory insects.

Measurement of cerebrovascular reserve by multimodal imaging for cerebral arterial occlusion or stenosis patients: protocol of a prospective, randomized, controlled clinical study.

BACKGROUND: Cerebrovascular reactivity (CVR) is the change in cerebral blood flow in response to a vaso-active stimulus, and may assist the treatment strategy of ischemic stroke. However, previous studies reported that a therapeutic strategy for stroke mainly depends on the degree of vascular stenosis with steady-state vascular parameters (e.g., cerebral blood flow and CVR). Hence, measurement of CVR by multimodal imaging techniques may improve the treatment of ischemic stroke. METHODS/DESIGN: This is a prospective, randomized, controlled clinical trial that aimed to examine the capability of multimodal imaging techniques for the evaluation of CVR to improve treatment of patients with ischemic stroke. A total of 66 eligible patients will be recruited from Renji Hospital, Shanghai Jiaotong University School of Medicine. The patients will be categorized based on CVR into two subgroups as follows: CVR > 10% group and CVR < 10% group. The patients will be randomly assigned to medical management, percutaneous transluminal angioplasty and stenting, and intracranial and extra-cranial bypass groups in a 1:1:1 ratio. The primary endpoint is all adverse events and ipsilateral stroke recurrence at 6, 12, and 24 months after management. The secondary outcomes include the CVR, the National Institute of Health stroke scale and the Modified Rankin Scale at 6, 12, and 24 months. DISCUSSION: Measurement of cerebrovascular reserve by multimodal image is recommended by most recent studies to guide the treatment of ischemic stroke, and thus its efficacy and evaluation accuracy need to be established in randomized controlled settings. This prospective, parallel, randomized, controlled registry study, together with other ongoing studies, should present more evidence for optimal individualized accurate treatment of ischemic stroke. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-IOR-16009635; Registered on 16 October 2016. All items are from the World Health Organization Trial Registration Data Set and registration in the Chinese Clinical Trial Registry: ChiCTR-IOR-16009635.

Efficacy and safety of bempedoic acid alone or combining with other lipid-lowering therapies in hypercholesterolemic patients: a meta-analysis of randomized controlled trials.

BACKGROUND: Bempedoic acid is a new drug that reduces cholesterol synthesis via inhibiting ATP citrate lyase. It remains unclear whether the combination of bempedoic acid and other lipid-lowering drugs is better than these drugs alone. This study systematically reviewed the efficacy and safety of bempedoic acid monotherapy or combination togethers in hypercholesterolemic patients. METHODS: Randomized controlled trials were searched across Medline, Embase, Cochrane library, web of science, etc. The net change scores [least squares mean (LSM) percentage change] in LDL-C level were meta-analyzed using weighted mean difference. The reductions in other lipids including total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein (ApoB) and high sensitivity C reactive protein (hsCRP) were also assessed. Odds ratio (OR) of the incidence of adverse events (AEs) were calculated to evaluate the safety of bempedoic acid. RESULTS: A total of 13 trials (4858 participates) were included. Pooled data showed that the combination togethers resulted in greater reductions in LDL-C level than monotherapies (bempedoic acid + statin vs. statin: LSM difference (%), - 18.37, 95% CI, - 20.16 to - 16.57, I2 = 0; bempedoic acid + ezetimibe vs. ezetimibe: LSM difference (%), - 18.89, 95% CI, - 29.66 to - 8.13, I2 = 87%). But the difference in efficacy between bempedoic acid and ezetimibe was not obvious. Meta-regression analysis showed the treatment duration was a source of heterogeneity (adj R2 = 16.92, 95% CI, 0.04 to 0.72). Furthermore, the background therapy of statin before screening decreased the efficacy of bempedoic acid. In addition, bempedoic acid also resulted in a significant reduction in TC, non-HDL-C, ApoB and hsCRP level. The OR of muscle-related AEs by the combination of bempedoic acid and statin was 1.29 (95% CI, 1.00 to 1.67, I2 = 0) when compared with statin alone. CONCLUSION: This study showed the efficacy of combination togethers were similar but stronger than these drugs alone. Of note, a trend of high risk of muscle-related AEs by the combination of bempedoic acid and statin was observed, though it is not statistically significant, such risk is needed to be confirmed by more trials, because it is important for us to determine which is the better combinative administration for statin-intolerant patients.

Selection of Patients' Recumbent Position Laterality According to Physician Handedness Bias Increases the Success Rate of Lumbar Puncture: A Multicenter Study.

BACKGROUND: Lumbar puncture (LP) is a medical procedure required during spinal anesthesia and for obtaining cerebrospinal fluid samples in the diagnosis of neurological disorders. The aim of this study was to assess the effects of physicians' handedness bias and the laterality of patients' recumbent position on the success rate of LPs. METHODS AND PATIENTS: A prospective multicenter study including 36 physicians (18 left-handed and 18 right-handed) and 7200 patients was conducted in 6 medical centers. In each center, 1200 patients were randomized into group L (LPs performed by left-handed physicians) or group R (LPs performed by right-handed physicians). Each physician performed 200 cases of LPs, of which the laterality of the recumbent position (either on the left or right side) was decided after a second randomization. A successful LP was considered when the free flow of cerebrospinal fluid was observed upon the first attempt. RESULTS: There was no significant difference in patient characteristics between groups L and R. Right-handed physicians had a significantly higher LP success rate with patients in the left lateral recumbent position (LRP) (1595/1800 vs. 1408/1800; odds ratio, 0.539; 95% confidence interval, 0.348-0.836; P=0.006). For left-handed physicians, the LP success rate was higher when patients were in the right LRP (1424/1800 vs. 1593/1800, odds ratio, 0.449; 95% confidence interval, 0.283-0.711; P=0.001). Patients' age, sex, height, and weight were not statistically related to LP success during multivariate analyses. CONCLUSIONS: Physicians handedness bias and patient laterality of recumbent position affects the success of LPs. Right-handed physicians have a greater chance of performing successful LPs when patients are in the left LRP, and vice versa.

Role of Vascular Endothelial-Cadherin and p120-Catenin in the Formation of Experimental Intracranial Aneurysm in Animals.

BACKGROUND: Dysfunction of endothelial cells (ECs) constitutes a critical factor in the formation of intracranial aneurysms (IAs). However, little is known about the response of ECs to hemodynamic insults and its contribution to IA formation. METHODS: IAs models were constructed in both adult female New Zealand white rabbits and male Sprague-Dawley rats. Morphologic changes of vessel wall were detected by hematoxylin and eosin staining. Molecular and cellular changes, including p120-catenin (p120ctn) and vascular endothelial-cadherin, in the median sagittal section of the artery bifurcation were analyzed by fluorescent staining. RESULTS: Destructive aneurysmal remodeling and the formation of morphologic IAs were observed at the basilar termini of experimental rabbits and the anterior cerebral artery-olfactory artery bifurcation of rats. The expression of p120ctn colocalized with vascular endothelial-cadherin in ECs decreased. Moreover, the expression of p120ctn colocalized with nucleus of ECs increased. These events suggested that p120ctn was transported from the membrane to the nucleus of ECs. CONCLUSIONS: The potential mechanism, that IAs are always localizing in the bifurcation apices, may be that the endothelium injury of vessel wall can be induced by different hemodynamic conditions. Hemodynamic changes in artery bifurcation may initiate the formation of IAs.