Functions of Epimedin C in a zebrafish model of glucocorticoid-induced osteoporosis.

Epimedium is thought to enhance the integrity of tendons and bones, ease joint discomfort and rigidity and enhance kidney function. Although glucocorticoids are commonly used in clinical practice, the mechanism by which the active compound Epimedin C (EC) alleviates glucocorticoid-induced osteoporosis (GIOP) is not well understood. The therapeutic potential of EC in treating GIOP was evaluated using alizarin red S staining, calcein immersion and fluorescence imaging, and bone mineralization, bone mass accumulation and bone density in zebrafish larvae were determined. Using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the key signalling pathways related to bone development were identified. A protein-protein interaction network (PPIN) was constructed to identify osteoclast characteristic genes and the findings were verified using real-time quantitative PCR (RT-qPCR). The bone tissue damage caused by prednisolone was reduced by EC. It also altered physiological processes, improved bone density, boosted mineralization and increased bone mass and activity. Subsequent empirical investigations showed that EC impacted the major signalling pathways involved in bone development, such as osteoclast differentiation, oestrogen, MAPK, insulin resistance, PPAR and AMPK signalling pathways. It also decreased the expression of genes typical of osteoclasts. The results of our study uncover a previously unknown function of EC in controlling bone formation and emphasize the potential of EC as a therapeutic target. The osteoprotective effect of EC indicates its potential as a cost-effective strategy for treating GIOP.

Trial of Intensive Blood-Pressure Control in Older Patients with Hypertension.

BACKGROUND: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. RESULTS: Of the 9624 patients screened for eligibility, 8511 were enrolled in the trial; 4243 were randomly assigned to the intensive-treatment group and 4268 to the standard-treatment group. At 1 year of follow-up, the mean systolic blood pressure was 127.5 mm Hg in the intensive-treatment group and 135.3 mm Hg in the standard-treatment group. During a median follow-up period of 3.34 years, primary-outcome events occurred in 147 patients (3.5%) in the intensive-treatment group, as compared with 196 patients (4.6%) in the standard-treatment group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.92; P = 0.007). The results for most of the individual components of the primary outcome also favored intensive treatment: the hazard ratio for stroke was 0.67 (95% CI, 0.47 to 0.97), acute coronary syndrome 0.67 (95% CI, 0.47 to 0.94), acute decompensated heart failure 0.27 (95% CI, 0.08 to 0.98), coronary revascularization 0.69 (95% CI, 0.40 to 1.18), atrial fibrillation 0.96 (95% CI, 0.55 to 1.68), and death from cardiovascular causes 0.72 (95% CI, 0.39 to 1.32). The results for safety and renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension, which was higher in the intensive-treatment group. CONCLUSIONS: In older patients with hypertension, intensive treatment with a systolic blood-pressure target of 110 to less than 130 mm Hg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mm Hg. (Funded by the Chinese Academy of Medical Sciences and others; STEP ClinicalTrials.gov number, NCT03015311.).

Exploring gut-lung axis crosstalk in SARS-CoV-2 infection: Insights from a hACE2 mouse model.

Based on the forefront of clinical research, there is a growing recognition that the gut microbiota, which plays a pivotal role in shaping both the innate and adaptive immune systems, may significantly contribute to the pathogenesis of coronavirus disease 2019 (COVID-19). Although an association between altered gut microbiota and COVID-19 pathogenesis has been established, the causative mechanisms remain incompletely understood. Additionally, the validation of the precise functional alterations within the gut microbiota relevant to COVID-19 pathogenesis has been limited by a scarcity of suitable animal experimental models. In the present investigation, we employed a newly developed humanized ACE2 knock-in (hACE2-KI) mouse model, capable of recapitulating critical aspects of pulmonary and intestinal infection, to explore the modifications in the gut microbiota following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Examination of fecal samples using 16S rRNA gene profiling unveiled a notable reduction in species richness and conspicuous alterations in microbiota composition at 6 days postinfection (dpi). These alterations were primarily characterized by a decline in beneficial bacterial species and an escalation in certain opportunistic pathogens. Moreover, our analysis entailed a correlation study between the gut microbiota and plasma cytokine concentrations, revealing the potential involvement of the Lachnospiraceae_NK4A136_group and unclassified_f_Lachnospiraceae genera in attenuating hyperinflammatory responses triggered by the infection. Furthermore, integration of gut microbiota data with RNA-seq analysis results suggested that the increased presence of Staphylococcus in fecal samples may signify the potential for bacterial coinfection in lung tissues via gut translocation. In summary, our hACE2-KI mouse model effectively recapitulated the observed alterations in the gut microbiota during SARS-CoV-2 infection. This model presents a valuable tool for elucidating gut microbiota-targeted strategies aimed at mitigating COVID-19.

Photocatalytic Cyclization Cascades by Radical Relay toward Pyrrolo[1,2-a]indoles: Synthesis, Mechanism, and Application.

A photocatalytic annulation cascade of unactivated N-alkene-linked indoles with Langlois' reagent by a radical relay is developed at room temperature under blue LED irradiation. The reaction afforded a series of tri/difluoromethylated pyrrolo[1,2-a]indoles in moderate to good yields. The DFT study suggests that the reaction is ascribed to a rhodamine 6G-induced cyclization cascade involving vinyl addition-radical relay and hydrogen-atom-abstraction (HAA) processes, and interestingly, pyrrolo[1,2-a]indoles are applied as fluorescent dyes into the fluorescence spectrum and live-cell imaging. This paper represents an initial example on photocatalytic cyclization cascades by radical relay and the HAA process.

COVID-19 related acute necrotizing encephalopathy and acute myocarditis in an adult female: a novel case report of brain injury and myocarditis.

BACKGROUND: Acute necrotizing encephalopathy (ANE) and myocarditis are both acute, life-threatening conditions that can be triggered by COVID-19. We report a case of sequential ANE and myocarditis following a COVID-19 infection. CASE PRESENTATION: A 27-year-old female patient was brought to the emergency department due to episodes of fever for two days and a 9-h altered state of consciousness. Her condition rapidly developed into stuporous and hemodynamic instability within serval hours. Veno-arterial extracorporeal membrane oxygenation (ECMO) was rapidly initiated with other supportive treatments. The following-up MRI showed bilateral, symmetrically distributed lesions in the brainstem, bilateral hippocampal regions, and bilateral basal ganglia, consistent with ANE. The diagnosis was confirmed through the detection of SARS-CoV-2 and the exclusion of other potential causes. After weeks of medical treatment, her condition stabilized, and she was transferred for further rehabilitation treatment. CONCLUSIONS: This case study indicates that COVID-19 may simultaneously and rapidly affect the central nervous system and cardiovascular system, leading to poor outcomes. Accurate diagnosis and timely invasive bridging therapy, when necessary, can be lifesaving. Further exploration of potential mechanisms underlying COVID-19 central nervous system (CNS) and cardiovascular system manifestations will be important.

Significance of Oxidative Stress in the Diagnosis and Subtype Classification of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a common illness of aging, and its pathophysiological process is mainly manifested by cell aging and apoptosis, an imbalance in the production and catabolism of extracellular matrix, and an inflammatory response. Oxidative stress (OS) is an imbalance that decreases the body's intrinsic antioxidant defense system and/or raises the formation of reactive oxygen species and performs multiple biological functions in the body. However, our current knowledge of the effect of OS on the progression and treatment of IVDD is still extremely limited. In this study, we obtained 35 DEGs by differential expression analysis of 437 OS-related genes (OSRGs) between IVDD patients and healthy individuals from GSE124272 and GSE150408. Then, we identified six hub OSRGs (ATP7A, MELK, NCF1, NOX1, RHOB, and SP1) from 35 DEGs, and the high accuracy of these hub genes was confirmed by constructing ROC curves. In addition, to forecast the risk of IVDD patients, we developed a nomogram. We obtained two OSRG clusters (clusters A and B) by consensus clustering based on the six hub genes. Then, 3147 DEGs were obtained by differential expression analysis in the two clusters, and all samples were further divided into two gene clusters (A and B). We investigated differences in immune cell infiltration levels between different clusters and found that most immune cells had higher infiltration levels in OSRG cluster B or gene cluster B. In conclusion, OS is important in the formation and progression of IVDD, and we believe that our work will help guide future research on OS in IVDD.

Risk assessment, fitness cost and transcriptome analysis of cyantraniliprole resistance in Spodoptera frugiperda.

Spodoptera frugiperda is a notorious invasive pest causing substantial yield losses of crops and has developed resistance to various types of insecticides. In this study, a cyantraniliprole-resistant strain, SfCYAN-R, was obtained from a susceptible strain, SfCYAN-S, after 13 generations of selection with cyantraniliprole. The fitness cost in SfCYAN-R strain was evaluated, and the putative resistance-related genes were explored by RNA-seq analysis. The results showed that SfCYAN-R strain developed 23.97-fold resistance to cyantraniliprole with the realistic heritability of 0.127. The development time of eggs, larvae, prepupae and pupae in SfCYAN-R strain was significantly prolonged than that in SfCYAN-S strain, but no difference in pupation rate, emergence rate and female fecundity was observed between SfCYAN-R and SfCYAN-S strains. Comparative gene expression analysis between SfCYAN-R and SfCYAN-S strains identified 776 significant differentially expressed genes (DEGs), among which several DEGs associated with xenobiotic metabolism were upregulated in SfCYAN-R strain. These results provide insights into the resistance mechanisms of cyantraniliprole and would be helpful for resistance management of S. frugiperda.

Low concentrations of cyantraniliprole negatively affects the development of Spodoptera frugiperda by disruption of ecdysteroid biosynthesis and carbohydrate and lipid metabolism.

In addition to the acute lethal toxicity, insecticides might affect population dynamics of insect pests by inducing life history trait changes under low concentrations, however, the underlying mechanisms remain not well understood. Here we examined systemic impacts on development and reproduction caused by low concentration exposures to cyantraniliprole in the fall armyworm (FAW), Spodoptera frugiperda, and the putative underlying mechanisms were investigated. The results showed that exposure of third-instar larvae to LC10 and LC30 of cyantraniliprole significantly extended larvae duration by 1.46 and 5.41 days, respectively. Treatment with LC30 of cyantraniliprole significantly decreased the pupae weight and pupation rate as well as the longevity, fecundity and egg hatchability of female adults. Consistently, we found that exposure of FAW to LC30 cyantraniliprole downregulated the mRNA expression of four ecdysteroid biosynthesis genes including SfNobo, SfShd, SfSpo and SfDib and one ecdysone response gene SfE75 in the larvae as well as the gene encoding vitellogenin (SfVg) in the female adults. We also found that treatment with LC30 of cyantraniliprole significantly decreased the whole body levels of glucose, trehalose, glycogen and triglyceride in the larvae. Our results indicate that low concentration of cyantraniliprole inhibited FAW development by disruption of ecdysteroid biosynthesis as well as carbohydrate and lipid metabolism, which have applied implications for the control of FAW.

Populus euphratica GRP2 Interacts with Target mRNAs to Negatively Regulate Salt Tolerance by Interfering with Photosynthesis, Na+, and ROS Homeostasis.

The transcription of glycine-rich RNA-binding protein 2 (PeGRP2) transiently increased in the roots and shoots of Populus euphratica (a salt-resistant poplar) upon initial salt exposure and tended to decrease after long-term NaCl stress (100 mM, 12 days). PeGRP2 overexpression in the hybrid Populus tremula × P. alba '717-1B4' (P. × canescens) increased its salt sensitivity, which was reflected in the plant's growth and photosynthesis. PeGRP2 contains a conserved RNA recognition motif domain at the N-terminus, and RNA affinity purification (RAP) sequencing was developed to enrich the target mRNAs that physically interacted with PeGRP2 in P. × canescens. RAP sequencing combined with RT-qPCR revealed that NaCl decreased the transcripts of PeGRP2-interacting mRNAs encoding photosynthetic proteins, antioxidative enzymes, ATPases, and Na+/H+ antiporters in this transgenic poplar. Specifically, PeGRP2 negatively affected the stability of the target mRNAs encoding the photosynthetic proteins PETC and RBCMT; antioxidant enzymes SOD[Mn], CDSP32, and CYB1-2; ATPases AHA11, ACA8, and ACA9; and the Na+/H+ antiporter NHA1. This resulted in (i) a greater reduction in Fv/Fm, YII, ETR, and Pn; (ii) less pronounced activation of antioxidative enzymes; and (iii) a reduced ability to maintain Na+ homeostasis in the transgenic poplars during long-term salt stress, leading to their lowered ability to tolerate salinity stress.

Populus euphratica CPK21 Interacts with NF-YC3 to Enhance Cadmium Tolerance in Arabidopsis.

The toxic metal cadmium (Cd) poses a serious threat to plant growth and human health. Populus euphratica calcium-dependent protein kinase 21 (CPK21) has previously been shown to attenuate Cd toxicity by reducing Cd accumulation, enhancing antioxidant defense and improving water balance in transgenic Arabidopsis. Here, we confirmed a protein-protein interaction between PeCPK21 and Arabidopsis nuclear transcription factor YC3 (AtNF-YC3) by yeast two-hybrid and bimolecular fluorescence complementation assays. AtNF-YC3 was induced by Cd and strongly expressed in PeCPK21-overexpressed plants. Overexpression of AtNF-YC3 in Arabidopsis reduced the Cd inhibition of root length, fresh weight and membrane stability under Cd stress conditions (100 µM, 7 d), suggesting that AtNF-YC3 appears to contribute to the improvement of Cd stress tolerance. AtNF-YC3 improved Cd tolerance by limiting Cd uptake and accumulation, activating antioxidant enzymes and reducing hydrogen peroxide (H2O2) production under Cd stress. We conclude that PeCPK21 interacts with AtNF-YC3 to limit Cd accumulation and enhance the reactive oxygen species (ROS) scavenging system and thereby positively regulate plant adaptation to Cd environments. This study highlights the interaction between PeCPK21 and AtNF-YC3 under Cd stress conditions, which can be utilized to improve Cd tolerance in higher plants.

Populus trichocarpa EXPA6 Facilitates Radial and Longitudinal Transport of Na+ under Salt Stress.

Expansins are cell wall (CW) proteins that mediate the CW loosening and regulate salt tolerance in a positive or negative way. However, the role of Populus trichocarpa expansin A6 (PtEXPA6) in salt tolerance and the relevance to cell wall loosening is still unclear in poplars. PtEXPA6 gene was transferred into the hybrid species, Populus alba × P. tremula var. glandulosa (84K) and Populus tremula × P. alba INRA '717-1B4' (717-1B4). Under salt stress, the stem growth, gas exchange, chlorophyll fluorescence, activity and transcription of antioxidant enzymes, Na+ content, and Na+ flux of root xylem and petiole vascular bundle were investigated in wild-type and transgenic poplars. The correlation analysis and principal component analysis (PCA) were used to analyze the correlations among the characteristics and principal components. Our results show that the transcription of PtEXPA6 was downregulated upon a prolonged duration of salt stress (48 h) after a transient increase induced by NaCl (100 mM). The PtEXPA6-transgenic poplars of 84K and 717-1B4 showed a greater reduction (42-65%) in stem height and diameter growth after 15 days of NaCl treatment compared with wild-type (WT) poplars (11-41%). The Na+ accumulation in roots, stems, and leaves was 14-83% higher in the transgenic lines than in the WT. The Na+ buildup in the transgenic poplars affects photosynthesis; the activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT); and the transcription of PODa2, SOD [Cu-Zn], and CAT1. Transient flux kinetics showed that the Na+ efflux of root xylem and leaf petiole vascular bundle were 1.9-3.5-fold greater in the PtEXPA6-transgenic poplars than in the WT poplars. PtEXPA6 overexpression increased root contractility and extensibility by 33% and 32%, indicating that PtEXPA6 increased the CW loosening in the transgenic poplars of 84K and 717-1B4. Noteworthily, the PtEXPA6-promoted CW loosening was shown to facilitate Na+ efflux of root xylem and petiole vascular bundle in the transgenic poplars. We conclude that the overexpression of PtEXPA6 leads to CW loosening that facilitates the radial translocation of Na+ into the root xylem and the subsequent Na+ translocation from roots to leaves, resulting in an excessive Na+ accumulation and consequently, reducing salt tolerance in transgenic poplars. Therefore, the downregulation of PtEXPA6 in NaCl-treated Populus trichocarpa favors the maintenance of ionic and reactive oxygen species (ROS) homeostasis under long-term salt stress.

Variation in central venous oxygen saturation to evaluate fluid responsiveness: a systematic review and meta-analysis.

BACKGROUND: Since oxygen content and oxygen consumption typically remain unchanged within a short period, variation in central venous oxygen saturation (ΔScvO2) during fluid challenge can theoretically track the changes in cardiac output (CO). We conducted this meta-analysis to systematically assess the diagnostic performance of ΔScvO2 during a fluid challenge for fluid responsiveness in mechanically ventilated patients receiving volume expansion. METHODS: Electronic databases were systematically searched to identify relevant studies published before October 24, 2022. As the cutoff value of ΔScvO2 was expected to vary across the included studies, we estimated the area under the hierarchical summary receiver operating characteristic curve (AUHSROC) as the primary measure of diagnostic accuracy. The optimal threshold of ΔScvO2 and the corresponding 95% confidential interval (CI) were also estimated. RESULTS: This meta-analysis included 5 observational studies comprising 240 participants, of whom 133 (55%) were fluid responders. Overall, the ΔScvO2 during the fluid challenge exhibited excellent performance for defining fluid responsiveness in mechanically ventilated patients receiving volume expansion, with an AUHSROC of 0.86 (95% CI 0.83-0.89), a pooled sensitivity of 0.78 (95% CI 0.69-0.85), a pooled specificity of 0.84 (95% CI 0.72-0.91), and a pooled diagnostic odds ratio of 17.7 (95% CI 5.9-53.2). The distribution of the cutoff values was nearly conically symmetrical and concentered between 3 and 5%; the mean and median cutoff values were 4% (95% CI 3-5%) and 4% (95% CI not estimable), respectively. CONCLUSIONS: In mechanically ventilated patients receiving volume expansion, the ΔScvO2 during the fluid challenge is a reliable indicator of fluid responsiveness. Clinical trial registration PROSPERO, https://www.crd.york.ac.uk/prospero/ , registry number: CRD42022370192.

Prophylactic noninvasive respiratory support in the immediate postoperative period after cardiac surgery - a systematic review and network meta-analysis.

BACKGROUND: Noninvasive respiratory support has been increasingly applied in the immediate postoperative period to prevent postoperative pulmonary complications (PPCs). However, the optimal approach remains uncertain. We sought to evaluate the comparative effectiveness of various noninvasive respiratory strategies used in the immediate postoperative period after cardiac surgery. METHODS: We conducted a frequentist random-effect network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing the prophylactic use of noninvasive ventilation (NIV), continuous positive airway pressure (CPAP), high flow nasal cannula (HFNC), or postoperative usual care (PUC) in the immediate postoperative period after cardiac surgery. Databases were systematically searched through September 28, 2022. Study selection, data extraction, and quality assessment were performed in duplicate. The primary outcome was the incidence of PPCs. RESULTS: Sixteen RCTs enrolling 3011 patients were included. Compared with PUC, NIV significantly reduced the incidence of PPCs [relative risk (RR) 0.67, 95% confidence interval (CI): 0.49 to 0.93; absolute risk reduction (ARR) 7.6%, 95% CI: 1.6-11.8%; low certainty] and the incidence of atelectasis (RR 0.65, 95% CI: 0.45 to 0.93; ARR 19.3%, 95% CI: 3.9-30.4%; moderate certainty); however, prophylactic NIV was not associated with a decreased reintubation rate (RR 0.82, 95% CI: 0.29 to 2.34; low certainty) or reduced short-term mortality (RR 0.64, 95% CI: 0.16 to 2.52; very low certainty). As compared to PUC, the preventive use of CPAP (RR 0.85, 95% CI: 0.60 to 1.20; very low certainty) or HFNC (RR 0.74, 95% CI: 0.46 to 1.20; low certainty) had no significant beneficial effect on the incidence of PPCs, despite exhibiting a downward trend. Based on the surface under the cumulative ranking curve, the highest-ranked treatment for reducing the incidence of PPCs was NIV (83.0%), followed by HFNC (62.5%), CPAP (44.3%), and PUC (10.2%). CONCLUSIONS: Current evidence suggest that the prophylactic use of NIV in the immediate postoperative period is probably the most effective noninvasive respiratory approach to prevent PPCs in patients undergoing cardiac surgery. Given the overall low certainty of the evidence, further high-quality research is warranted to better understand the relative benefits of each noninvasive ventilatory support. CLINICAL TRIAL REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/prospero/ , registry number: CRD42022303904.

Mechanisms underlying the effects of low concentrations of chlorantraniliprole on development and reproduction of the fall armyworm, Spodoptera frugiperda.

It is well known that sublethal dose of insecticides induces life history trait changes of both target and non-target insect species, however, the underlying mechanisms remain not well understood. In this study, the effects of low concentrations of the anthranilic diamide insecticide chlorantraniliprole on the development and reproduction of the fall armyworm (FAW), Spodoptera frugiperda, were evaluated, and the underlying mechanisms were explored. The results showed that exposure of FAW to LC10 and LC30 chlorantraniliprole prolonged the larvae duration, decreased the mean weight of the larvae and pupae, and lowered the pupation rate as well as emergence rate. The fecundity of female adults was also negatively affected by treatment with low concentrations of chlorantraniliprole. Consistently, we found that exposure of FAW to LC30 chlorantraniliprole downregulated the mRNA expression of juvenile hormone (JH) esterase (SfJHE), leading to the increase of JH titer in larvae. We also found that treatment with low concentrations of chlorantraniliprole suppressed the expression of ribosomal protein S6 kinase1 (SfS6K1) in female adults, resulting in the downregulation of the gene encoding vitellogenin (SfVg). These results provided insights into the mechanisms underlying the effects of low concentrations of insecticides on insect pests, and had applied implications for the control of FAW.

Populus euphratica GLABRA3 Binds PLDδ Promoters to Enhance Salt Tolerance.

High NaCl (200 mM) increases the transcription of phospholipase Dδ (PLDδ) in roots and leaves of the salt-resistant woody species Populus euphratica. We isolated a 1138 bp promoter fragment upstream of the translation initiation codon of PePLDδ. A promoter-reporter construct, PePLDδ-pro::GUS, was introduced into Arabidopsis plants (Arabidopsis thaliana) to demonstrate the NaCl-induced PePLDδ promoter activity in root and leaf tissues. Mass spectrometry analysis of DNA pull-down-enriched proteins in P. euphratica revealed that PeGLABRA3, a basic helix-loop-helix transcription factor, was the target transcription factor for binding the promoter region of PePLDδ. The PeGLABRA3 binding to PePLDδ-pro was further verified by virus-induced gene silencing, luciferase reporter assay (LRA), yeast one-hybrid assay, and electrophoretic mobility shift assay (EMSA). In addition, the PeGLABRA3 gene was cloned and overexpressed in Arabidopsis to determine the function of PeGLABRA3 in salt tolerance. PeGLABRA3-overexpressed Arabidopsis lines (OE1 and OE2) had a greater capacity to scavenge reactive oxygen species (ROS) and to extrude Na+ under salinity stress. Furthermore, the EMSA and LRA results confirmed that PeGLABRA3 interacted with the promoter of AtPLDδ in transgenic plants. The upregulated AtPLDδ in PeGLABRA3-transgenic lines resulted in an increase in phosphatidic acid species under no-salt and saline conditions. We conclude that PeGLABRA3 activated AtPLDδ transcription under salt stress by binding to the AtPLDδ promoter region, conferring Na+ and ROS homeostasis control via signaling pathways mediated by PLDδ and phosphatidic acid.

Comparison of robotic camera holders with human assistants in endoscopic surgery: a systematic review and meta-analysis.

BACKGROUND: Robotic camera holders can overcome the shortcomings of human assistants, such as shaking and accidental rotation in endoscopic surgery. Robotic camera holder is not affected by the operation time and surgical position and reduces the size of the team. However, there is still controversy over the practicality of robotic camera holders. MATERIAL AND METHODS: We searched PubMed, Web of Science, Embase, Cochrane Library PubMed, Embase, Cochrane Library and Web of Science. The last database search was performed on 30 April 2022. Two reviewers independently reviewed the studies. RESULTS: A total of eight studies (n = 698, 354 controls and 344 robotic camera holders) were included in our analysis. The results showed that the robotic camera holder significantly outperformed human assistants on the frequency of lens cleaning (SMD, -0.48; 95% CI, -0.90 to -0.05) and inappropriate movements (MD, -3.57; 95% CI, -4.93 to -2.21). There was no difference in total operation time (MD, 6.99; 95% CI, -2.47 to 16.72), preparation time (MD, 2.43; 95% CI, -0.32 to 5.18) or blood loss (MD, 34.47; 95% CI, -8.05 to 76.98) between the robotic camera holder and human assistant. However, the robotic camera holder was significantly slower in the core operation (MD, 5.06; 95% CI, 1.18 to 8.94), and surgeons had mixed reviews of robotic systems. CONCLUSIONS: The robotic camera holder provided the surgeon with a highly stable environment. Although the robotic camera holder will not increase the total time, it still needs to improve the core operation time. There is much room for improvement in robotic camera holders. Further development of devices with intuitive control systems and a greater range of motion will be required to accommodate more complex surgeries.

PCSK9 inhibitor recaticimab for hypercholesterolemia on stable statin dose: a randomized, double-blind, placebo-controlled phase 1b/2 study.

BACKGROUND: Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in patients with hypercholesterolemia. METHODS: In this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule). RESULTS: A total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from -48.37 to -59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase. CONCLUSION: Recaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov , number NCT03944109.

The ROX index as a predictor of high-flow nasal cannula outcome in pneumonia patients with acute hypoxemic respiratory failure: a systematic review and meta-analysis.

BACKGROUND: The respiratory rate-oxygenation (ROX) index has been increasingly applied to predict the outcome of high-flow nasal cannula (HFNC) in pneumonia patients with acute hypoxemic respiratory failure (AHRF). However, its diagnostic accuracy for the HFNC outcome has not yet been systematically assessed. This meta-analysis sought to evaluate the predictive performance of the ROC index for the successful weaning from HFNC in pneumonia patients with AHRF. METHODS: A literature search was conducted on electronic databases through February 12, 2022, to retrieve studies that investigated the diagnostic accuracy of the ROC index for the outcome of HFNC application in pneumonia patients with AHRF. The area under the hierarchical summary receiver operating characteristic curve (AUHSROC) was estimated as the primary measure of diagnostic accuracy due to the varied cutoff values of the index. We observed the distribution of the cutoff values and estimated the optimal threshold with corresponding 95% confidential interval (CI). RESULTS: Thirteen observational studies comprising 1751 patients were included, of whom 1003 (57.3%) successfully weaned from HFNC. The ROC index exhibits good performance for predicting the successful weaning from HFNC in pneumonia patients with AHRF, with an AUHSROC of 0.81 (95% CI 0.77-0.84), a pooled sensitivity of 0.71 (95% CI 0.64-0.78), and a pooled specificity of 0.78 (95% CI 0.70-0.84). The cutoff values of the ROX index were nearly conically symmetrically distributed; most data were centered between 4.5 and 6.0, and the mean and median values were 4.8 (95% CI 4.2-5.4) and 5.3 (95% CI 4.2-5.5), respectively. Moreover, the AUHSROC in the subgroup of measurement within 6 h after commencing HFNC was comparable to that in the subgroup of measurement during 6-12 h. The stratified analyses also suggested that the ROC index was a reliable predictor of HFNC success in pneumonia patients with coronavirus disease 2019. CONCLUSIONS: In pneumonia patients with AHRF, the ROX index measured within 12 h after HFNC initiation is a good predictor of successful weaning from HFNC. The range of 4.2-5.4 may represent the optimal confidence interval for the prediction of HFNC outcome.

Spinal cord infarction secondary to pulmonary embolism-induced cardiac arrest: a case report.

BACKGROUND: Pulmonary embolism is a common cause of cardiac arrest. Pulmonary embolism-induced cardiac arrest typically suffers from ischemic injuries to various organs, including the central nervous system. However, spinal cord infarction is a rare complication of pulmonary embolism-induced cardiac arrest. At present, there is no case report on the occurrence of spinal cord infarction secondary to pulmonary embolism-induced cardiac arrest without accompanied cerebral complications. CASE PRESENTATION: A 72-year-old woman with dyspnea and chest tightness was admitted to the emergency room. Cardiac arrest occurred within a short period after admission. Subsequent computed tomographic pulmonary angiography revealed multiple pulmonary thromboses, which were highly suspected to be the cause of cardiac arrest. Thrombolytic therapy with alteplase was given after the return of spontaneous circulation. Unfortunately, she was found to be paraplegic in both lower extremities after regaining consciousness. Spinal cord infarction was confirmed by thoracic magnetic resonance imaging. CONCLUSIONS: Despite receiving high-quality cardiopulmonary resuscitation, patients with cardiac arrest are at high risk of ischemic injury to the central nervous system. After the recovery of consciousness, clinicians should pay more attention to preclude the possibility of spinal cord infarction.

Optimizing left ventricular-arterial coupling during the initial resuscitation in septic shock - a pilot prospective randomized study.

BACKGROUND: Left ventricular-arterial coupling (VAC), defined as the ratio of effective arterial elastance (Ea) to left ventricular end-systolic elastance (Ees), has been extensively described as a key determinant of cardiovascular work efficacy. Previous studies indicated that left ventricular-arterial uncoupling was associated with worse tissue perfusion and increased mortality in shock patients. Therefore, this study aims to investigate whether a resuscitation algorithm based on optimizing left VAC during the initial resuscitation can improve prognosis in patients with septic shock. METHODS: This pilot study was conducted in an intensive care unit (ICU) of a tertiary teaching hospital in China. A total of 83 septic shock patients with left ventricular-arterial uncoupling (i.e., the Ea/Ees ratio ≥ 1.36) were randomly assigned to receive usual care (usual care group, n = 42) or an algorithm-based resuscitation that attempt to reduce the Ea/Ees ratio to 1 within the first 6 h after randomization (VAC-optimized group, n = 41). The left VAC was evaluated by transthoracic echocardiography every 2 h during the study period. The primary endpoint was 28-days mortality. The secondary endpoints included lactate clearance rate, length of ICU stay, and duration of invasive mechanical ventilation (IMV). RESULTS: Eighty-two patients (98.8%) completed the study and were included in the final analysis. The Ea/Ees ratio was reduced in both groups, and the decrease in Ea/Ees ratio in the VAC-optimized group was significantly greater than that in the usual care group [median (interquartile range), 0.39 (0.26, 0.45) vs. 0.1 (0.06, 0.22); P < 0.001]. Compared with the usual care group, the VAC-optimized group likely exhibited the potential to reduce the 28-days mortality (33% vs. 50%; log-rank hazard ratio = 0.526, 95% confidence interval: 0.268 to 1.033). Moreover, the VAC-optimized group had a higher lactate clearance rate than the usual care group [27.7 (11.9, 45.7) % vs. 18.3 (- 5.7, 32.1) %; P = 0.038]. No significant difference was observed in terms of the length of ICU stay or duration of IMV. CONCLUSIONS: During the initial resuscitation of septic shock, optimizing left ventricular-arterial coupling was associated with improved lactate clearance, while likely having a beneficial effect on prognosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024031 . Registered 23 June 2019 - Retrospectively registered.