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Introduction A patient record review study conducted in 2006 in a random sample of 21 Dutch hospitals found that 51%–77% of adverse events are related to perioperative care, while Centers for Disease Control and Prevention data in USA in 2013 estimated that the medical error is the third-leading cause of mortality. To capitalise on the potential of apps to enhance perioperative medical quality, there is a need for interventions developed in consultation with real-world users designed to support integrated management for perioperative adverse events (PAEs). This study aims: (1) to access the knowledge, attitude and practices for PAEs among physicians, nurses and administrators, and to identify the needs of healthcare providers for a mobile-based PAEs tool; (2) to develop a data-driven app for integrated PAE management that meets those needs and (3) to test the usability, clinical efficacy and cost-effectiveness of the developed app.Methods and analysis We will adopt an embedded mixed-methods research technique; qualitative data will be used to assess user needs and app adoption, while quantitative data will provide crucial insights to establish the demand for the app, and measure the app effects. Phase 1 will enrol surgery-related healthcare providers from the West China Hospital and identify their latent demand for mobile-based PAEs management using a self-designed questionnaire underpinned by the knowledge, attitude and practice model, as well as expert interviews. In phase 2, we will develop the app for integrated PAE management and test its effectiveness and sustainability. In phase 3, the effects on the total number and severity of reported PAEs will be evaluated using Poisson regression with interrupted time-series analysis over a 2-year period, while users’ engagement, adherence, process evaluation and cost-effectiveness will be evaluated using quarterly surveys and interviews.Ethics and dissemination The West China Hospital of Sichuan University’s Institutional Review Board authorised this study after approving the study protocol, permission forms and questionnaires (number: 2022-1364). Participants will be provided with study information, and informed written consent will be obtained. Study findings will be disseminated through peer-reviewed publications and conference presentations.

Genes with sex-biased expression are thought to underlie sexually dimorphic phenotypes and are therefore subject to different selection pressures in males and females. Many authors have proposed that sexual conflict leads to the evolution of sex-biased expression, which allows males and females to reach separate phenotypic and fitness optima. The selection pressures associated with domestication may cause changes in population architectures and mating systems, which in turn can alter their direction and strength. We compared sex-biased expression and genetic signatures in wild and domestic ducks (Anas platyrhynchos), and observed changes of sexual selection and identified the genomic divergence affected by selection forces. The extent of sex-biased expression in both sexes is positively correlated with the level of both dN/dS and nucleotide diversity. This observed changing pattern may mainly be owing to relaxed genetic constraints. We also demonstrate a clear link between domestication and sex-biased evolutionary rate in a comparative framework. Decreased polymorphism and evolutionary rate in domesticated populations generally matched life-history phenotypes known to experience artificial selection. Taken together, our work suggests the important implications of domestication in sex-biased evolution and the roles of artificial selection and sexual selection for shaping the diversity and evolutionary rate of the genome.

The blood-brain barrier (BBB) is an important barrier separating the central nervous system from the periphery. The composition includes endothelial cells, pericytes, astrocytes, synapses and tight junction proteins. During the perioperative period, anesthesia and surgical operations are also a kind of stress to the body, which may be accompanied by blood-brain barrier damage and brain metabolism dysfunction. Perioperative blood-brain barrier destruction is closely associated with cognitive impairment and may increase the risk of postoperative mortality, which is not conducive to enhanced recovery after surgery. However, the potential pathophysiological process and specific mechanism of blood-brain barrier damage during the perioperative period have not been fully elucidated. Changes in blood-brain barrier permeability, inflammation and neuroinflammation, oxidative stress, ferroptosis, and intestinal dysbiosis may be involved in blood-brain barrier damage. We aim to review the research progress of perioperative blood-brain barrier damage and its potential adverse effects and potential molecular mechanisms, and provide ideas for the study of homeostasis maintenance of brain function and precision anesthesia.

BackgroundPrevious studies have implicated a vital association between gut microbiota/gut microbial metabolites and low back pain (LBP), but their causal relationship is still unclear. Therefore, we aim to comprehensively investigate their causal relationship and identify the effect of gut microbiota/gut microbial metabolites on risk of LBP using a two-sample Mendelian randomization (MR) study.MethodsSummary data from genome-wide association studies (GWAS) of gut microbiota (18,340 participants), gut microbial metabolites (2,076 participants) and LBP (FinnGen biobank) were separately obtained. The inverse variance-weighted (IVW) method was used as the main MR analysis. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were conducted to evaluate the horizontal pleiotropy and to eliminate outlier single-nucleotide polymorphisms (SNPs). Cochran’s Q-test was applied for heterogeneity detection. Besides, leave-one-out analysis was conducted to determine whether the causal association signals were driven by any single SNP. Finally, a reverse MR was performed to evaluate the possibility of reverse causation.ResultsWe discovered that 20 gut microbial taxa and 2 gut microbial metabolites were causally related to LBP (p 0.05). Besides, MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy (p > 0.05). Furthermore, leave-one-out analysis confirmed the robustness of MR results. After adding BMI to the multivariate MR analysis, the 17 gut microbial taxa exposure-outcome effect were significantly attenuated and tended to be null.ConclusionOur findings confirm the the potential causal effect of specific gut microbiota and gut microbial metabolites on LBP, which offers new insights into the gut microbiota-mediated mechanism of LBP and provides the theoretical basis for further explorations of targeted prevention strategies.

Cancers have become the primary cause of death among Chinese residents, seriously affecting their health and life. Oncology nursing is a specialized nursing practice focusing on cancer education, prevention, screening, early detection, and palliative and hospice care. China has made tremendous progress in developing oncology nursing. However, to ensure more individuals can get cancer care, the country’s healthcare system still confronts several problems in oncology nursing that need to be addressed to ensure that more individuals can receive cancer care. This article reviews the current development of oncology nursing in China, especially in pain symptom control, palliative care, end-of-life care, education and training. The challenges faced in oncology nursing in China and the suggestions for developing oncology nursing in China are also discussed and proposed in this review. The growth of research on oncology nursing by Chinese nursing scholars and concerned policymakers is anticipated to ultimately improve oncology nursing and the quality of life of patients with cancer in China.

BackgroundThe preoperative elevated neutrophil-to-lymphocyte ratio (NLR) was reported to be associated with poorer outcomes after cancer and cardiovascular surgeries. It is unclear, however, if the predictive value is particular or if it may be applied to other types of surgery. We aimed to assess the prognostic value of preoperative NLR levels for morbidity and mortality after various surgery and determine an optimal threshold for NLR.MethodsWe conducted a cohort analysis on patients receiving surgery at Sichuan University West China Hospital between 2018 and 2020. Multivariable piecewise regression analysis were used to determine the optimal cutoff value of NLR. Subgroup analysis were performed to verify the correlation. Sensitivity analysis was used to explore the effect of different thresholds.ResultsWe obtained data from 136,347 patients. The optimal cutoff of NLR was determined as 3.6 [95% CI (3.0, 4.1)] by piecewise regression method. After multivariable adjustment, preoperative high NLR remained significantly associated with increased in-hospital mortality (aOR, 2.19; 95% CI, 1.90–2.52; p < 0.001) and ICU admission after surgery (aOR, 1.69; 95% CI, 1.59–1.79; p < 0.001). Subgroup analyses confirmed the predictive value of high NLR in multiple surgical subgroups, including general, orthopedic, neurosurgical, and thoracic surgery subgroups, otorhinolaryngology, head and neck surgery, and burn plastic surgery. A NLR threshold of 3.6 gave excellent predictive value, whether employed alone or added in an extended model.ConclusionsIn conclusion, the association of elevated NLR with higher mortality and ICU admission can be extended to a wider range of procedures. NLR threshold of 3.6 could provide good prognostic value for the prognostic model.

Abstract Bone injury caused changes to surrounding tissues, leading to a large number of osteoclasts appeared to clear the damaged bone tissue before bone regeneration. However, overactive osteoclasts will inhibit bone formation. In this study, we prepared methacrylylated gelatin (GelMA)‐based hydrogel to co‐crosslink with OP3‐4 peptide, a receptor activator of NF‐κB ligand (RANKL) binding agent, to achieve the slow release of OP3‐4 peptide to inhibit the activation of osteoclasts, thus preventing the long‐term existence of osteoclasts from affecting bone regeneration, and promoting osteogenic differentiation. Moreover, CXCL9 secreted by osteoblasts will bind to endogenous VEGF and inhibit vascularization, finally hinder bone formation. Thus, anti‐CXCL9 antibodies (A‐CXCL9) were also loaded in the hydrogel to neutralize excess CXCL9. The hydrogel slow released of OP3‐4 cyclic peptide and A‐CXCL9 to simultaneously inhibiting osteoclast activation and promoting vascularization, thereby accelerating the healing of femur defect. Further analysis of osteogenic protein expression and signal pathways showed that the hydrogel may be through activating the AKT‐RUNX2‐ALP pathway and ultimately promote osteogenic differentiation. This dual‐acting hydrogel can effectively prevent nonunion caused by low vascularization and provide long‐term support for the treatment of bone injury.

IntroductionIntrinsically, chronic obstructive pulmonary disease (COPD) is a highly heterogonous disease. Several sex differences in COPD, such as risk factors and prevalence, were identified. However, sex differences in clinical features of acute exacerbation chronic obstructive pulmonary disease (AECOPD) were not well explored. Machine learning showed a promising role in medical practice, including diagnosis prediction and classification. Then, sex differences in clinical manifestations of AECOPD were explored by machine learning approaches in this study.MethodsIn this cross-sectional study, 278 male patients and 81 female patients hospitalized with AECOPD were included. Baseline characteristics, clinical symptoms, and laboratory parameters were analyzed. The K-prototype algorithm was used to explore the degree of sex differences. Binary logistic regression, random forest, and XGBoost models were performed to identify sex-associated clinical manifestations in AECOPD. Nomogram and its associated curves were established to visualize and validate binary logistic regression.ResultsThe predictive accuracy of sex was 83.930% using the k-prototype algorithm. Binary logistic regression revealed that eight variables were independently associated with sex in AECOPD, which was visualized by using a nomogram. The AUC of the ROC curve was 0.945. The DCA curve showed that the nomogram had more clinical benefits, with thresholds from 0.02 to 0.99. The top 15 sex-associated important variables were identified by random forest and XGBoost, respectively. Subsequently, seven clinical features, including smoking, biomass fuel exposure, GOLD stages, PaO2, serum potassium, serum calcium, and blood urea nitrogen (BUN), were concurrently identified by three models. However, CAD was not identified by machine learning models.ConclusionsOverall, our results support that the clinical features differ markedly by sex in AECOPD. Male patients presented worse lung function and oxygenation, less biomass fuel exposure, more smoking, renal dysfunction, and hyperkalemia than female patients with AECOPD. Furthermore, our results also suggest that machine learning is a promising and powerful tool in clinical decision-making.

Introduction COVID-19 infections have become a global public health emergency. Although COVID-19 is primarily a respiratory disease, some of hospitalised patients exhibit cognitive impairment-related neurological damage. Using a systematic review and meta-analysis, we aim to investigate the risk factors for cognitive impairment in patients with COVID-19.Methods and analysis This meta-analysis has been registered with the International Prospective Register of Systematic Reviews. From inception to 5 August 2022, we will search PubMed, Web of Science, Embase via Ovid, the Chinese Biological Medical Database and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant studies . We will also look for additional studies in the reference lists of selected articles. To ensure data quality and accuracy, only researches published in English and Chinese will be included. Fixed or random-effects model will be used to calculate the relative risk (RR) or odds ratio (OR) and 95% CIs for pooled data about dichotomous outcomes. We will also assess heterogeneity using Cochrane’s Q and I2 tests. Cognitive impairment RR or OR is the primary outcome.Ethics and dissemination Data will be extracted from published studies, so ethical approval is not required. The outcomes of this meta-analysis will be published in a journal with peer review.PROSPERO registration number CRD42022351011.

Posttranslational modifications of antibody products affect their stability, charge distribution, and drug activity and are thus a critical quality attribute. The comprehensive mapping of antibody modifications and different charge isomers (CIs) is of utmost importance, but is challenging. We intended to quantitatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity. The CIs of antibodies were fractionated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection, followed by stepwise structural characterization at three levels. First, the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach; this showed differences in glycoforms and deamidation status. Second, at the peptide level, common modifications of oxidation, deamidation, and glycosylation were identified. Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs. In total, 10 N-glycoforms were detected by peptide mapping. Finally, an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides. Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms. The results revealed that sialic acid modification is a critical factor accounting for charge heterogeneity, which is otherwise missed in peptide mapping and intact molecular weight analyses. This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.

This article presents a geochemical analysis of the major and trace elements in the wall-rocks and ores at different elevations in the Zhoujiashan and Shazhou ore deposits of the Xiangshan uranium orefield. Combining the analysis results with alteration characteristics of the deposits, we aims to understand the source of ore-forming materials and fluids. The variation trend of the typical major elements shows that the Xiangshan orefield has obvious vertical alteration zonings. The alteration rocks exposed in the shallow part of the Zoujiashan deposit mainly show alkaline alteration, while those exposed in the Shazhou deposit mainly show acidic alteration, which confirms the alteration characteristics of "alkaline alteration in the north and acidic alteration in the west" in the Xiangshan area. Correlation analysis and Q-type cluster analysis of the trace elements in the two deposits show that the geochemical characteristics of the two deposits are similar. Mo, Sr, Th, Tl, U, V, La and Ba are closely related to mineralization. The above two analysis together with the study on loading relations of orthogonal factors reveal that the ore-forming hydrothermal fluids of the two deposits are derived from the same deep fluid. Moreover, the loading relations analysis of orthogonal factors also shows that rhyolite is strongly correlated with ore, suggesting that ore-forming materials are most likely derived from rhyolite magma.

BackgroundAccumulating evidence has demonstrated that an association between chronic pain and autoimmune diseases (AIDs). Nevertheless, it is unclear whether these associations refer to a causal relationship. We used a two-sample Mendelian randomization (MR) method to determine the causal relationship between chronic pain and AIDs.MethodsWe assessed genome-wide association study (GWAS) summary statistics for chronic pain [multisite chronic pain (MCP) and chronic widespread pain (CWP)], and eight common AIDs, namely, amyotrophic lateral sclerosis (ALS), celiac disease (CeD), inflammatory bowel disease (IBD), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), type 1 diabetes (T1D) and psoriasis. Summary statistics data were from publicly available and relatively large-scale GWAS meta-analyses to date. The two-sample MR analyses were first performed to identify the causal effect of chronic pain on AIDs. The two-step MR and multivariable MR were used to determine if mediators (BMI and smoking) causally mediated any connection and to estimate the proportion of the association mediated by these factors combined.ResultsWith the utilization of MR analysis, multisite chronic pain was associated with a higher risk of MS [odds ratio (OR) = 1.59, 95% confidence interval (CI) = 1.01-2.49, P = 0.044] and RA (OR = 1.72, 95% CI = 1.06-2.77, P = 0.028). However, multisite chronic pain had no significant effect on ALS (OR = 1.26, 95% CI = 0.92-1.71, P = 0.150), CeD (OR = 0.24, 95% CI = 0.02-3.64, P = 0.303), IBD (OR = 0.46, 95% CI = 0.09-2.27, P = 0.338), SLE (OR = 1.78, 95% CI = 0.82-3.88, P = 0.144), T1D (OR = 1.15, 95% CI = 0.65-2.02, P = 0.627) or Psoriasis (OR = 1.59, 95% CI = 0.22-11.26, P = 0.644). We also found positive causal effects of MCP on BMI and causal effects of BMI on MS and RA. Moreover, there were no causal connections between genetically predicted chronic widespread pain and the risk of most types of AIDs disease.ConclusionOur MR analysis implied a causal relationship between MCP and MS/RA, and the effect of MCP on MS and RA may be partially mediated by BMI.

Solidago canadensis is an invasive plant that can adapt to variable environmental conditions. To explore the molecular mechanism of the response to nitrogen (N) addition conditions in S. canadensis, physiology and transcriptome analysis were performed with samples that cultured by natural and three N level conditions. Comparative analysis detected many differentially expressed genes (DEGs), including the function of plant growth and development, photosynthesis, antioxidant, sugar metabolism and secondary metabolism pathways. Most genes encoding proteins involved in plant growth, circadian rhythm and photosynthesis were upregulated. Furthermore, secondary metabolism-related genes were specifically expressed among the different groups; for example, most DEGs related to phenol and flavonoid synthesis were downregulated in the N-level environment. Most DEGs related to diterpenoid and monoterpenoid biosynthesis were upregulated. In addition, many physiological responses, such as antioxidant enzyme activities and chlorophyll and soluble sugar contents, were elevated by the N environment, which was consistent with the gene expression levels in each group. Collectively, our observations indicated that S. canadensis may be promoted by N deposition conditions with the alteration of plant growth, secondary metabolism and physiological accumulation.

Salt intake is too high nowadays. It has been widely recognized that there is a close relationship between hypertension (HTN) and dietary salt intake. Investigations reveal that long-term high salt intake, mainly sodium intake, induces a relevant increase in blood pressure in hypertensive and normotensive individuals. According to most scientific evidence, a diet with high salt intake in public increases cardiovascular risk, salted-related HTN, and other HTN-associated outcomes. Given the clinical importance, this review aims to present the prevalence of HTN and trends in salt intake in the Chinese population and will comprehensively discuss the risk factors, causes, and mechanisms of the association between salt intake and HTN. The review also highlights the education of Chinese people regarding salt intake and the cost-effectiveness of salt reduction from a global perspective. Finally, the review will emphasize the need to customize the unique Chinese practices to reduce salt intake and how awareness changes people's eating lifestyle and helps adopt diet salt reduction strategies.

Poly (ADP-ribose) polymerase 1 (PARP1) is a key DNA damage sensor that is recruited to damaged sites after DNA strand breaks to initiate DNA repair. This is achieved by catalyzing attachment of ADP-ribose moieties, which are donated from NAD+, on the amino acid residues of itself or other acceptor proteins. PARP inhibitors (PARPi) that inhibit PARP catalytic activity and induce PARP trapping are commonly used for treating BRCA1/2-deficient breast and ovarian cancers through synergistic lethality. Unfortunately, resistance to PARPi frequently occurs. In this review, we present the novel substrates and regulators of the PARP1-catalyzed poly (ADP-ribosyl)ation (PARylatison) that have been identified in the last 3 years. The overall aim is the presentation of protein interactions of potential therapeutic intervention for overcoming the resistance to PARPi.

Introduction Awake tracheal intubation (ATI) involves placing a tracheal tube in an awake, spontaneously breathing patient. Superior laryngeal nerve block (SLNB) can effectively abolish the glottic closure reflex, and blunt the sensation of the structures above the cords. A method that consists of SLNB along with translaryngeal injection (TLI) can provide satisfactory anaesthesia and intubating conditions. We present a novel modified access of SLNB, ultrasound (US)-guided anterior SLNB, to aid awake videolaryngoscopes-assisted endotracheal intubation in adult elective surgery patients, and we compare the effectiveness and safety to traditional US-guided posterior SLNB.Methods and analysis A total of 100 adult elective surgery patients requiring general endotracheal anaesthesia will be randomly assigned to the modified group (modified US-guided anterior SLNB) or the traditional group (traditional US-guided posterior SLNB). After SLNB, all participants will be performed with TLI. The primary outcome is the proportion of acceptable intubation conditions based on intubation scores. Secondary outcomes include: (a) the first-attempt intubation success rate, (b) haemodynamic changes during ATI, (c) time taken for airway anaesthesia and intubation, (d) recall of intubation, (e) participant perception of comfort during intubation, (f) perioperative complication rate. This report describes the study design of this randomised controlled trial.Ethics and dissemination The study protocol has been approved by an ethical committee of the West China Hospital (Sichuan University), and registered at the Chinese Clinical Trials Register (www.chictr.org.cn). Results will be published in a peer-reviewed journal.Trial registration number ChiCTR2200058086.

The examination of parity symmetry in gravitational interactions has drawn increasing attention. Although Einstein’s General Relativity is parity-conserved, numerous theories of parity-violating (PV) gravity in different frameworks have recently been proposed for different motivations. In this review, we briefly summarize the recent progress of these theories, and focus on the observable effects of PV terms in the gravitational waves (GWs), which are mainly reflected in the difference between the left-hand and right-hand polarization modes. We are primarily concerned with the implications of these theories for GWs generated by the compact binary coalescences and the primordial GWs generated in the early Universe. The deviation of GW waveforms and/or primordial power spectrum can always be quantified by the energy scale of parity violation of the theory. Applying the current and future GW observation from laser interferometers and cosmic microwave background radiation, the current and potential constraints on the PV energy scales are presented, which indicates that the parity symmetry of gravity can be tested in high energy scale in this new era of gravitational waves.

In recent decades, great changes have taken place in the anesthesiology of China in anesthesia equipment, anesthesiology theory of basic, clinical research, and clinical anesthesia technology. Despite this, there is still a shortage of doctors with higher medical education in anesthesiology, which is also a major problem facing for anesthesia discipline of China, especially in Tibet, Xinjiang, and Inner Mongolia and other regions. Due to the high cold and low oxygen environment in the Tibet Autonomous Region, the development of medical education is backward, especially anesthesia medical education. With the improvement of anesthesia medical technology, we should continue to optimize and reform the local anesthesia medical teaching methods, so as to make substantial reform of anesthesia medical education in Tibet. This paper discusses the main problems in anesthesia medical education and clinical anesthesia in Tibet, as well as its reform ideas and methods. It aims to improve the level of anesthesiology education in Tibet, so as to improve the clinical professional ability of doctor anesthesia, and then better benefit to the local people.

Ischemic stroke (IS) is a neurological disorder prevalent worldwide with a high disability and mortality rate. In the clinic setting, tissue plasminogen activator (tPA) and thrombectomy could restore blood flow of the occlusion region and improve the outcomes of IS patients; however, these therapies are restricted by a narrow time window. Although several preclinical trials have revealed the molecular and cellular mechanisms underlying infarct lesions, the translatability of most findings is unsatisfactory, which contributes to the emergence of new biomaterials, such as hydrogels and nanomaterials, for the treatment of IS. Biomaterials function as structural scaffolds or are combined with other compounds to release therapeutic drugs. Biomaterial-mediated drug delivery approaches could optimize the therapeutic effects based on their brain-targeting property, biocompatibility, and functionality. This review summarizes the advances in biomaterials in the last several years, aiming to discuss the therapeutic potential of new biomaterials from the bench to bedside. The promising prospects of new biomaterials indicate the possibility of an organic combination between materialogy and medicine, which is a novel field under exploration.

BackgroundTo determine the immunogenicity, efficacy, reactogenicity, and safety of a single dose of recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV, 5 × 1010 viral particles per 0.5 mL dose), we conducted a single-dose, randomised, double-blind, placebo-controlled, parallel group (3:1 Ad5-nCoV:placebo), phase 3 trial (Prometheus).MethodsFrom 11-September-2020 to 05-May-2021, across six sites in the Russian Federation, 496 participants were injected with either placebo or Ad5-nCoV expressing the full-length spike (S) protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).ResultsSeroconversion (the primary endpoint) rates of 78.5% (95% CI: 73.9; 82.6) against receptor binding domain (RBD), 90.6% (95% CI: 87.2; 93.4) against S protein and 59.0% (95% CI: 53.3; 64.6) seroconversion of neutralising antibodies against SARS-CoV-2 at 28 days post-vaccination were observed. Geometric mean titres (GMTs) were also elevated for antibodies against the RBD (405 [95% CI: 366; 449]) and S protein (677 [95% CI: 608; 753]) compared to the GMT of neutralising antibodies against SARS-CoV-2 (16.7 [95% CI: 15.3; 18.3]). Using an IFN-γ ELISpot assay after stimulating the cells with recombinant S protein ectodomain we showed that the Ad5-nCoV vaccine induced the most robust cellular immune response on Days 14 and 28. Up to Day 28, the primary and all secondary endpoints of the Ad5-nCoV vaccine were statistically significant compared with the placebo (рConclusionA single-dose of Ad5-nCoV vaccine induced a marked specific humoral and cellular immune response with a favourable safety profile.Trial registrationTrial registration: ClinicalTrials.gov: NCT04540419.

BackgroundVolatile anesthetics including sevoflurane and isoflurane enhance oscillations of cortical electroencephalogram (EEG), partly by their modulations on glutamate-mediated excitatory synaptic transmission. Expression of NMDA receptors is increased during neonatal development. However, how the development of NMDA receptors influences EEG under volatile anesthesia remains unclear.MethodsExpressions of NMDA receptor subtypes (NR1, NR2A, and NR2B) during neonatal development were measured by Western blotting. MAC (minimal alveolar concentration) of isoflurane and sevoflurane that inducing loss of righting reflex (LORR) and no response to tail-clamp (immobility) were measured to verify the effect of NR1 expression on anesthetic potency during neonatal development. Cortical electroencephalogram recording was used to examine the influence of NR1 expression on the power density of EEG.ResultsThe expressions of GluNR1, GluNR2A and GluNR2B receptors were gradually increased during neonatal development in cortex, hippocampus and thalamus of rats. Knockdown of NR1 enhanced the sedative potency of volatile anesthetics but not on immobility potency in postnatal day 14 (P14)-P17 rats. For cortical EEG, along with the increased concentration of volatile anesthetics, cortical slow-delta oscillations of P5 rats were inhibited, theta and alpha oscillations were not changed significantly; while these oscillations were enhanced until high anesthetic concentrations in P21 rats. Knockdown of NR1 in forebrain suppressed the enhancement of cortical EEG oscillations in P21 rats.ConclusionThe development of NMDA receptors may contribute to the enhancement of cortical EEG oscillations under volatile anesthetics.

The use of air springs has become widespread in various industries due to their exceptional superelastic properties; however, their strong nonlinear characteristics have become a hindrance to numerical simulations of air springs and have garnered increasing attention. This paper examined the nonlinear dynamic mechanical characteristics of air springs from a fluid–structure interaction perspective and verified the accuracy of the simulation analysis model through quasistatic tension and compression experiments. The average relative errors for air spring load and gas pressure were found to be 8.1% and 7.7%, respectively, which supports the validity of the model. The impact of frequency and amplitude excitations on the axial load characteristics of air springs was investigated through tension and torsion testing. The results showed that increasing the excitation frequency improves the stability of the axial load, while increasing the excitation amplitude enhances the axial load value. The change in axial compression was found to be more significant than that in axial tension, as it was affected not only by the axial load but also by the radial load, which is a key factor affecting the dynamic characteristics of air springs. A radial load analysis model was established to study the influence of frequency and amplitude excitations on the axial load characteristics of air springs. The simulation results indicated that under different amplitudes, the radial load of air springs goes through four stages: a steady period, rising period, steady period, and falling period. Additionally, under the same amplitude, the radial load value increases with an increase in frequency. This research on the dynamic load characteristics of air springs under amplitude and frequency excitations is important for their application in low-frequency and low-amplitude vibration environments, and its findings can be utilized to improve the technical parameters of air springs for suspension damping.

Human Activity Recognition (HAR) systems have made significant progress in recognizing and classifying human activities using sensor data from a variety of sensors. Nevertheless, they have struggled to automatically discover novel activity classes within massive amounts of unlabeled sensor data without external supervision. This restricts their ability to classify new activities of unlabeled sensor data in real-world deployments where fully supervised settings are not applicable. To address this limitation, this paper presents the Novel Class Discovery (NCD) problem, which aims to classify new class activities of unlabeled sensor data by fully utilizing existing activities of labeled data. To address this problem, we propose a new end-to-end framework called More Reliable Neighborhood Contrastive Learning (MRNCL), which is a variant of the Neighborhood Contrastive Learning (NCL) framework commonly used in visual domain. Compared to NCL, our proposed MRNCL framework is more lightweight and introduces an effective similarity measure that can find more reliable k-nearest neighbors of an unlabeled query sample in the embedding space. These neighbors contribute to contrastive learning to facilitate the model. Extensive experiments on three public sensor datasets demonstrate that the proposed model outperforms existing methods in the NCD task in sensor-based HAR, as indicated by the fact that our model performs better in clustering performance of new activity class instances.

In this paper, we study analytical approximate solutions for second-order homogeneous differential equations with the existence of only two turning points (but without poles) by using the uniform asymptotic approximation (UAA) method. To be more concrete, we consider the Pöschl–Teller (PT) potential, for which analytical solutions are known. Depending on the values of the parameters involved in the PT potential, we find that the upper bounds of the errors of the approximate solutions in general are ≲0.15∼10% for the first-order approximation of the UAA method. The approximations can be easily extended to high orders, for which the errors are expected to be much smaller. Such obtained analytical solutions can be used to study cosmological perturbations in the framework of quantum cosmology as well as quasi-normal modes of black holes.

The venting of methane from coal mining is China’s main source of methane emissions. Accurate and up-to-date methane emission factors for coal mines are significant for reporting and controlling methane emissions in China. This study takes a typical coal mine in Shanxi Province as the research object and divides the coal mine into different zones based on the occurrence structure of methane in Shanxi Province. The methane emission characteristics of underground coal mine types and monitoring modes were studied. The emissions of methane from coal seams and ventilation methane of six typical coal mine groups in Shanxi Province were monitored. The measured methane concentration data were corrected by substituting them into the methane emission formula, and the future methane emissions were predicted by the coal production and methane emission factors. The results show that the number of methane mines and predicted reserves in Zone I of Shanxi Province are the highest. The average methane concentration emitted from coal and gas outburst mines is about 22.52%, and the average methane concentration emitted from high-gas mines is about 10.68%. The methane emissions from coal and gas outburst mines to the atmosphere account for about 64% of the total net methane emissions. The predicted methane emission factor for Shanxi coal mines is expected to increase from 8.859 m3/t in 2016 to 9.136 m3/t in 2025, and the methane emissions from Shanxi coal mines will reach 8.43 Tg in 2025.

The high-speed collision issue brought on by railway vehicles’ intensive and high-speed operation has become a critical concern for operational safety. Therefore, it is necessary to research the high-speed collision problem of trains. Firstly, a train collision dynamic model suitable for higher collision velocities is established. This model includes a 38-degree-of-freedom (DOF) three-dimensional vehicle model and a three-layered vibrating fixed-track model. Corresponding mathematical models are developed for nonlinear factors such as wheel–rail contact, car–end contact, and coupler overload representation in the model. Then, the Train Collision State Score (TCSS) is proposed, enabling quantitative safety evaluation under different collision conditions. Finally, the influence of the energy-absorbing device’s initial attitude and leading car parameters on collisions is studied. The results indicate that initial vertical height difference and pitching angle significantly increase TCSS. As the force level of the energy-absorbing device of the leading car increases, the effects of two intermediate coupler overload states on TCSS show opposite trends.

Abstract Background The relationship between the type of anesthesia and the survival outcomes of gastric cancer patients is uncertain. This study compared the overall outcome of gastric cancer patients after surgery with total intravenous anesthesia (TIVA) or inhalation anesthesia (IHA). Methods Clinicopathological variables of gastric cancer patients were retrieved from the database of the Surgical Gastric Cancer Patient Registry in West China Hospital, Sichuan University. Patients were grouped according to whether they received TIVA or IHA during the operation. Propensity score (PS) matching was used to balance the baseline variables, and survival outcomes were compared between these two groups. In addition, studies comparing survival outcomes between TIVA and IHA used for gastric cancer surgery and published before April 20th, 2020, were identified, and their data were pooled. Results A total of 2827 patients who underwent surgical treatment from Jan 2009 to Dec 2016 were included. There were 323 patients in the TIVA group and 645 patients in the IHA group, with 1:2 PS matching. There was no significant difference in overall survival outcomes between the TIVA and IHA groups before matching the cohort (p = 0.566) or after matching the cohort (p = 0.679) by log-rank tests. In the Cox hazard regression model, there was no significant difference between the TIVA and IHA groups before (HR: 1.054, 95% CI: 0.881–1.262, p = 0.566) or after (HR: 0.957, 95% CI: 0.779–1.177, p = 0.679) PS matching. The meta-analysis of survival outcomes between the TIVA and IHA groups found critical statistical value in the before PS matching cohort (HR 0.74, 95% CI: 0.57–0.96 p

Abstract Although increasing evidence has confirmed that the apoptosis of renal tubular epithelial cells (RTECs) is a crucial contributor to the onset and development of septic acute kidney injury (AKI), the pathological mechanism by which RTEC apoptosis is upregulated during septic AKI is not entirely clear. In this study, a rat model of septic AKI was induced by a cecal ligation puncture procedure or lipopolysaccharide (LPS) injection. Four differentially expressed long noncoding RNAs (DE-Lncs) in the rat model of septic AKI were determined using RNA-sequencing and verified by qRT-PCR. Among the four DE-Lncs, the expression level of lncRNA NONRATG019935.2 (9935) exhibited the most significant reduction in both septic AKI rats and LPS-treated NRK-52E cells (a rat RTEC line). The overexpression of 9935 suppressed cell apoptosis and p53 protein level in LPS-treated NRK-52E cells, and retarded septic AKI development in the rat model of septic AKI. Mechanistically, 9935 decreased the human antigen R (HuR)-mediated Tp53 mRNA stability by limiting the combination of HuR and the 3′UTR region of Tp53 mRNA in RTECs. The overexpression of HuR abrogated the inhibitory effect of pcDNA-9935 on the LPS-induced apoptosis of NRK-52E and rat primary RTECs. In conclusion, 9935 exerts its role in septic AKI by suppressing the p53-mediated apoptosis of RTECs, and this essential role of 9935 relies on its destructive effect on HuR-mediated Tp53 mRNA stability.

Abstract Background This study investigated the protective effects of L. reuteri ZJ617 on intestinal and liver injury and the underlying mechanisms in modulating inflammatory, autophagy, and apoptosis signaling pathways in a piglet challenged with lipopolysaccharide (LPS). Methods Duroc × Landrace × Large White piglets were assigned to 3 groups (n = 6/group): control (CON) and LPS groups received oral phosphate-buffered saline for 2 weeks before intraperitoneal injection (i.p.) of physiological saline or LPS (25 μg/kg body weight), respectively, while the ZJ617 + LPS group was orally inoculated with ZJ617 for 2 weeks before i.p. of LPS. Piglets were sacrificed 4 h after LPS injection to determine intestinal integrity, serum biochemical parameters, inflammatory signaling involved in molecular and liver injury pathways. Results Compared with controls, LPS stimulation significantly increased intestinal phosphorylated-p38 MAPK, phosphorylated-ERK and JNK protein levels and decreased IκBα protein expression, while serum LPS, TNF-α, and IL-6 concentrations (P

Morphology of organic thin film, including the in-plane and out-of-plane directions, plays a crucial role in determining the performance of organic solar cells, yet the characterisation is challenging for the out-of-plane direction. Here, the authors use GTSAXS to uncover the nanomorphology in this dimension, and show how it affects exciton dissociation and charge transfer.

Abstract Background The invasion of Solidago canadensis probably related to polyploidy, which may promotes its potential of sexual reproductive. S. canadensis as an invasive species which rapidly widespread through yield huge numbers of seed, but the mechanism remains unknown. To better understand the advantages of sexual reproduction in hexaploid S. canadensis, transcriptome and small RNA sequencing of diploid and hexaploid cytotypes in flower bud and fruit development stages were performed in this study. Results The transcriptome analysis showed that in the flower bud stage, 29 DEGs were MADS-box related genes with 14 up-regulated and 15 down-regulated in hexaploid S. canadensis; 12 SPL genes were detected differentially expressed with 5 up-regulated and 7 down-regulated. In the fruit development stage, 26 MADS-box related genes with 20 up-regulated and 6 down-regulated in hexaploid S. canadensis; 5 SPL genes were all up-regulated; 28 seed storage protein related genes with 18 were up-regulated and 10 down-regulated. The weighted gene co-expression network analysis (WGCNA) identified 19 modules which consisted of co-expressed DEGs with functions such as sexual reproduction, secondary metabolism and transcription factors. Furthermore, we discovered 326 miRNAs with 67 known miRNAs and 259 novel miRNAs. Some of miRNAs, such as miR156, miR156a and miR156f, which target the sexual reproduction related genes. Conclusion Our study provides a global view of the advantages of sexual reproduction in hexaploid S. canadensis based on the molecular mechanisms, which may promote hexaploid S. canadensis owing higher yield and fruit quality in the process of sexual reproduction and higher germination rate of seeds, and finally conductive to diffusion, faster propagation process and enhanced invasiveness.

Abstract Three‐dimensional (3D) organic–inorganic metal halide perovskite materials possess great potential applications for approaching efficient optoelectronics due to the unique optoelectronic properties of perovskite materials and cost‐effective manufacturing possibilities of optoelectronics. However, the scientific and technical challenges of 3D perovskite materials were their inferior long‐term stability, which hampered their practical applications. The low‐dimensional perovskite materials composed of alternating organic and inorganic layers are one of the most credible paths toward stable perovskite photovoltaics and optoelectronics. In this short review, we first present a discussion of the crystal structure and nontrivial optoelectronic properties of the low‐dimensional halide perovskites. The synthetic methods for the preparation of the low‐dimensional halide perovskites are reviewed. After that, we focus on the recent development of perovskite photovoltaics, light‐emitting diodes, and lasers by the low‐dimensional halide perovskites. Finally, we outline the challenges of the low‐dimensional halide perovskites and their applications.

Abstract Background Domestication alters several phenotypic, neurological, and physiological traits in domestic animals compared to those in their wild ancestors. Domestic ducks originated from mallards, and some studies have shown that spot-billed ducks may have also made minor genetic contributions to domestication. Compared with the two ancestral species, domestic ducks generally differ in body size and bone morphology. In this study, we performed both genomic and transcriptomic analyses to identify candidate genes for elucidating the genetic mechanisms underlying phenotypic variation. Methods In this study, the duck genome data from eight domestic breeds and two wild species were collected to study the genetic changes during domestication. And the transcriptome data of different tissues from wild ducks and seven domestic ducks were used to reveal the expression difference between wild and domestic ducks. Results Using fixation index (Fst) algorithm and transcriptome data, we found that the genes related to skeletal development had high Fst values in wild and domestic breeds, and the differentially expressed genes were mainly enriched in the ossification pathway. Our data strongly suggest that the skeletal systems of domestic ducks were changed to adapt to artificial selection for larger sizes. In addition, by combining the genome and transcriptome data, we found that some Fst candidate genes exhibited different expression patterns, and these genes were found to be involved in digestive, immune, and metabolic functions. Conclusions A wide range of phenotypic differences exists between domestic and wild ducks. Through both genome and transcriptome analyses, we found that genes related to the skeletal system in domestic ducks were strongly selected. Our findings provide new insight into duck domestication and selection effects during the domestication.

Objective This research was carried out to investigate the effects of corn particle size on the apparent total tract digestibility (ATTD) of energy and nutrients fed to pigs at four different growth stages and therefore to provide basis for better application of corn in pig feeds. Methods Eighteen weanling piglets, 18 growing barrows, 24 gestating sows and 24 lactating sows were used in this study. Within each stage, pigs were allotted to 1 of 3 or 4 corn-soybean meal diets which were formulated with different corn particle size in a completely randomized design with 6 replicate pigs per diet. Each stage lasted for 19 days, including 7 days for cages adaptation, 7 days for adaptation to diets and followed by 5 days for total collection of feces and urine. Results For nursery and growing stages, the results showed that digestible energy content and ATTD of gross energy (GE), dry matter (DM), neutral detergent fiber (NDF), and acid detergent fiber (ADF) was increased (p

Abstract Antibody-dependent cellular cytotoxicity (ADCC) responses to viral infection are a form of antibody regulated immune responses mediated through the Fc fragment. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered ADCC responses contributes to COVID-19 disease development is currently not well understood. To understand the potential correlation between ADCC responses and COVID-19 disease development, we analyzed the ADCC activity and neutralizing antibody response in 255 individuals ranging from asymptomatic to fatal infections over 1 year post disease. ADCC was elicited by 10 days post-infection, peaked by 11–20 days, and remained detectable until 400 days post-infection. In general, patients with severe disease had higher ADCC activities. Notably, patients who had severe disease and recovered had higher ADCC activities than patients who had severe disease and deceased. Importantly, ADCC activities were mediated by a diversity of epitopes in SARS-COV-2-infected mice and induced to comparable levels against SARS-CoV-2 variants of concern (VOCs) (B.1.1.7, B.1.351, and P.1) as that against the D614G mutant in human patients and vaccinated mice. Our study indicates anti-SARS-CoV-2 ADCC as a major trait of COVID-19 patients with various conditions, which can be applied to estimate the extra-neutralization level against COVID-19, especially lethal COVID-19.

Chicken plumage color is an inheritable phenotype that was naturally and artificially selected for during domestication. The Baicheng You chicken is an indigenous Chinese chicken breed presenting three main feather colors, lavender, black, and yellow plumages. To explore the genetic mechanisms underlying the pigmentation in Baicheng You chickens, we re-sequenced the whole genome of Baicheng You chicken with the three plumage colors. By analyzing the divergent regions of the genome among the chickens with different feather colors, we identified some candidate genomic regions associated with the feather colors in Baicheng You chickens. We found that EGR1, MLPH, RAB17, SOX5, and GRM5 genes were the potential genes for black, lavender, and yellow feathers. MLPH, GRM5, and SOX5 genes have been found to be related to plumage colors in birds. Our results showed that EGR1 is a most plausible candidate gene for black plumage, RAB17, MLPH, and SOX5 for lavender plumage, and GRM5 for yellow plumage in Baicheng You chicken.

Chronic pain (CP) is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage lasting longer than 3 months. CP is the main reason why people seek medical care and exerts an enormous economic burden. Genome-wide expression analysis has revealed that diverse essential genetic elements are altered in CP patients. Although many possible mechanisms of CP have been revealed, we are still unable to meet all the analgesic needs of patients. In recent years, non-coding RNAs (ncRNAs) have been shown to play essential roles in peripheral neuropathy and axon regeneration, which is associated with CP occurrence and development. Multiple key ncRNAs have been identified in animal models of CP, such as microRNA-30c-5p, ciRS-7, and lncRNA MRAK009713. This review highlights different kinds of ncRNAs in the regulation of CP, which provides a more comprehensive understanding of the pathogenesis of the disease. It mainly focuses on the contributions of miRNAs, circRNAs, and lncRNAs to CP, specifically peripheral neuropathic pain (NP), diabetic NP, central NP associated with spinal cord injury, complex regional pain syndrome, inflammatory pain, and cancer-induced pain. In addition, we summarize some potential ncRNAs as novel biomarkers for CP and its complications. With an in-depth understanding of the mechanism of CP, ncRNAs may provide novel insight into CP and could become new therapeutic targets in the future.

Neuroinflammation contributes to the generation of epilepsy and has been proposed as an effective therapeutic target. Recent studies have uncovered the potential effects of the anti-fungal drug miconazole for treating various brain diseases by suppressing neuroinflammation but have not yet been studied in epilepsy. Here, we investigated the effects of different doses of miconazole (5, 20, 80 mg/kg) on seizure threshold, inflammatory cytokines release, and glial cells activation in the pilocarpine (PILO) pentylenetetrazole (PTZ), and intrahippocampal kainic acid (IHKA) models. We demonstrated that 5 and 20 mg/kg miconazole increased seizure threshold, but only 20 mg/kg miconazole reduced inflammatory cytokines release, glial cells activation, and morphological alteration during the early post-induction period (24 h, 3 days). We further investigated the effects of 20 mg/kg miconazole on epilepsy (4 weeks after KA injection). We found that miconazole significantly attenuated cytokines production, glial cells activation, microglial morphological changes, frequency and duration of recurrent hippocampal paroxysmal discharges (HPDs), and neuronal and synaptic damage in the hippocampus during epilepsy. In addition, miconazole suppressed the KA-induced activation of the NF-κB pathway and iNOS production. Our results indicated miconazole to be an effective drug for disease-modifying effects during epilepsy, which may act by attenuating neuroinflammation through the suppression of NF-κB activation and iNOS production. At appropriate doses, miconazole may be a safe and effective approved drug that can easily be repositioned for clinical practice.

Acute lung injury (ALI) is a pulmonary illness with a high burden of morbidity and mortality around the world. Chronic lung diseases also represent life-threatening situations. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a type of long non-coding RNA (lncRNA) and is highly abundant in lung tissues. MALAT1 can function as a competitive endogenous RNA (ceRNA) to impair the microRNA (miRNA) inhibition on targeted messenger RNAs (mRNAs). In this review, we summarized that MALAT1 mainly participates in pulmonary cell biology and lung inflammation. Therefore, MALAT1 can positively or negatively regulate ALI and chronic lung diseases (e.g., chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD), pulmonary fibrosis, asthma, and pulmonary hypertension (PH)). Besides, we also found a MALAT1-miRNA-mRNA ceRNA regulatory network in acute and chronic lung diseases. Through this review, we hope to cast light on the regulatory mechanisms of MALAT1 in ALI and chronic lung disease and provide a promising approach for lung disease treatment.

ObjectiveTo evaluate the efficacy and safety of extracorporeal shockwave therapy (ESWT) for postherpetic neuralgia.DesignRandomized single-blind clinical study.PatientsPatients with postherpetic neuralgia.MethodsPatients were randomly divided into the control group and the ESWT group. The control group received conventional treatment while the ESWT group received conventional treatment and ESWT. The primary outcome is pain degree as assessed by the numeric rating scale (NRS), and secondary outcomes include brief pain inventory (BPI), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and Pittsburgh Sleep Quality Index (PSQI). Data were collected at baseline and at weeks 1, 4, and 12. Linear mixed-effects models were applied to repeated measurement data.ResultsThe scores on the NRS, BPI, SAS, SDS, and PSQI decreased over time in both groups. The NRS and SDS scores of the ESWT group were statistically lower than the control group. There was no time × group interaction in the mixed model analysis. Baseline age was correlated with NRS scores and BPI scores, and invasive treatment was related to PSQI scores, with no interaction effect for baseline confounders observed. No adverse events were observed during the process of this trial.ConclusionExtracorporeal shockwave therapy combined with conventional treatment could relieve pain and improve the psychological state in patients with postherpetic neuralgia without serious adverse effects.

BackgroundWe aimed to evaluate survival, complications, and prognostic factors in patients with IB2/IIA2 (FIGO 2009, bulky early-stage) cervical cancer (CC) who were primarily treated with radical surgery (RS).MethodsFrom January 2011 to January 2018, patients with stage IB2/IIA2 CC who underwent RS ± adjuvant therapy were enrolled and retrospectively evaluated. Survival was estimated using the Kaplan–Meier method. Significance was determined using the log-rank test. Multivariate regression analyses were performed to determine prognostic factors.ResultsOf the 975 enrolled patients, 877 (89.9%) received adjuvant therapy. The median follow-up was 48 months, the 5-year overall survival (OS) was 85.9%, and the 5-year progression-free survival (PFS) rate was 80.8%. Multivariate analysis showed that histological type, pelvic lymph nodes, and para-aortic lymph nodes were independent prognostic factors for PFS and OS. Tumor diameter was also an independent prognostic factor with OS. Recurrent disease developed in 14.3% (140) of patients., including local, distant, and both recurrences in 55 (5.6%), 71 (7.3%), and 14 (1.4%) patients, respectively. Grade 3–4 short-term complications occurred in 196 (20.1%) patients, and long-term complications occurred in 86 (8.8%) patients. Short-term hematological complications occurred in 99 cases (10.2%). No significant differences in non-hematological complications were detected between the RS and RS + adjuvant therapy groups.ConclusionsRS followed by adjuvant therapy is a feasible and effective treatment for IB2/IIA2 CC, with a high 5-year survival rate and an acceptable incidence of complications. Positive pelvic lymph nodes and para-aortic abdominal lymph nodes significantly impact PFS and OS. Evaluation of lymph node status before surgery is important. RS is recommended for patients with negative lymph node metastasis.

Background: Previous observational studies have suggested the involvement of 25-hydroxyvitamin D [25(OH)D] in chronic pain. However, whether the 25(OH)D is a novel target for management, the causality remains unclear.Methods: A two-sample Mendelian randomization (MR) study was conducted to identify the causal association between 25(OH)D and low back pain (LBP). The primary analysis was revealing causality from serum 25(OH)D level (n = 417,580) on LBP (21,140 cases and 227,388 controls). The replicated analysis was performing MR estimates from circulating 25(OH)D concentration (n = 79,366) on LBP experienced last month (118,471 cases and 343,386 controls). Inverse variance weighted (IVW) was used as the main analysis. In addition, we used weighted median and MR-Egger to enhance the robustness. Sensitivity analysis was conducted to evaluate the robustness of MR results.Results: IVW estimation indicated strong evidence that higher serum 25(OH)D levels exerted a protective effect on LBP (OR = 0.89, 95% CI = 0.83–0.96, p = 0.002). Similar trends were also found in replicate analysis (OR = 0.98, 95% CI = 0.96–1.00, p = 0.07). After meta-analysis combining primary and replicated analysis, the causal effect is significant (p = 0.03). Sensitivity analysis supported that the MR estimates were robust.Conclusion: In our MR study, genetically increased serum 25(OH)D levels were associated with a reduced risk of LBP in the European population. This might have an implication for clinicians that vitamin D supplements might be effective for patients with LBP in clinical practice.

Chronic pain remains to be a clinical challenge and is recognized as a major health problem with varying impacts on quality of life. Currently, the first-line therapy for chronic pain is opioids, which are often accompanied by unwanted psychoactive side effects. Thus, new and effective treatments for chronic pain are urgently needed and eagerly pursued. Inflammatory cytokines, especially interleukin-17 (IL-17), are reportedly potential therapeutic targets owing to their pivotal role in chronic pain from the neuroinflammation perspective. Recently, substantial evidence confirmed that IL-17 and IL-17 receptors (IL-17Rs) were increased in neuropathic, inflammatory, and cancer pain models. Notably, IL-17/IL-17R antibodies also reportedly relieve or cure inflammatory- and pain-related diseases. However, existing studies have reported controversial results regarding IL-17/IL-17Rs as potential therapeutic targets in diverse animal models of chronic pain. In this review, we present a summary of published studies and discuss the evidence, from basic to clinical to research, regarding the role and mechanism of action between IL-17 and diverse kinds of chronic pain in animal models and clinical patients. Furthermore, we evaluated IL-17-based therapy as a potential therapeutic strategy for inflammatory- and pain-related disease. Importantly, we also discussed clinical trials of IL-17/IL-17R targeting monoclonal antibodies. Overall, we found that IL-17 is a potential therapeutic target for chronic pain from the perspective of neuroinflammation.

Enhanced recovery after surgery (ERAS) can accelerate patient recovery. However, little research has been done on optimizing the ERAS-related measures and how the measures interact with each other. The Bayesian network (BN) is a graphical model that describes the dependencies between variables and is also a model for uncertainty reasoning. In this study, we aimed to develop a method for optimizing anesthetic decisions in ERAS and then investigate the relationship between anesthetic decisions and outcomes. First, assuming that the indicators used were independent, the effects of combinations of single indicators were analyzed based on BN. Additionally, the impact indicators for outcomes were selected with statistical tests. Then, based on the previously selected indicators, the Bayesian network was constructed using the proposed structure learning method based on Strongly Connected Components (SCC) Local Structure determination by Hill Climbing Twice (LSHCT) and adjusted according to the expert’s knowledge. Finally, the relationship is analyzed. The proposed method is validated by the real clinical data of patients with benign gynecological tumors from 3 hospitals in China. Postoperative length of stay (LOS) and total cost (TC) were chosen as the outcomes. Experimental results show that the ERAS protocol has some pivotal indicators influencing LOS and TC. Identifying the relationship between these indicators can help anesthesiologists optimize the ERAS protocol and make individualized decisions.

Blocking of hydrological connectivity could greatly impact the sediment deposition process and change water and salinity conditions, which in turn affect plant germination, growth, and development in delta wetlands. A 2-year experiment, which included the effects of soil burial, water, and salinity on germination, growth, and production, was conducted to examine the function of hydrological connectivity blocking on the development of Suaeda salsa, a halophyte species. The results demonstrated that soil burial, water, and salinity all had significant effects on seed germination, plant growth, and production (p < 0.05). Seed germination decreased as soil buried depth increased (< 4 cm), and seeds did not germinate successfully when the buried depth was > 4 cm. Seed germination was the highest at 0 cm burial. However, moderate burial was beneficial for seedling emergence; therefore, the survival rate was the lowest when seeds were distributed at the surface (0 cm). Water and salinity both significantly affected the germination, growth, and productivity of S. salsa. Moderate salinity (10–20 g/kg) and fluctuating water (0–10 cm water depth) were suitable for seed germination and plant growth. Low salinity (< 10 g/kg), High salinity (>20 g/kg), drought, and high water levels (long-term flooding with water depth > 10 cm) were not conducive to the growth of S. salsa, and biomass and seed yield were also reduced. As a halophyte, salinity that is too low or too high is unsuitable for S. salsa population. Water and salinity also significantly affected S. salsa population (p < 0.05). In particular, water can offset the hazards of high salt concentrations. Blocking of hydrological connectivity can influence seed germination, yield, and vitality. In this case, S. salsa may have died out from the coastal wetland due to the lack of hydrological connectivity restoration.