Design of dissimilar material joint for defect-free multi-material additive manufacturing via laser-directed energy deposition.

Additive manufacturing technology has advanced beyond creating optimized features, from strengthening materials to make them lightweight to fabricating multi-material combinations that offer functionalities beyond the capabilities of individual materials. In this study, a lamination method for laser-directed energy deposition (LDED) is developed to achieve dense multi-material features, and a design that combines different and dissimilar materials is developed. To evaluate these novel developments, two materials-AISI 316L stainless steel and Inconel 625-are introduced. Tensile specimens, fabricated via multi-material additive manufacturing using LDED, are subjected to tensile tests that are recorded on video for digital image correlation. After the tests, fracture surface analyses of the fractured specimens are performed via scanning electron microscopy, and optical monitoring analyses are performed on the specimens that are not subjected to the tensile tests. The results indicate that the specimens demonstrate varied mechanical properties due to the influence of lamination direction and order, which affect the formation of critical cracks and pores.

Metabolites of pathogenic microorganisms database (MPMdb) and its seed metabolite applications.

Seed metabolites are the combination of essential compounds required by an organism across various potential environmental conditions. The seed metabolites screening framework based on the network topology approach can capture important biological information of species. This study aims to identify comprehensively the relationship between seed metabolites and pathogenic bacteria. A large-scale data set was compiled, describing the seed metabolite sets and metabolite sets of 124,192 pathogenic strains from 34 genera, by constructing genome-scale metabolic models. The enrichment analysis method was used to screen the specific seed metabolites of each species/genus of pathogenic bacteria. The metabolites of pathogenic microorganisms database (MPMdb) (http://qyzhanglab.hzau.edu.cn/MPMdb/) was established for browsing, searching, predicting, or downloading metabolites and seed metabolites of pathogenic microorganisms. Based on the MPMdb, taxonomic and phylogenetic analyses of pathogenic bacteria were performed according to the function of seed metabolites and metabolites. The results showed that the seed metabolites could be used as a feature for microorganism chemotaxonomy, and they could mirror the phylogeny of pathogenic bacteria. In addition, our screened specific seed metabolites of pathogenic bacteria can be used not only for further tapping the nutritional resources and identifying auxotrophies of pathogenic bacteria but also for designing targeted bactericidal compounds by combining with existing antimicrobial agents.IMPORTANCEMetabolites serve as key communication links between pathogenic microorganisms and hosts, with seed metabolites being crucial for microbial growth, reproduction, external communication, and host infection. However, the large-scale screening of metabolites and the identification of seed metabolites have always been the main technical bottleneck due to the low throughput and costly analysis. Genome-scale metabolic models have become a recognized research paradigm to investigate the metabolic characteristics of species. The developed metabolites of pathogenic microorganisms database in this study is committed to systematically predicting and identifying the metabolites and seed metabolites of pathogenic microorganisms, which could provide a powerful resource platform for pathogenic bacteria research.

ACC SYNTHASE4 inhibits gibberellin biosynthesis and FLOWERING LOCUS T expression during citrus flowering.

Flowering is an essential process in fruit trees. Flower number and timing have a substantial impact on the yield and maturity of fruit. Ethylene and gibberellin (GA) play vital roles in flowering, but the mechanism of coordinated regulation of flowering in woody plants by GA and ethylene is still unclear. In this study, a lemon (Citrus limon L. Burm) 1-aminocyclopropane-1-carboxylic acid synthase gene (CiACS4) was overexpressed in Nicotiana tabacum and resulted in late flowering and increased flower number. Further transformation of citrus revealed that ethylene and starch content increased, and soluble sugar content decreased in 35S:CiACS4 lemon. Inhibition of CiACS4 in lemon resulted in effects opposite to that of 35S:CiACS4 in transgenic plants. Overexpression of the CiACS4-interacting protein ETHYLENE RESPONSE FACTOR3 (CiERF3) in N. tabacum resulted in delayed flowering and more flowers. Further experiments revealed that the CiACS4-CiERF3 complex can bind the promoters of FLOWERING LOCUS T (CiFT) and GOLDEN2-LIKE (CiFE) and suppress their expression. Moreover, overexpression of CiFE in N. tabacum led to early flowering and decreased flowers, and ethylene, starch, and soluble sugar contents were opposite to those in 35S:CiACS4 transgenic plants. Interestingly, CiFE also bound the promoter of CiFT. Additionally, GA3 and 1-aminocyclopropanecarboxylic acid (ACC) treatments delayed flowering in adult citrus, and treatment with GA and ethylene inhibitors increased flower number. ACC treatment also inhibited the expression of CiFT and CiFE. This study provides a theoretical basis for the application of ethylene to regulate flower number and mitigate the impacts of extreme weather on citrus yield due to delayed flowering.

Characterization of brain resilience in Alzheimer's disease using polygenic risk scores and further improvement by integrating mitochondria-associated loci.

INTRODUCTION: Identification of high-risk people for Alzheimer's disease (AD) is critical for prognosis and early management. Longitudinal epidemiologic studies have observed heterogeneity in the brain and cognitive aging. Brain resilience was described as above-expected cognitive function. The "resilience" framework has been shown to correlate with individual characteristics such as genetic factors and age. Besides, accumulative evidence has confirmed the association of mitochondria with the pathogenesis of AD. However, it is challenging to assess resilience through genetic metrics, in particular incorporating mitochondria-associated loci. OBJECTIVES: In this paper, we first demonstrated that polygenic risk scores (PRS) could characterize individuals' resilience levels. Then, we indicated that mitochondria-associated loci could improve the performance of PRSs, providing more reliable measurements for the prevention and diagnosis of AD. METHODS: The discovery (N = 1,550) and independent validation samples (N = 2,090) were used to construct nine types of PRSs containing mitochondria-related loci (PRSMT) from both biological and statistical aspects and combined them with known AD risk loci derived from genome-wide association studies (GWAS).Individuals' levels of brain resilience were comprehensively measured by linear regression models using eight pathological characteristics. RESULTS: It was found that PRSs could characterize brain resilience levels (e.g., Pearson correlation test Pmin = 7.96×10-9). Moreover, the performance of PRS models could be efficiently improved by incorporating a small number of mitochondria-related loci (e.g., Pearson correlation test P improved from 1.41×10-3 to 6.09×10-6). PRSs' ability to characterize brain resilience was validated. More importantly, by incorporating some mitochondria-related loci, the performance of PRSs in measuring brain resilience could be significantly improved. CONCLUSION: Our findings imply that mitochondria may play an important role in brain resilience, and targeting mitochondria may open a new door to AD prevention and therapy.

Research progress and potential medical applications of anaplastic lymphoma kinase in treatment of non-small cell lung cancer / 中国药理学通报

During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.

Strong dual-channel nonreciprocal radiation with guided mode resonances.

A dual-channel thermal emitter, which is composed of an InAs layer atop an aluminum grating backed with a continuous aluminum film, is proposed and studied. Two resonant absorption and emission peaks are achieved at different wavelengths, leading to the achievement of dual-channel strong nonreciprocal radiations at two different wavelengths for an applied magnetic field of 2 T when the angle of incidence is 17°. The physical origin is revealed through illustrating the electromagnetic field distributions at both resonances and also verified through impedance matching. In addition, the perfect nonreciprocity remains stable within a wide range of structure parameters, lowering the cost of manufacture. Moreover, the nonreciprocal radiations for different incident angles and different magnetic fields are also investigated in detail. The concept and conclusions proposed here will be interesting for the development of novel energy conversion and capture devices.

The relationship between obesity associated weight-adjusted waist index and the prevalence of hypertension in US adults aged ≥60 years: a brief report.

Objectives: The main objective was to examine the relationship between weight-adjusted waist index (WWI) and the prevalence of hypertension among individuals aged ≥60 years who participated in the NHANES between 2011 and 2018 years. Methods: The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2011-2018. In this population-based study, we focused on participants who were over 60 years old. Data were collected from the aforementioned survey, and the variable of interest was WWI, which was calculated as waist (cm) divided by the square root of body weight (kg). Multivariable logistic regression model was applied to calculate adjusted ORs with 95% CIs in order to explore any possible correlation between WWI and the prevalence of hypertension. Subgroup analysis were used to verify the stability of the relationship between WWI and the prevalence of hypertension. The interaction tests were also conducted in this research. Results: Results revealed that adults aged ≥60 years who were in the highest WWI quartile had significantly higher chances of developing hypertension when compared to those in the lowest quartile, after adjusting for covariates and potential confounders (p < 0.001). Conclusion: These findings suggest that there is a strong correlation between elevated levels of WWI and the risk of developing hypertension among older adults. As such, WWI could serve as a unique and valuable biomarker for identifying hypertension risk at an earlier stage in the older adults population.

How construction and demolition waste management has addressed sustainable development goals: Exploring academic and industrial trends.

With the rapid growth of the construction industry and urbanization, the construction and demolition waste (CDW) has constituted the most major solid waste flow in the world. The unsustainable management of CDW causes serious societal and environmental issues, as well as leads to resource waste, which directly and indirectly impact on United Nations' Sustainable Development Goals (SDGs). Due to the awareness of the destructive effect by CDW, the academic and industry have devoted to offer a sustainable pathway for CDWM, which characterizes minimizing carbon footprints as well as proposing circular approaches. In this context, CDW can be reused, recycled and recovery as a value resource. Therefore, this study proposed a unique research method that combines qualitative and quantitative approaches in the form of bigdata analysis and machine learning, which aims to explore the CDWM related knowledge and innovation from academic and industrial perspective respectively. Especially, what is different trends in CDWM-related of academia and industry between pre- and post-SDGs declaration era(s)? What aspects of SDGs have been addressed by academia and industry in pre- and post-SDGs declaration era(s)? The study witnessed that a 350% increase in the growth of academic literature and a 278% increase in the growth in industrial patents compared to pre-SDGs declaration period. In the academia, the emerging topics of research has shifted to management, circular economy, life cycle assessment, and ETC. Similarly, patent citation illustrated that the attention of stakeholders on CDWM in the construction industry has shifted from a linear point to a circular view. Moreover, the result showed that SDG6 (Clean Water and Sanitation), SDG12 (Responsible Consumption and Production) and SDG11 (Sustainable Cities and Communities) have noted as most seriously addressed concerns by academia and industry.

Dissecting Mitochondrial Mechanisms of Alzheimer's Disease Using Gene Dependency Network and Its Implications for Discovering Nutrients Combatting the Disease.

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia, with its prevalence increasing as the global population ages. AD is a multifactorial and intricate neurodegenerative disease with pathological changes varying from person to person. Because the mechanism of AD is highly controversial, effective treatments remain a distant prospect. Currently, one of the most promising hypotheses posits mitochondrial dysfunction as an early event in AD diagnosis and a potential therapeutic target. OBJECTIVE: Here, we adopted a systems medicine strategy to explore the mitochondria-related mechanisms of AD. Then, its implications for discovering nutrients combatting the disease were demonstrated. METHODS: We employed conditional mutual information (CMI) to construct AD gene dependency networks. Furthermore, the GeneRank algorithm was applied to prioritize the gene importance of AD patients and identify potential anti-AD nutrients targeting crucial genes. RESULTS: The results suggested that two highly interconnected networks of mitochondrial ribosomal proteins (MRPs) play an important role in the regulation of AD pathology. The close association between mitochondrial ribosome dysfunction and AD was identified. Additionally, we proposed seven nutrients with potential preventive and ameliorative effects on AD, five of which have been supported by experimental reports. CONCLUSIONS: Our study explored the important regulatory role of MRP genes in AD, which has significant implications for AD prevention and treatment.

Identification of necroptosis-related genes in Parkinson's disease by integrated bioinformatics analysis and experimental validation.

Background: Parkinson's disease (PD) is the second most common neurodegeneration disease worldwide. Necroptosis, which is a new form of programmed cell death with high relationship with inflammation, plays a vital role in the progression of PD. However, the key necroptosis related genes in PD are not fully elucidated. Purpose: Identification of key necroptosis-related genes in PD. Method: The PD associated datasets and necroptosis related genes were downloaded from the GEO Database and GeneCards platform, respectively. The DEGs associated with necroptosis in PD were obtained by gap analysis, and followed by cluster analysis, enrichment analysis and WGCNA analysis. Moreover, the key necroptosis related genes were generated by PPI network analysis and their relationship by spearman correlation analysis. Immune infiltration analysis was used for explore the immune state of PD brain accompanied with the expression levels of these genes in various types of immune cells. Finally, the gene expression levels of these key necroptosis related genes were validated by an external dataset, blood samples from PD patients and toxin-induced PD cell model using real-time PCR analysis. Result: Twelve key necroptosis-related genes including ASGR2, CCNA1, FGF10, FGF19, HJURP, NTF3, OIP5, RRM2, SLC22A1, SLC28A3, WNT1 and WNT10B were identified by integrated bioinformatics analysis of PD related dataset GSE7621. According to the correlation analysis of these genes, RRM2 and WNT1 were positively and negatively correlated with SLC22A1 respectively, while WNT10B was positively correlated with both OIF5 and FGF19. As the results from immune infiltration analysis, M2 macrophage was the highest population of immune cell in analyzed PD brain samples. Moreover, we found that 3 genes (CCNA1, OIP5 and WNT10B) and 9 genes (ASGR2, FGF10, FGF19, HJURP, NTF3, RRM2, SLC22A1, SLC28A3 and WNT1) were down- and up- regulated in an external dataset GSE20141, respectively. All the mRNA expression levels of these 12 genes were obviously upregulated in 6-OHDA-induced SH-SY5Y cell PD model while CCNA1 and OIP5 were up- and down- regulated, respectively, in peripheral blood lymphocytes of PD patients. Conclusion: Necroptosis and its associated inflammation play fundamental roles in the progression of PD and these identified 12 key genes might be served as new diagnostic markers and therapeutic targets for PD.

Transporter proteins knowledge graph construction and its application in drug development.

Transporters are the main determinant for pharmacokinetics characteristics of drugs, such as absorption, distribution, and excretion of drugs in humans. However, it is difficult to perform drug transporter validation and structure analysis of membrane transporter proteins by experimental methods. Many studies have demonstrated that knowledge graphs (KG) could effectively excavate potential association information between different entities. To improve the effectiveness of drug discovery, a transporter-related KG was constructed in this study. Meanwhile, a predictive frame (AutoInt_KG) and a generative frame (MolGPT_KG) were established based on the heterogeneity information obtained from the transporter-related KG by the RESCAL model. Natural product Luteolin with known transporters was selected to verify the reliability of the AutoInt_KG frame, its ROC-AUC (1:1), ROC-AUC (1:10), PR-AUC (1:1), PR-AUC (1:10) are 0.91, 0.94, 0.91 and 0.78, respectively. Subsequently, the MolGPT_KG frame was constructed to implement efficient drug design based on transporter structure. The evaluation results showed that the MolGPT_KG could generate novel and valid molecules and that these molecules were further confirmed by molecular docking analysis. The docking results showed that they could bind to important amino acids at the active site of the target transporter. Our findings will provide rich information resources and guidance for the further development of the transporter-related drugs.

Periplaneta Americana Extract Ameliorates LPS-induced Acute Lung Injury Via Reducing Inflammation and Oxidative Stress.

OBJECTIVE: Acute lung injury (ALI) is an acute clinical syndrome characterized by uncontrolled inflammation response, which causes high mortality and poor prognosis. The present study determined the protective effect and underlying mechanism of Periplaneta americana extract (PAE) against lipopolysaccharide (LPS)-induced ALI. METHODS: The viability of MH-S cells was measured by MTT. ALI was induced in BALB/c mice by intranasal administration of LPS (5 mg/kg), and the pathological changes, oxidative stress, myeloperoxidase activity, lactate dehydrogenase activity, inflammatory cytokine expression, edema formation, and signal pathway activation in lung tissues and bronchoalveolar lavage fluid (BALF) were examined by H&E staining, MDA, SOD and CAT assays, MPO assay, ELISA, wet/dry analysis, immunofluorescence staining and Western blotting, respectively. RESULTS: The results revealed that PAE obviously inhibited the release of proinflammatory TNF-α, IL-6 and IL-1ß by suppressing the activation of MAPK/Akt/NF-κB signaling pathways in LPS-treated MH-S cells. Furthermore, PAE suppressed the neutrophil infiltration, permeability increase, pathological changes, cellular damage and death, pro-inflammatory cytokines expression, and oxidative stress upregulation, which was associated with its blockage of the MAPK/Akt/NF-κB pathway in lung tissues of ALI mice. CONCLUSION: PAE may serve as a potential agent for ALI treatment due to its anti-inflammatory and anti-oxidative properties, which correlate to the blockage of the MAPK/NF-κB and AKT signaling pathways.

Evolution-strengthened knowledge graph enables predicting the targetability and druggability of genes.

Identifying promising targets is a critical step in modern drug discovery, with causative genes of diseases that are an important source of successful targets. Previous studies have found that the pathogeneses of various diseases are closely related to the evolutionary events of organisms. Accordingly, evolutionary knowledge can facilitate the prediction of causative genes and further accelerate target identification. With the development of modern biotechnology, massive biomedical data have been accumulated, and knowledge graphs (KGs) have emerged as a powerful approach for integrating and utilizing vast amounts of data. In this study, we constructed an evolution-strengthened knowledge graph (ESKG) and validated applications of ESKG in the identification of causative genes. More importantly, we developed an ESKG-based machine learning model named GraphEvo, which can effectively predict the targetability and the druggability of genes. We further investigated the explainability of the ESKG in druggability prediction by dissecting the evolutionary hallmarks of successful targets. Our study highlights the importance of evolutionary knowledge in biomedical research and demonstrates the potential power of ESKG in promising target identification. The data set of ESKG and the code of GraphEvo can be downloaded from https://github.com/Zhankun-Xiong/GraphEvo.

A multi-band nonreciprocal thermal emitter involving a Weyl semimetal with a Thue-Morse multilayer.

The giant enhancement of multi-band nonreciprocal radiation based on the Weyl semimetal-dielectric spacer-Thue-Morse multilayer-metallic mirror structure, is investigated. As an illustration, a novel dual-band nonreciprocal thermal emitter based on the proposed scheme is designed and studied. The results show that two pairs of nonoverlapping absorptivity and emissivity spectra could be realized, which results in the realization of strong dual-band nonreciprocal radiation. The physical origin behind this phenomenon is revealed by the amplitude distribution of the magnetic field and confirmed by impedance matching theory. The dependence of the nonreciprocal radiation properties on the incident angle and the structure dimensions is investigated, and it is shown that the nonreciprocal performance remains stable in a large range of dimensions, which lowers the costs of fabrication. In addition, a multi-band nonreciprocal thermal emitter with a band number larger than two can be easily achieved by increasing the generation of the Thue-Morse multilayer. It is believed that the proposed scheme will promote the development of novel multi-band nonreciprocal thermal emitters.

Light-Triggered Reversible Tuning of Second-Harmonic Generation in a Photoactive Plasmonic Molecular Nanocavity.

The ultrasmall mode volume and ultralarge local field enhancement of compact plasmonic nanocavities have been widely explored to amplify a variety of optical phenomena at the nanoscale. Other than passively generating near-field enhancements, dynamic tuning of their intensity and associated nonlinear optical processes such as second-harmonic generation (SHG) play vital roles in the field of active nanophotonics. Here we apply a host-guest molecular complex to construct a photoswitchable molecule-sandwiched metallic particle-on-film nanocavity (MPoFN) and demonstrate both light-controlled linear and nonlinear optical tuning. Under alternating illumination of ultraviolet (UV) and visible light, the photoactive plasmonic molecular nanocavity shows reversible switching of both surface-enhanced Raman scattering (SERS) and plasmon resonance. Surprisingly, we observe more significant modulation of SHG from this photoactive MPoFN, which can be explained qualitatively by the quantum conductivity theory (QCT). Our study could pave the way for developing miniaturized integrated optical circuits for ultrafast all-optical information processing and communication.

Tunable near-perfect nonreciprocal radiation with a Weyl semimetal and graphene.

A tunable near-perfect nonreciprocal thermal emitter, consisting of a dielectric plane and a monolayer graphene sandwiched between a subwavelength grating and a Weyl semimetal plane, is proposed and investigated. Near-complete nonreciprocal radiation can be achieved at resonance, breaking the traditional Kirchhoff's law. The underlying physical mechanism, resulting from a guided mode resonance, is disclosed by illustrating the magnetic field distribution. Moreover, the strong nonreciprocity remains well within a wide range of geometrical parameters. What's more, the performance of the near-perfect spectral nonreciprocity can be flexibly controlled in a wide spectral range through varying the Fermi level of graphene and the axial vector of the Weyl semimetal, which reduces the cost and should be interesting for real application. The conclusions of this paper should prompt the further development of tunable nonreciprocal thermal emitters.

Citrus ACC synthase CiACS4 regulates plant height by inhibiting gibberellin biosynthesis.

Dwarfism is an agronomic trait that has substantial effects on crop yield, lodging resistance, planting density, and a high harvest index. Ethylene plays an important role in plant growth and development, including the determination of plant height. However, the mechanism by which ethylene regulates plant height, especially in woody plants, remains unclear. In this study, a 1-aminocyclopropane-1-carboxylic acid synthase (ACC) gene (ACS), which is involved in ethylene biosynthesis, was isolated from lemon (Citrus limon L. Burm) and named CiACS4. Overexpression of CiACS4 resulted in a dwarf phenotype in Nicotiana tabacum and lemon and increased ethylene release and decreased gibberellin (GA) content in transgenic plants. Inhibition of CiACS4 expression in transgenic citrus significantly increased plant height compared with the controls. Yeast two-hybrid assays revealed that CiACS4 interacted with an ethylene response factor (ERF), CiERF3. Further experiments revealed that the CiACS4-CiERF3 complex can bind to the promoters of 2 citrus GA20-oxidase genes, CiGA20ox1 and CiGA20ox2, and suppress their expression. In addition, another ERF transcription factor, CiERF023, identified using yeast one-hybrid assays, promoted CiACS4 expression by binding to its promoter. Overexpression of CiERF023 in N. tabacum caused a dwarfing phenotype. CiACS4, CiERF3, and CiERF023 expression was inhibited and induced by GA3 and ACC treatments, respectively. These results suggest that the CiACS4-CiERF3 complex may be involved in the regulation of plant height by regulating CiGA20ox1 and CiGA20ox2 expression levels in citrus.

Unveil of the role of fungal taxa in iron(III) reduction in paddy soil.

Hitherto, research on iron(III)-reduction has mainly focused on bacteria rather than fungal communities. To acquire insight into fungi involved in iron(III) reduction, typical organic matters (containing cellulose, glucose, lactate, and acetate) and ferrihydrite were used as electron donors and acceptors, respectively, in the presence of antibiotics. After antibiotic addition, microbial iron(III) reduction was still detected at quite high rates. In comparison, rates of iron(III) reduction were significantly lower in cellulose-amended groups than those with glucose, lactate, and acetate under the antibiotic-added condition. Patterns of intermediate (e.g., acetate, pyruvate, glucose) turnover were markedly different between treatments with and without antibiotics during organic degradation. A total of 20 genera of potential respiratory and fermentative iron(III)-reducing fungi were discovered based on ITS sequencing and genome annotation. This study provided an insight into the diversity of iron(III)-reducing fungi, indicating the underestimated contribution of fungi to iron and the coupled carbon biogeochemical cycling in environments.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair (version 2023) / 中华创伤杂志

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.