Prognostic values of left atrial strain analyzed by four-dimensional speckle tracking echocardiography in uremia with preserved ejection fraction.

Little is known about the prognostic value of left atrial strain by four-dimensional speckle-tracking echocardiography in end-stage renal disease patients with preserved left ventricular ejection fraction. This prospective study collected clinical and echocardiographic data from 80 stable dialysis patients (mean age 57 ± 10 years; 62.5% men). All patients underwent the dedicated four-dimensional speckle-tracking echocardiography to measure LASr (peak longitudinal strain of reservoir function), LAScd (peak longitudinal strain of conduit function), LASct (peak longitudinal strain of contractile function), LASr_c (peak circumferential strain of reservoir function), LAScd_c (peak circumferential strain of conduit function) and LASct_c (peak circumferential strain of contractile function). These patients were enrolled from August 2021 to August 2023 and followed-up for 19 months (interquartile-range 15 to 20 months). The primary outcome was a composite of all-cause mortality or major adverse cardiovascular events (MACEs). The study patients were classified into event (developed mortality or MACEs) and event-free group according to the primary outcome. Multivariate Cox regression analysis was used to investigate risk factors for all-cause mortality or MACEs. The event group had lower LASr (16.4% vs. 21.2%, P = 0.0003), LASct (8.2% vs. 11.2%, P = 0.01), LASr_c (25.2% vs. 35.0%, P = 0.0004) and LASct_c (14.9% vs. 20.9%, P = 0.001) than the event-free group. Using optimal cut-off value determined by ROC curve, the less LASr (LASr < 18.5%), LASct (LASct < 8.5%), LASr_c (LASr_c < 28.5%), and LASct_c (LASct_c < 17.5%) group had a higher mortality or MACEs rate. Multivariate cox regression analyses revealed that LASr (HR = 0.81, 95% CI [0.17; 0.91], P = 0.0005, per 1% increase) and LASr_c (HR = 0.93, 95% CI [0.87; 0.98], P = 0.01, per 1% increase) were independent predictors of all-cause mortality or MACEs. Less peak longitudinal and circumferential strains of reservoir function are predictive of poor prognosis among end-stage renal disease patients with preserved left ventricular ejection fraction.

Gestational Diabetes Mellitus-Induced Milk Fat Globule Membrane Protein Changes of Human Mature Milk Based on TMT Proteomic Analysis.

Breastfeeding by mothers with gestational diabetes mellitus (GDM) has been shown to reduce maternal insulin demands and diminish the risks of diabetes in infants, leading to improved long-term health outcomes. Milk fat globule membrane (MFGM) proteins play a crucial role in influencing the immunity and cognitive development of infants. Understanding the alterations in MFGM proteins in breastmilk from mothers with GDM is essential for enhancing their self-efficacy and increase breastfeeding rates. The objective of this study is to investigate and compare MFGM proteins in milk from mothers with GDM and without based on tandem mass tag (TMT) labeling and liquid chromatography tandem mass spectrometry (LC-MS) techniques. A total of 5402 proteins were identified, including 4 upregulated proteins and 24 downregulated proteins. These significantly altered proteins were found to be associated with human diseases, cellular processes, and metabolism pathways. Additionally, the oxidative phosphorylation pathway emerged as the predominant pathway through Gene Set Enrichment Analysis (GSEA) involving all genes.

The timeline of overseas imported cases acts as a strong indicator of dengue outbreak in mainland China.

The emergence of dengue viruses in new, susceptible human populations worldwide is increasingly influenced by a combination of local and global human movements and favorable environmental conditions. While various mathematical models have explored the impact of environmental factors on dengue outbreaks, the significant role of human mobility both internationally and domestically in transmitting the disease has been less frequently addressed. In this context, we introduce a modeling framework that integrates the effects of international travel-induced imported cases, climatic conditions, and local human movements to assess the spatiotemporal dynamics of dengue transmission. Utilizing the generation matrix method, we calculate the basic reproduction number and its sensitivity to various model parameters. Through numerical simulations using data on climate, human mobility, and reported dengue cases in mainland China, our model demonstrates a good agreement with observed data upon validation. Our findings reveal that while climatic conditions are a key driver for the rapid dengue transmission, human mobility plays a crucial role in its local spread. Importantly, the model highlights the significant impact of imported cases from overseas on the initiation of dengue outbreaks and their contribution to increasing the disease incidence rate by 34.6%. Furthermore, the analysis identifies that dengue cases originating from regions, such as Cambodia and Myanmar internationally, and Guangzhou and Xishuangbanna domestically, have the potential to significantly increase the disease burden in mainland China. These insights emphasize the critical need to include data on imported cases and domestic travel patterns in disease outbreak models to improve the precision of predictions, thereby enhancing dengue prevention, surveillance, and response strategies.

Association between organophosphorus insecticides exposure and osteoarthritis in patients with arteriosclerotic cardiovascular disease.

BACKGROUND: Organic phosphorus insecticides (OPPs) are a class of environmental pollutants widely used worldwide with potential human health risks. We aimed to assess the association between exposure to OPPs and osteoarthritis (OA) particularly in participants with atherosclerotic cardiovascular disease (ASCVD). METHODS: Participants' information was obtained from data in the National Health and Nutrition Examination (NHANES). Weighted logistic regression models were utilized to detect associations between OPPs metabolites and OA. Restricted cubic spline plots (RCS) were drawn to visualize the dose-response relationship between each metabolite and OA prevalence. Weighted quantile sum (WQS) regression and Bayesian kernel-machine regression (BKMR), were applied to investigate the joint effect of mixtures of OPPs on OA. RESULTS: A total of 6871 samples were included in our study, no significant associations between OPPs exposure and OA incidence were found in whole population. However, in a subset of 475 individuals with ASCVD, significant associations between DMP (odds ratio [OR] as a continuous variable = 1.22, 95% confidence interval [CI]: 1.07,1.28), DEP ((odds ratio [OR] of the highest tertile compared to the lowest = 2.43, 95% confidence interval [CI]: 1.21,4.86), and OA were observed. DMP and DEP showed an increasing dose-response relationship to the prevalence of OA, while DMTP, DETP, DMDTP and DEDTP showed a nonlinear relationship. Multi-contamination modeling revealed a 1.34-fold (95% confidence intervals:0.80, 2.26) higher prevalence of OA in participants with high co-exposure to OPPs compared to those with low co-exposure, with a preponderant weighting (0.87) for the dimethyl dialkyl phosphate metabolites (DMAPs). The BKMR also showed that co-exposure of mixed OPPs was associated with an increased prevalence of OA, with DMP showing a significant dose-response relationship. CONCLUSION: High levels of urine dialkyl phosphate metabolites (DAP) of multiple OPPs are associated with an increased prevalence of OA in patients with ASCVD, suggesting the need to prevent exposure to OPPs in ASCVD patients to avoid triggering OA and further avoid the occurrence of cardiovascular events caused by OA.

Lysozyme 1 Inflamed CCR2+ Macrophages Promote Obesity-Induced Cardiac Dysfunction.

BACKGROUND: Macrophages are key players in obesity-associated cardiovascular diseases, which are marked by inflammatory and immune alterations. However, the pathophysiological mechanisms underlying macrophage's role in obesity-induced cardiac inflammation are incompletely understood. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response. METHODS: In this study, we used single-cell RNA-sequencing analysis of Cd45+CD11b+F4/80+ cardiac macrophages to explore the heterogeneity of cardiac macrophages. The CCR2+ (C-C chemokine receptor 2) macrophages were specifically removed by a dual recombinase approach, and the macrophage CCR2 was deleted to investigate their functions. We also performed cleavage under target and tagmentation analysis, chromatin immunoprecipitation-polymerase chain reaction, luciferase assay, and macrophage-specific lentivirus transfection to define the impact of lysozyme C in macrophages on obesity-induced inflammation. RESULTS: We find that the Ccr2 cluster undergoes a functional transition from homeostatic maintenance to proinflammation. Our data highlight specific changes in macrophage behavior during cardiac dysfunction under metabolic challenge. Consistently, inducible ablation of CCR2+CX3CR1+ macrophages or selective deletion of macrophage CCR2 prevents obesity-induced cardiac dysfunction. At the mechanistic level, we demonstrate that the obesity-induced functional shift of CCR2-expressing macrophages is mediated by the CCR2/activating transcription factor 3/lysozyme 1/NF-κB (nuclear factor kappa B) signaling. Finally, we uncover a noncanonical role for lysozyme 1 as a transcription activator, binding to the RelA promoter, driving NF-κB signaling, and strongly promoting inflammation and cardiac dysfunction in obesity. CONCLUSIONS: Our findings suggest that lysozyme 1 may represent a potential target for the diagnosis of obesity-induced inflammation and the treatment of obesity-induced heart disease.

Transcriptomic Analysis Under Drought and Salt Stress Provides Insight into Genes Putatively Involved in Ginsenoside Biosynthesis in Panax japonicus Meyer.

Panax japonicus Meyer, a perennial herb of the dicotyledonaceae family Araliaceae, is a rare folk traditional Chinese medicine, known as "the king of herbal medicine" in China. To understand the genes involved in secondary pathways under drought and salt stress, the transcriptomic analysis of P. japonicus is of vital importance. The transcriptome of underground rhizomes, stems, and leaves under drought and salt stress in P. japonicus were performed using the Illumina HiSeq platform. After de novo assembly of transcripts, expression profiling and identified differentially expressed genes (DEGs) were performed. Furthermore, putative functions of identified DEGs correlated with ginsenoside in P. japonicus were explored using Gene Ontology terms and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis. A total of 221,804 unigenes were obtained from the transcriptome of P. japonicus. The further analysis revealed that 10,839 unigenes were mapped to 91 KEGG pathways. Furthermore, a total of two metabolic pathways of P. japonicus in response to drought and salt stress related to triterpene saponin synthesis were screened. The sesquiterpene and triterpene metabolic pathways were annotated and finally putatively involved in ginsenoside content and correlation analysis of the expression of these genes were analyzed to identify four genes, ß-amyrin synthase, isoprene synthase, squalene epoxidase, and 1-deoxy-D-ketose-5-phosphate synthase, respectively. Our results paves the way for screening highly expressed genes and mining genes related to triterpenoid saponin synthesis. It also provides valuable references for the study of genes involved in ginsenoside biosynthesis and signal pathway of P. japonicus.

The critical role of toll-like receptor 4 in bone remodeling of osteoporosis: from inflammation recognition to immunity.

Osteoporosis is a common chronic metabolic bone disorder. Recently, increasing numbers of studies have demonstrated that Toll-like receptor 4 (TLR4, a receptor located on the surface of osteoclasts and osteoblasts) plays a pivotal role in the development of osteoporosis. Herein, we performed a comprehensive review to summarize the findings from the relevant studies within this topic. Clinical data showed that TLR4 polymorphisms and aberrant TLR4 expression have been associated with the clinical significance of osteoporosis. Mechanistically, dysregulation of osteoblasts and osteoclasts induced by abnormal expression of TLR4 is the main molecular mechanism underlying the pathological processes of osteoporosis, which may be associated with the interactions between TLR4 and NF-κB pathway, proinflammatory effects, ncRNAs, and RUNX2. In vivo and in vitro studies demonstrate that many promising substances or agents (i.e., methionine, dioscin, miR-1906 mimic, artesunate, AEG-1 deletion, patchouli alcohol, and Bacteroides vulgatus) have been able to improve bone metabolism (i.e., inhibits bone resorption and promotes bone formation), which may partially attribute to the inhibition of TLR4 expression. The present review highlights the important role of TLR4 in the clinical significance and the pathogenesis of osteoporosis from the aspects of inflammation and immunity. Future therapeutic strategies targeting TLR4 may provide a new insight for osteoporosis treatment.

Mechanism and ecological environmental risk assessment of peroxymonosulfate for the treatment of heavy metals in soil.

Oxidation technologies based on peroxymonosulfate (PMS) have been effectively used for the remediation of soil organic pollutants due to their high efficiency. However, the effects of advanced PMS-based oxidation technologies on other soil pollutants, such as heavy metals, remain unknown. In this study, changes in the form of heavy metals in soil after using PMS and the risk of pollution to the ecological environment were investigated. Furthermore, two risk assessment methods, the mung bean germination toxicity test and groundwater leaching soil column test, were employed to evaluate the soil before and after PMS treatment. The results showed that PMS has a strong ability to degrade complex compounds, enabling the transformation of heavy metals, such as Cd, Pb, and Zn, from stable to active states in the soil. The risk assessments showed that PMS treatment activated heavy metals in the soil, which delayed the growth of plants, increased heavy metal content in plant tissues and the risk of groundwater pollution. These findings provide a new perspective for understanding the effects of PMS on soil, thus facilitating the sustained and reliable development of future research in the field of advanced oxidation applied to soil treatment.

A convenient and reproducible protocol for acquisition of the hepatocyte phase for liver function-impaired patients in gadoxetic acid disodium-enhanced magnetic resonance imaging.

Background: The hepatocyte phase (HCP) in gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) plays an important role in the detection and characterization of liver lesions, treatment planning, and liver function evaluation. However, the imaging protocol is complicated and time-consuming. This cross-sectional study aimed to develop a convenient and reproducible protocol for the HCP acquisition in Gd-EOB-DTPA-enhanced MRI. Methods: A total of 107 patients were prospectively included and assigned to three groups based on Child-Pugh (CP) classification, with 37, 40, and 30 in the non-cirrhosis, CP A, and CP B groups, respectively. Dynamic HCPs were acquired every 5 min after the Gd-EOB-DTPA administration and ended in 25 min in non-cirrhosis patients and 40 min in cirrhotic patients. The HCP acquired 5 min after the initial visualization of the intrahepatic bile duct (IBD) was selected from the dynamic HCPs as the adequate HCP (HCPproposed) and the corresponding acquisition time was recorded as Timeproposed. In addition, according to the 2016 Expert Consensus (EC) on the definition of the adequate HCP from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the adequate HCPEC and the corresponding TimeEC were also determined from the dynamic HCPs. The hepatic relative enhancement ratio (RER), the contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of hepatic focal lesions in the HCPEC and HCPproposed images, as well as the TimeEC and Timeproposed were compared by the paired t-test for the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed was compared by the χ2 test. Results: The RER, CNR, and SNR showed no significant difference between the HCPEC and HCPproposed in all three groups (all P>0.05). The paired differences between TimeEC and Timeproposed were 1.08±3.56 min (P=0.07), 2.88±4.22 min (P<0.001), and 5.83±5.27 min (P<0.001) in the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed were 0.804 (86/107) and 0.962 (103/107), respectively (χ²=13.09, P=0.001). Conclusions: The adequate HCP could be acquired 5 min after the initial visualization of the IBD, which could serve as a convenient and reproducible protocol for the HCP imaging.

Stabilizing 3D-printed metal alloys.

A design strategy overcomes the strength-ductility trade-off in alloy manufacturing.

Fish microplastic ingestion may induce tipping points of aquatic ecosystems.

Microplastics can be ingested by a wide range of aquatic animals. Extensive studies have demonstrated that microplastic ingestion-albeit often not lethal-can affect a range of species life-history traits. However, it remains unclear how the sublethal effects of microplastics on individual levels scale up to influence ecosystem-level dynamics through cascading trophic interactions. Here we employ a well-studied, empirically fed three-species trophic chain model, which was parameterized to mimic a common type of aquatic ecosystems to examine how microplastic ingestion by fish on an intermediate trophic level can produce cascading effects on the species at both upper and lower trophic levels. We show that gradually increasing microplastics in the ingested substances of planktivorous fish may cause population structure effects such as skewed size distributions (i.e. reduced average body length vs. increased maximal body size), and induce abrupt declines in fish biomass and reproduction. Our model analysis demonstrates that these abrupt changes correspond to an ecosystem-level tipping point, crossing which difficult-to-reverse ecosystem degradation can happen. Importantly, microplastic pollution may interact with other anthropogenic stressors to reduce safe operating space of aquatic ecosystems. Our work contributes to better understanding complex effects of microplastic pollution and anticipating tipping points of aquatic ecosystems in a changing world. It also calls attention to an emerging threat that novel microplastic contaminants may lead to unexpected and abrupt degradation of aquatic ecosystems, and invites systematic studies on the ecosystem-level consequences of microplastic exposure.

Monte Carlo simulations and phantom modeling for spatial frequency domain imaging of surgical wound monitoring.

Significance: Postoperative surgical wound infection is a serious problem around the globe, including in countries with advanced healthcare systems, and a method for early detection of infection is urgently required. Aim: We explore spatial frequency domain imaging (SFDI) for distinguishing changes in surgical wound healing based on the tissue scattering properties and surgical wound width measurements. Approach: A comprehensive numerical method is developed by applying a three-dimensional Monte Carlo simulation to a vertical heterogeneous wound model. The Monte Carlo simulation results are validated using resin phantom imaging experiments. Results: We report on the SFDI lateral resolution with varying reduced scattering value and wound width and discuss the partial volume effect at the sharp vertical boundaries present in a surgical incision. The detection sensitivity of this method is dependent on spatial frequency, wound reduced scattering coefficient, and wound width. Conclusions: We provide guidelines for future SFDI instrument design and explanation for the expected error in SFDI measurements.

LMNB1 targets FOXD1 to promote progression of prostate cancer.

Forkhead box D1 (FOXD1) expression is upregulated in various types of human cancer. To the best of our knowledge, the roles of FOXD1 in prostate cancer (PC) remain largely unknown. The Cancer Genome Atlas dataset was used for the bioinformatics analysis of FOXD1 in PC. FOXD1 expression levels in normal immortalized human prostate epithelial cells (RWPE-1) and prostate cancer cells were detected by reverse transcription-quantitative PCR. PC cell viability was detected using Cell Counting Kit-8 assay. Transwell assays were performed to assess the migration and invasion of PC cells. Luciferase reporter gene assay was used to validate the association between FOXD1 and lamin (LMN)B1. LMNB1 is an important part of the cytoskeleton, which serves an important role in the process of tumor occurrence and development, regulating apoptosis and DNA repair. FOXD1 expression was upregulated in PC tissues, with its high expression being associated with clinical stage and survival in PC. Knockdown of FOXD1 inhibited viability, migration and invasion of PC cells. FOXD1 positively regulated LMNB1 expression. The effect of FOXD1 knockdown on PC cells was reversed by LMNB1 overexpression. In conclusion, FOXD1, positively regulated by LMNB1, served as an oncogene in PC and may be a potential biomarker and treatment target for PC.

Gallic acid improves the metformin effects on diabetic kidney disease in mice.

OBJECTIVES: Metformin is an antidiabetic agent that is used as the first-line treatment of type 2 diabetes mellitus. Gallic acid is a type of phenolic acid that has been shown to be a potential drug candidate to treat diabetic kidney disease, an important complication of diabetes. We aimed to test whether a combination of gallic acid and metformin can exert synergetic effect on diabetic kidney disease in diabetic mice model. METHODS: Streptozotocin (65 mg/kg) intraperitoneal injection was used to induce diabetic kidney disease in mice. The diabetic mice were treated with saline (Vehicle), gallic acid (GA) (30 mg/kg), metformin (MET) (200 mg/kg), or the combination of gallic acid (30 mg/kg) and metformin (200 mg/kg) (GA + MET). RESULTS: Our results demonstrated that compared to the untreated diabetic mice, all three strategies (GA, MET, and GA + MET) exhibited various effects on improving renal morphology and functions, reducing oxidative stress in kidney tissues, and restoring AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1) signaling in kidney tissues of diabetic mice. Notably, the combination strategy (GA + MET) provided the most potent renal protection effects than any single strategies (GA or MET). CONCLUSION: Our results support the hypothesis that gallic acid might serve as a potential supplement to metformin to enhance the therapeutical effect of metformin.

Roles of the HIF-1α pathway in the development and progression of keloids.

Keloids, a pathological scar that is induced by the consequence of aberrant wound healing, is still a major global health concern for its unsatisfactory treatment outcomes. HIF-1α, a main regulator of hypoxia, mainly acts through some proteins or signaling pathways and plays important roles in a variety of biological processes. Accumulating evidence has shown that HIF-1α played a crucial role in the process of keloid formation. In this review, we attempted to summarize the current knowledge on the association between HIF-1α expression and the development and progression of keloids. Through a comprehensive analysis, the molecular mechanisms underlying HIF-1α in keloids were shown to be correlated to the proliferation of fibroblasts, angiogenesis, and collagen deposits. The affected proteins and the signaling pathways were multiple. For instance, HIF-1α was reported to promote keloids formation by enhancing angiogenesis, fibroblast proliferation, and collagen deposition through the activation of periostin PI3K/Akt, TGF-ß/Smad and TLR4/MyD88/NF-κB pathway. However, the specific effects of HIF-1α on keloids keloid illnesses in clinical practice is are entirely unclear, and further studies in clinical trials are still warranted. Therefore, an in-depth understanding of the biological mechanisms of HIF-1α in keloid formation is significant to develop promising therapeutic targets for the treatment of keloids in clinical practice.

The Role of Lithium in the Aging Precipitation Process of Al-Zn-Mg-Cu Alloys and Its Effect on the Properties.

It is well known that the development of lightweight alloys with improved comprehensive performance and application value are the future development directions for the ultra-high-strength 7xxx series Al-Zn-Mg-Cu alloys used in the aircraft field. As the lightest metal element in nature, lithium (Li) has outstanding advantages in reducing the density and increasing the elastic modulus in aluminum alloys, so Al-Zn-Mg-Cu alloys containing Li have gained widespread attention. Furthermore, since the Al-Zn-Mg-Cu alloy is usually strengthened by aging treatment, it is crucial to understand how Li addition affects its aging precipitation process. As such, in this article, the effects and mechanism of Li on the aging precipitation behavior and the impact of Li content on the aging precipitation phase of Al-Zn-Mg-Cu alloys are briefly reviewed, and the influence of Li on the service properties, including mechanical properties, wear resistance, and fatigue resistance, of Al-Zn-Mg-Cu alloys are explained. In addition, the corresponding development prospects and challenges of the Al-Zn-Mg-Cu-Li alloy are also proposed. This review is helpful to further understand the role of Li in Al-Zn-Mg-Cu alloys and provides a reference for the development of high-strength aluminum alloys containing Li with good comprehensive properties.

Defect Engineering of a High-Entropy Metallic Glass Surface for High-Performance Overall Water Splitting at Ampere-Level Current Densities.

Platinum-based electrocatalysts possess high water electrolysis activity and are essential components for hydrogen evolution reaction (HER). A major challenge, however, is how to break the cost-efficiency trade-off. Here, a novel defect engineering strategy is presented to construct a nanoporous (FeCoNiB0.75 )97 Pt3 (atomic %) high-entropy metallic glass (HEMG) with a nanocrystalline surface structure that contains large amounts of lattice distortion and stacking faults to achieve excellent electrocatalytic performance using only 3 at% of Pt. The defect-rich HEMG achieves ultralow overpotentials at ampere-level current density of 1000 mA cm-2 for HER (104 mV) and oxygen evolution reaction (301 mV) under alkaline conditions, while retains a long-term durability exceeding 200 h at 100 mA cm-2 . Moreover, it only requires 81 and 122 mV to drive the current densities of 1000 and 100 mA cm-2 for HER under acidic and neutral conditions, respectively. Modelling results reveal that lattice distortion and stacking fault defects help to optimize atomic configuration and modulate electronic interaction, while the surface nanoporous architecture provides abundant active sites, thus synergistically contributing to the reduced energy barrier for water electrolysis. This defect engineering approach combined with a HEMG design strategy is expected to be widely applicable for development of high-performance alloy catalysts.

Medium and long-term radiographic and clinical outcomes of Dynesys dynamic stabilization versus instrumented fusion for degenerative lumbar spine diseases.

BACKGROUND: Dynesys stabilization (DS) is utilized to preserve mobility at the instrumental segments and prevent adjacent segment pathology in clinical practice. However, the advantages of DS method in medium and long-term follow-up remain controversial. OBJECTIVE: To compare the radiographic and clinical outcomes between DS and instrumented fusion in the treatment of degenerative lumbar spine disease with or without grade I spondylolisthesis with a minimum follow-up period of 2 years. METHODS: We conducted a comprehensive search of PubMed, EMBASE, Cochrane, and Web of Science databases, Chinese National Knowledge Databases, and Wanfang Database for potentially eligible articles. Clinical outcomes were assessed in terms of VAS and ODI scores, screw loosening and breakage, and surgical revision. Radiographic outcomes were assessed in terms of postoperative range of movement (ROM) and disc heigh. Moreover, adjacent segment degeneration (ASDeg) and adjacent segment disease (ASDis) were evaluated. RESULTS: Seventeen studies with 1296 patients were included in the meta-analysis. The DS group was associated with significantly lower postoperative VAS scores for low-back and leg pain, and lower rate of surgical revision than the fusion group. Moreover, the Dynesys group showed significantly less ASDeg than the fusion group but showed no significant advantage over the fusion group in terms of preventing ASDis. Additionally, the ROM at the stabilized segments of the fusion group decreased significantly and that at the adjacent segments increased significantly compared with those of the DS group. CONCLUSION: DS showed comparable clinical outcomes and provided benefits in preserving the motion at the stabilized segments, thus limiting the hypermobility at the adjacent segments and preventing ASDeg compared with the fusion method in degenerative disease with or without grade I spondylolisthesis.

Investigation on the Mechanisms of Zanthoxylum bungeanum for Treating Diabetes Mellitus Based on Network Pharmacology, Molecular Docking, and Experiment Verification.

Objective: The aim of the study was to explore the potential mechanism of Zanthoxylum bungeanum in the treatment of diabetes mellitus (DM) using network pharmacology. Methods: The DrugBank database and TCMSP platform were used to search for the main chemical components and their targets of Zanthoxylum bungeanum, and the genes related to diabetes mellitus were obtained from the genecards database. Import the data into the Venny 2.1.0 platform for intersection analysis to obtain the Zanthoxylum bungeanum-DM-gene dataset. The protein-protein interaction (PPI) analysis of Zanthoxylum bungeanum-DM gene was performed using the String data platform, and the visualization and network topology analysis were performed using Cytoscape 3.8.2. The KEGG pathway enrichment and biological process of GO enrichment analysis were carried out using the David platform. The active ingredients and key targets of Zanthoxylum bungeanum were molecularly docked to verify their biological activities by using Discovery Studio 2019 software. Zanthoxylum bungeanum was extracted and isolated by ethanol and dichloromethane. HepG2 cells were cultured, and cell viability assay was utilized to choose the suitable concentration of Zanthoxylum bungeanum extract (ZBE). The western blot assay was used for measuring the expression of AKT1, IL6, HSP90AA1, FOS, and JUN proteins in HepG2 cells. Results: A total of 5 main compounds, 339 targets, and 16656 disease genes were obtained and retrieved, respectively. A total of 187 common genes were screened, and 20 core genes were finally obtained after further screening. The antidiabetic active ingredients of Zanthoxylum bungeanum are kokusaginin, skimmianin, diosmetin, beta-sitosterol, and quercetin, respectively. The main targets for its antidiabetic effect are AKT1, IL6, HSP90AA1, FOS, and JUN, respectively. GO enrichment analysis revealed that the biological process of Zanthoxylum bungeanum and DM is related to a positive regulation of gene expression, positive regulation of transcription, positive regulation of transcription from RNA polymerase II promoter, response to drug, positive regulation of apoptotic process, and positive regulation of cell proliferation, etc. KEGG enrichment analysis revealed that common biological pathways mainly including the phospholipase D signaling pathway, MAPK signaling pathway, beta-alanine metabolism, estrogen signaling pathway, PPAR signaling pathway, and TNF signaling pathway. Molecular docking results showed that AKT1 with beta-sitosterol and quercetin, IL-6 with diosmetin and skimmianin, HSP90AA1 with diosmetin and quercetin, FOS with beta-sitosterol and quercetin, and JUN with beta-sitosterol and diosmetin have relatively strong binding activity, respectively. Experiment verification results showed that DM could be significantly improved by downregulating the expression of AKT1, IL6, HSP90AA1, FOS, and JUN proteins after being treated at concentrations of 20 µmol/L and 40 µmol/L of ZBE. Conclusion: The active components of Zanthoxylum bungeanum mainly including kokusaginin, skimmianin, diosmetin, beta-sitosterol, and quercetin. The therapeutic effect of Zanthoxylum bungeanum on DM may be achieved by downregulating core target genes including AKT1, IL6, HSP90AA1, FOS, and JUN, respectively. Zanthoxylum bungeanum is an effective drug in treatment of DM related to the above targets.