A diagnostic model for differentiating tuberculous spondylodiscitis from pyogenic spondylodiscitis based on pathogen-confirmed patients.

OBJECTIVE: This study aimed to distinguish tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) based on laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) findings. Further, a novel diagnostic model for differential diagnosis was developed. METHODS: We obtained MRI, CT and laboratory data from TS and PS patients. Predictive models were built using binary logistic regression analysis. The receiver operating characteristic curve was analyzed. Both internal and external validation was performed. RESULTS: A total of 81 patients with PS (n = 46) or TS (n = 35) were enrolled. All patients had etiological evidence from the focal lesion. Disc signal or height preservation, skip lesion or multi segment (involved segments ≥ 3) involvement, paravertebral calcification, massive sequestra formation, subligamentous bone destruction, bone erosion with osteosclerotic margin, higher White Blood Cell Count (WBC) and positive result of tuberculosis infection T cell spot test (T-SPOT.TB) were more prevalent in the TS group. A diagnostic model was developed and included four predictors: WBC<7.265 * (10^9/L), skip lesion or involved segments ≥ 3, massive sequestra formation and subligamentous bone destruction. The model showed good sensitivity, specificity, and total accuracy (91.4%, 95.7%, and 93.8%, respectively); the area under the receiver operating characteristic curve (AUC) was 0.981, similar to the results of internal validation using bootstrap resampling (1000 replicates) and external validation set, indicating good clinical predictive ability. CONCLUSIONS: This study develop a good diagnostic model based on both CT and MRI, as well as laboratory findings, which may help clinicians distinguish between TS and PS.

Association between single and multiple cardiometabolic diseases and all-cause mortality among Chinese older adults: A prospective, nationwide cohort study.

BACKGROUND AND AIM: Cardiometabolic diseases (CMDs) are leading causes of death and disability, but little is known about the additive mortality effects of multiple CMDs. This study aimed to examine the association between single and multiple CMDs and all-cause mortality among older Chinese population. METHODS AND RESULTS: Using the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database, we analyzed data from 2008 to 2018 to assess the relationship between CMDs and mortality. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for single and multiple CMDs. At baseline, 11,351 participants (56.9% female) aged 60 years or older were included. 11.91% of participants had a single CMD, 1.51% had two CMDs, and 0.22% had three CMDs. Over a decade follow-up, 8992 deaths (79.2%) were recorded. A dose-response relationship was observed, with the mortality risk increasing by 17% for each additional disease. The fully-adjusted HRs for all-cause mortality were 1.16, 1.36, and 2.03 for one, two, and three CMDs, respectively. Larger effects of single and multiple CMDs were observed in the male group (P = 0.015) and the younger senior group (P < 0.001). CONCLUSIONS: This large-scale study found that CMDs multiply mortality risks, especially in younger seniors and males. The risk is highest when heart disease and stroke coexist, and diabetes further increases it. Public health efforts should prioritize evidence-based management and prevention of CMDs.

Reduction in chemotherapy relative dose intensity decreases overall survival of neoadjuvant chemoradiotherapy in patients with locally advanced esophageal carcinoma.

BACKGROUND: Many patients undergo dose reduction or early termination of chemotherapy to reduce chemoradiotherapy-related toxicity, which may increase their risk of survival. However, this strategy may result in underdosing patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). This study aimed to analyze the relationship between the relative dose intensity (RDI) and survival outcomes in patients with LA-ESCC. METHODS: This retrospective study assessed patients with LA-ESCC (cT2N + M0, cT3-4NanyM0) receiving neoadjuvant chemoradiotherapy (NCRT) with curative-intent esophagectomy. The patients received 2 courses of paclitaxel plus carboplatin (TC) combination radiotherapy prior to undergoing surgery. During NCRT, RDI was computed, defined as the received dose as a percentage of the standard dose, and the incidence of dose delays was estimated (≥ 7 days in any course cycle). The best RDI cutoff value (0.7) was obtained using ROC curve. The Kaplan-Meier survival curves were compared using the log-rank test, the treatment effect was measured using hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: We included 132 patients in this study, divided into RDI < 0.7 and RDI ≥ 0.7 groups using cut-off value of 0.7. RDI grade was an independent prognostic factor for OS. Baseline demographic and clinical characteristics were well balanced between the groups. There was no evidence that patients with RDI < 0.7 experienced less toxicity or those with RDI ≥ 0.7 resulted in more toxicity. However, patients with RDI < 0.7 who were given reduced doses had a worse overall survival [HR 0.49, 95% CI 0.27-0.88, P = 0.015]. The risk of a lower RDI increased with a longer dose delay time (P < 0.001). CONCLUSION: The RDI below 0.7 for avoiding chemoradiotherapy toxicity administration led to a reduction in the dose intensity of treatment and decreased overall survival.

Functional Group-driven Competing Mechanism in Electrochemical Reaction and Adsorption/Desorption Processes toward High-capacity Aluminum-Porphyrin Batteries.

Nonaqueous organic aluminum batteries are considered as promising high-safety energy storage devices due to stable ionic liquid electrolytes and Al metals. However, the stability and capacity of organic positive electrodes are limited by their inherent high solubility and low active organic molecules. To address such issues, here porphyrin compounds with rigid molecular structures present stable and reversible capability in electrochemically storing AlCl2+. Comparison between the porphyrin molecules with electron-donating groups (TPP-EDG) and with electron-withdrawing groups (TPP-EWG) suggests that EDG is responsible for increasing both HOMO and LUMO energy levels, resulting in decreased redox potentials. On the other hand, EWG is associated with decreasing both HOMO and LUMO energy levels, leading to promoted redox potentials. EDG and EWG play critical roles in regulating electron density of porphyrin π bond and electrochemical energy storage kinetics behavior. The competitive mechanism between electrochemical redox reaction and de/adsorption processes suggests that TPP-OCH3 delivers the highest specific capacity ~171.8 mAh g-1, approaching a record in the organic Al batteries.

Rhino-orbital-cerebral mucormycosis caused by Rhizopus arrhizus diagnosis via metagenomics next-generation sequencing: a case report.

Rhino-orbital-cerebral mucormycosis (ROCM) is a rare, invasive, and fatal fungal disease that is often easily misdiagnosed in the early stages due to the lack of specific clinical manifestations and adequate auxiliary examinations. Early diagnosis and timely therapy are essential for successful treatment. In this report, we presented a 46-year-old man with diabetes who experienced gradual vision loss, right ptosis, swelling, and headaches that progressively worsened to death within 4 days after admission. It was finally confirmed as a fungal Rhizopus arrhizus infection by metagenomics next-generation sequencing (mNGS). Our report has proved that mNGS testing should be strongly recommended in highly suspected patients.

Multi-Shell Nanourchin-Integrated Dual Mode Lateral Flow Immunoassay for Sensitive and Rapid Detection of Clinical Cardiac Myosin-Binding Protein C.

Cardiac myosin-binding protein C (cMyBP-C) is a novel cardiac marker of acute myocardial infarction (AMI) and acute cardiac injuries (ACI). Construction of point-of-care testing techniques capable of sensing cMyBP-C with high sensitivity and precision is urgently needed. Herein, we synthesized an Au@NGQDs@Au/Ag multi-shell nanoUrchins (MSNUs), and then applied it in a colorimetric/SERS dual-mode immunoassay for detection of cMyBP-C. The MSNUs displayed superior stability, colorimetric brightness, and SERS enhancement ability with an enhanced factor of 5.4 × 109, which were beneficial to improve the detection capability of test strips. The developed MSNU-based test strips can achieve an ultrasensitive immunochromatographic assay of cMyBP-C in both colorimetric and SERS modes with the limits of detection as low as 19.3 and 0.77 pg/mL, respectively. Strikingly, this strip was successfully applied to analyze actual plasma samples with significantly better sensitivity, negative predictive value, and accuracy than commercially available gold test strips. Notably, this method possessed a wide range of application scenarios via combining with a color recognizer application named Color Grab on the smartphone, which can meet various needs of different users. Overall, our MSNU-based test strip as a mobile health monitoring tool shows excellent sensitivity, reproducibility, and rapid detection of the cMyBP-C, which holds great potential for the early clinic diagnosis of AMI and ACI.

Lactate Contributes to Remote Ischemic Preconditioning-Mediated Protection Against Myocardial Ischemia Reperfusion Injury by Facilitating Autophagy via the AMPK-Mammalian Target of Rapamycin-Transcription Factor EB-Connexin 43 Axis.

Remote ischemic preconditioning (RIPC) exerts a protective role on myocardial ischemia/reperfusion (I/R) injury by the release of various humoral factors. Lactate is a common metabolite in ischemic tissues. Nevertheless, little is known about the role lactate plays in myocardial I/R injury and its underlying mechanism. This investigation revealed that RIPC elevated the level of lactate in blood and myocardium. Furthermore, AZD3965, a selective monocarboxylate transporter 1 inhibitor, and 2-deoxy-d-glucose, a glycolysis inhibitor, mitigated the effects of RIPC-induced elevated lactate in the myocardium and prevented RIPC against myocardial I/R injury. In an in vitro hypoxia/reoxygenation model, lactate markedly mitigated hypoxia/reoxygenation-induced cell damage in H9c2 cells. Meanwhile, further studies suggested that lactate contributed to RIPC, rescuing I/R-induced autophagy deficiency by promoting transcription factor EB (TFEB) translocation to the nucleus through activating the AMPK-mammalian target of rapamycin (mTOR) pathway without influencing the phosphatidylinositol 3-kinase-Akt pathway, thus reducing cardiomyocyte damage. Interestingly, we also found that lactate up-regulated the mRNA and protein expression of connexin 43 (CX43) by facilitating the binding of TFEB to CX43 promoter in the myocardium. Functionally, silencing of TFEB attenuated the protective effect of lactate on cell damage, which was reversed by overexpression of CX43. Further mechanistic studies suggested lactate facilitated CX43-regulated autophagy via the AMPK-mTOR-TFEB signaling pathway. Collectively, our research demonstrates that RIPC protects against myocardial I/R injury through lactate-mediated myocardial autophagy via the AMPK-mTOR-TFEB-CX43 axis.

Enhanced Cataluminescence Sensor Based on SiO2/MIL-53(Al) for Detecting Isobutylaldehyde.

A simple, rapid, and reliable method for detecting harmful gases is urgently required in environmental security fields. In this study, a highly effective cataluminescence sensor based on SiO2/MIL-53(Al) composites was developed to detect trace isobutylaldehyde. The sensor was designed using isobutylaldehyde to generate an interesting cataluminescence phenomenon in SiO2/MIL-53(Al). Under optimized conditions, a positive linear relationship was observed between the signal intensity of the cataluminescence and isobutylaldehyde concentration. The isobutylaldehyde concentration range of 1.55-310 ppm responded well to the sensing test, with an excellent correlation coefficient of 0.9996. The minimum detectable concentration signal-to-noise ratio (S/N = 3) was found to be 0.49 ppm. In addition, the sensor was effectively utilized for analyzing trace isobutylaldehyde; the analysis resulted in recoveries ranging from 83.4% to 105%, with relative standard deviations (RSDs) of 4.8% to 9.4%. Furthermore, the mechanism of cataluminescence between SiO2/MIL-53(Al) and isobutylaldehyde was explored using GC-MS analysis and density functional theory. We expect that this cataluminescence methodology will provide an approach for the environmental monitoring of isobutylaldehyde.

A mapped dataset of surface ocean acidification indicators in large marine ecosystems of the United States.

Mapped monthly data products of surface ocean acidification indicators from 1998 to 2022 on a 0.25° by 0.25° spatial grid have been developed for eleven U.S. large marine ecosystems (LMEs). The data products were constructed using observations from the Surface Ocean CO2 Atlas, co-located surface ocean properties, and two types of machine learning algorithms: Gaussian mixture models to organize LMEs into clusters of similar environmental variability and random forest regressions (RFRs) that were trained and applied within each cluster to spatiotemporally interpolate the observational data. The data products, called RFR-LMEs, have been averaged into regional timeseries to summarize the status of ocean acidification in U.S. coastal waters, showing a domain-wide carbon dioxide partial pressure increase of 1.4 ± 0.4 µatm yr-1 and pH decrease of 0.0014 ± 0.0004 yr-1. RFR-LMEs have been evaluated via comparisons to discrete shipboard data, fixed timeseries, and other mapped surface ocean carbon chemistry data products. Regionally averaged timeseries of RFR-LME indicators are provided online through the NOAA National Marine Ecosystem Status web portal.

Chloroplast genome of plantago major, a medicinal plant in China.

Plantago major (Plantaginaceae) is a medicinal plant in Chinese folk culture, known for its famous medicinal components such as plantagomain. In this study, we conducted genome sequencing of P. major using Illumina sequencing technology. The assembled complete chloroplast genome had a length of 165,044 bp, comprising a large single-copy regions (82,963 bp), a small single-copy regions (4,633 bp), and a pair of inverted repeat regions (38,724 bp). A total of 140 genes were detected, including 94 CDS, 38 tRNA, and 8 rRNA. Phylogenetic analysis revealed a close genetic relationship between P. major and P. rigida. These findings provide valuable data for a comprehensive understanding of the biological characteristics of P. major.

A phased small interfering RNA-derived pathway mediates lead stress tolerance in maize.

Phased small interfering RNAs (phasiRNAs) are a distinct class of endogenous small interfering RNAs, which regulate plant growth, development and environmental stress response. To determine the effect of phasiRNAs on maize (Zea mays L.) tolerance to lead (Pb) stress, the roots of 305 maize lines under Pb treatment were subjected to generation of individual databases of small RNAs. We identified 55 high-confidence phasiRNAs derived from 13 PHAS genes (genes producing phasiRNAs) in this maize panel, of which 41 derived from nine PHAS loci were negatively correlated with Pb content in the roots. The potential targets of the 41 phasiRNAs were enriched in ion transport and import. Only the expression of PHAS_1 (ZmTAS3j, Trans-Acting Short Interference RNA3) was regulated by its cis-expression quantitative trait locus and thus affected the Pb content in the roots. Using the Nicotiana benthamiana (N. benthamiana) transient expression system, 5'-rapid amplification of cDNA ends, and Arabidopsis heterologously expressed, we verified that ZmTAS3j was cleaved by zma-miR390 and thus generated tasiRNA targeting ARF genes (tasiARFs), and that the 5' and 3' zma-miR390 target sites of ZmTAS3j were both necessary for efficient biosynthesis and functional integrity of tasiARFs. We validated the involvement of the zma-miR390-ZmTAS3j-tasiARF-ZmARF3-ZmHMA3 pathway in Pb accumulation in maize seedlings using genetic, molecular, and cytological methods. Moreover, the increased Pb tolerance in ZmTAS3j-overexpressed lines was likely attributed to the zma-miR390-ZmTAS3j-tasiARF-ZmARF3-SAURs pathway, which elevated indole acetic acid levels and thus reactive oxygen species scavenging capacity in maize roots. Our study reveals the importance of the TAS3-derived tasiRNA pathway in plant adaptation to Pb stress.

Factors governing the dynamics of soil organic carbon and nitrogen in wetlands undergoing management changes in a semi-arid region.

Soil organic carbon and nitrogen play pivotal roles as indicators of soil quality and ecological functioning in wetlands. The escalating impact of human activities and climate change has led to a severe degradation of wetland soils, particularly in semi-arid regions. However, an understanding of the factors governing the dynamics of total soil organic carbon (TSOC) and total soil nitrogen (TSN) in semi-arid areas remains elusive, impeding a comprehensive understanding of wetland ecological functions. The present study investigated variations in TSOC and TSN content as well as vegetation and soil physicochemical properties under five different land management practices (mowed wetlands, mowed and slightly grazed wetlands, moderately grazed wetlands, heavily grazed wetlands, and natural wetlands unaffected by human interference) in the semi-arid Songnen Plain region of China. The results revealed significant decreases in TSOC and TSN content within managed wetlands compared to natural wetlands. Moreover, positive correlations were observed between pairs of SOC-TN or their storage values for SOC (TSOC)-TN (TSN). Furthermore, TSOC and TSN exhibited significant positive associations with aboveground and belowground biomass levels, stem C:N, stem C:P, soil C:P, and soil N:P. Additionally, redundancy analysis indicated that species diversity accounted for 37.4% of the variations in TSOC-TSN while belowground biomass accounted for 8.5% of the variations. Furthermore, nutrient content within stems (particularly N content and C:P) contributed to a 37.2% variation in TSOC and TSN whereas root nutrient content (especially N:P, C:N, and C:P) contributed to a 15.3% variation. Soil C:P, C:N, and total phosphorous (TP) content accounted for 65.7%, 9.6%, and 7.5% of variations of TSOC and TSN, respectively. Besides, variation partitioning analysis revealed that plant community characteristics, community nutrient content, and soil physicochemical properties collectively influenced the dynamics of TSOC and TSN. Among these factors, soil physicochemical properties emerged as the primary drivers of carbon and nitrogen dynamics in degraded wetlands in semi-arid regions. The impact on TSN was more pronounced than that of TSOC. This study provides valuable insights for understanding the processes and mechanisms underlying carbon and nitrogen accumulation in degraded wetlands, facilitating the development of regionally adaptive management plans under different management practices.

PROTAC-Mediated HDAC7 Protein Degradation Unveils Its Deacetylase-Independent Proinflammatory Function in Macrophages.

Class IIa histone deacetylases (Class IIa HDACs) play critical roles in regulating essential cellular metabolism and inflammatory pathways. However, dissecting the specific roles of each class IIa HDAC isoform is hindered by the pan-inhibitory effect of current inhibitors and a lack of tools to probe their functions beyond epigenetic regulation. In this study, a novel PROTAC-based compound B4 is developed, which selectively targets and degrades HDAC7, resulting in the effective attenuation of a specific set of proinflammatory cytokines in both lipopolysaccharide (LPS)-stimulated macrophages and a mouse model. By employing B4 as a molecular probe, evidence is found for a previously explored role of HDAC7 that surpasses its deacetylase function, suggesting broader implications in inflammatory processes. Mechanistic investigations reveal the critical involvement of HDAC7 in the Toll-like receptor 4 (TLR4) signaling pathway by directly interacting with the TNF receptor-associated factor 6 and TGFß-activated kinase 1 (TRAF6-TAK1) complex, thereby initiating the activation of the downstream mitogen-activated protein kinase/nuclear factor-κB (MAPK/NF-κB) signaling cascade and subsequent gene transcription. This study expands the insight into HDAC7's role within intricate inflammatory networks and highlights its therapeutic potential as a novel target for anti-inflammatory treatments.

Widely targeted metabolomics and flavoromics reveal the effect of Wickerhamomyces anomalus fermentation on the volatile and nonvolatile metabolites of black garlic juice.

Black garlic has a variety of biological activities, but many consumers cannot accept it because of the garlic odor and the bitter taste. In this study, fermentation with yeast Wickerhamomyces anomalus was adopted to improve the flavor of black garlic juice. Although fermentation reduced antioxidant activities, the garlicky odor and bitter taste were weakened. Metabolomic analysis revealed 141 metabolites were significantly differentially regulated. The upregulated metabolites were mainly related to nucleotides, organic acids and their derivatives, while the downregulated metabolites were mainly related to amino acids, lipids and their derivatives. Flavoromics analysis revealed that 137 metabolites were significantly differentially regulated, particularly garlicky and pungent volatiles were significantly downregulated. Correlation analysis indicated that esters are most closely related to nonvolatile metabolites, and lipids degradation was significantly correlated with volatiles. The results indicated that W. anomalus fermentation is an effective strategy to improve the flavor of black garlic juice.

Proteomics and Metabolic Characteristics of Boar Seminal Plasma Extracellular Vesicles Reveal Biomarker Candidates Related to Sperm Motility.

Although seminal plasma extracellular vesicles (SPEVs) play important roles in sperm function, little is known about their metabolite compositions and roles in sperm motility. Here, we performed metabolomics and proteomics analysis of boar SPEVs with high or low sperm motility to investigate specific biomarkers affecting sperm motility. In total, 140 proteins and 32 metabolites were obtained through differentially expressed analysis and weighted gene coexpression network analysis (WGCNA). Seven differentially expressed proteins (DEPs) (ADIRF, EPS8L1, PRCP, CD81, PTPRD, CSK, LOC100736569) and six differentially expressed metabolites (DEMs) (adenosine, beclomethasone, 1,2-benzenedicarboxylic acid, urea, 1-methyl-l-histidine, and palmitic acid) were also identified in WGCNA significant modules. Joint pathway analysis revealed that three DEPs (GART, ADCY7, and NTPCR) and two DEMs (urea and adenosine) were involved in purine metabolism. Our results suggested that there was significant correlation between proteins and metabolites, such as IL4I1 and urea (r = 0.86). Furthermore, we detected the expression level of GART, ADCY7, and CDC42 in sperm of two groups, which further verified the experimental results. This study revealed that several proteins and metabolites in SPEVs play important roles in sperm motility. Our results offered new insights into the complex mechanism of sperm motility and identified potential biomarkers for male reproductive diseases.

High levels of mitochondrial dynamics, autophagy, and apoptosis contribute to stable testicular status in hibernating Daurian ground squirrels.

Daurian ground squirrels (Spermophilus dauricus) experience various stress states during winter hibernation, but the impact on testicular function remains unclear. This study focused on the effects of changes in testicular autophagy, apoptosis, and mitochondrial homeostasis signaling pathways at various stages on the testes of Daurian ground squirrels. Results indicated that: (1) During winter hibernation, there was a significant increase in seminiferous tubule diameter and seminiferous epithelium thickness compared to summer. Spermatogonia number and testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were higher during inter-bout arousal, suggesting that the testes remained stable during hibernation. (2) An increased number of mitochondria with intact morphology were observed during hibernation, indicating that mitochondrial homeostasis may contribute to testicular stability. (3) DNA fragmentation was evident in the testes during the hibernation and inter-bout arousal stages, with the highest level of caspase3 enzyme activity detected during inter-bout arousal, together with elevated levels of Bax/Bcl-2 and Lc3 II/Lc3 I, indicating an up-regulation of apoptosis and autophagy signaling pathways during hibernation. (4) The abundance of DRP1, MFF, OPA1, and MFN2 proteins was increased, suggesting an up-regulation of mitochondrial dynamics-related pathways. Overall, testicular autophagy, apoptosis, and mitochondrial homeostasis-related signaling pathways were notably active in the extreme winter environment. The well-maintained mitochondrial morphology may favor the production of reproductive hormones and support stable testicular morphology.

Unraveling the relationship between gut microbiota and site-specific endometriosis: a Mendelian randomization analysis.

Background: Although numerous studies have illustrated the connection between gut microbiota and endometriosis, a conspicuous gap exists in research focusing on the pathogenesis of endometriosis at various sites and its linkage with infertility. Methods: In this study, we used a two-sample Mendelian randomization analysis to investigate the effect of gut microbiota on the development of endometriosis in different regions, including the uterus, ovary, fallopian tube, pelvic peritoneum, vagina, and rectovaginal septum, as well as the intestine. Additionally, we explored the correlation between gut microbiota and endometriosis-induced infertility. Genetic associations with gut microbes were obtained from genome-wide association study (GWAS) datasets provided by the MiBioGen consortium, whereas endometriosis-related GWAS data were sourced from the FinnGen dataset. In our analysis, single-nucleotide polymorphisms were used as instrumental variables, with the primary estimation of the causal effect performed via the inverse variance weighting method. Our sensitivity analyses incorporated heterogeneity tests, pleiotropy tests, and the leave-one-out method. Results: We identified associations at the genus level between four bacterial communities and endometriosis. Subsequently, several associations between the gut microbiota and various subtypes of endometriosis at different anatomical sites were recognized. Specifically, three genera were linked with ovarian endometriosis, six genera were associated with tubal endometriosis, four genera showed links with pelvic peritoneum endometriosis, five genera were connected with vaginal and rectovaginal septum endometriosis, and seven genera demonstrated linkages with intestinal endometriosis. Additionally, one genus was associated with adenomyosis, and three genera exhibited associations with endometriosis-induced infertility. Conclusion: Our study elucidates associations between gut microbiota and site-specific endometriosis, thereby augmenting our understanding of the pathophysiology of endometriosis. Moreover, our findings pave the way for potential therapeutic strategies targeting gut microbiota for individuals grappling with endometriosis-related infertility.

[A multicenter clinical study of critically ill patients with sepsis complicated with acute kidney injury in Beijing: incidence, clinical characteristics and outcomes].

OBJECTIVE: To investigate the epidemiological characteristics and prognosis of critically ill patients with sepsis combined with acute kidney injury (AKI) in intensive care unit (ICU) in Beijing, and to analyze the risk factors associated with in-hospital mortality among these critically ill patients. METHODS: Data were collected from the Beijing AKI Trial (BAKIT) database, including 9 049 patients consecutively admitted to 30 ICUs in 28 tertiary hospitals in Beijing from March 1 to August 31, 2012. Patients were divided into non-AKI and non-sepsis group, AKI and non-sepsis group, non-AKI and sepsis group, AKI and sepsis group. Clinical data recorded included demographic characteristics, primary reasons for ICU admission, comorbidities, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II(APACHE II) within 24 hours of ICU admission, physiological and laboratory indexes, treatment in the ICU, AKI staging based on the Kidney Disease: Improving Global Outcomes (KDIGO), as well as the prognostic indicators including length of stay in ICU, length of stay in hospital, ICU and in-hospital mortality. The primary endpoint was discharge or in-hospital death. Multivariate Logistic regression analysis was used to investigate the risk factors for hospital death in ICU patients. Kaplan-Meier survival curve was drawn to analyze the cumulative survival of ICU patients during hospitalization. RESULTS: A total of 3 107 critically ill patients were ultimately enrolled, including 1 259 cases in the non-AKI and non-sepsis group, 931 cases in the AKI and non-sepsis group, 264 cases in the non-AKI and sepsis groups, and 653 cases in the AKI and sepsis group. Compared with the other three group, patients in the AKI and sepsis group were the oldest, had the lowest mean arterial pressure (MAP), and the highest APACHE II score, SOFA score, blood urea nitrogen (BUN), and serum creatinine (SCr) levels, and they also had the highest proportion of receiving mechanical ventilation, requiring vasopressor support, and undergoing renal replacement therapy (RRT), all P < 0.01. Of these 3 107 patients, 1 584 (51.0%) were diagnosed with AKI, and the incidence of AKI in patients with sepsis was significantly higher than in those without sepsis [71.2% (653/917) vs. 42.5% (931/2 190), P < 0.01]. The highest proportion of KDIGO 0 stage was observed in the non-sepsis group (57.5%), while the highest proportion of KDIGO 3 stage was observed in the sepsis group (32.2%). Within the same KDIGO stage, the mortality of patients with sepsis was significantly higher than that of non-sepsis patients (0 stage: 17.8% vs. 3.1%, 1 stage: 36.3% vs. 7.4%, 2 stage: 42.7% vs. 17.1%, 3 stage: 54.6% vs. 28.6%, AKI: 46.1% vs. 14.2%). The ICU mortality (38.7%) and in-hospital mortality (46.1%) in the AKI and sepsis group were significantly higher than those in the other three groups. Kaplan-Meier survival curves further showed that the cumulative survival rate of patients with AKI and sepsis during hospitalization was significantly lower than that of the other three groups (53.9% vs. 96.9%, 85.8%, 82.2%, Log-Rank: χ 2 = 379.901, P < 0.001). Subgroup analysis showed that among surviving patients, length of ICU stay and total length of hospital stay were significantly longer in the AKI and sepsis group than those in the other three groups (both P < 0.01). Multivariate regression analysis showed that age, APACHE II score and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, sepsis, and AKI combined with sepsis were independent risk factors for ICU mortality in patients (all P < 0.05). After adjusting for covariates, AKI, sepsis, and sepsis combined with AKI were significantly associated with higher ICU and in-hospital mortality, with the highest ICU mortality [adjusted odds ratio (OR) = 14.82, 95% confidence interval (95%CI) was 8.10-27.12; Hosmer-Lemeshow test: P = 0.816] and in-hospital mortality (adjusted OR = 7.40, 95%CI was 4.94-11.08; Hosmer-Lemeshow test: P = 0.708) observed in patients with sepsis combined with AKI. CONCLUSIONS: The incidence of AKI is high in sepsis patients, and those with both AKI and sepsis have a higher disease burden, more abnormalities in physiological and laboratory indicators, and significantly increased ICU and in-hospital mortality. Among surviving patients, the length of ICU stay and total length of hospital stay are also longer in the AKI and sepsis group. Age, APACHE II score and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, and sepsis are independent risk factors for in-hospital mortality in ICU patients.

New Monoterpenoid Glycosides from the Fruits of Hypericum patulum Thunb.

The whole Hypericum patulum Thunb. plant is utilized in traditional medicine for its properties of clearing heat, detoxifying, soothing meridians, relaxing the liver, and stopping bleeding. In folk medicine, it is frequently used to treat hepatitis, colds, tonsillitis, and bruises. Phytochemical investigation of a 30% ethanol extract of the fresh ripe fruits of H. patulum has resulted in the isolation of two new pinane-type monoterpenoid glycosides 1-2, named patulumside E-F, and three new chain-shaped monoterpenoid glycosides 3-5, named patulumside G-H, J. Their structures were determined using extensive spectroscopic techniques, such as HR-ESI-MS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD) calculation. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. This research represents the inaugural comprehensive phytochemical study of H. patulum, paving the way for further exploration of monoterpenoid glycosides.

Santalum album L. alleviates cardiac function injury in heart failure by synergistically inhibiting inflammation, oxidative stress and apoptosis through multiple components.

BACKGROUND: Heart failure (HF) is a complex cardiovascular syndrome with high mortality. Santalum album L. (SAL) is a traditional Chinese medicine broadly applied for various diseases treatment including HF. However, the potential active compounds and molecular mechanisms of SAL in HF treatment are not well understood. METHODS: The active compounds and possible mechanisms of action of SAL were analyzed and validated by a systems pharmacology framework and an ISO-induced mouse HF model. RESULTS: We initially confirmed that SAL alleviates heart damage in ISO-induced HF model. A total of 17 potentially active components in SAL were identified, with Luteolin (Lut) and Syringaldehyde (SYD) in SAL been identified as the most effective combination through probabilistic ensemble aggregation (PEA) analysis. These compounds, individually and in their combination (COMB), showed significant therapeutic effects on HF by targeting multiple pathways involved in anti-oxidation, anti-inflammation, and anti-apoptosis. The active ingredients in SAL effectively suppressed inflammatory mediators and pro-apoptotic proteins while enhancing the expression of anti-apoptotic factors and antioxidant markers. Furthermore, the synergistic effects of SAL on YAP and PI3K-AKT signaling pathways were further elucidated. CONCLUSIONS: Mechanistically, the anti-HF effect of SAL is responsible for the synergistic effect of anti-inflammation, antioxidation and anti-apoptosis, delineating a multi-targeted therapeutic strategy for HF.