Effects of Aromatherapy on Physical and Mental Health of Cancer Patients Undergoing Radiotherapy and/or Chemotherapy: A Meta-Analysis.

BACKGROUP: Currently, aromatherapy is being increasingly utilized in clinical practice, particularly in managing the side effects associated with radiotherapy and chemoradiotherapy. However, it remains to be established whether aromatherapy can effectively alleviate these symptoms. OBJECTIVE: To investigate the effects of aromatherapy on the physical and mental health of patients with cancer undergoing radiotherapy and chemotherapy. METHODS: Seven databases were researched from inception until September 29, 2023, including PubMed, Scopus, and Web of Science, Chinese National Knowledge Infrastructure, Wanfang database, China Biology Medicine disc and VIP Chinese Medical Journal Database. Review Manager version 5.3 was utilized for data analysis. The Cochrane Risk of Bias tool RoB2 was employed to evaluate the quality of the literature included in the study. Evidence quality rating was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach through the GRADEpro GDT online tool. RESULTS: Nineteen studies involving 1,541 patients were included. Aromatherapy can alleviate nausea [relative risk (RR)=0.64, 95% confidence interval (CI): 0.53 to 0.78, P<0.05, I2=46%; standardized mean difference (SMD)=-0.86, 95% CI: -1.21 to -0.51, P<0.05, I2=64%] and vomiting (RR=0.54, 95% CI: 0.42 to 0.69, P<0.05, I2=35%; SMD=-1.28, 95% CI: -1.52 to -1.03, P<0.05, I2=92%), improve sleep disorders [mean difference (MD)=-3.39, 95% CI: -3.95 to -2.84, P<0.05, I2=0%], relieve pain (SMD=-1.58, 95% CI: -1.96 to -1.21, P<0.05, I2=0%), mitigate fatigue (SMD=-1.28, 95% CI: -2.44 to -0.11, P<0.05, I2=93%) and enhance quality of life (SMD=0.50, 95% CI: 0.22 to 0.79, P<0.05, I2=0%) in cancer patients after radiotherapy and chemotherapy, but it may not have a significant effect on anxiety. The risk of bias was high in the included studies using the Cochrane Risk of Bias tool RoB2, and no studies were considered to be of high grade according to the GRADE system. CONCLUSIONS: Aromatherapy is an efficacious, safe and economic adjunctive therapy for cancer patients, which can mend the physical symptoms and mental health of cancer patients. However, more high-quality studies are needed to verify it. (PROSPERO registration No. CRD42023390171).

Attributable mortality of ARDS among critically ill patients with sepsis: a multicenter, retrospective cohort study.

BACKGROUND: Both sepsis and acute respiratory distress syndrome (ARDS) are common severe diseases in the intensive care unit (ICU). There is no large-scale multicenter study to clarify the attributable mortality of ARDS among septic patients. This study aimed to evaluate the excess mortality of ARDS in critically ill patients with sepsis. METHODS: The data were obtained from a multicenter, prospective cohort study in 18 Chinese ICUs between January 2014 and August 2015. The study population was septic patients after ICU admission. The patients were categorized into two groups: those who developed ARDS (ARDS group) within seven days following a sepsis diagnosis and those who did not develop ARDS (non-ARDS group). Applying propensity score matching (PSM), patients were matched 1:1 as ARDS and non-ARDS groups. Mortality attributed to ARDS was calculated. Subsequently, we conducted a survival analysis to estimate the impact of ARDS on mortality. The primary endpoint was 30-day mortality after sepsis diagnosis. RESULTS: 2323 septic patients were eligible, 67.8% developed ARDS. After PSM, 737 patients with ARDS were matched 1:1 with 737 non-ARDS patients. ARDS's overall 30-day attributable mortality was 11.9% (95% CI 7.5-16.3%, p < 0.001). Subgroup analysis showed that the 30-day attributable mortality of mild, moderate, and severe ARDS was 10.5% (95% CI 4.0-16.8%, p < 0.001), 11.6% (95% CI 4.7-18.4%, p < 0.001) and 18.1% (95% CI 4.5-30.9%, p = 0.006), respectively. ARDS was an independent risk factor for 30-day mortality, with adjusted hazard ratios of 1.30 (95% CI 1.03-1.64, p = 0.027), 1.49 (95% CI 1.20-1.85, p < 0.001), and 1.95 (95% CI 1.51-2.52, p < 0.001) for mild, moderate, and severe ARDS, respectively. CONCLUSIONS: The overall 30-day attributable mortality of ARDS among critically ill patients with sepsis was 11.9%. Compared with mild and moderate ARDS, severe ARDS contributed more to death. ARDS was significantly associated with an increase in the 30-day mortality.

Association between the levels of urinary cell cycle biomarkers and non-recovery of renal function among critically ill geriatric patients with acute kidney injury.

The lack of early renal function recovery among geriatric patients with acute kidney injury (AKI) in the intensive care unit (ICU) is a commonly observed and acknowledged poor prognostic factor, especially for older adults. However, no reliable prognostic biomarker is available for identifying individuals at risk of renal non-recovery or mortality in older adults. In this prospective observational cohort study, we enrolled critically ill older adults (aged ≥ 60 years) with AKI from the ICU and followed their disease progression. The primary endpoint was renal non-recovery within seven days of follow-up, while the secondary endpoint was the determinants of 30-day mortality after AKI. We assessed the predictive accuracy using receiver operating characteristic curves and performed between-group comparisons using the log-rank test. Among 209 older adults, 117 (56.0%) experienced renal recovery. Multiple regression analysis revealed that urine levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) multiplied by insulin-like growth factor-binding protein 7 (IGFBP7) ([TIMP-2]*[IGFBP7]), AKI stages 2-3, and the Acute Physiology and Chronic Health Evaluation (APACHE II) score were independently associated with renal non-recovery. The regression model incorporating [TIMP-2]*[IGFBP7] demonstrated a fair predictive value (AUC 0.774, p < 0.001), with the optimal threshold set at 0.81 (ng/mL)2/1000. When [TIMP-2]*[IGFBP7] was combined with AKI severity and the APACHE score, the AUC increased to 0.851. In conclusion, urine [TIMP-2]*[IGFBP7] is a reliable biomarker associated with renal non-recovery in critically ill older adults, and its predictive efficacy can be further enhanced when combined with AKI severity and the APACHE score.

A landscape of gene expression regulation for synovium in arthritis.

The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition. We identify 4765 independent primary and 616 secondary cis-expression quantitative trait loci (cis-eQTLs) in the synovium and find that the eQTLs with multiple independent signals have stronger effects and heritability than single independent eQTLs. Integration of genome-wide association studies (GWASs) and eQTLs identifies 84 arthritis related genes, revealing 38 novel genes which have not been reported by previous studies using eQTL data from the GTEx project or immune cells. We further develop a method called eQTac to identify variants that could affect gene expression by affecting chromatin accessibility and identify 1517 regions with potential regulatory function of chromatin accessibility. Altogether, our study provides a comprehensive synovium multi-omics resource for arthritic diseases and gains new insights into the regulation of gene expression.

Digital Health Interventions for Quality Improvements in Chronic Kidney Disease Primary Care: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Chronic kidney disease (CKD) is a significant public health issue globally. The importance of its timely identification and early intervention is paramount. However, a systematic approach for early CKD management in the primary care setting is currently lacking, receiving less attention compared to upstream risk factors such as diabetes and hypertension. This oversight may lead to a failure in meeting quality-of-care indicators. Digital health interventions (DHIs), which leverage digital tools to enhance healthcare delivery, have shown effectiveness in managing chronic diseases and improving the quality, safety, and efficiency of primary care. Our research aimed to evaluate the effectiveness of DHIs in the care process, focusing on their reach, uptake, and feasibility. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for randomized controlled trials (RCTs) assessing DHIs' effectiveness in CKD patient care among adults in primary care settings. The search, conducted on 30 June 2023, included studies published in English from 1 January 2009. Screening was conducted using Covidence, adhering to Cochrane's guidelines for data extraction. We primarily evaluated changes in care processes (testing, documentation, medication use, etc.) and the use of renin-angiotensin-aldosterone system inhibitors (RAASi), referrals, among others. Multilevel meta-analysis was employed to address within-study clustering, and meta-regression analyzed the impact of study characteristics on heterogeneity in effect sizes. Clinical endpoints were recorded where available. Bias risk was assessed using the Cochrane Risk of Bias 2 tool. Data on reach, uptake, and feasibility were narratively summarized. The study is registered with PROSPERO (CRD42023449098). RESULTS: From 679 records, 12 RCTs were included in the narrative synthesis, and 6 studies (encompassing 7 trials) in the meta-analysis. The trials indicated a -0.85% change (95%CI, -5.82% to 4.11%) in the proportion of patients receiving desired care. This result showed considerable heterogeneity (I2 = 91.9%). One study characteristic (co-intervention, education) correlated with larger effects. Although including co-intervention in multivariable meta-regression was significant, it did not diminish heterogeneity. The reported reach varied and was not high, while the uptake was relatively high. Most studies did not explicitly address feasibility, though some statements implied its evaluation. CONCLUSIONS: The current literature on the impact of DHIs in community-based CKD care is limited. The studies suggest a non-significant effect of DHIs on enhancing CKD management in community settings, marked by significant heterogeneity. Future research should focus on rigorous, methodologically sound implementations to better assess the effectiveness of DHIs in the primary care management of CKD.

The quantitative parameters derived from IDEAL-IQ in the lumbar vertebrae of healthy children: a pilot study of bone development.

Background: Early childhood bone development affects that of bone disease in adolescence and adulthood. Many diseases can affect the cancellous bone or bone marrow. Therefore, it is of great significance to quantify the bone development of healthy children. The evaluation methods of bone development include bone age (BA) assessment and dual-energy X-ray bone mineral densitometry (DXA), both of which have strong subjectivity. The present study was conducted to improve our understanding of the bone development of healthy children using the quantitative parameters derived from iterative decomposition of water and fat with echo asymmetry and least squares estimation quantification (IDEAL-IQ) sequence. Methods: Our study enrolled healthy children between January 2022 to December 2022 consecutively in Children's Hospital of Shanxi. The inclusion criteria were as follows: (I) age ≤18 years; (II) no contraindications (surgical and interventional devices for ferromagnetic materials, cardiac implantable electronic devices, cochlear implants, insulin pumps, dental implants containing metal or alloy) to magnetic resonance imaging (MRI) scan. The exclusion criteria were as follows: (I) previous malignant disease, (II) previous chemoradiotherapy, (III) previous spine surgery, (IV) previous or acute vertebral compression fracture, (V) artifacts present in images. Participants underwent MRI scans using IDEAL-IQ sequence in the lumbar vertebrae. The IDEAL-IQ parameters [proton density fat fraction (PDFF), 1/T2* (R2*)] were obtained. The factor analysis of variance was applied to compare the differences of PDFF and R2* in different lumbar vertebral groups. The Kruskal-Wallis H test or Mann-Whitney U test was applied to compare the differences of quantitative data among different gender or age groups. Spearman correlation analysis was applied to study the relationship among the age, PDFF, and R2*. Results: A total of 145 participants (76 males, 69 females) were evaluated. There were no significant differences in PDFF and R2* of different lumbar vertebrae (PPDFF=0.338, PR2*=0.868). The average age was 36 [13-72] months. They were assigned into 4 groups (0-11, 12-35, 36-71, and 72-144 months). As the age increased, the average PDFF and R2* both increased significantly (rPDFF=0.659, rR2*=0.359, P<0.001). There were significant statistical differences in PDFF and R2* between the 4 age groups (ZPDFF=46.651, ZR2*=27.537, P<0.001). Moreover, the PDFF was also positively correlated with R2* (r=0.576, P<0.001). No association was found between the gender and PDFF, R2* (PPDFF=0.949, PR2*=0.177). Conclusions: The quantitative parameters derived from IDEAL-IQ in the lumbar vertebrae of healthy children will improve our understanding of bone development and provide a basis for further exploring the diseases that affect children's bone development.

A biosensing array for multiplex clinical evaluation of glucose, creatinine, and uric acid.

The multiplex and simultaneous determination of blood glucose, creatinine and uric acid is essential for the early screening of chronic diseases or regular disease monitoring. Here, we report for the first time a biosensing array for the multiplex and simultaneous determination of plasma glucose, creatinine and uric acid. The sensing electrodes are fabricated on a PET surface, including three working electrodes, one reference electrode, and one counter electrode. Each specific enzyme is immobilized on its corresponding working electrode. The biosensing array can exhibit high sensitivity and selectivity for the simultaneous determination of blood glucose, creatinine and uric acid in real blood samples, and the measurement results are accurate and consistent with those from the clinical biochemistry analyzer in the hospital. It is expected that this work could provide new avenues for the fundamental study of biosensing device construction, as well as practical applications of the detection of biomarkers in chronic diseases.

Urinary cell cycle biomarkers for the prediction of renal non-recovery in patients with septic acute kidney injury: a prospective study.

BACKGROUND: Poor prognosis has been associated with the absence of renal recovery after acute kidney injury (AKI). This study aimed to investigate whether urinary biomarkers at 0 and 24 h could be used independently or in conjunction with a clinical model to predict renal non-recovery in septic AKI. METHODS: A prospective observational study was conducted to measure the urinary levels of insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2) at the time of AKI diagnosis (0 h) and 24 h later. Renal non-recovery within 7 days was defined as the outcome. The predictive value of urinary biomarkers for renal non-recovery in septic AKI was assessed using the area under the curve (AUC). RESULTS: A total of 198 individuals with septic AKI were included in the final analysis. Among them, 38.9% (n = 77) did not experience renal recovery within 7 days. The combination of urinary IGFBP7 and TIMP-2 at the initial time point demonstrated prognostic value for non-recovery of renal function, with an AUC of 0.782. When [TIMP-2]*[IGFBP7] was measured at 0 h, the clinical prognostic model, incorporating AKI stage 2-3 and the non-renal sequential organ failure assessment score, showed an improved AUC of 0.822 (with a sensitivity of 88.3% and specificity of 59.5%). CONCLUSIONS: The combination of urinary [TIMP-2]*[IGFBP7] at 0 h exhibited moderate predictive ability for renal non-recovery in cases of septic AKI. However, there is potential to enhance the prognostic capabilities of the [TIMP-2]*[IGFBP7]-clinical prediction model.

PAK2/beta-catenin/c-Myc/PKM2 signal transduction suppresses ovarian granulosa cell apoptosis in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) exhibits the highest morbidity among endocrine diseases in women ranging from age 18 to 44. However, its pathogenesis remains unclear. The imbalance between systemic and ovarian oxidative stress (OS) is a key characteristic of PCOS, and accumulating evidence indicates that the antioxidative protein nuclear factor erythroid-2-related factor 2 (Nrf2) is implicated in cell apoptosis and inflammation caused by OS. The activated kinase 2 (PAK2)/-catenin/c-Myc/pyruvate kinase M2 (PKM2) axis is a newly identified signaling pathway that may regulate Nrf2 expression and thereby influence OS. In this study, we sought to identify PAK2 expression and function in PCOS cells. PAK2 and downstream PKM2 expression in KGN cells and tissues were detected by microarray and qPCR. Cell viability was determined using CCK-8 and colony formation assays (CFAs). Apoptosis was examined by flow cytometry. qPCR and ELISA were used to examine cell inflammation. Oxidant and OS-related enzymes were examined by ELISA. We found that PAK2 and PKM2 expression levels were reduced in KGN cells and PCOS ovarian cortex tissues. PAK2 overexpression activated ß-catenin/c-Myc/PKM2 while PAK2 silencing deactivated it. PAK2 overexpression was reduced, whereas PAK2 silencing promoted, KGN cell proliferation and colony formation. Cell apoptosis and inflammation were also induced by PAK2 overexpression but were alleviated by its silencing. Furthermore, increased peroxidation product levels decreased antioxidative protein activities, and deactivated antioxidative Nrf2/HO-1 pathway were detected in PAK2-overexpressing KGN cells, whereas these effects were counteracted in PAK2 silenced cells. Our data suggest that PAK2 and its associated ß-catenin/c-Myc/PKM2 inhibited cell viability and induced apoptosis and inflammation by triggering OS by deactivating the Nrf2/HO-1 pathway, suggesting the potential of PAK2 as a therapeutic PCOS treatment target.

Predictive Value of Perioperative Cardiac Troponin I in Patients Undergone Liver Transplantation: A Retrospective Cohort Study.

Objective: To examine the change rule and clinical significance of cardiac troponin I (cTnI) in the perioperative period of liver transplantation in adults, as well as its association with 28-day mortality. Methods: This was a retrospective cohort study: patients who underwent elective orthotopic liver transplantation (OLT) in Beijing Chao-Yang Hospital between June 2015 and June 2020 were selected, and plasma cTnI values were collected through the electronic medical record system within 7 days after surgery. Furthermore, the baseline clinical data of these patients were collected, and the change curve of cTnI values following liver transplantation was plotted. Using univariate and multivariate logistic regression models, the relationship between the level of postoperative cTnI and short-term mortality was investigated. The primary study endpoint was mortality within 28 days after surgery. Results: We included 414 patients who had undergone liver transplantation in this study, 48 of whom died within 28 days after surgery. cTnI, a specific marker of myocardial injury, could predict that the postoperative cardiovascular complications were higher in the death group and significantly affect the short-term prognosis of patients; however, its prognostic cut-off value was approximately 0.545 ng/mL (13×URL), indicating that a minor elevation of cTnI after liver transplantation did not significantly affect the prognosis. Moreover, a comparison of the baseline data and postoperative ICU management scores of the two groups revealed that diabetes, maximum value of cTnI >0.545 ng/mL within 7 days, and the need for postoperative renal replacement therapy (RRT) were independent prognostic factors of death within 28 days after liver transplantation. Conclusion: Within 7 days after surgery, an increase in cTnI to the maximum value of 0.545 ng/mL (13×URL) could have a significant impact on the short-term prognosis of patients. Diabetes and postoperative RRT were two independent prognostic factors for liver transplantation perioperative mortality.

Age-related self-DNA accumulation may accelerate arthritis in rats and in human rheumatoid arthritis.

The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant-induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA.

Short-chain fatty acid-butyric acid ameliorates granulosa cells inflammation through regulating METTL3-mediated N6-methyladenosine modification of FOSL2 in polycystic ovarian syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder characterized by chronic low-grade inflammation. Previous studies have demonstrated that the gut microbiome can affect the host tissue cells' mRNA N6-methyladenosine (m6A) modifications. This study aimed to understand the role of intestinal flora in ovarian cells inflammation by regulating mRNA m6A modification particularly the inflammatory state in PCOS. The gut microbiome composition of PCOS and Control groups was analyzed by 16S rRNA sequencing, and the short chain fatty acids were detected in patients' serum by mass spectrometry methods. The level of butyric acid was found to be decreased in the serum of the obese PCOS group (FAT) compared to other groups, and this was correlated with increased Streptococcaceae and decreased Rikenellaceae based on the Spearman's rank test. Additionally, we identified FOSL2 as a potential METTL3 target using RNA-seq and MeRIP-seq methodologies. Cellular experiments demonstrated that the addition of butyric acid led to a decrease in FOSL2 m6A methylation levels and mRNA expression by suppressing the expression of METTL3, an m6A methyltransferase. Additionally, NLRP3 protein expression and the expression of inflammatory cytokines (IL-6 and TNF-α) were downregulated in KGN cells. Butyric acid supplementation in obese PCOS mice improved ovarian function and decreased the expression of local inflammatory factors in the ovary. Taken together, the correlation between the gut microbiome and PCOS may unveil crucial mechanisms for the role of specific gut microbiota in the pathogenesis of PCOS. Furthermore, butyric acid may present new prospects for future PCOS treatments.

Analysis of urinary C-C motif chemokine ligand 14 (CCL14) and first-generation urinary biomarkers for predicting renal recovery from acute kidney injury: a prospective exploratory study.

BACKGROUND: Acute kidney injury (AKI) is a frequent syndrome in the intensive care unit (ICU). AKI patients with kidney function recovery have better short-term and long-term prognoses compared with those with non-recovery. Numerous studies focus on biomarkers to distinguish them. To better understand the predictive performance of urinary biomarkers of renal recovery in patients with AKI, we evaluated C-C motif chemokine ligand 14 (CCL14) and two first-generation biomarkers (cell cycle arrest biomarkers and neutrophil gelatinase-associated lipocalin) in two ICU settings. METHODS: We performed a prospective study to analyze urinary biomarkers for predicting renal recovery from AKI. Patients who developed AKI after ICU admission were enrolled and urinary biomarkers including tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), CCL14, and neutrophil gelatinase-associated lipocalin (NGAL) were detected on the day of AKI diagnosis. The primary endpoint was non-recovery from AKI within 7 days. The individual discriminative ability of CCL14, [TIMP-2] × [IGFBP7] and NGAL to predict renal non-recovery were evaluated by the area under receiver operating characteristics curve (AUC). RESULTS: Of 164 AKI patients, 64 (39.0%) failed to recover from AKI onset. CCL14 showed a fair prediction ability for renal non-recovery with an AUC of 0.71 (95% CI 0.63-0.77, p < 0.001). [TIMP-2] × [IGFBP7] showed the best prediction for renal non-recovery with an AUC of 0.78 (95% CI 0.71-0.84, p < 0.001). However, NGAL had no use in predicting non-recovery with an AUC of 0.53 (95% CI 0.45-0.60, p = 0.562). A two-parameter model (non-renal SOFA score and AKI stage) predicted renal non-recovery with an AUC of 0.77 (95% CI 0.77-0.83, p = 0.004). When [TIMP-2] × [IGFBP7] was combined with the clinical factors, the AUC was significantly improved to 0.82 (95% CI 0.74-0.87, p = 0.049). CONCLUSIONS: Urinary CCL14 and [TIMP-2] × [IGFBP7] were fair predictors of renal non-recovery from AKI. Combing urinary [TIMP-2] × [IGFBP7] with a clinical model consisting of non-renal SOFA score and AKI stage enhanced the predictive power for renal non-recovery. Urinary CCL14 showed no significant advantage in predicting renal non-recovery compared to [TIMP-2] × [IGFBP7].

ESKD Risk Prediction Model in a Multicenter Chronic Kidney Disease Cohort in China: A Derivation, Validation, and Comparison Study.

BACKGROUND AND OBJECTIVES: In light of the growing burden of chronic kidney disease (CKD), it is of particular importance to create disease prediction models that can assist healthcare providers in identifying cases of CKD individual risk and integrate risk-based care for disease progress management. The objective of this study was to develop and validate a new pragmatic end-stage kidney disease (ESKD) risk prediction utilizing the Cox proportional hazards model (Cox) and machine learning (ML). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE), a multicenter CKD cohort in China, was employed as the model's training and testing datasets, with a split ratio of 7:3. A cohort from Peking University First Hospital (PKUFH cohort) served as the external validation dataset. The participants' laboratory tests in those cohorts were conducted at PKUFH. We included individuals with CKD stages 1~4 at baseline. The incidence of kidney replacement therapy (KRT) was defined as the outcome. We constructed the Peking University-CKD (PKU-CKD) risk prediction model employing the Cox and ML methods, which include extreme gradient boosting (XGBoost) and survival support vector machine (SSVM). These models discriminate metrics by applying Harrell's concordance index (Harrell's C-index) and Uno's concordance (Uno's C). The calibration performance was measured by the Brier score and plots. RESULTS: Of the 3216 C-STRIDE and 342 PKUFH participants, 411 (12.8%) and 25 (7.3%) experienced KRT with mean follow-up periods of 4.45 and 3.37 years, respectively. The features included in the PKU-CKD model were age, gender, estimated glomerular filtration rate (eGFR), urinary albumin-creatinine ratio (UACR), albumin, hemoglobin, medical history of type 2 diabetes mellitus (T2DM), and hypertension. In the test dataset, the values of the Cox model for Harrell's C-index, Uno's C-index, and Brier score were 0.834, 0.833, and 0.065, respectively. The XGBoost algorithm values for these metrics were 0.826, 0.825, and 0.066, respectively. The SSVM model yielded values of 0.748, 0.747, and 0.070, respectively, for the above parameters. The comparative analysis revealed no significant difference between XGBoost and Cox, in terms of Harrell's C, Uno's C, and the Brier score (p = 0.186, 0.213, and 0.41, respectively) in the test dataset. The SSVM model was significantly inferior to the previous two models (p < 0.001), in terms of discrimination and calibration. The validation dataset showed that XGBoost was superior to Cox, regarding Harrell's C, Uno's C, and the Brier score (p = 0.003, 0.027, and 0.032, respectively), while Cox and SSVM were almost identical concerning these three parameters (p = 0.102, 0.092, and 0.048, respectively). CONCLUSIONS: We developed and validated a new ESKD risk prediction model for patients with CKD, employing commonly measured indicators in clinical practice, and its overall performance was satisfactory. The conventional Cox regression and certain ML models exhibited equal accuracy in predicting the course of CKD.

Hyperoside alleviates toxicity of ß-amyloid via endoplasmic reticulum-mitochondrial calcium signal transduction cascade in APP/PS1 double transgenic Alzheimer's disease mice.

Alzheimer's disease is a neurodegenerative disorder characterized by a decline in cognitive function. The ß-amyloid (Aß) hypothesis suggests that Aß peptides can spontaneously aggregate into ß-fragment-containing oligomers and protofibrils, and this activation of the amyloid pathway alters Ca2+ signaling in neurons, leading to neurotoxicity and thus apoptosis of neuronal cells. In our study, a blood-brain barrier crossing flavonol glycoside hyperoside was identified with anti-Aß aggregation, BACE inhibitory, and neuroprotective effect in cellular or APP/PSEN1 double transgenic Alzheimer's disease mice model. While our pharmacokinetic data confirmed that intranasal administration of hyperoside resulted in a higher bio-availability in mice brain, further in vivo studies revealed that it improved motor deficit, spatial memory and learning ability of APP/PSEN1 mice with reducing level of Aß plaques and GFAP in the cortex and hippocampus. Bioinformatics, computational docking and in vitro assay results suggested that hyperoside bind to Aß and interacted with ryanodine receptors, then regulated cellular apoptosis via endoplasmic reticulum-mitochondrial calcium (Ca2+) signaling pathway. Consistently, it was confirmed that hyperoside increased Bcl2, decreased Bax and cyto-c protein levels, and ameliorated neuronal cell death in both in vitro and in vivo model. By regulating Aß-induced cell death via regulation on Ca2+ signaling cascade and mitochondrial membrane potential, our study suggested that hyperoside may work as a potential therapeutic agent or preventive remedy for Alzheimer's disease.

The attributable mortality of sepsis for acute kidney injury: a propensity-matched analysis based on multicenter prospective cohort study.

BACKGROUND: Both sepsis and AKI are diseases of major concern in intensive care unit (ICU). This study aimed to evaluate the excess mortality attributable to sepsis for acute kidney injury (AKI). METHODS: A propensity score-matched analysis on a multicenter prospective cohort study in 18 Chinese ICUs was performed. Propensity score was sequentially conducted to match AKI patients with and without sepsis on day 1, day 2, and day 3-5. The primary outcome was hospital death of AKI patients. RESULTS: A total of 2008 AKI patients (40.9%) were eligible for the study. Of the 1010 AKI patients with sepsis, 619 (61.3%) were matched to 619 AKI patients in whom sepsis did not develop during the screening period of the study. The hospital mortality rate of matched AKI patients with sepsis was 205 of 619 (33.1%) compared with 150 of 619 (24.0%) for their matched AKI controls without sepsis (p = 0.001). The attributable mortality of total sepsis for AKI patients was 9.1% (95% CI: 4.8-13.3%). Of the matched patients with sepsis, 328 (53.0%) diagnosed septic shock. The attributable mortality of septic shock for AKI was 16.2% (95% CI: 11.3-20.8%, p < 0.001). Further, the attributable mortality of sepsis for AKI was 1.4% (95% CI: 4.1-5.9%, p = 0.825). CONCLUSIONS: The attributable hospital mortality of total sepsis for AKI were 9.1%. Septic shock contributes to major excess mortality rate for AKI than sepsis. REGISTRATION FOR THE MULTICENTER PROSPECTIVE COHORT STUDY: registration number ChiCTR-ECH-13003934.

Screening of cold hardiness-related indexes and establishment of a comprehensive evaluation method for grapevines (V. vinifera).

The goals of this work were to screen physiological and biochemical indexes to assess a set of V. vinifera germplasm resources, to compare evaluation methods for cold hardiness, and to establish a comprehensive method that can be used for more accurate screening for cold hardiness in V. vinifera. Four single methods were used to evaluate the cold hardiness of 20 germplasms resources and 18 physiological and biochemical indexes related to cold hardiness were determined. The LT50 values determined by electrical conductivity (EL), 2,3,5-triphenyltetrazolium chloride staining (TTC), differential thermal analysis (DTA), and recovery growth (RG) methods showed extremely significant positive correlation. Bound water content (BW), proline content (Pro), total soluble sugar content (TSS), malondialdehyde content (MDA), catalase content (CAT), and ascorbic acid content (ASA) exhibited significant correlation with LT50 values measured by different evaluation methods. The comprehensive cold hardiness index calculated by principal component analysis (PCA) combined with subordinate function (SF) was negatively correlated with LT50 values measured by different evaluation methods. Meili and Ecolly exhibited the highest cold hardiness, indicating their potential for use as parents for cold hardiness breeding. EL, DTA, TTC, and RG methods successfully distinguished cold hardiness among different V. vinifera germplasm lines. Measurements of BW, Pro, TSS, MDA, CAT, and ASA in dormant shoots also can be used as main physiological and biochemical indexes related to cold hardiness of V. vinifera. Comprehensive evaluation by PCA combined with SF can accurately screen cold hardiness in V. vinifera. This study provides a reference and accurate identification method for the selection of cold hardiness parents and the evaluation of cold hardiness of germplasm of V. vinifera.

Calprotectin as a diagnostic marker for sepsis: A meta-analysis.

Introduction: Sepsis is a life-threatening condition, and biomarkers are needed to diagnose sepsis fast and accurately. We aimed to perform this meta-analysis to investigate the diagnostic value of calprotectin on sepsis in critically ill patients. Methods: The investigators searched MEDLINE, Embase, Web of Science and Cochrane Library. Studies were included if they assessed the diagnostic accuracy of serum calprotectin for sepsis in intensive care unit (ICU). We estimated its diagnostic value and explored the source of heterogeneity. The bivariate model and the hierarchical summary receiver operating characteristic (HSROC) curve were used in the meta-analysis. Results: Six records assessing 821 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), and diagnostic odds ratio (DOR) were separately as 0.77, 0.85, 5.20, 0.27, respectively. The Fagan's nomogram showed post-test probabilities of 91% and 35% for positive and negative outcomes, respectively. Subgroup analysis indicated that sepsis definition could be a possible source of heterogeneity, but there's no sufficient data to investigate sepsis-3 definition. Sensitivity analysis suggested that two studies could affect the stability of pooled results. Conclusion: On the basis of our meta-analysis, calprotectin is a helpful marker for early diagnosis of sepsis on ICU admission.

Sprayed biodegradable liquid film improved the freezing tolerance of cv. Cabernet Sauvignon by up-regulating soluble protein and carbohydrate levels and alleviating oxidative damage.

Most cultivars of Vitis vinifera L. are very sensitive to cold. As an exogenous protectant, Biodegradable Liquid Film (BLF) is considered to protect winegrapes from low temperatures and dry winds for safe overwintering. This study aimed to reveal the physiological and biochemical mechanisms of BLF regulating the freezing tolerance of wine grapes. Groups of ten-year-old vines (Cabernet Sauvignon) were sprayed with BLF in November 2020 and 2021, or left untreated as a control treatment, and field plant mortality after overwintering were investigated. Branch samples were collected monthly for determination of biochemical indicators. Dormant two-year-old cuttings (Cabernet Sauvignon) were also used for the determination of relative expression levels of key genes. The results showed that the application of BLF reduced the branch semi-lethal temperature in January and February samples compared with control, and reduced the mortality of above-ground parts, branches and buds. The physiological status of shoots was greatly affected by the climatic conditions of the year, but BLF treatment increased the levels of soluble protein and soluble sugar, and also decreased the content of superoxide anion and malondialdehyde at most sampling times. Correlation analysis showed that the differences in freezing tolerance between BLF and no treated overwintering(CK) vines were mainly related to peroxidase activity, soluble sugar, reducing sugar and starch content. Low temperature stress activated the over expression of ICE1, CBF1, and CBF3, especially for 12h. BLF treatment significantly increased the expression levels of CBF1 and CBF3 under low temperature stress. Overall, these results demonstrate that BLF treatment protects vines from freezing damage by upregulating osmo-regulatory substances and alleviating oxidative damage.

A structural MRI study of global developmental delay in infants (<2 years old).

Objective: To use structural magnetic resonance imaging (3D-MRI) to evaluate the abnormal development of the cerebral cortex in infants with global developmental delay (GDD). Methods: The GDD group includes 67 infants aged between 112 and 699 days with global developmental delay and who underwent T1-weighted MRI scans in Shanxi Children's Hospital from December 2019 to March 2022. The healthy control (HC) group includes 135 normal developing infants aged between 88 and 725 days in Shanxi Children's Hospital from September 2020 to August 2021. Whole-brain T1-weighted MRI scans were carried out with a 3.0-T magnetic resonance scanner, which was later processed using InfantSurfer to perform MR image processing and cortical surface reconstruction. Two morphological features of the cortical surface of the 68 brain regions were computed, i.e., the cortical thickness (CT) and cortical surface area (SA), and compared between the GDD and HC groups. Results: With regard to the CT, the HC group showed a rapid decrease at first and then a slow increase after birth, and the CT of the GDD group decreased slowly and then became relatively stable. The GDD group showed bilaterally higher hemispherical average CT than those in the HC group. In detail, for the left hemisphere, except in the entorhinal and temporal poles in which the average CT values of the two brain regions were lower than those of the HC group, the CT of the 26 brain regions in the GDD group was higher than those of the HC group (p < 0.05). For the right hemisphere, the CT of the entorhinal in the GDD group was lower than that in the HC group. Otherwise, the CT of the remaining 28 brain regions was higher than those in the HC group (p < 0.05). With regard to the SA, both groups showed a rapid increase after birth till 23 months and remained quite stable afterward. The GDD group shows lower SA bilaterally than that in the HC group. In detail, SA in the GDD group was lower in most cortical regions of both hemispheres than in the HC group (p < 0.05), except for the right temporal pole and entorhinal. When testing for brain asymmetry, we found that the HC group showed obvious asymmetry of CT and SA, while only a few cortical regions in the GDD group showed asymmetry.