Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly recognized for their role in reducing the risk and improving the prognosis of heart failure (HF). However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in mitigating the risk of HF. METHODS: A two-sample, two-step Mendelian Randomization (MR) approach was employed to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship. MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium. The Genome-wide association study (GWAS) data for 92 inflammatory biomarkers were obtained from two datasets, which included 14,824 and 575,531 individuals of European ancestry, respectively. GWAS data for HF was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) and 95% confidence interval (CI) for HF were calculated per 1 unit change of HbA1c. RESULTS: Genetically predicted SGLT-2 inhibition was associated with a reduced risk of HF (OR 0.42 [95% CI 0.30-0.59], P < 0.0001). Of the 92 inflammatory biomarkers studied, two inflammatory biomarkers (C-X-C motif chemokine ligand 10 [CXCL10] and leukemia inhibitory factor) were associated with both SGLT-2 inhibition and HF. Multivariable MR analysis revealed that CXCL10 was the primary inflammatory cytokine related to HF (MIP = 0.861, MACE = 0.224, FDR-adjusted P = 0.0844). The effect of SGLT-2 inhibition on HF was mediated by CXCL10 by 17.85% of the total effect (95% CI [3.03%-32.68%], P = 0.0183). CONCLUSIONS: This study provides genetic evidence supporting the anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing the risk of HF. CXCL10 emerged as a potential mediator, offering a novel intervention pathway for HF treatment.

Dual substitution of host lattice ions to enhance the luminescence properties of Zn2TiO4:Cr3+ phosphor.

Near-infrared light sources have potential applications in many fields. Cr3+ is a good luminescence centre to prepare near-infrared phosphors. Improving the performance of existing near-infrared luminescent materials has indeed attracted great interest from researchers. The luminescence properties of Zn2TiO4:Cr3+ were improved by crystal field engineering strategies. Zn2+-Ti4+ was partially replaced using a Li+-Nb5+ ion pair based on the Zn2TiO4:Cr3+ phosphors. Luminescence Cr3+-activated luminescent materials are sensitive to changes in the local crystal structure and crystal field environment. Doping of Li+-Nb5+ increased the luminescence intensity up to 2.7 times that of the undoped sample. Also, the thermal stability of the phosphor was greatly increased by the replacement of Li+-Nb5+.

Social cognition, socioeconomic status and subjective well-being of Chinese migrant workers.

Subjective well-being is based on the unity of internal and external needs, as well as material and non-material needs. However, existing research lacks consideration of the impact of both objective material conditions and subjective psychological cognition on the subjective well-being of migrant workers. Thus, based on data from the 2017 China General Social Survey, this paper applies ordered logit models and OLS models to investigate the impact of social cognition and socioeconomic status on the subjective well-being of migrant workers and their intergenerational differences. The results indicate that: (1) Social cognition has a significant impact, and the impact of fairness perception is more pronounced than depression perception and class change perception; (2) among socioeconomic status, personal income did not have a significant effect as education level, car ownership and house property ownership; (3) there are intergenerational differences. The emotional state of the older generation is the most critical factor influencing their subjective well-being. In contrast, the new generation is more concerned with their feelings about future expectations. The older generation is more concerned with their house property ownership, while the increase in income, education and car ownership can significantly increase the subjective well-being of the new generation. For this reason, we believe that the Chinese government should gradually change the existing urban and rural management system to create a fair and just social environment; make migrant workers receive the same protection as urban residents and improve the income distribution mechanism; pay attention to the social security of the older generation of migrant workers and the development opportunities of the new generation of migrant workers and their ability to integrate into the city to improve their subjective well-being.

Chloroplast Methyltransferase Homolog RMT2 is Involved in Photosystem I Biogenesis.

Oxygen (O2), a dominant element in the atmosphere and essential for most life on Earth, is produced by the photosynthetic oxidation of water. However, metabolic activity can cause accumulation of reactive O2 species (ROS) and severe cell damage. To identify and characterize mechanisms enabling cells to cope with ROS, we performed a high-throughput O2 sensitivity screen on a genome-wide insertional mutant library of the unicellular alga Chlamydomonas reinhardtii. This screen led to identification of a gene encoding a protein designated Rubisco methyltransferase 2 (RMT2). Although homologous to methyltransferases, RMT2 has not been experimentally demonstrated to have methyltransferase activity. Furthermore, the rmt2 mutant was not compromised for Rubisco (first enzyme of Calvin-Benson Cycle) levels but did exhibit a marked decrease in accumulation/activity of photosystem I (PSI), which causes light sensitivity, with much less of an impact on other photosynthetic complexes. This mutant also shows increased accumulation of Ycf3 and Ycf4, proteins critical for PSI assembly. Rescue of the mutant phenotype with a wild-type (WT) copy of RMT2 fused to the mNeonGreen fluorophore indicates that the protein localizes to the chloroplast and appears to be enriched in/around the pyrenoid, an intrachloroplast compartment present in many algae that is packed with Rubisco and potentially hypoxic. These results indicate that RMT2 serves an important role in PSI biogenesis which, although still speculative, may be enriched around or within the pyrenoid.

The mixed effect of Endocrine-Disrupting chemicals on biological age Acceleration: Unveiling the mechanism and potential intervention target.

INTRODUCTION: Although previous studies investigated the potential adverse effects of endocrine-disrupting chemicals (EDCs) on biological age acceleration and aging-related diseases, the mixed effect of multiple types of EDCs on biological age acceleration, including its potential underlying mechanism, remains unclear. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) were used to analyze biological age measures, including Klemera-Doubal method biological age (KDM-BA), phenotypic age, and homeostatic dysregulation (HD). Weight quantile sum (WQS) regression was performed to screen biological age-related EDCs (BA-EDCs) and assess the mixed effect of BA-EDCs on biological age acceleration and aging-related disease. Targets of BA-EDCs were obtained from three databases, while heart aging-related genes were obtained from the Aging Anno database. Protein-protein interaction (PPI) network and MCODE algorithm were applied to identify potential interactions between BA-EDC targets and heart aging-related genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to identify related pathways. RESULTS: This cross-sectional study included 1,439 participants. A decile increase in BA-EDCs co-exposure was associated with 0.31 years and 0.17 years of KDM-BA and phenotypic age acceleration, respectively. The mixed effect of BA-EDCs was associated with an increased prevalence of atherosclerotic cardiovascular disease (ASCVD). Vitamins C and E demonstrated a significant interaction effect on the association between BA-EDCs and KDM-BA acceleration. PPI network and functional enrichment analysis indicated that the AGE-RAGE signaling pathway in diabetic complications was significantly enriched. CONCLUSION: Our results showed that the co-exposure effect of BA-EDCs was associated with biological age acceleration and ASCVD, with the AGE-RAGE signaling pathway being the underlying mechanism. Vitamins C and E may also be an actionable target for preventing EDC-induced biological aging.

Crystal structure and luminescence properties of a novel near-infrared phosphor LiAlO2:Fe3.

Cr3+-free near-infrared (NIR) phosphors are currently gaining significant attention in various application fields. A novel Fe3+-activated LiAlO2 NIR phosphor was successfully synthesized by high-temperature solid-state method. Under excitation of 391 nm and 467 nm, the phosphor emits near-infrared light with wavelengths ranging from 600 to 850 nm. The emission bands with peaks at 725 nm correspond to the transition from 4T1(4G) to the ground state energy level 6A1(6S). The optical band gap of LiAlO2 was calculated using Density Function Theory (DFT) and diffuse reflectance spectrum, respectively. The thermal stability of the sample was measured under 391 nm and 467 nm excitation, showing that the emission intensity at 413 K is 55.3 % and 52.4 % of the emission intensity at room temperature.

Vacciniumchaozhouense (Ericaceae), a new species from East Guangdong, China.

Vacciniumchaozhouense (Ericaceae), a new species from East Guangdong Province, China is described and illustrated. This new species is morphologically similar to V.wrightii by having flowers with persistent and leaf-like bracts, long pedicels, and white spherical-urceolate corollas, but is distinguished by having glandular trichomes on the abaxial surface of the leaf blade, shorter pedicels, sparsely pilose corolla ridges, and anther thecae longer than the tubules. A key to the new species and morphologically similar species is also provided.

Effect and mechanism of ultrasound on acid loading in the preparation of silicon-based sulfonic solid acids.

Silicon-based sulfonic solid acids have the advantages of high catalytic activity and selectivity, easy separation from products, low equipment corrosion, and environmental protection, and sulfuric acid loading is the key to their preparation. To overcome the shortcomings of low acid loading and uneven distribution in the existing preparation methods of micron-sized silicon-based sulfonic solid acids, a method was proposed to prepare micron-sized silicon-based sulfonic solid acids using ultrasonic enhanced technology. The effect of different reaction parameters, such as time, power, and temperature of ultrasonication, sulfonation temperature and time, and sulfuric acid concentration, on acid loading in solid acid was investigated in this work. The results showed that a micron-sized mesoporous silica-based solid acid was successfully synthesized with a high acid content of 0.8633 mmol/g, uniform acid distribution, high specific surface area of 269.332 m2/g, and large average particle size of 172.142 µm in this work. The introduction of ultrasound was found to expand the carrier's pore volume and increase the carrier's specific surface area and the number of hydroxyl groups, thereby increasing the acid loading capacity and the specific surface area of the solid acid sample by 66.6 % and 10.97 % respectively, compared with the case without ultrasound.

Bearing Fault-Detection Method Based on Improved Grey Wolf Algorithm to Optimize Parameters of Multistable Stochastic Resonance.

In an effort to overcome the problem that the traditional stochastic resonance system cannot adjust the structural parameters adaptively in bearing fault-signal detection, this article proposes an adaptive-parameter bearing fault-detection method. First of all, the four strategies of Sobol sequence initialization, exponential convergence factor, adaptive position update, and Cauchy-Gaussian hybrid variation are used to improve the basic grey wolf optimization algorithm, which effectively improves the optimization performance of the algorithm. Then, based on the multistable stochastic resonance model, the structure parameters of the multistable stochastic resonance are optimized through improving the grey wolf algorithm, so as to enhance the fault signal and realize the effective detection of the bearing fault signal. Finally, the proposed bearing fault-detection method is used to analyze and diagnose two open-source bearing data sets, and comparative experiments are conducted with the optimization results of other improved algorithms. Meanwhile, the method proposed in this paper is used to diagnose the fault of the bearing in the lifting device of a single-crystal furnace. The experimental results show that the fault frequency of the inner ring of the first bearing data set diagnosed using the proposed method was 158 Hz, and the fault frequency of the outer ring of the second bearing data set diagnosed using the proposed method was 162 Hz. The fault-diagnosis results of the two bearings were equal to the results derived from the theory. Compared with the optimization results of other improved algorithms, the proposed method has a faster convergence speed and a higher output signal-to-noise ratio. At the same time, the fault frequency of the bearing of the lifting device of the single-crystal furnace was effectively diagnosed as 35 Hz, and the bearing fault signal was effectively detected.

Analysis of effectiveness and outcome of traumatic brain injury treatment in ED during COVID-19 pandemic: A multicenter in Taiwan.

The coronavirus disease 2019 has become a threat to global healthcare because of its rapid spread and evolution. In severe cases, the initial management of the disease is mainly supportive therapy and mechanical ventilation. Therefore, we investigated whether a modified emergency department workflow affects the efficacy will influence the efficacy and patient outcomes of traumatic brain injury (TBI) in Taiwan. This retrospective observational study used the Chang Gung Research Database in Taiwan from 7 hospitals in the Chang Gung Memorial Hospital System. Clinical index parameters and treatment efficiencies were analyzed between the locally transmitted period (January 20, 2020-June 7, 2020, period 2) and the community spread period (May 19, 2021-July 27, 2021, period 4) with the same interval of the pre-pandemic in 2019 as a reference period. During the locally transmitted period, only the time interval for patients who had to wait for a brain CT examination was, on average, 7.7 minutes shorter, which reached statistical significance. In addition, the number of TBI patients under 18 years of age decreased significantly during the community spread period. The "Door to the operating room (OR)," with polymerase chain reaction (PCR) testing, was on average 109.7 minutes slower than without the PCR testing in the reference period 2019. TBI treatment efficiency was delayed because of the PCR test. However, the surgical volume and functional outcome during these 2 periods were statistically insignificant compared to the pre-pandemic period because the spread of the virus was well controlled and hospital capacity was increased.

A novel Mn4+ -activated far-red Sr2 MgWO6 phosphor: synthesis, luminescence enhancement, and application prospect.

A novel far-red emitting phosphor Sr2 MgWO6 : Mn4+ was fabricated using high-temperature solid-state reaction. X-ray diffraction patterns, scanning electron microscopy images, and photoluminescence excitation and photoluminescence spectra for this phosphor were analyzed in detail. The analysis revealed that its emission ranged from 600 to 800 nm and peaked at 699 nm, which was attributed to the 2 Eg →4 A2g transition of Mn4+ under 314 nm excitation. Moreover, we introduced rare-earth Yb3+ ions into the Sr2 MgWO6 :Mn4+ to improve its far-red emitting intensity. The photoluminescence (PL) intensity of the Yb3+ co-doped phosphor was three times higher than that of the single-doped phosphor. Therefore charge compensation is an efficient approach to improving PL intensity. The phosphor emitted a far-red light that resembled the pigments essential for plant growth in terms of the absorption spectrum. Therefore, the obtained phosphor, Sr2 MgWO6 :0.006Mn4+ ,0.2Yb3+ , had the potential to be a new type of far-red luminescent powder for indoor plant growth LEDs.

Chlamydomonas mutants lacking chloroplast TRIOSE PHOSPHATE TRANSPORTER3 are metabolically compromised and light sensitive.

Modulation of photoassimilate export from the chloroplast is essential for controlling the distribution of fixed carbon in the cell and maintaining optimum photosynthetic rates. In this study, we identified chloroplast TRIOSE PHOSPHATE/PHOSPHATE TRANSLOCATOR 2 (CreTPT2) and CreTPT3 in the green alga Chlamydomonas (Chlamydomonas reinhardtii), which exhibit similar substrate specificities but whose encoding genes are differentially expressed over the diurnal cycle. We focused mostly on CreTPT3 because of its high level of expression and the severe phenotype exhibited by tpt3 relative to tpt2 mutants. Null mutants for CreTPT3 had a pleiotropic phenotype that affected growth, photosynthetic activities, metabolite profiles, carbon partitioning, and organelle-specific accumulation of H2O2. These analyses demonstrated that CreTPT3 is a dominant conduit on the chloroplast envelope for the transport of photoassimilates. In addition, CreTPT3 can serve as a safety valve that moves excess reductant out of the chloroplast and appears to be essential for preventing cells from experiencing oxidative stress and accumulating reactive oxygen species, even under low/moderate light intensities. Finally, our studies indicate subfunctionalization of the TRIOSE PHOSPHATE/PHOSPHATE TRANSLOCATOR (CreTPT) transporters and suggest that there are differences in managing the export of photoassimilates from the chloroplasts of Chlamydomonas and vascular plants.

High-density lipoprotein cholesterol modifies the association between blood lead and uric acid: results from NHANES 2005-2016.

BACKGROUND: The association between blood lead (PbB) and uric acid (SUA) remains unclear in US adults without a high level of lead exposure. Additionally, the effects of high-density lipoprotein cholesterol (HDL-C) modifying this association are still unclear. Therefore, this study aims to assess the effect of modification of high-density lipoprotein cholesterol on the association between PbB and SUA. METHOD: This research analyzed National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2016. Through several screenings, 18,578 participants over the age of 20 were eligible for the analysis. Multivariable linear regression was used to evaluate the association between PbB and SUA. By having stratified participants based on the HDL-C intake category (low HDL-C intake < 50 mg/dl; high HDL-C intake ≥ 50 mg/dl), effect modification by HDL-C was assessed through a likelihood ratio test between PbB and SUA. RESULT: Multivariable linear regression indicated that PbB positively affects SUA (ß = 0.19, 95% CI 0.16-0.22). The relationship between PbB and SUA was different in the low and high HDL-C intake group (ß 0.12 95% Cl 0.08-0.16 vs. ß 0.26 95% Cl 0.22 ~ - 0.30). Furthermore, high-density lipoprotein cholesterol significantly modified the relationship between PbB and SUA in all models which indicates that the interaction of lead exposure and HDL-C is more dangerous than the sum of the individual effects. CONCLUSIONS: Our study shows that high-density lipoprotein cholesterol and blood lead have an interactive effect on increasing uric acid, which may have great importance for clinical medication.

Clinical benefit of sodium-glucose transport protein-2 inhibitors in patients with heart failure: An updated meta-analysis and trial sequential analysis.

To assess whether the current body of accumulated data can give convincing evidence in favor of sodium-glucose transport protein-2 inhibitor (SGLT-2i) in all types of heart failure (HF). We searched for randomized controlled trials contrasting the effectiveness of SGLT-2i to placebo or other hypoglycemic medications on clinicaltrials.gov, PubMed, and the Cochrane Library database. To gauge effect size, hazard ratios (HR) were employed as measurements. The composite outcome of cardiovascular death or hospitalization owing to HF was the primary endpoint. Eleven studies were included. In comparison to the control group, the data demonstrated that SGLT-2i is related with a decreased incidence of composite outcome (HR: 0.77, 95% CIs: 0.73-0.81, I 2 = 0%, P < 0.01), CV death (HR: 0.87, 95% CIs: 0.81-0.94, I 2 = 3%, P < 0.01), all-cause mortality (HR: 0.90, 95% CIs: 0.84-0.96, I 2 = 10%, P < 0.01), and hospitalization due to HF (HHF) (HR: 0.70, 95% CIs: 0.66-0.75, I 2 = 0%, P < 0.01). The trial sequential analysis found strong evidence of a decrease in the incidence of all clinical outcomes with SGLT-2i when compared to the control group. Subgroup analysis demonstrated that the association between SGLT-2i and clinical outcome was independent of population characteristics. We confirm that the present evidence supports the use of SGLT-2i in a wide range of HF patients. Systematic review registration: [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42022333279].

Complications of Full-Endoscopic Lumbar Discectomy versus Open Lumbar Microdiscectomy: A Systematic Review and Meta-Analysis.

OBJECTIVE: Endoscopic lumbar discectomy has been an alternative for treating lumbar disc herniation. Evidence-based study for the benefit zone of full-endoscopic lumbar discectomy (FELD) is necessary. The study compared the complication risks between the FELD and open discectomy or microdiscectomy. METHODS: The literature search was from 4 online databases for randomized controlled trials (RCTs) and cohort studies. The meta-analysis of different study designs was conducted separately. Complication rates were considered primary outcomes, and the recurrence and revision rates were considered secondary outcomes. RESULTS: Six RCTs and thirteen cohort studies met the eligibility criteria. The meta-analysis was conducted separately. From the pooled RCT meta-analysis, the overall complication rates of FELD and open discectomy/microdiscectomy were 5.5% and 10.4%, respectively. The moderate-quality evidence suggested that FELD had a lower risk of overall complications (risk ratio [RR] = 0.55, 95% confidence interval [CI] = 0.31-0.98). There was no significant difference in specific complications and recurrence. The analysis of cohort studies revealed no significant difference in overall complications, but there was significant heterogeneity in the results. The risk of dural injury was significantly lower for FELD (RR = 0.46, 95% CI = 0.22-0.96). The pooled meta-analysis from cohort studies suggested a higher risk of transient dysesthesia (RR = 3.70, 95% CI = 1.54-8.89), residual fragment (RR = 5.29, 95% CI = 2.67-10.45), and revision surgeries (RR = 1.53, 95% CI = 1.12-2.08) for FELD. CONCLUSIONS: The current evidence showed a lower risk of overall complications for FELD. The quality of evidence was moderate to low, and the risk of bias from the primary literature should be concerned.

Prognostic value and immunological characteristics of a novel cuproptosis-related long noncoding RNAs risk signature in kidney renal clear cell carcinoma.

Background: Cuproptosis has been found as a novel cell death mode significantly associated with mitochondrial metabolism, which may be significantly associated with the occurrence and growth of tumors. LncRNAs take on critical significance in regulating the development of kidney renal clear cell carcinoma (KIRC), whereas the correlation between cuproptosis-related LncRNAs (CRLs) and KIRC is not clear at present. Therefore, this study built a prognosis signature based on CRLs, which can achieve accurate prediction of the outcome of KIRC patients. Methods: The TCGA database provided the expression profile information and relevant clinical information of KIRC patients. Univariate Cox, Lasso, and multivariate Cox were employed for building a risk signature based on CRLs. Kaplan-Meier (K-M) survival analysis and time-dependent receiver operating characteristic (ROC) curve were employed for the verification and evaluation of the reliability and accuracy of risk signature. Then, qRT-PCR analysis of risk LncRNAs was conducted. Finally, the possible effect of the developed risk signature on the microenvironment for tumor immunization was speculated in accordance with ssGSEA and ESTIMATE algorithms. Results: A prognosis signature composed of APCDD1L-DT, MINCR, AL161782.1, and AC026401.3 was built based on CRLs. As revealed by the results of the K-M survival study, the OS rate and progression-free survival rate of highrisk KIRC patients were lower than those of lowrisk KIRC patients, and the areas under ROC curves of 1, 3, and 5 years were 0.828, 0.780, and 0.794, separately. The results of the immune analysis showed that there were significant differences in the status of immunization and the microenvironment of tumor between groups at low-risk and at high-risk. The qRT-PCR results showed that the relative expression level of MINCR and APCDD1L-DT were higher in 786-O and 769-P tumor cells than in HK-2 cells, which were normal renal tubular epithelial cells. Conclusion: The developed risk signature takes on critical significance in the prediction of the prognosis of patients with KIRC, and it can bring a novel direction for immunotherapy and clinical drug treatment of KIRC. In addition, 4 identified risk LncRNAs (especially APCDD1L-DT and MINCR) can be novel targets for immunotherapy of KIRC patients.

Association between vitamin D serum levels and insulin resistance assessed by HOMA-IR among non-diabetic adults in the United States: Results from NHANES 2007-2014.

Insulin resistance, a pathological response to insulin hormone in insulin-dependent cells, is characterized by the presence of high glucose and insulin concentrations. The homeostasis model of insulin resistance (HOMA-IR) is one of the most used indexes to estimate insulin resistance by assessing the fasting glucose and insulin levels. An association was observed between vitamin D levels and insulin resistance, which varied in different ethnic groups, and there is some evidence that vitamin D supplementation could contribute to the improvement of insulin resistance. This study assessed the association between 25-hydroxyvitamin D (25[OH]D) concentration and HOMA-IR in American adults aged 20 years and older, without diabetes and other chronic diseases that can influence insulin resistance. The data from the National Health and Nutrition Examination Survey (NHANES) 2007-2014 were used by exploiting the free and publicly-accessible web datasets. Linear regression models were performed to evaluate the association between serum 25(OH)D concentration and HOMA-IR, and a negative association was observed, which remained significant following the adjustment for age, gender, race/ethnicity, education, body mass index (BMI), physical activity, the season of examination, current smoking, hypertension, the use of drugs which can influence insulin resistance, serum bicarbonates, triglycerides, and calcium and phosphorus levels. Only in non-Hispanic Blacks was this inverse association between vitamin D and HOMA-IR not observed in the fully adjusted model. Further studies are needed to explain the mechanisms of the observed ethnic/racial differences in the association of vitamin D levels with HOMA-IR.

Association between Wait Time for Transthoracic Echocardiography and 28-Day Mortality in Patients with Septic Shock: A Cohort Study.

Background: the optimal timing of Transthoracic echocardiography (TTE) performance for patients with septic shock remains unexplored. Methods: a retrospective cohort study included patients with septic shock in the MIMIC-Ⅲ database. Risk-adjusted restricted cubic splines modeled the 28-day mortality according to time elapsed from ICU admission to receive TTE. The cut point when a smooth curve inflected was selected to define early and delayed group. We applied propensity score matching (PSM) to ensure our findings were reliable. Causal mediation analysis was used to assess the intermediate effect of fluid balance within 72 h after ICU admission. Results: 3264 participants were enrolled and the risk of 28-day mortality increased until the wait time was around 10 h (Early group) and then was relatively flat afterwards (Delayed group). A beneficial effect of early TTE in terms of the 28-day mortality was observed (HRs 0.73−0.78, all p < 0.05) in the PSM. The indirect effect brought by the fluid balance on day 2 and 3 was significant (both p = 0.006). Conclusion: early TTE performance might be associated with lower risk-adjusted 28-day mortality in patients with septic shock. Better fluid balance may have mediated this effect. A wait time within 10 h after ICU may represent a threshold defining progressively increasing risk.

A Novel M7G-Related MicroRNAs Risk Signature Predicts the Prognosis and Tumor Microenvironment of Kidney Renal Clear Cell Carcinoma.

Background: M7G modification is extremely vital for the development of many cancers, especially tumor immunity. M7G modification is a novel functional regulator of miRNA, and the researches on m7G-related miRNAs in kidney renal clear cell carcinoma (KIRC) are still insufficient. This research aims to establish a risk signature on the foundation of m7G-associated miRNAs, which can precisely forecast the prognosis of KIRC patients. Methods: Transcriptome data and clinical data used in this study come from The Cancer Genome Atlas database. Our team utilized univariable Cox, Lasso and multivariable Cox analyses to construct a m7G-associated miRNAs risk signature that can forecast the prognosis of KIRC patients. Kaplan-Meier method, time-dependent receiver operating characteristic (ROC) curve, and the independent analysis of risk signatures were employed to verify the predictability and accuracy of the risk signature. Subsequently, based on CIBERSORT, ESTIMATE and ssGSEA algorithms, we speculated the potential impact of the proposed risk signature on tumor immune microenvironment. Ultimately, by virtue of the risk signature and tumor immunity, the hub genes affecting the prognosis of KIRC patients were screened out. Results: Our team established and verified a prognostic signature comprising 7 m7G-associated miRNAs (miR-342-3p, miR-221-3p, miR-222-3p, miR-1277-3p, miR-6718-5p, miR-1251-5p, and miR-486-5p). The results of the Kaplan-Meier survival analysis revealed that the prognosis of KIRC sufferers in the high-risk group was often unsatisfactory. The accuracy of the prediction ability of the risk signature was verified by calculating the area under the ROC curve. Univariate-multivariate Cox analyses further showed that this risk signature could be utilized as an independent prognosis-related biomarker for KIRC sufferers. The results of the immune analysis revealed that remarkable diversities existed in immune status and tumor microenvironment between high-risk and low-risk groups. On the foundation of the proposed risk signature and other clinical factors, a nomogram was established to quantitatively forecast the survival of KIRC sufferers at 1, 3 and 5 years. Conclusion: Based on m7G-related miRNAs, a risk signature was successfully constructed, which could precisely forecast the prognosis of sufferers and guide personalized immunotherapy for KIRC patients.

Percutaneous radiofrequency trigeminal rhizotomy benefits in patients with refractory trigeminal neuralgia.

ABSTRACT: A significant number of patients suffers from refractory trigeminal neuralgia (TN) after receiving microvascular decompression (MVD) or other neuro-destructive procedure such as gamma knife radiosurgery (GKRS). This study aims to demonstrate a remediable, reproducible approach to treating refractory pain effectively by percutaneous radiofrequency trigeminal rhizotomy (RF-TR).A total of 392 patients with TN were treated by RF-TR during the past 10 years. Among these patients, 48 cases who had received either MVD, GKRS alone, or a combination of both were assigned to group A. Those who had not received any form of treatment (125 patients) or failed to respond medically (130 patients) were assigned as the control group (group B). All the RF-TR were performed by a single surgeon with the aid of intraoperative computed tomography (iCT)-based neuronavigation with magnetic resonance (MR) image fusion. The outcome measure was the numerical rating scale (NRS) expressed subjectively by patients. The paired Student t test and the analysis of covariance (ANCOVA) were used for statistical analysis.In group A, 21 of 24 patients (88%) had significant improvement (NRS change ≥5) in facial pain after RF-TR. The average NRS score was 9.75 ±â€Š0.53 before the procedure and 1.92 ±â€Š3.35 post-treatment (significant NRS decrease [P = .000]). On the other hand, in group B, 226 of 255 patients (89%) also had dramatic amelioration of facial pain after RF-TR. The average NRS score was 9.46 ±â€Š0.69 before the procedure and 1.62 ±â€Š2.85 post-treatment (7.84 ±â€Š2.82 in NRS decrease [P = .008]). By using a univariate ANCOVA, no statistical significance was found in NRS score improvement between the two groups.Repeated MVD and GKRS for refractory TN may be less desirable due to a greater risk of mortality (up to 0.8%) and morbidity (4% of serious complications). Conversely, RF-TR administration with the novel navigation technique by using iCT and MR image fusion is free from any remarkable and irreversible morbidities. In this study, RF-TR not only provided an alternative and effective strategy if TN recurred but also resulted in the same NRS score improvement regardless of the status of prior treatment.