Association Between Glycemic Variability and Persistent Acute Kidney Injury After Noncardiac Major Surgery: A Multicenter Retrospective Cohort Study.

BACKGROUND: While the relationship between glycemic variability (GV) and acute kidney injury (AKI) has been a subject of interest, the specific association of GV with persistent AKI beyond 48 hours postoperative after noncardiac surgery is not well-established. METHODS: This retrospective cohort study aimed to describe the patterns of different GV metrics in the immediate 48 hours after noncardiac surgery, evaluate the association between GV indices and persistent AKI within the 7-day postoperative window, and compare the risk identification capabilities of various GV for persistent AKI. A total of 10,937 patients who underwent major noncardiac surgery across 3 medical centers in eastern China between January 2015 and September 2023 were enrolled. GV was characterized using the coefficient of variations (CV), mean amplitude of glycemic excursions (MAGE), and the blood glucose risk index (BGRI). Multivariable logistic regression was used to examine the relationship between GV and AKI. Optimal cutoff values for GV metrics were calculated through the risk identification models, and an independent cohort from the INformative Surgical Patient dataset for Innovative Research Environment (INSPIRE) database with 7714 eligible cases served to externally validate the risk identification capability. RESULTS: Overall, 274 (2.5%) of the 10,937 patients undergoing major noncardiac surgery met the criteria of persistent AKI. Higher GV was associated with an increased risk of persistent AKI (CV: odds ratio [OR] = 1.26, 95% confidence interval [CI], 1.08-1.46; MAGE: OR = 1.31, 95% CI, 1.15-1.49; BGRI: OR = 1.18, 95% CI, 1.08-1.29). Compared to models that did not consider glycemic factors, MAGE and BGRI independently contributed to predicting persistent AKI (MAGE: areas under the curve [AUC] = 0.768, P = .011; BGRI: AUC = 0.764, P = .014), with cutoff points of 3.78 for MAGE, and 3.02 for BGRI. The classification of both the internal and external validation cohorts using cutoffs demonstrated good performance, achieving the best AUC values of 0.768 for MAGE in the internal cohort and 0.777 for MAGE in the external cohort. CONCLUSIONS: GV measured within 48 hours postoperative period is an independent risk factor for persistent AKI in patients undergoing noncardiac surgery. Specific cutoff points can be used to stratify at-risk patients. These findings indicate that stabilizing GV may potentially mitigate adverse kidney outcomes after noncardiac surgery, highlighting the importance of glycemic control in the perioperative period.

Comparison of Carotid Blood Flow Measured by Ultrasound and Cardiac Output in Patients Undergoing Cardiac Surgery.

BACKGROUND: In general, cerebral blood flow accounts for 10-15% of cardiac output (CO), of which about 75% is delivered through the carotid arteries. Hence, if carotid blood flow (CBF) is constantly proportional to CO with high reproducibility and reliability, it would be of great value to measure CBF as an alternative to CO. The aim of this study was to investigate the direct correlation between CBF and CO. We hypothesized that measurement of CBF could be a good substitute for CO, even under more extreme hemodynamic conditions, for a wider range of critically ill patients. METHODS: Patients aged 65-80 years, undergoing elective cardiac surgery were included in this study. CBF in different cardiac cycles were measured by ultrasound: systolic carotid blood flow (SCF), diastolic carotid blood flow (DCF), and total (systolic and diastolic) carotid blood flow (TCF). CO simultaneously was measured by transesophageal echocardiography. RESULTS: For all patients, the correlation coefficients between SCF and CO, TCF and CO were 0.45 and 0.30, respectively, which were statistically significant, but not between DCF and CO. There was no significant correlation between either SCF, TCF or DCF and CO, when CO was <3.5 L/min. CONCLUSIONS: Systolic carotid blood flow may be used as a better index to replace CO. However, the method of direct measurement of CO is essential when the patient's heart function is poor.

Intraoperative venous congestion rather than hypotension is associated with acute adverse kidney events after cardiac surgery: a retrospective cohort study.

BACKGROUND: The pathophysiological mechanisms by which venous congestion and hypotension lead to acute adverse kidney events after cardiac surgery with cardiopulmonary bypass have not been elucidated. We tested the hypothesis that intraoperative hypotension and venous congestion are associated with acute kidney injury and acute kidney disease. METHODS: Primary exposures were venous congestion and intraoperative hypotension defined by central venous pressure ≥12, 16, or 20 mm Hg or mean arterial pressure ≤55, 65, or 75 mm Hg. The primary outcomes were acute kidney injury and acute kidney disease. Multivariable logistic regression and Cox proportional hazard models were used, adjusted for relevant confounding factors and multiple comparisons. RESULTS: Of 5127 eligible subjects, 1070 (20.9%) and 327 (7.2%) developed acute kidney injury and acute kidney disease, respectively. The occurrence of acute kidney injury was statistically associated with both venous congestion and intraoperative hypotension. The cumulative incidence rate for new onset acute kidney disease was 1.34 (95% confidence interval [CI], 1.21-1.60) per 100 person-days. Acute kidney disease was significantly associated with each 10 min epoch of central venous pressure ≥12 mm Hg (hazard ratio [HR]=1.03; 99% CI, 1.01-1.06; P<0.001), ≥16 mm Hg (HR=1.04; 99% CI, 1.01-1.07; P<0.001), and ≥20 mm Hg (HR=1.07; 99% CI, 1.02-1.13; P<0.001). Venous congestion was associated with an 8-17% increased risk for de novo renal replacement therapy. In contrast, intraoperative hypotension was not associated with development of acute kidney disease. CONCLUSION: Although both venous congestion and intraoperative hypotension are associated with acute kidney injury, only venous congestion correlates with acute kidney disease among patients undergoing cardiac surgery requiring cardiopulmonary bypass. The reported associations are suggestive of a pathophysiological role of venous congestion in acute kidney disease.

Value of respiratory variation of aortic peak velocity in predicting children receiving mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: Accurate volume assessment is crucial in children under fluid therapy. Over the last decade, respiratory variation of aortic peak velocity (△VPeak) has been applied in intensive care unit and surgeries to help clinicians guide fluid management. The aim of this systematic review and meta-analysis was to test diagnostic performance of △VPeak in predicting fluid responsiveness of ventilated children and to explore the potential factors that influence the accuracy of △VPeak. METHODS: We searched PubMed, Embase, and Cochrane from inception to April 2019 that evaluated association between △VPeak and fluid responsiveness after fluid challenge in children receiving mechanical ventilation. Data synthesis was performed within the bivariate mixed-effects regression model modified for synthesis of diagnostic test data. RESULTS: Eleven studies with a total of 302 pediatric patients were included in our meta-analysis. The pooled sensitivity and specificity of △VPeak was 0.89 (95%CI = 0.77 to 0.95) and 0.85 (95%CI = 0.77 to 0.91), respectively. The diagnostic odds ratio (DOR) of △VPeak was 48 (95%CI = 15 to 155). SROC yielded an area under the curve of 0.91 (95%CI = 0.88-0.93). The △VPeak cutoff value was nearly conically symmetrical distribution and varied from 7 to 20%. After excluding several extreme studies, most data were centered between 12 and 13%. The medium and mean cutoff values of △VPeak were 12.2% and 12.7%, respectively. In subgroup analysis, compared to total data analysis, △VPeak performed weaker in the younger children group (mean ages < 25 months), with lower area under the summary receiver operating characteristic curve (AUSROC) of 0.80 (0.76 to 0.83), but stronger in the older children group (mean ages > 25 months), with AUSROC of 0.96 (0.94 to 0.97). CONCLUSIONS: Overall, △VPeak has a good ability in predicting fluid responsiveness of children receiving mechanical ventilation, but this ability decreases in younger children (mean age < 25 months). The optimal threshold of △VPeak to predict fluid responsiveness in ventilated children is reliable between 12 and 13%. TRIAL REGISTRATION: The study protocol was registered prospectively on PROSPERO no. CRD42019129361.

High-loading Fe2O3/SWNT composite films for lithium-ion battery applications.

Single-walled carbon nanotube (SWNT) films are a potential candidate as porous conductive electrodes for energy conversion and storage; tailoring the loading and distribution of active materials grafted on SWNTs is critical for achieving maximum performance. Here, we show that as-synthesized SWNT samples containing residual Fe catalyst can be directly converted to Fe2O3/SWNT composite films by thermal annealing in air. The mass loading of Fe2O3 nanoparticles is tunable from 63 wt% up to 96 wt%, depending on the annealing temperature (from 450 °C to 600 °C), while maintaining the porous network structure. Interconnected SWNT networks containing high-loading active oxides lead to synergistic effect as an anode material for lithium ion batteries. The performance is improved consistently with increasing Fe2O3 loading. As a result, our Fe2O3/SWNT composite films exhibit a high reversible capacity (1007.1 mA h g-1 at a current density of 200 mA g-1), excellent rate capability (384.9 mA h g-1 at 5 A g-1) and stable cycling performance with the discharge capacity up to 567.1 mA h g-1 after 600 cycles at 2 A g-1. The high-loading Fe2O3/SWNT composite films have potential applications as nanostructured electrodes for various energy devices such as supercapacitors and Li-ion batteries.

Network Meta-Analysis on the Efficacy of Dexmedetomidine, Midazolam, Ketamine, Propofol, and Fentanyl for the Prevention of Sevoflurane-Related Emergence Agitation in Children.

Sevoflurane is associated with a relatively high incidence of emergence agitation (EA) in children. Prophylactic treatment, including midazolam, dexmedetomidine, ketamine, fentanyl and propofol, has been used to prevent EA. However, the question of which prophylactic treatment should be preferred to decrease the incidence of EA is still unclear. We conducted a network meta-analysis of randomized controlled trials to investigate the comparative efficacy of midazolam, dexmedetomidine, ketamine, fentanyl, and propofol for the prevention of sevoflurane-related EA in children. First, we used the odds ratios and 95% confidence interval as effect size. The results revealed that dexmedetomidine 0.19 (0.14-0.27), midazolam 0.22 (0.07-0.60), ketamine 0.28 (0.16-0.51), propofol 0.23 (0.10-0.53), and fentanyl 0.25 (0.17-0.36) led to a significant reduction of the incidence of EA when compared with placebo. With placebo as the standard of comparison, the degree of incoherence (a measure of how closely the entire network fits together) was small (ω = 8.66728e-08). The logor were dexmedetomidine -1.75 (-2.11 to -1.39), midazolam -1.07 (-1.54 to -0.60), ketamine -1.292 (-1.92 to -0.66), and fentanyl -1.13 (-1.56 to -0.70). When compared with dexmedetomidine, the logor were placebo 1.75 (1.39-2.11), midazolam 0.67 (0.09-1.25), ketamine 0.45 (-0.25-1.15), propofol 0.75 (0.19-1.31), and fentanyl 0.617 (0.13-1.11). When compared with ketamine, the logor were placebo 1.29 (0.66-1.92), midazolam 0.22 (-0.56 to 1.00), dexmedetomidine -0.45 (-1.15-0.25); propofol 0.29 (-0.45-1.03); and fentanyl 0.16 (-0.59-0.92). The study that showed dexmedetomidine, midazolam, ketamine, propofol, and fentanyl could significantly decrease the incidence of EA when compared with placebo. One interesting finding of this network meta-analysis is that dexmedetomidine might be the best choice to prevent EA. However, there is weak evidence that dexmedetomidine is better than ketamine for the prevention of sevoflurane-related EA in children. As a result, more studies are needed to compare dexmedetomidine with ketamine.

Transesophageal Echocardiographic Measurement of Cardiac Index by the Prosthetic Mitral Valve Method Is Not Similar to the Continuous Thermodilution Method Via a Pulmonary Artery Catheter.

OBJECTIVE: To compare the agreement of cardiac index measurements between transesophageal echocardiography across the prosthetic mitral valve and the continuous thermodilution method through a pulmonary artery catheter (PAC-TD) in patients undergoing double-valve replacement. DESIGN: Observational prospective study. SETTING: University hospital. PARTICIPANTS: Twenty-five patients undergoing double-valve replacement (12 men and 13 women, age 25-78 years, ASA III-IV, NYHA II-III, LVEF≥45%). Patients were grouped according to their prosthesis (mechanical prosthesis v bioprosthesis). INTERVENTIONS: All patients underwent cardiac index assessment during double-valve replacement. MEASUREMENTS AND MAIN RESULTS: Cardiac index across the prosthetic mitral valve was measured simultaneously using transesophageal echocardiography (CI(MV)) and PAC-TD (CI(PAC)) at 15, 30, 45, and 60 minutes after weaning from cardiopulmonary bypass, and at 0, 15, and 30 minutes after incision closure. A correlation was present between CI(MV) and CI(PAC) in both groups (mechanical prosthesis: r = 0.47, p<0.01; bioprosthesis: r = 0.60, p<0.01). In the mechanical prosthesis group, the bias between techniques (CI(PAC) v CI(MV)) was-0.5 L/min/m(2) (95% CI:-1.97 to 0.97), and error was 55%. In the bioprosthesis group, the bias between both techniques was-1.3 L/min/m(2) (95% CI:-3.1 to 0.5), and error was 56%. CONCLUSIONS: A relatively weak correlation and lack of agreement between values of CI(PAC) and CI(MV) were observed in patients undergoing double-valve replacement. Therefore, transesophageal echocardiography might not be interchangeable with PAC-TD for measuring cardiac output or cardiac index. A regression equation is needed to correct the probable value of CI(PAC). CI(MV) might be useful as a quantitative or semi-quantitative cardiac output measurement.

[Effects of ulinastatin on cognitive function in patients with coronary artery bypass grafting].

OBJECTIVE: To investigate the effects of ulinastatin(UTI) on postoperative cognitive function in patients undergoing coronary artery bypass grafting. METHODS: One hundred and twenty-seven patients undergoing elective coronary artery bypass surgery were randomly divided into three groups:high-dose UTI group(16000 U/kg i.v.), low-dose UTI group(8000 U/kg i.v.) and control group(normal saline). The levels of plasma cortisol were measured before and one day after surgery. The level of IL-6, IL-10, TNF-α and S100ß were measured before operation(T0), at open chest(T1), end of operation(T2), 6 h(T3)and 24 h(T4) after operation. A neuropsychological test scale was to evaluate the cognitive function 1 day before operation, 1 week and 3 months after operation. RESULTS: Ninety-three patients completed the study. There was no significant difference in general information of patients among three groups(P>0.05). The level of plasma cortisol one day after operation was significantly higher than that before operation in control group(P<0.01). The levels of plasma cortisol in high-dose UTI group and low-dose UTI group were lower than that of control group(P<0.01). In all groups, the level of plasma IL-6, IL-10, TNF-α and S100B increased remarkably at T2, T3, T4 compared to those at T0(all P<0.05). The level of plasma IL-6, TNF-α(at T2, T3, T4)and S100ß(at T3)in high-dose UTI group and low-dose UTI group were all lower than those of control group(P<0.05),while there were no significant differences between high-dose UTI group and low-dose UTI group(P>0.05). The incidence of postoperative cognitive dysfunction in POCD 1 week after operation in high-dose UTI and low-dose UTI groups(25.8% and 23.3%)was lower than that in control group(50.0%), while there were no significant difference 1 month after operation between high-dose UTI group(12.9%) or low-dose UTI group(16.7%)and control group(28.1%). The level of plasma S100ß at T2 of POCD patients(n=31)was higher than that of non-POCD group(n=62)(P<0.05). CONCLUSION: Ulinastatin can reduce the incidence of postoperative cognitive dusfunction 1 week after coronary artery bypass surgery, which might be associated with inhibition of inflammation and S100ß expression.

Preconditioning effects of physiological cyclic stretch on pathologically mechanical stretch-induced alveolar epithelial cell apoptosis and barrier dysfunction.

BACKGROUND: We aim to investigate the effects of preconditioning of physiological cyclic stretch on the alveolar epithelial cell apoptosis induced by pathologically mechanical stretch and barrier dysfunction and how these effects are linked to differential expression of small GTPases Rac and Rho mRNA. METHODS: Pulmonary alveolar epithelial cells were subjected to different treatments of cyclic stretch (CS) at 5% and 20% elongation, respectively. Cells maintained in normal cell culture were used as negative control. On the other hand, cell apoptosis and Rac/Rho activities in cells with or without preconditioning of physiologically relevant magnitudes of CS (5% CS) with different durations (0, 15, 30, 60 and 120 min) in prior to 6-h treatment with pathological CS stimulation (20% CS) were compared and measured. RESULTS: Pathological CS could cause a significant increase in apoptosis rate, which is considered to be associated with the repression of Rac mRNA and activation of Rho mRNA. In contrast, physiological 5%-CS preconditioning suppressed cell apoptosis and induced nearly complete monolayer recovery with fewer actin stress fibers and paracellular gap formation. Consistent with differential effects on cell apoptosis and epithelial cell integrity, physiological CS preconditioning enhanced expression of Rac mRNA but inhibited Rho activation. CONCLUSIONS: Physiological CS preconditioning has an inhibitory effect on cell apoptosis while exerts a stimulatory impact on epithelial cell recovery via regulation of Rac and Rho activities.

[Effects of ultrasound-guided stellate ganglion block on cerebral oxygen metabolism and postoperative cognitive dysfunction in the elderly].

To observe the effects of ultrasound-guided stellate ganglion block (SGB) on cerebral oxygen metabolism and postoperative cognitive dysfunction (POCD) of elderly patients, we collected 80 elderly patients undergoing selective coronary artery bypass graft under cardiopulmonary bypass. The Mini Mental State Examination (MMSE) was applied to test the cognitive function. The SjvO2, Da-jvO2 and CEO2 were used for the analysis of the cerebral oxygen metabolism. We found that POCD was related to disequilibrium of cerebral oxygen metabolism. Ultrasound-guided SGB before surgery reduced the incidence of POCD because of the improvement of cerebral oxygen metabolism.

[Incidence and risk factors of postoperative cognitive dysfunction in patients underwent coronary artery bypass grafting surgery].

OBJECTIVE: To investigate the incidence rate and the risk factors for postoperative cognitive dysfunction (POCD) in patients underwent coronary artery bypass grafting surgery. METHODS: A total of 147 patients underwent elective coronary artery bypass grafting (CABG) surgery between January to July 2013 were included in this study. POCD was diagnosed using a neuropsychological test battery. All enrolled patients were interviewed on the day before surgery, the seventh day and 3 months after surgery, respectively, by the same researcher, and were divided into two groups based on the results: the POCD group and the non-POCD group. The information, including age, sex, body mass index, educational status, comorbidities, history of smoking and drinking, ASA grade, left ventricular ejection fraction, operation method, duration of operations, regional cerebral oxygen saturation, the lowest haemoglobin concentrations and the haemoglobin concentration decline rate during the operation, tracheal catheter retention time, postoperative pain on visual analogue scales (VAS) and systemic inflammatory response syndrome score (SIRS score), were recorded based on a schedule of survey. Multivariate logistic regression was used to analyze the risk factors for POCD. RESULTS: A total of 101 patients finished this study. On 7 days and 3 months after surgery, 38 and 21 cases showed POCD, with an incidence rate at 37.6% and 20.8%, respectively. Interestingly, there was no significant difference in incidence of POCD between CABG and OPCABG group on both 7 days and 3 months after surgery (P>0.05). The logistic stepwise regression analysis indicated that the risk factors for POCD included advanced age (OR=1.177, 95%CI 1.071-1.292, P=0.001), the haemoglobin concentration decline rate (OR=1.334, 95%CI 1.152-1.545, P<0.05) and SIRS score (OR=2.815, 95%CI 1.014-7.818, P=0.047). CONCLUSION: The incidence rate of POCD was 37.6% and 20.8% on 7 days and 3 months after surgery respectively. Advanced age, the haemoglobin concentration decline rate and SIRS score are independent risk factors for POCD in patients underwent coronary artery bypass grafting surgery.

Genetically supported causality between gut microbiota, immune cells, and ischemic stroke: a two-sample Mendelian randomization study.

Background: Previous studies have highlighted a robust correlation between gut microbiota/immune cells and ischemic stroke (IS). However, the precise nature of their causal relationship remains uncertain. To address this gap, our study aims to meticulously investigate the causal association between gut microbiota/immune cells and the likelihood of developing IS, employing a two-sample Mendelian randomization (MR) analysis. Methods: Our comprehensive analysis utilized summary statistics from genome-wide association studies (GWAS) on gut microbiota, immune cells, and IS. The primary MR method employed was the inverse variance-weighted (IVW) approach. To address potential pleiotropy and identify outlier genetic variants, we incorporated the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) technique, along with MR-Egger regression. Heterogeneity was assessed using Cochran's Q-test. Additionally, leave-one-out analysis was conducted to pinpoint any individual genetic variant influencing the observed causal associations. Finally, a reverse MR analysis was performed to explore the potential of reverse causation. Results: Our investigation revealed four gut microbial taxa and 16 immune cells with a significant causal relationship with IS (p < 0.05). Notably, two bacterial features and five immunophenotypes were strongly associated with a lower IS risk: genus.Barnesiella.id.944 (OR: 0.907, 95% CI: 0.836-0.983, p = 0.018), genus.LachnospiraceaeNK4A136group.id.11319 (OR: 0.918, 95% CI: 0.853-0.983, p = 0.988), Activated & resting Treg % CD4++ (OR: 0.977, 95% CI: 0.956-0.998, p = 0.028). Additionally, significant associations between IS risk and two bacterial features along with eleven immunophenotypes were observed: genus.Paraprevotella.id.962 (OR: 1.106, 95% CI: 1.043-1.172, p < 0.001), genus.Streptococcus.id.1853 (OR: 1.119, 95% CI: 1.034-1.210, p = 0.005), CD127 on granulocyte (OR: 1.039, 95% CI: 1.009-1.070, p = 0.011). Our analyses did not reveal heterogeneity based on the Cochrane's Q-test (p > 0.05) nor indicate instances of horizontal pleiotropy according to MR-Egger and MR-PRESSO analyses (p > 0.05). Furthermore, the robustness of our MR results was confirmed through leave-one-out analysis. Conclusion: Our study provides further evidence supporting the potential association between gut microbiota and immune cells in relation to IS, shedding light on the underlying mechanisms that may contribute to this condition. These findings lay a solid foundation for future investigations into targeted prevention strategies.

Risk factors for postoperative delirium in frail elderly patients undergoing on-pump cardiac surgery and development of a prediction model-a prospective observational study.

Background: To identify the risk factors for postoperative delirium (POD) after cardiac surgery in frail elderly patients and develop a receiver operating characteristic (ROC) prediction model to confirm the effectiveness. Methods: This was a prospective observational study, patients were assessed preoperatively according to the frailty index (FI) scale. Cerebral (SctO2) was assessed at different time points using near-infrared spectroscopy (NIRS). On the basis of the occurrence of POD within 7 days after surgery, patients were divided into POD and non-POD groups. Risk factors were analyzed using logistic regression analysis, while their predictive values were evaluated using the receiver operating characteristic curve analysis. Results: POD was significantly associated with frailty, lower preoperative MMSE scores, hyperlipidemia, diabetes, cerebrovascular disease, lower hemoglobin level, lower albumin level, longer operation time, longer CPB time, lower SctO2 at T5, and lower SctO2baseline (P < 0.05). SrtO2 and SmtO2 did not differ significantly between groups. FI, preoperative MMSE score, and operation time as independent risk factors (P < 0.05). Significant predictive value was demonstrated in all 3 variables (P < 0.001; respectively). Among them, high sensitivity and specificity were observed with the FI (cut-off value 0.27, sensitivity 75%, specificity 73.5%) and operation time (cut-off value 237.5, sensitivity 62.5%, specificity 78.6%). Conclusions: The FI, preoperative MMSE score, and operation time were independent risk factors for POD in elderly patients after cardiac surgery, with high predictive value observed with the FI and operation time. Cerebral oxygen saturation was associated with POD but was not an independent risk factor. Clinical Trial Registration: Chinese Clinical Trail Registry, No: chictr2200056038.

The Cytidine N-Acetyltransferase NAT10 Promotes Thalamus Hemorrhage-Induced Central Poststroke Pain by Stabilizing Fn14 Expression in Thalamic Neurons.

The recognition of RNA N4-acetylcytidine (ac4C) modification as a significant type of gene regulation is growing; nevertheless, whether ac4C modification or the N-acetyltransferase 10 protein (NAT10, the only ac4C "writer" that is presently known) participates in thalamus hemorrhage (TH)-induced central poststroke pain (CPSP) is unknown. Here, we observed NAT10 was primarily located in the neuronal nuclei of the thalamus of mice, with Fn14 and p65. An increase of NAT10 mRNA and protein expression levels in the ipsilateral thalamus was observed from days 1 to 14 after TH. Inhibition of NAT10 by several different approaches attenuated Fn14 and p65 upregulation of TH mice, as well as tissue injury in the thalamus on the ipsilateral side, and the development and maintenance of contralateral nociceptive hypersensitivities. NAT10 overexpression increased Fn14 and p65 expression and elicited nociceptive hypersensitivities in naïve mice. Our findings suggest that ac4C modification and NAT10 participate in TH-induced CPSP by activating the NF-κB pathway through upregulating Fn14 in thalamic neurons. NAT10 could serve as a promising new target for CPSP treatment.

Piezo2 Contributes to Traumatic Brain Injury by Activating the RhoA/ROCK1 Pathways.

Traumatic brain injury (TBI) can lead to short-term and long-term physical and cognitive impairments, which have significant impacts on patients, families, and society. Currently, treatment outcomes for this disease are often unsatisfactory, due at least in part to the fact that the molecular mechanisms underlying the development of TBI are largely unknown. Here, we observed significant upregulation of Piezo2, a key mechanosensitive ion channel protein, in the injured brain tissue of a mouse model of TBI induced by controlled cortical impact. Pharmacological inhibition and genetic knockdown of Piezo2 after TBI attenuated neuronal death, brain edema, brain tissue necrosis, and deficits in neural function and cognitive function. Mechanistically, the increase in Piezo2 expression contributed to TBI-induced neuronal death and subsequent production of TNF-α and IL-1ß, likely through activation of the RhoA/ROCK1 pathways in the central nervous system. Our findings suggest that Piezo2 is a key player in and a potential therapeutic target for TBI.

Genetically supported causality between gut microbiota and frailty: a two-sample Mendelian randomization study.

Background: A mounting body of evidence suggests a strong connection between gut microbiota and the risk of frailty. However, the question of causality remains unanswered. In this study, we employed a Mendelian randomization (MR) approach to assess potential causal relationships between gut microbiota and the risk of frailty. Materials and methods: Summary statistics for the gut microbiome were obtained from a genome wide association study (GWAS) meta-analysis of the MiBioGen consortium (N = 18,340). Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). Our primary analysis utilized the inverse variance weighted (IVW) method. To enhance the robustness of our results, we also applied weighted median methods, MR Egger regression, and MR pleiotropy residual sum and outlier test. Finally, we conducted reverse MR analysis to investigate the potential for reverse causality. Results: IVW method identified 7 bacterial taxa nominally associated with the risk of FI. Class Bacteroidia (p = 0.033) and genus Eubacterium ruminantium group (p = 0.028) were protective against FI. In addition, class Betaproteobacteria (p = 0.042), genus Allisonella (p = 0.012), genus Bifidobacterium (p = 0.013), genus Clostridium innocuum group (p = 0.036) and genus Eubacterium coprostanoligenes group (p = 0.003) were associated with a higher risk of FI. No pleiotropy or heterogeneity were found. Conclusion: The MR analysis indicates a causal relationship between specific gut microbiota and FI, offering new insights into the mechanisms underlying FI mediated by gut microbiota.

Genetically supported causality between gut microbiota, immune cells and morphine tolerance: a two-sample Mendelian randomization study.

Background: Previous researches have suggested a significant connection between the gut microbiota/immune cells and morphine tolerance (MT), but there is still uncertainty regarding their causal relationship. Hence, our objective is to inverstigate this causal association and reveal the impact of gut microbiota/immune cells on the risk of developing MT using a two-sample Mendelian randomization (MR) study. Methods: We conducted a comprehensive analysis using genome-wide association study (GWAS) summary statistics for gut microbiota, immune cells, and MT. The main approach employed was the inverse variance-weighted (IVW) method in MR. To assess horizontal pleiotropy and remove outlier single-nucleotide polymorphisms (SNPs), we utilized the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) technique as well as MR-Egger regression. Heterogeneity detection was performed using Cochran's Q-test. Additionally, leave-one-out analysis was carried out to determine if any single SNP drove the causal association signals. Finally, we conducted a reverse MR to evaluate the potential of reverse causation. Results: We discovered that 6 gut microbial taxa and 16 immune cells were causally related to MT (p < 0.05). Among them, 2 bacterial features and 9 immunophenotypes retained a strong causal relationship with lower risk of MT: genus. Lachnospiraceae NK4A136group (OR: 0.962, 95% CI: 0.940-0.987, p = 0.030), genus. RuminococcaceaeUCG011 (OR: 0.960, 95% CI: 0.946-0.976, p = 0.003), BAFF-R on B cell (OR: 0.972, 95% CI: 0.947-0.998, p = 0.013). Furthermore, 4 bacterial features and 7 immunophenotypes were identified to be significantly associated with MT risk: genus. Flavonifractor (OR: 1.044, 95% CI: 1.017-1.069, p = 0.029), genus. Prevotella9 (OR: 1.054, 95% CI: 1.020-1.090, p = 0.037), B cell % CD3-lymphocyte (OR: 1.976, 95% CI: 1.027-1.129, p = 0.026). The Cochrane's Q test revealed no heterogeneity (p > 0.05). Furthermore, the MR-Egger and MR-PRESSO analyses reveal no instances of horizontal pleiotropy (p > 0.05). Besides, leave-one-out analysis confirmed the robustness of MR results. After adding BMI to the multivariate MR analysis, the gut microbial taxa and immune cells exposure-outcome effect were attenuated. Conclusion: Our research confirm the potential link between gut microbiota and immune cells with MT, shedding light on the mechanism by which gut microbiota and immune cells may contribute to MT. These findings lay the groundwork for future investigations into targeted prevention strategies.

Temporal Distribution Patterns of Cryptic Brachionus calyciflorus (Rotifera) Species in Relation to Biogeographical Gradient Associated with Latitude.

Sympatric distribution and temporal overlap of cryptic zooplankton species pose a challenge to the framework of the niche differentiation theory and the mechanisms allowing competitor coexistence. We applied the methods of phylogenetic analysis, DNA taxonomy, and statistical analysis to study the temporal distribution patterns of the cryptic B. calyciflorus species, an excellent model, in three lakes, and to explore the putative mechanisms for their seasonal succession and temporal overlap. The results showed that in the warm-temperate Lake Yunlong, B. fernandoi and B. calyciflorus s.s. underwent a seasonal succession, which was largely attributed to their differential adaptation to water temperature. In the subtropical Lake Jinghu, B. fernandoi, B. calyciflorus s.s., and B. dorcas exhibited both seasonal succession and temporal overlap. Seasonal successions were largely attributed to their differential adaptation to temperature, and temporal overlap resulted from their differential responses to algal food concentration. In the tropical Lake Jinniu, B. calyciflorus s.s. persisted throughout the year and overlapped with B. dorcas for 5 months. The temporal overlap resulted from their differential responses to copepod predation. These results indicated that the temporal distribution pattern of the cryptic B. calyciforus species and the mechanism that allows competitor coexistence vary with different climate zones.

T(2)-weighted combined with diffusion-weighted images for evaluating prostatic transition zone tumors at 3 Tesla.

AIM: We hypothesize that the combination of T(2)-weighted (T(2)W) MRI with diffusion-weighted imaging (DWI) methods provides a powerful clinical application for the differential diagnosis of prostate cancer and benign lesion in the prostatic transition zone (TZ). METHODS: This retrospective study included 113 patients who were diagnosed with TZ lesions by MRI. The apparent diffusion coefficient values were compared between biopsy-proven benign and malignant lesions. RESULTS: The apparent diffusion coefficient values for the malignant nodules were significantly lower than those of the benign nodules. The area under the curve values for T(2)W imaging combined with DWI and T(2)W imaging alone were 0.991 and 0.884, respectively. CONCLUSION: T(2)W combined with DWI provides a powerful tool for noninvasive differentiation between malignant and benign prostatic hyperplasia nodules in the prostatic TZ.