Super-relaxed myosins contribute to respiratory muscle hibernation in mechanically ventilated patients.

Patients receiving mechanical ventilation in the intensive care unit (ICU) frequently develop contractile weakness of the diaphragm. Consequently, they may experience difficulty weaning from mechanical ventilation, which increases mortality and poses a high economic burden. Because of a lack of knowledge regarding the molecular changes in the diaphragm, no treatment is currently available to improve diaphragm contractility. We compared diaphragm biopsies from ventilated ICU patients (N = 54) to those of non-ICU patients undergoing thoracic surgery (N = 27). By integrating data from myofiber force measurements, x-ray diffraction experiments, and biochemical assays with clinical data, we found that in myofibers isolated from the diaphragm of ventilated ICU patients, myosin is trapped in an energy-sparing, super-relaxed state, which impairs the binding of myosin to actin during diaphragm contraction. Studies on quadriceps biopsies of ICU patients and on the diaphragm of previously healthy mechanically ventilated rats suggested that the super-relaxed myosins are specific to the diaphragm and not a result of critical illness. Exposing slow- and fast-twitch myofibers isolated from the diaphragm biopsies to small-molecule compounds activating troponin restored contractile force in vitro. These findings support the continued development of drugs that target sarcomere proteins to increase the calcium sensitivity of myofibers for the treatment of ICU-acquired diaphragm weakness.

Second-trimester triglyceride-glucose index to predict adverse outcomes in women with gestational diabetes mellitus: A retrospective multicenter cohort study.

AIMS/INTRODUCTION: Women with gestational diabetes mellitus are at high risk for adverse maternal and neonatal outcomes. The study aimed to evaluate the performance of the triglyceride-glucose index in predicting the risk of developing adverse outcomes in women with gestational diabetes mellitus. MATERIALS AND METHODS: This retrospective multicenter cohort study included 8,808 pregnant women with gestational diabetes mellitus in two grade-A tertiary hospitals in China during 2018-2022. The triglyceride-glucose index was defined as ln [triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. Significant adverse gestational diabetes mellitus outcomes were chosen by generalized linear models as the main outcomes. Multivariable logistic regression models evaluated their association with the triglyceride-glucose index. Areas under the receiver operating characteristic curves predicted adverse pregnancy outcomes. The prediction efficiency was validated in the sensitivity analysis dataset and validation cohort. RESULTS: The triglyceride-glucose index was associated with preeclampsia, severe preeclampsia, preterm birth, placenta accreta spectrum, and macrosomia before and after adjusting for confounding factors (P < 0.05). The predictive performance of the triglyceride-glucose index was relatively moderate. Incorporating the triglyceride-glucose index into the baseline clinical risk model improved the area under curves for the diagnosis of preeclampsia (0.749 [0.714-0.784] vs 0.766 [0.734-0.798], P = 0.033) and macrosomia (0.664 [0.644-0.685] vs 0.676 [0.656-0.697], P = 0.002). These predictive models exhibited good calibration and robustness. CONCLUSIONS: The triglyceride-glucose index is positively associated with preeclampsia, severe preeclampsia, preterm birth, placenta accreta spectrum, and macrosomia and is useful for the early prediction and prevention of adverse outcomes in women with gestational diabetes mellitus.

The effect of intraoperative intermittent pneumatic compression on deep venous thrombosis prophylaxis in patients undergoing elective craniotomy.

Objective: Postoperative deep venous thrombosis (DVT) is commonly observed in patients undergoing craniotomy and is associated with a high incidence of pulmonary embolism and poor clinical outcomes. Herein, we investigated the prophylactic effect of DVT of intraoperative intermittent pneumatic compression (IPC) in patients undergoing craniotomy. Methods: A total of 516 patients who underwent elective craniotomy between December 2021 and December 2022 were enrolled in this study. Patients were randomly assigned to the intervention group (received intraoperative IPC) or control group (without IPC). Lower extremity ultrasound was performed on both legs before and after surgery (1 h, 24 h, and 7 days post-intervention). DVT was defined as the visualization of a thrombus within the vein lumen of the leg. Coagulation and platelet function were measured at the start and end of the craniotomy. Results: A total of 504 patients (251 in the intervention group and 253 in the control group) completed the study. Among these patients, 20.4% (103/504) developed postoperative DVT within the first week after surgery, with 16.7% occurring within 24 h. The incidence of postoperative DVT in the intervention group (9.6%, 24/251) was significantly lower than that in the control group (22.9%, 58/253, p < 0.001). Intraoperative IPC reduced the risk of DVT by 64.6% (0.354, 95% CI, 0.223-0.564, p < 0.001). There was no significant difference in coagulation and platelet function between the two groups (all p > 0.05). Conclusion: DVT may develop within 24 h after the craniotomy. Intraoperative application of IPC reduces the incidence of postoperative DVT.

Oroxin A alleviates early brain injury after subarachnoid hemorrhage by regulating ferroptosis and neuroinflammation.

BACKGROUND: Subarachnoid hemorrhage (SAH), a severe subtype of stroke, is characterized by notably high mortality and morbidity, largely due to the lack of effective therapeutic options. Although the neuroprotective potential of PPARg and Nrf2 has been recognized, investigative efforts into oroxin A (OA), remain limited in preclinical studies. METHODS: SAH was modeled in vivo through filament perforation in male C57BL/6 mice and in vitro by exposing HT22 cells to hemin to induce neuronal damage. Following the administration of OA, a series of methods were employed to assess neurological behaviors, brain water content, neuronal damage, cell ferroptosis, and the extent of neuroinflammation. RESULTS: The findings indicated that OA treatment markedly improved survival rates, enhanced neurological functions, mitigated neuronal death and brain edema, and attenuated the inflammatory response. These effects of OA were linked to the suppression of microglial activation. Moreover, OA administration was found to diminish ferroptosis in neuronal cells, a critical factor in early brain injury (EBI) following SAH. Further mechanistic investigations uncovered that OA facilitated the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm to the nucleus, thereby activating the Nrf2/GPX4 pathway. Importantly, OA also upregulated the expression of FSP1, suggesting a significant and parallel protective effect against ferroptosis in EBI following SAH in synergy with GPX4. CONCLUSION: In summary, this research indicated that the PPARg activator OA augmented the neurological results in rodent models and diminished neuronal death. This neuroprotection was achieved primarily by suppressing neuronal ferroptosis. The underlying mechanism was associated with the alleviation of cellular death through the Nrf2/GPX4 and FSP1/CoQ10 pathways.

Decompressive craniectomy for patients with malignant infarction of the middle cerebral artery: A pooled analysis of two randomized controlled trials.

BACKGROUND: Decompressive craniectomy (DC) reduces mortality without increasing the risk of very severe disability among patients with life-threatening massive cerebral infarction. However, its efficacy was demonstrated before the era of endovascular thrombectomy trials. It remains uncertain whether DC improves the prognosis of patients with malignant middle cerebral artery (MCA) infarction receiving endovascular therapy. METHODS: We pooled data from two trials (DEVT and RESCUE BT studies in China) and patients with malignant MCA infarction were included to assess outcomes and heterogeneity of DC therapy effect. Patients with herniation were dichotomized into DC and conservative groups according to their treatment strategy. The primary outcome was the rate of mortality at 90 days. Secondary outcomes included disability level at 90 days as measured by the modified Rankin Scale score (mRS) and quality-of-life score. The associations of DC with clinical outcomes were performed using multivariable logistic regression. RESULTS: Of 98 patients with herniation, 37 received DC surgery and 61 received conservative treatment. The median (interquartile range) was 70 (62-76) years and 40.8% of the patients were women. The mortality rate at 90 days was 59.5% in the DC group compared with 85.2% in the conservative group (adjusted odds ratio, 0.31 [95% confidence interval (CI), 0.10-0.94]; P=0.04). There were 21.6% of patients in the DC group and 6.6% in the conservative group who had a mRS score of 4 (moderately severe disability); and 10.8% and 4.9%, respectively, had a score of 5 (severe disability). The quality-of-life score was higher in the DC group (0.00 [0.00-0.14] vs 0.00 [0.00-0.00], P=0.004), but DC treatment was not associated with better quality-of-life score in multivariable analyses (adjusted ß Coefficient, 0.02 [95% CI, -0.08-0.11]; p=0.75). CONCLUSIONS: DC was associated with decreased mortality among patients with malignant MCA infarction who received endovascular therapy. The majority of survivors remained moderately severe disability and required improvement on quality of life. CLINICAL TRIAL REGISTRATION: The DEVT trial: http://www.chictr.org. Identifier, ChiCTR-IOR-17013568. The RESCUE BT trial: URL: http://www.chictr.org. Identifier, ChiCTR-INR-17014167.

The performance of a new type accelerator uRT-linac 506c evaluated by a quality assurance automation system.

PURPOSE: The purpose of this study was to evaluate the performance of our quality assurance (QA) automation system and to evaluate the machine performance of a new type linear accelerator uRT-linac 506c within 6 months using this system. METHODS: This QA automation system consists of a hollow cylindrical phantom with 18 steel balls in the phantom surface and an analysis software to process electronic portal imaging device (EPID) measurement image data and report the results. The performance of the QA automation system was evaluated by the tests of repeatability, archivable precision, detectability of introduced errors, and the impact of set-up errors on QA results. The performance of this linac was evaluated by 31 items using this QA system over 6 months. RESULTS: This QA system was able to automatically deliver QA plan, EPID image acquisition, and automatic analysis. All images acquiring and analysis took approximately 4.6 min per energy. The preset error of 0.1 mm in multi-leaf collimator (MLC) leaf were detected as 0.12 ± 0.01 mm for Bank A and 0.10 ± 0.01 mm in Bank B. The 2 mm setup error was detected as -1.95 ± 0.01 mm, -2.02 ± 0.01 mm, 2.01 ± 0.01 mm for X, Y, Z directions, respectively. And data from the tests of repeatability and detectability of introduced errors showed the standard deviation were all within 0.1 mm and 0.1°. and data of the machine performance were all within the tolerance specified by AAPM TG-142. CONCLUSIONS: The QA automation system has high precision and good performance, and it can improve the QA efficiency. The performance of the new accelerator has also performed very well during the testing period.

Association between metal mixture exposure and abnormal glucose metabolism in multiple mixture exposure models: Evidence from NHANES 2015-2016.

Previous studies primarily focused on the single metal exposure and one-sided glucose metabolism disordered states, leading to conflicting results. Herein, we combined diabetes and prediabetes as abnormal glucose metabolism (AGM) to describe the effect of metal mixture exposure on it. Eligible data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2015-2016. In the generalized linear model (GLM), Cd (OR: 1.060, 95 %CI: 1.032-1.089, P value < 0.001) and Tl (OR: 1.039, 95 %CI: 1.004-1.075, P value = 0.031) exposure were positively associated with AGM. In the weighted quantile sum (WQS) regression model, the positive index was obviously associated with AGM (OR: 1.358, 95 %CI: 1.007-1.832, P value = 0.045). In the least absolute shrinkage and selection operator (LASSO) regression model, Cd and Tl were selected as the most contributors. In the Bayesian kernel machine regression (BKMR) model, the effect of co-exposure to metal mixture was associated with AGM, and Cd exposure showed a significantly positive trend. In conclusion, Cd and Tl exposure exhibited independent positive effects on AGM among metal mixture exposure, consistent with their effects on prediabetes.

Impact of Preoperative Sleep Disturbances on Postoperative Delirium in Patients with Intracranial Tumors: A Prospective, Observational, Cohort Study.

Background: Postoperative delirium (POD) is prevalent in craniotomy patients and is associated with high mortality. Sleep disturbances are receiving increasing attention from clinicians as associated risk factors for postoperative complications. This study aimed to determine the impact of preoperative sleep disturbances on POD in craniotomy patients. Methods: We recruited 130 patients undergoing elective craniotomy for intracranial tumors between May 1st and December 30th, 2022. Preoperative subjective sleep disturbances were assessed using the Pittsburgh Sleep Quality Index on the day of admission. We also measured objective perioperative sleep patterns using a dedicated sleep monitoring device 3 days before and 3 days after the surgery. POD was assessed twice daily using the Confusion Assessment Model for the Intensive Care Unit within the first week after craniotomy. Results: Preoperative sleep disturbances were diagnosed in 49% of the study patients, and POD was diagnosed in 22% of all the study patients. Sleep disturbances were an independent risk factor for POD (OR: 2.709, 95% CI: 1.020-7.192, P = 0.045). Other risk factors for POD were age (OR: 3.038, 95% CI: 1.195-7.719, P = 0.020) and the duration of urinary catheterization (OR: 1.246, 95% CI: 1.025-1.513, P = 0.027). Perioperative sleep patterns (including sleep latency, deep sleep duration, frequency of awakenings, apnea-hypopnea index, and sleep efficiency) were significantly associated with POD. Conclusion: This study demonstrated that preoperative sleep disturbances predispose patients undergoing craniotomy to POD, also inferred a correlation between perioperative sleep patterns and POD. The targeted screening and intervention specifically for sleep disturbances during the perioperative period are immensely required.

Do psychological distress and digital sports influence the willingness to take the vaccine and precautionary saving? Empirical evidence from Shanghai.

Aim: The COVID-19 epidemic has caused risk and uncertainty. This study answers whether and how psychological distress and digital sports influence willingness to take the vaccine and precautionary savings. Subject and methods: We conducted a cross-sectional study with an online survey sample of 1016 Shanghai residents who live and work there and are aged between 16-60. All of them experienced the COVID-19 lockdown in Shanghai. We used logistic regressions to examine the relationships between the variables of interest. Results: Three findings were demonstrated. First, psychologically distressed individuals are less inclined to take the vaccine. Second, those engaged in fitness activities via digital media platforms are more willing to get vaccinated. Third, psychologically distressed individuals and digital video-based physical exercisers are more likely to precautionary save. Conclusions: This study contributes to the literature by documenting how people changed their life from the perspective of finance and health during the lockdown and providing practical implications.

Metal artifacts reduction in kV-CT images with polymetallic dentures and complex metals based on MV-CBCT images in radiotherapy.

This paper proposes a metal artifact reduction method of using MV-CBCT images to correct metal artifacts in kV-CT images, especially for the complex metal artifacts caused by multi-metal interaction of patients with head and neck tumors. The different tissue regions are segmented in the MV-CBCT images to obtain template images and the metal region is segmented in the kV-CT images. Forward projection is performed to get sinogram of the template images, kV-CT images and metal region images. Artifact images can be reconstructed through those sonograms. Corrected images is generated by subtracting the artifact images from the original kV-CT images. After the first correction, the template images are generated again and brought into the previous step for iteration to get better correction result. CT data set of 7 patients are used in this study, compared with linear interpolation metal artifact (LIMAR) and normalized metal artifact reduction method, mean relative error of CT value is reduced by 50.5% and 63.3%, noise is reduced by 56.2% and 58.9%. The Identifiability Score of the tooth, upper/lower jaw, tongue, lips, masseter muscle and cavity in the corrected images by the proposed method have significantly improved (P < 0.05) than original images. The artifacts correction method proposed in this paper can effectively remove the metal artifacts in the images and greatly improve the CT value accuracy, especially in the case of multi-metal and complex metal implantation.

Astragaloside IV alleviates stroke-triggered early brain injury by modulating neuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

PURPOSE: Stroke is an acute cerebrovascular disease. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with an established therapeutic effect on central nervous system diseases. This study examined the neuroprotective properties and possible mechanisms of AS-IV in stroke-triggered early brain injury (EBI) in a rat transient middle cerebral artery occlusion (MCAO) model. METHODS: The neurological scores and brain water content were analyzed. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was utilized to determine the infarct volume, neuroinflammatory cytokine levels, and ferroptosis-related genes and proteins, and neuronal damage and molecular mechanisms were evaluated by terminal deoxynucleotidyl transferase dutp nick-end labeling (TUNEL) staining, western blotting, and real-time polymerase chain reaction. RESULTS: AS-IV administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6, and NF-κB, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. CONCLUSIONS: Hence, the findings of this research illustrate that AS-IV administration can improve delayed ischemic neurological deficits and decrease neuronal death by modulating nuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

Maternal circulating metabolic biomarkers and their prediction performance for gestational diabetes mellitus related macrosomia.

INTRODUCTION: Gestational diabetes mellitus (GDM), a metabolism-related pregnancy complication, is significantly associated with an increased risk of macrosomia. We hypothesized that maternal circulating metabolic biomarkers differed between women with GDM and macrosomia (GDM-M) and women with GDM and normal neonatal weight (GDM-N), and had good prediction performance for GDM-M. METHODS: Plasma samples from 44 GDM-M and 44 GDM-N were analyzed using Olink Proseek multiplex metabolism assay targeting 92 biomarkers. Combined different clinical characteristics and Olink markers, LASSO regression was used to optimize variable selection, and Logistic regression was applied to build a predictive model. Nomogram was developed based on the selected variables visually. Receiver operating characteristic (ROC) curve, calibration plot, and clinical impact curve were used to validate the model. RESULTS: We found 4 metabolism-related biomarkers differing between groups [CLUL1 (Clusterin-like protein 1), VCAN (Versican core protein), FCRL1 (Fc receptor-like protein 1), RNASE3 (Eosinophil cationic protein), FDR <  0.05]. Based on the different clinical characteristics and Olink markers, a total of nine predictors, namely pre-pregnancy body mass index (BMI), weight gain at 24 gestational weeks (gw), parity, oral glucose tolerance test (OGTT) 2 h glucose at 24 gw, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) at 24 gw, and plasma expression of CLUL1, VCAN and RNASE3 at 24 gw, were identified by LASSO regression. The model constructed using these 9 predictors displayed good prediction performance for GDM-M, with an area under the ROC of 0.970 (sensitivity = 0.955, specificity = 0.886), and was well calibrated (P Hosmer-Lemeshow test = 0.897). CONCLUSION: The Model included pre-pregnancy BMI, weight gain at 24 gw, parity, OGTT 2 h glucose at 24 gw, HDL and LDL at 24 gw, and plasma expression of CLUL1, VCAN and RNASE3 at 24 gw had good prediction performance for predicting macrosomia in women with GDM.

Astragaloside IV alleviates stroke-triggered early brain injury by modulating neuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway

Purpose: Stroke is an acute cerebrovascular disease. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with an established therapeutic effect on central nervous system diseases. This study examined the neuroprotective properties and possible mechanisms of AS-IV in stroke-triggered early brain injury (EBI) in a rat transient middle cerebral artery occlusion (MCAO) model. Methods: The neurological scores and brain water content were analyzed. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was utilized to determine the infarct volume, neuroinflammatory cytokine levels, and ferroptosis-related genes and proteins, and neuronal damage and molecular mechanisms were evaluated by terminal deoxynucleotidyl transferase dutp nickend labeling (TUNEL) staining, western blotting, and real-time polymerase chain reaction. Results: AS-IV administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6, and NF-κB, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. Conclusion: Hence, the findings of this research illustrate that AS-IV administration can improve delayed ischemic neurological deficits and decrease neuronal death by modulating nuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

Corrigendum: m6A regulatory gene-mediated methylation modification in glioma survival prediction.

[This corrects the article DOI: 10.3389/fgene.2022.873764.].

Trial of Thrombectomy 6 to 24 Hours after Stroke Due to Basilar-Artery Occlusion.

BACKGROUND: The effects and risks of endovascular thrombectomy 6 to 24 hours after stroke onset due to basilar-artery occlusion have not been extensively studied. METHODS: In a trial conducted over a 5-year period in China, we randomly assigned, in a 1:1 ratio, patients with basilar-artery stroke who presented between 6 to 24 hours after symptom onset to receive either medical therapy plus thrombectomy or medical therapy only (control). The original primary outcome, a score of 0 to 4 on the modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 4 moderately severe disability, and 6 death) at 90 days, was changed to a good functional status (a modified Rankin scale score of 0 to 3, with a score of 3 indicating moderate disability). Primary safety outcomes were symptomatic intracranial hemorrhage at 24 hours and 90-day mortality. RESULTS: A total of 217 patients (110 in the thrombectomy group and 107 in the control group) were included in the analysis; randomization occurred at a median of 663 minutes after symptom onset. Enrollment was halted at a prespecified interim analysis because of the superiority of thrombectomy. Thrombolysis was used in 14% of the patients in the thrombectomy group and in 21% of those in the control group. A modified Rankin scale score of 0 to 3 (primary outcome) occurred in 51 patients (46%) in the thrombectomy group and in 26 (24%) in the control group (adjusted rate ratio, 1.81; 95% confidence interval [CI], 1.26 to 2.60; P<0.001). The results for the original primary outcome of a modified Rankin scale score of 0 to 4 were 55% and 43%, respectively (adjusted rate ratio, 1.21; 95% CI, 0.95 to 1.54). Symptomatic intracranial hemorrhage occurred in 6 of 102 patients (6%) in the thrombectomy group and in 1 of 88 (1%) in the control group (risk ratio, 5.18; 95% CI, 0.64 to 42.18). Mortality at 90 days was 31% in the thrombectomy group and 42% in the control group (adjusted risk ratio, 0.75; 95% CI, 0.54 to 1.04). Procedural complications occurred in 11% of the patients who underwent thrombectomy. CONCLUSIONS: Among patients with stroke due to basilar-artery occlusion who presented 6 to 24 hours after symptom onset, thrombectomy led to a higher percentage with good functional status at 90 days than medical therapy but was associated with procedural complications and more cerebral hemorrhages. (Funded by the Chinese National Ministry of Science and Technology; BAOCHE ClinicalTrials.gov number, NCT02737189.).

Role of the Gut Microbiota in the Increased Infant Body Mass Index Induced by Gestational Diabetes Mellitus.

The connection between gestational diabetes mellitus (GDM) and the offspring's development, such as obesity, is well established. Emerging evidence indicates that the microbiota of the neonate's meconium is associated with maternal GDM status. To explore whether the association between GDM and infant body mass index (BMI) in early childhood is affected by the meconium microbiota, we recruited 120 mothers (60 healthy women and 60 with GDM) and their newborns from the Women's Hospital of Nanjing Medical University. Meconium of 120 neonates was collected within a few hours after birth and sequenced using 16S rRNA sequencing analysis. Children's BMI was measured at 12 months of age. The results revealed that infants born to mothers with GDM had increased BMI Z-scores at 12 months old and that the ß-diversity of their meconium microbiota was reduced. Several genera were observed to be significantly different between the GDM and control groups. The genus Burkholderia-Caballeronia-Paraburkholderia and an untitled genus in the family Enterobacteriaceae enriched in neonates born to healthy mothers were found to be negatively associated with infant BMI by using regression analysis. A coabundance group depleted in the GDM group was correlated negatively with 12-month BMI and mediated 21.65% of the association between GDM and infant BMI by mediation analyses. This study provided evidence for the associations among maternal GDM, the meconium microbiota, and infant BMI. Maternal GDM was demonstrated to affect infant BMI, mediated by the gut microbiome. Gut microbiome interventions might represent a novel technique to decrease the risk of GDM-induced childhood obesity. IMPORTANCE Using 16S rRNA sequencing analysis, regression analysis and mediation analysis were used to explore whether maternal gestational diabetes mellitus (GDM) changed the function and composition of the meconium microbiota and whether this explained the GDM-induced alterations of infant body mass index (BMI). This study showed that gut microbiome dysbiosis induced by maternal GDM might play an important role in the increased infant BMI during the first 12 months of life. Therefore, gut microbiome interventions might represent a novel technique to decrease the risk of GDM-induced childhood obesity.

Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke: The RESCUE BT Randomized Clinical Trial.

Importance: Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well. Recruitment took place between October 10, 2018, and October 31, 2021, with final follow-up on January 15, 2022. Interventions: Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was disability level at 90 days as measured by overall distribution of the modified Rankin Scale scores from 0 (no symptoms) to 6 (death). The primary safety outcome was the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 948 patients randomized (mean age, 67 years; 391 [41.2%] women), 948 (100%) completed the trial. The median (IQR) 90-day modified Rankin Scale score in the tirofiban group vs placebo group was 3 (1-4) vs 3 (1-4). The adjusted common odds ratio for a lower level of disability with tirofiban vs placebo was 1.08 (95% CI, 0.86-1.36). Incidence of symptomatic intracranial hemorrhage was 9.7% in the tirofiban group vs 6.4% in the placebo group (difference, 3.3% [95% CI, -0.2% to 6.8%]). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke undergoing endovascular thrombectomy, treatment with intravenous tirofiban, compared with placebo, before endovascular therapy resulted in no significant difference in disability severity at 90 days. The findings do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.

m6A Regulatory Gene-Mediated Methylation Modification in Glioma Survival Prediction.

The median survival of patients with gliomas is relatively short. To investigate the epigenetic mechanisms associated with poor survival, we analyzed publicly available datasets from patients with glioma. This analysis revealed 12 prognosis-related m6A regulatory genes that may be responsible for poor prognosis. These genes may be involved in genomic changes inherent to oxidative phosphorylation, adipogenesis, hedgehog signaling, and Myc signaling. We reconstructed a risk model with univariate and multivariate Cox analyses and identified older age and the m6A risk score as independent risk factors for predicting the prognosis of glioma patients, which is associated with glioma immune infiltration. In conclusion, m6A regulatory genes may serve as both reliable biomarkers and potential targets to increase the chance of survival of patients with glioma.