The prognostic and immune significance of PLBD1 in pan-cancer and its roles in proliferation and invasion of glioma.

Cancer is a destructive disease and is currently the leading cause of major threats to human health. PLBD1 is a transcription factor that regulates phospholipid metabolism, but its role in tumors is unknown. We assessed pan-cancer expression, methylation, and mutation data of PLBD1 by multiple databases to investigate its clinical prognostic value. In addition, we examined the pan-cancer immunological signature of PLBD1, particularly in gliomas. Furthermore, we assessed the impact of PLBD1 knockdown on the proliferation and invasive capacity of glioma cells by in vitro experiments. Our results suggest that PLBD1 is highly expressed in multiple types of cancers, and it can serve as an independent prognostic factor for gliomas. In addition, we found that the epigenetic alterations of PLBD1 were highly heterogeneous in a variety of cancers, including gliomas, and that its high methylation was associated with poor prognosis in a broad range of cancers. Immunological profiling demonstrated that PLBD1 was significantly associated with immune cell infiltration and multiple immune checkpoints in gliomas and is a potential biomarker for gliomas. Furthermore, cellular experiments showed that knockdown of PLBD1 significantly inhibited the proliferation and invasive ability of glioma cells. In conclusion, PLBD1 is a potential tumor prognostic biomarker and immunotherapeutic target that plays a crucial role in glioma cell proliferation, invasion and immunotherapy.

Risk Factors for Acute Kidney Injury in Adult Patients Under Veno-Arterial Extracorporeal Membrane Oxygenation Support.

OBJECTIVE: To investigate the incidence and risk factors of acute kidney injury (AKI) stage 3 in adult patients under veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. DESIGN: A retrospective case-control study. SETTING: Single center, Fuwai Hospital. PARTICIPANTS: Adult VA-ECMO patients age ≥18 years and older treated between January 2020 and December 2022 were included. INTERVENTIONS: The patients were grouped by whether they developed AKI Kidney Disease: Improving Global Outcomes (KDIGO) stage 3 or <3. Multivariate logistic regression was performed t"o evaluate risk factors of AKI stage 3. MEASUREMENTS AND MAIN RESULTS: Among enrolled patients, 40 (53.3%) developed AKI stage 3. The in-hospital mortality of AKI stage 3 patients was significantly higher than that of AKI stage <3 patients (67.5% vs 34.3%; p = 0.004). Multivariate logistic regression analysis revealed that concomitant hypertension (odds ratio [OR], 0.250; 95% confidence interval [CI], 0.063, 0.987), p = 0.048), pre-ECMO hemoglobin (OR, 0.969; 95% CI, 0.947-0.992; p = 0.009), pre-ECMO lactate (OR, 1.173; 95% CI, 1.028-1.339; p = 0.018), and pre-ECMO creatinine (OR, 1.014; 95% CI, 1.003-1.025; p = 0.011) were independent risk factors for AKI stage 3. CONCLUSIONS: This study found a high incidence (53.3%) of AKI stage 3 in adult patients with VA-ECMO support and an association with increased in-hospital mortality. Concomitant hypertension, low pre-ECMO hemoglobin, and elevated pre-ECMO lactate and pre-ECMO creatinine were independent risk factors for AKI stage 3 in patients receiving VA-ECMO. It is imperative to identify and adjust these risk factors to enhance outcomes for those supported by VA-ECMO.

Nonintubated spontaneous ventilation versus intubated mechanical ventilation anesthesia for video-assisted thoracic surgery in terms of perioperative complications and practitioners' workload assessments: a pilot randomized control study.

BACKGROUND: The use of nonintubated video-assisted thoracoscopic surgery (NI-VATS) has been increasingly reported to yield favourable outcomes. However, this technology has not been routinely used because its advantages and safety have not been fully confirmed. The aim of this study was to assess the safety and feasibility of nonintubated spontaneous ventilation (NI-SV) anesthesia compared to intubated mechanical ventilation (I-MV) anesthesia in VATS by evaluating of perioperative complications and practitioners' workloads. METHODS: Patients who underwent uniportal VATS were randomly assigned at a 1:1 ratio to receive NI-SV or I-MV anesthesia. The primary outcome was the occurrence of intraoperative airway intervention events, including transient MV, conversion to intubation and repositioning of the double-lumen tube. The secondary outcomes included perioperative complications and modified National Aeronautics and Space Administration Task Load Index (NASA-TLX) scores from anesthesiologists and surgeons. RESULTS: Thirty-five patients in each group were enrolled in the intention-to-treat analysis. The incidence of intraoperative airway intervention events was greater in the NI-SV group than in the I-MV group (12 [34.3%] vs. 3 [8.6%]; OR = 0.180; 95% CI = 0.045-0.710; p = 0.009). No significant difference was found in the postoperative pulmonary complications between the groups (p > 0.05). The median of the anesthesiologists' overall NASA-TLX score was 37.5 (29-52) when administering the NI-SV, which was greater than the 25 (19-34.5) when the I-MV was administered (p < 0.001). The surgeons' overall NASA-TLX score was comparable between the two ventilation strategies (28 [21-38.5] vs. 27 [20.5-38.5], p = 0.814). CONCLUSION: The NI-SV anesthesia was feasible for VATS in the selected patients, with a greater incidence of intraoperative airway intervention events than I-MV anesthesia, and with more surgical effort required by anesthesiologists. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055427. https://www.chictr.org.cn/showproj.html?proj=147872 was registered on January 09, 2022.

Is There an Optimal Time Window of Placement of Intracranial Pressure (ICP) Monitor for Elderly Patients With Severe Traumatic Brain Injury? An 11-Year Institutional Cohort Study With Restricted Cubic Spline Analysis.

Severe traumatic brain injury (sTBI) is a prominent contributor to both morbidity and mortality in the elderly population. The monitoring of intracranial pressure (ICP) is crucial in the management of sTBI patients. Nevertheless, the appropriate timing for the placement of ICP monitor in elderly sTBI patients remains uncertain. To determine the optimal timing for the placement of ICP monitor in elderly sTBI patients, in this retrospective cohort study, we collected data from elderly patients (> 65 years) who suffered sTBI and received ICP monitors at Tangdu Hospital, The Fourth Military Medical University, between January 2011 and December 2021. To examine the relationship between the time of ICP monitor placement and in-hospital mortality, we conducted a multi-variate-adjusted restricted cubic spline (RCS) analysis. Additionally, logistic regression analysis was applied to further analyze the influencing factors contributing to early or late ICP monitor placements. A total of 283 eligible elderly TBI patients were included in the current analysis. The in-hospital mortality rate was 73 out of 283 (26%). The RCS analysis demonstrated an inverted U-shaped curve in the relationship between the timing of ICP monitor placement and in-hospital mortality. For the elderly sTBI patient cohort, 6 h was identified as the crucial moment for the treatment strategy. In addition, the protective time window for ICP placement was less than 4.92 h for the GCS 3-5 group, and less than 8.26 h for the GCS 6-8 group. However, the clinical benefit of ICP placement decreased gradually over time. The relationship between ICP placement and in-hospital mortality was non-linear, exhibiting an inverted U-shaped curve in elderly patients with sTBI. For elderly patients with sTBI, early (≤ 6 h) ICP placement was associated with reduced in-hospital mortality. The clinical benefit of ICP placement decreased beyond the optimal time window.

The Development and Potential Applications of an Automated Method for Detecting and Classifying Continuous Glucose Monitoring Patterns.

INTRODUCTION: Continuous glucose monitoring (CGM) is emerging as a transformative tool for helping people with diabetes self-manage their glucose and supporting clinicians in effective treatment. Unfortunately, many CGM users, and clinicians, find interpreting the large volume of CGM data to be overwhelming and complex. To address this challenge, an efficient, intelligent method for detecting and classifying discernable patterns in CGM data was desired. METHODS: We developed an automated artificial intelligence (AI)-driven method to detect and classify different discernable CGM patterns which called "CGM events." We trained different models using 60 days of CGM data from 27 individuals with diabetes from a publicly available data set and then evaluated model performance using separate test data from the same group. Each event is classified according to clinical significance based on three parameters: (1) glucose category at or near the beginning of the CGM event; (2) a calculated severity score that encompasses both signal shape and temporal characteristics (e.g., how high the CGM curve goes (measured in mg/dL) and how long it stays above target (as established by published consensus guidelines); and (3) the glucose category at or near the end of the event. RESULTS: The system accurately detected and classified events from actual CGM data. This was also validated with expert diabetes clinicians. CONCLUSIONS: Advanced pattern recognition methods can be used to detect and classify CGM events of interest and may be used to provide actionable insights and self-management support to CGM users and decision support to the clinicians caring for them.

Study on Improved Computed Tomography Scanning Parameters for Patients with Nasal Bone Fracture Based on ITK Three-dimensional Labelling.

OBJECTIVE: To investigate the influence of improved exposure parameters on the image quality of multi-slice spiral computed tomography in nasal bone fracture imaging. METHODS: Fifty patients with optimised parameters combined with coronal scanning were allocated to the modified group and 50 patients with routine scanning parameters to the routine group. The image quality and nasal bone display of the two groups were assessed and statistically analysed, and the quality of scanned images before and after parameter optimisation was compared. RESULTS: The optimised image quality was better than that of conventional scanning parameters. The parameters used were 120 kv, 180 mA, a layer thickness of 0.625 mm, a layer spacing of 0.312 mm, a pitch of 0.516:1, a frame speed of 1 s, a scanning field of 12 cm and a reconstructed layer thickness for scanning of 0.625 mm; the scanned image was clear, and the parameter optimisation was achieved. This ensures that the annotation data in ITK labelling is more accurate. CONCLUSION: The optimised parameters and scanned coronal plane show the nasal bone and its surrounding structures more comprehensively, which is of high diagnostic value for nasal bone fractures. The three-dimensional annotation data based on ITK is more standardised, laying a foundation for the subsequent research of artificial intelligence modelling.

Maintaining Drosha expression with Cdk5 inhibitors as a potential therapeutic strategy for early intervention after TBI.

Traumatic brain injury (TBI) is a major cause of death and disability in adults. The pathological process of TBI involves a multifactorial cascade in which kinases have been proven contribute to interactions between relevant factors and amplification of signaling cascades. Cyclin-dependent kinase 5 (Cdk5) is a promising kinase that has been implicated in various brain disorders, including TBI. However, the mechanism by which Cdk5 induces neuronal damage remains unclear. Here, we show for the first time that Drosha, a key enzyme in microRNA biogenesis, is a pivotal substrate of abnormally activated Cdk5. Cdk5-mediated phosphorylation decreases Drosha expression and exacerbates nerve injury in TBI. We proved that maintaining Drosha expression via the administration of repurposed Cdk5 inhibitors that were previously studied in clinical trials is a promising approach for the early treatment of TBI. Together, our work identifies Drosha as a novel target for neuroprotective strategies after TBI and suggests Cdk5-mediated regulation of Drosha expression as a potential therapeutic strategy for early TBI intervention.

Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer.

MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) orchestrates diverse environmental signals to facilitate cell growth and is frequently activated in cancer. Translocation of MTORC1 from the cytosol to the lysosomal surface by the RRAG GTPases is the key step in MTORC1 activation. Here, we demonstrated that transcription factors MEF2A and MEF2D synergistically regulated MTORC1 activation via modulating its cyto-lysosome shutting. Mechanically, MEF2A and MEF2D controlled the transcription of FNIP1 and FNIP2, the components of the FLCN-FNIP1 or FNIP2 complex that acts as a RRAGC-RRAGD GTPase-activating element to promote the recruitment of MTORC1 to lysosome and its activation. Furthermore, we determined that the pro-oncogenic protein kinase SRC/c-Src directly phosphorylated MEF2D at three conserved tyrosine residues. The tyrosine phosphorylation enhanced MEF2D transcriptional activity and was indispensable for MTORC1 activation. Finally, both the protein and tyrosine phosphorylation levels of MEF2D are elevated in human pancreatic cancers, positively correlating with MTORC1 activity. Depletion of both MEF2A and MEF2D or expressing the unphosphorylatable MEF2D mutant suppressed tumor cell growth. Thus, our study revealed a transcriptional regulatory mechanism of MTORC1 that promoted cell anabolism and proliferation and uncovered its critical role in pancreatic cancer progression.Abbreviation: ACTB: actin beta; ChIP: chromatin immunoprecipitation; EGF: epidermal growth factor; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; FLCN: folliculin; FNIP1: folliculin interacting protein 1; FNIP2: folliculin interacting protein 2; GAP: GTPase activator protein; GEF: guanine nucleotide exchange factors; GTPase: guanosine triphosphatase; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MEF2: myocyte enhancer factor 2; MEF2A: myocyte enhancer factor 2A; MEF2D: myocyte enhancer factor 2D; MEF2D-3YF: Y131F, Y333F, Y337F mutant; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; NR4A1: nuclear receptor subfamily 4 group A member 1; RPTOR: regulatory associated protein of MTOR complex 1; RHEB: Ras homolog, mTORC1 binding; RPS6KB1: ribosomal protein S6 kinase B1; RRAG: Ras related GTP binding; RT-qPCR: real time-quantitative PCR; SRC: SRC proto-oncogene, non-receptor tyrosine kinase; TMEM192: transmembrane protein 192; WT: wild-type.

FGF21 alleviates endothelial mitochondrial damage and prevents BBB from disruption after intracranial hemorrhage through a mechanism involving SIRT6.

BACKGROUND: Disruption of the BBB is a harmful event after intracranial hemorrhage (ICH), and this disruption contributes to a series of secondary injuries. We hypothesized that FGF21 may have protective effects after intracranial hemorrhage (ICH) and investigated possible underlying molecular mechanisms. METHODS: Blood samples of ICH patients were collected to determine the relationship between the serum level of FGF21 and the [Formula: see text]GCS%. Wild-type mice, SIRT6flox/flox mice, endothelial-specific SIRT6-homozygous-knockout mice (eSIRT6-/- mice) and cultured human brain microvascular endothelial cells (HCMECs) were used to determine the protective effects of FGF21 on the BBB. RESULTS: We obtained original clinical evidence from patient data identifying a positive correlation between the serum level of FGF21 and [Formula: see text]GCS%. In mice, we found that FGF21 treatment is capable of alleviating BBB damage, mitigating brain edema, reducing lesion volume and improving neurofunction after ICH. In vitro, after oxyhemoglobin injury, we further explored the protective effects of FGF21 on endothelial cells (ECs), which are a significant component of the BBB. Mitochondria play crucial roles during various types of stress reactions. FGF21 significantly improved mitochondrial biology and function in ECs, as evidenced by alleviated mitochondrial morphology damage, reduced ROS accumulation, and restored ATP production. Moreover, we found that the crucial regulatory mitochondrial factor deacylase sirtuin 6 (SIRT6) played an irreplaceable role in the effects of FGF21. Using endothelial-specific SIRT6-knockout mice, we found that SIRT6 deficiency largely diminished these neuroprotective effects of FGF21. Then, we revealed that FGF21 might promote the expression of SIRT6 via the AMPK-Foxo3a pathway. CONCLUSIONS: We provide the first evidence that FGF21 is capable of protecting the BBB after ICH by improving SIRT6-mediated mitochondrial homeostasis.

Reducing CSF complications by a recycled Hadad's flap combined with autologous mucosa in secondary endoscope transsphenoidal surgery.

Background: Transsphenoidal secondary operations are a minority but not a rare occurrence. How to viably prevent cerebral fluid (CSF)-related complications and confine surgery-caused injury in secondary surgery as minimally as possible is a huge challenge. This article shares our solution of recycling a prior Hadad-Bassagasteguy flap (HBF) along with a using small piece of free autologous mucosa to reconstruct the skull base. Methods: Of 69 patients, fitted criteria were assigned into 2 different groups: a recycled HBF incorporated with an autologous free mucosa and a recycled HBF incorporated with an artificial dura to rebuild the skull base in secondary transsphenoidal surgery. The postoperative morbidities of pseudomeningocele, CSF leakage and meningitis were recorded and analyzed. Results: A recycled HBF incorporated with an autologous mucosa is capable of reducing CSF complications compared to that of the matched group, particularly decreasing the morbidity of meningitis in secondary transsphenoidal surgery. Diabetes mellitus, craniopharyngioma, chordoma and the utilization of artificial dura were independent risk factors for CSF complications in secondary transsphenoidal surgery through univariate and multivariate logistic regression. In addition, diabetes mellitus and artificial dura are more likely to induce CSF leakage and meningitis. Patients suffering from craniopharyngioma are more susceptible to meningitis. Chordoma indiscriminately increased the risk of each CSF complication. Conclusion: A recycled HBF incorporated with an autologous mucosa is reliable for reconstructing the skull base in secondary transsphenoidal surgery, especially for patients simultaneously suffering from diabetes mellitus and central skull base tumors.

Refined imaging features of culprit plaques improve the prediction of recurrence in intracranial atherosclerotic stroke within the middle cerebral artery territory.

Recurrence is a significant adverse outcome of ischemic stroke (IS), particularly in cases of intracranial arteriosclerosis (ICAS). In this study, we investigated the impact of imaging features of culprit plaque using high-resolution magnetic resonance vessel wall imaging (HR-MR-VWI) on the prediction of IS recurrence. A total of 86 patients diagnosed with ICAS-related IS within the middle cerebral artery (MCA) territory were included, of which 23.25% experienced recurrent IS within one year. Our findings revealed significant differences between the recurrence and non-recurrence groups in terms of age (p = 0.007), diabetes mellitus (p = 0.031), hyperhomocysteinemia (p = 0.021), artery-artery embolism (AAE) infarction (p = 0.019), prominent enhancement (p = 0.013), and surface irregularity of the culprit plaque (p = 0.009). Age (HR = 1.063, p = 0.005), AAE infarction (HR = 5.708, p = 0.008), and prominent enhancement of the culprit plaque (HR = 4.105, p = 0.025) were identified as independent risk factors for stroke recurrence. The areas under the receiver operating characteristic curve (AUCs) for predicting IS recurrence using clinical factors, conventional imaging findings, HR-MR-VWI plaque features, and a combination of clinical and conventional imaging models were 0.728, 0.645, 0.705, and 0.814, respectively. Notably, the combination model demonstrated superior predictive performance with an AUC of 0.870. Similarly, AUC of combination model for predicting IS recurrence in validation cohort which enrolled another 37 patients was 0.865. In conclusion, the presence of obvious enhancement in culprit plaque on HR-MR-VWI is a valuable factor in predicting IS recurrence in ICAS-related strokes within the MCA territory. Furthermore, our combination model, incorporating plaque features, exhibited improved prediction accuracy.

A Six-Surface System to Describe Anatomy of Anterior Clinoid Process and Its Application in Anterior Clinoidectomy and Resection of Paraclinoid Meningioma.

OBJECTIVE: The anterior clinoid process (ACP) is surrounded by nerves and vessels that, together, constitute an intricate anatomical structure with variations that challenges the performance of individualized anterior clinoidectomy in treating lesions with different extents of invasion. In the present study, we established a 6-surface system for the ACP based on anatomical landmarks and analyzed its value in guiding ACP drilling and resection of paraclinoid meningiomas. METHODS: Using the anatomical characteristics of 10 dry skull specimens, we set 9 anatomical landmarks to delineate the ACP into 6 surfaces. Guided by our 6-surface system and eggshell technique, 5 colored silicone-injected anatomical specimens were dissected via a frontotemporal craniotomy to perform anterior clinoidectomy. Next, 3 typical cases of paraclinoid meningioma were selected to determine the value of using our 6-surface system in tumor resection. RESULTS: Nine points (A-H and T) were proposed to delineate the ACP surface into frontal, temporal, optic nerve, internal carotid artery, cranial nerve III, and optic strut surfaces according to the adjacent tissues. Either intradurally or extradurally, the frontal and temporal surfaces could be identified and drilled into depth, followed by skeletonization of the optic nerve, cranial nerve III, internal carotid artery, and optic strut surfaces. After the residual bone was removed, the ACP was drilled off. In surgery of paraclinoid meningiomas, our 6-surface system provided great benefit in locating the dura, nerves, and vessels, thus, increasing the safety of opening the optic canal and relaxing the oculomotor or optic nerves and allowing for individualized ACP drilling for meningioma removal. CONCLUSIONS: Our 6-surface system adds much anatomical information to the classic Dolenc triangle and can help neurosurgeons, especially junior ones, to increase their understanding of the paraclinoid spatial structure and accomplish individualized surgical procedures with high safety and minimal invasiveness.

USP30 impairs mitochondrial quality control and aggravates oxidative damage after traumatic brain injury.

Clinical progress in the treatment of traumatic brain injury (TBI) is hindered by the poor understanding of the molecular mechanisms that underlie secondary brain injury (SBI). USP30, a mitochondrial deubiquitinase, has been implicated in the pathological progress of various diseases. However, the precise role of USP30 in TBI-induced SBI remains unclear. In this study, we found that USP30 was differentially upregulated after TBI in humans and mice. Immunofluorescence staining further revealed that the enhanced USP30 mainly localized in neurons. Neuron-specific knockout of USP30 reduced lesion volumes, mitigated brain edema, and attenuated neurological deficits after TBI in mice. Additionally, we found that USP30 deficiency effectively suppressed oxidative stress and neuronal apoptosis in TBI. Those protective effects of USP30 loss may be attributed, at least partially, to the reduction of TBI-induced impairment of mitochondrial quality control, including mitochondrial dynamics, function, and mitophagy. Collectively, our findings identify a previously undisclosed role of USP30 in the pathophysiology of TBI and lay a preliminary foundation for future research in this field.

The clinical and neurocognitive functional changes with awake brain mapping for gliomas invading eloquent areas: Institutional experience and the utility of The Montreal Cognitive Assessment.

Objective: Awake craniotomy with intraoperative brain functional mapping effectively reduces the potential risk of neurological deficits in patients with glioma invading the eloquent areas. However, glioma patients frequently present with impaired neurocognitive function. The present study aimed to investigate the neurocognitive and functional outcomes of glioma patients after awake brain mapping and assess the experience of a tertiary neurosurgical center in China over eight years. Methods: This retrospective study included 80 patients who underwent awake brain mapping for gliomas invading the eloquent cortex between January 2013 and December 2021. Clinical and surgical factors, such as the extent of resection (EOR), perioperative Karnofsky Performance Score (KPS), progression-free survival (PFS), and overall survival (OS), were evaluated. We also used the Montreal Cognitive Assessment (MoCA) to assess the neurocognitive status changes. Results: The most frequently observed location of glioma was the frontal lobe (33/80, 41.25%), whereas the tumor primarily invaded the language-related cortex (36/80, 45%). Most patients had supratotal resection (11/80, 13.75%) and total resection (45/80, 56.25%). The median PFS was 43.2 months, and the median OS was 48.9 months in our cohort. The transient (less than seven days) neurological deficit rate was 17.5%, whereas the rate of persistent deficit (lasting for three months) was 15%. At three months of follow-up, most patients (72/80, 90%) had KPS scores > 80. Meanwhile, compared to the preoperative baseline tests, the changes in MoCA scores presented significant improvements at discharge and three months follow-up tests. Conclusion: Awake brain mapping is a feasible and safe method for treating glioma invading the eloquent cortex, with the benefit of minimizing neurological deficits, increasing EOR, and extending survival time. The results of MoCA test indicated that brain mapping plays a critical role in preserving neurocognitive function during tumor resection.

P7C3-A20 Attenuates Microglial Inflammation and Brain Injury after ICH through Activating the NAD+/Sirt3 Pathway.

Intracerebral hemorrhage (ICH) is lethal but lacks effective therapies. Nicotinamide adenine dinucleotide (NAD+) is a central metabolite indispensable for a broader range of fundamental intracellular biological functions. Reduction of NAD+ usually occurs after acute brain insults, and supplementation of NAD+ has been proven neuroprotective. P7C3-A20 is a novel compound featuring its ability to facilitate the flux of NAD+. In this study, we sought to determine the potential therapeutic value of P7C3-A20 in ICH. In collagenase-induced ICH mouse models, we found that P7C3-A20 treatment could diminish lesion volume, reduce blood-brain barrier (BBB) damage, mitigate brain edema, attenuate neural apoptosis, and improve neurological outcomes after ICH. Further, RNA sequencing and subsequent experiments revealed that ICH-induced neuroinflammation and microglial proinflammatory activities were significantly suppressed following P7C3-A20 treatment. Mitochondrial damage is an important trigger of inflammatory response. We examined mitochondrial morphology and function and found that P7C3-A20 could attenuate OxyHb-induced impairment of mitochondrial dynamics and functions in vitro. Mechanistically, Sirt3, an NAD+-dependent deacetylase located in mitochondria, was then found to play a vital role in the protection of P7C3-A20 against mitochondrial damage and inflammatory response. In rescue experiments, P7C3-A20 failed to exert those protective effects in microglia-specific Sirt3 conditional knockout (CKO) mice. Finally, preclinical research revealed a correlation between the plasma NAD+ level and the neurological outcome in ICH patients. These results demonstrate that P7C3-A20 is a promising therapeutic agent for neuroinflammatory injury after ICH and exerts protective actions, at least partly, in a Sirt3-dependent manner.

Dose-dependent influence of red blood cell transfusion volume on adverse outcomes in cardiac surgery.

INTRODUCTION: Red blood cell (RBC) transfusion is associated with adverse outcomes, but there are few studies on the RBC volume. This study aimed to evaluate the relationship between intraoperative RBC volume and postoperative adverse outcomes for on-pump cardiac surgery. METHODS: Adult patients undergoing on-pump cardiac surgery from 1 January 2017 to 31 December 2018 were included. Those transfused with more than 6 units of RBC were excluded. The clinical characteristics of four groups with various RBC volume were compared. We analyzed the relationship between RBC volume and adverse outcomes through multivariable logistic regression. RESULTS: 12,143 patients were analyzed, of which 3353 (27.6%) were transfused with 1-6U RBC intraoperatively. The incidence of death, overall morbidity, acute kidney injury and prolonged mechanical ventilation were increased stepwise along with incremental RBC volume. After adjusting for possible confounders, patients transfused with 1-2U were associated with a 1.42-fold risk of death (99% CI, 1.21-2.34, p = 0.01) compared with patients without RBC, patients with 3-4U were associated with a 1.57-fold risk (99% CI, 1.32-2.80, p = 0.005) and patients with 5-6U had a 2.26-fold risk of death (99% CI, 1.65-3.88, p < 0.001). Similarly, the incidence of overall morbidity, acute kidney injury and prolonged mechanical ventilation increased several folds as the RBC numbers increased. CONCLUSIONS: There was a significant dose-dependent influence of incremental intraoperative RBC volume on increased risk of adverse outcomes for on-pump cardiac surgery patients. Patient blood management practice should aim to reduce not only transfusion rate but also the volume of blood use.

Assessment of artificial intelligence-aided reading in the detection of nasal bone fractures.

BACKGROUND: Artificial intelligence (AI) technology is a promising diagnostic adjunct in fracture detection. However, few studies describe the improvement of clinicians' diagnostic accuracy for nasal bone fractures with the aid of AI technology. OBJECTIVE: This study aims to determine the value of the AI model in improving the diagnostic accuracy for nasal bone fractures compared with manual reading. METHODS: A total of 252 consecutive patients who had undergone facial computed tomography (CT) between January 2020 and January 2021 were enrolled in this study. The presence or absence of a nasal bone fracture was determined by two experienced radiologists. An AI algorithm based on the deep-learning algorithm was engineered, trained and validated to detect fractures on CT images. Twenty readers with various experience were invited to read CT images with or without AI. The accuracy, sensitivity and specificity with the aid of the AI model were calculated by the readers. RESULTS: The deep-learning AI model had 84.78% sensitivity, 86.67% specificity, 0.857 area under the curve (AUC) and a 0.714 Youden index in identifying nasal bone fractures. For all readers, regardless of experience, AI-aided reading had higher sensitivity ([94.00 ± 3.17]% vs [83.52 ± 10.16]%, P< 0.001), specificity ([89.75 ± 6.15]% vs [77.55 ± 11.38]%, P< 0.001) and AUC (0.92 ± 0.04 vs 0.81 ± 0.10, P< 0.001) compared with reading without AI. With the aid of AI, the sensitivity, specificity and AUC were significantly improved in readers with 1-5 years or 6-10 years of experience (all P< 0.05, Table 4). For readers with 11-15 years of experience, no evidence suggested that AI could improve sensitivity and AUC (P= 0.124 and 0.152, respectively). CONCLUSION: The AI model might aid less experienced physicians and radiologists in improving their diagnostic performance for the localisation of nasal bone fractures on CT images.

Use self-gravitation traction to treat lumbar disc herniation: Study protocol for a double-center, single-blind randomized controlled trial.

BACKGROUND: Self-gravitation traction is 1 of the most popular treatments for lumbar disc herniation (LDH). This study aims to evaluate the effectiveness and safety of the self-gravitation traction device in the treatment of LDH and to confirm its positive treatment effect. METHODOLOGY: This trial is designed as a pragmatic double-center, single-blind, and 3-arm (1:1:1 ratio) randomized controlled trial. The recruited patients with LDH will be randomly allocated to the intervention (traction weight is 40% or 60% of its body weight) or control (traction weight is 20% of its body weight) group. Traction will be completed within 6 consecutive weeks (3 times a week), with 10 minutes of traction for the first 3 weeks, 20 minutes of traction for the next 3 weeks. After the experiment is completed, we will establish an experiment-related database. The software of SPSS, version 21 (SPSS Inc. Chicago, IL) will be used for statistical analysis, and measurement data will be expressed via mean and standard deviation (mean ±â€…SD). DISCUSSION: Once the trial is completed, we will publish the study in journals in both Chinese and English to promote the dissemination and use of the results. In addition, we also plan to promote the research results at various academic conferences both domestically and internationally.