Mechanistic Interrogation on Wound Healing and Scar Removing by the Mo4/3B2-x Nanoscaffold Revealed Regulated Amino Acid and Purine Metabolism.

Wound rehabilitation is invariably time-consuming, scar formation further weakens therapeutic efficacy, and detailed mechanisms at the molecular level remain unclear. In this work, a Mo4/3B2-x nanoscaffold was fabricated and utilized for wound healing and scar removing in a mice model, while metabolomics was used to study the metabolic reprogramming of metabolome during therapy at the molecular level. The results showed that transition metal borides, called Mo4/3B2-x nanoscaffolds, could mimic superoxide dismutase and glutathione peroxidase to eliminate excess reactive oxygen species (ROS) in the wound microenvironment. During the therapeutic process, the Mo4/3B2-x nanoscaffold could facilitate the regeneration of wounds and removal of scars by regulating the biosynthesis of collagen, fibers, and blood vessels at the pathological, imaging, and molecular levels. Subsequent metabolomics study revealed that the Mo4/3B2-x nanoscaffold effectively ameliorated metabolic disorders in both wound and scar microenvironments through regulating ROS-related pathways including the amino acid metabolic process (including glycine and serine metabolism and glutamate metabolism) and the purine metabolic process. This study is anticipated to illuminate the potential clinical application of the Mo4/3B2-x nanoscaffold as an effective therapeutic agent in traumatic diseases and provide insights into the development of analytical methodology for interrogating wound healing and scar removal-related metabolic mechanisms.

Nanometabolomics Elucidated Biological Prospective of Mo4/3B2-x Nanosheets: Toward Metabolic Reprogramming of Amino Acid Metabolism.

Mo4/3B2-x nanosheets are newly developed, and 2D transition metal borides (MBene) were reported in 2021, but there is no report on their further applications and modification; hence, this article sheds light on the significance of potential biological prospects for future biomedical applications. Therefore, elucidation of the biocompatibility, biotoxicology, and bioactivity of Mo4/3B2-x nanosheets has been an urgent need to be fulfilled. Nanometabolomics (also referred as nanomaterials-based metabolomics) was first proposed and utilized in our previous work, which specialized in interpreting nanomaterials-induced metabolic reprogramming through aqueous metabolomics and lipidomics approach. Hence, nanometabolomics could be considered as a novel concept combining nanoscience and metabolomics to provide bioinformation on nanomaterials' biomedical applications. In this work, the safe range of concentration (<50 mg/L) with good biosafety toward human umbilical vein endothelial cells (HUVECs) was discovered. The low concentration (5 mg/L) and high concentration (50 mg/L) of Mo4/3B2-x nanosheets were utilized for the in vitro Mo4/3B2-x-cell interaction. Nanometabolomics has elucidated the biological prospective of Mo4/3B2-x nanosheets via monitoring its biocompatibility and metabolic shift of HUVECs. The results revealed that 50 mg/L Mo4/3B2-x nanosheets could lead to a stronger alteration of amino acid metabolism with disturbance of the corresponding amino acid-related pathways (including amino acid metabolism, amino acid degradation, fatty acid biosynthesis, and lipid biosynthesis and metabolism). These interesting results were closely involved with the oxidative stress and production of excess ROS. This work could be regarded as a pathbreaking study on Mo4/3B2-x nanosheets at a biological level, which also designates their further biochemical, medical, and industrial application and development based on nanometabolomics bioinformation.

Integrated metabolomics revealed the photothermal therapy of melanoma by Mo2C nanosheets: toward rehabilitated homeostasis in metabolome combined lipidome.

Melanoma, the most aggressive and life-threatening form of skin cancer, lacks innovative therapeutic approaches and deeper bioinformation. In this study, we developed a photothermal therapy (PTT) based on Mo2C nanosheets to eliminate melanoma while utilizing integrated metabolomics to investigate the metabolic shift of metabolome combined lipidome during PTT at the molecular level. Our results demonstrated that 1 mg ml-1 Mo2C nanosheets could efficiently convert laser energy into heat with a strong and stable photothermal effect (74 ± 0.9 °C within 7 cycles). Furthermore, Mo2C-based PTT led to a rapid decrease in melanoma volume (from 3.299 to 0 cm2) on the sixth day, indicating the effective elimination of melanoma. Subsequent integrated metabolomics analysis revealed significant changes in aqueous metabolites (including organic acids, amino acids, fatty acids, and amines) and lipid classes (including phospholipids, lysophospholipids, and sphingolipids), suggesting that melanoma caused substantial fluctuations in both metabolome and lipidome, while Mo2C-based PTT helped improve amino acid metabolism-related biological events (such as tryptophan metabolism) impaired by melanoma. These findings suggest that Mo2C nanosheets hold significant potential as an effective therapeutic agent for skin tumors, such as melanoma. Moreover, through exploring multidimensional bioinformation, integrated metabolomics technology provides novel insights for studying the metabolic effects of tumors, monitoring the correction of metabolic abnormalities by Mo2C nanosheet therapy, and evaluating the therapeutic effect on tumors.

Trends and patterns in the global burden of intracerebral hemorrhage: a comprehensive analysis from 1990 to 2019.

Objective: Intracerebral hemorrhage (ICH) is a significant cause of global mortality and morbidity. This study aimed to analyze the burden of ICH and its variation trends across 204 countries and territories from 1990 to 2019. Materials and methods: The study population comprised individuals of all ages and genders with ICH in 204 countries and regions between 1990 and 2019. Utilizing data from the Global Burden of Disease (GBD) study 2019, we collected information on age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and disability-adjusted life-years (DALYs) rate, which were compared by age, gender, and socio-demographic index (SDI). Results: In 2019, there were an estimated 3.4 million (3.0-3.9) incident cases, resulting in 2.8 million (2.6-3.0) deaths and 68.5 million (63.2-73.6) DALYs due to ICH. Between 1990 and 2019, the absolute number of incident cases, deaths, and DALYs increased by 43.0% (41.0-45.0), 37.0% (22.0-51.0), and 25.0% (12.0-36.0), respectively. However, the ASIR, ASDR, and DALYs showed a decreasing trend of-29.0% (-28.0 to -30.0), -36.0% (-29.0 to -43.0), and - 37.0% (-43.0 to -31.0), respectively. Countries with lower SDI tended to have higher ASIR, ASDR, and DALY rates. Conclusion: While the ASDR and DALY rates decreased from 1990 to 2019, the decline in ASIR was less pronounced. The global burden of ICH remains high, exhibiting significant variation across different genders, age groups, and SDI levels.

Surgical technique of temporal muscle resuspension during cranioplasty for minimizing temporal hollowing: A case series.

Background: Temporal hollowing is a common but often overlooked complication following cranioplasty. To minimize temporal hollowing caused by temporal muscle contraction, we present the novel technique for temporal muscle resuspension during cranioplasty. Methods: This is a retrospective case series which were done by a single surgeon at our university tertiary-A hospital between January 2019 and February 2020. The surgical technique was performed according to the forms of temporal muscle based on preoperative 3-D reconstruction and intraoperative images. All patients were followed up and evaluated on esthetic and functional outcomes. Results: 17 patients with an average age of 39.35 years, frontotemporoparietal cranial defect size of 78.85 cm2, and median follow-up of 7 months were included. The main cause of decompressive craniectomy was trauma (n = 15). Techniques of temporal muscle augmentative resuspension were performed. The follow-up esthetic and functional outcome evaluation showed that all patients had good postoperative results. No revision surgery was found among the patients. Conclusions: This study proposes methods of temporal muscle augmentative resuspension based on forms of the muscle. We believe this might be of use in minimizing temporal hollowing after cranioplasty.

40 Hz Blue LED Relieves the Gamma Oscillations Changes Caused by Traumatic Brain Injury in Rat.

Background: Photobiomodulation (PBM) using low-level light-emitting diodes (LEDs) can be rapidly applied to various neurological disorders safely and non-invasively. Materials and Methods: Forty-eight rats were involved in this study. The traumatic brain injury (TBI) model of rat was set up by a controlled cortical impact (CCI) injury. An 8-channel cortex electrode EEG was fixed to two hemispheres, and gamma oscillations were extracted according to each electrode. A 40 hz blue LED stimulation was set at four points of the frontal and parietal regions for 60 s each, six times per day for 1 week. Modified Neurologic Severity Scores (mNSS) were used to evaluate the level of neurological function. Results: In the right-side TBI model, the gamma oscillation decreased in electrodes Fp2, T4, C4, and O2; but significantly increased after 1 week of 40 hz Blue LED intervention. In the left-side TBI model, the gamma oscillation decreased in electrodes Fp1, T3, C3, and O1; and similarly increased after 1 week of 40 hz Blue LED intervention. Both left and right side TBI rats performed significantly better in mNSS after 40 hz Blue LED intervention. Conclusion: TBI causes the decrease of gamma oscillations on the injured side of the brain of rats. The 40 hz Blue LED therapy could relieve the gamma oscillation changes caused by TBI and improve the prognosis of TBI.

Association of Preoperative Cerebrospinal Fluids Parameters With Early Shunt Obstruction in Patients With Post-hemorrhagic Hydrocephalus Treated by Lumboperitoneal Shunt.

Background: Early shunt obstruction (SO) remains the most common cause of lumboperitoneal shunt (LPS) failure. Although there is anecdotal evidence that the level of cerebrospinal fluid (CSF) parameters might affect shunt performance, its association with early LPS obstruction in adults with post-hemorrhagic hydrocephalus (PHH) is unclear. Methods: The retrospective study was performed by reviewing the adults with PHH treated by LPS from years 2014 to 2018. We included patients with CSF samples analyzed within 1 week prior to shunt insertion or at the time of shunt insertion. Baseline characteristics of each patient were collected. The primary outcomes were the incidence rate and associated factors of SO occurring within 3 months of shunt placement. The secondary outcomes included scores on the National Institute of Health Stroke Scale (NIHSS) and Evans Index at discharge. Results: A total of 76 eligible patients were analyzed, of whom 61 were obstruction-free and 15 were early SO. The overall rate of early SO was 15.6%. The RBCs count and nucleated cells count in preoperative CSF were actually higher in patients with early SO, compared to patients in the control group. Multivariate analysis identified RBC elevation (>0 × 106/L; OR: 10.629, 95% CI: 1.238-91.224, p = 0.031) as a dependent risk factor for early SO. NIHSS dramatically decreased at discharge while the alteration of ventricular size was not observed. Conclusions: This study suggested that the presence of RBCs in preoperative CSF was associated with early SO in patients with PHH treated by LPS.

Shunting outcomes in communicating hydrocephalus: protocol for a multicentre, open-label, randomised controlled trial.

INTRODUCTION: Ventriculoperitoneal shunt (VPS) remains the most widely used methods to treat communicating hydrocephalus. More recently, lumboperitoneal shunt (LPS) has been suggested as a reasonable option in some studies. However, there is lack of high-quality studies comparing these two techniques in order to certain the benefits and harms to use one of these two methods. The purpose of the current study is to determine the effectiveness and safety of the LPS versus the VPS in patients with communicating hydrocephalus. METHODS AND ANALYSIS: All eligible patients aged 18-90 years with communicating hydrocephalus will be recruited and then randomly allocated into LPS or VPS group in a ratio of 1:1. All patients will be analysed before shunt insertion, at the time of discharge, 1 month, 6 months, 12 months and 24 months postoperatively. The primary outcome measure is the rate of shunt failure at a 2-year follow-up term. The secondary outcomes include Keifer's Hydrocephalus Scale, National Institute of Health Stroke Scale, Glasgow Outcome Scale Extended, Evans index, safety endpoints and cost-effectiveness of hospital stay. ETHICS AND DISSEMINATION: The study will be performed in compliance with the Declaration of Helsinki (2002) of the World Medical Association. The study was approved by Institutional Review Board of West China Hospital. All patients will be fully informed the potential benefits, potential risks and responsibilities, those who will sign the informed consents once they are included. Preliminary and final results will be published in peer-reviewed journals and presented at national and international congresses. TRIAL REGISTRATION NUMBER: ChiCTR2100043839.

Comparison of ventriculoperitoneal shunt to lumboperitoneal shunt in the treatment of idiopathic: A monocentric, assessor-blinded, randomized controlled trial.

BACKGROUND: Ventriculoperitoneal shunt (VPS) and lumboperitoneal shunt (LPS) remain the mainstay of idiopathic normal pressure hydrocephalus (INPH). There are no randomized controlled trials completed to compare the efficacy of these 2 shunt techniques. METHODS/DESIGN: We will conduct a monocentric, assessor-blinded, and randomized controlled trial titled "Comparison of Ventriculoperitoneal Shunt to Lumboperitoneal Shunt for the treatment of Idiopathic Normal Pressure Hydrocephalus: Phase I (COVLINPH-1)" trial and recruit patients at West China Hospital of Sichuan University since June 2021. And this trial is expected to end in December 2030. Eligible participants will be randomly assigned into LPS group and VPS group at ratio of 1:1 followed by evaluation before surgery, 1 month, 12 months, and 5 years after surgery. The primary outcome is the rate of shunt failure within 5 years. The secondary outcomes include modified Rankin Scale (mRS), INPH grading scale (INPHGS), mini-mental state examination (MMSE), and Evans index. We will calculate the rate of favorable outcome, which is defined as shunt success and an improvement of more than 1 point in the mRS at evaluation point. We will also analyze the complications throughout the study within 5 years after shunt insertion. DISCUSSION: The results of this trial will provide state-of-the-art evidence on the treatment option for patients with INPH, and will also generate the discussion regarding this subject. TRIAL REGISTRATION NUMBER: ChiCTR2000031555; Pre-results.

Microglial Exosome miR-7239-3p Promotes Glioma Progression by Regulating Circadian Genes.

Glioma-associated microglial cells, a key component of the tumor microenvironment, play an important role in glioma progression. In this study, the mouse glioma cell line GL261 and the mouse microglia cell line BV2 were chosen. First, circadian gene expression in glioma cells co-cultured with either M1 or M2 microglia was assessed and the exosomes of M2-polarized and unpolarized BV-2 microglia were extracted. Subsequently, we labeled the exosomes with PKH67 and treated GL261 cells with them to investigate the exosome distribution. GL261 cell phenotypes and related protein expression were used to explore the role of M2 microglial exosomes in gliomas. Then a specific miR-7239-3p inhibitor was added to verify miR-7239-3p functions. Finally, the mouse subcutaneous tumorigenic model was used to verify the tumorigenic effect of M2 microglial exosomes in vivo. Our results showed that in gliomas co-cultured with M2 microglia, the expression of the BMAL1 protein was decreased (P < 0.01), while the expression of the CLOCK protein was increased (P < 0.05); opposite results were obtained in gliomas co-cultured with M1 microglia. After treatment with M2 microglial exosomes, the apoptosis of GL261 cells decreased (P < 0.001), while the viability, proliferation, and migration of GL261 cells increased. Increased expression of N-cadherin and Vimentin, and decreased E-cadherin expression occurred upon treatment with M2 microglial exosomes. Addition of an miR-7239-3p inhibitor to M2 microglial exosomes reversed these results. In summary, we found that miR-7239-3p in the glioma microenvironment is recruited to glioma cells by exosomes and inhibits Bmal1 expression. M2 microglial exosomes promote the proliferation and migration of gliomas by regulating tumor-related protein expression and reducing apoptosis.

Preoperative evaluation using external lumbar drainage for patients with posthemorrhagic hydrocephalus: A prospective, monocentric, randomized controlled trial.

BACKGROUND: External lumbar drainage (ELD) remains the most common used methods with a higher sensitivity before lumboperitoneal shunt (LPS) implantation to predict the shunt outcomes in the treatment of idiopathic normal pressure hydrocephalus. However, the benefits of such supplemental test have not been tested in the treatment of post-hemorrhagic hydrocephalus (PHH). METHODS AND DESIGN: In the current trial, 100 eligible patients with PHH will be recruited and randomly assigned to the ELD group (study group) and non-ELD group (control group). Lumbar puncture (LP) will be performed for participants in non-ELD group. LP plus ELD will be performed for participants in ELD group, those who will then be investigated the suitability of potential LPS 4 days after ELD. Two independent and practiced assessors will collect the baseline data and evaluate each participant 4 days after ELD or LP, 1 day after LPS, at the time of discharge and 1 month after LPS. The primary outcome is the shunting outcomes 1 month after surgery. The secondary outcomes include the complications related to ELD, complications related to LPS, and Evens index at each evaluation point. Meanwhile, serious adverse events occurring at any time is recorded to determine the safety of this trial. DISCUSSION: The results of this trial will demonstrate whether preoperative evaluation using temporary ELD for patients with PHH could attenuate the risk of LPS failure. TRIAL REGISTRATION NUMBER: ChiCTR2000034094; Pre-results.

Evaluation of titanium cranioplasty and polyetheretherketone cranioplasty after decompressive craniectomy for traumatic brain injury: A prospective, multicenter, non-randomized controlled trial.

INTRODUCTION: Cranioplasty following decompressive craniectomy is routinely performed to restore integrity of skull and improve neurological function. However, reconstructing the cranial defect brings many challenges to neurosurgeons and search for ideal implant materials is one of the most controversial issues. Although many studies have compared the outcomes of titanium and polyetheretherketone (PEEK) cranioplasty, yet no prospective study exists to guide the choice of titanium and PEEK materials. METHODS/DESIGN: A non-randomized, partially blinded, prospective cohort study is described that comprehensively compares the long-term outcomes of titanium cranioplasty versus PEEK cranioplasty. One hundred forty-five patients for each group will be recruited. Eligible patients are those with cranial defect due to traumatic brain injury (≥ 16 years), defect size is over 25 cm and they must agree to participate in the trial. Each participant is evaluated before surgery, on discharge, 3, 6, and 12 months after cranioplasty. The primary outcome is the infection, implant failure and implant deformation requiring revision surgery within 12 months. Secondary outcomes include postoperative complication rate, neurological outcomes, motor function, and cosmetic outcome over a 6-month period. DISCUSSION: Search for ideal implant materials is throughout the history of cranioplasty. This study will provide robust evidence for the choice of cranioplasty materials. TRIAL REGISTRATION NUMBER: ChiCTR2000033406.

Shunting outcomes in post-hemorrhagic hydrocephalus: A protocol for systematic review and meta-analysis.

BACKGROUND: The best treatment option for patients with post-hemorrhagic hydrocephalus (PHH) remains controversial. The objective of the current meta-analysis is to systematically evaluate the long-term outcomes of patients with PHH treated by ventriculoperitoneal shunt (VPS) and lumboperitoneal shunt (LPS). METHODS: We search literatures through PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), the Chinese Science and Technology Periodical Database (VIP) and Wan fang databases, and Chinese Biomedical Literature Database (CBM) from its beginning to June 15, 2020. Randomized controlled trials (RCTs) and non-RCTs in English or Chinese studies will be considered. The primary outcome is the rate of shunt failure after shunt implantationThe secondary outcome is the rate of complications that are associated with shunt surgery. RESULTS AND CONCLUSION: The study will compare the 2 types of shunt surgery in the treatment of PHH, providing evidence for the treatment option for the patients with PHH. STUDY REGISTRATION NUMBER: The study is priorly registered through International Platform of Registered Systematic Review and Meta-analysis Protocols on June 17, 2020 (INPLASY202060063).

Comparison of ventriculoperitoneal shunt to lumboperitoneal shunt in the treatment of posthemorrhagic hydrocephalus: A prospective, monocentric, non-randomized controlled trial.

BACKGROUND: Ventriculoperitoneal shunt (VPS) surgery remains the most widely accepted and used option method to treat post-hemorrhagic hydrocephalus (PHH) worldwide while lumboperitoneal shunt (LPS) serves as an effectively alternative treatment. However, the outcomes of VPS and LPS in the treatment of PHH have not been compared in a prospective trial. METHODS AND DESIGN: In this monocentric, assessor-blinded, non-randomized controlled trial, 75 eligible patients with PHH for each group will be recruited to compare the outcomes of VPS cohort with that of LPS cohort. Each participant is evaluated before surgery, at the time of discharge, 3, and 6 months after surgery by experienced and practiced assessors. The primary outcome is the rate of shunt failure 6 months after shunt surgery. The secondary measure of efficacy is National Institute of Health stroke scale, together along with Glasgow coma scale, modified Rankin Scale, and Evans index at the evaluation point. A favorable outcome is defined as shunt success with an improvement of more than 1 point in the National Institute of Health stroke scale. Complication events occurring within 6 months after surgery are investigated. A serious adverse events throughout the study are recorded regarding the safety of shunts. DISCUSSION: The results of this trial will provide evidence for the treatment options for patients with PHH.

Risk factors for bone flap resorption after autologous bone cranioplasty: Protocol for a systematic review and meta-analysis.

BACKGROUND: One of the most common complications following autologous cranioplasty is bone flap resorption (BFR). Severe BFR can lead to revision surgery with implantation of synthetic bone flap and also necessarily lead to higher hospital expenses. This study aims to perform a meta-analysis to summarize available evidence regarding risk factors of BFR requiring a second surgery in patients with autologous cranioplasty. METHODS: Cohort, case-control, and cross-sectional studies that report the incidence and risk factors of BFR among patients with autologous cranioplasty, published in English, will be considered for selection. Three databases from inception to May 2020 will be searched. The process of data selection, quality assessment, and data extraction will be assessed by 2 authors independently. The study quality will be assessed by Newcastle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality checklist.The statistical analysis of this meta-analysis will be calculated by Review manager version 5.3. RESULTS: The results of this systematic review and meta-analysis will be disseminated through academic conferences and expected to publish in a peer-reviewed journal CONCLUSION:: This study will offer high-quality evidence about risk factors for BFR after autologous cranioplasty. REGISTRATION NUMBER: INPLASY202050063.