Efficacy of esketamine for the treatment of postpartum depression and pain control following cesarean section: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Postpartum depression (PPD) following a cesarean delivery is a frequently seen complication. Despite the prophylactic effects of ketamine, the impact of esketamine on PPD in women undergoing cesarean section remains uncertain. This study aimed to assess the effectiveness of esketamine as an adjunct to patient-controlled intravenous analgesia (PCIA) in preventing PPD in women undergoing caesarean section. METHODS: A total of 275 parturients undergoing caesarean section and subsequent patient-controlled intravenous analgesia (PCIA) were randomly assigned to receive either the control treatment (sufentanil 2 µg/kg + tropisetron 10 mg) or the experimental treatment with additional esketamine (1.5 mg/kg). The primary outcome measured was the incidence of postpartum depression (PPD), classified by Edinburgh Postnatal Depression Scale (EPDS) scores equal to or greater than 13 indicating PPD. Secondary outcomes included cumulative sufentanil consumption during specific time periods (0-24 h, 24-48 h, and 0-48 h) after the surgical procedure and numerical rating scale (NRS) scores at rest and during movements. RESULTS: The final analysis included a total of 246 postpartum women who had undergone caesarean delivery. On postoperative day 42, the incidence of depression among the control group was 17.6%, which was significantly higher compared to the esketamine group with a rate of 8.2% (P = 0.02). The EPDS scores also showed a significant difference between the two groups, with a mean score of 9.02 ± 2.21 in the control group and 6.87 ± 2.14 in the esketamine group (p < 0.0001). In terms of pain management, the esketamine group showed lower sufentanil consumption in the 0-24 h (42.5 ± 4.58 µg vs. 50.15 ± 5.47 µg, P = 0.04) and 0-48 h (87.40 ± 9.51 µg vs. 95.10 ± 9.36 µg, P = 0.04) postoperative periods compared to the control group. Differences in movement were also observed between the two groups at 24 and 48 h after the cesarean Sect. (3.39 ± 1.57 vs. 4.50 ± 0.80, P = 0.02; 2.43 ± 0.87 vs. 3.56 ± 0.76, P = 0.02). It is worth noting that the frequency of side effects observed in both groups was comparable. CONCLUSIONS: Esketamine at a dose of 1.5 mg/kg, when used as a supplement in PCIA, has been shown to significantly reduce the occurrence of PPD within 42 days. Additionally, it has been found to decrease cumulative consumption of sufentanil over a 48-hour period following cesarean operation, all without increasing the rate of adverse effects. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2200067054) on December 26, 2022.

Mortality and cardiac arrest rates of emergency surgery in developed and developing countries: a systematic review and meta-analysis.

BACKGROUND: The magnitude of the risk of death and cardiac arrest associated with emergency surgery and anesthesia is not well understood. Our aim was to assess whether the risk of perioperative and anesthesia-related death and cardiac arrest has decreased over the years, and whether the rates of decrease are consistent between developed and developing countries. METHODS: A systematic review was performed using electronic databases to identify studies in which patients underwent emergency surgery with rates of perioperative mortality, 30-day postoperative mortality, or perioperative cardiac arrest. Meta-regression and proportional meta-analysis with 95% confidence intervals (CIs) were performed to evaluate global data on the above three indicators over time and according to country Human Development Index (HDI), and to compare these results according to country HDI status (low vs. high HDI) and time period (pre-2000s vs. post-2000s). RESULTS: 35 studies met the inclusion criteria, representing more than 3.09 million anesthetic administrations to patients undergoing anesthesia for emergency surgery. Meta-regression showed a significant association between the risk of perioperative mortality and time (slope: -0.0421, 95%CI: from - 0.0685 to -0.0157; P = 0.0018). Perioperative mortality decreased over time from 227 per 10,000 (95% CI 134-380) before the 2000s to 46 (16-132) in the 2000-2020 s (p < 0-0001), but not with increasing HDI. 30-day postoperative mortality did not change significantly (346 [95% CI: 303-395] before the 2000s to 292 [95% CI: 201-423] in the 2000s-2020 period, P = 0.36) and did not decrease with increasing HDI status. Perioperative cardiac arrest rates decreased over time, from 113 per 10,000 (95% CI: 31-409) before the 2000s to 31 (14-70) in the 2000-2020 s, and also with increasing HDI (68 [95% CI: 29-160] in the low-HDI group to 21 [95% CI: 6-76] in the high-HDI group, P = 0.012). CONCLUSIONS: Despite increasing baseline patient risk, perioperative mortality has decreased significantly over the past decades, but 30-day postoperative mortality has not. A global priority should be to increase long-term survival in both developed and developing countries and to reduce overall perioperative cardiac arrest through evidence-based best practice in developing countries.

The immunometabolite S-2-hydroxyglutarate exacerbates perioperative ischemic brain injury and cognitive dysfunction by enhancing CD8+ T lymphocyte-mediated neurotoxicity.

BACKGROUND: Metabolic dysregulation and disruption of immune homeostasis have been widely associated with perioperative complications including perioperative ischemic stroke. Although immunometabolite S-2-hydroxyglutarate (S-2HG) is an emerging regulator of immune cells and thus triggers the immune response, it is unclear whether and how S-2HG elicits perioperative ischemic brain injury and exacerbates post-stroke cognitive dysfunction. METHODS: Perioperative ischemic stroke was induced by transient middle cerebral artery occlusion for 60 min in C57BL/6 mice 1 day after ileocecal resection. CD8+ T lymphocyte activation and invasion of the cerebrovascular compartment were measured using flow cytometry. Untargeted metabolomic profiling was performed to detect metabolic changes in sorted CD8+ T lymphocytes after ischemia. CD8+ T lymphocytes were transfected with lentivirus ex vivo to mobilize cell proliferation and differentiation before being transferred into recombination activating gene 1 (Rag1-/-) stroke mice. RESULTS: The perioperative stroke mice exhibit more severe cerebral ischemic injury and neurological dysfunction than the stroke-only mice. CD8+ T lymphocyte invasion of brain parenchyma and neurotoxicity augment cerebral ischemic injury in the perioperative stroke mice. CD8+ T lymphocyte depletion reverses exacerbated immune-mediated cerebral ischemic brain injury in perioperative stroke mice. Perioperative ischemic stroke triggers aberrant metabolic alterations in peripheral CD8+ T cells, in which S-2HG is more abundant. S-2HG alters CD8+ T lymphocyte proliferation and differentiation ex vivo and modulates the immune-mediated ischemic brain injury and post-stroke cognitive dysfunction by enhancing CD8+ T lymphocyte-mediated neurotoxicity. CONCLUSION: Our study establishes that S-2HG signaling-mediated activation and neurotoxicity of CD8+ T lymphocytes might exacerbate perioperative ischemic brain injury and may represent a promising immunotherapy target in perioperative ischemic stroke.

Comparison of analgesic effect of oxycodone and morphine on patients with moderate and advanced cancer pain: a meta-analysis.

BACKGROUND: Morphine and oxycodone are considered as wide-spreadly used opioids for moderate/severe cancer pain. However, debate exists about the evidence regarding their relative tolerability and underlying results. METHODS: A systematic search of online electronic databases, including PubMed, Embase, Cochrane library updated on October 2017 were conducted. The meta-analysis was performed including the studies that were designed as randomized controlled trials. RESULTS: In total, seven randomized clinical trials met our inclusion criteria. No statistical differences in analgesic effect between oxycodone and morphine were observed. Both the pooled analysis of API (MD =0.01, 95% CI -0.22 - 0.23; p = 0.96) and WPI (MD = - 0.05, 95% CI -0.21 - 0.30; p = 0.72) demonstrated clinical non-inferiority of the efficacy of morphine compared with oxycodone, respectively. Additionally, no significant difference in PRR response was observed in either oxycodone or morphine that were used in patients (MD =0.99, 95% CI -0.88 - 1.11; p = 0.87). With the pooled result of AEs indicating the comparable safety profiles between the 2 treatment groups, the meta-analysis on the nausea (OR = 1.20, 95% CI 0.90-1.59; p = 0.22), vomiting (OR = 1.33, 95% CI 0.75-2.38; p = 0.33), somnolence (OR = 1.35, 95% CI 0.95-1.93; p = 0.10), diarrhea (OR = 1.01, 95% CI 0.60-1,67; p = 0.98), and constipation (OR = 1.04, 95% CI 0.77-1.41; p = 0.79) was conducted, respectively. CONCLUSIONS: In the current study, no remarkable difference was identified either in analgesic efficacy or in tolerability of oxycodone and morphine as the first-line therapy for patients with moderate to severe cancer pain. Thus, no sufficient clinical evidence on the superior effects of oxycodone to morphine was provided in this experimental hypothesis.

Correction to: Comparison of analgesic effect of oxycodone and morphine on patients with moderate and advanced cancer pain: a meta-analysis.

After publication of this article [1], the authors noted that the corresponding email address is incorrect.

Rapid focus map surveying for whole slide imaging with continuous sample motion.

Whole slide imaging (WSI) has recently been cleared for primary diagnosis in the U.S. A critical challenge of WSI is to perform accurate focusing in high speed. Traditional systems create a focus map prior to scanning. For each focus point on the map, a sample needs to be static in the x-y plane, and axial scanning is needed to maximize the contrast. Here we report a novel focus map surveying method for WSI. In this method, we illuminate the sample with two LEDs and recover the focus points based on 1D autocorrelation analysis. The reported method requires no axial scanning, no additional camera and lens, works for stained and transparent samples, and allows continuous sample motion in the surveying process. By using a 20× objective lens, we demonstrate a mean focusing error of ∼0.08 µm in the static mode and ∼0.17 µm in the continuous motion mode. The reported method may provide a turnkey solution for most existing WSI systems due to its simplicity, robustness, accuracy, and high speed. It may also standardize the imaging performance of WSI systems for digital pathology and find other applications in high-content microscopy, such as time-lapse live-cell imaging.

Angular light modulator using optical blinds.

Spatial light modulator (SLM) is widely used in imaging applications for modulating light intensity and phase delay. In this paper, we report a novel device concept termed angular light modulator (ALM). Different from the SLM, the reported ALM employs a tunable blind structure to modulate the angular components of the incoming light waves. For spatial-domain light modulation, the ALM can be directly placed in front of an image sensor for selecting different angular light components. In this case, we can sweep the slat angle of the blind structure and capture multiple images corresponding to different perspectives. These images can then be back-projected for 3D tomographic refocusing. By using a fixed slat angle, we can also convert the incident-angle information into intensity variations for wavefront sensing or introduce a translational shift to the defocused object for high-speed autofocusing. For Fourier-domain light modulation, the ALM can be placed at the pupil plane of an optical system for reinforcing the light propagating trajectories. We show that a pupil-plane-modulated system is able to achieve a better resolution for out-of-focus objects while maintaining the same resolution for in-focus objects. The reported ALM can be fabricated on the chip level and controlled by an external magnetic field. It may provide new insights for developing novel imaging and vision devices.

Optimization of sampling pattern and the design of Fourier ptychographic illuminator.

Fourier ptychography (FP) is a recently developed imaging approach that facilitates high-resolution imaging beyond the cutoff frequency of the employed optics. In the original FP approach, a periodic LED array is used for sample illumination, and therefore, the scanning pattern is a uniform grid in the Fourier space. Such a uniform sampling scheme leads to 3 major problems for FP, namely: 1) it requires a large number of raw images, 2) it introduces the raster grid artefacts in the reconstruction process, and 3) it requires a high-dynamic-range detector. Here, we investigate scanning sequences and sampling patterns to optimize the FP approach. For most biological samples, signal energy is concentrated at low-frequency region, and as such, we can perform non-uniform Fourier sampling in FP by considering the signal structure. In contrast, conventional ptychography perform uniform sampling over the entire real space. To implement the non-uniform Fourier sampling scheme in FP, we have designed and built an illuminator using LEDs mounted on a 3D-printed plastic case. The advantages of this illuminator are threefold in that: 1) it reduces the number of image acquisitions by at least 50% (68 raw images versus 137 in the original FP setup), 2) it departs from the translational symmetry of sampling to solve the raster grid artifact problem, and 3) it reduces the dynamic range of the captured images 6 fold. The results reported in this paper significantly shortened acquisition time and improved quality of FP reconstructions. It may provide new insights for developing Fourier ptychographic imaging platforms and find important applications in digital pathology.

LCD-based digital eyeglass for modulating spatial-angular information.

Using programmable aperture to modulate spatial-angular information of light field is well-known in computational photography and microscopy. Inspired by this concept, we report a digital eyeglass design that adaptively modulates light field entering human eyes. The main hardware includes a transparent liquid crystal display (LCD) and a mini-camera. The device analyzes the spatial-angular information of the camera image in real time and subsequently sends a command to form a certain pattern on the LCD. We show that, the eyeglass prototype can adaptively reduce light transmission from bright sources by ~80% and retain transparency to other dim objects meanwhile. One application of the reported device is to reduce discomforting glare caused by vehicle headlamps. To this end, we report the preliminary result of using the reported device in a road test. The reported device may also find applications in military operations (sniper scope), laser counter measure, STEM education, and enhancing visual contrast for visually impaired patients and elderly people with low vision.

Recovering higher dimensional image data using multiplexed structured illumination.

Structured illumination (SI) using non-uniform intensity patterns is well-known for improving lateral resolution in microscopy. Here, we propose a multiplexed SI technique for recovering images with higher lateral resolution and with higher dimensional information at the same time. In this framework, we use unknown non-uniform intensity patterns for incoherent sample illumination and use the corresponding acquisitions for image recovery. In the first example, we use the reported framework to recover sample images with higher lateral resolution and separate different sections of the sample along the z-direction. In the second example, we recover the sample images with higher lateral resolution and separate the images at different spectral bands. The reported multiplexed-SI framework may find applications in general imaging settings where higher dimensional information is mixed in 2D image measurements. It can also be used in microscopy settings for computational sectioning and multispectral imaging.

Fourier ptychographic reconstruction using Wirtinger flow optimization.

Recently Fourier Ptychography (FP) has attracted great attention, due to its marked effectiveness in leveraging snapshot numbers for spatial resolution in large field-of-view imaging. To acquire high signal-to-noise-ratio (SNR) images under angularly varying illuminations for subsequent reconstruction, FP requires long exposure time, which largely limits its practical applications. In this paper, based on the recently reported Wirtinger flow algorithm, we propose an iterative optimization framework incorporating phase retrieval and noise relaxation together, to realize FP reconstruction using low SNR images captured under short exposure time. Experiments on both synthetic and real captured data validate the effectiveness of the proposed reconstruction method. Specifically, the proposed technique could save ~ 80% exposure time to achieve similar retrieval accuracy compared to the conventional FP. Besides, we have released our source code for non-commercial use.

High-resolution fluorescence imaging via pattern-illuminated Fourier ptychography.

Fluorescence microscopy plays a vital role in modern biological research and clinical diagnosis. Here, we report an imaging approach, termed pattern-illuminated Fourier ptychography (FP), for fluorescence imaging beyond the diffraction limit of the employed optics. This approach iteratively recovers a high-resolution fluorescence image from many pattern-illuminated low-resolution intensity measurements. The recovery process starts with one low-resolution measurement as the initial guess. This initial guess is then sequentially updated by other measurements, both in the spatial and Fourier domains. In the spatial domain, we use the pattern-illuminated low-resolution images as intensity constraints for the sample estimate. In the Fourier domain, we use the incoherent optical-transfer-function of the objective lens as the object support constraint for the solution. The sequential updating process is then repeated until the sample estimate converges, typically for 5-20 times. Different from the conventional structured illumination microscopy, any unknown pattern can be used for sample illumination in the reported framework. In particular, we are able to recover both the high-resolution sample image and the unknown illumination pattern at the same time. As a demonstration, we improved the resolution of a conventional fluorescence microscope beyond the diffraction limit of the employed optics. The reported approach may provide an alternative solution for structure illumination microscopy and find applications in wide-field, high-resolution fluorescence imaging.

Aperture-scanning Fourier ptychography for 3D refocusing and super-resolution macroscopic imaging.

We report an imaging scheme, termed aperture-scanning Fourier ptychography, for 3D refocusing and super-resolution macroscopic imaging. The reported scheme scans an aperture at the Fourier plane of an optical system and acquires the corresponding intensity images of the object. The acquired images are then synthesized in the frequency domain to recover a high-resolution complex sample wavefront; no phase information is needed in the recovery process. We demonstrate two applications of the reported scheme. In the first example, we use an aperture-scanning Fourier ptychography platform to recover the complex hologram of extended objects. The recovered hologram is then digitally propagated into different planes along the optical axis to examine the 3D structure of the object. We also demonstrate a reconstruction resolution better than the detector pixel limit (i.e., pixel super-resolution). In the second example, we develop a camera-scanning Fourier ptychography platform for super-resolution macroscopic imaging. By simply scanning the camera over different positions, we bypass the diffraction limit of the photographic lens and recover a super-resolution image of an object placed at the far field. This platform's maximum achievable resolution is ultimately determined by the camera's traveling range, not the aperture size of the lens. The FP scheme reported in this work may find applications in 3D object tracking, synthetic aperture imaging, remote sensing, and optical/electron/X-ray microscopy.

Gas-self-filter-based erbium-doped fiber loop laser for gas detection.

An erbium-doped fiber (EDF) loop laser, based on a gas-self-filter (GSF), is developed with single or multiple wavelength emission. The GSF is a type of Mach-Zehnder interferometer with a gas cell in one arm. By matching the destructive wavelength of the interferometer with the gas absorption line, the self-filtering function is achieved. A GSF-based multi-wavelength laser with a side-mode suppression ratio of ~50 dB is performed. As an example, C2H2 gas is detected using a single-wavelength GSF-based laser with correlation spectroscopy, and a good linearity of the measurement is obtained. The present laser has the potential advantage for multiple gas detection, e.g., being free of wavelength calibration.

Innovations in intracranial aneurysm treatment: a pilot study on the Choydar flow diverter.

Background: The flow diverter (FD) has emerged as a promising treatment option for intracranial aneurysms. Recently, a novel flow-diverting stent, the Choydar FD device, has been developed within our nation. Objective: To introduce the newly developed Choydar FD device and present our preliminary clinical experience with its application in the treatment of intracranial aneurysms. Methods: A total of 23 patients with 23 unruptured intracranial aneurysms, comprising 20 (87.0%) aneurysms located at the internal carotid artery and 3 (13.0%) at the vertebral artery, were treated with the Choydar FD device between December 2021 and April 2022. Patient baseline data, clinical and angiographic outcomes were collected and analyzed. Results: The Choydar FD device was successfully deployed in all patients (100%), with 18 aneurysms (78.3%) additionally treated with coils. One patient experienced an ischemic event with sensory disturbance during the perioperative period. At the 1-year follow-up, all patients demonstrated good clinical outcomes. Of the 23 aneurysms with available angiographic follow-up, 22 (95.7%) achieved complete occlusion, and one patient exhibited in-stent stenosis without neurological deficits. Conclusion: The initial clinical results of the Choydar FD device are encouraging, and it appears to be a useful option for treating intracranial aneurysms with acceptable efficacy and safety. Future studies with larger sample sizes and longer follow-up durations are warranted to validate these findings.

Flow-Diverting Devices in the Treatment of Vertebral Artery Aneurysms: Insights into Efficacy and Safety from a Systematic Review and Meta-analysis.

The objective of this study is to conduct a systematic review and meta-analysis aimed at evaluating the efficacy and safety of flow-diverting devices (FDs) treatment for intracranial vertebral artery (VA) aneurysms. We searched PubMed, Web of Science, OVID, and Embase for English-language studies up to February 2024 and included clinical studies on FD treatment of intracranial VA aneurysms. Sensitivity analysis evaluated outcome stability. Of 2273 articles, 29 studies involving 541 aneurysms treated with FDs were included. Based on the Methodological Index for Non-Randomized Studies (MINORS), six were high-quality and 23 moderate quality. FD treatment showed a 95% rate of favorable clinical outcomes (95% CI, 89-99%), 81% (95% CI, 74-88%) complete aneurysmal occlusion, 4% (95% CI, 2-7%) ischemic complication incidence, 1% (95% CI, 0-3%) hemorrhagic complication incidence, 95% (95% CI, 87-100%) posterior inferior cerebellar artery (PICA) preservation, and 6% (95% CI, 3-10%) in-stent stenosis or occlusion across clinical and angiographic follow-up periods of 13.62 months (95% CI, 10.72-16.52) and 11.85 months (95% CI, 9.36-14.33), respectively. Subgroup analyses, based on a 12-month angiographic follow-up threshold, indicated no statistically significant differences in rates of complete aneurysm occlusion, PICA preservation, or in-stent stenosis or occlusion incidence (p > 0.05) between subgroups. Moreover, significant differences were observed in clinical and angiographic outcomes between ruptured and unruptured aneurysms, particularly in hemorrhagic complications (p < 0.05), without significant disparity in ischemic complications (p > 0.05). The results' stability was confirmed via sensitivity analysis. FDs treatment for VA aneurysms is efficacious and safe, offering high rates of positive clinical and angiographic outcomes with minimal complications, underscoring FDs' viability as a treatment option for VA aneurysms. The study was registered with PROSPERO (registration number: CRD42024499894).

Rapamycin inhibits B16 melanoma cell viability invitro and invivo by inducing autophagy and inhibiting the mTOR/p70­S6k pathway.

Rapamycin is an immunosuppressant that has been shown to prevent tumor growth following organ transplantation. However, its exact mode of antitumor action remains unknown. The present study used the B16-F10 (B16) murine melanoma model to explore the antitumor mechanism of rapamycin, and it was revealed that rapamycin reduced B16 cell viability in vitro and in vivo. In addition, in vitro and in vivo, the results of western blotting showed that rapamycin reduced Bcl2 expression, and enhanced the protein expression levels of cleaved caspase 3 and Bax, indicating that it can induce the apoptosis of B16 melanoma cells. Furthermore, the results of cell cycle analysis and western blotting showed that rapamycin induced B16 cell cycle arrest in the G1 phase, based on the reduction in the protein expression levels of CDK1, cyclin D1 and CDK4, as well as the increase in the percentage of cells in G1 phase. Rapamycin also significantly increased the number of autophagosomes in B16 melanoma cells, as determined by transmission electron microscopy. Furthermore, the results of RT-qPCR and western blotting showed that rapamycin upregulated the protein expression levels of microtubule-associated protein light chain 3 (LC3) and Beclin-1, while downregulating the expression of p62 in vitro and in vivo, thus indicating that rapamycin could trigger cellular autophagy. The present study revealed that rapamycin in combination with chloroquine (CQ) further increased LC3 expression compared with that in the CQ group, suggesting that rapamycin induced an increase in autophagy in B16 cells. Furthermore, the results of western blotting showed that rapamycin blocked the phosphorylation of p70 ribosomal S6 kinase (p70-S6k) and mammalian target of rapamycin (mTOR) proteins in vitro and in vivo, thus suggesting that rapamycin may exert its antitumor effect by inhibiting the phosphorylation of the mTOR/p70-S6k pathway. In conclusion, rapamycin may inhibit tumor growth by inducing cellular G1 phase arrest and apoptosis. In addition, rapamycin may exert its antitumor effects by inducing the autophagy of B16 melanoma cells in vitro and in vivo, and the mTOR/p70-S6k signaling pathway may be involved in this process.

Differences and Correlations of Morphological and Hemodynamic Parameters between Anterior Circulation Bifurcation and Side-wall Aneurysms.

OBJECTIVE: The objective of this research was to explore the difference and correlation of the morphological and hemodynamic features between sidewall and bifurcation aneurysms in anterior circulation arteries, utilizing computational fluid dynamics as a tool for analysis. METHODS: In line with the designated inclusion criteria, this study covered 160 aneurysms identified in 131 patients who received treatment at Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, China, from January 2021 to September 2022. Utilizing follow-up digital subtraction angiography (DSA) data, these cases were classified into two distinct groups: the sidewall aneurysm group and the bifurcation aneurysm group. Morphological and hemodynamic parameters in the immediate preoperative period were meticulously calculated and examined in both groups using a three-dimensional DSA reconstruction model. RESULTS: No significant differences were found in the morphological or hemodynamic parameters of bifurcation aneurysms at varied locations within the anterior circulation. However, pronounced differences were identified between sidewall and bifurcation aneurysms in terms of morphological parameters such as the diameter of the parent vessel (Dvessel), inflow angle (θF), and size ratio (SR), as well as the hemodynamic parameter of inflow concentration index (ICI) (P<0.001). Notably, only the SR exhibited a significant correlation with multiple hemodynamic parameters (P<0.001), while the ICI was closely related to several morphological parameters (R>0.5, P<0.001). CONCLUSIONS: The significant differences in certain morphological and hemodynamic parameters between sidewall and bifurcation aneurysms emphasize the importance to contemplate variances in threshold values for these parameters when evaluating the risk of rupture in anterior circulation aneurysms. Whether it is a bifurcation or sidewall aneurysm, these disparities should be considered. The morphological parameter SR has the potential to be a valuable clinical tool for promptly distinguishing the distinct rupture risks associated with sidewall and bifurcation aneurysms.

Progression of m6A in the tumor microenvironment: hypoxia, immune and metabolic reprogramming.

Recently, N6-methyladenosine (m6A) has aroused widespread discussion in the scientific community as a mode of RNA modification. m6A comprises writers, erasers, and readers, which regulates RNA production, nuclear export, and translation and is very important for human health. A large number of studies have found that the regulation of m6A is closely related to the occurrence and invasion of tumors, while the homeostasis and function of the tumor microenvironment (TME) determine the occurrence and development of tumors to some extent. TME is composed of a variety of immune cells (T cells, B cells, etc.) and nonimmune cells (tumor-associated mesenchymal stem cells (TA-MSCs), cancer-associated fibroblasts (CAFs), etc.). Current studies suggest that m6A is involved in regulating the function of various cells in the TME, thereby affecting tumor progression. In this manuscript, we present the composition of m6A and TME, the relationship between m6A methylation and characteristic changes in TME, the role of m6A methylation in TME, and potential therapeutic strategies to provide new perspectives for better treatment of tumors in clinical work.

Case Report: A novel heterozygous nonsense mutation in KRIT1 cause hereditary cerebral cavernous malformation.

Cerebral cavernous malformation (CCM) is a vascular malformation of the central nervous system and mainly characterized by enlarged capillary cavities without intervening brain parenchyma. Genetic studies have identified three disease-causing genes (CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10) responsible for CCM. Here, we characterized a four-generation family diagnosed with CCM and identified a novel heterozygous mutation c.1159C>T, p.Q387X in KRIT1 gene by whole exome sequencing and Sanger sequencing. The Q387X mutation resulted in premature termination of KRIT1 protein, which was predicted to be deleterious by the ACMG/AMP 2015 guideline. Our results provide novel genetic evidence support that KRIT1 mutations cause CCM, and are helpful to the treatment and genetic diagnosis of CCM.