No abstract

Subarachnoid hemorrhage (SAH) is a neurological emergency characterized by dysfunctional inflammatory response. However, no effective therapeutic options have been reported so far. Microglia polarization has been proposed to exert an essential role in modulating inflammatory response after SAH. Sestrin2 is a stress response protein. Growing evidence has reported that sestrin2 could inhibit M1 microglia and promote M2 microglia polarization. The current study investigated the effects of sestrin2 on microglia phenotype switching and the subsequent brain injury and sought to elucidate the underlying mechanism. We conducted an endovascular perforation SAH model in mice. It was found that sestrin2 was significantly increased after SAH and was mainly distributed in neurons and microglia. Exogenous recombinant human sestrin2 (rh-sestrin2) evidently alleviated inflammatory insults and oxidative stress, and improved neurofunction after SAH. Moreover, rh-sestrin2 increased M2-like microglia polarization and suppressed the number of M1-like microglia after SAH. The protection by rh-sestrin2 was correlated with the activation of Nrf2 signaling. Nrf2 inhibition by ML385 abated the cerebroprotective effects of rh-sestrin2 against SAH and further manifested M1 microglia polarization. In conclusion, promoting microglia polarization from the M1 to M2 phenotype and inducing Nrf2 signaling might be the major mechanism by which sestrin2 protects against SAH insults. Sestrin2 might be a new molecular target for treating SAH.

<b><i>Introduction:</i></b> The aim of the study was to provide an overview of trends in the indications and surgical techniques for corneal transplantation in adults in East China from 2010 to 2019. <b><i>Methods:</i></b> The medical charts of all patients (aged ≥18 years old) undergoing keratoplasty at the Eye, Ear, Nose and Throat Hospital of Fudan University between January 2010 and December 2019 were retrospectively reviewed. The indications for keratoplasty and the surgical techniques were collected. <b><i>Results:</i></b> A total of 2,929 cases were included. Acquired nontraumatic corneal diseases (<i>n</i> = 1,927, 65.8%) have been the leading indication for corneal transplantation during the past decade. Although infectious keratitis was still the leading indication among acquired nontraumatic diseases, its absolute number and proportion gradually decreased during this decade (<i>p</i> &#x3c; 0.001). In contrast, the proportion of endothelial dysfunction/bullous keratopathy increased from 7.8% in 2010 to 12.4% in 2019 (<i>p</i> = 0.029). Penetrating keratoplasty (PKP) has been the predominant surgical technique (<i>n</i> = 1,854, 63.3%), followed by deep anterior lamellar keratoplasty (DALK) (<i>n</i> = 361, 12.3%) and endothelial keratoplasty (EK) (<i>n</i> = 305, 10.4%). Nevertheless, the proportion of PKP decreased from 77.6% in 2010 to 56.9% in 2019 (<i>p</i> = 0.002) and was gradually replaced by DALK (from 7.8% to 16.3%, <i>p</i> &#x3c; 0.001) and EK (from 3.4% to 10.4%, <i>p</i> = 0.009). <b><i>Conclusions:</i></b> Over the past decade, infectious keratitis and endothelial dysfunction/bullous keratopathy have been the leading indications for keratoplasty in adults. Preferred surgical techniques for keratoplasty have been shifting from PKP to more customized lamellar keratoplasties.

Purpose. To analyze the indications and surgical procedures for repeat keratoplasty in eastern China from 2008 to 2019. Methods. This retrospective descriptive study included 418 eyes of 411 patients who underwent no less than 2 keratoplasties at the Eye, Ear, Nose and Throat Hospital of Fudan University from 2008 to 2019. Medical charts were reviewed. The primary indications for repeat keratoplasty, the reasons for regrafting, and the surgical techniques used in the treatment were collected and analyzed. Results. Among 418 eyes, 337 eyes (80.6%) had one repeat keratoplasty, and 81 eyes (19.4%) had multiple repeat keratoplasties (≥2 repeat keratoplasties). The median interval between the initial keratoplasty and the first repeat keratoplasty was 25 months, and that between two keratoplasties after the first repeat keratoplasty was 27.5 months. Infectious keratitis was the leading primary indication for single repeat keratoplasty (80 cases, 23.7%) and multiple repeat keratoplasties (19 cases, 23.5%). The second most common primary indication was bullous keratopathy for single repeat keratoplasty (49 eyes, 14.5%) and chemical injury for multiple repeat keratoplasties (14 eyes, 17.3%). The main reason for regrafting was allograft rejection (262 cases, 49.3%), followed by endothelial dysfunction (92 cases, 17.3%), and for vision improvement after tectonic keratoplasty (60 cases, 11.3%). Penetrating keratoplasty (PKP) was the major technique used in repeat keratoplasty (447 cases, 84.2%). However, Descemet stripping endothelial keratoplasty was more frequently used than PKP (72.4% vs. 27.6%, P < 0.001 ) in the treatment of failed endothelial keratoplasty. Conclusion. Infectious keratitis was still the leading cause of repeat keratoplasty in eastern China. Although PKP remains the major technique of repeat keratoplasty, the application of customized lamellar keratoplasty has greatly expanded in the last decade. Cautious selection of indications, surgical techniques, and timing for surgery is crucial for a good prognosis after repeat keratoplasty.

ObjectiveAneurysmal subarachnoid hemorrhage (aSAH) is a major cause of death and disability worldwide and imposes serious burdens on society and individuals. However, predicting the long‐term outcomes in aSAH patients requiring mechanical ventilation remains challenging. We sought to establish a model utilizing the Least Absolute Shrinkage and Selection Operator (LASSO)‐penalized Cox regression to estimate the prognosis of aSAH patients requiring mechanical ventilation, based on regularly utilized and easily accessible clinical variables.MethodsData were retrieved from the Dryad Digital Repository. Potentially relevant features were selected using LASSO regression analysis. Multiple Cox proportional hazards analyses were performed to develop a model using the training set. Receiver operating characteristics and calibration curves were used to assess its predictive accuracy and discriminative power. Kaplan–Meier and decision curve analyses (DCA) were used to evaluate the clinical utility of the model.ResultsIndependent prognostic factors, including the Simplified Acute Physiology Score 2, early brain injury, rebleeding, and length of intensive care unit stay, were identified and included in the nomogram. In the training set, the area under the curve values for 1‐, 2‐, and 4‐year survival predictions were 0.82, 0.81, and 0.80, respectively. In the validation set, the nomogram exhibited excellent discrimination ability and good calibration. Moreover, DCA demonstrated that the nomogram was clinically beneficial. Finally, a web‐based nomogram was constructed (https://rehablitation.shinyapps.io/aSAH).InterpretationOur model is a useful tool for accurately predicting long‐term outcomes in patients with aSAH who require mechanical ventilation and can assist in making individualized interventions by providing valuable information.