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Endocrine-resistant ER+HER2- breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine-resistant BC remain elusive. Here, analysis of the RNA-sequencing data from ER+HER2- BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine-resistant BC cells, not immune cells. Indeed, compared with endocrine-sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS-STING pathway is attenuated in endocrine-resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS-STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2- BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine-resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine-resistant BC., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: To estimate the impacts of different anesthetic protocols on the speed and quality of postoperative resuscitation in patients undergoing painless gastroscopy. Methods: This was a prospectively designed randomized control study that included 150 patients who underwent painless gastroscopy in Hainan Cancer Hospital affiliated to Hainan Medical College between April and December of 2023. All the patients, classified as American Society of Aneshesiologists (ASA) Grade Ⅰ or Ⅱ, were randomly divided into three groups with different anesthetic protocols, including propofol group (group P), remimazolam group (group R) and remimazolam with flumazenil group (group RF). There were eventually 50 patients in each group. The three groups of patients were compared for their resuscitation time and the time that they stayed in the resuscitation room (addressed as"room time"below). At 10 min and 20 min after resuscitation, each patient was tested for recognition ability (orientation score), walking ability and fine motor skill (including reaction speed, quick-click ability and visual memory), respectively, with possible adverse reactions recorded spontaneously, such as hypotension, dizziness, nausea and vomitus. Results: There were 29 males and 21 females in group P with an average age of (34±6) years, 27 males and 23 females in group R with an average age of (36±8) years, and 26 males and 24 females in group RF with an average age of (33±7) years, respectively. All examinations for each patient were successfully completed with no interruptions. The resuscitation time and room time of group RF were (47±15) s and (26±5) min,respectively, which were both shorter than those in either group R [(489±92) s and (35±6) min] or group P [(196±61) s and (31±7) min] (all P <0.05). The orientation score of patients in group RF at 10 min after resuscitation was (79.0±10.5), which was significantly higher than that in group R (70.0±11.7) ( P <0.05). The patients' walking ability score of group RF at 10 min and 20 min after resuscitation were [(23.6±10.8), (48.0±4.5)], which were better than those in group R[(15.4±11.1), (47.6±4.8)] (both P <0.05). The patients' reaction speed and quick-click scores of group RF were [(851.0±150.9), (547.0±114.0) ms] and [(758.0±73.2), (629.0±128.9) ms], which were better than those in either group R [(1 151.0±206.0), (732.0±135.1) ms], [(893.0±110.9), (765.8±125.8) ms] or group P [(985.0±225.3), (613.0±123.2) ms], [(831.0±87.7), (691.0±115.8) ms] (all P <0.05). The incidence rate of hypotension in group P was 18% (9/50), higher than that in either Group R [4% (2/50)] or group RF [2% (1/50)] (all P <0.05). The incidence rates of dizziness, nausea and vomitus were comparable among all the three groups with no statistical differences (all P >0.05). Conclusion: In patients undergoing anesthesia with remazolam, the use of flumazenil can not only shorten the resuscitation time and the time that the patients need to stay in the resuscitation room, but also speed up the recovery of the patients' recognition, walking and fine motor skill abilities.

Background: Previous studies had explored the diagnostic or prognostic value of NRP-1/CD304 in blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), and B-cell acute lymphoblastic leukemia (B-ALL), whereas the expression and application value of NRP-1/CD304 in other common hematological diseases have not been reported., Methods: Bone marrow samples from 297 newly diagnosed patients with various hematological diseases were collected to detect the expression of NRP-1/CD304 by flow cytometry (FCM). The diagnostic efficacy of NRP-1/ CD304-positive diseases was analyzed by receiver operating characteristic (ROC) curve, and the area under the ROC curve (AUC) was compared., Results: In the research cohort, the total positive rate of NRP-1/CD304 was 14.81% (44/297), mainly distributed in BPDCN (100%, 6/6), B-ALL (48.61%, 35/72), and AML (4.48%, 3/67), with statistically significant differences (p < 0.01). Other diseases, such as T-cell acute lymphoblastic leukemia (T-ALL), B-cell non-Hodgkin lymphoma (B-NHL), T/NK-cell lymphoma and plasma cell neoplasms, did not express NRP-1/CD304. The AUC of NRP-1/CD304 was 0.936 (95% CI 0.898-0.973), 0.723 (95% CI 0.646-0.801), and 0.435 (95% CI 0.435) in BPDCN, B-ALL and AML, respectively. Besides, CD304 was commonly expressed in B-ALL with BCR-ABL1 gene rearrangement (p = 0.000), and CD304 expression was positively correlated with CD34 co-expression (p = 0.009) and CD10 co-expression (p = 0.007)., Conclusions: NRP-1/CD304 is only expressed in BPDCN, B-ALL and AML, but not in other common hematological diseases. This indicates that NRP-1/CD304 has no obvious diagnostic and follow-up study value in hematological diseases other than BPDCN, B-ALL, and AML., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Previous studies have suggested that point-of-care ultrasound could help to evaluate and diagnose pediatric skull fracture for the closed scalp hematoma from blunt trauma. However, relevant data in Chinese children are missing, especially in children 0-6 years old., Objectives: Our study aimed to evaluate the efficacy of point-of-care ultrasound to diagnose skull fracture in children 0-6 years old with scalp hematoma in China., Methods: We performed a prospective observational study and screened children 0-6 years old with closed scalp hematoma and a Glasgow coma scale of 14-15 at Hospital in China. Enrolled children ( N  = 152) were first evaluated for skull fracture with point-of-care ultrasound by the emergency physician and then received a head computed tomography scan., Results: The point-of-care ultrasound examination and computed tomography scan revealed skull fracture in 13 (8.6%) and 12 (7.9%) children, respectively. The kappa test showed a satisfactory agreement between two examinations (P < 0.0001), with kappa = 0.87 (95% confidence interval, i.e., 95% CI, [0.69, 1.00]) and area under the curve = 0.95 (95% CI [0.86, 1], P  < 0.0001). The point-of-care ultrasound examination had the sensitivity of 91.7% (95% CI [62.5%, 100%]), specificity of 98.6% (95% CI [94.6%, 100%]), positive predictive value of 84.6% (95% CI [56.5%, 96.9%]), negative predictive value of 99.2% (95% CI [95.6%, 100%]), and accuracy of 98.0% (95% CI [94.1%, 99.6%])., Conclusions: While our study is preliminary in nature, our findings may guide future larger studies in assessing the utility of point-of-care ultrasound examination in diagnosing skull fractures in children with scalp hematoma from minor head trauma., Competing Interests: The authors declare no competing interests., (©2023PublishedbyElsevierLtd.)