Ischemic stroke is a devastating neuro-logical disease worldwide,with high global burden.The microglial activation-driven neuroinflammation plays a critical role in pathophysiology of ischemic stroke.After the ictus of brain ischemic attack,cy-tosolic double-stranded DNA(dsDNA)released by necrotic neuronal cells is a potential damage-asso-ciated molecular pattern(DAMP)to activate cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.cGAS-STING sig-naling pathway has emerged as a key player in mi-croglial activation,sterile neuroinflammation,and cell death following ischemic stroke.Targeting this pathway holds promise for developing novel thera-peutics that effectively mitigate neuroinflamma-tion,prevent cell death,and enhance patient out-comes.In this review,we first outline the principal elements of the cGAS-STING signaling cascade,then discusses the pivotal role of the cGAS-STING pathway in ischemic stroke.Then,we outline selec-tive small-molecules modulators that function as cGAS-STING inhibitors and summarize their mecha-nisms to treat Ischemic stroke.Finally,we discuss key limitations of the current therapeutic paradigm and generate possible strategies to overcome them.

Ischemic stroke is a devastating neuro-logical disease worldwide,with high global burden.The microglial activation-driven neuroinflammation plays a critical role in pathophysiology of ischemic stroke.After the ictus of brain ischemic attack,cy-tosolic double-stranded DNA(dsDNA)released by necrotic neuronal cells is a potential damage-asso-ciated molecular pattern(DAMP)to activate cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.cGAS-STING sig-naling pathway has emerged as a key player in mi-croglial activation,sterile neuroinflammation,and cell death following ischemic stroke.Targeting this pathway holds promise for developing novel thera-peutics that effectively mitigate neuroinflamma-tion,prevent cell death,and enhance patient out-comes.In this review,we first outline the principal elements of the cGAS-STING signaling cascade,then discusses the pivotal role of the cGAS-STING pathway in ischemic stroke.Then,we outline selec-tive small-molecules modulators that function as cGAS-STING inhibitors and summarize their mecha-nisms to treat Ischemic stroke.Finally,we discuss key limitations of the current therapeutic paradigm and generate possible strategies to overcome them.

Objective:To explore the current status of physical frailty in elderly patients with chronic obstructive pulmonary disease (COPD) and analyze its influencing factors.Methods:A total of 278 COPD patients who were admitted to Geriatric Medicine Center of Xinjiang Uygur Autonomous Region People's Hospital from February 2018 to February 2020 were selected as the research objects by the convenient sampling method. FRAIL Scale was used to assess frailty status of the patients. General information questionnaire and clinical questionnaires were used to investigate. Ordinal Logistic regression model was used to analyze the influencing factors of frailty in elderly COPD patients.Results:A total of 278 questionnaires were issued and 260 valid questionnaires were returned, including 120 cases without frailty, 97 cases in early frailty and 43 cases in frailty. The results of ordinal logistic regression analysis showed that age [ OR=1.324, 95% CI: (1.011-1.632) ], whether exercise regularly [ OR=0.265, 95% CI: (0.004-0.765) ], whether lack of nutrition [ OR=1.335, 95% CI: (0.258-1.985) ], with or without comorbidities [ OR=1.654, 95% CI: (0.521-1.865) ], lung function classification [ OR=2.356, 95% CI: (1.520-3.690) ], whether inflammation [ OR=1.258, 95% CI: (0.024-1.821) ] and prolonged length of stay in hospital due to exacerbation of COPD in the past 1 year [ OR=0.854, 95% CI: (0.214-1.662) ]were influencing factors of frailty in elderly COPD patients (all P<0.05) . Conclusions:The frailty of elderly patients with COPD is affected by factors such as age, exercise, nutritional status, length of stay in hospital, lung function, inflammation and complications. Nursing staff should prevent frailty and delay the progression of frailty in COPD patients through effective intervention.