1.Autophagy inducer spermidine improves brain injury after intracerebral hemorrhage
Lingxiao QI ; Gaili YAN ; Mengzhou XUE
Journal of Army Medical University 2025;47(7):639-648
Objective To investigate the role and underlying mechanism of spermidine(SPD)in intracerebral hemorrhage(ICH).Methods Male C57BL/6 mice were subjected to establish a collagenase-induced ICH model.The 108 mice were randomly divided into Sham group,ICH group and ICH+SPD group(intraperitoneal injection of 15 mg/kg SPD for 3 consecutive days after modeling),with 36 mice in each group.On the 3rd day after ICH,neurological deficits were evaluated using modified Garcia scoring and forelimb placing test;brain pathological damage was assessed with HE staining;activation of microglia/macrophages(Iba-1)and astrocytes(GFAP)was detected by immunofluorescence assay;expression of autophagy markers(Beclin-1,P62)and inflammatory factors(MMP-9,NLRP3,COX-2)was measured with Western blotting.In in vitro experiments,hemin was used to stimulate HT-22 cells to mimic ICH.The HT-22 cells were randomly divided into Control group,Hemin group,Hemin+SPD group,and Hemin+SPD+3-methyladenine(3-MA,an autophagy inhibitor)group(n=7).After 24 h of hemin treatment,cell viability was detected with CCK-8 assay,the expression of autophagy-related proteins(LC3-Ⅱ and P62)were detected with Western blotting,and oxidative stress was determined by measuring superoxide dismutase(SOD)activity and malondialdehyde(MDA)content.Results On day 3 post-ICH,SPD significantly reduced the area of brain damage(P<0.05),improved neurological recovery(P<0.05),activated autophagy with up-regulation of Beclin-1 while down-regulation of P62(P<0.05),suppressed the activation of microglia/macrophage and astrocytes(P<0.01),reduced the expression of MMP-9,NLRP3 and COX-2,and enhanced SOD activity and decreased MDA content(P<0.05)when compared with the ICH group.SPD increased the viability of HT-22 cells(P<0.05),improved SOD activity and reduced MDA content(P<0.01).Autophagy inhibitor 3-MA effectively blocked the down-regulation of LC3-Ⅱ and up-regulation of P62,and completely reversed above protective effects caused by SPD(P<0.05).Conclusion SPD activates autophagy after ICH and improves post-ICH brain injury by suppressing neuroinflammation and oxidative stress.
2.Meta-analysis of diagnostic efficiency of 99Tc m-PYP SPECT/CT scintigraphy for transthyretin-related cardiac amyloidosis
Taiping LIAO ; Yueting SHEN ; Qinling QI ; Li LI ; Guoxu FU ; Lingxiao LI ; Yongjun LONG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(8):484-489
Objective:To discuss the performance of visual score and heart-to-contralateral lung (H/CL) ratio of 99Tc m-pyrophosphate (PYP) SPECT/CT scintigraphy for diagnosing transthyretin-related cardiac amyloidosis (ATTR-CA) by using Meta-analysis. Methods:Relevant studies on 99Tc m-PYP SPECT/CT diagnosis of ATTR-CA published before August 20, 2023 from databases including Pubmed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and China Science and Technology Journal Database (VIP) were retrieved. Articles were screened and indices which reflect the diagnostic efficiency such as sensitivity and specificity were extracted. Forest plots were drawn, and subgroup analysis was performed to analyze the heterogeneity. Results:A total of 160 articles were retrieved, and 11 articles involving 1 802 patients were enrolled, of whom 605 were diagnosed with ATTR-CA. All 11 articles were enrolled when analyzing the diagnostic efficiency of visual score for diagnosing ATTR-CA. After integration, the sensitivity and specificity were 0.95(95% CI: 0.91-0.97) and 0.95(95% CI: 0.90-0.98), respectively. Ten articles (1 611 patients) were enrolled when analyzing the diagnostic efficiency of H/CL ratio for diagnosing ATTR-CA. After integration, the sensitivity and specificity were 0.93(95% CI: 0.82-0.98) and 0.99(95% CI: 0.90-1.00), respectively. Subgroup analysis indicated that lack of uniformity in diagnostic criteria was the primary source of heterogeneity. Conclusion:99Tc m-PYP SPECT/CT scintigraphy exhibits high diagnostic efficiency for ATTR-CA.
3.Risk factors of muscle necrosis in patients with acute compartment syndrome
Lingxiao HE ; Qi CHEN ; Huan ZHANG ; Dengbin LIAO ; Xiaoling HOU ; Yan JIANG
Chinese Journal of Trauma 2021;37(12):1068-1073
Objective:To investigate the risk factors of muscle necrosis in patients with acute compartment syndrome(ACS).Methods:A retrospective case-control study was conducted for clinical data of 111 ACS patients admitted to West China Hospital, Sichuan University from January 2010 to December 2020, including 84 males and 27 females; age 18-76 years [45(36, 55)years]. Muscle necrosis was presented in 35 patients(necrotic muscle group), but was not seen in 76 patients(non-necrotic muscle group). The univariate analysis was performed for the two groups in the demographic data(sex, age, ethnicity, body mass index, smoking history, chronic comorbidities), injury patterns [ mechianism of injury(low energy injury, high energy injury, crush injury, other injury), time from injury to treatment, first visit or not, combination with bone fracture or not, open injury or not, presence of tension blisters or not], medical treatment(number of debridements, fasciotomy or not)and laboratory indicators [hemoglobin(Hb), platelet count(PLT), white blood cell count(WBC), prothrombin time(PT), international normalized ratio(INR), partially activated prothrombin time(APTT), fibrinogen(FIB), D-Dimer(D-D), alanine aminotransferase(ALT), aspartate aminotransferase(AST), albumin(ALB), intravenous blood glucose(GLU), creatine kinase(CK), peak value of CK during hospitalization(natural logarithmic conversion, lnCK), serum sodium(NA), serum potassium(K), serum calcium(CA)]. Further multivariate logistic regression was performed to analyze the independent risk factors of muscle necrosis in ACS patients.Results:The univariate analysis showed that there were statistically significant differences between the two groups in the mechanism of injury, first visit or not, combination with bone fracture or not, number of debridements, Hb, PT, INR, D-D, AST, ALB, GLU, CK and lnCK( P<0.05), while not in the basic data, time from injury to treatment, open injury or not, presence of tension blisters or not, fasciotomy or not, PLT, WBC, APTT, FIB, ALT, NA, K and CA( P>0.05). The multivariate logistic regression analysis showed that high energy injury( OR=5.143, 95% CI 1.216-21.758, P<0.05), crush injury( OR=22.313, 95% CI 2.625-189.635, P<0.05), other mechanism of injury( OR=9.019, 95% CI 1.036-78.554, P<0.05), first visit or not( OR=0.071, 95% CI 0.006-0.819, P<0.05), Hb( OR=0.979, 95% CI 0.961-0.998, P<0.05), GLU( OR=1.218, 95% CI 1.020-1.455, P<0.05)and lnCK( OR=1.805, 95% CI 1.235-2.639, P<0.05)were significantly related with muscle necrosis. Conclusion:The mechanism of injury, first visit or not, Hb, GLU and lnCK are the independent risk factors of muscle necrosis in patients with ACS.

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