Perfusion deficit and vessel wall characteristics to predict recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion.

BACKGROUND: To investigate the association between perfusion deficit, vessel wall characteristics, and risk of recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. METHODS: We retrospectively reviewed chronic symptomatic patients due to anterior circulation large vessel occlusion in our center. All patients received multiparametric magnetic resonance imaging (including perfusion-weighted imaging and high-resolution vessel wall imaging) within 4 weeks to 3 months after symptom onset. The association between baseline clinical or imaging variables and recurrent ischemic events was assessed in bivariate models and multivariable logistic regression to identify independent predictors of recurrence. RESULTS: Among 71 enrolled patients, 21.1% (15/71) patients had recurrent ischemic events (nine ischemic strokes and six transient ischemic attacks) during a 2-year follow-up. In bivariate models, hypertension, occlusion with hyperintense signals, the presence of intraluminal thrombus, Tmax >4 s volume, Tmax >6 s volume, Tmax >8 s volume, and Tmax >10 s volume were associated with recurrence (all p < 0.05). In multivariate analysis, hypertension (p = 0.039, OR 10.057 (95% CI, 1.123-90.048)), higher deficit volume of Tmax >4 s (p = 0.011, OR 1.012 (95% CI, 1.003-1.021)) and occlusion with hyperintense signal (p = 0.030, OR 6.732 (95% CI, 1.200-37.772)) were still independent predictors of recurrent ischemic events. CONCLUSIONS: Besides hypertension history, higher deficit volume of Tmax >4 s and occlusion with hyperintense signal determined using multiparametric MRI are strongly associated with risk for recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. Future studies are needed to determine the utility of revascularization strategies in such high-risk patients.

Gravitational Raman Scattering in Effective Field Theory: A Scalar Tidal Matching at O(G

We present a framework to compute amplitudes for the gravitational analog of the Raman process, a quasielastic scattering of waves off compact objects, in worldline effective field theory. As an example, we calculate third post-Minkowskian order [O(G^{3})], or two-loop, phase shifts for the scattering of a massless scalar field including all tidal effects and dissipation. Our calculation unveils two sources of the classical renormalization-group flow of dynamical Love numbers: a universal running independent of the nature of the compact object, and a running self-induced by tides. Restricting to the black hole case, we find that our effective field theory phase shifts agree exactly with those from general relativity, provided that the relevant static Love numbers are set to zero. In addition, we carry out a complete matching of the leading scalar dynamical Love number required to renormalize a universal short scale divergence in the S wave. Our results pave the way for systematic calculations of gravitational Raman scattering at higher post-Minkowskian orders.

Recombinant Human Collagen Type III Improves Hypertrophic Scarring by Regulating the Ratio of Type I/III Collagen.

Hypertrophic scar development is a complication associated with wound healing, impacting local appearance and function. The type I/III collagen ratio affects the extent of hypertrophic scarring; a reduced ratio can ameliorate this. In this study, recombinant human collagen type III was developed. Liquid chromatography-tandem mass spectrometry was used to determine its amino acid sequence and confirm its high level of homology with natural human type III collagen. Recombinant human collagen type III displayed no cytotoxicity and did not confer skin irritation and sensitization. Immunofluorescence and western blot analyses of histidine following incubation with fibroblasts suggested cell entry of recombinant human collagen type III. Furthermore, recombinant human collagen type III promoted the synthesis of the natural type III collagen in fibroblasts, resulting in a more obvious increase of type III collagen content in fibroblasts than that of type I collagen, and then decreased the ratio of type I/III collagen. The results of 5-ethynyl-2'-deoxyuridine staining assay suggested enhanced fibroblast proliferation. Following local injection of recombinant human collagen type III, rabbit ear scarring was significantly reduced after 60 days. Vancouver Scar Scale evaluation showed that all index scores were significantly reduced. Western blotting and Picro-Sirius red staining showed that the natural type III collagen increase in scar tissue was greater than that of type I collagen, decreasing the type I/III ratio. In summary, recombinant human collagen type III can be taken up by fibroblasts and promote natural collagen synthesis-especially that of type III-thereby reducing the type I/III ratio and improving hypertrophic scarring.

Role of clinical pharmacists in multidisciplinary collaborative management of blood glucose in COVID-19 patients with hyperglycemia.

BACKGROUND: During the ongoing global pandemic of COVID-19, the association between hyperglycemia and COVID-19 infection has emerged as a notable concern. Therefore, finding effective methods to manage hyperglycemia in patients with COVID-19 is crucial. OBJECTIVE: To introduce the clinical pharmacists participating in multidisciplinary collaborative whole hospital blood glucose management mode, and to explore its effect on blood glucose control in patients with coronavirus disease 2019 infection and complicated with hyperglycemia. METHODS: Patients with COVID-19 treated at Nanjing Drum Tower Hospital from December 2022 to January 2023 were assigned to routine diagnosis and treatment group and whole hospital blood glucose management group according to the blood glucose management plan received by patients. The groups were compared in regards to their adherence to management advice, blood glucose levels, fluctuation, inflammation-related indicators, medical service-related indicators, and incidence of hypoglycemia and adverse events. RESULTS: After 5 days of glucose management, both groups showed a decrease in fasting and postprandial blood glucose. Postprandial blood glucose in the whole hospital glucose management group was significantly lower than the routine group (P < 0.05). The whole hospital glucose management group showed a significant increase in compliance rate, improved inflammation-related indicators, and higher detection rates for hemoglobin and islet function (P < 0.05). Implementation rates for medical orders and treatment plans were also higher in the whole hospital group (P < 0.05). There was no significant difference in incidence of adverse events. CONCLUSIONS: Multidisciplinary blood glucose management is highly recommended for patients with COVID-19 who have hyperglycemia due to its effectiveness, standardization, safety, and improvement of inflammation indicators.

Expression and role of triggering receptor expressed on myeloid cells 2 in high glucose-treated microglia / 基础医学与临床

Objective To explore the expression of triggering receptor expressed on myeloid cells 2(TREM2)in high-glucose microglia and to investigate the role of TREM2 in the proliferation,migration and phagocytosis of high-glucose microglia.Methods Microglia cells were divided into control group and high-glucose treatment group(67.5 mmol/L glucose,24 h).The microglia cells were counted and the expression of Iba1 and TREM2 was de-tected.TREM2 siRNA was transfected to detect the proliferation and migration of microglia.The amyloid β-peptide(Aβ)with a fluorescent tag was added to observe the phagocytosis of Aβ by microglia.Results Compared to normal microglia,the number of microglia significantly decreased after high-glucose treatment(P＜0.001),while the ex-pression of TREM2 and Iba1 markedly increased(P＜0.001).High glucose and TREM2 did not affect the prolifer-ation of microglia.Compared to the normal group,the migration of microglia significantly decreased after high-glu-cose treatment(P＜0.05)and TREM2 did not affect the migration ability of high-glucose microglia.Compared to the normal group,the phagocytosis of Aβ by microglia significantly decreased in the high-glucose treated group(P＜0.001).Furthermore,TREM2 knockdown further decreased the phagocytosis of Aβ by high-glucose microglia(P＜0.001).Conclusions The expression of TREM2 in microglia significantly increases after high-glucose treat-ment,which significantly affects phagocytosis of Aβ by microglia.

Evaluation of 99m Tc-HYNIC-TOC and 131 I-MIBG imaging in diagnosis of pheochromocytoma and paraganglioma / 基础医学与临床

Objective To evaluate 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging in clinical diag-nostic of pheochromocytoma and paraganglioma(PPGL).Methods This was a retrospective study.359 PPGL pa-tients diagnosed by pathology microscopy were included.The diagnostic sensitivity and influencing factors on 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging were analyzed.Results The positive rate of 99mTc-HYN-IC-TOC somatostatin receptor scintigraphy was 57.7%(184/319)and 131I-MIBG imaging was 83.2%(232/279).The positive rates of 99m Tc-HYNIC-TOC somatostatin receptor imaging in the adrenal glands,retroperitoneum,head and neck,heart and mediastinum,pelvis and bladder were 53.3%,62.5%,95.0%,66.7%,50.0%and 11.0%respec-tively and the positive rates of 131I-MIBG imaging were 86.7%,88.5%,45.4%,50.0%,75.0%and 33.3%respec-tively.The positive rate of the two imaging did not showed difference among patients with different genetic back-grounds(SDH,VHL,RET mutations).The median maximum diameter of tumors was 4.4(3.0,6.1)cm.and the diag-nostic sensitivity of somatostatin receptor imaging and 131 I-MIBG imaging for larger tumors(≥4.4 cm)was signifi-cantly higher than those for the smaller tumor group(＜4.4 cm)(64.0%vs.51.3%;92.3%vs.74.1%)(P＜0.01).Tumors in 19 patients(5.3%)failed to uptake neither imaging method.Conclusions This is the largest PPGL cohort in China concerning 99m Tc-HYNIC-TOC somatostatin receptor imaging and 131 I-MIBG imaging.The sensitivity of 131 I-MIBG imaging is higher than that of 99m Tc-HYNIC-TOC somatostatin receptor imaging,but for some tumors,such as head and neck paraganglioma,the latter has obvious advantages.These two imagings technol-ogies are complementary and the choice of them should depend the individual situation of patients.

Association of NSE level with clinical features in pheochromocytoma/paraganglioma / 基础医学与临床

Objective To study the relationship between serum neuron-specific enolase(NSE)and clinical features of pheochromocytoma/paraganglioma(PPGL).Methods Totally 501 PPGL patients diagnosed from January 2019 to December 2022 were divided into normal NSE group(NSE≤16.3 ng/mL)and elevated NSE group(NSE＞16.3 ng/mL).The clinical characteristics were compared between the two groups.Results Compared with normal NSE group,patients in the elevated NSE group had larger diameter in primary tumor(5.00 cm vs.4.60 cm),higher 24-hour urinary norepinephrine(NE)and 24-hour urinary dopamine(DA)levels,and a higher rate of metasta-sis(31.6%vs.13.7%)(P＜0.05).NSE level was positively correlated with the primary tumor size(r=0.131,P＜0.05),24-hour urinary NE level(r=0.195,P＜0.05)and 24-hour urinary DA level(r=0.119,P＜0.05).Conclusions The level of NSE is related to tumor size,secretion function and metastasis in PPGL patients.

Chronic inflammation regulates adipose tissue fibrosis / 中国组织工程研究

BACKGROUND:In recent years,studies have shown that obesity is closely related to chronic inflammation.Due to excessive energy intake,inflammatory macrophage infiltration and inflammatory response occur in visceral adipose tissue,which is crucial for the regulation of adipose tissue fibrosis. OBJECTIVE:To summarize the molecular mechanism of inflammation-related signals involved in the regulation of adipose tissue fibrosis and to provide reference for the treatment of adipose tissue fibrosis and related metabolic diseases through anti-inflammatory pathways. METHODS:Relevant documents were retrieved from CNKI and PubMed,and the Chinese and English search words were"inflammation,inflammatory factors,inflammatory signals,lip fibrosis,adipose fibrosis,adipose tissue fibrosis"respectively.The search period was from January 2003 to December 2022.Finally,52 documents meeting the criteria were included for review. RESULTS AND CONCLUSION:During obesity,visceral adipose tissue expands through adipocyte proliferation and hypertrophy to store excess energy,and defects caused by remodeling or functional changes mainly include impaired angiogenesis,adipocyte apoptosis promoted by white adipose tissue hypoxia,macrophage infiltration,and adipocyte fibrosis.Adipose tissue fibrosis has adverse effects on the natural growth of adipose cells.The factors that trigger chronic inflammation of adipose tissue include a variety of signal stimuli,such as adipocyte death caused by hypoxia,mechanical signal transduction caused by extracellular matrix remodeling and lipogenic factor imbalance.Inflammatory factors such as interleukin-1β,tumor necrosis factor-α,C-type lectins and adiponectin secreted by adipocytes and other inflammatory signaling pathways such as nuclear factor-κB,transforming growth factor-β/Smad and MAPK jointly regulate the process of adipose tissue fibrosis.

Genetic and clinical features of two cases with familial hyperaldosteronism type Ⅲ / 中华内分泌代谢杂志

Familial hyperaldosteronism type Ⅲ(FH-Ⅲ) is extremely rare, and there are no reported cases in China. Herein, we reported two cases with FH Ⅲ, both of which presented with severe hypertension and hypokalemia in their early childhood. One patient had significantly enlarged adrenal glands and developed clinical manifestations of Cushing′s syndrome at the age of 20. Complete relief of symptoms was achieved after bilateral adrenalectomy. The other case had normal adrenal imaging, and with spironolactone treatment, blood pressure and potassium levels were well-controlled. Both cases had germline mutation of KCNJ5 gene which were c. 433G>C(p.Glu145Gln) and c. 452G>A(p.Gly151Glu), respectively.

Applications and advances of digital technology in spinal surgery: from 3d printing to large language model / 中华创伤骨科杂志

With advancement of science and technology and consequent increasing demands, digital technology has become more and more important in the field of spinal surgery. It provides spinal surgeons with more information, support and assistance to improve the diagnostic accuracy, surgical efficiency, surgical safety, and surgical quality. It also offers new possibilities and opportunities for education, communication, and doctor-patient interaction in medicine. This article reviews the applications and advances of digital technology in the field of spinal surgery, mainly covering 3D printing, surgical navigation, virtual reality and augmented reality, surgical robots, and artificial intelligence. It also analyzes the latest research progress at home and abroad, limitations and challenges, and the future development trends of digital technology.

[Key Prediction Genes of Nasopharyngeal Carcinoma:Screening Based on Systematic Bioinformatics and Validation by Cell Experiments].

Objective To screen out the potential prediction genes for nasopharyngeal carcinoma(NPC)from the gene microarray data of NPC samples and then verify the genes by cell experiments.Methods The NPC dataset was downloaded from Gene Expression Omnibus,and limma package was employed to screen out the differentially expressed genes.Weighted correlation network analysis package was used for weighted gene co-expression network analysis,and Venn diagram was drawn to find the common genes.The gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment were then performed for the common genes.The biomarkers for NPC were further explored by protein-protein interaction network,LASSO regression,and non-parametric tests.Real-time quantitative PCR and Western blotting were employed to determine the mRNA and protein levels of key predictors of NPC,so as to verify the screening results.Results There were 622 up-regulated genes and 351 down-regulated genes in the GSE12452 dataset.A total of 116 common genes were obtained by limma analysis and weighted gene co-expression network analysis.The common genes were mainly involved in the biological processes of cell proliferation and regulation and regulation of intercellular adhesion.They were mainly enriched in Rap1,Ras,and tumor necrosis factor signaling pathways.Six key genes were screened out,encoding angiopoietin-2(ANGPT2),dual oxidase 2(DUOX2),coagulation factor Ⅲ(F3),interleukin-15(IL-15),lipocalin-2,and retinoic acid receptor-related orphan receptor B(RORB).Real-time quantitative PCR and Western blotting showed that the NPC cells had up-regulated mRNA and protein levels of ANGPT2 and IL-15 and down-regulated mRNA and protein levels of DUOX2,F3,and RORB,which was consistent with the results predicted by bioinformatics.Conclusion ANGPT2,DUOX2,F3,IL-15 and RORB are potential predictive molecular markers and therapeutic targets for NPC,which may be involved in Rap1,Ras,tumor necrosis factor and other signaling pathways.

Endovascular recanalization for symptomatic chronic internal carotid artery occlusion: proposal of a modified angiographic classification and clinical outcomes.

PURPOSE: To stratify angiographic images of chronic internal carotid artery occlusion (CICAO) into a newly modified angiographic classification, and identify suitable candidates for endovascular recanalization. METHODS: This study included 51 consecutive patients with symptomatic CICAO who underwent endovascular recanalization at our institution. Patients' clinical information, angiographic findings, procedural results, and outcomes were recorded. We attempted to stratify all angiographic images into categories based on morphological occlusive patterns and distal internal carotid artery (ICA) lumen reconstitution on digital subtraction angiography (DSA). RESULTS: Four types (I-IV) of CICAO were identified based on angiographic characteristics. We defined type I as having a tapered (IA) or blunt stump (IB) and distal ICA lumen reconstitution with collateral filling; type II as having no stump but with distal ICA lumen reconstitution; type III as having a tapered (IIIA) or blunt stump (IIIB) but no distal ICA lumen reconstitution; type IV as having no stump and no distal ICA lumen reconstitution. The rate of successful recanalization was 90.3 % for type I, 60.0 % for type II, 50.0 % for type III, 0 % for type IV, respectively (P = 0.002). The overall intraoperative complication rate was 11.8 %, and none of them led to severe neurological damage or death. The follow-up modified Rankin Scale (mRS) scores were significantly decreased in successfully revascularized patients, whilst there were no significant changes in the other failed patients. CONCLUSION: For symptomatic CICAO, our newly modified angiographic classification may be comprehensive and useful in selecting suitable patients for recanalization and grading the difficulty of the procedures.

A MYCN-independent mechanism mediating secretome reprogramming and metastasis in MYCN-amplified neuroblastoma.

MYCN amplification (MNA) is a defining feature of high-risk neuroblastoma (NB) and predicts poor prognosis. However, whether genes within or in close proximity to the MYCN amplicon also contribute to MNA+ NB remains poorly understood. Here, we identify that GREB1, a transcription factor encoding gene neighboring the MYCN locus, is frequently coexpressed with MYCN and promotes cell survival in MNA+ NB. GREB1 controls gene expression independently of MYCN, among which we uncover myosin 1B (MYO1B) as being highly expressed in MNA+ NB and, using a chick chorioallantoic membrane (CAM) model, as a crucial regulator of invasion and metastasis. Global secretome and proteome profiling further delineates MYO1B in regulating secretome reprogramming in MNA+ NB cells, and the cytokine MIF as an important pro-invasive and pro-metastatic mediator of MYO1B activity. Together, we have identified a putative GREB1-MYO1B-MIF axis as an unconventional mechanism promoting aggressive behavior in MNA+ NB and independently of MYCN.

ASPECTS-based net water uptake outperforms target mismatch for outcome prediction in patients with acute ischemic stroke and late therapeutic window.

OBJECTIVE: To compare the prognostic value of net water uptake (NWU) and target mismatch (TM) on CT perfusion (CTP) in acute ischemic stroke (AIS) patients with late time window. METHODS: One hundred and nine consecutive AIS patients with anterior-circulation large vessel occlusion presenting within 6-24 h from onset/last seen well were enrolled. Automated Alberta Stroke Program Early CT Score-based NWU (ASPECTS-NWU) was calculated from admission CT. The correlation between ASPECTS-NWU and CTP parameters was assessed. Predictors for favorable outcome (modified Rankin Scale score ≤ 2) at 90 days were assessed using logistic regression analysis. The ability of outcome prediction between ASPECTS-NWU and TM (an ischemic core < 70 mL, a mismatch ratio ≥ 1.8, and an absolute difference ≥ 15 mL) was compared using receiver operating characteristic (ROC) curve. RESULTS: A higher level of ASPECTS-NWU was associated with a larger ischemic core (r = 0.66, p < 0.001) and a larger hypoperfusion volume (r = 0.38, p < 0.001). ASPECTS-NWU performed better than TM for outcome stratification (area under the curve [AUC], 0.738 vs 0.583, p = 0.004) and was the only independent neuroimaging marker associated with favorable outcomes compared with CTP parameters (odds ratio, 0.73; 95% confidence interval [CI] 0.62-0.87, p < 0.001). An outcome prediction model including ASPECTS-NWU and clinical variables (National Institutes of Health Stroke Scale scores and age) yielded an AUC of 0.828 (95% CI 0.744-0.893; sensitivity 65.4%; specificity 87.7%). CONCLUSION: ASPECTS-NWU performed better than TM for outcome prediction in AIS patients with late time window and might be an alternative imaging biomarker to CTP for patient selection. CLINICAL RELEVANCE STATEMENT: Automated Alberta Stroke Program Early CT Score-based net water uptake outperforms target mismatch on CT perfusion for the outcome prediction in patients with acute ischemic stroke and can be an alternative imaging biomarker for patient selection in late therapeutic window. KEY POINTS: • A higher ASPECTS-based net water uptake was associated with larger ischemic cores and hypoperfusion volumes on CT perfusion. • ASPECTS-based net water uptake outperformed target mismatch for outcome prediction in acute ischemic stroke with extended therapeutic window. • ASPECTS-based net water uptake can be an alternative biomarker to target mismatch for selecting acute ischemic stroke patients with late therapeutic window.

Effect of Truncal-Type Occlusion Based on Multiphase or Single-Phase Computed Tomographic Angiography in Predicting Intracranial Atherosclerotic Stenosis-Related Acute Middle Cerebral Artery Occlusion.

OBJECTIVE: To investigate whether truncal-type occlusion based on multiphase computed tomographic angiography (mpCTA) was more effective for predicting intracranial atherosclerotic stenosis-related occlusion (ICAS-O) than occlusion type based on single-phase computed tomographic angiography (spCTA) in patients with acute ischemic stroke with large-vessel occlusion (AIS-LVO) in the middle cerebral artery (MCA). METHODS: Data were retrospectively collected from 72 patients with AIS-LVO in the MCA between January 2018 and December 2019. The occlusion types included truncal-type and branching-site occlusions. The association between ICAS-O and occlusion type based on the 2 computed tomographic angiography patterns was analyzed, and receiver operating characteristic curves were plotted for assessment. The areas under the curve were compared to determine the difference between the predictive powers of truncal-type occlusion based on mpCTA and spCTA. RESULTS: Among the 72 patients, 16 were classified as having ICAS-O and 56 as having embolisms. In univariate analysis, truncal-type occlusion was significantly associated with ICAS-O ( P < 0.001 for mpCTA and P = 0.001 for spCTA). After multivariable analysis, truncal-type occlusion based on both mpCTA and spCTA remained independently associated with ICAS-O ( P = 0.002 for mpCTA and P = 0.029 for spCTA). The areas under the curve were 0.821 for mpCTA and 0.683 for spCTA; this difference was statistically significant ( P = 0.024). CONCLUSIONS: In patients with AIS-LVO in the MCA, truncal-type occlusion based on mpCTA enables more accurate detection of ICAS-O than that based on spCTA.

Early plasma D-dimer as a predictor of acute intracranial atherosclerosis-related large vessel occlusion in acute ischemic stroke.

BACKGROUND: Intracranial atherosclerosis-related large vessel occlusion (ICAS+LVO) poses an important technical challenge for endovascular thrombectomy (EVT). PURPOSE: To evaluate the value of D-dimer in predicting ICAS+LVO alone and in combination with other clinical and imaging predictors. MATERIAL AND METHODS: Consecutive patients who underwent EVT at our center between January 2018 and June 2021 were retrospectively reviewed. Patients were classified to the ICAS+LVO or ICAS-LVO group according to angiographic findings. Collateral gradings were evaluated based on computed tomography angiography and categorized as follows: score 0-1 unfavorable collaterals and score 2-3 favorable collaterals. Receiver operating characteristic curve was analyzed to evaluate the predictive value of D-dimer and the combination of other predictors for ICAS+LVO. RESULTS: A total of 374 patients were enrolled, among them, 107 (28.6%) had an ICAS+LVO, while ICAS-LVO was determined in 267 (71.4%) patients. Median D-dimer levels were lower (0.36 vs. 1.18 mg/L; P < 0.001) while the proportion of favorable collaterals was higher (85.0% vs. 22.5%; P < 0.001) in the ICAS+LVO group than the ICAS-LVO group. After multivariable analysis, D-dimer (adjusted odds ratio [OR]=0.32, 95% confidence interval [CI]=0.21-0.50; P < 0.001) and collaterals (adjusted OR=16.25, 95% CI=7.58-34.84; P < 0.001) remained independent predictors of ICAS+LVO. The area under the curve of D-dimer, collaterals, and combination for identification of ICAS+LVO was 0.82, 0.85, and 0.92, respectively. CONCLUSION: Low early plasma D-dimer levels are a significant and independent predictor of ICAS+LVO, and predictive value strengthens when in a combined model using D-dimer and collateral grading.

Predictors of ghost infarct core on baseline computed tomography perfusion in stroke patients with successful recanalization after mechanical thrombectomy.

OBJECTIVES: To assess the predictors of ghost infarct core (GIC) in stroke patients achieving successful recanalization after mechanical thrombectomy (MT), based on final infarct volume (FIV) calculated from follow-up diffusion-weighted imaging (DWI). METHODS: A total of 115 consecutive stroke patients who had undergone baseline computed tomography perfusion (CTP) scan, achieved successful recanalization after MT, and finished follow-up DWI evaluation were retrospectively enrolled. Ischemic core volume was automatically generated from baseline CTP, and FIV was determined manually based on follow-up DWI. Stroke-related risk factors and demographic, clinical, imaging, and procedural data were collected and assessed. Univariate and multivariate analyses were applied to identify the predictors of GIC. RESULTS: Of the 115 included patients (31 women and 84 men; median age, 66 years), 18 patients (15.7%) showed a GIC. The GIC group showed significantly shorter time interval from stroke onset to CTP scan and that from stroke onset to recanalization (both p < 0.001), but higher ischemic core volume (p < 0.001), hypoperfused area volume (p < 0.001), mismatch area volume (p = 0.006), and hypoperfusion ratio (p = 0.001) than the no-GIC group. In multivariate analysis, time interval from stroke onset to CTP scan (odds ratio [OR], 0.983; p = 0.005) and ischemic core volume (OR, 1.073; p < 0.001) were independently associated with the occurrence of GIC. CONCLUSIONS: In stroke patients achieving successful recanalization after MT, time interval from stroke onset to CTP and ischemic core volume are associated with the occurrence of GIC. Patients cannot be excluded from MT solely based on baseline CTP-derived ischemic core volume, especially for patients with a shorter onset time. KEY POINTS: • Ghost infarct core (GIC) was found in 15.7% of patients with acute ischemic stroke (AIS) in our study cohort. • GIC was associated with stroke onset time, volumetric parameters derived from CTP, and collateral status indicated by HIR. • Time interval from stroke onset to CTP scan and ischemic core volume were independent predictors of GIC.

CT perfusion with increased temporal sampling interval to predict target mismatch status in patients with acute ischemic stroke.

PURPOSE: To evaluate the feasibility of using CT perfusion (CTP) with increased temporal sampling interval to predict the target mismatch status in acute ischemic stroke (AIS) patients with anterior circular large-vessel occlusion (LVO). METHODS: CTP with a sampling interval of 1.7 s (CTP1.7 s) was scanned in 77 AIS patients for pre-treatment evaluation. Simulated CTP data with sampling interval of 3.4 s (CTP3.4 s) or 5.1 s (CTP5.1 s) were reconstructed, respectively. Target mismatch was defined according to the EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trial criteria, respectively. Pearson correlation analysis, Mann-Whitney U test, Bland-Altman analysis, and chi-square test were used for statistical analysis as appropriate. RESULTS: Significant correlations were found on the volume of ischemic core, hypo-perfused area, mismatch area, and ratio between CTP1.7 s and CTP3.4 s or CTP5.1 s (all p < 0.001). There was no significant difference on the volume of ischemic core, hypo-perfused area, mismatch area, and mismatch ratio between CTP1.7 s and CTP3.4 s or CTP5.1 s (all p > 0.05). Compared with CTP1.7 s, CTP3.4 s or CTP5.1 s showed comparable performance in predicting the target mismatch status in the AIS patients with LVO (both p > 0.05). CONCLUSIONS: CTPs with increased temporal sampling intervals that lead to reduced radiation doses are feasible and may provide comparable performance in predicting target mismatch status in AIS patients with LVO.

Iron-based and BRD4-downregulated strategy for amplified ferroptosis based on pH-sensitive/NIR-II-boosted nano-matchbox

Ferroptosis (FPT), a novel form of programmed cell death, is characterized by overwhelming iron/reactive oxygen species (ROS)-dependent accumulation of lipid peroxidation (LPO). However, the insufficiency of endogenous iron and ROS level limited the FPT therapeutic efficacy to a large extent. To overcome this obstacle, the bromodomain-containing protein 4 (BRD4)-inhibitor (+)-JQ1 (JQ1) and iron-supplement ferric ammonium citrate (FAC)-loaded gold nanorods (GNRs) are encapsulated into the zeolitic imidazolate framework-8 (ZIF-8) to form matchbox-like GNRs@JF/ZIF-8 for the amplified FPT therapy. The existence of matchbox (ZIF-8) is stable in physiologically neutral conditions but degradable in acidic environment, which could prevent the loaded agents from prematurely reacting. Moreover, GNRs as the drug-carriers induce the photothermal therapy (PTT) effect under the irradiation of near-infrared II (NIR-II) light owing to the absorption by localized surface plasmon resonance (LSPR), while the hyperthermia also boosts the JQ1 and FAC releasing in the tumor microenvironment (TME). On one hand, the FAC-induced Fenton/Fenton-like reactions in TME can simultaneously generate iron (Fe3+/Fe2+) and ROS to initiate the FPT treatment by LPO elevation. On the other hand, JQ1 as a small molecule inhibitor of BRD4 protein can amplify FPT through downregulating the expression of glutathione peroxidase 4 (GPX4), thus inhibiting the ROS elimination and leading to the LPO accumulation. Both in vitro and in vivo studies reveal that this pH-sensitive nano-matchbox achieves obvious suppression of tumor growth with good biosafety and biocompatibility. As a result, our study points out a PTT combined iron-based/BRD4-downregulated strategy for amplified ferrotherapy which also opens the door of future exploitation of ferrotherapy systems.

Periplaneta americana extract CⅡ-3 induces senescence of leukemia K562 cells via SIRT1/mTOR signaling pathway / 中国中药杂志

This study aims to investigate the role of slient mating-type information regulation 2 homolog 1(SIRT1)/tuberous sclerosis complex 2(TSC2)/mammalian target of rapamycin(mTOR) signaling pathways in the Periplaneta americana extract CⅡ-3-induced senescence of human leukemia K562 cells. K562 cells were cultured in vitro and treated with 0(control), 5, 10, 20, 40, 80, and 160 μg·mL~(-1) of P. americana extract CⅡ-3. Cell counting kit-8(CCK-8) and flow cytometry were employed to examine the proliferation and cell cycle of the K562 cells. Senescence-associated β-galactosidase stain kit(SA-β-gal) was used to detect the positive rate of senescent cells. Mitochondrial membrane potential was detected by flow cytometry. The relative mRNA level of telomerase reverse transcriptase(TERT) was determined by fluorescence quantitative PCR. The mRNA and protein levels of SIRT1, TSC2, and mTOR were determined by fluorescence quantitative PCR and Western blot, respectively. The results showed that CⅡ-3 significantly inhibited the proliferation of K562 cells and the treatment with 80 μg·mL~(-1) CⅡ-3 for 72 h had the highest inhibition rate. Therefore, 80 μg·mL~(-1) CⅡ-3 treatment for 72 h was selected as the standard for subsequent experiments. Compared with the control group, CⅡ-3 increased the proportion of cells arrested in G_0/G_1 phase, decreased the proportion of cells in S phase, increased the positive rate of SA-β-Gal staining, elevated the mitochondrial membrane potential and down-regulated the mRNA expression of TERT. Furthermore, the mRNA expression of SIRT1 and TSC2 was down-regulated, while the mRNA expression of mTOR was up-regulated. The protein expression of SIRT1 and p-TSC2 was down-regulated, while the protein expression of p-mTOR was up-regulated. The results indicated that P. americana extract CⅡ-3 induced the senescence of K562 cells via the SIRT1/mTOR signaling pathway.