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Abstract Background The extubation time is critical during the intensive care unit stay in aneurysmal subarachnoid hemorrhage (aSAH) patients. The current conventional parameters for predicting extubation failure (EF) and extubation time may not be suitable for this population. Here, we aimed to identify factors associated with EF in aSAH patients. Methods From a single-center observational study on aSAH patients with computed tomography angiography from 2019 to 2021, patients who received microsurgery were enrolled and divided into two groups according to whether EF occurred. Multivariable logistic regression was conducted to evaluate disease severity, medical history, and extubation time differences between patients with and without EF. Results Of 335 patients included, EF occurred with a rate of 0.14. Delayed cerebral ischemia (67.4% vs. 13.5%) and acute hydrocephalus (6.5% vs. 1.4%) were frequently observed in patients with EF. Also, patients who develop EF presented higher disability (65.9% vs. 17.4%) and mortality (10.9% vs. 0.7%) rates. Multivariable analysis demonstrated that age (OR 1.038; 95% CI 1.004–1.073; P = 0.028), onset to admission time (OR 0.731; 95% CI 0.566–0.943; p = 0.016), WFNS grade > 3 (OR 4.309; 95% CI 1.639–11.330; p = 0.003), and extubation time 3 have a high risk of developing EF, which is amplified by the ultra-early extubation. Moreover, in patients with two or more risk factors, a prolonged intubation recommendation requires consideration to avoid the EF.

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurosurgical emergency with a high mortality rate. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) are delayed products of early brain injury (EBI), which may constitute the principal determinant of an unfavorable patient prognosis. Consequently, the mitigation of DCI and CVS assumes paramount significance in the pursuit of enhanced patient outcomes. However, except for oral nimodipine, there is no effective therapy available in the current guideline. Hence, the exigency arises to proffer novel treatment paradigms. The diversity of hydrogen therapeutic targets has been largely reported in basic research, unveiling its latent capacity to ameliorate EBI in aSAH patients. Methods Early Hydrogen–Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA), a single-center, prospective, open-labeled, randomized controlled clinical trial, endeavors to evaluate the efficacy and safety of hydrogen–oxygen gas mixture inhalation therapy in aSAH patients. A cohort of 206 patients will be randomized to either hydrogen–oxygen gas mixture inhalation group (8 h per day, 3 L/min, hydrogen concentration of 67%, oxygen concentration of 33%) or oxygen inhalation group (8 h per day, 3 L/min, oxygen concentration of 33%) within 72 h after aSAH and treated for 7 days in the ICU ward. The primary outcomes are the incidence of DCI and CVS during hospitalization. Discussion The HOMA aims to evaluate the effectiveness of hydrogen–oxygen gas mixture inhalation therapy in preventing DCI or CVS and improving outcomes in aSAH patients. Notably, this is the first large-scale trial of hydrogen therapy in aSAH patients. Given that the Chinese population represents a significant portion of the global population and the increasing incidence of stroke due to aging, optimizing patient care is vital. Given the current challenges in aSAH patient outcomes, initiating more prospective clinical trials is essential. Recent research has shown hydrogen’s therapeutic potential, aligning with EBI in aSAH, driving our exploration of hydrogen therapy’s mechanisms in post-aneurysm rupture damage. Ethics and dissemination The protocol for the HOMA study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (KY 2022–020-02). All results of the present study will be published in peer-reviewed journals and presented at relevant conferences. Trial registration ClinicalTrials.gov NCT05282836. Registered on March 16, 2022.

Objective: This investigation explored the association between postoperative/preoperative platelet ratio (PPR) and the incidence of unfavorable outcomes within 90 days in individuals with aneurysmal subarachnoid hemorrhage (aSAH). Methods: This investigation, utilizing data from 2015 to 2022, concentrated on patients diagnosed with aSAH, categorizing them into four groups based on PPR quartiles. The association between PPR levels and clinical outcomes—comprising in-hospital complications, mortality, and modified Rankin Scale (mRS) scores at discharge and 90 days after that—was evaluated through logistic regression analyses. To explore potential non-linear associations between PPR levels and outcomes, restricted cubic spline (RCS) regression was applied. Further, mediation analysis was performed to elucidate the role of in-hospital complications in modulating the impact of PPR levels on 90-day outcomes. Results: This study analyzed data from 948 patients. Upon adjustment for confounding variables, it was observed that patients in the higher quartiles showed reduced incidences of anemia, hypoproteinemia, and pneumonia, alongside a decreased frequency of unfavorable outcomes within a 90-day follow-up period. The RCS analysis indicated a linear association of PPR with pneumonia, hypoproteinemia, and adverse 90-day outcomes (p for nonlinear = 0.61, 0.52, and 0.96, respectively). Moreover, the association of PPR with anemia was found to be nonlinear (p for nonlinear = 0.01). Mediation analysis further indicated that anemia and pneumonia significantly influenced the association between PPR and unfavorable outcomes at 90 days, accounting for 15.49 % and 27.61 % of the effect, respectively. Conclusions: This study establishes a significant correlation between decreased PPR levels and 90-day adverse outcomes following aSAH, potentially relating to pneumonia and anemia.

Abstract Objective Our study aims to investigate the association between the Hounsfield unit (Hu) value of the insular cortex (IC) during emergency admission and the subsequent occurrence of post‐operative neurocardiogenic injury (NCI) among patients afflicted with aneurysmal subarachnoid hemorrhage (aSAH). Methods Patients baseline characteristics were juxtaposed between those with and without NCI. The significant variables were incorporated into a multivariable stepwise logistic regression model. Receiver operating characteristic (ROC) curves were drafted for each significant variable, yielding cutoff values and the area under the curve (AUC). Subgroup and sensitivity analyses were performed to assess the predictive performance across various cohorts and ascertain result stability. Propensity score matching (PSM) was ultimately employed to redress any baseline characteristic disparities. Results Patients displaying a right IC Hu value surpassing 28.65 exhibited an escalated risk of postoperative NCI upon confounder adjustment (p

BackgroundStress-related gastrointestinal bleeding (SRGB) is one of the major complications after aneurysmal subarachnoid hemorrhage (aSAH), and it can present challenges in patient care and treatment. The aim of this study was to explore the clinical significance of the caudate Hounsfield unit (HU) value in the Alberta Stroke Program Early CT (ASPECT) score for predicting SRGB in patients with aSAH.MethodsWe retrospectively analyzed the data of 531 aSAH patients admitted to our institution between 2019 and 2022. Potential predictors of SRGB were identified using multivariate Cox regression analysis. We used a restricted cubic spline (RCS) to evaluate whether there is a nonlinear relationship between the right caudate HU value and SRGB. MaxStat analysis (titled as maximally selected rank statistics) was performed to identify the optimal cutoff point for the right caudate HU value. Another Kaplan–Meier method with the log-rank test was used to analyze the right caudate HU value in predicting the occurrence of SRGB.ResultsThe incidence rate of SRGB was 17.9%. In the multivariate Cox regression analysis, the right caudate HU value was an independent predictor of SRGB [Hazard ratio (HR) = 0.913; 95% confidence interval (CI): 0.847–0.983, and p = 0.016]. The RCS indicated that the incidence of developing SRGB reduces with increasing right caudate HU values (nonlinear p = 0.78). The optimal cut-off value of the right caudate HU was 25.1.ConclusionAmong aSAH patients, lower right caudate HU values indicated a higher risk of developing SRGB. Our findings provide further evidence for the relationship between the gastrointestinal system and the brain.

Abstract Background Brain arteriovenous malformation (AVM) is an important cause of hemorrhagic stroke in young adults, which can lead to severe neurological impairment. The registry of Multimodality treatment for brain ArTeriovenous malformation in mainland CHina (MATCH) is a national prospective registry to identify the natural history of AVMs in Asian population; to investigate traditional and emerging hemorrhagic predictors; and to explore the superiority of the multidisciplinary assessment in improving the long-term outcomes. Methods Consecutive AVM patients will be enrolled from 52 participating hospitals in mainland China. Baseline demographic, clinical and imaging data will be collected prospectively. Conservation, microsurgery, embolization, stereotactic radiosurgery (SRS), and multimodal strategies are all included in this study. Patients will be divided into experimental and control group according to whether the treatment protocols are formulated by multidisciplinary team. Neurofunctional status, subsequent hemorrhage, seizure, and novel neurofunctional deficit will be queried at 3 months, annually (1 and 2 years), 3 years, and 10 years follow-up. Results Between August 2011 and April 2021, 3241 AVMs were enrolled in 11 participating sites. Among them, 59.0% were male with an average age of 28.4 ± 14.6 years, 61.2% had rupture history and 2268 hemorrhagic events occurred before admission. The median Spetzler-Martin grade and Lawton-Young grade was 3 and 5, respectively. Microsurgery is the dominant strategy (35.7%), with a similar proportion of embolization, SRS, and a combination of both (12.7%; 14.8%; 11.8%; respectively). Among them, 15.43% underwent multidisciplinary assessment and received standardized treatment. At the most recent follow-up, 7.8% were lost and the median follow-up duration was 5.6 years. Conclusions The MATCH study is a large-sample nationwide prospective registry to investigate multimodality management strategy for AVMs. Data from this registry may also provide the opportunity for individualized risk assessment and the development of optimal individual management strategies. Trial registration ClinicalTrials.gov Registry ( NCT04572568 ).

ObjectivePostoperative pneumonia (POP) is one of the major complications after aneurysmal subarachnoid hemorrhage (aSAH) associated with postoperative mortality, prolonged hospitalization, and increased medical cost. Early recognition of pneumonia and more aggressive management may improve patient outcomes.MethodsWe retrospectively reviewed all patients with aSAH who were admitted to our institution between January 2015 and December 2020. Baseline clinical characteristics, imaging data, and inflammatory biomarkers were reviewed. The risk factors derived from multivariate logistic regression of surgical clipping (SC) and endovascular coiling (EC) were analyzed. The area under the receiver operating characteristic (ROC) curve (AUC) was used to calculate each independent predictor's prediction ability.ResultsA total of 843 patients were enrolled. Compared with patients in the EC group, the incidence of POP was higher in the SC group [143/414 (34.54%) vs. 114/429 (26.57%), p = 0.015]. In the EC group, multivariate analysis revealed that age [p = 0.001; odds ratio (OR) = 1.04, 95% CI = 1.02–1.07], posterior circulation aneurysms (p = 0.021; OR = 2.07, 95% CI = 1.14–3.83), higher neutrophil (NEUT; p < 0.001; OR = 1.13, 95% CI = 1.06–1.21), World Federation of Neurosurgical Societies (WFNS) grade 4 or 5 (p < 0.001; OR = 4.84, 95% CI = 2.67–8.79), modified Fisher Scale (mFS) grade 3 or 4 (p = 0.022; OR = 2.60, 95% CI = 1.15–5.89), and acute hydrocephalus (p = 0.048; OR = 1.74, 95% CI = 1.01–3.00) were independent risk factors for POP. In the SC group, multivariate analysis revealed that age (p = 0.015; OR = 1.03, 95% CI = 1.01–1.05), WFNS grade 4 or 5 (p = 0.037; OR = 1.76, 95% CI = 1.03–3.00), heart disease (p < 0.001; OR = 5.02, 95% CI = 2.03–12.45), higher white blood cell (WBC; p < 0.001; OR = 1.13, 95% CI = 1.07–1.20), and mFS grade 3 or 4 (p = 0.019; OR = 2.34, 95% CI = 1.15–4.77) were independent risk factors for POP.ConclusionPatients treated with SC are more likely to develop POP. Comprehensive preoperative evaluation of patients may help physicians to better predict POP and implement preventive measures to improve outcomes.

Objective: Glioma is the most prevalent and fatal intracranial malignant tumor. Extracellular matrix protein 2 (ECM2) has rarely been studied in gliomas. Therefore, we explored the role of ECM2 in lower-grade gliomas (LGGs). Methods: The RNA-seq and clinicopathology data were obtained from the TCGA database. The immunohistochemical (IHC) staining was used to verify the expression of ECM2. Functional enrichment analyses, immune-related analyses, drug sensitivity, and mutation profile analyses were further conducted. Cox regression and Kaplan–Meier curves were utilized for survival analyses, while four external datasets were used to validate the prognostic role of ECM2. Furthermore, qRT-PCR, CCK-8, wound healing, and transwell assays were performed to confirm the function of ECM2 in gliomas. Results: The study found a significant upregulation of ECM2 expression with increasing glioma grades and a significant association between ECM2 expression and tumor immune infiltration. Cox regression verified the prognostic role of ECM2 in LGG patients (HR = 1.656, 95%CI = 1.055–2.600, p = 0.028). High ECM2 expression was significantly associated with poor outcome (p < 0.001). Four external datasets validated its prognostic value. After the knockdown of ECM2, the functional experiments showed a significant decrease in proliferation, migration, and invasion in glioma cell lines. Conclusion: The study suggested the potential of ECM2 as a novel immune-associated prognostic biomarker and therapeutic target for glioma patients.

The comorbidity of aneurysmal subarachnoid hemorrhage (aSAH) with intracranial atherosclerotic stenosis (ICAS) has been suggested to increase the risk of postoperative ischemic stroke. Logistic regression models were established to explore the association between computed tomography perfusion (CTP) parameters and 3-month neurological outcomes and delayed cerebral ischemia (DCI). Prognostic-related perfusion parameters were added to the existing prognostic prediction models to evaluate model performance improvement. Tmax > 4.0 s volume > 0 mL was significantly associated with 3-month unfavorable neurological outcomes after adjusting for potential confounders (OR 3.90, 95% CI 1.11–13.73), whereas the stenosis degree of ICAS was not. Although the cross-validated area under the curve (AUC) was similar after the addition of the Tmax > 4.0 s volume > 0 mL (SAHIT: p = 0.591; TAPS: p = 0.379), the continuous net reclassification index (cNRI) and integrated discrimination index (IDI) showed that the perfusion parameters significantly improved the performance of the two models (p < 0.001 for all comparisons). Patients with coexistent aSAH and ICAS, Tmax > 4.0 s volume > 0 mL is an independent factor of 3-month neurological outcomes. A quantitative assessment of cerebral perfusion may help accurately screen patients with poor outcomes due to the coexistence of aSAH and ICAS.

ObjectiveElevated ICP is a well-recognized phenomenon in aneurysmal subarachnoid hemorrhage (aSAH) that has been demonstrated to lead to poor outcomes. Delayed cerebral ischemia (DCI) is the most important reason for a poor clinical outcome after a subarachnoid hemorrhage. DCI is understood as a multifactorial process that evolves over time, largely caused by the sequelae of increased intracranial pressure (ICP). The study aimed to assess how to better define the association between ICP and DCI, and whether rational ICP management can improve the outcome of aSAH patients.MethodsWe prospectively reviewed patients diagnosed with aSAH and received microsurgery clipping at our department from December 2019 to January 2021. Subdural ICP monitoring devices were kept to monitor the ICP. The ICP values were recorded every 1-h epochs. ICP -guided dehydration treatments were routinely performed to control the ICP level of patients after surgery. To evaluate whether the subdural ICP-directed management improved the prognosis of the aSAH patients, we compared the outcome data of the patients in our cohort with those treated at another ward of our hospital at the same period.ResultsIn total, 144 consecutive aSAH patients received microsurgery clipping at our department, 68 of whom underwent ICP monitoring. A total of 11,424 1-h ICP measurements were recorded for the included patients (1.30 years of recordings). Of 68 patients with ICP monitoring, 27 (27/68, 39.7%) patients developed DCI. Univariate analysis showed that higher Hunt-Hess grade (OR 2.138, 95% CI 1.025–4.459, p = 0.043), higher preoperative modified Rankin Scale score (OR 1.534, 95% CI 1.033–2.276, p = 0.034), and the max ICP value of each day value >28.5 mmHg (OR 4.442, 95% CI 1.509–13.082, p = 0.007) were associated with DCI. Also, patients with ICP-directed treatment showed a significantly lower DCI incidence than patients without ICP monitoring.ConclusionOur study suggests that I less than 15 mmHg possibly constitute normal values and that 28.5 mmHg is the ICP threshold most strongly associated with the occurrence of DCI in aSAH patients. Patients who received the ICP-directed treatment presented a lower incidence of DCI. Our findings provide a basis for the recommendation of ICP-directed treatment after aSAH.Trial Registration NumberNCT04785976.

An inflammatory response after an aneurysmal subarachnoid hemorrhage (aSAH) has always been in the spotlight. However, few studies have compared the prognostic impact of inflammatory biomarkers. Moreover, why these inflammatory biomarkers contribute to a poor prognosis is also unclear. We retrospectively reviewed aSAH patients admitted to our institution between January 2015 and December 2020. The 90-day unfavorable functional outcome was defined as a modified Rankin scale (mRS) of ≥ 3. Independent inflammatory biomarker-related risk factors associated with 90-day unfavorable outcomes were derived from a forward stepwise multivariate analysis. Receiver operating characteristic curve analysis was conducted to identify the best cut-off value of inflammatory biomarkers. Then, patients were divided into two groups according to each biomarker’s cut-off value. To eliminate the imbalances in baseline characteristics, propensity score matching (PSM) was carried out to assess the impact of each biomarker on in-hospital complications. A total of 543 patients were enrolled in this study and 96 (17.7%) patients had unfavorable 90-day outcomes. A multivariate analysis showed that the white blood cell (WBC) count, the systemic inflammation response index, the neutrophil count, the neutrophil-to-albumin ratio, the monocyte count, and the monocyte-to-lymphocyte ratio were independently associated with 90-day unfavorable outcomes. The WBC count showed the best predictive ability (area under the curve (AUC) = 0.710, 95% CI = 0.652–0.769, p < 0.001). After PSM, almost all abnormal levels of inflammatory biomarkers were associated with a higher incidence of pneumonia during hospitalization. The WBC count had the strongest association with poor outcomes. Similar to nearly all other inflammatory biomarkers, the cause of poor prognosis may be the higher incidence of in-hospital pneumonia.

The main reasons for disability and death in aneurysmal subarachnoid hemorrhage (aSAH) may be early brain injury (EBI) and delayed cerebral ischemia (DCI). Despite studies reporting and progressing when DCI is well-treated clinically, the prognosis is not well-improved. According to the present situation, we regard EBI as the main target of future studies, and one of the key phenotype-oxidative stresses may be called for attention in EBI after laboratory subarachnoid hemorrhage (SAH). We summarized the research progress and updated the literature that has been published about the relationship between experimental and clinical SAH-induced EBI and oxidative stress (OS) in PubMed from January 2016 to June 2021. Many signaling pathways are related to the mechanism of OS in EBI after SAH. Several antioxidative stress drugs were studied and showed a protective response against EBI after SAH. The systematical study of antioxidative stress in EBI after laboratory and clinical SAH may supply us with new therapies about SAH.

Aim: It remains a challenge in surgical treatments of brain arteriovenous malformations (AVMs) in Spetzler-Martin Grade (SMG) IV and V to achieve both optimal neurological outcomes and complete obliteration. The authors reported a series of patients with AVMs in SMG IV and V who underwent a surgical paradigm of endovascular embolization and simultaneous microsurgical resection based on the one-staged hybrid operation.Methods: Participants in the multicenter prospective clinical trial (NCT 03774017) between January 2016 and December 2019 were enrolled. Patients who received endovascular embolization plus microsurgical resection (EE+MRS) and those who received intraoperative digital subtraction angiography plus microsurgical resection (iDSA+MRS) were divided into two groups. Information on clinical features, operative details, and clinical outcomes were extracted from the database. Deterioration of neurological deficits (DNDs) was defined as the primary outcome, which represented neurological outcomes. The time of microsurgical operation and blood loss were defined as the secondary outcomes representing microsurgical risks and difficulties. Outcomes and technical details were compared between groups.Results: Thirty-eight cases (male: female = 23:15) were enrolled, with 24 cases in the EE+MRS group and 14 in the iDSA+MRS group. Five cases (13.2%) were in SMG V and 33 cases (86.8%) were in SMG IV. Fourteen cases (36.8%) underwent the paradigm of microsurgical resection plus intraoperative DSA. Twenty-four cases (63.2%, n = 24) underwent the paradigm of endovascular embolization plus simultaneous microsurgical resection. Degradations of SMG were achieved in 15 cases. Of the cases, two cases got the residual nidus detected via intraoperative DSA and resected. Deterioration of neurological deficits occurred in 23.7% of cases (n = 9) when discharged, and in 13.5, 13.5, 8.1% of cases at the follow-ups of 3, 6, and 12 months, respectively, without significant difference between groups (P > 0.05). Intracranial hemorrhagic complications were reported in three cases (7.9%) of the EE+MRS group only. The embolization did not significantly affect the surgical time and intraoperative blood loss. The subtotal embolization or the degradation of size by 2 points resulted in no DNDs.Conclusions: The paradigms based on the one-staged hybrid operation were practical and effective in treating high-grade AVMs. Appropriate intraoperative embolization could help decrease operative risks and difficulties and improve neurological outcomes.

Object: Patients with aneurysmal subarachnoid hemorrhage (aSAH) have an increased incidence of cardiac events and short-term unfavorable neurological outcomes during the acute phase of bleeding. We studied whether troponin I elevation after ictus can predict future major adverse cardiac events (MACEs) and long-term neurological outcomes after 2 years.Methods: Consecutive aSAH patients within 3 days of bleeding were eligible for review from a prospective observational cohort (ClinicalTrials.gov Identifier: NCT04785976). Potential predictors of future MACEs and unfavorable long-term neurological outcomes were calculated by Cox and logistic regression analyses. Additional Kaplan–Meier curves were performed.Results: A total of 213 patients were enrolled with an average follow-up duration of 34.3 months. Individuals were divided into two groups: elevated cTnI group and unelevated cTnI group. By the last available follow-up, 20 patients had died, with an overall all-cause mortality rate of 9.4% and an annual all-cause mortality rate of 3.8%. Patients with elevated cTnI had a significantly higher risk of future MACEs (10.6 vs. 2.1%, p = 0.024, and 95% CI: 1.256–23.875) and unfavorable neurological outcomes at discharge, 3-month, 1-, 2-years, and last follow-up (p = 0.001, p < 0.001, p = 0.001, p < 0.001, and p < 0.001, respectively). In the Cox analysis for future MACE, elevated cTnI was the only independent predictor (HR = 5.980; 95% CI: 1.428–25.407, and p = 0.014). In the multivariable logistic analysis for unfavorable neurological outcomes, peak cTnI was significant (OR = 2.951; 95% CI: 1.376–6.323; p = 0.005). Kaplan–Meier analysis indicated that the elevated cTnI was correlated with future MACE (log-rank test, p = 0.007) and subsequent death (log-rank test, p = 0.004).Conclusion: cTnI elevation after aSAH could predict future MACEs and unfavorable neurological outcomes.

Delayed anastomotic occlusion occurred in a considerable proportion of hemorrhagic moyamoya disease (MMD) patients undergoing direct revascularization. This study aimed to investigate the predictors and outcomes of delayed anastomotic occlusion in adult hemorrhagic MMD. The authors retrospectively reviewed 87 adult hemorrhagic MMD patients. Univariate and multivariate logistic regression analyses were performed. After an average of 9.1 ± 6.9 months of angiographic follow-up, the long-term graft patency rates were 79.8%. The occluded group had significantly worse angiogenesis than the non-occluded group (p < 0.001). However, the improvement of dilated anterior choroidal artery–posterior communicating artery was similar (p = 0.090). After an average of 4.0 ± 2.5 years of clinical follow-up, the neurological statues and postoperative annualized rupture risk were similar between the occluded and non-occluded groups (p = 0.750; p = 0.679; respectively). In the multivariate logistic regression analysis, collateral circulation Grade III (OR, 4.772; 95% CI, 1.184–19.230; p = 0.028) and preoperative computed tomography perfusion (CTP) Grade I–II (OR, 4.129; 95% CI, 1.294–13.175; p = 0.017) were independent predictors of delayed anastomotic occlusion. Delayed anastomotic occlusion in adult hemorrhagic MMD might be a benign phenomenon. Good collateral circulation (Grade III) and compensable preoperative intracranial perfusion (CTP Grade I–II) are independent predictors for this phenomenon. Moreover, the delayed anastomotic occlusion has no significant correlations with the long-term angiographic and neurological outcomes, except neoangiogenesis.

5-Fluorouracil (5-FU) is widely used in the treatment of gastric cancer, and the emergence of drug resistance and toxic effects has limited its application. Therefore, there is an urgent need for safe and effective novel drugs or new therapies. β-Ionone (BI) is found in vegetables and fruits and possesses an inhibitory proliferation of tumor cells in vitro and in vivo. In this study, we investigated whether BI could enhance the inhibitory effects of 5-FU on the proliferation of gastric adenocarcinoma cells and the growth of gastric cancer cell xenografts in a mouse model. The effects of BI and 5-FU alone or their combination on the cell viability, apoptosis, and mitochondrial membrane potential, the cell cycle, and its related proteins—Cyclin D1, and CDK4 as well as PCNA and GSK-3β were evaluated in SGC-7901 cells and MKN45 cells by MTT, MB, flow cytometry and Western blot. In addition, the effects of BI and 5-FU alone or their combination on the growth of SGC-7901 cell xenografts in nude mice were investigated. The results showed that BI significantly enhanced the sensitivity of gastric adenocarcinoma cells to 5-FU in vitro and in vivo, i.e. proliferation inhibited, apoptosis induced and GSK-3β protein activated. Therefore, our results suggest that BI increases the antitumor effect of 5-FU on gastric adenocarcinoma cells, at least partly from an activated GSK-3β signaling pathway. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the incidence and related factors of extrauterine growth retardation (EUGR) and “true EUGR” in very preterm infants (VPI) from different regions of China.Materials and methodsClinical data of VPI were prospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. The infants were divided into a small for gestational age (SGA) group or non-SGA group at birth, with non-SGA infants at 36 weeks of gestation or at discharge being further divided into a EUGR group or a non-EUGR group. Infants in the EUGR and non-SGA group were defined as “true EUGR.” The general information of VPI, such as maternal complications during pregnancy, use of enteral nutrition and parenteral nutrition, and complications during hospitalization were compared between the groups.ResultsAmong the 2,514 VPI included in this study, 47.3, 41.5, and 33.3% of VPI were below the 10th percentile, and 22.6, 22.4, and 16.0% of VPI were below the 3rd percentile for weight, height, and head circumference at 36 weeks of gestation or at discharge, respectively, by the percentile on the 2013 Fenton curve. The incidences of EUGR and “true EUGR” evaluated by weight were 47.3 and 44.5%, respectively. Univariate analysis showed that there were statistically significant differences in the aspects of perinatal and nutritional characteristics, treatment, and complications between the groups. Multivariate analysis showed that in non-SGA infants, the cumulative caloric intake during the first week was a protective factor for “true EUGR,” while days to reach total enteral nutrition, late initiation of human milk fortifier, and moderate to severe bronchopulmonary dysplasia were independent risk factors for “true EUGR.”ConclusionMore attention should be paid to the nutritional management of VPI to prevent “true EUGR.” Cumulative caloric intake should be ensured and increased during the first week, total enteral nutrition should be achieved as early as possible, human milk fortifier should be added early, and moderate to severe bronchopulmonary dysplasia should be prevented. These strategies are very important for reducing the incidence of “true EUGR” in VPI.