BACKGROUND: Inflammation plays a critical role in severe cerebral venous thrombosis (CVT) pathogenesis, but the benefits of anti-inflammatory therapies remain unclear. This study aimed to investigate the association between steroid therapy combined with anticoagulation and the prognosis of acute/subacute severe CVT patients. METHODS: A prospective cohort study enrolled patients with acute/subacute severe CVT at Xuanwu Hospital (July 2020-January 2024). Patients were allocated into steroid and non-steroid groups based on the treatment they received. Functional outcomes (modified Rankin scale [mRS]) were evaluated at admission, discharge, and 6 months after discharge. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cerebrospinal fluid (CSF) IL-6, and intracranial pressure were measured at admission and discharge in the steroid group. Fundoscopic Frisén grades were assessed at admission and 6 months after discharge. Univariate and multivariate logistic regression were used to evaluat associations between steroid use and favorable outcomes (mRS ≤2) at the 6-month follow-up. Paired tests assessed changes in hs-CRP and other variables before and after treatment, and Spearman's correlations were used to analyze relationships between these changes and functional improvements. RESULTS: A total of 107 and 58 patients in the steroid and non-steroid groups, respectively, were included in the analysis. Compared with the non-steroid group, the steroid group had a higher likelihood of achieving an mRS score of 0-2 (93.5% vs . 82.5%, odds ratio [OR] = 2.98, P  = 0.037) at the 6-month follow-up. After adjusting for confounding factors, the result remained consistent. Pulsed steroid therapy did not increase mortality during hospitalization or follow-up, nor did it lead to severe steroid-related complications (all P  >0.05). Patients in the steroid group showed a significant reduction in serum hs-CRP, IL-6, CSF IL-6, and intracranial pressure at discharge compared to at admission, as well as a significant reduction in the fundoscopic Frisén grade at the 6-month follow-up compare to at admission (all P  <0.001). A reduction in serum inflammatory marker levels during hospitalization positively correlated with improvements in functional outcomes ( P  <0.05). CONCLUSION: Short-term steroid use may be an effective and safe adjuvant therapy for acute/subacute severe CVT when used alongside standard anticoagulant treatments, which are likely due to suppression of the inflammatory response. However, these findings require further validation in randomized controlled trials. TRAIL REGISTRATION ClinicalTrials.gov , NCT05990894.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Anticoagulants/therapeutic use* ; C-Reactive Protein/metabolism* ; Interleukin-6/metabolism* ; Intracranial Thrombosis/drug therapy* ; Prospective Studies ; Steroids/therapeutic use* ; Venous Thrombosis/drug therapy*

Objective:To explore the impact of treatment duration with human urinary kallidinogenase (HUK) on the efficacy and safety of acute ischemic stroke (AIS).Methods:In this subgroup analysis of RESK study, a total of 990 AIS patients recruited from 65 centers in China between August 2015 and June 2020 were included and divided into short medication group (HUK for 8 days, n=185) or long medication group (HUK for 15 days or 21 days, n=805). The proportions of patients with modified Rankin Scale (mRS) score of 0, 0-1, 0-2 at 90 days, National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 22 days, the proportions of patients with Barthel index (BI)≥95 at 90 days, and the incidences of adverse events were analyzed. Comparisons between groups were conducted using chi-square test, single factor and multivariate Logistic regression analysis, etc. Results:Multivariate regression analysis showed that the proportions of patients with 90-day mRS score of 0-2 [74.1% (137/185) vs 75.0% (604/805); OR=1.047, 95% CI 0.676-1.620, P=0.838] and 22-day NIHSS score change from baseline (4.60±2.00 vs 4.26±2.80; OR=-0.390, 95% CI -1.125-0.344, P=0.297) showed no statistically significant difference between the short medication and long medication groups; the proportions of patients with 90-day mRS score of 0-1 [48.1% (89/185) vs 59.1% (476/805); OR=0.674, 95%CI 0.463-0.983, P=0.041] and 90-day BI≥95 [43.6% (79/181) vs 55.1% (442/802); OR=0.614, 95%CI 0.420-0.897, P=0.012] were significantly lower in the short medication group than in the long medication group. There was no statistically significant difference in the incidences of adverse events between these 2 groups. Conclusions:In AIS patients, consecutive 8-day dosing of HUK improved immediate (22-day NIHSS score) and long-term outcome (90-day mRS score 0-2) and was safely tolerated. When applicable, extended duration of HUK could improve long-term disability-free rate (90-day mRS score 0-1) and quality of life (90-day BI) without increasing the risk of adverse events.

Objective To observe the relationship between functional connectivity(FC)of frontoparietal network(FPN)and cognitive function in patients with cerebral small vessel disease(CSVD)using resting-state functional MRI(rs-fMRI).Methods rs-fMRI of 50 CSVD patients with cognitive impairment(CI group),65 CSVD patients with normal cognition(NC group)and 60 healthy controls(HC group),as well as outcomes of neuropsychological tests were retrospectively analyzed.Brain regions with different FC of FPN were compared among 3 groups and between each 2 groups.Partial correlation analysis was used to evaluate the correlations of FC of brain regions value being statistically different between CI and NC groups and cognitive scores.Results Significant differences of FC in bilateral cingulate gyrus,left middle frontal gyrus,right supramarginal gyrus,right inferior parietal lobule and right medial superior frontal gyrus were found among groups(FWE correction,all P＜0.05).Compared with NC group,FC of left cingulate gyrus decreased,of right inferior frontal gyrus and right medial superior frontal gyrus increased in CI group(FWE correction,all P＜0.05).The decreased FC value of left cingulate gyrus was negatively correlated with clock drawing test score in CSVD patients(r=-0.159,P=0.049).Conclusion CSVD patients with or without CI had extensive abnormal FC of FPN,and the left cingulate gyrus was associated with patient's cognitive function.

Objective:To explore the protective effects of Zhenzhu Tongluo Pills on cerebral ischemia reperfusion injury in rats.Methods:Totally 15 healthy SD rats were randomly divided into sham-operation group, model group and TCM group according to random number table method, with 5 rats in each group. Except for the sham-operation group, cerebral ischemia models in the other two groups were induced by temporary middle cerebral artery occlusion. After the establishment of ischemia models, the TCM group was administered Zhenzhu Tongluo Pills solutions (1 ml/100 g) intragastrically at a dose of 0.5 g/(kg·d), and the sham-operation group and model group were treated with normal saline, for 14 consecutive days. Neurological deficit score was used to evaluate the degree of neurological deficit in cerebral ischemia rats. TTC staining were used for determining the infarct weights. The nerve cell damage was observed using HE staining method. Immunohistochemistry staining was used to observe the expression levels of GFAP, Nestin, and NeuN.Results:Compared with that at the 3 hours after reperfusion, the Bederson score in the TCM group decreased at the 30 minutes after the last administration ( P<0.05); compared with the model group, the infarction ratio of rats in the TCM group decreased ( P<0.05); the NeuN staining of neurons around the ischemic lesion in the model group rats was light, while Nestin and GFAP staining were deep; the Nestin and GFAP staining of neurons in the TCM group was light, while NeuN staining was deeper. Conclusion:Zhenzhu Tongluo Pills can improve the symptom of neurological deficits, reduce the volume of infarction, and protect neurons from injury in rats with cerebral ischemia.

Objective:To examine whether the combination of quantitative regional apparent diffusion coefficient (ADC) and amplitude-integrated electroencephalogram (aEEG) can predict the outcome of comatose patients with severe traumatic brain injury (sTBI).Methods:A prospective study was conducted. The patients with coma caused by sTBI [Glasgow coma scale (GCS) < 8] admitted to Suqian First Hospital from January 2016 to June 2019 were enrolled. All patients underwent aEEG examination and magnetic resonance imaging (MRI) scan within 1 week after emergency treatment. The ADC values of 9 regions of interest (frontal gray matter and white matter, parietal gray matter and white matter, temporal gray matter and white matter, caudate nucleus of basal ganglia, lenticular nucleus and thalamus) were measured by head MRI, and the mean ADC values of frontal lobe, parietal lobe, temporal lobe and basal ganglia were calculated respectively. According to the follow-up results after 12 months, the differences of each index between patients with poor prognosis [Glasgow outcome score (GOS) 1-2] and patients with good prognosis (GOS 3-5) were compared; the receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive ability of aEEG and ADC for the good prognosis of patients with sTBI, and the predictive value of the combination of aEEG and ADC.Results:A total of 52 patients with sTBI were enrolled, with mean age of (36.7±13.9) years old, 35 of whom were male. Within 12 months follow-up, 29 patients had achieved favorable outcomes and 23 patients had unfavorable outcome. There were 21, 17 and 14 patients with aEEG , and grade, respectively, and 19, 10 and 0 patients had good prognosis respectively. ADC values of 9 regions of interest in patients with good prognosis were significantly higher than those in patients with poor prognosis (×10 -6 mm 2/s: 924±107 vs. 531±87 in frontal gray matter, 804±95 vs. 481±74 in frontal white matter, 831±93 vs. 683±72 in temporal gray matter, 726±87 vs. 654±63 in temporal white matter, 767±79 vs. 690±75 in parietal gray matter, 716±84 vs. 642±62 in parietal white matter, 689±70 vs. 465±68 in caudate nucleus, 723±84 vs. 587±71 in lenticular nucleus, 807±79 vs. 497±67 in thalamus, all P < 0.01). ROC curve analysis showed that the area under ROC curve (AUC) of aEEG for predicting good prognosis of sTBI patients was 0.826, when the cut-off value of aEEG was < 1.5, the sensitivity was 94.7% and the specificity was 72.8%. Among the ADC value prediction abilities in the interested areas, the prediction of ADC value in frontal lobe and basal ganglia area were better than that in sTBI patients. AUC was 0.817 and 0.903 respectively. The best cut-off values were > 726×10 -6 mm 2/s and > 624×10 -6 mm 2/s respectively, the sensitivity of predicting prognosis were both 100%, and the specificity was 63.4% and 61.8%. A model combining frontal ADC and basal ganglia ADC with aEEG was 91.0% sensitive and 93.7% specific for favorable outcome of sTBI patients. Conclusion:Combination of the quantitative measurement of regional ADC and aEEG may be useful for predicting the outcome of the patients with sTBI.

Objective:To analyze any changes in the functional connectivity between the seed points of the dorsolateral prefrontal cortex (DLPFC) and the whole brain, as well as any fluctuations in the low-frequency amplitude among persons with post-stroke depression (PSD). The aim was to develop correlations among functional imaging results, clinical scales, and inflammation indicators including high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), interleukin 2 (IL-2), interleukin 10 (IL-10), interleukin 17a (IL-17a) and interferon-γ (IFN-γ).Methods:Between 2016 and 2020, 55 ischemic stroke survivors were tested. The 28 scoring 7 or more on the Hamilton Depression Scale (HAMD-17) formed the PSD group, while the 27 others formed the control group. Functional magnetic resonance images were collected, and serum inflammation indicators were determined.Results:When seed points in the left DLPFC were used, in the PSD group the frontal cortex (FC) decreased in one cluster, with a voxel of 129mm3 and the MNI coordinates (x=9, y=30, z=33) indicating that the anatomical automatic labeling (AAL) brain regions were the Cingulum_Ant_L, Cingulum_Mid_R and the frontal_Sup_Medial_L. When the right DLPFC was used as the seed point the FC again decreased in one cluster, with voxels of 44mm 3 and the MNI coordinates (x=-27, y=12, z=47) referring to the AAL brain region of the frontal_Mid_L. In the PSD group, the FC value of abnormal brain areas with the R-DLPFC as the seed point was positively correlated with time since stroke. In the control group, the FC value of abnormal brain areas with L-DLPFC as the seed point was negatively correlated with MoCA, while with R-DLPFC as the seed point it was positively correlated with IFN-γ. The FC values of abnormal areas of the brain showed no significant correlation with other clinical scales, inflammation indicators or lesion volume. Conclusion:Abnormal functional connections within the executive control network and between the salience networks may participate in the mechanism of PSD, and may be related to the time since stroke, cognitive functioning, and IFN-γ levels.

Objective:To explore clinical application value of immediate breast reconstruction with silicone prosthesis after nipple areolar sparing mastectomy for breast cancer.Methods:The clinical data of 30 breast cancer patients underwent immediate breast reconstruction with the silicone prosthesis after nipple areolar sparing mastectomy from January 2016 to January 2018 were collected. In the observation group, 15 patients underwent immediate breast reconstruction with the silicone prosthesis after nipple areolar sparing mastectomy. In the control group, 15 patients underwent conventional modified radical mastectomy only. The differences of operation indicator and postoperative complications between the two groups were compared, and the postoperative cosmetic effects were evaluated.Results:The patients successfully completed prosthetic breast reconstruction in the observation group. The surgical time and indwelling time of the drainage tube in the observation group were both increased compared with the control group, and the difference was statistically significant ( t=118.8 and t=23.9, P<0.05). There were no statistically significant differences between the two groups in the complications of postoperative flap necrosis, subcutaneous hematoma, intraoperative infection and incision dehiscence ( P>0.05). The total complications rate of the observation group was 40%, compared with the control group (20%), there were not statistically significant differences ( P>0.05). The postoperative aesthetic effect evaluation showed that the reconstructed breast was full in shape and basically symmetrical to the contralateral side, with an excellent and good rate of 83.3%. The patients were satisfied with the appearance of the breast. All patients were followed up for 12 to 36 months with the average time of 24 months, and local recurrence and distant metastasis were not observed. Conclusions:In the modified radical mastectomy for breast cancer with preserved nipple and areola, the immediate application of silicone prosthesis for breast reconstruction has the advantages of less trauma, faster postoperative recovery and better cosmetic effect, which is worthy of clinical application.

Stroke is an acute cerebro-vascular disease with high incidence and poor prognosis, most commonly ischemic in nature. In recent years, increasing attention has been paid to inflammatory reactions as symptoms of a stroke. However, the role of inflammation in stroke and its underlying mechanisms require exploration. In this study, we evaluated the inflammatory reactions induced by acute ischemia and found that pyroptosis occurred after acute ischemia both in vivo and in vitro, as determined by interleukin-1β, apoptosis-associated speck-like protein, and caspase-1. The early inflammation resulted in irreversible ischemic injury, indicating that it deserves thorough investigation. Meanwhile, acute ischemia decreased the Sirtuin 1 (Sirt1) protein levels, and increased the TRAF6 (TNF receptor associated factor 6) protein and reactive oxygen species (ROS) levels. In further exploration, both Sirt1 suppression and TRAF6 activation were found to contribute to this pyroptosis. Reduced Sirt1 levels were responsible for the production of ROS and increased TRAF6 protein levels after ischemic exposure. Moreover, N-acetyl-L-cysteine, an ROS scavenger, suppressed the TRAF6 accumulation induced by oxygen-glucose deprivation via suppression of ROS bursts. These phenomena indicate that Sirt1 is upstream of ROS, and ROS bursts result in increased TRAF6 levels. Further, the activation of Sirt1 during the period of ischemia reduced ischemia-induced injury after 72 h of reperfusion in mice with middle cerebral artery occlusion. In sum, these results indicate that pyroptosis-dependent machinery contributes to the neural injury during acute ischemia via the Sirt1-ROS-TRAF6 signaling pathway. We propose that inflammatory reactions occur soon after oxidative stress and are detrimental to neuronal survival; this provides a promising therapeutic target against ischemic injuries such as a stroke.

Objective:To explore the clinical significance of recurrent laryngeal nerve inlet zone(RLNIZ) lymph node metastasis in papillary thyroid cancer(PTC).Methods:The clinical data of the clinicopathologic characteristics of 738 cases with papillary thyroid cancer at our centers from Jul 2017 to Jun 2018 was retrospectively reviewed. 108 cases with RLNIZ lymph node dissection for pathological examination were included. The relationship between metastasis of RLNIZ lymph node and clinicopathologic characteristics was analyzed.Results:RLNIZ lymph node was detected in 12.3%(91/738)cases, the mean lymph node number in RLNIZ was 1.5±0.7, and 30.8%(28/91) cases suffered RLNIZ lymph node metastasis. RLNIZ lymph node metastasis(LNM) is associated with tumor size( P=0.028), capsular invasion( P=0.019), No. of central compartment LNM( P<0.001) and lateral neck LNM( P<0.001). No. of central compartment LNM was found to be the independent risk factor of RLNIZ lymph node metastasis. The incidence of dysphagia and inferior parathyroid damage was 0.9%(1/108)respectively. Conclusions:RLNIZ lymph node metastasis is common among PTC patients , therefore, RLNIZ lymph node should be routinely removed especially in patients with tumor size over 1cm、suspected capsular invasion and lateral neck lymph node metastasis confirmed by preoperative imaging examination.

Vascular cerebral dysfunction refers to a brain dysfunction syndrome caused by cerebrovascular etiologies and diseases that lead to disorders of sensorimotor function,cognitive function and neuro-psychiatry. In the past decades,with the maturity of diagnostic concepts and advances of brain imaging technology,the detection of vascular burden in brain dysfunction has progressed remarkably. However,in daily practice,the definitive diagnosis of vascular brain dysfunction is still challenging. Because of the interindividual heterogeneity, very few general therapeutic principles which are applicable to all patients exist. Individualized therapeutic decision must be made from existing methods, including symptomatic treatment, supportive care and vascular risk factors management. It is hoped that there will be targeted etiological treatment in the future.