BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Objective:To explore the effectiveness of the Exowalk gait training robot in improving the walking ability of stroke survivors.Methods:Forty stroke survivors were randomly divided into a control group and an experimental group, each of 20. In their rehabilitation, the control group was given routine walking training, while the experimental group′s training was assisted with the Exowalk robot. Both groups trained for 60 minutes a day, five days a week for four weeks. Before as well as after 2 and 4 weeks of training functional ambulatory categories (FACs), the Berg balance scale (BBS), the 6-minute walking test (6MWT), the 10-minute walking test (10MWT), the Rivermead mobility index and an exercise index were used to evaluate those in both groups.Results:After 2 weeks significant improvement was observed in the average FAC, BBS, 6MWT and 10MWT results of both groups, without significant differences between them. After 4 weeks there was still no significant difference in the groups′ average BBS scores. However, the average FAC rating in the experimental group had improved significantly while there was no significant increase in the control group′s average score.Conclusions:The Exowalk robot can help to improve the balance and walking ability of hemiplegic stroke survivors.

Objective:To clarify the characteristics of renal cortical microcirculation and its relationship with the expression of plasma endothelial microparticle (EMP) in septic rats, and to evaluate the effect of Xuebijing injection as an adjuvant therapy of antibiotics on septic AKI.Methods:The 8-10 weeks old specific pathogen free (SPF) male Sprague-Dawley (SD) rats were divided into sham operation group (Sham group), positive drug control group and Xuebijing group by the random number table method, with 10 rats in each group. The cecal ligation and puncture (CLP) with large ligation (ligated 75% of the cecum) was used to prepare a rat high-grade sepsis model; in the Sham group, the cecum was stretched without ligation or puncture. Due to the high mortality of CLP with large ligation, Xuebijing injection (4 mL/kg, 12 hours per time) and imipenem/cilastatin injection (90 mg/kg, 6 hours per time) were administered to the rats in the Xuebijing group via the tail vein immediately after the model was produced. Normal saline and imipenem/cilastatin were administered to the rats by the same methods in the positive drug control group. The rats in the Sham group were treated with the same volume of normal saline as any of the other two groups at the same frequency. At 48 hours after model reproduction, the mean arterial pressure (MAP) and blood lactic acid (Lac) of the rats were measured. The renal cortical microcirculation was monitored by using side stream dark-field imaging. Renal hypoxia signals were assessed by pimonidazole chloride immunohistochemistry. Plasma EMP levels were determined by using flow cytometry, and then the correlation between EMP and microcirculation parameters of renal cortex was analyzed. At the same time, the serum creatinine (SCr) was measured, and the renal injury score (Paller score) was used to evaluate the severity of renal tissue pathological damage.Results:Compared with the Sham group, perfused vessel density (PVD), microvascular flow index (MFI) and MAP in the positive drug control group and the Xuebijing group decreased significantly, the positive expression of hypoxia probe (pimonidazole) increased, Lac, EMP, Paller score and SCr increased significantly. However, compared with the positive drug control group, the renal cortical microcirculation in the Xuebijing group was improved significantly, PVD and MFI were increased significantly [PVD (mm/mm 2): 16.20±1.20 vs. 9.77±1.12, MFI: 2.46±0.05 vs. 1.85±0.15, both P < 0.05], Lac was reduced significantly (mmol/L: 4.81±1.23 vs. 6.08±1.09, P < 0.05), MAP increased slightly [mmHg (1 mmHg = 0.133 kPa): 84.00±2.00 vs. 80.00±2.00, P > 0.05], suggested that Xuebijing injection improved renal microcirculation perfusion in septic rats, and this effect did not depend on the change of MAP. The positive expression of pemonidazole in renal cortex of the Xuebijing group was significantly lower than that of the positive drug control group [(35.89±1.13)% vs. (44.93±1.37) %, P < 0.05], suggested that Xuebijing injection alleviated renal hypoxia. The plasma EMP levels of rats in the Xuebijing group were significantly lower than those in the positive drug control group (×10 6/L: 3.49±0.17 vs. 5.78±0.22, P < 0.05), and the EMP levels were significantly negatively correlated with PVD and MFI ( r values were -0.94 and -0.95, respectively, both P < 0.05), indicated that the increase of plasma EMP was highly correlated with renal microcirculation disorder, and Xuebijing injection inhibited the increase of plasma EMP levels. The Paller score in the Xuebijing group was significantly lower than that in the positive drug control group (46.90±3.84 vs. 62.70±3.05, P < 0.05), and the level of SCr was also significantly lower than that in the positive drug control group (μmol/L: 121.1±12.4 vs. 192.7±23.9, P < 0.05), which suggested that Xuebijing injection relieved kidney injury and improved renal function in septic rats. Conclusion:As an adjuvant therapy of antibiotics, Xuebijing injection could inhibit the expression of plasma EMP in rats with sepsis, improve renal cortex microcirculation, and reduce kidney injury.

Objective To evaluate different inflammation markers for predicting the risk of acute kidney injury (AKI) in sepsis patients. Methods A retrospective observational study was conducted. The adult patients with sepsis for more than 24 hours admitted to intensive care unit (ICU) of Beijing Friendship Hospital, Capital Medical University from March 1st, 2010 to November 1st, 2017 were enrolled. Inflammatory markers such as white blood cell count (WBC), erythrocyte sedimentation rata (ESR), neutrophil and lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), etc. were collected at ICU admission. The patients were divided into different groups according to the 24-hour AKI, and subgroup analysis was conducted according to the criteria of the Global Renal Disease Prognostic Organization (KDIGO)-AKI staging. The receiver operating characteristic curve (ROC) was plotted with statistically significant inflammatory markers to assess the predictive value of AKI for patients with systemic infection. Results A total of 753 patients with sepsis were enrolled. 405 AKI patients were diagnosed within 24 hours, with a prevalence of 53.8%. There were 118 cases (15.7%) in AKI stage 1, 48 cases (6.4%) in stage 2 and 239 cases (31.7%) in stage 3. PCT in AKI group was significantly higher than that in non-AKI group [μg/L: 4.98 (1.51, 32.75) vs. 3.00 (0.37, 11.40), P < 0.01]. PCT of AKI stage 2 group was significantly higher than that of AKI stage 1 and 3 groups [μg/L: 27.86 (4.80, 37.26) vs. 3.00 (0.98, 16.10), 4.98 (1.51, 42.55), both P < 0.01]. Although ESR in AKI group was lower than that of non-AKI group (mm/1 h: 45.25±37.42 vs. 52.28±34.89, P < 0.01), there was no significant difference among the subgroups. CRP in AKI group was slightly higher than the non-AKI group [mg/L: 96.00 (42.20, 160.00) vs. 73.60 (21.01, 157.50)], but the difference was not statistically significant (P > 0.05). There was no significant difference in WBC or NLR between AKI group and non-AKI group. It was shown by ROC curve analysis that the area under ROC curve (AUC) of PCT in predicting the occurrence of septic AKI was 0.619, with the 95% confidence interval (95%CI) of 0.545-0.689 (P < 0.01). When the cut-off value of PCT > 0.4 μg/L, the sensitivity was 94.2%, the specificity was 26.5%, the accuracy was 64.2%, the positive predictive value was 61.6%, and the negative predictive value was 78.6%. Conclusion PCT could be a marker to predict AKI with sepsis patients.

Objective To analyze the diagnostic value of serum procalcitonin ( PCT ) for early postoperative bacterial infection after pediatric living donor liver transplantation.Methods A retrospective study was conducted in pediatric patients after living donor liver transplantation recipients admitted to department of critical care medicine of Beijing Friendship Hospital affiliated to Capital Medical University during June 2013 to October 2015.According to the clinical data , all pediatric patients were divided into infection group(n=60) and non-infection group (n=100).Primary disease, PCT post operation day 1 to day 5 for non-infection group and day 1 to day 9 for infection group , temperature , white blood cell , cold ischemia time, warm ischemia time, operation time, volume of blood loss during operation were recorded.All parameters above were compared between groups.Receiver operating characteristic ( ROC) curve was plotted, and the diagnostic value of PCT was evaluated.Results PCT of both groups were elevated after liver transplantation , there was a markedly resolution in non-infection group within 48 to 72 hours.PCT of pediatric patients with bacterial infection was significantly higher than that of non-infected patients , and the difference was of greatly significant (4.62 ±1.39) ng/ml vs (0.85 ±0.19) ng/ml,t=26.56,P=0.00.ROC curve showed that the peak level of PCT might be valuable in the diagnosis of bacterial infection ( AUC=0.985).There was no significant difference of cold ischemia time [(109.92 ±19.22) min vs (108.04 ± 13.20) min, t=1.05, P=0.29], warm ischemia time[(1.49 ±0.17) min vs (1.52 ±0.12) min, t=1.08, P=0.28], operation time[(8.01 ±0.77)vs (8.00 ±1.05) h, t=0.06, P=0.94], WBC[(8.95 ±1.69) ×109/L vs (8.98 ±2.00) ×109/L,t=-0.08, P=0.93]and body temperature[(37.5 ±0.7) vs (37.5 ±0.8) ℃,t=-0.05, P=0.96] on the first day after surgery between infection and non-infection groups.Amount of bleeding in infection group was higher than that of non infection group [ ( 650.87 ± 90.36) ml vs (240.29 ±67.67) ml, t=32.33, P=0.00], there was longer length of ICU stay in the infection group[(11.01 ±1.81)d vs (6.03 ±1.65)d, t=17.78, P=0.00].Conclusion Peak PCT level was a valuable indicator for early postoperative bacterial infection after pediatric living donor liver transplantation.

Objective Post-transcription RNA interference (RNAi) is more and more widely applied in multigene therapy.This study aimed to establish an subcutaneous xenotransplanted tumor (SXT) model of human HT-29 colon carcinoma in nude mice and investigate the effects of the survivin shRNA-APC double gene co-expression lentiviral vector on the growth of SXT.Methods Thirty-five nude mice were equally divided into five groups, double-gene survivin shRNA, survivin shRNA, APC, empty vector, and blank, and injected into the left anterior axillary with respective stably transfected cell lines and human HT-29 colon carcinoma cells, all at 2×106/mL, to establish an SXT model of human HT-29 colon carcinoma.The inhibition rate of tumor growth was calculated by measuring the size and weight of the SXT, the expressions of survivin mRNA and protein in the tumor tissue detected by real time PCR and immunohistochemistry respectively, and the apoptosis of the HT-29 colon carcinoma cells determined by TUNEL.Results The mean size and weight of the SXT were significantly reduced in the double-gene survivin shRNA-APC, survivin shRNA, and APC groups as compared with the blank and empty vector groups (P<0.05), though increased in the survivin shRNA and APC groups in comparison with the double-gene group (P<0.05).The expressions of survivin mRNA and protein in the tumor tissue were remarkably lower in the double-gene survivin shRNA-APC, survivin shRNA, and APC groups than in the blank and empty vector groups (P<0.05), even lower in the double-gene group than in the survivin shRNA, and APC groups (P<0.05).The apoptosis rate of the HT-29 colon carcinoma cells was markedly up-regulated in the double-gene survivin shRNA-APC ([56.72±3.17]%), survivin shRNA ([33.64±2.03]%), and APC groups ([31.19±1.79]%) as compared with the blank ([9.89±0.31]%) and empty vector groups ([10.06±0.43]%) (P<0.05), even more significantly in the double-gene than in the survivin shRNA and APC groups (P<0.05).Conclusion The survivin shRNA-APC double gene co-expression lentiviral vector can reduce the expression level the survivin gene, promote the apoptosis of colon carcinoma cells, and suppress the growth of the subcutaneous xenotransplanted tumor.

Objective Studies show that the abnormal ex-pressions of APC and survivin play important roles in the development and progression of colon cancer .Survivin shRNA and APC double gene co-expression lentiviral vector was constructed to observe whether it could be successfully expressed in HT-29 colon cancer cells and whether it could impact on colon cancer cell apoptosis . Methods We selected the best shRNA interference fragment from the construc-tion of three pairs of complementary shRNA fragments and connected it with the effective fragment of APC ( aa1020-1698 ) to construct a double gene co-expression lentiviral vector .HT-29 cells were divid-ed into experimental group , empty loading group and blank group .HT-29 cells were observed by fluorescence microscopy after infec-tion.Survivin and APC expression levels were observed by real time PCR and western blot .Apoptosis was detected by caspase-3 activi-ty assay. Results ①We successfully constructed three pairs of shRNA sequences and proved that they had no human gene homolo -gous to the rest.Real time PCR analysis showed that the best sequence was shRNA 3.②After the sequence alignment of constructed shRNA vectors, three pairs of shRNA sequences were completely the same with the first designed sequence .Green fluorescence was observed in HT-29 cells by fluorescence microscope .The survivin content in experiment group (31.71 ±1.49) was significantly de-creased compared with empty loading group (100 ±0) and blank group(95.12 ±2.15)(P<0.05).The expression level of APC mR-NA was significantly increased compared with empty loading group (0 ±0) and blank group(0.51 ±0.15)(P<0.05).③The relative ratio of apoptosis in experiment group (0.573 ±0.050) was significantly increased compared with empty loading group (0.390 ± 0.040) and blank group(0.407 ±0.030)(P<0.05). Conclusion We have successfully constructed survivin-shRNA-APC double gene co-expression lentiviral vector which can be successfully expressed in HT-29 colon cancer cells , providing references for subse-quent gene therapy by the use of the carrier .

ObjectiveTo study the correlation between the etiology and clinical features of erythroderma.MethodsThe clinical data on 182 patients with erythroderma were retrospectively collected and analyzed.ResultsThe male-to-female ratio was 2.8 ∶ 1 and the average age at onset was 58.6 ± 14.6 years.Of the 182 cases,135 (74.2％) were due to pre-existing dermatoses,14 (7.7％) to drug reaction,8 (4.4％) to malignancies,while 25(13.7％) had no obvious precipitating factors.The most frequent triggering factor was systemic consumption of drugs(52 patients,28.6％ ),and glucocorticosteroid was the most prevalent causative drug.Seventy-six patients were followed up,recurrence was observed in 14 patients but not in 58 patients,and 5 patients died,2 patients with idiopathic erythroderma were finally diagnosed with mycosis fungoides (MF)after multiple skin biopsies.ConclusionsPre-existing dermatoses are the most frequent cause of erythroderma.Idiopathic erythroderma is liable to relapse,possibly associated with malignancies,and should be closely followed up.