Reteplase versus Alteplase for Acute Ischemic Stroke.

BACKGROUND: Alteplase is the standard agent used in early reperfusion therapy, but alternative thrombolytic agents are needed. The efficacy and safety of reteplase as compared with alteplase in patients with acute ischemic stroke are unclear. METHODS: We randomly assigned patients with ischemic stroke within 4.5 hours after symptom onset in a 1:1 ratio to receive intravenous reteplase (a bolus of 18 mg followed 30 minutes later by a second bolus of 18 mg) or intravenous alteplase (0.9 mg per kilogram of body weight; maximum dose, 90 mg). The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]) at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after symptom onset. RESULTS: A total of 707 patients were assigned to receive reteplase, and 705 were assigned to receive alteplase. An excellent functional outcome occurred in 79.5% of the patients in the reteplase group and in 70.4% of those in the alteplase group (risk ratio, 1.13; 95% confidence interval [CI], 1.05 to 1.21; P<0.001 for noninferiority and P = 0.002 for superiority). Symptomatic intracranial hemorrhage within 36 hours after disease onset was observed in 17 of 700 patients (2.4%) in the reteplase group and in 14 of 699 (2.0%) of those in the alteplase group (risk ratio, 1.21; 95% CI, 0.54 to 2.75). The incidence of any intracranial hemorrhage at 90 days was higher with reteplase than with alteplase (7.7% vs. 4.9%; risk ratio, 1.59; 95% CI, 1.00 to 2.51), as was the incidence of adverse events (91.6% vs. 82.4%; risk ratio, 1.11; 95% CI, 1.03 to 1.20). CONCLUSIONS: Among patients with ischemic stroke within 4.5 hours after symptom onset, reteplase was more likely to result in an excellent functional outcome than alteplase. (Funded by China Resources Angde Biotech Pharma and others; RAISE ClinicalTrials.gov number, NCT05295173.).

Association of levonorgestrel-releasing intrauterine device with gynecologic and breast cancers: a national cohort study in Sweden.

BACKGROUND: The levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive. OBJECTIVE: We aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer. STUDY DESIGN: A total of 514,719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1,544,157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users as well as for their matched comparisons and ended at the date of diagnosis of gynecologic and breast cancers, date of death from any cause, and the end of the study period, whichever came first. The Cox proportional hazard model with a competing risk analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, while multiplicative interaction was calculated by including a product term in the regression model. RESULTS: The use of LNG-IUD was associated with a 13% higher risk of breast cancer (adjusted HR, 1.13; 95% CI, 1.10-1.17), a 33% lower risk of endometrial cancer (adjusted HR, 0.67; 95% CI, 0.56-0.80), a 14% lower risk of ovarian cancer (adjusted HR, 0.86; 95% CI, 0.75-0.99), and a 9% reduced risk of cervical cancer (adjusted HR, 0.91; 95% CI, 0.84-0.99) compared to women who did not use LNG-IUD. A significant additive interaction between LNG-IUD use and family history of cancer was observed in breast cancer, indicating a relative 19% excess risk for interaction (P<.002), and 1.63 additional cases per 10,000 person-years. CONCLUSION: The risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It is important to note that the observed effect is small for breast cancer and the results are limited by the observational study design. Clinical recommendations regarding the use of LNG-IUD should carefully weigh its potential benefits and risks. Close monitoring is advisable for the potential development of breast cancer, particularly among women with a family history of breast cancer.

Performance of the MeltPro TB assay as initial test for diagnosis of pulmonary tuberculosis with drug-resistance detection.

BACKGROUND: The MeltPro TB assay (MeltPro) is a molecular rapid diagnostic test designed for detecting resistance to antituberculosis drugs. However, the performance of MeltPro as an initial diagnostic test for simultaneously detecting the presence of Mycobacterium tuberculosis (MTB) and drug resistance has not been evaluated. This study aims to assess the performance of MeltPro as initial diagnostic test for simultaneous detection of MTB and drug resistance in clinical samples from patients with presumptive pulmonary tuberculosis (PTB). METHODS: A retrospective analysis was conducted on 1283 patients with presumptive PTB from two clinical centers, out of which 875 were diagnosed with PTB. The diagnostic accuracy of MeltPro, Xpert MTB/RIF (Xpert), and MGIT 960 for PTB detection was evaluated. Rifampicin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and fluoroquinolone (FQ) resistance were detected using MeltPro, with Xpert and/or the broth microdilution plate method (MYCOTB) results as references. RESULTS: For the diagnosis of PTB, MeltPro showed a sensitivity of 69.0%, which was similar to Xpert (72.7%; P > 0.05) and higher than MGIT (58.1%; P < 0.001). The specificity of MeltPro was 97.1%, similar to Xpert (98.0%; P > 0.05). In smear-negative patients, MeltPro's sensitivity was 50.9%, similar to Xpert (56.5%; P > 0.05), and higher than MGIT (33.1%; P < 0.001). Based on Xpert and/or MYCOTB results, MeltPro exhibited a sensitivity and specificity of 98.3% and 99.2%, respectively, for detecting RIF resistance. Based on MYCOTB results, MeltPro's sensitivity for detecting resistance to INH, EMB, STR, and FQ was 96.4%, 89.1%, 97.5%, and 90.3%, respectively, with specificities of 96.0%, 96.0%, 95.2%, and 99.4%, respectively. CONCLUSION: The MeltPro TB assay could potentially be an effective alternative as the initial test for rapid diagnosis of PTB with drug-resistance detection in clinical practice.

Assessment of rehabilitation following subarachnoid haemorrhage in China: findings from the Chinese Stroke Center Alliance.

BACKGROUND: Rehabilitation improves functional recovery in subarachnoid hemorrhage (SAH) patients, and assessing patients for rehabilitation is the first step in this process. However, little is known about clinical practice in China regarding the assessment and provision of rehabilitation for patients with SAH. METHODS: To identify patients hospitalized with SAH and to analyze rehabilitation assessment rates, we used data for 11,234 SAH patients admitted to 861 hospitals from the China Stroke Center Alliance from August 2015 to July 2019. We examined factors for rehabilitation assessment and analyzed the relationship between rehabilitation assessment and outcomes in these patients. RESULTS: Among 11,234 patients with SAH, 6,513 (58.0%) were assessed for rehabilitation. Assessed patients had an increased length of stay (mean ± SD days: 17.3 ± 12.5 versus 11.6 ± 10.5, P = 49.4), a higher Glasgow Coma Scale (GCS) score on admission (mean ± SD GCS score: 12.3 ± 3.8 versus 11.8 ± 4.4, P = 12.2), and were more likely to be admitted to the stroke unit (19.6% versus 13.8%, P = 15.6). In multivariable analysis, factors associated with an increased likelihood of a rehabilitation assessment (p < 0.05) included a longer length of stay (odds ratio [OR], 1.04; 95% confidence interval (CI), 1.04 to 1.05) and care such as dysphagia screening (OR, 1.88; 95% CI, 1.73 to 2.04), DVT prophylaxis (OR, 1.56; 95% CI, 1.41 to 1.72) and vessel evaluation (OR, 1.80; 95% CI, 1.63 to 1.98). For the multivariate analysis of outcomes, patients undergoing rehabilitation assessment had a longer length of stay (OR, 1.96; 95% CI, 1.81 to 2.12), a higher modified Rankin Scale (mRS) score at discharge (OR, 1.49; 95% CI, 1.36 to 1.64), and higher rates of discharge to a rehabilitation center (OR, 3.23; 95% CI, 1.81-5.75). CONCLUSION: More than two-fifths of SAH patients were not assessed for rehabilitation. Rates vary considerably among hospital grades, and there is a need to improve adherence to recommended care for SAH patients.

Short- and long-term outcomes of patients with minor stroke and nonvalvular atrial fibrillation.

BACKGROUND AND PURPOSE: Nonvalvular atrial fibrillation (NVAF) is a risk factor for stroke. This study was undertaken to determine the influence of NVAF on the mortality and recurrent stroke after a minor stroke event. METHODS: Data were derived from the Third China National Stroke Registry (CNSR-III) which enrolled 15,166 subjects during August 2015 through March 2018 in China. Patients with minor stroke (NIHSS ≤ 5) within 24 h after onset were included. Clinical outcomes including all-cause mortality, cardiovascular death, recurrent ischemic stroke, and recurrent hemorrhagic stroke were collected. The Cox proportional hazards models were used to determine the association between NVAF and clinical outcomes. RESULTS: A total of 4,753 patients were included in our study. Of them, 222 patients had NVAF (4.7%) (mean age, 71.1 years) and 4,531 patients were without AF (95.3%) (mean age, 61.4 years). NVAF was associated with 12-month cardiovascular mortality in both univariate (hazards ratio [HR], 4.13; 95% confidence interval [CI], 1.84 to 9.31; P < 0.001) and multivariate analyses (HR, 4.66; 95% CI, 1.79 to 12.15; P = 0.001). There was no difference in the in-hospital ischemic stroke recurrence rate between the two groups (HR, 0.45 [95% CI, 0.19 to 1.05] P = 0.07 at discharge). However, patients with NVAF had a lower rate of recurrent ischemic stroke at medium- (3 months and 6 months) and long-term (12 months) follow-up (HR, 0.33 [95% CI, 0.16 to 0.68] P = 0.003 at 3 months; 0.49 [95% CI, 0.27 to 0.89] P = 0.02 at 6 months; 0.55 [95% CI, 0.32 to 0.94] P = 0.03 at 12 months, respectively) compared with those without. There was no difference in all-cause mortality and hemorrhagic stroke between the two groups during follow-up. CONCLUSIONS: Minor stroke patients with NVAF were at higher risk of cardiovascular death but had a lower rate of recurrent ischemic stroke compared to those without during the subsequent year after stroke event. A more accurate stroke risk prediction model for NVAF is warranted for optimal patient care strategies.

Sex Differences in Short-Term and Long-Term Outcomes Among Patients With Acute Ischemic Stroke in China.

BACKGROUND: Sex differences in stroke outcomes are crucial to secondary prevention, but previous reports showed inconsistent results. We aimed to explore the sex differences in stroke outcomes in the Third China National Stroke Registry, a prospective multicenter registry study. METHODS: Among the 15 166 patients enrolled between 2015 and 2018, 9038 patients with acute ischemic stroke (AIS) were included. The primary outcomes were stroke recurrence, mortality, and unfavorable functional outcome (modified Rankin Scale > 2) at 3, 6, and 12 months. Cox regression model was used for stroke recurrence and mortality and logistic regression was used for the unfavorable functional outcome, and adjusted as follows: (1) Model 1: without adjustment; (2) Model 2: adjusted for potential risk factors, National Institutes of Health Stroke Scale at admission, prestroke modified Rankin Scale, tPA (tissue-type plasminogen activator) treatment, TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification, and onset-to-door time; (3) Model 3: adjusted for covariates from model 2 in addition to blood pressure and blood serum covariates. Multiple imputation was used for missing values, and sensitivity analyses were conducted to describe sex differences by age groups. RESULTS: One-third (2802/9038) of the patients were women. Women were significantly older than men (64.78±10.84 versus 61.26±11.42, P<0.001). In the fully adjusted model, female patients were more likely to have unfavorable functional outcomes at 3 months (odds ratio, 1.28 [1.09-1.50]), especially among patients aged 65 years or older (odds ratio, 1.39 [1.14-1.70]), but no difference was discovered in patients aged <65 years. There were no sex differences in stroke recurrence and mortality at 3, 6, or 12 months or unfavorable functional outcomes at 6 or 12 months after adjustment. CONCLUSIONS: Compared with men, women with AIS were less likely to have favorable outcomes at 3 months in China, especially among those over 65 years of age. Experts should aim to tailor secondary prevention strategies for high-risk patients.

Sex differences in vascular risk factors, in-hospital management, and outcomes of patients with acute ischemic stroke in China.

BACKGROUND: Previous assessments of sex differences for patients with acute ischemic stroke were limited in a specific region or population, narrow scope, or small sample size. METHODS: Patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals were analyzed. Absolute standardized differences (ASDs) were used to assess sex differences in vascular risk factors, guideline-recommended in-hospital management measures and outcomes, including stroke severity (National Institutes of Health Stroke Scale≥16), death/discharge against medical advice, major adverse cardiovascular events, pneumonia, and disability (modified Rankin Scale≥3). RESULTS: Of 838,229 patients analyzed, 524351 (62.6%) were men and 313,878 (37.4%) were women. Compared with men, women were older (68.6 vs. 64.7 years), had higher prevalence of hypertension (67.7% vs. 62.4%), diabetes (24.7% vs. 19.5%), and atrial fibrillation (7.1% vs. 4.3%), but lower prevalence of smoking (4.5% vs. 56.6%) and drinking (2.6% vs 35.8%) (ASDs >10%). No sex differences were seen in guideline-directed management measures, indicated by risk-adjusted individual measures and the all-or-null summary measure (34.5% vs 34.9%, ASD = 1.0%). Compared to men, women tended to have strokes that were more severe at presentation (6.5% vs. 4.5%, ASD = 8.8%) and more disabilities at discharge (34.9% vs 30.5%, ASD =9.4%). However, all sex-related differences in outcomes were attenuated to null after risk adjustments (ASDs<2%). CONCLUSIONS: Compared to male patients, female patients had more vascular risk factors and received similar in-hospital care. They had strokes that were more severe at presentation and more disabilities at discharge, both of which may be explained by worse vascular risk profiles.

Machine learning is an effective method to predict the 90-day prognosis of patients with transient ischemic attack and minor stroke.

OBJECTIVE: We aimed to investigate factors related to the 90-day poor prognosis (mRS≥3) in patients with transient ischemic attack (TIA) or minor stroke, construct 90-day poor prognosis prediction models for patients with TIA or minor stroke, and compare the predictive performance of machine learning models and Logistic model. METHOD: We selected TIA and minor stroke patients from a prospective registry study (CNSR-III). Demographic characteristics,smoking history, drinking history(≥20g/day), physiological data, medical history,secondary prevention treatment, in-hospital evaluation and education,laboratory data, neurological severity, mRS score and TOAST classification of patients were assessed. Univariate and multivariate logistic regression analyses were performed in the training set to identify predictors associated with poor outcome (mRS≥3). The predictors were used to establish machine learning models and the traditional Logistic model, which were randomly divided into the training set and test set according to the ratio of 70:30. The training set was used to construct the prediction model, and the test set was used to evaluate the effect of the model. The evaluation indicators of the model included the area under the curve (AUC) of the discrimination index and the Brier score (or calibration plot) of the calibration index. RESULT: A total of 10967 patients with TIA and minor stroke were enrolled in this study, with an average age of 61.77 ± 11.18 years, and women accounted for 30.68%. Factors associated with the poor prognosis in TIA and minor stroke patients included sex, age, stroke history, heart rate, D-dimer, creatinine, TOAST classification, admission mRS, discharge mRS, and discharge NIHSS score. All models, both those constructed by Logistic regression and those by machine learning, performed well in predicting the 90-day poor prognosis (AUC >0.800). The best performing AUC in the test set was the Catboost model (AUC=0.839), followed by the XGBoost, GBDT, random forest and Adaboost model (AUCs equal to 0.838, 0, 835, 0.832, 0.823, respectively). The performance of Catboost and XGBoost in predicting poor prognosis at 90-day was better than the Logistic model, and the difference was statistically significant(P<0.05). All models, both those constructed by Logistic regression and those by machine learning had good calibration. CONCLUSION: Machine learning algorithms were not inferior to the Logistic regression model in predicting the poor prognosis of patients with TIA and minor stroke at 90-day. Among them, the Catboost model had the best predictive performance. All models provided good discrimination.

Stimulating the expression of sphingosine kinase 1 (SphK1) is beneficial to reduce acrylamide-induced nerve cell damage.

Sphingosine kinase 1 (SphK1) is an important signaling molecule for cell proliferation and survival. However, the role of SphK1 in acrylamide (ACR)-induced nerve injury remains unclear. The purpose of this study was to investigate the role and potential mechanism of SphK1 in ACR-induced nerve injury. Liquid chromatography triple quadrupole tandem mass spectrometry (LC-MS/MS) and reverse transcription-quantitative PCR (RT-qPCR) were used to detect sphingosine 1-phosphate (S1P) content in serum and SphK1 content in whole blood from an occupational work group exposed to ACR compared to a non-exposed group. For in vitro experiments, SphK1 in human SH-SY5Y neuroblastoma cells was activated using SphK1-specific activator phorbol 12-myristate 13-acetate (PMA). Our research also utilized cell viability assays, flow cytometry, western blots, RT-qPCR and related protein detection to assess activity of the mitogen activated protein kinase (MAPK) signaling pathway. The results of the population study showed that the contents of SphK1 and S1P in the ACR-exposed occupational contact group were lower than in the non-exposed group. The results of in vitro experiments showed that expression of SphK1 decreased with the increase in ACR concentration. Activating SphK1 improved the survival rate of SH-SY5Y cells and decreased the apoptosis rate. Activating SphK1 in SH-SY5Y cells also regulated MAPK signaling, including enhancing the phosphorylation of extracellular signal-regulated protein kinases (ERK) and inhibiting the phosphorylation of c-Jun N-terminal kinase (JNK) and p38. These results suggest that activating SphK1 can protect against nerve cell damage caused by ACR.

P2Y12 Inhibitors Plus Aspirin Versus Aspirin Alone in Patients With Minor Stroke or High-Risk Transient Ischemic Attack.

BACKGROUND AND PURPOSE: We performed a systemic review and meta-analysis to elucidate the effectiveness and safety of dual antiplatelet (DAPT) therapy with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy in patients with mild ischemic stroke or high-risk transient ischemic attack. METHODS: Following Preferred Reported Items for Systematic Review and Meta-Analysis standards for meta-analyses, Medline, Embase, Cochrane Central Register of Controlled Trials, and the Cochrane Library were searched for randomized controlled trials that included patients with a diagnosis of an acute mild ischemic stroke or high-risk transient ischemic attack, intervention of DAPT therapy with clopidogrel/ticagrelor and aspirin versus aspirin alone from January 2012 to July 2020. The outcomes included subsequent stroke, all-cause mortality, cardiovascular death, hemorrhage (mild, moderate, or severe), and myocardial infarction. A DerSimonian-Laird random-effects model was used to estimate pooled risk ratio (RR) and corresponding 95% CI in R package meta. We assessed the heterogeneity of data across studies with use of the Cochran Q statistic and I2 test. RESULTS: Four eligible trials involving 21 493 participants were included in the meta-analysis. DAPT therapy started within 24 hours of symptom onset reduced the risk of stroke recurrence by 24% (RR, 0.76 [95% CI, 0.68-0.83], I2=0%) but was not associated with a change in all-cause mortality (RR, 1.30 [95% CI, 0.90-1.89], I2=0%), cardiovascular death (RR, 1.34 [95% CI, 0.56-3.17], I2=0%), mild bleeding (RR, 1.25 [95% CI, 0.37-4.29], I2=94%), or myocardial infarction (RR, 1.45 [95% CI, 0.62-3.39], I2=0%). However, DAPT was associated with an increased risk of severe or moderate bleeding (RR, 2.17 [95% CI, 1.16-4.08], I2=41%); further sensitivity tests found that the association was limited to trials with DAPT treatment duration over 21 days (RR, 2.86 [95% CI, 1.75-4.67], I2=0%) or ticagrelor (RR, 2.17 [95% CI, 1.16-4.08], I2=37%) but not within 21 days or clopidogrel. CONCLUSIONS: In patients with noncardioembolic mild stroke or high-risk transient ischemic attack, DAPT with aspirin and clopidogrel/ticagrelor is more effective than aspirin alone for recurrent stroke prevention with a small absolute increase in the risk of severe or moderate bleeding.

Feasibility of low-dose dexmedetomidine for prevention of postoperative delirium after intracranial operations: a pilot randomized controlled trial.

BACKGROUND: Clinical trials have shown that dexmedetomidine might decrease the occurrence of postoperative delirium after major surgery, but neurosurgical patients were excluded from these studies. We aimed to determine the feasibility of conducting a full-scale randomized controlled trial of the effect of prophylactic low-dose dexmedetomidine on postoperative delirium in patients after elective intracranial operation for brain tumors. METHODS: In this single-center, parallel-arm pilot randomized controlled trial, adult patients who underwent an elective intracranial operation for brain tumors were recruited. Dexmedetomidine (0.1 µg/kg/hour) or placebo was continuously infused from intensive care unit (ICU) admission on the day of surgery until 08:00 AM on postoperative day one. Adverse events during the study-drug administration were recorded. The primary feasibility endpoint was the occurrence of study-drug interruption. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU during the first five postoperative days. The assessable rate of delirium evaluation was documented. RESULTS: Sixty participants were randomly assigned to receive either dexmedetomidine (n = 30) or placebo (n = 30). The study-drug was stopped in two patients (6.7%) in the placebo group due to desaturation after new-onset unconsciousness and an unplanned reoperation for hematoma evacuation and in one patient (3.3%) in the dexmedetomidine group due to unplanned discharge from the ICU. The absolute difference (95% confidence interval) of study-drug interruption between the two groups was 3.3% (- 18.6 to 12.0%), with a noninferiority P value of 0.009. During the study-drug infusion, no bradycardia occurred, and hypotension occurred in one patient (3.3%) in the dexmedetomidine group. Dexmedetomidine tended to decrease the incidence of tachycardia (10.0% vs. 23.3%) and hypertension (3.3% vs. 23.3%). Respiratory depression, desaturation, and unconsciousness occurred in the same patient with study-drug interruption in the placebo group (3.3%). Delirium was evaluated 600 times, of which 590 (98.3%) attempts were assessable except in one patient in the placebo group who remained in a coma after an unplanned reoperation. CONCLUSIONS: The low rate of study-drug interruption and high assessable rate of delirium evaluation supported a fully powered trial to determine the effectiveness of low-dose dexmedetomidine on postoperative delirium in patients after intracranial operation for brain tumors. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT04494828) on 31/07/2020.

[Comparison of active ingredients and protective effects of Dendrobium huoshanense of different growth years on acute liver injury].

The differences of the active ingredients in Dendrobium huoshanense of different growth years and their protective effects on acute liver injury were studied to provide evidence for optimizing harvest time. The contents of polysaccharides, total flavonoids and total alkaloids in D. huoshanense of different growth years were determined by UV spectrophotometry, and the contents of gigantol in D. huoshanense were determined by HPLC. C57 BL/6 mice were randomly divided into blank control group(saline), modeling group(saline), high-dose(7.5 g·kg~(-1)) and low-dose(1.25 g·kg~(-1)) groups of D. huoshanense of different growth years. Each group was intragastrically administered every day for 2 weeks. 500 mg·kg~(-1) paracetamol was injected intraperitoneally 2 h after last treatment except the control group. After 12 hours, the serum and liver tissues were collected to detect the activities of ALT and AST, and the levels of SOD and MDA. The hepatic histopathological examination was performed. The results showed that the chemical constituents of D. huo-shanense of different growth years were significantly different(P<0.05). The contents of polysaccharide and gigantol of D. huoshanense of 2 growth years were the highest. The contents of flavonoids and alkaloids of D. huoshanense of 3 growth years were the hig-hest, followed by the D. huoshanense of 2 growth years, and the lowest were that of 1 growth year. Compared with the modeling group, D. huoshanense of different growth years could decrease the activities of ALT and AST in serum. Meanwhile, the levels of MDA reduced significantly, while those of SOD increased markedly. Histopathological results suggested that all D. huoshanense samples were effective in the reduction of the necrosis of hepatocytes in different degrees. The results of the multi-component SPSS paired tests showed that polysaccharide and gigantol probably played a leading role in the liver protection effects, while D. huoshanense of 2 growth years showed the best efficacy. The optimal harvesting time of D. huoshanense is 2 growth years.

Paroxetine suppresses reactive microglia-mediated but not lipopolysaccharide-induced inflammatory responses in primary astrocytes.

BACKGROUND: Astrocytes are the most abundant glial cells in a brain that mediate inflammatory responses and provide trophic support for neurons. We have previously disclosed that paroxetine, a common selective serotonin reuptake inhibitor, ameliorates LPS-induced microglia activation. However, it remains elusive for the role of paroxetine in astrocytic responses. METHODS: Isolated primary astrocytes were pretreated with paroxetine and stimulated with different stimuli, lipopolysaccharide (LPS) or microglia conditioned medium pre-activated with LPS (M/Lps). Inflammatory and neurotrophic responses, underlying mechanisms and the impact on neuronal survival were assessed. RESULTS: Paroxetine had no impact on LPS-stimulated iNOS, TNF-α, and IL-1ß expression, but inhibited M/Lps-induced TNF-α and IL-1ß expression in primary astrocytes. Paroxetine suppressed M/Lps- but not LPS-induced activation of NF-κB and had no impact on the activation of MAPKs and STAT3. Incubation with the resulted astrocyte conditioned media caused no change in the viability of SH-SY5Y cells. BDNF and MANF mRNA expressions were upregulated by M/Lps and paroxetine, respectively. However, M/Lps- or LPS-induced extracellular releases of NO, TNF-α, and/or BDNF in astrocytes were in minor amount compared to those by microglia. CONCLUSIONS: Paroxetine ameliorates the reactive microglia-mediated inflammatory responses in astrocytes partially via inhibition of the NF-κB pathway but has no impact on LPS-stimulated astrocyte activation. While the effects of paroxetine on secondary astrocytic responses are not robust compared to its effect on the innate immune responses of microglia, the results together may implicate a therapeutic potential of paroxetine against neuroinflammation-associated neurological disorders such as Parkinson's disease.

Efficient markerless gene deletions in Pseudomonas protegens Pf-5 using a upp-based counterselective system.

OBJECTIVES: Developing a counterselective system for efficient markerless gene deletions in biocontrol strain P. protegens Pf-5. RESULTS: We successfully implemented a markerless deletion of upp in Pf-5 to obtain the 5-FU resistant strain Pf5139. With this strain, we performed markerless gene deletions for each component of Gac/Rsm system and a 17 kb DNA fragment with the deletion ratio of 20 to 50%, and efficiently constructed a strain with triple deletions based on the suicide plasmid pJQ200UPP. In addition, there is no obvious connection between the deleted fragment length and the deletion ratio. CONCLUSION: The upp-based counterselective system in this study is efficient and valuable for markerless gene deletions in Pf-5, indicating that it has great potential in the study of gene function and in the application of genome reduction for Pseudomonas strains.

Incidence and risk factors of postoperative delirium in patients admitted to the ICU after elective intracranial surgery: A prospective cohort study.

BACKGROUND: Postoperative delirium (POD) has been confirmed as an important complication after major surgery. However, neurosurgical patients have usually been excluded in previous studies. To date, data on POD and risk factors in patients after intracranial surgery are scarce. OBJECTIVES: To determine the incidence and risk factors of POD in patients after intracranial surgery. DESIGN: Prospective cohort study. SETTING: A neurosurgical ICU of a university-affiliated hospital, Beijing, China. INTERVENTIONS: Adult patients admitted to the ICU after elective intracranial surgery under general anaesthesia were consecutively enrolled between 1 March 2017 and 2 February 2018. Delirium was assessed using the Confusion Assessment Method for the ICU. POD was diagnosed as Confusion Assessment Method for the ICU positive on either postoperative day 1 or day 3. Patients were classified into groups with or without POD. Data were collected for univariate and multivariate analyses to determine the risk factors for POD. RESULTS: A total of 800 patients were included. POD was diagnosed in 157 patients (19.6%, 95% confidence interval 16.9 to 22.4%). Independent risk factors for POD included age, nature of intracranial lesion, frontal approach craniotomy, duration of surgery, presence of an episode of low pulse oxygenation at ICU admission, presence of inadequate emergence and emergence delirium, postoperative pain and presence of immobilising events. POD was associated with adverse outcomes and high costs. CONCLUSION: POD is prevalent in patients after elective intracranial surgery. The identified risk factors for and the potential association of POD with adverse outcomes suggest that a comprehensive strategy involving screening for predisposing factors and early prevention of modifiable factors should be established in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT03087838.

Use of Emergency Medical Services and Timely Treatment Among Ischemic Stroke.

Background and Purpose- Emergency medical services (EMSs) are critical for early treatment of patients with ischemic stroke, yet data on EMS utilization and its association with timely treatment in China are still limited. Methods- We examined data from the Chinese Stroke Center Alliance for patients with ischemic stroke from June 2015 to June 2018. Absolute standardized difference was used for covariates' balance assessments. We used multivariable logistic models with the generalized estimating equations to account for intrahospital clustering in identifying demographic and clinical factors associated with EMS use as well as in evaluating the association of EMS use with timely treatment. Results- Of the 560 447 patients with ischemic stroke analyzed, only 69 841 (12.5%) were transported by EMS. Multivariable-adjusted results indicated that those with younger age, lower levels of education, less insurance coverage, lower income, lower stroke severity, hypertension, diabetes mellitus, and peripheral vascular disease were less likely to use EMS. However, a history of cardiovascular diseases was associated with increased EMS usage. Compared with self-transport, EMS transport was associated with significantly shorter onset-to-door time, door-to-needle time (if prenotification was sent), earlier arrival (adjusted odds ratio [95% CIs] were 2.07 [1.95-2.20] for onset-to-door time ≤2 hours, 2.32 [2.18-2.47] for onset-to-door time ≤3.5 hours), and more rapid treatment (2.96 [2.88-3.05] for IV-tPA [intravenous recombinant tissue-type plasminogen activator] in eligible patients, 1.70 [1.62-1.77] for treatment with IV-tPA by 3 hours if onset-to-door time ≤2 hours, and 1.76 [1.70-1.83] for treatment with IV-tPA by 4.5 hours if onset-to-door time ≤3.5 hours). Conclusions- Although EMS transportation is associated with substantial reductions in prehospital delay and improved likelihood of early arrival and timely treatment, rate of utilization is currently low among Chinese patients with ischemic stroke. Developing an efficient EMS system and promoting culture-adapted education efforts are necessary for improving EMS activation.

Atrial Fibrillation Known Before or Detected After Stroke Share Similar Risk of Ischemic Stroke Recurrence and Death.

Background and Purpose- We aim to compare the risk of 1-year ischemic stroke recurrence and death for atrial fibrillation diagnosed after stroke (AFDAS), atrial fibrillation known before stroke (KAF), and sinus rhythm (SR). Methods- From June 2012 to January 2013, 19 604 patients with acute ischemic stroke were admitted to 219 urban hospitals in the China National Stroke Registry II. Based on heart rhythm assessed during admission, we classified patients as AFDAS, KAF, or SR. We explored the relationship between heart rhythm groups and 1-year ischemic stroke recurrence or death by using Cox regression adjusted for multiple covariates. Considering that death is a competing risk for stroke recurrence, we used the competing risks analysis of Fine and Gray and subdistribution Cox proportional hazards to test the association between heart rhythm and 1-year outcomes. Results- Among 19 604 ischemic stroke patients, 17 727 had SR, 495 AFDAS, and 1382 KAF. At 1 year, 54 (10.9%) patients with AFDAS, 182 (13.2%) with KAF, and 1008 (5.7%) with SR had recurrent ischemic strokes ( P<0.0001). Mortality was 22.0% in patients with AFDAS, 22.1% in patients with KAF, and 7.0% in patients with SR ( P<0.0001). AFDAS-related ischemic stroke recurrence adjusted risk was higher than that of SR (adjusted subdistribution hazard ratios, 1.61; 95% CI, 1.29-2.01) but not different from that of KAF (adjusted subdistribution hazard ratio, 1.12; 95% CI, 0.87-1.45]). The adjusted risk of 1-year death for AFDAS was also higher than that of SR (hazard ratio, 1.70; 95% CI, 1.37-2.12) and not different from that of KAF (hazard ratio, 1.10; 95% CI, 0.86-1.41). Conclusions- This study showed that AFDAS had similar risk of 1-year ischemic stroke recurrence and mortality when compared with KAF and higher risk when compared with SR. The potential risk of AFDAS should be given more emphasis, and appropriate treatment is needed to achieve reduction in the incidence of stroke recurrence and mortality.

Population structure and genetic diversity of Vibrio parahaemolyticus from a coastal area of China based on a multi-locus sequence typing (MLST) scheme.

The Gram-negative marine bacterium Vibrio parahaemolyticus has been identified as a major cause of bacterial food poisoning in China. Here, the population structure and genetic diversity of V. parahaemolyticus from Weihai, a coastal city in China, was studied by the multi-locus sequence typing (MLST) method. In this survey, we isolated 40 strains including environmental and clinical samples of patients with acute gastroenteritis or diarrhea; isolates from other countries were also included for comparison. DnaSP Version5, START V2, eBURST version3 and Mega 6 were used to analyse the data. We found that ST3 and ST332 were the most prevalent clones and that they were closely associated with acute diarrhoeal diseases. These STs showed a low dN/dS ratio and significant linkage disequilibrium. All isolates were divided into four clonal complexes, six groups and nine singletons, showing a high degree of genetic diversity. 18 STs, mostly from environmental isolates, were recognised by the MLST analysis for the first time. In conclusion, ST3 and ST332 were the epidemic STs in the coastal area. ST332 might be a region-specific ST, which needs to be confirmed by further analysis. Thus, the long-term monitoring of V. parahaemolyticus plays an important role in preventing and controlling the transmission between environment and people in Weihai.

Clinical significance of HER2 and EGFR expression in colorectal cancer patients with ovarian metastasis.

BACKGROUND: EGFR and HER2 overexpression has been reported to play important roles in colorectal cancer (CRC) development and metastasis. Ovarian metastasis is rare yet is one of the most malignant metastases of CRC, but very few studies have focused on its biological features. This study aimed to investigate the expression of EGFR and HER2 in ovarian metastases of CRC and to reveal their clinical significance. METHODS: The expression of HER2 and EGFR in both primary tumours and ovarian metastases was analysed by immunohistochemistry (IHC) in 31 CRC patients with ovarian metastases as well as in the primary tumours of 26 CRC patients with non-ovarian metastases. The overall survival time was calculated with a Kaplan-Meier survival curve and compared with a log-rank test. RESULTS: HER2 positivity in primary tumours was significantly higher in patients with ovarian metastases than in those with non-ovarian metastases (54.5% vs. 36.4%, P < 0.05). The EGFR-positive rate in primary lesions was not significantly different between patients with ovarian metastases and those with non-ovarian metastases (63.6% vs. 58.3%, P > 0.05). HER2 expression was not correlated with age, primary tumour site, tumour differentiation, tumour diameter or vascular cancer embolus (P > 0.05). The positive rates of HER2 and EGFR in ovarian metastases were 44.8 and 69.0%, respectively. HER2 expression in ovarian metastases was correlated with peritoneal metastasis and bilateral ovarian metastasis (P < 0.05) but not with age, synchronous or metachronous ovarian metastases and the primary tumour site (P > 0.05). There was no significant correlation between EGFR expression and the clinicopathological features in ovarian metastases (P > 0.05). CRC patients with HER2-positive ovarian metastases showed a shortened overall survival time compared to that of CRC patients with HER2-negative metastases (17.0 ± 5.2 vs. 32.0 ± 8.3 months). CONCLUSION: Our studies revealed that EGFR and HER2 are highly expressed in the primary tumours and metastases of CRC patients with ovarian metastases. HER2 positivity may be a negative prognostic predictor in patients with ovarian metastases.

High admission rates and heavy inpatient service costs of urban tuberculosis patients in eastern China.

BACKGROUND: Tuberculosis patients often experience hospitalization. Inpatient services may result in high medical expenditures. It is important to explore the hospitalization rates of tuberculosis patients and the potential factors that are associated with admission rates and inpatient service expenditures. METHODS: Data from patients diagnosed and treated at the No.3 hospital of Zhenjiang City from Apr. 2014 to Mar. 2015 were obtained. Univariate and multivariate statistical analyses were applied for the analysis of potential factors associated with admission rates, average length of stay and cost. RESULTS: A total of 356 tuberculosis patients were treated at the No.3 hospital of Zhenjiang City. A total of 221 of the 356 patients were hospitalized. Sputum smear test results and type of health insurance were the potential factors associated with hospitalization rates. The average admission was (1.26 ± 0.64) per patient. The average length of stay of inpatients was 29.99 ± 25.83 days. Age, occupation, and sputum smear test were related to the average length of stay. The average total cost to inpatients was 13007.91 ± 5205.58 CNY. The sputum smear test results, type of health insurance, occupation and age were the main potential factors associated with TB inpatient expenditures. CONCLUSIONS: The admission rate of tuberculosis patients was high. Despite advances in TB insurance policies, there were substantial costs associated with TB diagnosis and treatment. TB patients still face a heavy financial burden. Health care providers should revise the service package and reform the health insurance regulations to ensure that TB patients receive appropriate care.