Sleeping Beauty mRNA-LNP enables stable rAAV transgene expression in mouse and NHP hepatocytes and improves vector potency.

Recombinant adeno-associated virus (rAAV) vector gene delivery systems have demonstrated great promise in clinical trials but continue to face durability and dose-related challenges. Unlike rAAV gene therapy, integrating gene addition approaches can provide curative expression in mitotically active cells and pediatric populations. We explored a novel in vivo delivery approach based on an engineered transposase, Sleeping Beauty (SB100X), delivered as an mRNA within a lipid nanoparticle (LNP), in combination with an rAAV-delivered transposable transgene. This combinatorial approach achieved correction of ornithine transcarbamylase deficiency in the neonatal Spfash mouse model following a single delivery to dividing hepatocytes in the newborn liver. Correction remained stable into adulthood, while a conventional rAAV approach resulted in a return to the disease state. In non-human primates, integration by transposition, mediated by this technology, improved gene expression 10-fold over conventional rAAV-mediated gene transfer while requiring 5-fold less vector. Additionally, integration site analysis confirmed a random profile while specifically targeting TA dinucleotides across the genome. Together, these findings demonstrate that transposable elements can improve rAAV-delivered therapies by lowering the vector dose requirement and associated toxicity while expanding target cell types.

Intracranial hypertension as the primary symptom of malignant melanoma: A case report.

BACKGROUND: The etiological diagnosis of intracranial hypertension is quite complicated but important in clinical practice. Some common causes are craniocerebral injury, intracranial space-occupying lesion, subarachnoid hemorrhage, and hydrocephalus. When a patient presents with intracranial hypertension, the common causes are to be considered first so that other causes would be dismissed. With the morbidity lower than 9%, neuromelanin is very rare. Common symptoms include nerve damage symptoms, epilepsy, psychiatric symptoms, and cognitive disorders. CASE SUMMARY: We present a patient with melanoma which manifested with isolated intracranial hypertension without any other neurological signs. A 22-year-old male had repeated nausea and vomiting for 2 mo with Babinski sign (+) on both sides, nuchal rigidity, and subarachnoid hemorrhage. He had been diagnosed with melanoma and was given surgery and whole-brain radiation. Ultimately, the patient died 2 mo later. CONCLUSION: Malignant melanoma should be taken into consideration in the differential diagnosis of intracranial hypertension.

Systemic neutrophils are triggered by respiratory Bacillus Calmette- Guérin and mediate pulmonary mycobacterial clearance in synergy with the triggering receptor expressed on myeloid cells 1.

Tuberculosis remains a threat to public health. The only approved vaccine, Bacillus Calmette-Guérin (BCG), is administered intradermally and provides limited protection, and its effect on innate immunity via the respiratory route has not been fully elucidated. A mouse model with genetically depleted TREM1 and seven-color flow cytometry staining were used to characterize the comprehensive immune response induced by respiratory BCG, through evaluating organ bacterial loads, lung histopathology, and lung immunohistochemistry. During respiratory BCG infection, the murine lungs displayed effective bacterial clearance. Notably, marked differences in neutrophils were observed between thymus and bone marrow cells, characterized by a significant increase in the expression of the triggering receptor expressed on myeloid cells 1 (TREM1). Subsequently, upon depletion of TREM1, a reduction in pulmonary neutrophils was observed, which further exacerbated bacterial loads and resulted in worsened pathology following respiratory BCG infection. In summary, up-regulated expression of TREM1 in rapidly increasing circulating neutrophil by pulmonary BCG is required for an efficient host response to BCG infection, and suggests the important role of TREM1 in neutrophil-related pulmonary bacteria clearance and pathology.

Gastrodin inhibits prostate cancer proliferation by targeting canonical Wnt/ß-catenin signaling pathway.

Prostate cancer is an epithelial malignant tumor occurring in the prostate and is the most common malignant tumor in the male genitourinary system. In recent years, the incidence of prostate cancer in China has shown a trend of sudden increase. The search for new and effective drugs to treat prostate cancer is therefore extremely important.The canonical Wnt/ß-catenin signaling pathway has been shown to be involved in the regulation of tumor proliferation, migration and differentiation. Activation of the canonical Wnt/ß-Catenin signaling pathway in the prostate has oncogenic effects. Drugs targeting the canonical Wnt/ß-catenin signaling pathway have great potential in the treatment of prostate cancer. In this study, we found that Gastrodin could significantly inhibit the proliferation of prostate cancer cell line PC3 and DU145. Oral administration Gastrodin could significantly inhibit the tumor growth of PC3 cells subcutaneously injected. Gastrodin has an inhibitory effect on canonical Wnt/ß-Catenin signaling pathway in Prostate cancer, and this inhibitory effect can be abolished by Wnt/ß-Catenin agonist LiCl. These findings raise the possibility that Gastrodin can be used in the treatment of Prostate cancer by targeting canonical Wnt/ß-Catenin signaling pathway.

How to use the Surveillance, Epidemiology, and End Results (SEER) data: research design and methodology.

In the United States (US), the Surveillance, Epidemiology, and End Results (SEER) program is the only comprehensive source of population-based information that includes stage of cancer at the time of diagnosis and patient survival data. This program aims to provide a database about cancer incidence and survival for studies of surveillance and the development of analytical and methodological tools in the cancer field. Currently, the SEER program covers approximately half of the total cancer patients in the US. A growing number of clinical studies have applied the SEER database in various aspects. However, the intrinsic features of the SEER database, such as the huge data volume and complexity of data types, have hindered its application. In this review, we provided a systematic overview of the commonly used methodologies and study designs for retrospective epidemiological research in order to illustrate the application of the SEER database. Therefore, the goal of this review is to assist researchers in the selection of appropriate methods and study designs for enhancing the robustness and reliability of clinical studies by mining the SEER database.

Fruit peel crude enzymes for enhancement of biohydrogen production from synthetic swine wastewater by improving biohydrogen-formation processes of dark fermentation.

Biohydrogen is a promising clean fuel but with a low yield. This study aims to enhance biohydrogen production from synthetic swine wastewater by employing crude enzymes obtained from different fruit peels (orange, mandarin, and banana) to improve the biohydrogen-formation processes of dark fermentation. Results indicated that dosing with crude enzymes affected volatile fatty acids (VFAs) and biogas composition insignificantly, while increased biohydrogen yield from 1.62 ± 0.00 (blank) to 1.90 ± 0.08 (orange peel), 2.01 ± 0.00 (mandarin peel), and 1.96 ± 0.01 (banana peel) mol H2/mol glucose, respectively. Banana peel crude enzyme was the most effective additive, with 1 g/L protein improving 97.41 ± 3.72 % of biohydrogen yield. The crude enzymes wielded less influence on acetic acid and butyric acid pathways but enhanced other biohydrogen production pathways. These observations demonstrated that fruit peel-based crude enzymes as additives are advantageous to improving biohydrogen yield towards higher biohydrogen production.

Therapeutic effect of fastigial nucleus stimulation is mediated by the microRNA-182 & microRNA-382/BDNF signaling pathways in the treatment of post-stroke depression.

The deregulation of Brain-Derived Neurotrophic Factor (BDNF) was reported to be responsible for the development of post-stroke depression (PSD), while the stimulation of the fastigial nucleus (FN) can be used to treat PDS by down-regulating the expression of miR-182 and miR-382. Therefore, we aim to test the hypothesis that the therapeutic effect of FN stimulation obtained in the treatment of PSD is mediated by the miR-382&miR-182/BDNF mRNA signaling pathways. Rat models of PSD were established and divided into sham, stroke, PSD and PSD + FNS groups to receive different treatments. Post-stroke depression-like behaviors were observed after the initiation of the treatments. TUNEL assay, Western Blot, IHC assay, real-time PCR, bioinformatics tools and luciferase assays were performed to examine the effect of FN stimulation on the expression of miR-182, miR-382 and BDNF mRNA/protein, as well as to further clarify the role of miR-382&miR-182/BDNF mRNA signaling pathways in FN stimulation. Post-stroke depression-like behaviors were significantly reduced in PSD rats. In contrary, the treatment by FN stimulation alleviated the symptoms of PSD and reduced the apoptosis index in the PSD group. Furthermore, in the PSD group, BDNF mRNA/protein levels were suppressed while the miR-382/miR-182 levels were both significantly up-regulated. After the treatment of FN stimulation, BDNF mRNA/protein levels were partly recovered, while miR-382/miR-182 levels was decreased. Furthermore, BDNF was identified as a virtual target of miR-382 and miR-182. In conclusion, FN stimulation increases the expression of BDNF via down-regulating the expression of miR-382/miR-182, thus exhibiting a positive effect in the management of PSD.

The lip gene contributes to the virulence of Aeromonas veronii strain TH0426.

Aeromonas veronii (A. veronii) is a pathogen that can infect aquatic organisms and mammals and has caused irrecoverable economic losses to the aquaculture industry. The results of an epidemiological investigation showed that the number of cases of A. veronii have increased gradually in recent years, and its drug resistance and virulence has shown an upward trend. In this study, we constructed an A. veronii mutant strain Δlip, by homologous recombination and studied its function. The results showed that there was no significant difference in the biofilm formation ability between the Δlip and the wild-type strain, but the toxicity of the Δlip to EPC cells and its ability to adhere to EPC cells were significantly reduced. The LD50 value of the Δlip to zebrafish was 7.40-fold higher than that of the wild-type strain. In addition, after 24 h and 72 h, the bacterial loads of the Δlip in the organs of crucian carp were significantly lower than those in the wild-type strain. In conclusion, the mutant strain Δlip led to a decrease in the adhesion and virulence of the wild-type strain, which lays a foundation to further understand lip gene function and the pathogenic mechanism of A. veronii.

China Stroke Statistics: an update on the 2019 report from the National Center for Healthcare Quality Management in Neurological Diseases, China National Clinical Research Center for Neurological Diseases, the Chinese Stroke Association, National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention and Institute for Global Neuroscience and Stroke Collaborations.

China faces the greatest challenge from stroke in the world. According to results from the Global Burden of Disease Study 2019, there were 3.94 million new stroke cases, 28.76 million prevalent cases and 2.19 million deaths due to stroke in China in 2019. Furthermore, stroke is also the leading cause of disability-adjusted life-year (DALY) in China, the number of DALYs reached 45.9 million in 2019. Several recent large-scale epidemiological surveys have updated the data on pre-existing conditions contributed to stroke. The age-adjusted prevalence of overweight among Chinese adults aged 18-69 years was 34.4%, and the prevalence of obesity was 16.8% in 2018. 50.9% of Chinese adults ≥18 years of age without history of hypertension had prehypertension in 2018. The weighted prevalence of hypertension in adults was 27.5% in 2018. The weighted prevalence of total diabetes and pre-diabetes diagnosed by the American Diabetes Association criteria were 12.8% and 35.2%, respectively, among Chinese adults ≥18 years of age in 2017. The weighted atrial fibrillation prevalence was 1.8% among Chinese adults ≥45 years of age and equates to being present in an estimated 7.9 million people in China. Data from 1672 tertiary public hospitals in the Hospital Quality Monitoring System (HQMS) showed that 3 411 168 stroke cases were admitted during 2019. Of those, 2 818 875 (82.6%) were ischaemic strokes (ISs), 485 474 (14.2%) were intracerebral haemorrhages (ICHs), 106 819 (3.1%) were subarachnoid haemorrhages (SAHs). The average age was 66 years old, and 59.6% were male. A total of 1379 (<0.1%), 2604 (0.5%), 1250 (1.2%) paediatric strokes (age <18 years) were identified among IS, ICH and SAH, respectively. Over one-third (1 231 519 (36.1%)) of the stroke cases were covered by urban resident basic medical insurance, followed by urban employee basic medical insurance (891 103 (26.1%)) and new rural cooperative medical schema (543 108 (15.9%)). The leading risk factor was hypertension (57.3% for IS, 69.9% for ICH and 44.1% for SAH), and the leading comorbidity was pneumonia or pulmonary infection (10.4% for IS, 34.6% for ICH and 29.7% for SAH). In-hospital death/discharge against medical advice rate was 8.5%, ranging from 6.0% for IS to 20.6% for SAH. The median and IQR of length of stay was 9.0 (6.0-13.0) days, ranging from 10.0 (7.0-13.0) in IS to 14.0 (8.0-22.0) in ICH. Similar data from 2847 secondary public hospitals or private hospitals in the HQMS were also reported. Data from HQMS showed that higher proportions of interprovincial admission to other provinces were seen in Inner Mongolia, Anhui, Tibet and Beijing. Higher proportions of interprovincial admission from other provinces were seen in Beijng, Tianjin, Shanghai and Ningxia. Data from 323 601 strokes from 1337 hospitals in the Chinese Stroke Center Alliance during 2019 demonstrated that the composite scores of guideline-recommended key performance indicators for patients with IS, ICH and SAH were 0.78±0.20, 0.69±0.27 and 0.60±0.31, respectively.

Indobufen versus aspirin in acute ischaemic stroke (INSURE): rationale and design of a multicentre randomised trial.

BACKGROUND: Indobufen can reversibly inhibit platelet aggregation and showed to be effective in the treatment of ischaemic heart and peripheral vascular diseases. However, it is unclear whether indobufen is an alternative antiplatelet agent for treatment of patients with ischaemic stroke. AIM: To test whether indobufen is non-inferior to aspirin in reducing the risk of new stroke at 3 months in patients with moderate to severe ischaemic stroke. DESIGN: The Indobufen vs Aspirin in Acute Ischaemic Stroke (INSURE) is a randomised, double-blind, double-dummy, positive drug control, non-inferior multicentre clinical trial conducted in 200 hospitals in China. Participants will be randomised at a 1:1 ratio to receive either 100 mg indofufen two times daily or 100 mg aspirin once daily within 72 hours of the onset of symptoms from day 1 to 3 months. STUDY OUTCOMES: The primary efficacy outcome is a new stroke (ischaemic or haemorrhagic) within 3 months and the primary safety outcome is a severe or moderate bleeding event within 3 months. DISCUSSION: The INSURE trial will evaluate whether indobufen is non-inferior to aspirin in reducing the risk of new stroke at 3 months in patients with moderate to severe ischaemic stroke. TRIAL REGISTRATION NUMBER: NCT03871517.

A New Nomogram for Predicting the Risk of Intracranial Hemorrhage in Acute Ischemic Stroke Patients After Intravenous Thrombolysis.

Background: We aimed to develop and validate a new nomogram for predicting the risk of intracranial hemorrhage (ICH) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). Methods: A retrospective study enrolled 553 patients with AIS treated with IVT. The patients were randomly divided into two cohorts: the training set (70%, n = 387) and the testing set (30%, n = 166). The factors in the predictive nomogram were filtered using multivariable logistic regression analysis. The performance of the nomogram was assessed based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA). Results: After multivariable logistic regression analysis, certain factors, such as smoking, National Institutes of Health of Stroke Scale (NIHSS) score, blood urea nitrogen-to-creatinine ratio (BUN/Cr), and neutrophil-to-lymphocyte ratio (NLR), were found to be independent predictors of ICH and were used to construct a nomogram. The AUC-ROC values of the nomogram were 0.887 (95% CI: 0.842-0.933) and 0.776 (95% CI: 0.681-0.872) in the training and testing sets, respectively. The AUC-ROC of the nomogram was higher than that of the Multicenter Stroke Survey (MSS), Glucose, Race, Age, Sex, Systolic blood Pressure, and Severity of stroke (GRASPS), and stroke prognostication using age and NIH Stroke Scale-100 positive index (SPAN-100) scores for predicting ICH in both the training and testing sets (p < 0.05). The calibration plot demonstrated good agreement in both the training and testing sets. DCA indicated that the nomogram was clinically useful. Conclusions: The new nomogram, which included smoking, NIHSS, BUN/Cr, and NLR as variables, had the potential for predicting the risk of ICH in patients with AIS after IVT.

Evaluating photoneutron dose equivalents for lung cancer using PMMA phantoms undergoing 15 MV IMRT.

BACKGROUND: According to statistics of the Ministry of Health and Welfare in 2017, the second leading cause of death in Taiwan was lung cancer. OBJECTIVE: Routine treatment planning does not consider photoneutron dose equivalent (PNDE) of patient induced secondary radiation resulting from primary exposure of lung cancer. However, such treatment is potentially important for improving estimates of health risks. METHODS: This study used 10, 30, 50, 70, and 90 kg of polymethylmethacrylate (PMMA) phantoms as patient to measure PNDE varying anatomical area during lung cancer of intensity modulated radiotherapy (IMRT) treatment. Paired thermoluminescent dosimeters (TLD-600 and 700) were calibrated using university reactor neutrons. TLDs were inserted into phantom which was closely corresponded of the represented tissues or organs. RESULTS: Neutron doses (ND) of organ or tissue (N⁢DT) were determined in these phantoms using paired TLDs approach. The risks of incurring fatal secondary malignancies, maximum statistical and total errors were estimated. Evaluated PNDE ranged from 0.80 ± 0.12 to 0.56 ± 0.08 mSv/Gy for these phantoms. CONCLUSION: The estimated N⁢DT decreased with increasing distance that is from the central axis. Evaluated PNDE and N⁢D𝑠𝑘𝑖𝑛 for these phantoms were discussed. This investigation also identified secondary risks associated with PNDE relating to radiation protection.

Impact factors and novel strategies for improving biohydrogen production in microbial electrolysis cells.

Microbial electrolysis cell (MEC) system is an environmentally friendly method for clean biohydrogen production from a wide range of biowastes owing to low greenhouse gas emissions. This approach has relatively higher yields and lower energy costs for biohydrogen production compared to conventional biological technologies and direct water electrolysis, respectively. However, biohydrogen production efficiency and operating costs of MEC still need further optimization to realize its large-scale application.This paper provides a unique review of impact factors influencing biohydrogen production in MECs, such as microorganisms and electrodes. Novel strategies, including inhibition of methanogens, development of novel cathode catalyst, advanced reactor design and integrated systems, to enhance low-cost biohydrogen production, are discussed based on recent publications in terms of their opportunities, bottlenecks and future directions. In addition, the current challenges, and effective future perspectives towards the practical application of MECs are described in this review.

Data mining in clinical big data: the frequently used databases, steps, and methodological models.

Many high quality studies have emerged from public databases, such as Surveillance, Epidemiology, and End Results (SEER), National Health and Nutrition Examination Survey (NHANES), The Cancer Genome Atlas (TCGA), and Medical Information Mart for Intensive Care (MIMIC); however, these data are often characterized by a high degree of dimensional heterogeneity, timeliness, scarcity, irregularity, and other characteristics, resulting in the value of these data not being fully utilized. Data-mining technology has been a frontier field in medical research, as it demonstrates excellent performance in evaluating patient risks and assisting clinical decision-making in building disease-prediction models. Therefore, data mining has unique advantages in clinical big-data research, especially in large-scale medical public databases. This article introduced the main medical public database and described the steps, tasks, and models of data mining in simple language. Additionally, we described data-mining methods along with their practical applications. The goal of this work was to aid clinical researchers in gaining a clear and intuitive understanding of the application of data-mining technology on clinical big-data in order to promote the production of research results that are beneficial to doctors and patients.

Interleukin-17A Contributes to Bacterial Clearance in a Mouse Model of Streptococcal Toxic Shock-Like Syndrome.

Streptococcus suis (S. suis), an emerging zoonotic pathogen, can cause streptococcal toxic shock-like syndrome (STSLS) in humans with high mortality. STSLS is characterized by high bacterial burden, an inflammatory cytokine storm, multi-organ dysfunction, and ultimately acute host death. Although it has been found that a significantly high level of IL-17A was induced in an NLRP3-dependent manner during STSLS development, the role of IL-17A on S. suis STSLS remains to be elucidated. In this study, we found that the epidemic strain SC 19 caused a significantly higher level of IL-17A than the non-epidemic strain P1/7. In addition, higher bacterial burden was observed from SC 19-infected il17a-/- mice than il17a+/+ mice, although acute death, tissue injury and inflammatory cytokines storm were observed in both types of mice. Furthermore, compared with il17a+/+ mice, the level of neutrophils recruitment was lower in il17a-/- mice, and the levels of induced antimicrobial proteins, such as CRAMP, S100A8 and lipocalin-2, were also decreased in il17a-/- mice. In conclusion, this study demonstrated that IL-17A does not contribute to the severe inflammation, although it may play a minor role for bacterial clearance by inducing antimicrobial proteins and promoting neutrophil recruitment during STSLS.

Convenient Agarose Preparation with Hydrogen Peroxide and Desulfation Process Analysis.

Agarose is a natural seaweed polysaccharide and widely used in the medicine, food, and biological fields because of its high gel strength, non-toxicity, and electrical neutrality. The sulfate group is one of the main charged groups that affect the performance of agarose. In the present study, a simple, eco-friendly, and efficient method was explored for agarose preparation. After desulfation with hydrogen peroxide (H2O2), the sulfate content of agar reached 0.21%. Together with gel strength, electroendosmosis, gelling and melting temperature, the indicators of desulfated agar met the standards of commercially available agarose. Notably, the desulfated agar can be used as an agarose gel electrophoresis medium to separate DNA molecules, and the separation effect is as good as that of commercially available agarose. Further, the H2O2 desulfation process was analyzed. The addition of a hydroxyl radical (HO•) scavenger remarkably decreased the H2O2 desulfation rate, indicating that HO• has a certain role in agar desulfation. Sulfate content detection indicated that sulfur was removed from agar molecules in the form of sulfate ions (SO42-) and metal sulfate. The band absence at 850 cm-1 indicated that the sulfate groups at C-4 of D-galactose in sulfated galactan were eliminated.

Study on environmental performance evaluation of different linkage development types of the logistics and manufacturing industries considering the unexpected output.

According to the different organizational forms of logistics in manufacturing, the types of linkage development between the logistics and manufacturing industries include two different logistics service modes: logistics outsourcing and logistics self-operation. This study considers two manufacturing clusters for comparison: the northeast region in China, mainly state-owned and self-operated, and the Yangtze River Delta region in China, mainly focusing on logistics outsourcing services. First, we construct a parallel network system considering heterogeneity and an unexpected super-efficiency slacks-based measure: the Grey Relational Analysis model. Second, considering the unexpected output, this study evaluates the environmental performance of the linkage development of the logistics and manufacturing industries and explains the types of linkage development between them. Finally, the spatial and temporal characteristics of linkage efficiency under different linkage modes are studied using an exploratory spatial data analysis method. The research results show that the efficiency of the two-industry linkage in different linkage types that consider the unexpected output presents different development characteristics. Regarding time characteristics and trends, we compare the development efficiency of the two-industry linkage at the overall level of the northeast and the Yangtze River Delta regions from 2009 to 2016. The Yangtze River Delta region showed a higher state of linkage while the northeast region showed a medium linkage state. Regarding spatial pattern evolution, the effect of the technical efficiency of the linkage between the two industries in the three northeastern provinces showed continuous evolution from the medium linkage stage to the weak linkage stage, and the Yangtze River Delta showed continuous evolution from the medium linkage to the strong linkage stage.Implications: Due to data availability, references to the relevant achievements of the research on the linkage between the manufacturing and logistics industries, the transportation industry, warehousing, and postal and telecommunications industry data are generally used as logistics industry data. Manufacturing data are replaced by industrial data. The manufacturing industry is the core industry of industrial systems. Its output value accounts for more than 90% of the industrial output. Thus, it can reflect the development trend of the manufacturing industry in general.

Combined therapy of intensive statin plus intravenous rt-PA in acute ischemic stroke: the INSPIRE randomized clinical trial.

OBJECTIVE: To investigate the safety and efficacy of intensive statin in the acute phase of ischemic stroke after intravenous thrombolysis therapy. METHODS: A total of 310 stroke patients treated with rt-PA were randomly scheduled into the intensive statin group (rosuvastatin 20 mg daily × 14 days) and the control group (rosuvastatin 5 mg daily × 14 days). The primary clinical endpoint was excellent functional outcome (mRS ≤ 1) at 3 months, and the primary safety endpoint was symptomatic intracranial hemorrhage (sICH) in 90 days. RESULTS: The intensive statin users did not achieve a favorable outcome in excellent functional outcome (mRS ≤ 1) at 3 months compared with controls (70.3% vs. 66.5%, p = 0.464). Intensive statin also not significantly improved the overall distribution of scores on the modified Rankin scale, as compared with controls (p = 0.82 by the Cochran-Mantel-Haenszel test). The incidence of primary safety endpoint events (sICH) in 90 days did not significantly differ between the intensive statin group and control group (0.6% vs. 1.3%, p > 0.999). CONCLUSION: The INSPIRE study indicated that intensive statin therapy may not improve clinical outcomes compared with the low dose of statin therapy in AIS patients undergoing intravenous thrombolysis, and the two groups had similar safety profile. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org . Unique identifier: ChiCTR-IPR-16008642.

Ambulatory blood pressure profile and stroke recurrence.

OBJECTIVES: To establish a new ambulatory blood pressure (ABP) parameter (24-hour ABP profile) and evaluated its performance on stroke outcome in ischaemic stroke (IS) or transient ischaemic attack (TIA) patients. METHODS: The prospective cohort consisted of 1996 IS/TIA patients enrolled for ABP monitoring and a 3-month follow-up for stroke recurrence as outcome. Profile groups of systolic blood pressure (SBP) were identified via an advanced functional clustering method, and the associations of the profile groups and conventional ABP parameters with stroke recurrence were examined in a Cox proportional hazards model. RESULTS: Three discrete profile groups (n=604, 781 and 611 in profiles 1, 2 and 3, respectively) in 24-hour ambulatory SBP were identified. Profile 1 resembled most to the normal diurnal blood pressure pattern; profile 2 also dropped at night, but climbed earlier and with higher morning surge; while profile 3 had sustained higher nocturnal SBP without significant nocturnal SBP decline. The incidence of stroke recurrence was 2.9%, 3.9% and 5.5% in profiles 1, 2 and 3, respectively. After adjustment for covariates, profile 3 was significantly associated with higher risk of stroke recurrence with profile 1 as reference (HR 1.76, 95% CI: 1.00 to 3.09), while no significant difference was observed between profiles 2 and 1 (HR 1.22, 95% CI: 0.66 to 2.25). None of conventional ABP parameters showed significant associations with the outcome. CONCLUSIONS: Ambulatory 24-hour SBP profile is associated with short-term stroke recurrence. Profiles of ABP may help improve identification of stroke recurrence by capturing the additive effects of individual ABP parameters.

Evaluation of linkage efficiency between manufacturing industry and logistics industry considering the output of unexpected pollutants.

Applied a non-radical non-oriented Slack Based Measure (SBM) model of Data Envelopment Analysis (DEA) to measure the linkage efficiency between the two sectors from 2009 to 2016. The paper analyzes the current situation of manufacturing and logistics efficiency, presents a way to improve the linkage efficiency of manufacturing and logistics industry, and using Tobit regression to analyze the environmental factors that affect the linkage efficiency. The results show that: Totality, the two industries in the three northeast provinces show a steady development trend in the period from 2009 to 2016, but the development of the two industries in northeast China is still insufficient. Unexpected pollutant output is the main reason for the decline of manufacturing efficiency in the regions. The redundancy of input factors is the main reason that affects the efficiency decline of the logistics industry. The results of Tobit regression analysis show that the investment of science and technology and opening to the outside world have a positive influence on the efficiency of the two industries, and government consumption has a negative effect on the efficiency of the two industries. This is to correctly understand and grasp the status of two industry linkage development in three northeast provinces. And it provides a certain basis for the development policy of the two-industry linkage development.Implications: Due to the availability of data, reference to the relevant achievements of the research on the linkage between manufacturing industry and logistics industry. The transportation industry, warehousing, and postal and telecommunications industry data are generally used as logistics industry data. Manufacturing data replaced by industrial data. The manufacturing industry is the core industry in the industrial system. Its output value accounts for more than 90% of industrial output value, so it can reflect the development trend of the manufacturing industry in general.