Integration of network pharmacology and experimental verifications reveals the Bian-Se-Tong mixture can alleviate constipation in STC rats by reducing apoptosis of Cajal cells via activating PI3K-Akt signaling pathway.

Bian-Se-Tong mixture (BSTM) is an optimized formulation based on the classical prescription "Zhizhu pill", which is widely used in the clinical treatment of slow-transit constipation (STC). The potential molecular mechanism of BSTM therapy for STC was investigated by network pharmacology prediction combined with animal experiments. The active components of BSTM were screened via the TCMSP platform. The GeneCards, OMIM and DrugBank databases were used to search for STC targets. With the help of the Biogenet tool, a protein interaction network between drugs and disease targets was constructed, and the intersection network of the two was extracted to obtain the key targets of BSTM in the treatment of STC. GO and KEGG enrichment analyses of key targets were carried out with Metascape. Loperamide hydrochloride was used to establish an STC rat model, and the key targets and related pathways were preliminarily verified. The important signaling pathways included the PI3K-Akt, MAPK, IL-17, cAMP, and cell cycle signaling pathways. The experimental results showed that BSTM treatment increased the body weight of STC rats and increased the fecal particle number, fecal water content and intestinal carbon ink promotion rate within 24 h. Further pathological changes in the colon of the rats were also observed. In-depth mechanistic studies have shown that BSTM can significantly reduce the apoptosis of intestinal Cajal cells, downregulate the expression of Bax and c-Caspase 3, upregulate the expression of Bcl-2 and c-kit, and promote the phosphorylation of AKT. The results showed that BSTM can significantly relieve constipation in STC rats via a mechanism related to activating the PI3K-Akt signaling pathway and improving Cajal cell apoptosis.

The Effect of Terbinafine and Its Ionic Salts on Certain Fungal Plant Pathogens.

Terbinafine, an inhibitor of squalene epoxidase in ergosterol biosynthesis, is chiefly utilized as an antifungal medication with potential uses in pesticide applications. This study explores the fungicidal efficacy of terbinafine against prevalent plant pathogens and confirms its effectiveness. To augment its water solubility, five ionic salts of terbinafine were synthesized by pairing them with organic acids. Among these salts, TIS 5 delivered the most impressive results, amplifying the water solubility of terbinafine by three orders of magnitude and lessening its surface tension to facilitate better dispersion during spraying. The in vivo experiments on cherry tomatoes showed that TIS 5 had a superior therapeutic activity compared to its parent compound and two commonly used broad-spectrum fungicides, pyraclostrobin and carbendazim. The results highlight the potential of terbinafine and its ionic salts, particularly TIS 5, for use as fungicides in agriculture due to their synergistic effects with furan-2-carboxylate.

Hsa_circ_0003602 Contributes to the Progression of Colorectal Cancer by Mediating the miR-149-5p/SLC38A1 Axis.

Background/Aims: We aimed to investigate the role and working mechanism of Homo sapiens circular RNA_0003602 (hsa_circ_0003602) in colorectal cancer (CRC) development. Methods: The expression of circ_0003602, miR-149-5p, and solute carrier family 38 member 1 (SLC38A1) was detected by quantitative real-time polymerase chain reaction. RNase R assays were conducted to determine the characteristics of circ_0003602. CCK-8 assays, flow cytometry analysis, transwell invasion assays, wound healing assays and tube formation assays were employed to evaluate cell viability, apoptosis, invasion, migration, and angiogenesis. All protein levels were examined by Western blot or immunohistochemistry assay. The glutamine metabolism was monitored by corresponding glutamine, α-ketoglutarate and glutamate assay kits. Dual-luciferase reporter assay was utilized to confirm the targeted combination between miR-149-5p and circ_0003602 or SLC38A1. A xenograft tumor model was established to analyze the role of circ_0003602 in CRC tumor growth in vivo. Results: Circ_0003602 was upregulated in CRC tissues and cell lines. Circ_0003602 silencing suppressed CRC cell viability, migration, invasion, angiogenesis, and glutaminolysis; induced cell apoptosis in vitro; and blocked tumor growth in vivo. Moreover, circ_0003602 directly interacted with miR-149-5p to negatively regulate its expression, and circ_0003602 knockdown suppressed the malignant behaviors of CRC cells largely by upregulating miR-149-5p. MiR-149-5p directly bound to the 3' untranslated region of SLC38A1 to induce its degradation, and miR-149-5p overexpression reduced the malignant potential of CRC cells largely by downregulating SLC38A1. Circ_0003602 positively regulated SLC38A1 expression by sponging miR-149-5p in CRC cells. Conclusions: Circ_0003602 knockdown impedes CRC development by targeting the miR-149-5p/SLC38A1 axis, which provides a novel theoretical basis and new insights for CRC treatment.

Conversion of fungicide cyprodinil to salts with organic acids: preparation, characterization, advantages.

BACKGROUND: As an effective strategy to improve the basic properties of drugs, salt formation was less used in the field of pesticides than the medicine field. It is worth trying to improve the inherent shortcomings of cyprodinil (high Kow values; polymorphism) in this way to enhance its practicality. RESULTS: Eight cyprodinil salts (CYP-Salts) were prepared. The properties of CYP-Salts, including solubility in various solvents, polymorphic behavior, soil absorption, photolysis in aquatic water, in vitro fungicidal activity and curative activity, were assessed. It was observed that compared with those of cyprodinil, CYP-Salts had lower soil adsorption, while also having lower log Kow values and could be more easily photodegraded in water. That is, CYP-Salts have lower impacts on water bodies and aquatic organisms than cyprodinil. Three CYP-Salts showed higher in vitro antifungal activities and curative activity. CYP-Salts have enhanced practicality, as they could avoid possible agglomeration caused by recrystallization. CONCLUSION: Salt forming enhanced the properties of Cyprodinil in many aspects. CYP-Salts may potentially become a better substitute for cyprodinil. This study offers a more economical and effective strategy to prepare better alternatives to existing fungicides. © 2022 Society of Chemical Industry.

Zhizhu Decoction Alleviates Intestinal Barrier Damage via Regulating SIRT1/FoxO1 Signaling Pathway in Slow Transit Constipation Model Mice.

OBJECTIVE: To explore the possible effects and mechanism of Zhizhu Decoction (ZZD) on the pathophysiology of slow transit constipation (STC). METHODS: A total of 54 C57BL/6 mice was randomly divided into the following 6 groups by a random number table, including control, STC model (model), positive control, and low-, medium- and high-doses ZZD treatment groups (5, 10, 20 g/kg, namely L, M-, and H-ZZD, respectively), 9 mice in each group. Following 2-week treatment, intestinal transport rate (ITR) and fecal water content were determined, and blood and colon tissue samples were collected. Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate the morphology of colon tissues and calculate the number of goblet cells. To determine intestinal permeability, serum levels of lipopolysaccharide (LPS), low-density lipoprotein (LDL) and mannose were measured using enzyme-linked immunosorbent assay (ELISA). Western blot analysis was carried out to detect the expression levels of intestinal tight junction proteins zona-occludens-1 (ZO-1), claudin-1, occludin and recombinant mucin 2 (MUC2). The mRNA expression levels of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-4, IL-10 and IL-22 were determined using reverse transcription-quantitative reverse transcription reaction. Colon indexes of oxidative stress were measured by ELISA, and protein expression levels of colon silent information regulator 1/forkhead box O transcription factor 1 (SIRT1/FoxO1) antioxidant signaling pathway were detected by Western blot. RESULTS: Compared with the model group, ITR and fecal moisture were significantly enhanced in STC mice in the M-ZZD and H-ZZD groups (P<0.01). Additionally, ZZD treatment notably increased the thickness of mucosal and muscular tissue, elevated the number of goblet cells in the colon of STC mice, reduced the secretion levels of LPS, LDL and mannose, and upregulated ZO-1, claudin-1, occludin and MUC2 expressions in the colon in a dose-dependent manner, compared with the model group (P<0.05 or P<0.01). In addition, ZZD significantly attenuated intestinal inflammation and oxidative stress and activated the SIRT1/FoxO1 signaling pathway (P<0.05 or P<0.01). CONCLUSION: ZZD exhibited beneficial effects on the intestinal system of STC mice and alleviated intestinal inflammation and oxidative stress via activating SIRT1/FoxO1 antioxidant signaling pathway in the colon.

Identification of molecular subtypes and prognostic model to reveal immune infiltration and predict prognosis based on immunogenic cell death-related genes in lung adenocarcinoma.

Immunogenic cell death (ICD) has been increasingly indicated to be related to caners. However, ICD's role in Lung adenocarcinoma (LUAD) is still not well investigated. Clinical data along with associated mRNA expression profiles from LUAD cases were collected in TCGA and GEO databases. 13 ICD-related genes were identified. Relations of ICD-related genes expression with prognosis of patients, tumor immune microenvironment (TIME) was analyzed. Then, candidate genes were identified and the prognostic signature were constructed. Afterwards, one nomogram incorporating those chosen clinical data together with risk scores were built. Finally, the effect of HSP90AA1, one gene of the prognostic signature, on LUAD cell were analyzed. Two clusters were identified, which were designated as the ICD-high or -low subtype according to ICD-related genes levels. ICD-high subgroup showed good prognosis, high immune cell infiltration degrees, and enhanced immune response signaling activity compared with ICD-low subtype. Moreover, we established and verified the risk signature based on ICD-related genes. High risk group predicted poor prognosis of LUAD independently and presented negative association with immune score and immune status. Furthermore, nomogram contributed to the accurate prediction of LUAD prognostic outcome. Finally, HSP90AA1 levels were remarkably elevated within tumor cells in comparison with healthy pulmonary epithelial cells. HSP90α, HSP90AA1 protein product, promoted growth, migration, and invasion of LUAD cells. Molecular subtypes and prognostic model were identified by incorporating ICD-related genes, and it was related to TIME and might be adopted for the accurate prediction of LUAD prognosis.

Upregulated NORAD is implicated in apoptosis, inflammation, and oxidative stress in ulcerative colitis through the nuclear factor-κappaB signaling.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon. It has been discovered that long non-coding RNA activated by DNA damage (NORAD) is upregulated in UC patient-derived serums, but its functional mechanism in UC has not been disclosed. METHODS: Relative levels of NORAD in colonic mucosal tissues and TNF-α-stimulated human normal colonic mucosal cells (FHCs) were detected. Functional experiments were executed to evaluate the effects of NORAD silencing on TNF-α-induced FHC proliferation, apoptosis, inflammation, and oxidative stress. The molecular mechanism related to NORAD was predicted by starBase and confirmed by dual-luciferase reporter and RIP assays. RESULTS: Our data exhibited higher levels of NORAD in UC patient-derived colonic mucosal tissues and TNF-α-stimulated FHCs. Functional experiments presented that NORAD inhibition impaired TNF-α-induced FHC apoptosis, inflammation, and oxidative stress. NORAD acted as a miR-552-3p sponge, and miR-552-3p silencing weakened NORAD inhibition-mediated effects on TNF-α-induced FHC apoptosis, inflammation, and oxidative stress. Myeloid differentiation primary response gene 88 (MYD88) was verified as a miR-552-3p target, and MYD88 overexpression whittled miR-552-3p mimic-mediated inhibition on TNF-α-induced FHC apoptosis, inflammation, and oxidative stress. Notably, TNF-α-induced NORAD regulated the nuclear factor-κappaB (NF-κB) signaling via the miR-552-3p/MYD88 axis. CONCLUSION: NORAD participates in TNF-α-induced FHC apoptosis, inflammation, and oxidative stress via the NF-κB signaling via the miR-552-3p/MYD88 axis, offering new insights into the pathogenesis of UC.

Automated multi-filtration cleanup with nitrogen-enriched activated carbon material as pesticide multi-residue analysis method in representative crop commodities.

An automated multi-filtration cleanup (Auto m-FC) method with nitrogen-enriched activated carbon material based on modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) extracts was developed. It was applied to pesticide multi-residue analysis in six representative crop commodities. The automatic device was aimed to improve the cleanup efficiency and reduce manual operation workload in cleanup step. By controlling extracts volume, flow rate and Auto m-FC cycles, the device could finish cleanup process accurately. In this work, nitrogen-enriched activated carbon mixed with alternative sorbents and anhydrous magnesium sulfate (MgSO4) was packed in a column for Auto m-FC and followed by liquid chromatography with tandem mass spectrometric (LC-MS/MS) detection. This newly developed carbon material showed excellent cleanup performance. It was validated by analyzing 23 pesticides in six representative matrices spiked at two concentration levels of 10 and 100µg/kg. Water addition volume, salts, sorbents, Auto m-FC procedure including the flow rate and the Auto m-FC cycles for each matrix were optimized. Then, three general Auto m-FC methods were introduced to high water content, high oil and starch content, difficult commodities. Spike recoveries were within 82 and 106% and 1-14% RSD for all analytes in the tested matrices. Matrix-matched calibrations were performed with the coefficients of determination over 0.997 between concentration levels of 10 and 1000µg/kg. The developed method was successfully applied to the determination of pesticide residues in market samples.

Long-Term Prognosis of Spontaneous Intracerebral Hemorrhage on the Tibetan Plateau: A Prospective Cohort Study at 2 Hospitals.

BACKGROUND: Patterns of intracerebral hemorrhage (ICH) and outcomes in Tibetans are poorly understood. We aimed to investigate the long-term outcomes of Tibetan ICH patients. METHODS: This prospective study involved a consecutive series of ICH patients admitted within 1 month of onset to West China Hospital (WCH) on the Chengdu Plain or People's Hospital of Garzê (PHG) on the Tibetan Plateau between January 2013 and December 2013. Basic characteristics and functional outcomes were compared between PHG and WCH groups. RESULTS: Of the 843 cases included, 105 (12.5%) were from PHG and 738 (87.5%) were from WCH. Compared with patients from WCH, patients from PHG were older and had higher blood pressure on admission, and a greater proportion had hypertension (all P < 0.001). Among patients from PHG, the 1-year death rate was 30.5%, similar to that in WCH (P = 0.987), and the adjusted 3-month disability risk was 2.0-fold higher than for WCH patients, while the adjusted 1-year disability risk was 2.5-fold higher than for WCH patients (both P ≤ 0.05). The adjusted 3-month risk of disability/death was 2.1-fold higher in PHG patients than in WCH patients, while the adjusted 1-year risk was 2.4-fold higher (both P ≤ 0.05). CONCLUSIONS: Most cases of ICH on the Tibetan Plateau involve concomitant hypertension. Tibetan patients are at higher risk of disability or disability/death on follow-up than are patients from Chengdu Plain.

Modulation of the wettability of excipients by surfactant and its impacts on the disintegration and release of tablets.

OBJECTIVE: To investigate the modulation of the wettability of excipients by different types of surfactants and its impacts on the disintegration of tablets and drug release. MATERIALS AND METHODS: The critical micelle concentration (CMC) of surfactants, including sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS), dodecyl trimethyl ammonium bromide (DTAB), cetyltrimethyl ammonium bromide (CTAB) and polysorbate (Tween-20 and Tween-80), was obtained using the platinum ring method. Contact angles of surfactant solutions on the excipient compacts and double-distilled water on the mixture of surfactant and the other excipient (magnesium stearate (MgSt) or sodium alginate (SA)) were measured by the sessile drop technique. Besides, surface free energy of excipients was calculated by the Owens method. Finally, the disintegration of tablets and in vitro dissolution testing were performed according to the method described in USP. RESULTS AND DISCUSSION: The wettability of excipients could be enhanced to different extent with low concentration of surfactant solutions and maintained stable basically after CMC. For MgSt (hydrophobic excipient), the shorter the hydrophobic chain (C12, including SDS and DTAB), the better the wettability with the addition of surfactant in the formulation, leading to the shorter disintegration time of tablets and higher drug release rate. In contrast, the wettability of SA (hydrophilic excipient) was reduced by adding surfactant, resulting in the longer disintegration time of tablets and lower release rate. CONCLUSION: The modulation of the wetting of pharmaceutical excipients by surfactant had changed the disintegration time of tablets and drug release rate to a greater extent.

Characteristics of etiological diagnostic workup across the past 10 years in patients with spontaneous intracerebral hemorrhage in a large general hospital.

OBJECTIVE: A swift and accurate diagnosis of etiology would lay the foundation of targeted management for patients with spontaneous intracerebral hemorrhage (SICH). It is unclear what the status of diagnostic workup related to etiology is in Chinese hospitals which treat the majority of the hemorrhagic patients in the world. We aim to demonstrate characteristics on diagnostic workup implemented routinely in both departments of Neurology and Neurosurgery in patients with SICH. METHODS: We enrolled patients with SICH from March 2002 to December 2011 from Chengdu stroke registry. Data on diagnostic workup were extracted. RESULTS: A total of 2264 patients diagnosed as SICH with rapid neuroimaging (computed tomography (CT) or magnetic resonance imaging (MRI)) scan were included. Patients in the department of Neurosurgery had a lower median Glasgow Coma Scale (GCS) score and a longer median length of stay. They had a significantly lower proportion of hyperlipidemia and heart disease, but a higher proportion of hypertension, alcohol consumption and history of stroke (all p < 0.05). Following diagnostic workups were more frequently undertaken in the Neurological Department than in the neurosurgical Department: digital subtraction angiography (DSA), plain CT, plain MRI, carotid duplex ultrasound (all p < 0.001). However, computed tomography angiography (CTA), contrast-enhanced MRI, and brain biopsy (all p < 0.001) were implemented more in the Neurosurgical Department. While no difference in the proportion of magnetic resonance angiography (MRA) was found between the two departments, the intracranial vascular imaging (workup contains at least one of CTA, MRA and DSA) was performed more frequently in the Department of Neurosurgery (29.8% vs. 9.1%, p < 0.001). The independent predictors contribute to the implementation of vascular examinations were gender, age, GCS score on admission, department of patients admitted in and the year patients were hospitalized in (all p < 0.05). CONCLUSIONS: Younger patients, females, with severe stroke onset (evaluated by GCS score), admitted in Department of Neurosurgery and hospitalized in recent years had undertaken more examinations on intracranial vascular. It is an urgency to explore a practical scheme of diagnostic workup for the etiology of SICH.

Differences Between Vascular Structural Abnormality and Hypertensive Intracerebral Hemorrhage.

BACKGROUND: How the clinical characteristics and prognosis of various types of vascular structural abnormality-related intracerebral hemorrhage (ICH) differ from those of hypertensive ICH is poorly understood. This lack of understanding poses a problem for differential diagnosis and prognosis. METHODS: Patients diagnosed with ICH between January 2012 and February 2014 at 50 tertiary and secondary hospitals in China were enrolled into this prospective cohort study. Patients were classified as having vascular structural abnormality-related ICH or hypertensive ICH, and data on the demographics and clinical characteristics of each group were compared. Multivariate logistic regression was used to explore associations while controlling for other risk factors for good outcome and mortality. RESULTS: Data for 281 patients showed that vascular structural abnormality-related ICH usually occurred in lobar areas and affected patients who were younger and had higher Glasgow Coma Scale (GCS) scores than those with hypertensive ICH. Mortality and good outcome at 3 months after ICH were significantly better among patients with vascular structural abnormality-related ICH (3.4% and 77.2%) than among patients with hypertensive ICH (15.2% and 49.9%, both P < .001). Multivariate logistic regression identified the following independent predictors of mortality: lower GCS score, old age, presence of intraventricular hemorrhage, larger hematoma volume, and surgery treatment. The regression also identified several independent predictors of good outcome at 3 months: ICH etiology due to vascular structural abnormality, higher GCS score, younger age, and smaller hematoma volume. CONCLUSIONS: Patients with vascular structural abnormality-related ICH are more likely to experience better clinical outcomes than those with hypertensive ICH. GCS score, age, hematoma volume, and ICH etiology are independent predictors of ICH outcome.

Is diabetes a predictor of worse outcome for spontaneous intracerebral hemorrhage?

BACKGROUND AND PURPOSE: Diabetes is common in acute stroke and is associated with worse outcome in ischemic stroke, but its influence on intracerebral hemorrhage (ICH) remains controversial. We examined the association between diabetes and clinical outcome in a large hospitalized population of Chinese patients with ICH. METHODS: We prospectively enrolled patients with ICH who were admitted within 3 days of stroke onset from March 2002 to December 2010. Data were analyzed on demographic and clinical characteristics such as age, gender, vascular risk factors, Glasgow Coma Scale (GCS) score at admission, site of hemorrhage and surgical treatment. Patient characteristics, functional outcome according to the modified Rankin scale (mRS) and mortality were compared between patients with and without diabetes. RESULTS: Of the 1438 ICH patients included, 118 (8.2%) had diabetes and this subgroup showed a significantly higher proportion of hypertension (OR=1.98, 95% CI 1.33-2.96, P=0.001) and hyperlipidemia (OR=3.22, 95% CI 1.16-8.89, P=0.024). Patients were followed up for a mean of 147.48 ± 3.59 days. Cox regression suggested that diabetes was not a significant predictor of mortality in our cohort (P>0.05), and repeated-measures ANOVA showed that variance in mRS over the course of follow-up was similar between patients with and without diabetes (P=0.463). CONCLUSION: Our data suggest that diabetes in Chinese patients with ICH is not associated with increased mortality or functional outcome. Future studies are needed to clarify possible confounders affecting prognosis after ICH.

VSARICHS: a simple grading scale for vascular structural abnormality-related intracerebral haemorrhage.

BACKGROUND AND PURPOSE: Vascular structural abnormality-related intracerebral haemorrhage (VSARICH) accounts for 10-20% of cases of intracerebral haemorrhage (ICH), but none of the grading scales for primary ICH are reliable for VSARICH. This study aimed to propose a grading scale based on clinical and anatomical parameters to predict short-term clinical outcome. METHODS: Data were prospectively collected from patients with ICH recruited consecutively from 50 secondary and tertiary hospitals in China. Demographic and clinicopathological factors associated with mortality and good clinical outcome were identified and used to develop a grading scale for VSARICH. RESULTS: The VSARICH was 10.8% and 13% in the derivation (n=335) and validation (n=109) cohorts, respectively. Data from 307 patients with VSARICH in the derivation cohort were used to generate a VSARICH score (VSARICHS) system ranging from 0 to 9. Points were assigned based on the Glasgow Coma Scale (GCS) score on admission (GCS 3-4=4 points; 5-12=2 points; 13-15=0 points), age (≥80 years=2 points; 79-60=1 point; ≤59=0 points), presence of subarachnoid haemorrhage (yes=1 point; no=0 points) and presence of herniation (yes=2 points; no=0 points). VSARICHS showed good discrimination in the derivation cohort (area under the receiver operating characteristic curves, AUCs)AUCs 0.837 for good clinical outcome; 0.942 for mortality) and validation cohort (AUCs 0.813 for good clinical outcome; 0.930 for mortality). CONCLUSIONS: VSARICHS appears to be a reliable clinical scoring system that may prove useful for guiding risk stratification, clinical treatment and research.

Early versus delayed mobilisation for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Rebleeding is an important cause of death and disability in patients with aneurysmal subarachnoid haemorrhage (SAH). In order to prevent rebleeding, the preferred strategy is aneurysm ablation (removal) as early as possible. However, in clinical practice some patients are not suitable for surgical treatment, or prefer conservative treatments. In some countries, therefore, total bedrest for four to six weeks has been considered one of the basic interventions to avoid rebleeding. However, the influence of bedrest on outcome in patients with SAH is not well known. OBJECTIVES: To establish whether early mobilisation (less than four weeks after symptom onset) compared with delayed mobilisation (defined as patients staying in bed for at least four weeks after symptom onset) in patients with aneurysmal subarachnoid haemorrhage (SAH), who have not had or could not have any surgical treatment for the aneurysm, will increase the proportion of deaths from rebleeding. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 6), the Chinese Stroke Trials Register (May 2012), MEDLINE (1950 to June 2012), EMBASE (1980 to June 2012), Web of Science Conference Proceedings (1990 to May 2012), CINAHL (1982 to June 2012), AMED (1985 to June 2012), PEDro (May 2012), REHABDATA (May 2012) and CIRRIE Database of International Rehabilitation Research (May 2012). In addition, we searched five Chinese databases, ongoing trials registers and relevant reference lists. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) comparing early mobilisation (within four weeks after symptom onset) with delayed mobilisation (after four weeks). DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and exclusion. We resolved disagreements by discussion. MAIN RESULTS: In the absence of any suitable RCTs addressing this topic, we were unable to perform a meta-analysis. Data from recent observational studies suggested the period of greatest risk for rebleeding occurs more frequently in the early period, especially within 24 hours of the initial SAH. The impact of bedrest on aneurysm care should be clarified. AUTHORS' CONCLUSIONS: There are no RCTs or controlled trials that provide evidence for, or against, staying in bed for at least four weeks after symptom onset in patients with aneurysmal SAH, who have not had, or could not have, surgical treatment for the aneurysm. Treatment strategies to reduce the risk of rebleeding in SAH patients before aneurysm ablation, or in those not suitable for surgical treatment, or who prefer conservative treatments, deserve attention.

[Design and implementation of pupil auto-tracking system in the perimeter].

The pupil auto-tracking system is a key component of the full-automatic perimeter. Taking the advantage of integral image in counting characteristic value rapidly, we studied the relationship between training stages and total error detection rate based on the training of Adaboost strong classifier. Besides, a testing strategy of amplification detection window was introduced, and a multi-stage cascaded eye classifier for eye detection was proposed finally. It kept the same detection rate as the commonly trained strong classifier with a much lower error detection rate. In the meantime, the present article explaines the main arithmetic implement functions, as well as designs the motion control program for the jaw bracket system.