Protective role for C3aR in experimental chronic pyelonephritis.

Emerging evidence suggest that C3aR plays important roles in homeostasis, host defense and disease. Although it is known that C3aR is protective in several models of acute bacterial infections, the role for C3aR in chronic infection is largely unknown. Here we show that C3aR is protective in experimental chronic pyelonephritis. Global C3aR deficient (C3ar-/- ) mice had higher renal bacterial load, more pronounced renal histological lesions, increased renal apoptotic cell accumulation, tissue inflammation and extracellular matrix deposition following renal infection with uropathogenic E. coli (UPEC) strain IH11128, compared to WT control mice. Myeloid C3aR deficient (Lyz2-C3ar-/- ) mice exhibited a similar disease phenotype to global C3ar-/- mice. Pharmacological treatment with a C3aR agonist reduced disease severity in experimental chronic pyelonephritis. Furthermore, macrophages of C3ar-/- mice exhibited impaired ability to phagocytose UPEC. Our data clearly demonstrate a protective role for C3aR against experimental chronic pyelonephritis, macrophage C3aR plays a major role in the protection, and C3aR is necessary for phagocytosis of UPEC by macrophages. Our observation that C3aR agonist curtailed the pathology suggests a therapeutic potential for activation of C3aR in chronic infection.

Two new antimicrobial monoterpenoid indole alkaloids from the roots of Rauvolfia yunnanensis.

Two new monoterpenoid indole alkaloids 3-hydroxylochnerine (1) and 10-hydroxyvinorine (2) were isolated from the roots of Rauvolfia yunnanensis. Their structures were elucidated based on the analysis of spectroscopic data and ECD calculation. Both compounds exhibited potent antimicrobial activity against Bacillus subtilis and Escherichia coli, and their activities were comparable to the well-known antibacterial drug berberine.

Cerebral venous sinus thrombosis caused by traumatic brain injury complicating thyroid storm: a case report and discussion.

INTRODUCTION: Cerebral venous sinus thrombosis (CVST) is an uncommon cerebrovascular disease with diverse predisposing factors. We report a case of CVST caused by a thyroid storm induced by traumatic brain injury. CASE PRESENTATION: A 29-year-old male patient with a history of Graves' disease with hyperthyroidism presented to our hospital with head trauma of cerebral contusion and laceration in both frontal lobes confirmed by admission CT scan. He received mannitol to lower intracranial pressure, haemostatic therapy, and antiepileptic treatment. Eight days later, he presented with signs of thyroid storms, such as tachycardia, hyperthermia, sweating and irritation, and his thyroid function tests revealed high levels of TPO-Ab, TR-Ab, TG-Ab, FT3 and FT4. Then, he entered a deep coma. His brain CT showed a thrombosis of multiple venous sinuses, along with the opening of peripheral collateral vessels, congestive infarction with haemorrhage and brain swelling. He regained consciousness after treatment with antithyroid drugs, anticoagulants, respiratory support and a regimen of sedation/analgesia. After a half-year follow-up, most of the patient's blocked cerebral venous sinuses had been recanalized, but there were still some sequelae, such as an impaired fine motor performance of the right hand and verbal expression defects. CONCLUSIONS: CVST can be induced by thyroid storms, and trauma-related thyroid storms can develop on the basis of hyperthyroidism. The purpose of this case report is to raise clinicians' awareness and improve their ability to diagnose CVST early in patients with traumatic brain injury complicating thyroid storms to improve the neurological prognosis among similar patients.

Increased normalized lactate load is associated with higher mortality in both sepsis and non-sepsis patients: an analysis of the MIMIC-IV database.

BACKGROUND: The present study aimed to evaluate the association between normalized lactate load, an index that incorporates the magnitude of change and the time interval of such evolution of lactate, and 28-day mortality in sepsis and non-sepsis patients. We also compared the accuracy of normalized lactate load in predicting mortality between these two populations. METHODS: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database. We defined lactate load as the sum of the area under the lactate concentration curve; we also defined normalized lactate load as the lactate load divided by time. The performance of maximum lactate, mean lactate and normalized lactate load in predicting 28-day mortality in sepsis and non-sepsis patients were compared by receiver-operating characteristic curves analysis. RESULTS: A total of 21,333 patients were included (4219 sepsis and 17,114 non-sepsis patients). Non-survivors had significantly higher normalized lactate load than survivors in sepsis and non-sepsis patients. The maximum lactate, mean lactate, and normalized lactate load AUCs were significantly greater in sepsis patients than in non-sepsis patients. Normalized lactate load had the greatest AUCs in predicting 28-day mortality in both sepsis and non-sepsis patients. Sensitivity analysis showed that the AUC of normalized lactate load increased in non-sepsis patients when more lactate measurement was obtained, but it was not improved in sepsis patients. CONCLUSIONS: Normalized lactate load has the strongest predictive power compared with maximum or mean lactate in both sepsis and non-sepsis patients. The accuracy of normalized lactate load in predicting mortality is better in sepsis patients than in non-sepsis patients.

Effect of increased positive end-expiratory pressure on intracranial pressure and cerebral oxygenation: impact of respiratory mechanics and hypovolemia.

BACKGROUND: To evaluate the impact of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) in animals with different respiratory mechanics, baseline ICP and volume status. METHODS: A total of 50 male adult Bama miniature pigs were involved in four different protocols (n = 20, 12, 12, and 6, respectively). Under the monitoring of ICP, brain tissue oxygen tension and hemodynamical parameters, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O. Measurements were taken in pigs with normal ICP and normovolemia (Series I), or with intracranial hypertension (via inflating intracranial balloon catheter) and normovolemia (Series II), or with intracranial hypertension and hypovolemia (via exsanguination) (Series III). Pigs randomized to the control group received only hydrochloride instillation while the intervention group received additional chest wall strapping. Common carotid arterial blood flow before and after exsanguination at each PEEP level was measured in pigs with intracranial hypertension and chest wall strapping (Series IV). RESULTS: ICP was elevated by increased PEEP in both normal ICP and intracranial hypertension conditions in animals with normal blood volume, while resulted in decreased ICP with PEEP increments in animals with hypovolemia. Increasing PEEP resulted in a decrease in brain tissue oxygen tension in both normovolemic and hypovolemic conditions. The impacts of PEEP on hemodynamical parameters, ICP and brain tissue oxygen tension became more evident with increased chest wall elastance. Compare to normovolemic condition, common carotid arterial blood flow was further lowered when PEEP was raised in the condition of hypovolemia. CONCLUSIONS: The impacts of PEEP on ICP and cerebral oxygenation are determined by both volume status and respiratory mechanics. Potential conditions that may increase chest wall elastance should also be ruled out to avoid the deleterious effects of PEEP.

Association between normalized lactate load and mortality in patients with septic shock: an analysis of the MIMIC-III database.

BACKGROUND: An index of dynamic lactate change that incorporates both the magnitude of change and the time interval of such change, termed "normalized lactate load," may reflect the hypoxic burden of septic shock. We aimed to evaluate the association between normalized lactate load and 28-day mortality in adult septic shock patients. METHODS: Patients with septic shock were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Lactate load was defined as the sum of the area under the curve (AUC) of serial lactate levels using the trapezoidal rule, and normalized lactate load was defined as the lactate load divided by time. Receiver-operating characteristic curves were constructed to determine the performance of initial lactate, maximum lactate and normalized lactate load in predicting 28-day mortality. RESULTS: A total of 1371 septic shock patients were included, and the 28-day mortality was 39.8%. Non-survivors had significantly higher initial lactate (means ± standard deviations: 3.9 ± 2.9 vs. 2.8 ± 1.7 mmol/L), maximum lactate (5.8 ± 3.8 vs. 4.3 ± 2.2 mmol/L), lactate load (94.3 ± 71.8 vs. 61.1 ± 36.4 mmol·hr./L) and normalized lactate load (3.9 ± 3.0 vs. 2.5 ± 1.5 mmol/L, all p <  0.001). The AUCs of initial lactate, maximum lactate and normalized lactate load were 0.623 (95% confidence interval: 0.596-0.648, with a cut-off value of 4.4 mmol/L), 0.606 (0.580-0.632, with a cut-off value of 2.6 mmol/L) and 0.681 (0.656-0.706, with a cut-off value of 2.6 mmol/L), respectively. The AUC of normalized lactate load was significantly greater than both initial lactate and maximum lactate (all p <  0.001). In the multivariate logistic regression model, normalized lactate load was identified as an independent risk factor for 28-day mortality. CONCLUSIONS: Normalized lactate load is an independent risk factor for 28-day mortality in adult septic shock patients. Normalized lactate load had better accuracy than both initial and maximum lactate in determining the prognosis of septic shock patients.

Domino Reaction of Aromatic Aldehydes and 1,3-Indanediones for Construction of Bicyclo[2.2.2]octanes and Dibenzo[b,g]indeno[1',2':3,4]fluoreno[1,2-d]oxonines.

Triethylamine promoted the pseudo-five-component reaction of aromatic aldehyde with four molecules of 1,3-indanediones in refluxing ethanol to give unique polycyclic bicyclo[2.2.2]octane derivatives containing bridged- and spiro-indanone scaffolds in good yields. The mechanistic studies supported that the reaction included base-catalyzed cyclotrimerization of 1,3-indanedione to give an active cyclic diene and the sequential Diels-Alder reaction with in situ generated 2-arylidene-1,3-indanediones as electron-deficient dienophiles. On the other hand, the pseudo-four-component reaction of salicylaldehyde with 1,3-indanedione afforded the dibenzo[b,g]indeno[1',2':3,4]fluoreno[1,2-d]oxonines in high yields. This reaction clearly demonstrated the high efficiency, molecular convergence, atom-economy, and impressive selectivity of multicomponent reactions.

Predictive value of high-sensitive cardiac troponin T (cTnT) for adverse cardiac events in patients undergoing primary total knee arthroplasty (TKA).

BACKGROUND: Elevated high-sensitive cardiac troponin T (cTnT) is a well-known biomarker to predict cardiac events following non-cardiac surgery. However, further information regarding high-sensitive cTnT in orthopedic surgery, especially total knee arthroplasty (TKA), is not present yet. This study aims to gain further insight into the predictive value of high-sensitive cTnT in adverse cardiac events in patients accepting TKA. METHODS: We performed a prospective study in our hospital with the aim to enrolling 789 consecutive patients. Included patients who underwent TKA had mean ages of 65 years, and 64.9% were female. High-sensitive cTnT measurements were performed for study purposes before operation and on 1st postoperative days respectively. Postoperative cardiac events (POCE) 2 months and 2 years postoperatively were used to be evaluated for present study and defined short-term and long-term POCE respectively. The cut-off value of high-sensitive cTnT predicting patients at increased risks of POCE was evaluated by the Receiver Operating Characteristic (ROC) curve analysis. RESULTS: Mean preoperative, postoperative cTnT and difference value between preoperative and postoperative cTnT (D-cTnT) were 20, 32, 12 ng/L respectively. 2-month and 2-year cardiac event rate following TKA were 2.3% and 3.4%. Using difference value between preoperative and postoperative cTnT (D-cTnT) to predict short-term cardiac events, the best cut-off was 23 ng litre-1, with an AUC of 0.84 (95% CI: 0.79-0.89, p < 0.001), which was better in comparison to preoperative and postoperative cTnT. In contrast, using preoperative cTnT to predict long-term cardiac events, the best cut-off was 25 ng litre-1 with an AUC of 0.78 (95% CI: 0.73-0.83, p < 0.001), which was better in comparison to postoperative and D-cTnT. CONCLUSIONS: D-cTnT best predicted short-term POCE in comparison to preoperative and postoperative cTnT, while preoperative cTnT level best predicted long-term POCE in comparison to postoperative cTnT and D-cTnT.

[Prediction of Pathological Subtypes of Lung Adenocarcinoma with Pure Ground Glass Nodules by Deep Learning Model].

Objective To make a preliminary pathological classification of lung adenocarcinoma with pure ground glass nodules(pGGN)on CT by using a deep learning model. Methods CT images and pathological data of 219 patients(240 lesions in total)with pGGN on CT and pathologically confirmed adenocarcinoma were collected.According to pathological subtypes,the lesions were divided into non-invasive lung adenocarcinoma group(which included atypical adenomatous hyperplasia and adenocarcinoma in situ and micro-invasive adenocarcinoma)and invasive lung adenocarcinoma group.First,the lesions were outlined and labeled by two young radiologists,and then the labeled data were randomly divided into two datasets:the training set(80%)and the test set(20%).The prediction Results of deep learning were compared with those of two experienced radiologists by using the test dataset. Results The deep learning model achieved high performance in predicting the pathological types(non-invasive and invasive)of pGGN lung adenocarcinoma.The accuracy rate in pGGN diagnosis was 0.8330(95% CI=0.7016-0.9157)for of deep learning model,0.5000(95% CI=0.3639-0.6361)for expert 1,0.5625(95% CI=0.4227-0.6931)for expert 2,and 0.5417(95% CI=0.4029-0.6743)for both two experts.Thus,the accuracy of the deep learning model was significantly higher than those of the experienced radiologists(P=0.002).The intra-observer agreements were good(Kappa values:0.939 and 0.799,respectively).The inter-observer agreement was general(Kappa value:0.667)(P=0.000). Conclusion The deep learning model showed better performance in predicting the pathological types of pGGN lung adenocarcinoma compared with experienced radiologists.

Real-time generation of dynamically patterned cholesteric liquid crystal fingerprint textures based on photoconductive effect.

We present a convenient approach to facilitate the real-time generation of updatable dynamically patterned cholesteric liquid crystal (CLC) fingerprint textures based on photoconductive effect. The photoconductive Bi12SiO20 (BSO) substrate acts as virtual electrode to obtain the desired states of CLCs by both electric and light fields. Owing to different boundary conditions, the switching of four states; that is, planar, fingerprint, metastable, and homeotropic states, and the rotation of fingerprint stripes can be achieved in planar alignment (PA) cell and hybrid alignment (HA) cell, respectively. With the aid of a digital micro-mirror (DMD)-based exposure system, binary and gray-scale images were successfully written and updated by light upon suitable voltages. This work provides an alternative approach to photoaddress CLC fingerprint patterns, without needing special photoalignment agents or photoresponsitive chiral dopants. We expect that it could be employed in the manipulation of nano/micro-objects by light.

Selective synthesis of spirooxindoles via a two-step reaction of N-phenacylpyridinium bromide, 1,3-indanedione and N-alkylisations.

The three-component reaction of 1,3-indanedione and N-alkylisatins with two molecular N-phenacylpyridinium salts in dry acetonitrile in the presence of triethylamine resulted in unique functionalized spiro[indoline-3,4'-naphtho[1,2-b]furan] derivatives in good yields, which were successfully converted to spiro[indoline-3,2'-naphthalen]-4'-yl acetate derivatives by acylation with acetyl chloride in methylene dichloride and alkoxy-substituted spiro[benzo[h]chromene-5,3'-indolines] by acid-catalyzed etherification reaction in alcohol. The reaction mechanism involved the sequential cycloaddition of the in situ-generated pyridinium ylide to dipolarophilic enone, ring-opening of 1,3-indanedione, and selective annulation.

Total saponins of Bolbostemma paniculatum (maxim.) Franquet exert antitumor activity against MDA-MB-231 human breast cancer cells via inhibiting PI3K/Akt/mTOR pathway.

BACKGROUND: The aim of the present study was to examine the effects of the Bolbostemma paniculatum (Maxim.) Franquet (BP) active compound, BP total saponins (BPTS), on MDA-MB-231 cells, and investigate the underlying mechanism regarding BPTS-mediated attenuation of the PI3K/Akt/mTOR pathway. METHODS: The effect of BPTS on cytotoxicity, induction of apoptosis and migration on MDA-MB-231 cells at three different concentrations was investigated. A CCK-8 assay, wound-healing assay and flow cytometry were used to demonstrate the effects of BPTS. Additionally, expression of the primary members of the PI3K/Akt/mTOR signaling pathway was assessed using western blotting. To verify the underlying mechanisms, a PI3K inhibitor and an mTOR inhibitor were used. RESULTS: BPTS inhibited proliferation of MDA-MB-231 cells with an IC50 value of 10 µg/mL at 48 h. BPTS inhibited migration of MDA-MB-231 cells, and the western blot results demonstrated that BPTS reduced p-PI3K, p-Akt and p-mTOR protein expression levels in MDA-MB-231 cells. Additionally, the results were confirmed using a PI3K inhibitor and an mTOR inhibitor. BPTS decreased proliferation and migration of MDA-MB-231 cells possibly through inhibiting the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: The results highlight the therapeutic potential of BPTS for treating patients with triple-negative breast cancer.

Ultrasound Combined with Microbubbles Enhances the Effects of Methylprednisolone in Lipopolysaccharide-Induced Human Mesangial Cells.

A novel drug delivery system mediated by ultrasound (US) combined with microbubbles (MBs) (US+MB) could improve local drug concentration to enhance its efficacy. To investigate the influence of US+MB on methylprednisolone (MP), the effect of US+MB combined with MP (US+MB+MP) on lipopolysaccharide (LPS)-induced human mesangial cells (HMCs) and the underlying mechanism were explored in this study. The results revealed that HMCs treated with LPS underwent significant proliferation and exhibited an increase in nuclear transcription factor-κB (NF-κB) and transforming growth factor-ß1 (TGF-ß1) expression and a decrease in cellular apoptosis. This effect was significantly inhibited by MP (30-100 µg/ml), US combined with MBs (3.22 × 107 and 8.05 × 107 bubbles/ml), and US combined with both MBs (1.29 × 107 bubbles/ml) and MP (12 µg/ml) (US+MB1+MP12). The effect of US+MB1+MP12 was better than the effect of 12 µg/ml of MP alone and was similar to the effect of 100 µg/ml of MP. Additionally, the intracellular free MP content was significantly higher in the US+MB1+MP12 group than in the MP12 group. US combined with MBs not only inhibited LPS-induced HMC proliferation and NF-κB and TGF-ß1 expression and increased cellular apoptosis but also synergized with the pharmacologic effect of MP. The mechanism is partially due to the US-assisted MB local drug delivery and the anti-inflammatory effect induced by US combined with MBs.

Photoalignment of dye-doped cholesteric liquid crystals for electrically tunable patterns with fingerprint textures.

We present a convenient photoalignment approach to fabricate rewritable fingerprint textures with designed geometrical patterns based on methyl red doped cholesteric liquid crystals (MDCLCs). MDCLC systems with/without nanoparticles of polyhedral oligomeric silsesquioxanes (POSS) were employed to realize two types of sophisticated binary patterns, respectively. Based on the understanding of involved mechanisms related to boundary conditions and middle-layer theory, we demonstrated the precise manipulation of fingerprint patterns by varying the fingerprint grating vectors in different domains. Notably, the hybrid-aligned liquid crystal configuration induced by POSS nanoparticles, which leads to the electrically rotatable grating, can be converted into the planar-aligned configuration by the adsorption of photoexcited methyl red molecules onto the indium-tin-oxide (ITO) surface. In this manner, the dynamic voltage-dependent behavior of fingerprint gratings is altered from the rotation mode (R-mode) to the on-off mode (O-mode).

Intracranial pressure responsiveness to positive end-expiratory pressure in different respiratory mechanics: a preliminary experimental study in pigs.

BACKGROUND: Respiratory mechanics affects the effect of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP). Respiratory mechanics of the lung and the chest wall was not differentiated in previous studies. In the present study, we investigated the influence of the following possible determinants of ICP responsiveness to PEEP: chest wall elastance (ECW), lung elastance (EL), and baseline ICP. METHODS: Eight healthy Bama miniature pigs were studied. The increase of EL was induced by instillation of hydrochloride, and the increase of ECW was induced by strapping the animals' chest wall and abdomen. A balloon-tipped catheter was placed intracranially for inducing intracranial hypertension. Six experimental conditions were investigated in sequence: 1) Normal; 2) Stiff Chest Wall; 3) Lung Injury; 4) Lung Injury + Stiff Chest Wall; 5) Lung Injury + Stiff Chest Wall + Intracranial Hypertension and 6) Lung Injury + Intracranial Hypertension. PEEP was gradually increased in a 5 cm H2O interval from 5 to 25 cm H2O in each condition. Blood pressure, central venous pressure, ICP, airway pressure and esophageal pressure were measured. RESULTS: Hydrochloride instillation significantly increased EL in conditions with lung injury. ECW significantly increased in the conditions with chest wall and abdomen strapping (all p <  0.05). ICP significantly increased with increments of PEEP in all non-intracranial hypertension conditions (p <  0.001). The greatest cumulative increase in ICP was observed in the Stiff Chest Wall condition (6 [5.3, 6.8] mm Hg), while the lowest cumulative increase in ICP was observed in the Lung Injury condition (2 [1.3, 3.8] mm Hg). ICP significantly decreased when PEEP was increased in the intracranial hypertension conditions (p <  0.001). There was no significant difference in cumulative ICP change between the two intracranial hypertension conditions (p = 0.924). CONCLUSIONS: Different respiratory mechanics models can be established via hydrochloride induced lung injury and chest wall and abdominal strapping. The effect of PEEP on ICP is determined by respiratory mechanics in pigs with normal ICP. However, the responsiveness of ICP to PEEP is independent of respiratory mechanics when there is intracranial hypertension.

Intracranial pressure responsiveness to positive end-expiratory pressure is influenced by chest wall elastance: a physiological study in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Respiratory system elastance (ERS) is an important determinant of the responsiveness of intracranial pressure (ICP) to positive end-expiratory pressure (PEEP). However, lung elastance (EL) and chest wall elastance (ECW) were not differentiated in previous studies. We tested the hypothesis that patients with high ECW or a high ECW/ERS ratio have greater ICP responsiveness to PEEP. METHODS: An esophageal balloon catheter was placed to measure esophageal pressure. PEEP was increased from 5 to 15 cmH2O. Airway pressure and esophageal pressure were measured and EL, ECW and ERS were calculated at the two PEEP levels. Patients were classified into either an ICP responder group or a non-responder group based on whether the change of ICP after PEEP adjustment was greater than or less than the median of the overall study population. RESULTS: The magnitude of the increase in esophageal pressure (median [interquartile range]) at end-expiratory occlusion was significantly increased in the responder group compared with that in the non-responder group (4.1 [2.7-4.1] versus 2.7 [0.0-2.7] cmH2O, p = 0.033) after PEEP adjustment. ECW and the ECW/ERS ratio were significantly higher in ICP responders than in non-responders at both low PEEP (p = 0.021 and 0.017) and high PEEP (p = 0.011 and 0.025) levels. No significant differences in ERS and EL were noted between the two groups at both PEEP levels. CONCLUSIONS: Patients with greater ICP responsiveness to increased PEEP exhibit higher ECW and a higher ECW/ERS ratio, suggesting the importance of ECW monitoring.

ANGPTL8/betatrophin alleviates insulin resistance via the Akt-GSK3ß or Akt-FoxO1 pathway in HepG2 cells.

Angiopoietin-like protein 8 (ANGPTL8)/betatrophin, a newly identified protein, is primarily expressed in the liver and regulates the glucose metabolic transition during fasting and re-feeding in mice with or without insulin resistance. These findings strongly suggest that ANGPTL8/betatrophin could be a novel glucose-lowering candidate medicine for type 2 diabetes. However, the molecular mechanisms by which ANGPTL8/betatrophin regulates glucose metabolism are poorly understood in human. Two sub-clones of HepG2 cells, ANGPTL8/betatrophin knockouts and ANGPTL8/betatrophin over-expressors, were established using TALENs (transcription activator-like effector nucleases) and through stable transfection, respectively. Over-expression of ANGPTL8/betatrophin enhanced the insulin-stimulated activation of the Akt-GSK3ß or Akt-FoxO1 pathway, no matter whether the cells were present with insulin resistance or not. In contrast, knockout of ANGPTL8/betatrophin did not affect the Akt-GSK3ß or Akt-FoxO1 pathway unless the HepG2 cells were preset with insulin resistance. Our results suggest that ANGPTL8/betatrophin might play an important role in glucose metabolism in the context of insulin resistance.

Bispectral Index Can Reliably Detect Deep Sedation in Mechanically Ventilated Patients: A Prospective Multicenter Validation Study.

BACKGROUND: Excessively deep sedation is prevalent in mechanically ventilated patients and often considered suboptimal. We hypothesized that the bispectral index (BIS), a quantified electroencephalogram instrument, would accurately detect deep levels of sedation. METHODS: We prospectively enrolled 90 critically ill mechanically ventilated patients who were receiving sedation. The BIS was monitored for 24 hours and compared with the Richmond Agitation Sedation Scale (RASS) evaluated every 4 hours. Deep sedation was defined as a RASS of -3 to -5. Threshold values of baseline BIS (the lowest value before RASS assessment) and stimulated BIS (the highest value after standardized assessment) for detecting deep sedation were determined in a training set (45 patients, 262 RASS assessments). Diagnostic accuracy was then analyzed in a validation set (45 patients, 264 RASS assessments). RESULTS: Deep sedation was only prescribed in 6 (6.7%) patients, but 76 patients (84.4%) had at least 1 episode of deep sedation. Thresholds for detecting deep sedation of 50 for baseline and 80 for stimulated BIS were identified, with respective areas under the receiver-operating characteristic curve of 0.771 (95% confidence interval, 0.714-0.828) and 0.805 (0.752-0.857). The sensitivity and specificity of baseline BIS were 94.0% and 66.5% and of stimulated BIS were 91.0% and 66.5%. When baseline and stimulated BIS were combined, the sensitivity, specificity, and clinical utility index were 85.0% (76.1%-91.1%), 85.9% (79.5%-90.7%), and 66.9% (57.8%-76.0%), respectively. CONCLUSIONS: Combining baseline and stimulated BIS may help detect deep sedation in mechanically ventilated patients.

Combination of intramedullary rod, wrapping bone grafting and Ilizarov's fixator for the treatment of Crawford type IV congenital pseudarthrosis of the tibia: mid-term follow up of 56 cases.

BACKGROUND: The purpose of this study was to investigate the initial union rate, refracture rate and residual deformities of congenital pseudarthrosis of the tibia (CPT), using combined surgery including pseudarthrosis resection, intramedullary rodding, autogenous iliac bone grafting and Ilizarov's fixator, with a mean 5.2 years follow-up. METHODS: We retrospectively reviewed the records and diagrams of patients with Crawford type IV congenital pseudarthrosis of the tibia between February 2007 and March 2010. Patients managed by pseudarthrosis resection, intramedullary rod of the tibia, wrapping autogenous iliac bone grafting and Ilizarov's fixator were enrolled. We evaluated the bone union rate, tibial alignment, limb length discrepancy (LLD), valgus deformity of the ankle and the frequencies of refracture during period of follow-up. RESULTS: There were 56 cases enrolled in the study, with a mean follow-up 5.2 years (range, 3 to 6.7 years). The mean age of the patients at surgery was 3.5 years (range, 1.5 to 12.4 years). Fifty (89.2 %) of the 56 patients had primary bone union at site of pseudarthrosis, while 5 obtained union after second surgery and 1 failed. The average time spent to obtain pseudarthrosis initial union was 4.5 months (range, 3.0 to 10.0 months) and mean duration of Ilizarov treatment was 4.7 months (range, 3.2 to 10.4 months). Eleven (19.6 %) patients had proximal tibial valgus with a mean angle of 9.5° (range, 5 to 24°), while 10 (17.9 %) patients had ankle valgus deformities with a mean of 12.3° (range, 6 to 21°). Sixteen (28.6 %) patients had an average 2.2 cm LLD (range, 1.5-4.2 cm). Of the 50 cases who obtained initial bone union of pseudarthrosis, 13 (26.0 %) had refracture which need cast immobilization or secondary surgery. CONCLUSIONS: This combined surgery obtained initial union rate of 89.2 % at primary surgery while the refracture rate is 26.0 %. However, residual deformities such as proximal tibial valgus, LLD and ankle valgus were also existed which should be pay more attention to and dealt with. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov under the name "The Effect of Combined Surgery in Management of Congenital Pseudarthrosis of Tibia" ( NCT02640040 ), which was released on August 31, 2015.

Ultrasound measurement of optic nerve diameter and optic nerve sheath diameter in healthy Chinese adults.

BACKGROUND: Measurement of optic nerve sheath diameter (ONSD) is a fast and non-invasive method in detecting elevated intracranial pressure. However, the reported normal range of ONSD was inconsistent. The objective of the study was to determine the normal range of ONSD in healthy Chinese adults. METHODS: Eyeball transverse diameter (ETD), optic nerve diameter (OND), and ONSD were measured by ultrasound examination in healthy adult volunteers. The OND and ONSD were assessed 3 mm behind the globe. The section showing maximal transverse diameter of the eyeball was frozen and the diameter was measured. Each ETD, OND and ONSD was examined twice and the mean value was calculated. RESULTS: A total of 519 healthy volunteers were included in the study. The median (interquartile range) of ETD, OND and ONSD were 22.3 (21.6 to 23.1) mm, 3.2 (2.9 to 3.4) mm, and 5.1 (4.7 to 5.4) mm, respectively. The 95% percentile of ONSD was 5.9 mm. There was no significant difference in ETD, OND or ONSD between male and female, or between left and right eye. ONSD was significantly correlated with OND (r = 0.62, P < 0.001), and the median OND/ONSD ratio (interquartile range) was 0.63 (0.59 to 0.67). CONCLUSIONS: The median and the 95% percentile of sonographic measurement of ONSD are 5.1 mm and 5.9 mm in healthy Chinese adults. The ONSD is correlated with OND, while independent of gender, age, height, weight and ETD. The median OND/ONSD ratio is 0.63 and this parameter warrants further investigation in patients with brain injury.