Upgrade of laser pump time-resolved X-ray probes in Beijing synchrotron.

The upgrade of the laser pump time-resolved X-ray probes, namely time-resolved X-ray absorption spectroscopy (TR-XAS) and X-ray diffraction (TR-XRD), implemented at the Beijing Synchrotron Radiation Facility, is described. The improvements include a superbunch fill, a high-efficiency fluorescence collection, an efficient spatial overlap protocol and a new data-acquisition scheme. After upgrade, the adequate TR-XAS signal is now obtained in a 0.3 mM solution, compared with a 6 mM solution in our previous report. Furthermore, to extend application in photophysics, the TR-XAS probe is applied on SrCoO2.5 thin film. And for the first time, TR-XAS is combined with TR-XRD to simultaneously detect the kinetic trace of structural changes in thin film.

Multimodal intraoperative monitoring during surgical correction of scoliosis to avoid neurologic damage.

The purpose of this study was to evaluate the application of multimodal intraoperative monitoring (MIOM) system in patients with congenital scoliosis (CS) and adolescent idiopathic scoliosis (AIS).Twelve patients who underwent posterior surgical correction of scoliosis for CS and AIS from June 2014 to July 2018 were enrolled in this study. During the operation, we monitored the functional status of the spinal cord by MIOM. An abnormal somatosensory evoked potential was defined as a prolonged latency of more than 10% or a peak-to-peak amplitude decline of more than 50% when compared to baseline. An abnormal transcranial motor evoked potential (TcMEP) was defined as a TcMEP amplitude decrease of more than 50%. A normal triggered electromyography response, which presented with the absence of an electrical response on stimulation at 8.2 mA, indicated that the pedicle screw was not in contact with the spinal cord or nerve root.A total of 12 patients underwent MIOM surgery, of which 9 patients with negative MIOM had no significant deterioration of neurological function postoperatively, and exhibited satisfactory surgical correction of scoliosis during follow-ups. However, the remaining 3 patients suffered from MIOM events, 2 patients had normal neurological function, and 1 patient had deteriorated neurological function postoperatively.Using MIOM in CS and AIS surgery could promptly detect iatrogenic neurological injury at the early stage. Therefore, rapid response by appropriate intraoperative interventions can be taken to minimize the injury. Besides, stable MIOM recordings encourage surgeons to correct scoliosis even when the Cobb angle of scoliosis was extremely large.

Combined 3D rapid prototyping and computer navigation facilitate surgical treatment of congenital scoliosis: A case report and description of technique.

RATIONALE: This study describes the technique of combined Orbic 3D navigation (O3DN) and 3D rapid prototyping (3DRP) to assist surgical correction of congenital scoliosis. PATIENT CONCERNS: A 12-year-old boy with congenital scoliosis. His father brought him to our hospital upon noticing the boy's asymmetry of the trunk. DIAGNOSES: Congenital scoliosis. INTERVENTIONS: O3DN and 3DRP were used to assist correction surgery in this patient. OUTCOMES: The Cobb angle of segmental scoliosis (T8-L2) was 46.9° preoperatively and 2.3° at the last postoperative follow-up; correction was 95.1%. The average segmental kyphosis (T5-T12) was 45.2° preoperatively and 18.6° at the postoperative follow-up; correction was 58.9%. The preoperative sagittal imbalance of 56.2 mm was improved to 9.7 mm. The mean distance between the center sacral vertical line and the C7 plumb line was reduced from 5.7 to 4.1 mm. Operative time and bleeding volume was impressively little, with no misplacement of pedicle screws or other surgical complications. LESSONS: Combined 3DRP and O3DN helped achieve satisfactory correction for this case of congenital scoliosis. The application of 3DRP aided by O3DN in surgical treatment of congenital scoliosis can reduce operative time, lessen blood loss, reduce screw misplacement, and avoid neurovascular damage. However, patients' hospital costs were greater. Our lessons learnt are that the relative position between the tracker and the pedicle must be static to ensure the accuracy of the whole system during the entire operation.

Development of picosecond time-resolved X-ray absorption spectroscopy by high-repetition-rate laser pump/X-ray probe at Beijing Synchrotron Radiation Facility.

A new setup and commissioning of transient X-ray absorption spectroscopy are described, based on the high-repetition-rate laser pump/X-ray probe method, at the 1W2B wiggler beamline at the Beijing Synchrotron Radiation Facility. A high-repetition-rate and high-power laser is incorporated into the setup with in-house-built avalanche photodiodes as detectors. A simple acquisition scheme was applied to obtain laser-on and laser-off signals simultaneously. The capability of picosecond transient X-ray absorption spectroscopy measurement was demonstrated for a photo-induced spin-crossover iron complex in 6 mM solution with 155 kHz repetition rate.

Early diagnosis and severity assessment of acute pancreatitis (AP) using MR elastography (MRE) with spin-echo echo-planar imaging.

PURPOSE: To evaluate the accuracy of magnetic resonance elastography (MRE) in comparison to contrast-enhanced computed tomography (CE-CT) for early diagnosis and prediction of severity in acute pancreatitis (AP). MATERIALS AND METHODS: This cross-sectional prospective study included 76 patients with suspected AP who underwent both CE-CT and 3.0T MRE within 24 hours of hospital admission. Pancreatic stiffness, CT severity index (CTSI), Acute Physiology and Chronic Health Evaluation (APACHE)-II, and Bedside Index for Severity in AP (BISAP) scores were comparatively evaluated using data from the first 24 hours of admission, and diagnosis and severity of AP were confirmed according to the revised Atlanta Classification (2012). The accuracy of MRE for predicting disease severity was compared with that of CE-CT and the clinical scoring systems using area under the receiver-operating curve (AUC) analysis. RESULTS: AP was confirmed in 56/76 patients (73.7%). Pancreatic stiffness values of >1.47 kPa showed significantly better diagnostic performance than CE-CT (AUC: 0.993 vs. 0.818, P < 0.001) along with greater sensitivity (96.4% vs. 78.6%, P = 0.006) and accuracy (96.1% vs. 81.6%, P = 0.007). Ten patients (10/76; 13.2%) had clinically severe AP. The accuracy of pancreatic stiffness >2.47 kPa was comparable to that of the CTSI, APACHE-II and BISAP scores for predicting severe AP (accuracy = 85.5%, 75.0%, 88.2%, and 78.9%, respectively). The pairwise comparisons were not significant after Bonferroni correction (P < 0.008 [0.05/6]), with P values of 0.008 (MRE vs. CTSI), 0.823 (MRE vs. APACHE-II) and 0.414 (MRE vs. BISAP). CONCLUSION: Early MRE is a useful, noninvasive method for both diagnosis and early severity assessment of AP. We recommend MRE at hospital admission for initial evaluation of AP. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1311-1319.

Implementation of ultrafast X-ray diffraction at the 1W2B wiggler beamline of Beijing Synchrotron Radiation Facility.

The implementation of a laser pump/X-ray probe scheme for performing picosecond-resolution X-ray diffraction at the 1W2B wiggler beamline at Beijing Synchrotron Radiation Facility is reported. With the hybrid fill pattern in top-up mode, a pixel array X-ray detector was optimized to gate out the signal from the singlet bunch with interval 85 ns from the bunch train. The singlet pulse intensity is ∼2.5 × 10(6) photons pulse(-1) at 10 keV. The laser pulse is synchronized to this singlet bunch at a 1 kHz repetition rate. A polycapillary X-ray lens was used for secondary focusing to obtain a 72 µm (FWHM) X-ray spot. Transient photo-induced strain in BiFeO3 film was observed at a ∼150 ps time resolution for demonstration.

Magnetic Resonance Elastography for the Evaluation of Liver Fibrosis in Chronic Hepatitis B and C by Using Both Gradient-Recalled Echo and Spin-Echo Echo Planar Imaging: A Prospective Study.

OBJECTIVES: Magnetic resonance elastography (MRE) with three-dimensional spin-echo echo planar imaging (3D-SE-EPI) is a newly emerging noninvasive method for assessing liver fibrosis. We hypothesized that 3D-SE-EPI might have better diagnostic accuracy than conventional two-dimensional gradient-recalled echo (2D-GRE). METHODS: We prospectively included 179 consecutive patients with chronic hepatitis B (CHB) or C (CHC) who underwent both MRE and liver biopsy. Liver stiffness was measured by both 3D-SE-EPI and 2D-GRE for staging biopsy-proven liver fibrosis (using METAVIR scores). A receiver-operating characteristic analysis using the area under the receiver-operating characteristic curve (AUC) was used to compare the diagnostic performance in predicting liver fibrosis between these two techniques, and compared them to serum markers of fibrosis. RESULTS: The technical failure rate of 3D-SE-EPI (2.2%, n=4/179) was lower compared with 2D-GRE (8.3%, n=15/179). The stiffness measured by 3D-SE-EPI was slightly lower compared with 2D-GRE, with the mean difference of 0.57 kPa (Bland and Altman plot, 95% limits of agreement: -0.32 and 1.45 kPa). AUCs for the characterization of ≥F1, ≥F2, ≥F3, and F4 were 0.957 (95% confidence interval (CI): 0.913-0.983), 0.971 (0.932-0.991), 0.991 (0.961-0.999), and 0.979 (0.942-0.995) for 3D-SE-EPI, which was slightly higher compared with the AUCs for 2D-GRE at each fibrosis stage (0.948 (0.901-0.977), 0.959 (0.915-0.981), 0.979 (0.943-0.995), and 0.976 (0.938-0.994), respectively), although none reached statistical significance (P=0.160-0.585). In an "intention-to-diagnose" analysis, the diagnostic accuracy (the proportion of well-classified patients) by EPI (86.7-91.3%, n=169) was higher compared with GRE (80.9-82.1%, n=158) after applying optimal cutoffs. Both 3D-SE-EPI and 2D-GRE performed better than serum fibrosis markers. CONCLUSIONS: With respect to 2D-GRE, 3D-SE-EPI has the advantage of lower failure rate with equivalent high diagnostic performance for staging liver fibrosis in CHB/CHC patients, and thus more helpful for those challenging cases in 2D-GRE.

Evolving Molecular Genetics of Glioblastoma.

OBJECTIVE: To summary the recent advances in molecular research of glioblastoma (GBM) and current trends in personalized therapy of this disease. DATA SOURCES: Data cited in this review were obtained mainly from PubMed in English up to 2015, with keywords "molecular", "genetics", "GBM", "isocitrate dehydrogenase", "telomerase reverse transcriptase", "epidermal growth factor receptor", "PTPRZ1-MET", and "clinical treatment". STUDY SELECTION: Articles regarding the morphological pathology of GBM, the epidemiology of GBM, genetic alteration of GBM, and the development of treatment for GBM patients were identified, retrieved, and reviewed. RESULTS: There is a large amount of data supporting the view that these recurrent genetic aberrations occur in a specific context of cellular origin, co-oncogenic hits and are present in distinct patient populations. Primary and secondary GBMs are distinct disease entities that affect different age groups of patients and develop through distinct genetic aberrations. These differences are important, especially because they may affect sensitivity to radio- and chemo-therapy and should thus be considered in the identification of targets for novel therapeutic approaches. CONCLUSION: This review highlights the molecular and genetic alterations of GBM, indicating that they are of potential value in the diagnosis and treatment for patients with GBM.

Association of sterol regulatory element binding protein 2 and insulin-like growth factor binding protein 3 genetic polymorphisms with avascular necrosis of the femoral head in the Chinese population.

BACKGROUND: Sterol regulatory element binding protein (SREBP)-2 plays a key role in lipid homeostasis by stimulating gene expression of cholesterol biosynthetic pathways. The insulin-like growth factor binding protein (IGFBP) family regulates growth and metabolism, especially bone cell metabolism, and correlates with osteonecrosis. However, association of their gene polymorphisms with risk of avascular necrosis of the femoral head (ANFH) has rarely been reported. We determined whether SREBP-2 and IGFBP-3 gene polymorphisms were associated with increased ANFH risk in the Chinese population. METHODS: Two single nucleotide polymorphisms of SREBP2 gene, rs2267439 and rs2267443, and one of IGFBP-3 gene, rs2453839, were selected and genotyped in 49 ANFH patients and 42 control individuals by direct sequencing assay. RESULTS: The frequencies of rs2267439 TT and rs2267443 GA of SREBP2 and rs2453839 TT and CT of IGFBP-3 in the ANFH group showed increased and decreased tendencies (against normal control group), respectively. Interaction analysis of genes revealed that the frequency of carrying rs2267439 TT and rs2267443 GA genotypes of SREBF-2 in ANFH patients was significantly higher than in the control group (P < 0.05). Association analysis between polymorphisms and clinical phenotype demonstrated that the disease course in ANFH patients with the rs2453839 TT genotype of IGFBP-3 was significantly shorter than that of CT + CC carriers (P < 0.01). CT + CC genotype frequency in patients with stage III/IV bilateral hip lesions was significantly higher than in those with stage III/IV unilateral lesions and stage II/III bilateral lesions (P < 0.05 - 0.02). CONCLUSIONS: Our results suggested that interaction of SREBP-2 gene polymorphisms and the relationship between the polymorphisms and clinical phenotype of IGFBP-3 were closely related to increased ANFH risk in the Chinese population. The most significant finding was that the CT + CC genotype carriers of IGFBP-3 rs2453839 were highly associated with the development of ANFH.

SUMO modification regulates inactivation of the voltage-gated potassium channel Kv1.5.

The voltage-gated potassium (Kv) channel Kv1.5 mediates the I(Kur) repolarizing current in human atrial myocytes and regulates vascular tone in multiple peripheral vascular beds. Understanding the complex regulation of Kv1.5 function is of substantial interest because it represents a promising pharmacological target for the treatment of atrial fibrillation and hypoxic pulmonary hypertension. Herein we demonstrate that posttranslational modification of Kv1.5 by small ubiquitin-like modifier (SUMO) proteins modulates Kv1.5 function. We have identified two membrane-proximal and highly conserved cytoplasmic sequences in Kv1.5 that conform to established SUMO modification sites in transcription factors. We find that Kv1.5 interacts specifically with the SUMO-conjugating enzyme Ubc9 and is a target for modification by SUMO-1, -2, and -3 in vivo. In addition, purified recombinant Kv1.5 serves as a substrate in a minimal in vitro reconstituted SUMOylation reaction. The SUMO-specific proteases SENP2 and Ulp1 efficiently deconjugate SUMO from Kv1.5 in vivo and in vitro, and disruption of the two identified target motifs results in a loss of the major SUMO-conjugated forms of Kv1.5. In whole-cell patch-clamp electrophysiological studies, loss of Kv1.5 SUMOylation, by either disruption of the conjugation sites or expression of the SUMO protease SENP2, leads to a selective approximately 15-mV hyperpolarizing shift in the voltage dependence of steady-state inactivation. Reversible control of voltage-sensitive channels through SUMOylation constitutes a unique and likely widespread mechanism for adaptive tuning of the electrical excitability of cells.

SPI-0211 activates T84 cell chloride transport and recombinant human ClC-2 chloride currents.

The purpose of this study was to determine the mechanism of action of SPI-0211 (lubiprostone), a novel bicyclic fatty acid in development for the treatment of bowel dysfunction. Adult rabbit intestine was shown to contain mRNA for ClC-2 using RT-PCR, Northern blot analysis, and in situ hybridization. T84 cells grown to confluence on permeable supports were shown to express ClC-2 channel protein in the apical membrane. SPI-0211 increased electrogenic Cl- transport across the apical membrane of T84 cells, with an EC50 of approximately 18 nM measured by short-circuit current (Isc) after permeabilization of the basolateral membrane with nystatin. SPI-0211 effects on Cl- currents were also measured by whole cell patch clamp using the human embryonic kidney (HEK)-293 cell line stably transfected with either recombinant human ClC-2 or recombinant human cystic fibrosis transmembrane regulator (CFTR). In these studies, SPI-0211 activated ClC-2 Cl- currents in a concentration-dependent manner, with an EC50 of approximately 17 nM, and had no effect in nontransfected HEK-293 cells. In contrast, SPI-0211 had no effect on CFTR Cl- channel currents measured in CFTR-transfected HEK-293 cells. Activation of ClC-2 by SPI-0211 was independent of PKA. Together, these studies demonstrate that SPI-0211 is a potent activator of ClC-2 Cl- channels and suggest a physiologically relevant role for ClC-2 Cl- channels in intestinal Cl- transport after SPI-0211 administration.