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Objective: The relationship between small subcortical ischemic infarction remains poorly characterized. Therefore, the present study aimed to investigate the association between artery-to-artery embolization and small subcortical infarctions. Methods: This retrospective observational cross-sectional study enrolling 230 patients with acute middle cerebral artery (MCA) stroke classified into the microembolic signals-positive (MES+) and MES-negative (MES−) groups. The diffusion weighted imaging (DWI) infarction patterns in the MCA were divided into the territorial, border zone (BZ), cortical, and subcortical infarcts. We set the standard of small subcortical infarction (SCI) into two levels: < 10 mm diameter and <5 mm diameter. Relevant DWI parameters were used to build a nomogram for MES+, using free statistics. Results: MES occurred in 38 of the 230 cases, yielding a positivity rate of 16.5%. BZ, SCI <10 mm, cortical ischemia (CI), stenosis, white blood cell count, and gender were compared between the MES+ and MES− groups. Multivariate analysis revealed that BZ, SCI < 10 mm, and CI were independently associated with MES. Based on DWI parameters, a nomogram model was built for MES+. The area under the curve of the model was 0.826 (95%CI 0.764 to 0.889). In internal cross-validation, the slope of the calibration curve was 1.000, indicating that the model accurately predicted unsuccessful treatment outcomes. Conclusion: Small subcortical infarctions are associated with MES. In the present study, we built a predictive nomogram model for MES+ based on small subcortical infarctions and other DWI parameters. This model demonstrated good performance in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to assess the influence of the major transporters at blood–brain barrier and blood–cerebrospinal fluid barrier on levofloxacin (LVFX) pharmacokinetics in rat. To explore the different effects of transporters on drug concentrations in cerebrospinal fluid (CSF) and brain extracellular fluid (ECF). Methods: High‐performance liquid chromatography coupled with microdialysis was used to continuously and synchronously measure unbound concentrations of LVFX in rat blood, hippocampal ECF, and lateral ventricle CSF for comprehensive characterization of brain pharmacokinetics. The role of transporters in the brain efflux mechanism of LVFX was analyzed in the absence and presence of various transporter inhibitors. Results: Following LVFX (50 mg/kg) administration, the unbound partition coefficient of LVFX in brain ECF and CSF (Kp,uu,ECF and Kp,uu,CSF) were 34.0 ± 1.7% and 41.2 ± 2.4%, respectively. When probenecid was coadministered with LVFX, the AUC and the mean residence time (MRT) in rat blood increased significantly (p < 0.05). After MK571 intervention, 1.35‐fold and 1.16‐fold increases in Kp,uu,ECF and Kp,uu,CSF were observed, respectively (p < 0.05). Treatment with Ko143 increased the levels of LVFX in brain ECF. The difference in LVFX concentration in brain ECF and CSF was <3‐fold with or without treatment with transporter inhibitors. Conclusion: Efflux of LVFX from the central nervous system (CNS) involves multidrug resistance‐associated proteins (MRPs), breast cancer resistance protein (BCRP), and organic anion transporters (OATs). MRPs play an important role in mediating the brain/CSF‐to‐blood efflux of LVFX. LVFX concentrations in CSF can be used as a surrogate to predict the concentrations inside brain parenchyma. [ABSTRACT FROM AUTHOR]

Background: Early and accurate diagnosis of fatal familial insomnia (FFI) is critical for effective screening; however, this rare disease remains difficult to recognize. This work aimed to propose a new diagnostic criterion for fatal familial insomnia (FFI) with optimal sensitivity, specificity, and likelihood ratio. Methods: An international group of experts was established and 128 genetically confirmed FFI cases and 281 non‐FFI prion disease controls are enrolled in the validation process. The new criteria were proposed based on the following steps with 2‐round expert consultation: 1) Validation of the 2018 FFI criteria. 2) Diagnostic item selection according to statistical analysis and expert consensus. 3) Validation of the new criteria. Results: The 2018 criteria for possible FFI had a sensitivity of 90.6%, specificity of 83.3%, the positive likelihood ratio (PLR) of 5.43, and negative likelihood ratio (NLR) of 0.11; the probable FFI criteria had a sensitivity of 83.6%, specificity of 92.9%, the PLR of 11.77, and NLR of 0.18. The new criteria included more specific and/or common clinical features, 2 exclusion items, and summarized a precise and flexible diagnostic hierarchy. The new criteria for possible FFI had a sensitivity of 92.2%, specificity of 96.1%, a PLR of 23.64, and NLR of 0.08, while the probable FFI criteria had a sensitivity of 90.6%, specificity of 98.2%, the PLR of 50.33, and NLR of 0.095. Conclusion: A new clinical diagnostic criteria was proposed for FFI, which will be practical at the clinic for early recognition of FFI and differentiation from other prion diseases then help further referral and genetic test. [ABSTRACT FROM AUTHOR]

The present geothermal characteristics and influencing factors are analyzed to conduct geothermal resource exploration in the Xiong'an New Area. Thermal conductivity data for 100 rock samples are obtained from different wells and a sedimentary strata thermal conductivity column is proposed. From these data, heat flow distribution in the area is mapped using equilibrium temperature logs obtained for 32 wells. The heat flow in this area is found to be 53.3–106.5 mW·m−2 (average: 73 mW·m−2). The uplift heat value in Niutuozhen and Rongcheng uplift is 106.5 and 90 mW·m−2, respectively. The sag heat flow is relatively low and the Baxian sag's heat flow value is 48.9–61.6 mW·m−2. Thermal conductivity differences among Cenozoic caprock, Proterozoic carbonate reservoirs, and basement rock mainly affects the geothermal distribution. The low and high thermal conductivities of the caprock and thermal reservoir as well as basement, respectively, cause heat flow redistribution in the surface during conduction. Groundwater rises to geothermal reservoirs through heat-controlling faults, causing convective heat transfer and increasing the geothermal reservoir temperature; therefore, high-temperature groundwater accumulates in the shallow uplift areas. The caprock's thin uplift area exhibits a high geothermal background due to water convergence. Understanding the geothermal characteristics and influencing factors is necessary for understanding the distribution law and factors influencing geothermal resources and guiding geothermal exploration and development in the Xiong'an New Area. [ABSTRACT FROM AUTHOR]

Purpose: To find the effect of lumbrokinase (LK) on P-selectin and E-selectin in ischemic rats., Methods: Male healthy Spragur-Dawley rats weighing 180-220 g (n = 90) were divided into 4 groups: (1) normal control group (n = 5), (2) sham-operated group (n = 35), (3) ischemic group (n = 35), (4) LK group (n = 15). LK 10 mg/kg (2000 UK activity of LK) was given by intraperitoneal injection in the LK group 30 minutes before experiment. Same volume of normal saline was given in the sham-operated group and ischemic group. The ischemic model was made by modified Haruo Nagasawa's method. Immunohistochemistry was used to observe the P-selectin and E-selectin positive cells in the ischemic region., Results: P-selectin and E-selectin positive cells in ischemic regions were observed in the ischemic group, and the peak of expression was at 6 hours and 12 hours, respectively. The similar changes were not observed in normal control group. There were only a few positive cells in the sham-operated group. In LK group, the P-selectin and E-selectin positive cells were significantly less than those in the ischemic group (P < 0.05 at 3 hours after the onset, P < 0.01 at 6 hours and P < 0.01 at 12 hours, respectively)., Conclusions: LK might significantly decrease the immunoreactions of P-selectin and E-selectin in ischemic lesion.