Vasculature injury occurs rarely in traumatic brain injury but increases lifetime risk of ischemic or hemorrhage stroke. The diverse and nonspecific clinical manifestations make the diagnosis and treatment of these injuries highly challenging. With advancements in device design, endovascular treatments have become widely adopted, playing an increasingly vital role in the management of vascular diseases. The purpose of this review is to introduce and summarize endovascular treatments of traumatic cerebrovascular injury and other related pathological states after traumatic brain injury. Given the innovations of neuroendovascular devices and improvements in the techniques over the past decade, this review will outline several recent advancements in endovascular treatment strategies for cerebrovascular pathologies. Popularizing more treatment options to clinicians will benefit in dealing with a variety of clinical scenarios and reduce the overall morbidity of traumatic cerebrovascular injury.
Humans ; Endovascular Procedures/methods* ; Brain Injuries, Traumatic/complications* ; Cerebrovascular Trauma/therapy*

Needle-free injection technology (NFIT) refers to the drug delivery systems in which drugs are propelled as high-speed jet streams using any of the pressure source to penetrate the skin to the required depth. NFIT is a promising drug delivery system as it enables the injection of liquids, powders, and depot/projectiles, and has the advantages of preventing needle stick accidents, improving drug bioavailability, eliminating needle-phobia, increasing vaccine immunity, simplifying operations and is convenient for patients to use. NFIT and its research background, the structure and classification of needle-free jet injectors (NFJI), drugs that can be delivered using NFJI and the factors affecting the injection effect are comprehensively reviewed in this paper. The limitations and potential development directions are summarized to provide a theoretical basis for the application and development of NFIT.

In this study, we investigated the effect of Cigu Xiaozhi formula on HSC-T6 activity in hypoxic microenvironment based on network pharmacology and computer-aided drug design, and predicted and verified its possible targets and related signaling pathways. The potential active components and targets of Cigu Xiaozhi formula were screened by searching Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Encyclopaedia of Traditional Chinese Medicine (ETCM) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) databases, and the liver fibrosis related targets retrieved from Gene Cards and Pharm GK database were integrated to obtain the potential targets of Cigu Xiaozhi formula in the treatment of liver fibrosis. GO enrichment analysis and KEGG signaling pathway enrichment analysis were performed on Omic Share platform, and Cytoscape software was used to construct the "potential active ingredient-key target-pathway" network. The active components and target proteins were subjected to molecular docking analysis by Auto Dock software. According to the results of molecular dynamics simulation and binding free energy calculation, the top 5 active components with degree were scored. The active components stigmasterol and β-sitosterol were subjected to molecular docking. CoCl₂ was used to induce HSC-T6 cells to construct hypoxia model in vitro. The cell viability was detected by CCK-8 assay, and the optimal time and concentration of hypoxia model of HSC-T6 cells was determined to be 100 µmol·L^-1 CoCl₂ for 24 h. Under hypoxia condition, HSC-T6 cells were activated, the wound healing rate was significantly increased, and the fluorescence signal of activation marker protein α-smooth muscle actin (α-SMA) was significantly enhanced. However, 6% drug-containing serum could inhibit the activation of HSC-T6 cells, and the wound healing rate was significantly decreased, and the fluorescence signal of α-SMA was significantly weakened. Further studies showed that the expressions of hypoxia-inducible factor-1α (HIF-1α), α-SMA and key proteins of Hedgehog (Hh) signaling pathway in HSC-T6 cells were up-regulated under hypoxia, while the expressions of HIF-1α, α-SMA, Patched-1 (Ptch-1) and glioma related oncogene homology-1 (Gli-1) were down-regulated in 6% drug-containing serum group, the YC-1 group and the cyclopamine group. These results indicated that HIF-1α and Hh signaling pathways were involved in the activation of HSC-T6 cells, and the traditional Chinese medicine Cigu Xiaozhi formula could inhibit the activation of HSC-T6 cells, and the mechanism may be related to the inhibition of HIF-1α expression and the blocking of Hh signaling pathway. In conclusion, Cigu Xiaozhi formula can inhibit the activation of HSC-T6 cells by directly acting on HIF-1α and Hh signaling pathway, and exert an anti-hepatic fibrosis effect. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Gansu University of Chinese Medicine, in compliance with the Institutional Animal Care Guidelines.

Objective: To summarize the clinical characteristics of epileptic seizure associated with neurofibromatosis type 1 (NF1). Methods: From January 2017 to July 2023 at Children's Hospital Capital Institute of Pediatrics, medical records of patients with both NF1 and epileptic seizure were reviewed in this case series study. The clinical characteristics, treatment and prognosis were analyzed retrospectively. Results: A total of 15 patients(12 boys and 3 girls) were collected. Café-au-lait macules were observed in all 15 patients. There were 6 patients with neurodevelopmental disorders and the main manifestations were intellectual disability or developmental delay. The age at the first epileptic seizure was 2.5 (1.2, 5.5) years. There were various seizure types, including generalized tonic-clonic seizures in 8 patients, focal motor seizures in 6 patients, epileptic spasm in 4 patients, tonic seizures in 1 patient, absence in 1 patient, generalized myoclonic seizure in 1 patient and focal to bilateral tonic-clonic seizure in 1 patient. Among 14 patients whose brain magnetic resonance imaging results were available, there were abnormal signals in corpus callosum, basal ganglia, thalamus or cerebellum in 6 patients, dilated ventricles of different degrees in 3 patients, blurred gray and white matter boundary in 2 patients, agenesis of corpus callosum in 1 patient and no obvious abnormalities in the other patients. Among 13 epilepsy patients, 8 were seizure-free with 1 or 2 antiseizure medications(ASM), 1 with drug resistant epilepsy was seizure-free after left temporal lobectomy, and the other 4 patients who have received 2 to 9 ASM had persistent seizures. One patient with complex febrile convulsion achieved seizure freedom after oral administration of diazepam on demand. One patient had only 1 unprovoked epileptic seizure and did not have another seizure without taking any ASM. Conclusions: The first epileptic seizure in NF1 patients usually occurs in infancy and early childhood, with the main seizure type of generalized tonic-clonic seizure and focal motor seizure. Some patients have intellectual disability or developmental delay. Most epilepsy patients achieve seizure freedom with ASM.
Male ; Female ; Humans ; Child, Preschool ; Child ; Neurofibromatosis 1/diagnosis* ; Retrospective Studies ; Intellectual Disability ; Electroencephalography ; Epilepsy/etiology* ; Seizures/etiology*

Landfill is one of the important sources of carbon tetrachloride (CT) pollution, and it is important to understand the degradation mechanism of CT in landfill cover for better control. In this study, a simulated landfill cover system was set up, and the biotransformation mechanism of CT and the associated micro-ecology were investigated. The results showed that three stable functional zones along the depth, i.e., aerobic zone (0-15 cm), anoxic zone (15-45 cm) and anaerobic zone (> 45 cm), were generated because of long-term biological oxidation in landfill cover. There were significant differences in redox condition and microbial community structure in each zone, which provided microbial resources and favorable conditions for CT degradation. The results of biodegradation indicated that dechlorination of CT produced chloroform (CF), dichloromethane (DCM) and Cl^- in anaerobic and anoxic zones. The highest concentration of dechlorination products occurred at 30 cm, which were degraded rapidly in aerobic zone. In addition, CT degradation rate was 13.2-103.6 μg/(m²·d), which decreased with the increase of landfill gas flux. The analysis of diversity sequencing revealed that Mesorhizobium, Thiobacillus and Intrasporangium were potential CT-degraders in aerobic, anaerobic and anoxic zone, respectively. Moreover, six species of dechlorination bacteria and eighteen species of methanotrophs were also responsible for anaerobic transformation of CT and aerobic degradation of CF and DCM, respectively. Interestingly, anaerobic dechlorination and aerobic transformation occurred simultaneously in the anoxic zone in landfill cover. Furthermore, analysis of degradation mechanism suggested that generation of stable anaerobic-anoxic-aerobic zone by regulation was very important for the harmless removal of full halogenated hydrocarbon in vadose zone, and the increase of anoxic zone scale enhanced their removal. These results provide theoretical guidance for the removal of chlorinated pollutants in landfills.
Bacteria/metabolism* ; Biodegradation, Environmental ; Carbon Tetrachloride/metabolism* ; Methane/metabolism* ; Waste Disposal Facilities

Objective:To identify the transdermal constituents of Euodiae Fructus and predict its molecular mechanism in treating diarrhea by transdermal drug delivery. Method:Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and integrated pharmacology methods were used. The rapid identification of transdermal constituents of Euodiae Fructus was realized by the means of comparison of reference substances， analysis of UNIFI system and mass spectrometry. On this basis， Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0， SymMap， DisGeNET databases and literature were used to collected potential targets of transdermal constituents of Euodiae Fructus and targets for diarrhea-related diseases. The disease targets and drug targets were topologically analyzed to obtain the core targets， which were used for the Gene Ontology （GO） function and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Finally， Cytoscape 3.6.0 was used to build up a network of transdermal constituents-core targets-key pathways. Result:A total of 19 chemical constituents were speculatively identified from Euodiae Fructus extract， including quinolone alkaloids， limonins， indole alkaloids， organic acids and sterols. A total of 174 core targets of Euodiae Fructus for treating diarrhea were obtained by a topology analysis， signaling pathways of inflammatory response， cell proliferation， nutrient regulation and energy metabolism， signal transduction， bacterial infection were obtained through the analysis of KEGG enrichment. Conclusion:In this study， the transdermal constituents of Euodiae Fructus are identified for the first time， they can participate in the regulation of intestinal inflammation， maintain the integrity of intestinal mucosa， repaire and adjust the metabolism of the body by acting on Rac protein family， phosphatidylinositol 3-kinase， cytochrome P450 enzymes and aldo-keto reductase， respectively. In general， the molecular mechanism of Euodiae Fructus in the treatment of diarrhea is preliminarily elucidated.

Objective:To investigate the effect of the production process of Zushima Guanjie Zhitong Gao from solvent method to hot-pressed method on in vitro kinetic behavior of this preparation. Method:Solvent and hot-pressed methods were used to prepare three batches of samples above pilot scale， and in vitro release and percutaneous penetration of the index components （7，8-dihydroxycoumarin and methyl salicylate） in Zushima Guanjie Zhitong Gao were investigated by modified Franz diffusing cells. Result:The contents of 7，8-dihydroxycoumarin and methyl salicylate in Zushima Guanjie Zhitong Gao prepared by solvent method were 73.72， 494.67 μg/patch， and their contents in hot-pressed method samples were 159.21， 2 638.99 μg/patch， respectively. In the solvent method samples， the average cumulative release amounts of 7，8-dihydroxycoumarin and methyl salicylate in 24 h were 2.04， 12.21 μg， and their average cumulative release amounts in 24 h of hot-pressed method samples were 2.16， 36.24 μg， respectively. In the solvent method samples， the average cumulative permeation amounts of 7，8-dihydroxycoumarin and methyl salicylate in 24 h were 0.38， 2.79 μg， and they were 0.40， 7.49 μg in hot-pressed method samples. The cumulative release and permeation amounts in 24 h of 7，8-dihydroxycoumarin in the hot-pressed method samples were basically the same as those of the solvent method samples， but the cumulative release and permeation amounts in 24 h of methyl salicylate in the hot-pressed method samples were significantly higher than those of the solvent method samples （P<0.05）. Conclusion:The retention of 7，8-dihydroxycoumarin and methyl salicylate by hot-pressed method is better than that of the solvent method. The process change has no significant effect on the in vitro kinetics of 7，8-dihydroxycoumarin in Zushima Guanjie Zhitong Gao， however， after the change from the solvent method to the hot-pressed method， the methyl salicylate in this preparation has a higher cumulative release and permeation amounts.

Objective: To investigate the impact of different levels of systolic blood pressure on all-cause, cardiovascular and cerebrovascular mortality in patients with nonvalvular atrial fibrillation (AF). Methods: This is a prospective cohort study. Patients with AF or atrial flutter diagnosed by 12 lead electrocardiogram during physical examination of Kailuan Group employees from July 2006 to December 2017 or previously diagnosed with AF in an inpatient setting at a level 2A hospital or above were eligible for the study. Baseline clinical characteristics including age, gender, systolic blood pressure were collected. According to the level of systolic blood pressure, patients were divided into systolic blood pressure<120 mmHg (1 mmHg=0.133 kPa)group, 120 mmHg ≤ systolic blood pressure<140 mmHg group, and systolic blood pressure ≥140 mmHg group. The time of first diagnosis with AF was defined as the start of follow-up and the final follow-up ended at December 2018. Primary endpoint was all-cause death. Related information was obtained through the social security system or inpatient medical records. The cause of death was defined according to the International Classification of Diseases disease (ICD-10) codes by professional medical stuffs. Multifactorial Cox proportional risk model was used to analyze the relative risk ratios for the occurrence of death in different systolic blood pressure level groups. The relationship between systolic blood pressure levels and mortality in the patients with AF was analyzed by using natural spline function curves. Results: A total of 1 721 patients with AF were enrolled (average age=(67.0±9.0) years), patients were followed up for (6.3±3.8) years. 544 out of 1 721 patients with AF died during the follow-up period (31.61%). The cumulative incidence rate of all-cause mortality, cardiovascular and cerebrovascular death was 26.13%, 25.59%, 36.96% and 14.86%, 11.87%, 19.76% respectively in the systolic blood pressure<120 mmHg, 120 mmHg ≤ systolic blood pressure<140 mmHg and systolic blood pressure ≥140 mmHg groups. The cumulative incidence rate of all-cause, cardiovascular and cerebrovascular death was significantly higher in the group with systolic blood pressure ≥140 mmHg than in 120 mmHg ≤ systolic blood pressure<140 mmHg group (P<0.05). Compared with 120 mmHg ≤ systolic blood pressure<140 mmHg group, multivariable Cox proportional hazards regression models showed that the HRs (95%CI) for all-cause, cardiovascular and cerebrovascular death were 1.47 (1.20 to 1.79) and 1.69 (1.27 to 2.26) for the group with systolic blood pressure ≥ 140 mmHg (P<0.05). In contrast, the HRs (95%CI) for all-cause, cardiovascular and cerebrovascular death in the systolic blood pressure<120 mmHg group were 0.99 (0.73-1.35) and 1.24 (0.82-1.89), respectively, with no statistically significant differences between the two groups (P>0.05). The natural spline curve showed that there was a "U" relationship between systolic blood pressure levels and all cause death and cardiovascular and cerebrovascular death in this patient cohort. Systolic blood pressure greater than or less than 123 mmHg was associated with increased risk of death of AF patients in this cohort. Conclusion: Compared with systolic blood pressure<120 mmHg and systolic blood pressure≥140 mmHg group, the risk of all-cause and cardiovascular and cerebrovascular death is the lowest in AF patients with 120 mmHg ≤ systolic blood pressure<140 mmHg in this cohort.

Acoustic Impedance Tests ; Ear Diseases/diagnosis* ; Ear, Middle ; Eustachian Tube ; Humans ; Myoclonus ; Otitis Media

OBJECTIVETo report on prenatal diagnosis and follow up of two patients with paternal uniparental disomy of chromosome 6 (pUPD6).

METHODSFetal cells were subjected to in situ culturing and G-banded chromosomal analysis. DNA samples of the fetuses and their parents were also analyzed with single nucleotide polymorphism microarray (SNP array).

RESULTSBoth fetuses had a normal male karyotype. SNP array analysis showed both have carried pUPD6.

CONCLUSIONpUPD6 can lead to transient neonatal diabetes mellitus type 1. Homozygous status of recessive mutations, disorder of gene imprinting, and its influence on placental function are the main factors to be considered during prenatal diagnosis and genetic counseling for pUPD6.