ObjectiveCentral nervous system （CNS） infiltration commonly occurs in children with acute lymphoblastic leukemia （ALL）. Early subclinical CNS infiltration in pediatric ALL is hard to detect with conventional methods. This study aimed to investigate the changes of brain structure volume parameters based on Synthetic MRI （SyMRI） in pediatric ALL without clinically diagnosed CNS infiltration. MethodsThirty-six ALL and twenty-nine typically developing （TD） children were prospectively collected and all underwent SyMRI. The Synthetic MR software was used to obtain brain volumetric parameters including total white matter volume （WMV）， gray matter volume （GMV）， cerebrospinal fluid （CSF） volume， etc. and their within-group differences were assessed by analysis of covariance. The Spearman correlation analysis was used to examine the correlation between biological characteristics and statistically significant brain volume parameters. ResultsALL children showed increased CSF volume （P_{FDR-corrected} = 0.009） and decreased GMV （P_{FDR-corrected} = 0.027） when compared to TD children. We also found a moderately negative association between GMV/intracranial volume and risk classification in pediatric ALL （rs = -0.380， P = 0.022）. ConclusionsPediatric ALL without clinically diagnosed CNS infiltration presented with accumulation of CSF and reduction of gray matter. The brain volumetric changes in subclinical CNS infiltration of pediatric ALL provides a new attempt for exploring the underlying mechanism and early detection of CNS infiltration in pediatric ALL.

AIM:To observe the toxic effects of zinc oxide nanoparticles(ZnO NPs)on cornea by constructing intoxicated model in vivo and in vitro.METHODS:Human corneal epithelial cells(HCEpiC)were cultured in vitro and exposed to different concentrations(0.5, 5, 12.5, 25, 50, 100, 250 μg/mL)of ZnO NPs for 24h. The cell culture medium without nano-solution was used as the blank control group. The viability of the cells was assessed by MTT assay. Three different concentrations(25, 50 and 100 μg/mL)of ZnONPs dispersions were exposed to the conjunctival sac of anesthetized mice three times a day for 7d consecutively. The phosphate buffered saline(PBS)eye group was the PBS control group. Corneal morphology was observed on 1, 3, 5 and 7d, and the eyes were removed on 8d for various laboratory examinations, including corneal pathological changes and expression levels of inflammatory factors(TNF-α, IL-6).RESULTS:After treatment of HCEpiC cells with different concentrations of ZnO NPs for 24h, the MTT results showed that Zno NPs cause damage to cells at 0.5 μg/mL, and the cell survival rate was about 80%(P<0.05). Half of the cells were killed at a dose of 5 μg/mL, the damaging effect on cells in the concentration range of 5～250 μg/mL was concentration-dependent(P<0.0001). After 7d of conjunctival capsule spotting in mice, dot-like staining of fluorescein was seen in the 25 μg/mL ZnO NPs and 50 μg/mL ZnO NPs groups. Localized circular fluorescein stained areas were seen in the corneas of the 100 μg/mL ZnO NPs group. HE staining showed that the corneal epithelial layer, stromal layer thickness and stromal layer immune cell number did not change significantly in the 25 μg/mL and 50 μg/mL ZnO NPs groups(all P>0.05), while the corneal epithelial layer thinned, the corneal stromal layer thickened and the stromal layer immune cells increased significantly in the 100 μg/mL ZnO NPs group(all P<0.05). Immunohistochemical staining showed that the number of corneal stromal immune cells producing TNF-α and IL-6 and the mean integral optical density(IOD)values of TNF-α and IL-6 were significantly higher in the 100 μg/mL ZnO NPs group than in the PBS control group(P<0.05), and the degree of inflammation response was concentration-dependent. Compared with the PBS control group, no significant increase in immune cell count and IOD values in the 25 μg/mL ZnO NPs and 50 μg/mL ZnO NPs groups(P>0.05).CONCLUSION:The toxic damaging effect of ZnO NPs on the cornea was confirmed from both in vitro and in vivo, which provided a theoretical basis for the ocular safety evaluation of ZnO NPs.

ObjectiveThe glymphatic system regulates cerebral spinal fluid and interstitial fluid transport which might be one of the pathways of central nervous system （CNS） leukemia at the early stage. This study aimed to investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space （DTI-ALPS） in pediatric acute lymphoblastic leukemia （ALL） without clinically diagnosed CNS infiltration. MethodsTwenty-five ALL and typically developing （TD） children were prospectively recruited， and all subjects underwent DTI. Group differences in brain water diffusivities and ALPS-index were evaluated using the analysis of covariance. The Spearman correlation analysis was used to evaluate the relationship between biological characteristics and significant parameters in pediatric ALL. ResultsCompared with TDs， decreased Dxassoc value （P_{FDR-corrected} = 0.048） and increased Dzassoc value （P_{FDR-corrected} = 0.033） were found in pediatric ALL. Hence， lower ALPS-index was found in children with ALL （P_{FDR-corrected} < 0.001）. ALPS-index was negatively associated with the risk classification （r_s = -0.47， P = 0.018） as well as immunophenotype （r_s = -0.40， P = 0.046） in pediatric ALL. ConclusionsOur results show dysfunction of the glymphatic system is presented in pediatric ALL without clinically diagnosed CNS infiltration， which suggests that the glymphatic system might be one of pathway in the early-stage of ALL CNS infiltration. The DTI-ALPS method can be used to evaluate the change of glymphatic system， providing a new method for exploring the underlying mechanisms and early detection of pediatric ALL CNS infiltration.

Objective: BMI may play a protective role in reducing the mortality rate of patients with chronic obstructive pulmonary disease (COPD), but its effect on acute exacerbation of COPD remain unclear. Methods: Subjects were selected from the COPD patients registration system established in 2014 in Pudong new district, Shanghai. COPD patients from 8 communities were selected by cluster sampling and follow up was conducted prospectively for 18 months. Basic information and BMI were obtained from baseline survey, and acute exacerbations were collected during follow-up. The association between BMI and risk of acute exacerbation was evaluated by using multiple negative binomial regression. Results: Among 328 community COPD patients, 295 who completed the follow up were included in the analysis, in whom 96.3% (284/295) were mild COPD patients. During the follow-up, 11.1% (33/295) of the patients reported acute exacerbation. The results of multiple negative binomial regression suggested that, the risk for acute exacerbation decreased with the increase of BMI (IRR=0.85, 95%CI:0.73-0.98), overweight patients with BMI ≥25.0 kg/m² (IRR=0.36, 95%CI:0.13-0.91) or moderate BMI (T₂ vs. T₁, IRR=0.31, 95%CI:0.11-0.77) had lower risk for acute exacerbation compared with the patients with normal or low BMI. BMI had a linear correlation with the risk of acute exacerbation. Conclusion: The risk for acute exacerbation in patients with mild or moderate COPD in communities decreased with the increase of BMI, and being overweight might be a protective factor for the acute exacerbation of COPD.
Body Mass Index ; China/epidemiology* ; Disease Progression ; Humans ; Overweight/complications* ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive/complications*

Objective: To investigate the clinical features and prognosis in patients with idiopathic sudden sensorineural hearing loss (ISSNHL) with blood-labyrinth barrier breakdown (BLB-B). Methods: Clinical data of patients with unilateral ISSNHL hospitalized from December 2017 to December 2018 were retrospectively analyzed. According to the results of 3D-FLAIR MRI and enhanced MRI scanning, these patients were divided into two groups, i.e., normal and abnormal inner ear groups. The patients in abnormal inner ear group were further divided into two subgroups: BLB-B and BLB-B with exudation. The differences and correlations among the groups in clinical characteristics, in terms of gender, age, deafness side, basic diseases, dizziness/vertigo, vestibular function, hearing loss degree, as well as classification of hearing curve, and prognosis were analyzed by statistical software SPSS 23.0. Results: Data were collected from 150 cases, in which 68 were male and 82 were female, aged (46.2±14.6) years, including 67 cases with normal inner ears and 83 cases with abnormal inner ears (13 cases with BLB-B; 70 cases with BLB-B and exudation). The dizziness/vertigo incidence, side ratio, hearing loss degree, classification of hearing curve, vestibular dysfunction (vestibular double temperature test, HIT and VAT) and therapeutic effect were different between normal and abnormal inner ear groups (P<0.05). The dizziness/vertigo incidence, side ratio, hearing loss degree, classification of hearing curve, vestibular dysfunction (vestibular double temperature test, o/cVEMP, HIT and VAT) and therapeutic effect were different among normal inner ear, BLB-B and BLB-B with exudation groups (P<0.05). Pairwise comparison between groups revealed that vestibular dysfunction (vestibular double temperature test, o/cVEMP, HIT and VAT) and therapeutic effect were different between normal inner ear and BLB-B groups (P<0.05); The dizziness/vertigo incidence, side ratio, hearing loss degree, classification of hearing curve, vestibular dysfunction (vestibular double temperature test, o/cVEMP, HIT and VAT) and therapeutic effect were different between normal inner ear and BLB-B with exudation groups (P<0.05). There was no significant different between BLB-B and BLB-B with exudation groups. Conclusion: BLB-B displayed by 3D-FLAIR MRI manifestation in ISSNHL patients indicates more serious cochlear and vestibular dysfunction, and worse therapeutic effect.
Dizziness ; Female ; Hearing Loss, Sensorineural ; Hearing Loss, Sudden ; Humans ; Male ; Prognosis ; Retrospective Studies ; Vertigo ; Vestibule, Labyrinth

The East Asian scorpion Buthus martensii Karsch (BmK) is one of the classical traditional Chinese medicines for treating epilepsy for over a thousand years. Neurotoxins purified from BmK venom are considered as the main active ingredients, acting on membrane ion channels. Voltage-gated sodium channels (VGSCs) play a crucial role in the occurrence of epilepsy, which make them become important drug targets for epilepsy. Long chain toxins of BmK, composed of 60-70 amino acid residues, could specifically recognize VGSCs. Among them, α-like neurotoxins, binding to the receptor site-3 of VGSC, induce epilepsy in rodents and can be used to establish seizure models. The β or β-like neurotoxins, binding to the receptor site-4 of VGSC, have significant anticonvulsant effects in epileptic models. This review aims to illuminate the anticonvulsant/convulsant effects of BmK polypeptides by acting on VGSCs, and provide potential frameworks for the anti-epileptic drug-design.
Animals ; Anticonvulsants/therapeutic use* ; Neurotoxins/pharmacology* ; Scorpion Venoms/pharmacology* ; Scorpions/chemistry* ; Voltage-Gated Sodium Channels

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.
Biomarkers ; Carcinoma, Hepatocellular ; Golgi Apparatus ; Humans ; Liver Cirrhosis ; Liver Neoplasms

Lower extremity deep vein thrombosis (DVT) is one of the main complications in patients with traumatic fractures, and for severe patients, the DVT can even affect arterial blood supply, resulting in insufficient limb blood supply. If the thrombus breaks off, pulmonary embolism may occur, with a high mortality. The treatment and rehabilitation strategies of thrombosis in patients with lower extremity fractures have its particularity. DVT in traumatic fractures patients has attracted extensive attention and been largely studied, and the measures for prevention and treatment of DVT are constantly developing. In recent years, a series of thrombosis prevention and treatment guidelines have been updated at home and abroad, but there are still many doubts about the prevention and treatment of DVT in patients with different traumatic fractures. Accordingly, on the basis of summarizing the latest evidence-based medical evidence at home and abroad and the clinical experience of the majority of experts, the authors summarize the clinical treatment and prevention protocols for DVT in patients with traumatic fractures, and make this consensus on the examination and assessment, treatment, prevention and preventive measures for DVT in patients with different fractures so as to provide a practicable approach suitable for China ′s national conditions and improve the prognosis and the life quality of patients.

Aged ; Antiviral Agents/therapeutic use* ; COVID-19/drug therapy* ; China/epidemiology* ; Cohort Studies ; Female ; Hospital Mortality ; Hospitalization ; Humans ; Male ; Middle Aged ; Patient Acuity ; SARS-CoV-2 ; Treatment Outcome

Based on the data mining technology, the rules of acupoint selection and prescription were analyzed for impotence treated with acupuncture and moxibustion in ancient recorded in
Acupuncture Points ; Acupuncture Therapy ; Data Mining ; Erectile Dysfunction ; Humans ; Male ; Meridians ; Moxibustion ; Technology