Objective To analyze the diagnostic value of 4 serum autoantibodies in nasopharyngeal carcinoma patients (anti-Rho-GDI-2, -HSP70, -CK19 and -LAP3 antibodies) using a serological proteomic approach. Methods The conditions for blocking, antigen concentrations and serum dilution were optimized to establish the ELISA method for detection of serum autoantibodies for Rho-GDI-2, HSP70, CK19 and LAP3. The serum concentrations of these autoantibodies were detected by the established method in 36 NPC patients, 20 other cancer patients and 20 healthy individuals. The statistical analysis was used to evaluate the diagnostic value of the 4 serum autoantibodies. Results The concentrations of 4 serum autoantibodies in the NPC patients were significantly higher than those in the healthy individuals(A450 values in NPC group of CK19, Rho-GDI-2, HSP70, LAP3 were 0. 188 8 ±0.047 3, 0.240 5 ± 0.024 7, 0. 116 8 ±0.025 3, 0.276 9 ±0.044 2 repectively. A450 values in healthy control group were 0.010 5 ±0.004 4, 0. 105 3 ±0. 016 9, 0. 098 6 ± 0. 014 0, 0. 149 8 ± 0. 033 1 respectively. F values were 4. 869, 15. 919, 10. 331,6. 369, respectively. P values were 0. 010, 0. 000, 0. 000, 0. 003, respectively). The sensitivities of antiRho-GDI-2, anti-HSP70, anti -CK19 and anti -LAP3 autoantibodies for diagnosis of NPC was 85.0%,75.0%, 75.0% and 75.0%, respectively, and the specificities were 58.9%, 80. 4%, 58. 9% and 57. 1%, respectively, anti-Rho-GDI-2 and anti-HSP70 achived the highest sensitivity and specificity respectively when single marker was analyzed. The sensitivity and specificity were 94. 4% and 95. 0%respectively when 4 markers was combined for analysis. Conclusion Detection of serum anti-Rbo-GDI-2,anti-HSP70, anti-CK19 and anti-IAP3 auotantibedios by ELISA may be of help in the screening and diagnosis for NPC.

Child, Preschool ; Hemophilia A ; classification ; diagnosis ; therapy ; Hemorrhage ; diagnosis ; therapy ; Humans ; Infant

This article reports a case with the chief complaint of “hepatosplenomegaly to be investigated” and a confirmed diagnosis of Niemann-Pick disease type B after various tests， and a literature review was conducted to summarize the heterogeneous manifestations of liver involvement in type B Niemann-Pick disease， in order to improve the clinical management of difficult and rare liver diseases.

OBJECTIVE: To investigate the effect of obstructive sleep apnea (OSA) on different sleep stages, and the relationship between N3 stage of non-rapid eye movement sleep and respiratory abnormal events. METHODS: A total of 188 adult patients who underwent overnight polysomnography(PSG)monitoring in Sir Run Run shaw Hospital of Zhejiang University from June 24th to December 26th 2019 were enrolled in the study. OSA patients were classified into 3 groups (mild, moderate and severe) according to the apnea-hypopnea index (AHI). PSG data, AHI and the lowest SPO in each stage of sleep were compared among three groups. RESULTS: There was no significant difference in total sleep time and sleep efficiency among patients with different severity of OSA (all >0.05). The proportion of N3 stage in moderate and severe OSA groups were significantly smaller than that in mild OSA group (all <0.05). The proportion of N3 stage in severe OSA group was also smaller than that in moderate OSA group (<0.05). In addition, severe OSA group had a longer latency of N3 stage than mild and moderate OSA groups (all <0.05). The latency of N3 stage in moderate OSA group was longer than that in mild OSA group (<0.05). The AHI in N3 stage was markedly lower than that in other sleep stages (all <0.01), regardless of the severity of OSA. Supine AHI in N3 stage in mild and moderate groups was significantly lower than that in N1, N2 and rapid eye movement (REM) stages (all <0.01). Supine AHI in N3 stage in severe group was also lower than that in N2 and REM stages (<0.05 or <0.01). The lowest SPO in N3 stage was significantly higher than that in N1, N2 and REM stages (<0.05 or <0.01), regardless of the severity of OSA. CONCLUSIONS s The proportion of N3 stage is lower in OSA patients, and N3 stage has less sleep respiratory events than non-N3 stages. The results suggest that the increased N3 stage proportion may indicate less severity of OSA.

OBJECTIVETo investigate the relationship of properties and drug release rate of hot melt pressure sensitive adhesive (HMPSA), and to provide a recommendation of preparing and selecting of HMPSA for transdermal use.

METHODHMPSA with different properties were prepared using styrene-isoprene-styrene triblock copolymer as main material, and the tacks, adhesions and cohesions were determined. Drug-in-adhesive type patches were prepared using alpha-asarone as model drug, and the drug release rates were investigated on single chamber diffusion cells using 60% ethanol solution as release media.

RESULTThe prepared HMPSAs had different tacks, adhesions and cohesions. The drug release rates of HMPSA patches were related to the cohesions. The release rate decreased when the cohesion increased.

CONCLUSIONThe HMPSA with appropriate cohesion should be selected when preparing patches to balance the drug release rate and patch property.

To develop estradiol transdermal film-forming spray (TFS), various polymers were screened using solvent appearance, spray ability, film-forming rate and appearance as indices. The influence of polymer type, plasticizer and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model, and transdermal flux of TFS was compared with commercial patch and gel. The drug existing state in the formed film was investigated by differential scanning calorimetry (DSC). The solvent appearances, spray abilities, film-forming rates and appearances of eudragit E PO, RL PO, hydroxypropyl cellulose EF, polyvinylpyrrolidone K30, Plasdone S630 and Agrimer VA64 were suitable for the preparation of TFS. TFS prepared by Eudragit RL PO had the biggest transdermal flux of estradiol among all the polymers investigated. Triethyl citrate, the plasticizer, decreased the transdermal flux. Azone increased the transdermal flux, while oleic acid, isopropyl myristate and menthol had opposite effects. TFS had a higher transdermal rate and a higher accumulative penetrated estradiol of 24 h than commercial patch and gel. The DSC result showed that estradiol was spread as molecule in the formed film of TFS. It was indicated that TFS could be expected to be an effective transdermal drug delivery system.
Administration, Cutaneous ; Aerosols ; Animals ; Azepines ; chemistry ; Calorimetry, Differential Scanning ; Cellulose ; analogs & derivatives ; chemistry ; Citrates ; chemistry ; Drug Delivery Systems ; Estradiol ; administration & dosage ; pharmacokinetics ; Plasticizers ; chemistry ; Polymers ; chemistry ; Skin Absorption ; Swine

Proteasome inhibitors have shown remarkable success in the treatment of hematologic neoplasm. There has been a lot of attention to applying these drugs for solid tumor treatment. Recent preclinical study has signified the effectiveness on cell proliferation inhibition in lung adenocarcinoma treated by carfilzomib (CFZ), a second generation proteasome inhibitor. However, no insight has been gained regarding the mechanism. In this study, we have systematically investigated the CFZ functions in cell proliferation and growth, cell cycle arrest, and apoptosis in lung adenocarcinoma cells. Flow cytometry experiments showed that CFZ significantly induced G2/M cell cycle arrest and apoptosis in lung adenocarcinoma. MTS and colony formation assays revealed that CFZ substantially inhibited survival of lung adenocarcinoma cells. All results were consistently correlated to the upregulation expression of Gadd45a, which is an important gene in modulating cell cycle arrest and apoptosis in response to physiologic and environmental stresses. Here, upregulation of Gadd45a expression was observed after CFZ treatment. Knocking down Gadd45a expression suppressed G2/M arrest and apoptosis in CFZ-treated cells, and reduced cytotoxicity of this drug. The protein expression analysis has further identified that the AKT/FOXO3a pathway is involved in Gadd45a upregulation after CFZ treatment. These findings unveil a novel mechanism of proteasome inhibitor in anti-solid tumor activity, and shed light on novel preferable therapeutic strategy for lung adenocarcinoma. We believe that Gadd45a expression can be a highly promising candidate predictor in evaluating the efficacy of proteasome inhibitors in solid tumor therapy.
Adenocarcinoma of Lung/pathology* ; Apoptosis/drug effects* ; Cell Cycle Checkpoints/drug effects* ; Cell Cycle Proteins/genetics* ; Cell Line, Tumor ; Forkhead Box Protein O3/physiology* ; Gene Expression Regulation, Neoplastic/drug effects* ; Humans ; Lung Neoplasms/pathology* ; Oligopeptides/pharmacology* ; Proto-Oncogene Proteins c-akt/physiology* ; Up-Regulation

OBJECTIVETo evaluate the application of various obstructive sleep apnea (OSA) screening scales in patients with acute ischemic stroke.

METHODSOne hundred and two patients with acute ischemic stroke were enrolled continuously during July 2016 and March 2017 from Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. All patients were assessed by the same physician with various OSA screening scales, including Epworth scale, Berlin questionnaire, STOP-Bang questionnaire, SOS scale, four-variable scale and its modified version. Polysomnography was performed in Sleeping Disorder Center on each patient. According to the apnea-hypopnea index (AHI) acquired from polysomnography, patients were divided into moderate-severe OSA group (AHI ≥ 15, =58) and normal-mild OSA group (AHI<15, =44). The efficiencies of the scales in identification of patients with moderate or severe OSA were analyzed and compared.

RESULTSThe ROC curves showed that the four-variable scale and its modified version had higher area under curve (0.806 and 0.807, both <0.01) for diagnosis of moderate-severe OSA, and the cut-off values for Epworth scale, Berlin questionnaire, STOP-Bang questionnaire, SOS scale, four-variable scale and its modified version were 9, 2, 4, 15, 11, 10, respectively. The sensitivities, specificities, positive and negative predictive values of four-variable scale and its modified version in diagnosis of moderate-severe OSA were higher than those of other scales.

CONCLUSIONSCompared with Epworth scale, Berlin questionnaire, STOP-Bang questionnaire and SOS scale, the four-variable scale and its modified version are more effective in screening of OSA for patients with acute ischemic stroke.