Accidents ; Child ; Dinitrobenzenes ; poisoning ; Humans ; Male

Twenty two cases of acute agranulocytosis were treated with fetal liver infusion (FLI) in this study. The total effective rate was 90.91%. The FLI group markedly increased leukocyte counts and absolute value of granulocytes as compared with the control group. There were no significant side effects. The result shows that FLI would be helpful in the treatment of acute agranulocytosis. The mechanism of treatment of acute agranulocytosis with FLI is also discussed.

The research and development of monoclonal antibodies (mAbs) is a rapidly developing field. From the first generation of murine mAbs to the fourth generation of fully human mAbs, the efficacy and safety of mAbs in the treatment of various diseases have been continuously improved. In order to regulate the development and evaluation of mAbs, drug regulatory agencies and pharmacopeias of America and China have tried to issue feasible test procedures and acceptance criteria for quality evaluation of mAbs and biosimilars. Mass spectrometry (MS) technique with high sensitivity, resolution, selectivity, and specificity has become an important tool to evaluate the quality characteristics of monoclonal antibody-related products or specify mAb quality. The research of MS-based monoclonal antibody study involves structure characterization, impurity analysis, pharmacokinetics/pharmacodynamics (PK/PD), etc. This review focuses on the current quality control requirements of mAb related products and the development of MS technique for mAb quality characterization and specification. It is expected to provide information and references for evaluating the quality of monoclonal antibodies under research and development.

In recent years, the biopharmaceutical industry has grown rapidly, and the market size of monoclonal antibody drugs has increased significantly. Accurate structural characterization and quality control are the supporting technologies for the development of monoclonal antibody drugs. As a significant post-translational modification of antibody drugs, glycosylation has an important influence on its efficacy, stability, and immunogenicity. The existing literature usually uses liquid chromatography-mass spectrometry to perform major glycosylation modifications of monoclonal antibody drugs. Characterization, there are few studies on low-abundance glycosylation, but the characterization and control of low-abundance glycosylation cannot be ignored. In this study, we have established a qualitative and quantitative analysis technology for N-glycans based on RapiFluor-MS reagent-labeled monoclonal antibody drugs. This method has a short sample processing time and high sensitivity. It can not only characterize the main glycoforms of three monoclonal antibody drugs (adalimumab, bevacizumab, and trastuzumab) but also can quantify low-abundance N-glycans. The results of the study showed that the main glycoforms specified in the Pharmacopoeia could be detected in different batches of monoclonal antibody drugs, but the content of N-glycans in different batches of samples is not identical. After that, we analyzed the N-glycans connection sites and glycoforms at the intact glycopeptide level, further enriching the N-glycans structure information of the monoclonal antibody. The qualitative and quantitative analysis technology of N-glycans based on RapiFluor-MS reagent-labeled monoclonal antibody drugs can realize the in-depth characterization and control of glycosylation modification of monoclonal antibody drugs.

OBJECTIVETo study the effect of ginsenoside Rb1 on GSKbeta/IDE signal transduction pathway and Abeta protein secretion in hippocampal neurons of high glucose-treated rats.

METHODHippocampal neurons of 24 h-old newly born SD rats were primarily cultured, inoculated in culture medium under different conditions, and then divided into the normal group, the high glucose group, the LiCl group and the Rb1 group. After being cultured for 72 h, the expressions of their phosphorylated GSK3beta, total GSK3beta and IDE protein were detected by Western blotting analysis. The mRNA expressions of GSK3beta and IDE were determined by RT-PCR. The ELISA assay was used to detect the secretion of Abeta protein in cell supernatant.

RESULTCompared with the normal group, the high glucose group showed increase in the p/tGSK3beta protein ratio and the secretion of Abeta protein and decrease in IDE protein and mRNA (P < 0.05). Compared with the high glucose group, both Rb1 and LiCl groups showed decrease in the p/tGSK3beta protein ratio and the expression of Abeta protein and increase in IDE protein and mRNA expression (P < 0.05). Compared with the LiCl group, the Rb1 group showed no significant difference in the expressions of p/tGSK3beta protein, IDE protein, mRNA and Abeta protein expression. In addition, the GSK3beta mRNA expression of the four groups had no significant difference.

CONCLUSIONGinsenoside Rb1 may reduce the secretion of Abeta protein in hippocampal neurons by reducing the phosphorylation of GSK3beta, down-regulating the ratio of pGSK3beta/GSK3beta and upregulating the expression of IDE.

Amyloid beta-Peptides ; genetics ; metabolism ; secretion ; Animals ; Dietary Carbohydrates ; adverse effects ; Gene Expression Regulation ; drug effects ; Ginsenosides ; pharmacology ; Glucose ; adverse effects ; Glycogen Synthase Kinase 3 ; genetics ; metabolism ; Glycogen Synthase Kinase 3 beta ; Hippocampus ; cytology ; Insulin ; metabolism ; Insulysin ; genetics ; metabolism ; Neurons ; cytology ; drug effects ; metabolism ; secretion ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects

Action Potentials ; Animals ; Female ; Heart ; physiology ; Male ; Membrane Transport Proteins ; genetics ; Mice ; Mice, Knockout ; Myocardium ; metabolism ; Patch-Clamp Techniques ; Sodium Channels ; physiology

The global incidence rate of nonalcoholic steatohepatitis (NASH) continues to rise. The pathogenesis of NASH is complex, and there is no effective clinical treatment. Previous study has shown that DEAD box protein 5 (DDX5) can significantly alleviate the NASH process in mice. This study screened the natural product library of the research group and found that the active compound hypercalin B (HB) in Hypericum beanii N. Robson, a traditional Chinese medicine, can upregulate the expression of DDX5 protein in a dose-dependent manner. In this study, an in vitro model of NASH stimulated by palmitic acid (PA) and an animal model of NASH induced by the methionine- and choline-deficient diet (MCD) were constructed. Different concentrations of HB were used to investigate the effect and mechanism of HB in alleviating NASH progression. All animal experiments in this paper were approved by the Ethics Committee of China Pharmaceutical University (NO: 2021-02-003). In vitro model results showed that HB significantly reduced the intracellular lipid deposition induced by free fatty acid (FFA). Animal experiments showed that HB improved liver injury by significantly reducing lipid accumulation in the liver of NASH mice, and reducing serum aspartate transaminase (AST) and alanine transaminase (ALT) levels. Moreover, HB could inhibit liver inflammation by reducing the mRNA levels of liver pro-inflammatory cytokines including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNFα). Further research showed that HB could reduce the phosphorylation level of the mechanical target of rapamycin (mTOR) and reduce the expression of sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN), thereby improving lipid metabolism and alleviating NASH progression, and the effects of HB against NASH were dependent on DDX5. In conclusion, HB can improve lipid metabolism and inhibit inflammatory activation by suppressing mTORC1 pathway via upregulating DDX5 protein, and showed promising anti-NASH activity in vitro and in vivo.

Adult ; Aged ; Breast Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Female ; Gene Amplification ; Genital Neoplasms, Male ; genetics ; metabolism ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Paget Disease, Extramammary ; genetics ; metabolism ; pathology ; surgery ; Paget's Disease, Mammary ; genetics ; metabolism ; pathology ; surgery ; Penile Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Receptor, ErbB-2 ; genetics ; metabolism ; Scrotum ; Vulvar Neoplasms ; genetics ; metabolism ; pathology ; surgery

Objective To compare the effect of active compression-decompression cardiopulmonary resuscitation(ACD-CPR) with standard- cardiopulmonary resuscitation(S-CPR) on ventricular function in a canine ventricular fibrillation model. Methods Ventricular fibrillation was induced in anesthetized and instrumented canine. Twenty-four dogs were randomly assigned to either ACD-CPR group or S-CPR group.After 4 minutes of untreated VF,two-dimension echocardiography was used to evaluate the left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV) and left ventricular ejection fraction (LVEF) of every canine of the two groups when they were undergoing cardiopulmonary resuscitation. Results During ventricular fibrillation, both ACD-CPR group and S-CPR group showed decreased LVEDV compared with pre-ventricular fibrillation, but not statistically significant( P ＞0.05).LVEDV was increased in ACD-CPR group compared with S-CPR group, but not statistically significant (P＞ 0. 05). Both ACD-CPR group and S-CPR group showed significantly increased LVESV compared with pre-ventricular fibrillation,of which the difference was statistically significant ( P ＜0. 001). Both ACD-CPRgroup and S-CPR group showed significantly decreased LVEF compared with pre-ventricular fibrillation,of which the difference was statistically significant (P ＜0. 001). LVEF was increased in ACD-CPR group compared with S-CPR group,of which the difference was statistically significant ( P = 0.019). Conclusions Compared with S-CPR,ACD-CPR resulted in higher LVEF.

BACKGROUND:The self-locking ROI-CTM interbody fusion has zero profile design which can significantly reduce the impact on the esophagus and pharynx, and also simplify the operation procedure. However, there is no report whether it has satisfactory outcomes in the treatment of Hangman fractures.
OBJECTIVE: To compare the clinical effects of ROI-CTM or titanium plate internal fixation on postoperative cervical stability and fusion rate in the treatment of Hangman fractures.
METHODS:Twenty-one cases of Hangman fractures were included, including 13 males and 8 females, aged 25-62 years old. Fifteen cases were treated with titanium plate internal fixation, and the other five cases were treated with ROI-CTM fusion device. Cervical anteroposterior and lateral radiographs, lateral flexion extension radiographs and CT scanning were carried out before, 3 days and 3 months after repair to assess angular displacement, horizontal displacement and fusion rate; visual analog scale score and Bazaz dysphagia score were determined.
RESULTS AND CONCLUSION:At 3 days after operation, the ROI-CTM group was significantly better than the titanium plate group in visual analog scale scores and Bazaz dysphagia grade (P < 0.05), and there were no significant differences in angular displacement and horizontal displacement (P > 0.05). However, at 3 months after operation, there was no significant difference between the two groups in visual analog scale score, Bazaz dysphagia grade, angular displacement and horizontal displacement and fusion rate (P > 0.05). Postoperative complete reduction rate of spondylolisthesis was higher in the ROI-CTM group than the titanium plate group (P < 0.05). In each group, the angular displacement and horizontal displacement were significantly reduced at 3 day and 3 months after operation (P < 0.05), but there was no significant difference at 3 days and 3 months after operation (P > 0.05). No rejection reaction, internal fixation fracture and loosening occurred in the two groups. These findings indicate that the self-locking ROI-CTM fusion for treatment of Hangman fractures are characterized as higher reduction rate of spondylolisthesis, less dysphagia, and less neck pain.