More and more therapeutic monoclonal antibodies(mAbs)are widely used for treating various illnesses such as cancer and autoimmune diseases due to the specific and efficient properties of mAbs.All of the currently licensed therapeutic mAbs are of the IgG class.Fc region of IgG has a N-glycan which is structural heterogeneity.The glycan on Fc region has many significant roles on the structure,the effector functions and pharmacokinetics of mAbs.The glycan of Fc region can be changed through genome editing and optimization of cell culture condition.This review presents an overview of the role of the various glycans in the effector functions of therapeutic mAbs and the impact of various parameters on glycosylation pattern of therapeutic mAbs.

Objectives To study the changes of gastrointestinal hormones in chronic constipation. Methods 17 outpatient chronic constipation patients, and 10 normal persons were respectively chosen as observation group and control group. Fasting blood samples were taken in all patients. The serum levels of somatostatin (SS) and substance P (SP) were tested using RIA method.Results The serum level of SS and SP in observation group were (120.57?27.84)pg/ml and (7.68?2.5)pg/ml respectively, significantly higher than that in control group (P

In modern surgeries, ESU is an important electrosurgical equipment. However, the interference caused by ESU usually affects real-time monitoring of the patient. To solve these problems, the paper introduces some new ideas in analog circuits. To the problem of interference and base-line excursion, this paper proposes an adaptive comb filter with Phase-Locked Loop(PLL), besides digital comb filters. Following the frequency of power and sampling accordingly, this method could easily clear the interference, which could make the cost reduced.

Objective To study effect of Taxol on protein O-GlcNAcylation levels and investigate whether protein O-GlcNAcylation levels can affect the sensitivity of breast cancer cells to Taxol.Methods Western blot analysis was performed to examine protein O-GlcNAcylation levels and the expression of enzymes related to O-GlcNAcylation biosynthesis in Taxol treated breast cancer cells.RT-qPCR was used to analyze the effects of Taxol on OGA and OGT mRNA expression in cancer cells.The sulforhodamine B colorimetric assay was used to determine the effect of alteration of protein O-GlcNAcylation on the anti-proliferation of Taxol in breast cancer cells by adding OGA inhibitor and OGT inhibitor, respectively.Results Taxol treatment enhanced protein O-GlcNAcylation levels in dose-and time-dependent manners in breast cancer cell MDA-MB-231 ( P <0.05 ) .Taxol increased the mRNA levels of OGT and OGA after MDA-MB-231 cells were treated for 24 h(P<0.05).As OGA inhibitors increased protein O-GlcNAcylation levels, the sensitivity of MDA-MB-231 to Taxol was increased.As OGT inhibitor decreased protein O-GlcNAcylation levels, the sensitivity of MDA-MB-231 to Taxol was reduced.Conclusion Taxol treatment can enhance protein O-GlcNAcylation levels and the changes of O-GlcNAcylation levels alter the sensitivity of breast cancer cell MDA-MB-231 to Taxol.

As an emerging tumor therapy, high intensity focused ultrasound (HIFU) therapy has difficulty in controlling its dosage due to the complex human tissues. The dosage is related to the tumor such as its depth, size, characteristics and the tissue performances of its growth site. The existing cases are applied to establishing a repository with the above-mentioned parameters of the tumor analyzed. Then reasoning and self-learning are performed. So, the therapeutic dosage can be provided to the clinician when a new case occurs.

Objective To learn the change of causes sequences, the pattern and dynamic trend of causes of death for the inhabitants in Jiaxing from 2009 to 2014, and to provide a major reference for health decisions and disease control and prevention. Method This study was based on chronic disease surveillance information management data in Zhejiang province from 2009 to 2014. ICD-10 criteria and method was used to classify the causes of death. To evaluate health status of those residents, the relative health indicators such as mortality rate, constituent ratio, PYLL, AYLL, PYLL‰were used. Results The average mortality rate of residents was 691.92/100 000 of Jiaxing from 2009 to 2014, with male 760.73/100 000 and female 624.64/100 000 (the average mortality rate of male was significantly higher than that of female, χ2=455.52, P<0.01). The top five causes of death of local residents were malignant neoplasm, respiratory system diseases, cerebrovascular diseases, injury and poisoning, heart diseases, which accounted for 87.95%of all deaths. The mortality caused by malignant neoplasm was 189.53/100 000, which accounted for 31.90% of five main death causes (the rate of male was significantly higher than that of female, χ2=3767.70, P<0.01). The PYLL of malignant neoplasm were 38 368 years, which was the main reason. The AYLL of injury and poisoning were 9.58 years. Conclusion The average mortality rate of residents has been declining across the Jiaxing, but the mortality rate of malignant neoplasm is increasing year by year. The data suggested that malignant neoplasm, cardiovascular disease, unintentional falls, motor vehicle traffic accidents and pneumonia are major factors affecting the health of the population.

Amplitude integrated electroencephalogram (aEEG), also known as cerebral function monitor (CFM), is a non-invasive detection of brain function, having good accuracy in early diagnosis and prognosis evaluation of neonatal brain damage. Today, doctors classify amplitude integrated electroencephalogram mainly based on its waveform and amplitude, then they make correct diagnosis of brain function of neonates. However, in some cases, the amplitude and waveform of aEEG are not very clearly shown, the only way is relying on doctors' experience to give out judgement, which has some subjective factors, so doctors can not present accurate diagnostic information. To solve this problem by the use of non-linear dynamics, we calculate and analyze the correlation dimension, Lyapunov exponent and approximate entropy of the aEEG for neonates with convulsions and for normal neonates; then we take these three characters as a three-dimensional vector; finally, the aEEG of neonates with convulsions and the aEEG of normal neonates are distributed into two parts in threedimensional space, thus the correlation dimension, Lyapunov exponent and approximate entropy of the aEEG can reflect the internal information of neonatal brain function. Therefore, it can be used as a new method for studying neonatal aEEG.
Brain ; physiology ; Electroencephalography ; methods ; Humans ; Infant, Newborn ; Neonatal Screening ; methods ; Nonlinear Dynamics ; Seizures ; diagnosis ; physiopathology ; Signal Processing, Computer-Assisted

It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.

Objective:To determine the clinical, pathological and imaging phenotypes of pediatric patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy to explore its diagnostic strategies.Methods:The clinical features of 10 pediatric patients with anti-HMGCR myopathy in the Department of Neurology, Peking University First Hospital from July 2014 to July 2021 were collected. Muscle biopsies were performed in all patients, with histological, enzymatic histochemical and immunohistochemical staining.Results:The male to female ratio was 6∶4, the age of onset was 3-16 (8.3±3.7) years, 2 cases had subacute onset, and 8 cases experienced chronic progressive onset. All patients presented with neck and proximal muscular weakness of all limbs. Skin rash was observed in 2 cases. Serum creatine kinase was 998-27 981 U/L. The electromyography results were available from 6 cases, who experienced myogenic changes. The muscle magnetic resonance imaging was performed in 5 cases and revealed muscle edema predominantly in posterior compartment of thigh, with mild fatty infiltrate in 2 cases. An initial diagnosis was limb-girdle muscular dystrophy in 7 cases, but with subsequently negative genetic testing. Muscle biopsies revealed scattered necrotic fibers and regenerating fibers, complement deposition in sarcolemma basement-membrane areas of non-necrotic fibers and a few of lymphocyte infiltrate in all specimens. Moreover, a high frequency of major histocompatibility complex Ⅰ expression in muscle fibers was observed in 9 cases, proliferation of connective tissue of endomysium in 8 cases, muscle fiber hypertrophy in 4 cases and vacuoles in 2 cases.Conclusions:Pediatric anti-HMGCR myopathy is frequently misdiagnosed as muscular dystrophy. Systematic consideration of anti-HMGCR myopathy and testing for myositis specific antibody in children with genetically unconfirmed muscular dystrophy may help the differential diagnosis.

Objective:To analyze the clinical characteristics, imaging, myopathology and outcomes of patients with COVID-19 related autoimmune myopathy.Methods:The clinical features, serum creatine kinase (CK), myositis antibodies, muscle magnetic resonance imaging, myopathology and therapy of 5 patients with COVID-19 related autoimmune myopathy diagnosed in Peking University First Hospital from December 2022 to April 2023 were collected. The effects of the therapy after a short term follow up were analyzed.Results:Among the 5 patients, there were 3 males and 2 females, with onset age of 42-86 years. All patients presented with proximal muscle weakness in the recovery term of COVID-19. Myalgia was noted in 3 cases, dysphagia in 1, skin damage in 2, interstitial lung disease in 1. The serum CK of the 5 patients was 1 663-16 000 IU/L, 1 patient had anti-3-hydroxy-3-methylglutaryl-CoA reductase autoantibodies and 1 patient had anti-signal recognition particle autoantibodies. The electromyography showed myogenic lesions in all patients. Muscle magnetic resonance imaging showed diffuse muscle edema in all patients, myofascial edema in 3 and subcutaneous-tissue edema in 3. The muscle biopsies in 4 patients revealed necrotic myopathy,with high P62 expression in muscle fibers. The electromicroscopy of 2 patients revealed vacuolated mitochondria and intranuclear tubulofilamentous inclusions in muscle fibers. Four patients were treated with glucocorticoids, of whom 2 patients combined with intravenous immunoglobulin, tacrolimus or cyclophosphamide. One case had close monitoring without drug therapy. They showed significant improvement, but the CK was still abnormal in 4 patients.Conclusions:COVID-19 leads to immune mediated myopathy. The manifestation of patients is characterized by proximal predominant weakness and high creatine kinase level. Muscle magnetic resonance imaging shows diffuse muscle edema. The muscle biopsies reveal necrotic myopathy. The effectiveness of immunosuppression needs to be further studied.