One-step synthesis of site-specific antibody-drug conjugates by reprograming IgG glycoengineering with LacNAc-based substrates

Glycosite-specific antibody‒drug conjugatess (gsADCs), harnessing Asn297 N-glycan of IgG Fc as the conjugation site for drug payloads, usually require multi-step glycoengineering with two or more enzymes, which limits the substrate diversification and complicates the preparation process. Herein, we report a series of novel disaccharide-based substrates, which reprogram the IgG glycoengineering to one-step synthesis of gsADCs, catalyzed by an endo-N-acetylglucosaminidase (ENGase) of Endo-S2. IgG glycoengineering via ENGases usually has two steps: deglycosylation by wild-type (WT) ENGases and transglycosylation by mutated ENGases. But in the current method, we have found that disaccharide LacNAc oxazoline can be efficiently assembled onto IgG by WT Endo-S2 without hydrolysis of the product, which enables the one-step glycoengineering directly from native antibodies. Further studies on substrate specificity revealed that this approach has excellent tolerance on various modification of 6-Gal motif of LacNAc. Within 1 h, one-step synthesis of gsADC was achieved using the LacNAc-toxin substrates including structures free of bioorthogonal groups. These gsADCs demonstrated good homogeneity, buffer stability, in vitro and in vivo anti-tumor activity. This work presents a novel strategy using LacNAc-based substrates to reprogram the multi-step IgG glycoengineering to a one-step manner for highly efficient synthesis of gsADCs.

Effects of Baduanjin and Balancer Exercise on Motor and Non-motor Symptoms of Parkinson's Disease / 中国康复理论与实践

Objective:To explore the effects of Baduanjin and balancer exercise on motor and non-motor symptoms for patients with mild to moderate Parkinson's disease (PD). Methods:From May, 2017 to September, 2018, 31 patients with PD were collected from the inpatients, outpatients and outside of our hospitals. The patients accepted Baduanjin and balancer exercise successively, three weeks for each exercise, and were assessed with Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I, II, III and IV, and Non-motor Symptoms Scale (NMSS) before and after each exercise. Results:Four cases dropped out during Baduanjin exercise. The total score, the scores of part I, II and III of MDS-UPDRS, and NMSS score (t > 3.274, P < 0.01) decreased significantly after Baduanjin exercise. Other three cases dropped out during balancer exercise. The total score and the score of part III of MDS-UPDRS decreased significantly after balancer exercise (t > 2.763, P < 0.05). Conclusion:Baduanjin exercise can improve the motor and non-motor symptoms of mild to moderate PD, but not significant for motor complications; while balancer exercise can improve the motor symptoms, but not significant for non-motor symptoms and motor complications.

Risk assessment of cadmium contamination and dietary exposure in market aquatic products in one district of Shanghai / 上海预防医学

Objective To investigate the status of cadmium contamination in commercially sold aquatic products and to analyze the risk of dietary intake of cadmium among residents in one district of Shanghai. Methods Multistage sampling was used to collect 397 animal aquatic products from agricultural markets and supermarkets in 11 communities (townships), the District from 2018 to 2019.Cadmium content was tested according to national standard.The status of cadmium contamination was assessed by single factor pollution index(Pi)method.Risk of dietary intake of cadmium among residents was assessed by point evaluation method in combination with food consumption and dietary survey in 2013 and calculation of safe limits for cadmium in various aquatic diets(MOS). Results The detection rate of cadmium was 75.06% in the 397 animal aquatic products and the content of cadmium in 10 samples which crabs were totally exceeded the standard, accounting for 2.52%.The average contents of cadmium in crabs, bivalves which were higher than in shrimps(11.0 μg/kg), gastropods(7.6 μg/kg) and marine fish(3.8 μg/kg) were respectively 140.0 μg/kg and 90.0 μg/kg(χ2=186.41, P < 0.005), but no cadmium was detected in freshwater fish.The single factor pollution index(Pi) of crabs was 0.280 which meant light pollution and the Pi of other kinds of aquatic products was respectively under 0.100 that meant no cadmium contamination.The consumption of animal aquatic products was the highest in freshwater fish followed by shrimps, marine fish and crabs.The MOS of every kind of aquatic products is higher than 1 which meant cadmium intake from commercially sold animal products was an acceptable health risk for the population. Conclusion The risk level of cadmium intake by residents in the district through commercially sold animal aquatic products is relatively low, but the cadmium pollution status of commercially sold crustacean crabs should be vigilant, and the intake of crabs is advised to be reduced as far as possible.Relevant departments should also pay attention and strengthen monitoring and management in this regard.

Theoretical and Clinical Evidences of Dispelling Wind and Eliminating Dampness Therapy for Allergic Rhinitis / 中国实验方剂学杂志

The pathological mechanism of allergic rhinitis (AR) involves hierarchically acute and chronic reactions among antigens, immunocytes, immunoglobulins and inflammatory factors. AR, which is characterized by heterogeneity, reacts differently to the current treatment on diverse individuals. Some patients receive unsatisfying clinical outcomes after the treatment. Chinese herbal medicine has become a frequent option to treat AR because it can improve clinical symptoms with excellent safety. The description of Biqiu in ancient Chinese medical literatures is very similar to the clinical manifestation of AR. The major pathogeneses of Biqiu included infection of wind-cold pathogens, deficiency and cold in the lung, and evil depression into heat and wind. Therefore, in modern traditional Chinese medicine （TCM）, Biqiu is considered as an integration of AR, allergic sinusitis and vasomotor rhinitis. According to the pathogenesis and clinical manifestations of Biqiu (including AR), this disease belongs to wind disease in TCM. But modern TCM focuses on deficiency of internal organs and ignores wind evil in syndrome differentiation, contrary to the fact that wind medicine is always used in treating AR. This even leads to an abnormal phenomenon that clinical studies attach little importance to syndrome differentiation. In this paper, we started from the phenomenon that wind medicine is always used in TCM for AR, considering TCM literatures and the study results of modern therapy for wind diseases, and put forward the ideas as follows: AR belongs to exogenous wind disease in TCM, and wind pathogen is the major pathogen, in clinical syndrome differentiation, we should attach more importance to wind evil, and dispelling wind and eliminating dampness is the key to treatment. Meanwhile, based on the fact that most of the classical prescriptions with good effectiveness for AR originated from Treatise on Febrile Disease, mainly including the wind medicines for treating exogenous diseases, it can be inferred that the wind-dispelling and itch-arresting effects of wind medicines are helpful to alleviate or block the allergic reaction of nasal mucus and achieve the goal of relieving itching and sneezing, and the wind-dispelling and dampness-eliminating effects are helpful to alleviate the edema of nasal mucus and achieve the goal of relieving running nose and nasal obstruction. In modern researches, it is also found that classical prescriptions which take wind medicine as a principle component and wind medicine used in AR treatment have good anti-inflammatory, anti-allergic and immune function adjusting effects. This indicates that dispelling wind and eliminating dampness and the wind medicine treatment under its instruction not only correspond to TCM theory, but also have modern science evidences.

Clinical value of D-dimer and CRP in evaluating the prognosis of 2019 novel coronavirus-infected pneumonia / 医学研究生学报

ObjectiveTo investigate the relationship between the levels of D-dimer and inflammatory factors C-reactive protein（CRP）and prognosis in patients with 2019 novel coronavirus-infected pneumonia（COVID-19）.Methods The clinical data of a total of 242 patients with COVID-19 who were treated in hospital from February 4th 2020 to February 18th 2020 were analyzed retrospectively. According to the classification standard,the patients with COVID-19 were divided into common patients(131 cases), severe patients（88 cases）, and critical patients（23 cases）. The difference between the levels of D-dimer and CRP in patients with pneumonia of different severity and clinical outcomes was compared and the correlation between D-dimer and CRP was analyzed.ResultsThe levels of D-dimer and CRP in severe and critical patients were significantly higher than those in common patients(P<0.05). The levels of CRP in critical patients were significantly higher than those in severe patients(P<0.05). These two indicator levels of patients who died of COVID-19 within 30 dayswere significantly higher than those who survived. Pearson correlation analysis showed that the levels of D-dimer were positively correlated with the levels of CRP(r=0.649，P<0.05).ConclusionD-dimer and CRP are highly expressed in severe and critical patients, and the severe abnormality of the two indicators in the early stage of COVID-19 predicted the poor prognosis. D-dimer and CRP have certain clinical value in evaluating the severity and prognosis of COVID-19.

An experimental study of Zn/Ca/P-containing coatings on titanium implant surface modified by plasma electrolytic oxidation / 中华口腔医学杂志

Objective@#To explore the osteogenic activity of Zn/Ca/P-containing coatings on titanium implant surface modified by plasma electrolytic oxidation (PEO).@*Methods@#Three groups implants including Zn/Ca/P-containing surface treated by PEO in experimental groups and Ca/P-containing and TiO2 sandblasted surface in control group were randomly inserted in the bilateral mandibular of rabbits. Mechanical testing and implant-bone interface observation were performed at 4, 6, 8, 10 and 12 weeks after implantion.@*Results@#Zn/Ca/P-containing coating presented a microporous structure. The push-out value indicated the statistical differences among the three groups at each observed time point (P<0.05), and implant-bone bonding power reached a maximum value at 12 weeks, those in the Zn/Ca/P-containing group [(1.57±0.26) MPa] was higher than those in the group with sandblasted surface [(0.83±0.24) MPa] (P<0.05). Histological examination and implant-bone interface observation using field scaning electron microscope (FSEM) showed that the new bone of implant-bone interface increased with healing time and the result from Zn/Ca/P-containing group was superior to that from the control groups at each observed time point.@*Conclusions@#Zn/Ca/P-containing coatings by PEO can accelerate bone formation and remodeling, and enhance bone-implant bonding force.

Inhibitory Effect of Cinnamaldehyde on Proliferation, Migration and Tube Formation of VEGF-induced Endothelial Cells via JAK2/STAT3 Pathway / 中国实验方剂学杂志

Objective: To investigate the effect and mechanism of cinnamaldehyde on the angiogenesis of diabetic retinopathy, and the effect of cinnamaldehyde on vascular endothelial growth factor (VEGF) induced proliferation, migration, tube formation and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway of EA.hy 926 cells were observed. Method:EA.hy 926 cells were divided into normal control group, model group (7 μg·L-1 VEGF), and VEGF+cinnamaldehyde group (60, 90, 120, 150 μmol·L-1). The methyl thiazolyl tetrazolium (MTT) assay and scratch test were used to observe the effect of cinnamaldehyde on the proliferation and migration of EA. hy 926 cells induced by VEGF. EA. hy 926 cells were divided into normal control group, model group (7 μg·L-1 VEGF), and VEGF+cinnamaldehyde group (90, 150 μmol·L-1). The tube formation experiment was used to observe the effect of cinnamaldehyde on the tube formation of EA. hy 926 cells induced by VEGF. EA. hy 926 cells were divided into normal control group, model group (7 μg·L-1 VEGF), VEGF+AG490 group (50 μmol·L-1), VEGF+cinnamaldehyde group (90 μmol·L-1), VEGF+cinnamaldehyde group (150 μmol·L-1), and VEGF+cinnamaldehyde group (150 μmol·L-1)+AG490 group (50 μmol·L-1). Western Blot method was used to explore the effect of cinnamaldehyde on the JAK2/STAT3 signaling pathway in EA.hy 926 cells induced by VEGF. Result:Compared with the control group, model group obviously promoted the proliferation and migration of EA.hy 926 cells(P-1) significantly suppressed VEGF-induced proliferation and migration of EA.hy 926 cells (P-1) showed an obvious inhibitory effect on the number of nodes, junctions and meshes of tubules (PPPP-1) significantly reduced the expressions of P-JAK2, P-STAT3, STAT3 proteins (P-1) obviously reduced the expressions of p-STAT3 and STAT3 proteins (PPConclusion:Cinnamaldehyde showed a significantly inhibitory effect on the proliferation, migration and tube formation of VEGF-induced EA.hy 926 cells, which was related to the inhibition of the activation of JAK2/STAT3 pathway.

Evaluation of implant-bone contact interface on active zinc coated implants / 国际生物医学工程杂志

Objective To evaluate the implant-bone interfaces on implants with active Zn coating in a rabbit model.Methods Pure titanium cylinder implants,fabricated by machining,were prepared by surface microarc oxidation (MAO).The MAO-Zn/Ca/P coated (experimental group) and the MAO-Ca/P coated (control group)implants were randomly placed in the rabbit mandible.The samples were harvested at 4 and 12 weeks postoperatively,histological analysis on the implant-bone interfaces of the two implants was performed,and the bone coverage was compared.Results The coatings of MAO presented micro-porous structure with dense and uniform features,in which size of micro-porous increased with zinc element.The histological examination of implant-bone contact interfaces showed that the bone tissues attached on the coatings increased with time.Further,the adhered bone tissue in the experimental group was thicker and denser and had a larger amount compared to that in the control group at 4 and 12 weeks postoperatively.The bone coverage in the experimental group (70.8％±13.6％) at 12 weeks postoperatively was significantly higher than that in the control group (55.9％±13.8％) (P＜0.05).The results of bone interface element showed that the apatite layer was precipitated at 12 weeks.Conclusion The addition of active zinc element can improve the biological activity of the coating,enhance the osteogenesis ability of the coating,and accelerate the osseointegration of implant-bone interfaces.

Effect of Tianhuang Granule on intracranial pressure and serum matrix metalloproteinase-9 in patients with acute cerebral hemorrhage / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effect and mechanism of Tianhuang Granule (, THG) on: hydrocephalus in the patients with acute cerebral hemorrhage (ACH) through intracranial pressure (ICP) monitoring, serum matrix metalloproteinase-9 (MMP-9) level observation, and National Institutes of Health Stroke Scale (NIHSS) scoring (for nerve function de ficit).</p><p><b>METHODS</b>Sixty patients with ACH were equally randomized: into two groups by lottery, the control group and the THG group; all were treated with conventional therapy, but to the patients in the THG group, THG was given orally in addition for 28 days. Changes of ICP, MMP-9 expression, and NIHSS scores, as well as the degree of cerebral hematoma and hydrocephalus (by cranial CT scanning) in the patients, were estimated and compared.</p><p><b>RESULTS</b>(1) ICP was lowered more significantly in the: THG group, showing a significant difference between groups on day 7 (P<0.05). (2) MMP-9 expression was down-regulated in the THG group more significantly and earlier than that in the control group. (3) The degrees of cerebral hematoma and hydrocephalus in the THG group on day 7 were reduced significantly as compared with those on day 3 (P<0.05), but in the control group, the day of significant reduction was delayed to day 14, and the degrees on day 7 and day 14 in the two groups were significantly different (P<0.05 and P<0.01). (4) NIHSS score was significantly lower in the THG group than that in the control group on day 14 and day 28 (P<0.05 and P<0.01).</p><p><b>CONCLUSION</b>THG can effectively lower ICP, down-regulate MMP-9 expression, promote the absorption: of cerebral hematoma and hydrocephalus, and improve the nerve function, showing a clinical effectiveness than conventional therapy.</p>

Study on the safety and immunogenicity of group A + C meningococcal polysaccharide vaccine / 中华流行病学杂志

<p><b>OBJECTIVE</b>In order to evaluate the safety and immunogenicity of group A + C meningococcal polysaccharide vaccine, a controlled field trial was performed among children at 6-24 months and 5-13 years old in Longsheng county, Guangxi Zhuang Autonomous Region.</p><p><b>METHODS</b>More than 600 children were selected in this trial. 428 children, aged 6-24 month-old and 5-13 year-old were involved in two experimental groups and were inoculated 100 microg of group A + C meningococcal polysaccharide vaccine. 103 children in positive control group were inoculated 50 microg of group A meningococcal polysaccharide vaccine while 94 children in negative control group were inoculated 30 microg of Typhoid Vi polysaccharide vaccine. Both systemic and local reactions were observed in each group at 6 h,24 h,48 h and 72 h after inoculation. Blood samples were collected in all children before and at 1 month after inoculation. Additionally, at least 50 blood samples were taken in each experimental group at 6 and 12 months after inoculation. Serum bactericidal antibody was tested by micro bactericidal test.</p><p><b>RESULTS</b>Both systemic and local reactions were mild in two experimental groups with only 3 children (0.7%) had > or = 37. 6 degrees C fever, 4 children (0.9%) appeared mild areola but all adverse reaction disappeared within 48 hours. In 5-13 year-old experimental group, the rates for four-fold increase of bactericidal antibody were 96.59% and 92.15% to group A and group C meningococcus respectively at 1 month after inoculation, and remained 90.91% and 90.08% at 12 months after inoculation.</p><p><b>CONCLUSION</b>Group A + C meningococal polysaccharide vaccine was safe and having good immunogenicity among Chinese children.</p>

The clinical significance of the epithelial cellular adhesion molecule(Ep-CAM)expression in esophageal squamous cell carcinoma(SCC) / 肿瘤研究与临床

Objective To evaluate the clinical significance of epithelial cellular adhesion molecule (Ep-CAM)expression in esophageal squamous cell carcinoma(SCC).Methods The Ep-CAM expression was immunohistochemically investigated in 70 normal esophageal mucosas,SCCs and 72 lymph nodes.Results Ep-CAM expression was observed in 94.3% of the tumors,but no expression in the normal mucosa.The Ep- CAM expression was not significantly different between different tumor scales and tumors invading depths,its expression level was relevant with the tumors differentiation and lymph node metastases(P

Isolation and identification of Japanese encephalitis virus in Liaoning Province / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To study arboviruses carried by mosquitoes in Liaoning Province in 2002.</p><p><b>METHODS</b>Totally 4927 mosquitoes were collected from Liaoning Province in July 2002. Virus strains were isolated by inoculating BHK-21, C6/36 and Vero cells. The newly isolated strains were identified by serological (ELISA and IFA) and molecular methods (Real-Time PCR and RT-PCR).</p><p><b>RESULTS</b>Two strains were isolated from mosquitoes causing cytopathogenic effect (CPE) on cells and were fatal to suckling mice. Serological tests showed that both were positive for the antibody to JEV. The PrM and E gene were cloned and sequenced. The phylogenetic analysis showed that the new isolates belonged to genotype I, JEV. Sequence analysis showed that the homology of nucleotide sequences and amino acid (AA) sequences between the two strains was 100%. Compared with the nucleotide sequences between the two strains and the standard JEV vaccine strain SA14-14-2, the difference was up to 4.11%, and the difference of AA was 0.6%.</p><p><b>CONCLUSION</b>Two strains of JEV were isolated and identified in Liaoning province, both belonged to genotype I JEV.</p>

Arbovirus survey in some regions in Heilongjiang province / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>Mosquitoes were collected in Heilongjiang province in 2002, four virus strains were isolated by inoculation of homogenates onto BHK cell lines. The viruses were identified. Multiple alignment and phylogenetic analysis were carried out by Clustal X (1.8) program.Amino acid (AA) analysis was carried out by GENEDOS (3.2).</p><p><b>RESULTS</b>Biological characters of four newly isolated strains were examined and it was found that all of them could produce cytopathogenic effect (CPE) in BHK cells, killing sucking mice. Serological tests showed that all of these stains reacted positively to JEV antibodies. PrM and E gene regions were amplified and sequenced. Phylogenic analysis showed that all the newly isolated JEV strains belong to genotype III. Using the vaccine strains (SA14-14-2) as control, analysis of the E gene of the new strains and two JEV strains (47, Ha-3) isolated previously from Heilongjiang province showed that these new strains' nucleotide sequence had a homology of up to 99.9% and the amino acid sequence homology up to 99.8%, respectively. Compared with the standard JE vaccine strain SA-14-14-2 and the four new strains, the nucleotide sequence homology was 97.3% and amino acid sequence homology was between 96.8% and 97.0%, respectively. Compared with vaccine strain, there were seven common variations in all the four newly isolated strains.</p><p><b>CONCLUSION</b>Four JE virus strains were isolated in Heilongjiang province. As compared to the vaccine strain, six variations were found in the newly isolated strains at the eight sites relevant to the virulence of the virus.</p>

Characteristics of the occurrence of silicosis in the workers exposed to uranium dust / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To understand the laws and characteristics of silicosis incidence of the workers exposed to the uranium dust from 1956 to 2002.</p><p><b>METHODS</b>The length of employment, age of occurrence of silicosis, and its duration and death age were compared between the uranium miners and uranium geological prospecting teams, and also between the miners exposed to uranium dust and those exposed to mixed uranium dust by single factor analysis method.</p><p><b>RESULTS</b>With time going on, the length of employment, age of occurrence of disease and its duration and death age were prolonged respectively in the workers exposed to uranium dust. The length of employment and age of occurrence of disease in uranium geological prospecting teams [(10.15 +/- 5.95) and (40.60 +/- 9.86) years respectively] were shorter than those in uranium miners [(14.23 +/- 8.12) and (41.38 +/- 10.98) years], but the duration (P(50)) and death age were longer [(14.29 years vs 12.52 years), (53.69 +/- 10.04) years vs (51.45 +/- 10.85) years respectively]. The length of employment and age of occurrence of disease in those exposed to uranium dust only [(11.78 +/- 8.06) and (38.04 +/- 9.89) years] were shorter than those exposed to mixed uranium dust [(12.74 +/- 6.29) years, (41.40 +/- 10.67) years], but the duration (P(50)) and death age were longer than the mixed uranium dust ones [(14.59 years vs 13.20 years), (53.93 +/- 10.60) years vs (51.82 +/- 10.20) years].</p><p><b>CONCLUSION</b>The difference in the occurrence of silicosis in the workers exposed to uranium dust may be attributed to the physical and chemical character of the uranium dust and the different working circumstance.</p>