Endo-beta-N-acetylglucosaminidase: Possible Functions and Mechanisms / 生物化学与生物物理进展

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Allergy Associated With N-glycans on Glycoprotein Allergens / 生物化学与生物物理进展

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

Thinking about development of multi-channel surveillance and multi-dimensional early warning system of emerging respiratory communicable diseases / 中华流行病学杂志

The world has paid a heavy price for the pandemic of the emerging respiratory communicable disease, so more concern about communicable disease surveillance and early warning has been aroused. This paper briefly reviews the establishment of the surveillance and early warning system of respiratory communicable diseases in China, discusses its future development and introduces the novel surveillance methods and early warning models for the purpose of establishment of a multi-channel surveillance and multi-dimensional early warning system of communicable diseases in the future and the improvement of the prevention and control of emerging respiratory communicable diseases in China.

Clinical characteristics and severe risk factors of tsutsugamushi disease / 中国热带医学

@#Abstract: Objective To investigate the clinical features and risk factors for severe tsutsugamushi disease, so as to provide reference for diagnosis and differentiation of severe tsutsugamushi disease as soon as possible. Methods The clinical data of 178 cases of inpatients with tsutsugamushi disease admitted to the Guangzhou Eighth People's Hospital, Guangzhou Medical University from January 2016 to September 2021 were collected and analyzed according to their gender, age, underlying diseases, clinical characteristics at admission, laboratory examination results within 24 hours of admission and epidemiological history. The patients were divided into the severe group and the non-severe group according to the diagnostic criteria. The data of clinical characteristics, laboratory examination and prognosis of the two groups were compared. Multivariate logistic regression analysis was performed on the variables with statistical significance and the receiver operating characteristic curve (ROC) was drawn. Results A total of 178 patients were included in this study, with 37 in the severe group and 141 in the non-severe group. Compared with the non-severe group, the age of the severe group was older, the underlying diseases were more, the incidence of dyspnea and the levels of white blood cell, total bilirubin, aspartate aminotransferase, lactate dehydrogenase, cystatin C, uric acid and serum creatinine were significantly increased, the levels of platelet and albumin were significantly decreased (all P<0.05). The dyspnea [odds ratio (OR value)=8.93, 95% confidence interval (CI): 1.200-66.424; P=0.032], total bilirubin (OR=1.091, 95%CI: 1.028-1.159; P=0.004) and serum creatinine (OR=1.052, 95%CI: 1.004-1.102; P=0.033) were independent risk factors for severe tsutsugamushi disease. The area under ROC curve of total bilirubin and serum creatinine were 0.777 and 0.764, respectively (both P<0.01), indicating high predictive value for severe tsutsugamushi disease. The optimal cut-off value for total bilirubin was 23.01 µmol/L, with a sensitivity of 54.10% and a specificity of 90.60%; the optimal cut-off value for creatinine was 126.45 µmol/L, with a sensitivity of 43.20% and a specificity of 100.00%. The case fatality rate of severe tsutsugamushi disease was 2.70%. Conclusions The patients with severe tsutsugamushi disease are older, and have more underlying diseases. Dyspnea, increased total bilirubin and elevated serum creatinine are independent risk factors for severe tsutsugamushi disease, which can help in the early identification of severe tsutsugamushi disease early.

Research progress on the burden of respiratory syncytial virus infection in the elderly / 中华预防医学杂志

Human Respiratory Syncytial Virus (HRSV) is a serious threat to the population health. The elderly are one of the susceptible populations. The prevalence of HRSV in the elderly is generally higher than that in other age groups except children, which has gradually attracted attention in recent years. This paper reviewed the prevalence, common complications and major complications of HRSV in the elderly, briefly expounded the economic burden of HRSV infection, and proposed that attention should be paid to the disease burden of the elderly after HRSV infection, timely treat common complications, so as to reduce the occurrence of adverse survival outcomes and provide scientific evidence for the prevention and control of HRSV infection in the elderly.

Research and reflection on the diversified method system of multi-stages and multi-scenarios surveillance and early warning of infectious diseases / 中华预防医学杂志

With the outbreak of infectious diseases, more and more attention has been paid to surveillance and early warning work. Timely and accurate monitoring data is the basis of infectious diseases prevention and control. Effective early warning methods for infectious diseases can improve the timeliness and sensitivity of early warning work. This paper briefly introduces the intelligent early warning model of infectious diseases, summarizes the emerging surveillance and early warning methods of infectious diseases, and seeks the possibility of diversified surveillance and early warning in different epidemic stages and different outbreak scenarios of infectious diseases. This paper puts forward the idea of constructing a diversified method system of infectious diseases surveillance and early warning based on multi-stages and multi-scenarios and discusses the future development trend of infectious diseases surveillance and early warning, in order to provide reference for improving the construction level of infectious diseases surveillance and early warning system in China.

Research and reflection on the diversified method system of multi-stages and multi-scenarios surveillance and early warning of infectious diseases / 中华预防医学杂志

With the outbreak of infectious diseases, more and more attention has been paid to surveillance and early warning work. Timely and accurate monitoring data is the basis of infectious diseases prevention and control. Effective early warning methods for infectious diseases can improve the timeliness and sensitivity of early warning work. This paper briefly introduces the intelligent early warning model of infectious diseases, summarizes the emerging surveillance and early warning methods of infectious diseases, and seeks the possibility of diversified surveillance and early warning in different epidemic stages and different outbreak scenarios of infectious diseases. This paper puts forward the idea of constructing a diversified method system of infectious diseases surveillance and early warning based on multi-stages and multi-scenarios and discusses the future development trend of infectious diseases surveillance and early warning, in order to provide reference for improving the construction level of infectious diseases surveillance and early warning system in China.

Comparison of the effect of microwave ablation and surgical resection in the treatment of primary liver cancer / 新乡医学院学报

Objective To compare the clinical effect of microwave ablation and surgical resection in the treatment of primary liver cancer.Methods A total of 76 patients with primary liver cancer were selected from May 2010 to June 2012 in the Fourth People's Hospital of Shangqiu City.The patients were divided into microwave ablation group (n =46) and hepatectomy group (n =30) according to the treatment.The operation time,blood loss,hospitalization time,the levels of serum alanine aminotransferase (ALT) and total bilirubin (TBIL) before and after operation,and postoperative complications were compared between the two groups.All patients were followed up for five years,and the disease-free survival rates of 1-,3-and 5-year were observed and compared between the two groups.Results The operation time and hospitalization time in the microwave ablation group were significantly shorter than those in the hepatectomy group (P ＜ 0.05),and the intraoperative blood loss in the microwave ablation group was significantly less than that in the hepatectomy group (P ＜ 0.05).There was no significant difference in the levels of serum ALT and TBIL between the two groups before operation (P ＞ 0.05).The levels of serum ALT and TBIL at the time points of one day and one week after operation were significantly higher than those before operation in the hepatectomy group (P ＜ 0.05).There was no significant differences in the levels of serum ALT and TBIL in the microwave ablation group between before operation and one day or one week after operation (P ＞ 0.05).The levels of serum ALT and TBIL in the microwave ablation group were significantly lower than those in the hepatectomy group at the time points of one day and one week after operation (P ＜ 0.05).The incidence of postoperative complication in the microwave ablation group and the hepatectomy group was 4.35％ (2/46) and 23.33％ (7/30) respectively,the incidence of postoperative complication in the microwave ablation group was significantly lower than that in the hepatectomy group (x2 =6.269,P ＜ 0.05).The disease-free survival rate of 1-,3-and 5-year was 67.39％ (31/46),39.13％ (18/46) and 28.26％ (13/46) respectively;and the tumor recurrence rate was 54.35％ (25/46) in the microwave ablation group.The disease-free survival rate of 1-,3-and 5-year was 70.00％ (21/30),50.00％ (15/30) and 33.33％ (10/30) respectively;and the tumor recurrence rate was 50.00％ (15/30) in the hepatectomy group.There was no significant difference in the disease-free survival rate of 1-,3-and 5-year and tumor recurrence rate between the two groups (P ＞ 0.05).Conclusion Microwave ablation therapy in the treatment of primary liver cancer has less trauma,less intraoperative blood loss,shorter hospitalization time,the lower incidence of postoperative complication,high safety and feasibility.Microwave ablation can better protect the liver function of patients.Microwave ablation and hepatectomy for primary liver cancer can achieve the similar disease-free survival rate and tumor recurrence rate.

Prevalence and Antimicrobial Susceptibility of Mycobacterium abscessus in a General Hospital, China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To gain greater insight into the prevalence drug resistant profiles of M. abscessus from a general hospital in Beijing, China.</p><p><b>METHODS</b>Partial gene sequencing of 16S, hsp65, and rpoB were used to distinguish the species of NTM isolates. All strains identified as M. abscessus were further enrolled in the drug susceptibility testing by using broth microdilution method.</p><p><b>RESULTS</b>We found that M. avium complex was the most frequent NTM organism, accounting for 54.1% (33/61) of all isolates. Behind MAC, the second most common organisms were M. abscessus (22 out of 61, 36.1%). Average rates of resistance were 4.5% for AMK, 9.1% for LZD, and 13.6% for CLA, respectively. In contrast, resistance to LEV (17/22, 77.3%), IMI (9/22, 40.9%), and SMX (10/22, 45.5%) was noted in more than 40% of M. abscessus isolates. DNA sequencing revealed that all the CLA-resistant isolates harbored nucleotide substitutions in position 2058 (1/3, 33.3%) or 2059 (2/3, 66.7%) of 23S rRNA.</p><p><b>CONCLUSION</b>In conclusion, our data demonstrated that M. intracellulare and M. abscessus were the most common NTM species in the general hospital of Beijing. CLA, AMK, LZD showed promising activity, where as LEV, IMI, and SMX exhibited poor activity against M. abscessus in vitro.</p>

Effect of curcumin on spinal cord injury repair via inhibiting NF-κB signalling pathway:research progress / 中国药理学与毒理学杂志

Inflammation response is the most crucial link in the pathogeneses of spinal cord injury (SCI),and is the basis of secondary damage. NF-κB Signalling pathway is activated excessively after SCI,so that numerous NF-κB possessing biological activities is quickly translocated into the nuclear and regulates the target genes,resulting in heightened inflammation and further tissue damage. Suppressing NF-κB signalling pathway and controlling inflammation response effectively are effective approaches to promoting SCI repair. It is found that curcumin has multiple target molecules to suppress NF-κB signalling pathway,block the excessive activation of NF-κB and reduce the expression of proinflammation cytokines,which plays an important role in SCI repair. This article discusses NF-κB signalling pathway,the contribution of NF-κB signalling pathway to SCI and the role of curcumins inhibition of NF-κB signalling pathway in SCI.

Establishment of prediction model for spontaneous rupture of primary liver cancer / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To establish a prediction model for spontaneous rupture of primary liver cancer.</p><p><b>METHODS</b>The clinical data of 77 patients with spontaneous rupture of primary liver cancer and 95 primary liver cancer patients without spontaneous rupture were collected and compared. The risk factors of spontaneous rupture of primary liver cancer were analyzed with multivariate logistic regression.</p><p><b>RESULTS</b>Multivariate logistic regression analysis revealed that moderate or severe ascites, liver cirrhosis, protrusion of tumor from the liver surface, tumor size ≥ 5 cm were independent risk factors of spontaneous rupture of primary liver cancer. The area under the receiver operating characteristic curve of the established model for spontaneous rupture was 0.862 (P<0.05).</p><p><b>CONCLUSION</b>The established model base on the severity of ascites, liver cirrhosis, protrusion of tumor and large tumor size can effectively estimate the risk of spontaneous rupture of primary liver cancer.</p>

Effect of alprostadil on recovery of renal transplant recipients with delayed graft function / 中国基层医药

Objective To assess the effect of alprostadil on accelerating early recovery of renal transplant patients with delayed graft function.Methods A randomized control clinical trial was designed in renal recipients with delayed graft function(DGF)who were administered with 50μg alprostadil each day after the operation.The effects of alprostadil were compared with the control group which included 14 recipients with DGF to determine the influences of alprostadil on urine,serum creatinine(SCr).Under Doppler ultrasound,the renal blood flow resistance-indexes(RI)were measured.The rates of acute renal graft rejection(AR)were also calculated in both groups,and the 1year patient/graft survival rates were compared between the two groups.Results Urine was significantly higher in alprostadil-treated group than in control group(P ＜ 0.05).On the contrary,SCr and RI were significantly lower in alprostadil-treated group than in control group(P ＜ 0.05).No significant differences were found between the two groups in AR rate(6.25％ vs 7.14％)and the 1-year patient/graft survival rates(P ＞ 0.05).Conclusion The application of alprostadil in renal recipients with DGF had beneficial effects on accelerating recovery of renal graft function.

Management of hypospadias cripples with two-staged repair / 中国基层医药

Objective To evaluate the two-stage repair in hypospadias cripples.Methods 35 patients with hypospadias cripples underwent two-stage repair.At the first stage,a full-thickness graft of skin or buccal mucosa was used for urethral plate reconstruction after the release of chordee.The second stage was performed 6 months after completion of the first stage.Tubularization of the replaced urethral plate was the preferred technique.Results There was no urethra stricture or “preplaced urethral plate ” atrophy.Fistula developed in 2 of 35 cases.Conclusion The twostaged technique was a useful strategy to deal with the myriad abnormalities encountered in crippled hypospadias.This technique could not only create a neourethra successfully,but also give the penis a near-normal shape and appearance.