1.Endo-beta-N-acetylglucosaminidase: Possible Functions and Mechanisms
Xin-Rong LU ; Yong-Liang TONG ; Wei-Li KONG ; Lin ZOU ; Dan-Feng SHEN ; Shao-Xian LÜ ; Rui-Jie LIU ; Shao-Xing ZHANG ; Yu-Xin ZHANG ; Lin-Lin HOU ; Gui-Qin SUN ; Li CHEN
Progress in Biochemistry and Biophysics 2024;51(5):985-999
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.
2.Effects of CYP3A5 gene polymorphism and Wuzhi capsule on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients
Qiulin XIANG ; Ling LIU ; Yi YANG ; Guoxing LI ; Song CHEN ; Yingying YANG ; Xian YU
China Pharmacy 2024;35(14):1765-1769
OBJECTIVE To investigate the effects of CYP3A5 gene polymorphism and Wuzhi capsule (WZ) on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients. METHODS A total of 132 patients who underwent renal transplantation and received tacrolimus + mycophenolic acids + prednisone after operation in our hospital from September 2021 to September 2023 were selected and divided into four groups according to genotypes (CYP3A5*1 or CYP3A5*3/*3) and with or without WZ (“ +WZ” meant drug combination, “ +NO WZ” meant without combination). The blood trough concentration/daily dose (c0/D) values of the four groups were analyzed on the 14th day, 1 month and 3 months after renal transplantation. The incidence of acute rejection and the incidence of tacrolimus-related adverse reactions within 3 months after transplantation were compared among 4 groups. RESULTS On the 14th day, 1 month and 3 months after surgery (except for the CYP3A5*1+WZ group), c0/D values of CYP3A5*1 genotype patients were significantly lower than those of CYP3A5*3/*3 genotype patients regardless of whether they were treated with WZ additionally (P<0.05). Within 3 months after surgery, although there was no significant difference in the incidence of acute rejection and tacrolimus-related adverse reactions among the four groups (P> 0.05), the incidence of hyperglycemia in patients with CYP3A5*3/*3 was higher (41.67%). CONCLUSIONS CYP3A5 gene polymorphism is significantly related to tacrolimus c0/D in kidney transplant patients. Under the premise of c0 monitoring of tacrolimus, patients with CYP3A5*1 genotype should be given WZ as soon as possible after surgery to accelerate tacrolimus to reach the therapeutic concentration range, while CYP3A5*3/*3 genotype is not recommended to be given WZ because of the higher risk of hyperglycemia.
3.Efficacy of roxallistat combined with polysaccharide iron complex and Shengxuening in the treatment of maintenance hemodialysis renal anemia with poor recombinant human erythropoietin
Rui-Feng CHEN ; Pei YU ; Zhi-Ting WANG ; Yan LI ; Rui-Xian ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(12):1704-1708
Objective To investigate the efficacy of roxallistat combined with polysaccharide iron complex and Shengxuening in the treatment of maintenance hemodialysis renal anemia with poor recombinant human erythropoiesis.Methods Maintenance hemodialysis renal anemia patients with poor recombinant human erythropoietin effect were divided into control group and treatment group according to random number table method.The control group took roxallistat orally with a body weight of>60 kg,120 mg each time,3 times a week,and 45-60 kg with 100 mg each time,3 times a week;oral polysaccharide iron complex,300 mg each time,once a day.The treatment group was given Shengxuening orally based on the control group,0.25-0.50 g each time,3 times a day.Both groups were treated for 3 months.The clinical efficacy,inflammatory factors,iron metabolism,renal function,anemia index,traditional Chinese medicine symptom score and adverse drug reaction were compared between the two groups.Results In the control group,34 cases were enrolled,1 case fell off,and finally 33 cases were included in the analysis.In the treatment group,35 cases were enrolled,1 case was shed,and 34 cases were finally included in the analysis.After treatment,the total effective rate of treatment group and control group was 97.06%(33 cases/34 cases)and 81.82%(27 cases/33 cases),respectively,and the difference was statistically significant(P<0.05).After treatment,the nuclear transcription factor kappa B(NK-κB)in treatment group and control group were(24.09±3.06)and(35.23±4.11)ng·L-1;interferon gamma(IFN-γ)were(41.39±4.13)and(50.10±5.27)ng·L-1;transferrin saturation(TAST)were(38.62±5.91)%and(31.16±4.73)%;serum ferritin(SF)were(28.13±5.77)and(22.47±4.65)μmol·L-1;serum iron(SI)were(15.66±3.76)and(13.19±2.94)μmol·L-1;urinary protein excretion rate(24 h UPE)were(1.85±0.41)and(2.91±0.62)g·24 h-1;blood urea nitrogen(BUN)were(5.16±0.67)and(6.89±0.97)mmol·L-1;hemoglobin(Hb)were(91.38±11.23)and(83.19±8.54)g·L-1;hematocrit(Hct)were(29.01±7.40)%and(24.56±5.69)%;main disease score were(5.29±1.05)and(7.15±1.53)scores;the secondary scores were(3.11±0.46)and(4.98±0.77)scores;the total scores were(8.40±1.49)and(12.13±2.30)scores,with statistical significance(all P<0.05).The total incidence of adverse drug reactions in treatment group and control group were 14.71%and 9.09%,with no statistical significance(P>0.05).Conclusion Roxallistat combined with polysaccharide and iron complex and Shengxuening have good therapeutic effect in the treatment of maintenance hemodialysis renal anemia with poor recombinant human erythropoietin effect;it can reduce inflammation,regulate iron metabolism,improve renal function,and reduce adverse drug reactions.
4.Study on the inhibition of ginkgo biloba flavonoids on PIK3CA mutation-driven lymphatic malformations
Yu CHEN ; Hui-Min CHEN ; Li-Dan WANG ; Xin-Xian LIU
The Chinese Journal of Clinical Pharmacology 2024;40(20):2998-3002
Objective To investigate the effect of ginkgo biloba flavonoids on children with lymphatic malformation(LM)driven by phosphatidylinoinosiol 3-kinase(PIK3CA)mutation and its mechanism.Methods The experiment was divided into human dermal lymphatic endothelial cell(HD-LEC)group(no treatment),lymphatic malformation lymphatic endothelial cell(LM-LEC)group(no treatment),ginkgo biflavone group(7.5 μmol·L-1 ginkgo biloba treated LM-LEC cells)and vascular endothelial growth factor-C(VEGF-C)inhibitor group(Sozinibercept group,treated LM-LEC cells with 1 μmol·L-1 VEGF-C inhibitor).The number of lumen and tube branches were observed in each group.Quantitative real-time polymerase chain reaction(qRT-qPCR)was used to detect the relative expression level of VEGF-C.The relative protein expression levels of vascular endothelial growth factor receptor 3(VEGFR3),neurofibrin-2(NRP2),protein kinase B(Akt)and extracellular regulatory protein kinase(ERK)were detected by Western blot.The positive expressions of VEGFR3 and NRP2 were detected by immunofluorescence assay.Results The relative expression levels of VEGF-C mRNA in LM-LEC group and HD-LEC group were 5.42±1.09 and 1.00±0.08;the relative expression levels of VEGFR3 protein were 2.79±0.54 and 1.00±0.10;the relative expression levels of NRP2 protein were 2.58±0.47 and 1.00±0.07;the phosphorylation levels of Akt S473 were 5.62±0.84 and 1.00±0.01;the phosphorylation levels of ERK were 2.37±0.62 and 1.00±0.05,respectively.The positive expressions of VEGFR3 in ginkgo diflavone group,Sozinibercept group and LM-LEC group were 0.35±0.08,0.29±0.08 and 1.00±0.16;the positive expressions of NRP2 were 0.33±0.07,0.31±0.05 and 1.00±0.09,respectively.The above indexes in LM-LEC group were significantly different from those in HD-LEC group,and the above indexes in ginkgo biloba flavonoids group and Sozinibercept group were significantly different from those in LM-LEC group(all P<0.05).Conclusion Ginkgo biflavone may inhibit the expression of VEGF-C by blocking the VEGF-C/VEGFR-3 signaling pathway,and thus inhibit the lymphatic malformation caused by PIK3CA H1047R mutation.
5.Blood security and management of transfusion-dependent thalassaemia(TDT)patients in Nanning:analysis of"col-lection-based-supply"blood management mode
Mei YU ; Yang CHEN ; Xian LI ; Qiuhong MO ; Linbin HUANG ; Xipeng YAN ; Baoren HE ; Bin LI ; Limin CHEN
Chinese Journal of Blood Transfusion 2024;37(5):567-574
Objective To retrospectively analyze the blood use of transfusion-dependent thalassemia(TDT)patients in 9 designated transfusion medical institutions from 2018 to 2023 in Nanning,and to evaluate the effect of"three designated"blood transfusion mode(hereby means TDT patients undergoing blood transfusion in designated transfusion medical institu-tions regularly)and"collection-based-supply"blood management mode on blood security of TDT patients.Methods The"three designated"blood transfusion mode was implemented to ensure that TDT patients registered in the local household registration(referred to as the"register")obtain the rights and interests of outpatient transfusion and blood security of des-ignated medical institutions.The"collection-based-supply"blood management mode was implemented to assess the blood needs of"register"TDT patients and meet their needs to the maximum extent according to the blood inventory(collection).Results From 2018 to 2023,the total blood supply of"register"TDT patients was 10.37%of the total red blood supply of all medical institutions(138 509.5 U/1 335 788.0 U),with the highest proportion of type O blood as 46.34%(64 181.0 U/138 509.5 U)and the lowest proportion of type AB blood as 3.85%(5 331.0 U/138 509.5 U).In 2018,9 transfusion medical institutions were designated for TDT patients.There were a total of 766 TDT patients in the register,with the per ca-pita annual blood transfusion volume increased from20.28 U(15 531.0 U/766 patients)in2018 to36.01 U(27 586.0 U/766 patients)in 2023,maintaining a positive growth every year(30.26%,4.94%,11.71%,8.61%,4.94%and 7.10%).Conclusion The"three designated"blood transfusion mode and the"collection-based-supply"blood management mode can effectively guarantee the blood supply of TDT patients.
6.Dynamic Changes of Volatile Components During Processing Process of Jianchangbang Characteristic Ginger Processed Xingpo Pieces Based on HS-GC-MS
Yuxun CHEN ; Wanai XU ; Jingyu WU ; Meiqi LU ; Lingbang MENG ; Cheng XU ; Hailian ZHENG ; Xian ZHANG ; Na ZHANG ; Qianfeng GONG ; Huan YU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):127-134
ObjectiveTo reveal the influence of Jianchangbang characteristic processing method on the change process of volatile components and the processing mechanism of reducing toxicity and increasing efficiency of Magnoliae Officinalis Cortex(MOC) by studying the changes in the composition and content of volatile components during the processing of ginger processed Xingpo pieces. MethodSamples of raw products, ginger juice moisturized products and stir-fried and heap moisturized products of MOC were taken according to the set time points, and headspace gas chromatography-mass spectrometry(HS-GC-MS) was used to determine the contents of volatile components in the samples, and the relative content of each component was obtained by peak area normalization. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were performed on the sample data using SIMCA 14.1 software, and the differential components during the processing were screened with variable importance in the projection(VIP) value>1 as the indicator. ResultA total of 68 volatile components were identified in the samples, among which some of the chemical components with similar structures showed similar trends of changes, and there was also the phenomenon of interconversion between compounds. Compared with the raw products, the contents of 42 components in ginger juice moisturized products increased, while the contents of 25 components decreased, 19 components were unique, and 4 components were unique to the raw products. Compared with ginger juice moisturized products, MOC in the early stage of piling had three unique components, and the contents of 11 components such as cyclosativene and (+)-α-pinene increased, and the contents of 5 components such as tricyclic terpene and α-curcumene decreased, and ginger juice moisturized products had four unique components. Compared with the early stage of piling, in the later stage, the contents of 8 components such as (+)-α-pinene and camphene significantly increased, while the contents of 6 components such as linalool and α-selinene significantly decreased. During the processing of MOC, there were significant changes in the chemical composition of the samples before and after 20 days. The differences between ginger juice moistening and the early stage of piling, the early stage and the later stage of piling could be clearly distinguished. ConclusionDuring the preparation process of ginger processed Xingpo pieces, the addition of ginger juice can reduce the contents of stimulating components, and the contents of active components continue to increase in several stages, such as the addition of ginger juice, frying and heap moisturizing, the quality of the decoction pieces may change significantly at about 20 d of processing. This study can provide a research basis for exploring the processing mechanism of ginger processed Xingpo pieces.
7.Clinical characteristics and outcomes of psoriasis patients with COVID-19: A retrospective, multicenter cohort study in China
Yanhua LIU ; Zhongrui XU ; Jian ZHOU ; Aijun CHEN ; Junling ZHANG ; Xiaojing KANG ; Xian JIANG ; Chengzhi LYU ; Chunrui SHI ; Yuling SHI ; Xiaoming LIU ; Fuqiu LI ; Bin YANG ; Yongmei HUANG ; Chen YU ; Gang WANG
Chinese Medical Journal 2024;137(14):1736-1743
Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.
8.Application Progress of RNA Fluorescence Aptamers in Biosensing and Imaging
Xing-Chen QIU ; Cun-Xia FAN ; Rui BAI ; Yu GU ; Chang-Ming LI ; Chun-Xian GUO
Chinese Journal of Analytical Chemistry 2024;52(4):481-491
RNA fluorescence aptamers are RNA sequences that can specifically bind to non-toxic,cell permeable,and self-fluorescent target molecules and activate their luminescent properties.These aptamers provide powerful tools for biosensing and imaging researches due to their simple structure,easy synthesis,and easy transfection.This article summarized the characteristics and development history of various RNA fluorescent aptamers,including Malachite Green,Spinach,Broccoli,Mango,Corn,and Pepper family,as well as their corresponding fluorescent groups.The applications of RNA fluorescent aptamers were also reviewed from two aspects:extracellular detection and cell imaging.This review might provide guidance for labeling,detection and interactions of molecules from proof of concept and clinical assessment to practical clinical and biomedical applications.
9.Risk factors for bronchopulmonary dysplasia in twin preterm infants:a multicenter study
Yu-Wei FAN ; Yi-Jia ZHANG ; He-Mei WEN ; Hong YAN ; Wei SHEN ; Yue-Qin DING ; Yun-Feng LONG ; Zhi-Gang ZHANG ; Gui-Fang LI ; Hong JIANG ; Hong-Ping RAO ; Jian-Wu QIU ; Xian WEI ; Ya-Yu ZHANG ; Ji-Bin ZENG ; Chang-Liang ZHAO ; Wei-Peng XU ; Fan WANG ; Li YUAN ; Xiu-Fang YANG ; Wei LI ; Ni-Yang LIN ; Qian CHEN ; Chang-Shun XIA ; Xin-Qi ZHONG ; Qi-Liang CUI
Chinese Journal of Contemporary Pediatrics 2024;26(6):611-618
Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.
10.Risk factors for recurrence of childhood acute lymphoblastic leukemia after treatment with the Chinese Children's Cancer Group ALL-2015 protocol
Xia CHEN ; Xiao-Ying LEI ; Xian-Min GUAN ; Ying DOU ; Xian-Hao WEN ; Yu-Xia GUO ; Hui-Qin GAO ; Jie YU
Chinese Journal of Contemporary Pediatrics 2024;26(7):701-707
Objective To investigate the cumulative incidence of recurrence(CIR)in children with acute lymphoblastic leukemia(ALL)after treatment with the Chinese Children's Cancer Group ALL-2015(CCCG-ALL-2015)protocol and the risk factors for recurrence.Methods A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019.CIR was calculated,and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia(B-ALL)were analyzed.Results Among the 852 children with ALL,146(17.1%)experienced recurrence,with an 8-year CIR of 19.8%±1.6%.There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group(P>0.05).For the 146 children with recurrence,recurrence was mainly observed in the very early stage(n=62,42.5%)and the early stage(n=46,31.5%),and there were 42 children with bone marrow recurrence alone(28.8%)in the very early stage and 27 children with bone marrow recurrence alone(18.5%)in the early stage.The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene(HR=4.177,95%CI:2.086-8.364,P<0.001)and minimal residual disease≥0.01%on day 46(HR=2.013,95%CI:1.163-3.483,P=0.012)were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol.Conclusions There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol,mainly bone marrow recurrence alone in the very early stage and the early stage,and minimal residual disease≥0.01%on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

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