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.

Objective:To compare the prognostic value of two predictive models based on C-reactive protein(CRP)and albumin(ALB),namely the CRP to ALB ratio(CAR)and the Glasgow prognostic score(GPS),in newly diagnosed patients with diffuse large B-cell lymphoma(DLBCL).Methods:The data of newly diagnosed DLBCL patients admitted to our center from May 2014 to January 2022 were reviewed.A total of 111 patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with detailed clinical,laboratory data and follow-up information were included.The receiver operating characteristic(ROC)curve was performed to evaluate the predictive value of pre-treatment CAR on disease progression and survival.Furthermore,the association between CAR and baseline clinical,laboratory characteristics of patients was evaluated,and progression-free survival(PFS)and overall survival(OS)were compared between different CAR and GPS subgroups.Finally,the univariate and multivariate COX propor-tional hazard regression models were used to analyze the factors affecting disease outcomes.Results:ROC curve showed that the area under the curve(AUC)of CAR predicting PFS and OS in DLBCL patients was 0.687(P=0.002)and 0.695(P=0.005),respectively,with the optimal cut-off value of 0.11 for both predicting PFS and OS.Compared with the lower CAR(＜0.11)group,the higher CAR(≥0.11)group had more clinical risk factors,including age＞60 years(P=0.025),ECOG score ≥2(P=0.004),Lugano stage Ⅲ-Ⅳ(P＜0.001),non-germinal center B-cell-like(non-GCB)subtype(P=0.035),elevated lactate dehydrogenase(LDH)(P＜0.001),extranodal involved site＞1(P=0.004)and IPI score＞2(P＜0.001).The interim response evaluation of patients showed that the overall response rate(ORR)and complete response rate(CRR)in the lower CAR group were both significantly better than those in the higher CAR group(ORR:96.9％vs 80.0％,P=0.035;CRR:63.6％vs 32.5％,P=0.008).With a median follow-up of 24 months,patients with lower CAR had significantly longer median PFS and OS than those with higher CAR(median PFS:not reached vs 67 months,P=0.0026;median OS:not reached vs 67 months,P=0.002),while there was no statistical difference in PFS(P=0.11)and OS(P=0.11)in patients with GPS of 0,1,and 2.Multivariate Cox regression analysis indicated that only sex(male)and IPI score＞2 were independent risk factors for both PFS and OS.Conclusion:CAR is significantly correlated with disease progression and survival in DLBCL patients;And compared with GPS,CAR has more advantages in predicting disease outcomes in DLBCL patients.

Objective:To compare the efficacy and safety of flumatinib (FM)and imatinib (IM)as first-line treatment in newly-diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP ) in real world. Methods:A total of 84 newly-diagnosed CP-CML patients in our center from December 2019 to December 2022 were retrospectively analyzed.Among them,32 cases received FM as first-line treatment,and 52 cases received IM. Molecular response (MR),disease progression,survival and incidence of adverse events (AEs)were compared between the two groups.Results:At 3 months of treatment,the incidences of early molecular response (EMR ),MR2.0 and MR3.0 were 96.7％,70.0％ and 20.0％ in FM group,respectively,which were significantly higher than 77.1％,29. 2％ and 0 in IM group (all P<0.05 ).At 6,9 and 12 months of treatment,the incidences of major molecular response (MMR)in FM group were 68.2％,85.7％ and 90.0％,respectively,which were significantly higher than 22.9％,34.0％ and 51.1％ in IM group (all P<0.01).The median time to achieve MMR in FM group was 6(6-9)months,which was significantly shorter than 18(12-22)months in IM group (P<0.001 ).The 3-year progression-free survival rate and 3-year event-free survival rate in FM group were 100％ and 68.8％,respectively,while in IM group were 98.1％ and 55.8％.There were no significant differences between the two groups (P>0.05). The incidence of grade 3-4 hematologic AEs in FM group was 21 .9％,which was slightly lower than 25.0％ in IM group,but the difference was not significant (P>0.05 ).Conclusion:In real clinical practice,FM as first-line treatment achieves MMR earlier than IM,and exhibits good safety profile in newly-diagnosed CML-CP patients,which potentially leads to improved long-term survival and treatment-free remission.

Objective:To explore the effects of RNF113A on the proliferation,migration,in-vasion,apoptosis,and autophagy of hepatocellular carcinoma cells.Methods:Hep3B cells were divided into control group and RNF113A overexpression group(RNF113A-OE),HepG2 was divided into control group and RNF113A knockdown group(si-RNF113A),CCK-8 assay was used to detect changes in cell viability,clone formation assay was used to detect changes in cell proliferation abili-ty,Transwell assay was used to detect changes in cell invasion ability,wound healing assay was used to detect changes in cell migration ability,and flow cytometry was used to detect changes in cell apoptosis ability,Western blot experiments were used to detect changes in protein expression of autophagy related genes and AMPK signaling pathway related genes.Results:Compared with the control group,the proliferation,cloning,invasion,and migration abilities of Hep3B cells in the RNF113A-OE group were improved,while apoptosis and autophagy abilities were decreased,and the AMPK signaling pathway was inhibited;In the si-RNF113A group,the proliferation,cloning,in-vasion,and migration abilities of HepG2 cells were significantly reduced,while apoptosis and au-tophagy abilities were increased,and the activation of the AMPK signaling pathway was promoted.Conclusion:RNF113A promotes the proliferation,cloning,invasion,and migration of hepatocel-lular carcinoma cells,and inhibited apoptosis and autophagy by inhibiting the AMPK signaling path-way.

By reviewing the relevant literature of ancient herbal works and modern codices， this paper sorted out the historical evolution and developmental venation of processing of Notoginseng Radix et Rhizoma. On this basis， the modern research of processed products of Notoginseng Radix et Rhizoma was used as the breakthrough point to analyze the literature in terms of processing technology， chemical composition changes and changes in pharmacological effects before and after processing. According to the research status of processing of Notoginseng Radix et Rhizoma， some existing problems were analyzed in this paper， such as not many ancient processing methods used in modern time， lack of standardized research on processing technology. And saponins， polysaccharides， amino acids， flavonoids and other chemical components in Notoginseng Radix et Rhizoma may change to different degrees before and after processing， which was the main reason for the difference of efficacy before and after processing. However， the current research on the pharmacological effects of Notoginseng Radix et Rhizoma mainly focuses on raw products， resulting in a lack of in-depth research on the transformation mechanism of Notoginseng Radix et Rhizoma in processing difference， and the scientific connotation of "Shengxiao Shubu" has not been clearly elaborated， which is not conducive to the standardized clinical use of drugs. Therefore， it is necessary to further analyze the material basis of Notoginseng Radix et Rhizoma and its processed products， and to explore the change rule of chemical components before and after processing and its correlation with pharmacodynamic activity， so as to clarify the processing mechanism for providing scientific basis for its standardized processing， quality control and clinical rational use.

OBJECTIVE: To investigate the value of pre-treatment albumin/fibrinogen ratio (AFR) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The data of DLBCL patients in the Affiliated Hospital of North Sichuan Medical College from April 2014 to March 2021 were retrieved, and 111 newly diagnosed patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with complete data were included in the study. The clinical, laboratory examination and follow-up data of the patients were collected, and the receiver operating characteristic curve (ROC) was drawn according to patients' AFR before treatment and the survival status at the end of the follow-up, which could be used to preliminarily evaluate the predictive value of AFR for disease progression and patients' survival outcome. Furthermore, the correlation of AFR with the clinical and laboratory characteristics, progression-free survival (PFS) and overall survival (OS) was analyzed, and finally, univariate and multivariate Cox proportional hazard regression models were used to analyze factors affecting PFS and OS of DLBCL patients. RESULTS: The ROC curve indicated that AFR level had a moderate predictive value for PFS and OS in DLBCL patients, with the area under the curve (AUC) of 0.616 (P =0.039) and 0.666 (P =0.004), respectively, and the optimal cut-off values were both 9.06 for PFS and OS. Compared with high-AFR (≥9.06) group, the low-AFR (<9.06) group had a higher proportion of patients with Lugano III-IV stage ( P <0.001), elevated lactate dehydrogenase (P =0.007) and B symptoms (P =0.038). The interim analysis of response showed that the overall response rate (ORR) in the high-AFR group was 89.7%, which was significantly higher than 62.8% in the low-AFR group (P =0.001). With a median follow-up of 18.5 (3-77) months, the median PFS of the high-AFR group was not reached, which was significantly superior to 17 months of the low-AFR group (P =0.009). Similarly, the median OS of high-AFR group was not reached, either, which was significantly superior to 48 months of the low-AFR group (P < 0.001). In multivariate Cox regression analysis, AFR <9.06 was an independent risk factor both for PFS and OS (HR _PFS=2.047, P =0.039; HR _OS=4.854, P =0.001). CONCLUSION Pre-treatment AFR has a significant value for the prognosis evaluation in newly diagnosed DLBCL patients.
Humans ; Prognosis ; Fibrinogen ; Disease-Free Survival ; Albumins/therapeutic use* ; Hemostatics/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Abstract: Objective　To investigate the relationship between the body mass index (BMI) levels and the negative conversion time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid in adult coronavirus disease 2019 (COVID-19) patients and the asymptomatic persons. Methods　Asymptomatic infected patients and confirmed COVID-19 patients admitted to Chengdu Public Health Clinic Center from February 2021 to November 2021 were dynamically included. The epidemiological and clinical characteristics of the objects were collected, and the SARS-CoV-2 nucleic acid testing of the objects during their hospitalization was continuously monitored, and the negative nucleic acid conversion time was recorded. The t test or Wilcoxon rank sum test, χ2 test or Fisher's exact probability method examine were used to distribute characteristics of each group of variables and the connection between different variables, respectively. Then the variables showed differences in distribution (P<0.05) between different BMI groups were included in the multivariate Cox proportional risk regression model. Results　A total of 253 subjects ranged from 18 to 63 years old, with M(P25, P75) age of 37.0 (30.0, 47.0) years old, were included in this study. The male to female ratio was 4.16 to 1. The BMI was (23.97±3.33) kg/m2. 50.59% (128/253) of the objects were overweight or obese, and 78.13% (100/128) were overweight. The negative time of SARS-CoV-2 nucleic acid conversion of all subjects ranged from 1 to 71 days, with M(P25, P75) of 7.0 (2.0, 18.0) days (P<0.001). The negative time of SARS-CoV-2 nucleic acid conversion of the normal weight or the thin, and the overweight or obese were 5.00 (2.00, 19.00) and 8.00 (2.00, 17.75) days respectively. The results of multivariate Cox's proportional hazards regression model showed that the BMI levels may not be associated with the negative conversion time of SARS-CoV-2 nucleic acid (HR=1.090, 95%CI: 0.843-1.410, P=0.510). Conclusions　Adult asymptomatic persons and confirmed COVID-19 patients are mainly middle-aged and young males, and overweight or obesity is relatively common. Overweight or obesity cannot be considered as an independent factor influencing the negative conversion time of SARS-CoV-2 nucleic acid.

BACKGROUND: The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR -mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR -mutated NSCLC patients with different BM statuses. METHODS: Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR -mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework. RESULTS: This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17-0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20-0.90; HR = 0.46, 95% CI: 0.31-0.68; HR = 0.51, 95% CI: 0.34-0.77; HR = 0.50, 95% CI: 0.38-0.66; HR = 0.62, 95% CI: 0.43-0.89; HR = 0.64, 95% CI: 0.44-0.94; HR = 0.61, 95% CI: 0.48-0.76; HR = 0.71, 95% CI: 0.50-1.00), PbCT (HR = 0.29, 95% CI: 0.11-0.74; HR = 0.31, 95% CI: 0.15-0.62; HR = 0.34, 95% CI: 0.17-0.69; HR = 0.34, 95% CI: 0.18-0.64; HR = 0.42, 95% CI: 0.21-0.82; HR = 0.43, 95% CI: 0.22-0.87; HR = 0.41, 95% CI: 0.22-0.74; HR = 0.48, 95% CI: 0.31-0.75), and PfCT (HR = 0.14, 95% CI: 0.06-0.32; HR = 0.15, 95% CI: 0.09-0.26; HR = 0.17, 95% CI: 0.09-0.29; HR = 0.16, 95% CI: 0.10-0.26; HR = 0.20, 95% CI: 0.12-0.35; HR = 0.21, 95% CI: 0.12-0.39; HR = 0.20, 95% CI: 0.12-0.31; HR = 0.23, 95% CI: 0.16-0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22-0.92) and PfCT (HR = 0.21, 95% CI: 0.12-0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42-1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84-2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06-4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06-0.32). For patients without BM, osimertinib + bevacizumab was most likely to rank the first, with cumulative probabilities of 47.1%. For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively. CONCLUSION Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR -mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Afatinib/therapeutic use* ; Lung Neoplasms/metabolism* ; Bevacizumab/therapeutic use* ; Bayes Theorem ; Network Meta-Analysis ; Protein Kinase Inhibitors/therapeutic use* ; Pemetrexed/therapeutic use* ; ErbB Receptors/genetics* ; Brain Neoplasms/genetics* ; Mutation/genetics*

PURPOSE: As common clinical screening tests cannot effectively predict a difficult airway, and unanticipated difficult laryngoscopy remains a challenge for physicians. We herein used ultrasound to develop some point-of-care predictors for difficult laryngoscopy. METHODS: This prospective observational study included 502 patients who underwent laryngoscopy and a detailed sonographic assessment. Patients under 18 years old, or with maxillofacial deformities or fractures, limited mouth opening, limited neck movement or history of neck surgery were excluded from the study. Laryngoscopic views of all patients were scored and grouping using the modified Cormack-Lehane (CL) scoring system. The measurements acquired comprised tongue width, the longitudinal cross-sectional area of the tongue, tongue volume, the mandible-hyoid bone distance, the hyoid bone-glottis distance, the mandible-hyoid bone-glottis angle, the skin-thyrohyoid membrane distance, the glottis-superior edge of the thyroid cartilage distance (DGTC), the skin-hyoid bone distance, and the epiglottis midway-skin distance. ANOVA and Chi-square were used to compare differences between groups. Logistic regression was used to identify risk factors for difficult laryngoscopy and it was visualized by receiver operating characteristic curves and nomogram. R version 3.6.3 and SPSS version 26.0 were used for statistical analyses. RESULTS: Difficult laryngoscopy was indicated in 49 patients (CL grade Ⅲ - Ⅳ) and easy laryngoscopy in 453 patients (CL grade Ⅰ - Ⅱ). The ultrasound-measured mandible-hyoid bone-glottis angle and DGTC significantly differed between the 2 groups (p < 0.001). Difficult laryngoscopy was predicted by an area under the curve (AUC) of 0.930 with a threshold mandible-hyoid bone-glottis angle of 125.5° and by an AUC of 0.722 with a threshold DGTC of 1.22 cm. The longitudinal cross-sectional area of the tongue, tongue width, tongue volume, the mandible-hyoid distance, and the hyoid-glottis distance did not significantly differ between the groups. CONCLUSION Difficult laryngoscopy may be anticipated in patients in whom the mandible-hyoid bone-glottis angle is smaller than 125.5° or DGTC is larger than 1.22 cm.
Humans ; Adolescent ; Laryngoscopy ; Prospective Studies ; Tongue/diagnostic imaging* ; Respiratory System ; Ultrasonography