摘要
International registration of herbal drugs is a necessary prerequisite for the internationalization of Chinese materia medica. North America and European Union occupy an important position in the world herbal drugs market, and their drug administration and quality supervision requirements are relatively complete and progressiveness. By summarizing the definition of herbal drugs in North America and European Union, combing and interpreting the relevant laws, regulations and policy documents, this article constructed the registration path of herbal drugs, and discussed the current status of market registration of herbal drugs in North America and European Union based on the examples of successful marketing of herbal drugs under current application and approval in overseas markets. This article believed that in the future, an internationally matched TCM quality standard evidence system should be built, clinical trials of TCM products in line with international standards should be carried out, standards that are the same or higher than international mainstream GMP should be developed, the registration path of TCM compounds should be explored, and professionals to establish an international registration application team should be recruited to provide theoretical and practical support for China's overseas registration of Chinese TCM products, promote TCM products to enter the world mainstream market, and achieve high-quality development of TCM internationalization.
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OBJECTIVE@#To compare the role and importance of fibular fixation in tibiofibular fractures by Meta-analysis.@*METHODS@#The literature related to the comparison of the efficacy of fixation of the fibula with or without fixation on the treatment of tibiofibular fractures was searched through the databases of China Knowledge Network, Wipu, Wanfang, The Cochrane Library, Web of science and Pubmed, and statistical analysis was performed using RevMan 5.3 software. The rates of malrotation, rotational deformity, internal/external deformity, anterior/posterior deformity, non-union, infection, secondary surgery and operative time were compared between the fibula fixation and non-fixation groups.@*RESULTS@#A total of 11 publications were included, six randomised controlled trials and five case-control trials, eight of which were of high quality. A total of 813 cases were included, of which 383 were treated with fibula fixation and 430 with unfixed fibulae.Meta-analysis results showed that fixation of the fibulae in the treatment of tibiofibular fractures reduced the rates of postoperative rotational deformity[RR=0.22, 95%CI(0.10, 0.45), P<0.000 1] and internal/external deformity[RR=0.34, 95%CI(0.14, 0.84), P=0.02] and promoted fracture healing [RR=0.76, 95%CI(0.58, 0.99), P=0.04]. In contrast, the rates of poor reduction [RR=0.48, 95% CI(0.10, 2.33), P=0.36], anterior/posterior deformity[RR=1.50, 95%CI(0.76, 2.96), P=0.24], infection[RR=1.43, 95%CI(0.76, 2.72), P=0.27], secondary surgery[RR=1.32, 95%CI(0.82, 2.11), P=0.25], and operative time[MD=10.21, 95%CI(-17.79, 38.21), P=0.47] were not statistically significant (P>0.05) for comparison.@*CONCLUSION@#Simultaneous fixation of the tibia and fibula is clinically more effective in the treatment of tibiofibular fractures.
Subject(s)
Humans , Fibula/surgery , Fractures, Bone/complications , Tibia/surgery , Fracture Healing , Fracture Fixation, Internal , Treatment Outcome摘要
Objective To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. Methods Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson’s trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. Results Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson’s trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/μm2 and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/μm2 and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). Conclusions E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.
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Aim To investigate the effect of long non- coding RNA p21 (LncRNA p21) regulating Hippo- Yes-associated protein (Hippo-YAP) signaling pathway on the formation of abdominal aortic aneurysm (AAA) in mice. Methods C57BL/6 ApoE
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Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.
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Background/Aims@#Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. @*Methods@#We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. @*Results@#The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. @*Conclusions@#Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.
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Background/Aims@#Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. @*Methods@#A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. @*Results@#Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. @*Conclusions@#In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.
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Background/Aims@#This study aims to evaluate the effects of acute codeine administration on primary and secondary esophageal peristalsis in patients with ineffective esophageal motility (IEM). @*Methods@#Eighteen IEM patients (8 women; mean age 37.8 years, range 23-64 years) were enrolled in the study. The patients underwent highresolution manometry exams, consisting of 10 single wet swallows, multiple rapid swallows, and ten 20 mL rapid air injections to trigger secondary peristalsis. All participants completed 2 separate sessions, including acute administration of codeine (60 mg) and placebo, in a randomized order. @*Results@#Codeine significantly increased the distal contractile integral (566 ± 81 mmHg · s · cm vs 247 ± 36 mmHg · s · cm, P = 0.001) andshortened distal latency (5.7 ± 0.2 seconds vs 6.5 ± 0.1 seconds, P < 0.001) for primary peristalsis compared with these parameters after placebo treatment. The mean total break length decreased significantly after codeine treatment compared with the length after placebo (P= 0.003). Codeine significantly increased esophagogastric junction-contractile integral (P= 0.028) but did not change the 4-second integrated relaxation pressure (P= 0.794). Codeine significantly decreased the frequency of weak (P= 0.039) and failed contractions (P= 0.009), resulting in increased frequency of normal primary peristalsis (P < 0.136). No significant differences in the ratio of impaired multiple rapid swallows inhibition and parameters of secondary peristalsis were detected. @*Conclusions@#In IEM patients, acute administration of codeine increases contraction vigor and reduces distal latency of primary esophageal peristalsis, but has no effect on secondary peristalsis. Future studies are required to further elucidate clinical relevance of these findings, especially in the setting of gastroesophageal reflux disease with IEM.
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Objective To investigate the value of histone deacetylase 3(HDAC3)in evaluating the risk of slow/no reflow in AMI patients after PCI.Methods A total of 280 AMI patients undergo-ing PCI in our hospital from June 2020 to June 2022 were recruited,and according to TIMI blood flow grading,they were divided into slow/no reflow group(TIMI≤grade 11,n=54)and normal flow group(TIMI>grade Ⅱ,n=226).The demographic characteristics,underlying diseases,baseline data at admission,and preoperative results of coronary angiography and laboratory tests were compared between the two groups.Multivariate logistic regression analysis was used to determine the influencing factors for slow/no reflow in AMI patients after PCI,and ROC curve was drawn to analyze the predictive value of related indicators for slow/no reflow.Results Obvi-ously larger proportions of smoking history and Killip grade Ⅱ,higher heart rate,longer reperfu-sion time,and higher serum levels of LDL-C,NLR,D-D and HDAC3 were observed in the slow/no reflow group than the normal flow group(P<0.05,P<0.01).Multivariate logistic regression analysis showed that reperfusion time,NLR and HDAC3 were influencing factors for slow/no reflow in AMI patients after PCI(P<0.05,P<0.01).The AUC value of reperfusion time+NLR in predicting the slow/no reflow after PCI in AMI patients was 0.798(95%CI:0.664-0.922,P=0.002),with a sensitivity and specificity of 0.87 and 0.73,respectively.And when serum HDAC3 level was combined in the prediction,the AUC value was 0.903(95%CI:0.790-0.922,P<0.01),with a sensitivity and specificity of 0.93 and 0.84,respectively.Conclusion Preoperative HDAC3 level is an influencing factor for slow/no reflow in AMI patients after PCI.Based on reperfusion time and NLR,combination of the 3 indicators can provide additional predictive value for slow/no reflow in these patients.
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Objective:To investigate the application effect of production-oriented approach (POA) for consulting ability teaching in general practice standardized residency training.Methods:Eighteen third-year general practice residents in the Second Affiliated Hospital of Harbin Medical University received a special training course on the consulting ability based on POA with the situational simulation teaching from September 2021 to March 2022. The consulting ability of residents was evaluated with Objective Structured Clinical Examination (OSCE) and Leichester Assessment Package (LAP) before and after the training, and the results were compared. Meanwhile, a questionnaire survey and semi-structured interviews were conducted to assess residents′ satisfaction with the course.Results:All 18 resident trainees (11 females and 7 males) aged 25 to 34 (27.3±2.4) years successfully completed the training. Both OSCE scores and LAP scores after the training were significantly higher than those before training (66.25±5.84 vs. 44.44±12.80, t=8.46, P<0.001; 65.78±7.05 vs. 38.33±14.2, t=1.47, P<0.001, respectively). The ability of medical history collection, physical examination, patient management, problem solving, doctor-patient relationship, preventive care and medical record writing were all significantly improved after the training compared with those before training ( t=2.464, 4.278, 8.997, 2.385, 10.35, 5.212, 7.578, all P<0.05). The questionnaire survey showed that all the 18 residents were satisfied with the reasonableness of the teaching content, the class time arrangement, the teaching progress arrangement and the instructors. In the dimension of training effectiveness, 18 participants all believed that the course was helpful to improve their humanistic quality and confidence in reception. In terms of self-promotion, all respondents believed that this course was able to promote their reflection ability and stimulate their learning interest. By coding and analyzing the contents of the semi-structured interviews with the residents, nine main themes were constructed, namely course deficiencies, course characteristics, course advantages, course suggestions, trainees′ deficiencies, trainees′ gains, trainees′ goals, previous teaching deficiencies, and instructor′s role. The results showed that all residents had a high degree of satisfaction with the course, and they thought the course was vivid and interesting and it is able to mobilize the enthusiasm of learning, promote learner to reflect. The residents also suggested to increase the teaching hours and to enrich teaching cases. Conclusion:The consulting ability training of general practice based on POA can effectively improve consulting ability, stimulate learning interest and improve independent learning ability of residents, which gains recognition from both faculty and trainees.
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BACKGROUND@#To perform anatomical anterior cruciate ligament reconstruction (ACLR), tunnels should be placed relatively higher in the femoral anterior cruciate ligament (ACL) footprint based on the findings of direct and indirect femoral insertion. But the clinical results of higher femoral tunnels (HFT) in double-bundle ACLR (DB-ACLR) remain unclear. The purpose was to investigate the clinical results of HFT and lower femoral tunnels (LFT) in DB-ACLR.@*METHODS@#From September 2014 to February 2016, 83 patients who underwent DB-ACLR and met the inclusion and exclusion criteria were divided into HFT-ACLR (group 1, n = 37) and LFT-ACLR (group 2, n = 46) according to the position of femoral tunnels. Preoperatively and at the final follow-up, clinical scores were evaluated with International Knee Documentation Committee (IKDC), Tegner activity, and Lysholm score. The stability of the knee was evaluated with KT-2000, Lachman test, and pivot-shift test. Cartilage degeneration grades of the International Cartilage Repair Society (ICRS) were evaluated on magnetic resonance imaging (MRI). Graft tension, continuity, and synovialization were evaluated by second-look arthroscopy. Return-to-sports was assessed at the final follow-up.@*RESULTS@#Significantly better improvement were found for KT-2000, Lachman test, and pivot-shift test postoperatively in group 1 ( P >0.05). Posterolateral bundles (PL) showed significantly better results in second-look arthroscopy regarding graft tension, continuity, and synovialization ( P <0.05), but not in anteromedial bundles in group 1. At the final follow-up, cartilage worsening was observed in groups 1 and 2, but it did not reach a stastistically significant difference ( P >0.05). No statistically significant differences were found in IKDC subjective score, Tegner activity, and Lysholm score between the two groups. Higher return-to-sports rate was found in group 1 with 86.8% (32/37) vs. 65.2% (30/46) in group 2 ( P = 0.027).@*CONCLUSION@#The HFT-ACLR group showed better stability results, better PL, and higher return-to-sports rate compared to the LFT-ACLR group.
Subject(s)
Humans , Follow-Up Studies , Anterior Cruciate Ligament/surgery , Knee Joint/surgery , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction/methods , Magnetic Resonance Imaging , Treatment Outcome摘要
Objective:To investigate the safety and efficiency of depilation with intense pulsed light (IPL) in congenital microtia patients during different phase of reconstruction treatment sessions.Methods:The hairy skin was treated with the M22TM system (Lumenis, German) using a filter of 695-1 200 mm. A three pluses mode of the radiant setting with a pulse width of 3.5 ms, a delay of 60 ms, and an energy density of 16-18 mJ/cm 2 was applied in the expanded patients. Depilation efficacy was evaluated as follows: excellent (hair density reduction >75%), good (50%-75%), fair (25%-50%), and poor (<25%). The depilation effect was compared between different phases. And the adverse effect was observed. Results:A total of 131 cases were included. There was no difference of the hair density reduction between patients with different expander volume after same IPL depilation treatments [15 (13-19) vs. 16 (15-19) root/cm 2, Wilcoxon rank analysis]. The hair density reduction in the expansion group was lower than the non-expansion group after two IPL depilation treatments [15 (13-19) vs. 17 (15-21) root/cm 2, P<0.05, Wilcoxon rank analysis]. The depilation efficacy was highly related with the numbers of IPL depilation treatments the patients received [Kendall′ stat b=0.74 (95% CI: 0.71-0.77), P<0.05]. There were 3 cases of folliculitis, 2 cases of blisters occurred in this study, and no expander exposure and cartilage absorption were observed. Conclusions:Hair removal with IPL is a safe and effective photo-epilation method during all stages of ear reconstruction using tissue expander. The volume of the expander does not significantly affect the hair removal efficiency. Depilation in the expansion phase is more efficient than that in the non-expansion phase, and the ideal result of " hair-free" or " less hairy" reconstructed ears can be achieved in 5 treatments, with suboptimal results in 3 treatments.
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ObjectiveTo evaluate the reliability and validity of the Dampness Syndrome Scale of Chinese Medicine (DSSCM) among patients with persistent asthma, and to explore the correlation between dampness syndrome and clinical characteristics of persistent asthma. MethodsA cross-sectional survey was conducted. Basic information, examination results, DSSCM, Asthma Control Test (ACT), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) scores were collected from 206 patients with persistent asthma to evaluate the reliability and validity of DSSCM and to explore the correlation between dampness syndrome and clinical characteristics. ResultsThe mean score of DSSCM among 206 patients was 14.59 ± 10.53. The overall Cronbach α coefficient and Spearman-Brown split-half reliability coefficient of the scale were both greater than 0.8, and the success rate of scale convergent and discriminant validity calibration were greater than 80%. The confirmatory factor analysis showed that the χ2/df was 2.309, and the root mean square error of approximation (RMSEA) was 0.08; the root mean square residual (RMR) was 0.049, whereas the comparative fit index (CFI), the goodness of fit index (GFI), the adjusted goodness of fit index (AGFI), the normed fit index (NFI) and the incremental fit index (IFI) were less than 0.9. Correlation analysis showed that DSSCM scores were positively correlated with disease duration, GAD-7 scores, and PHQ-9 scores (P<0.05), and negatively correlated with ACT scores (P<0.01). The DSSCM scores were significantly different between patients with different disease severity (H = 10.92, P = 0.01), and the DSSCM scores of allergic patients were higher than those of non-allergic patients (Z = -4.19, P<0.001). ConclusionDSSCM has acceptable reliability and validity for patients with persistent asthma. The scores of DSSCM correlated with the disease duration, ACT score, GAD-7 score, PHQ-9 score, disease severity and allergic status of persistent asthmatics.
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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.
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ObjectiveTePixD (Tll0078) is a blue light-using flavin (BLUF) photoreceptor protein from Thermosynechococcus elongatus BP-1. TePixD protein has a conserved Tyr8-Gln50-Met93 triad around the FAD pocket to mediate the proton-coupled electron transfer (PCET) process. But the detailed light response mechanism needs further study. We aimed to elucidate the structure and biochemical properties of TePixD mutants at key light response sites to analyze the light response process of TePixD. MethodsWe employed X-ray crystallography to resolve the crystal structure of the TePixD Y8F mutant. The side chain of Tyr8 is involved in PCET while Phe8 in mutation loses the function due to the loss of its hydroxyl group. We compared the structure of TePixD Y8F mutation to TePixD wild type (WT) and its homology protein SyPixD Y8F. Using multi-angle light scattering (MALS), we analyzed the oligomerization of multiple TePixD mutations (Y8F, Q50L, W91F, Y8F/W91F, and Q50L/W91F), focusing specifically on mutational sites that are critical residues for the protein’s photo response to dark and light conditions. ResultsWe resolved the crystal structure of TePixD Y8F mutant at a resolution of 2.54 Å and found that it shares a similar overall structure with the TePixD WT but exhibits significant differences from the SyPixD Y8F structure. Biochemical analysis revealed differences in molecular mass and elution profiles between the TePixD mutants and the WT under dark and light conditions, indicating the perturbation on the light-induced conformational change by the mutants. ConclusionOur structure determination and biochemical analyses will add information to reveal the light response mechanism of BLUF proteins.
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BACKGROUND:Ankylosing spondylitis is a chronic inflammatory disease with chronic rheumatic immunity.Soft tissue ossification and fusion and spinal stiffness can cause biomechanical changes. OBJECTIVE:To reconstruct the lumbar-sacral intervertebral disc in ankylosing spondylitis patients with lumbar kyphosis by finite element analysis,and to study the range of motion of each segment of T11-S1 and the biomechanical characteristics of annulus fibrosus and nucleus pulposus. METHODS:The imaging data were obtained from an ankylosing spondylitis patient with lumbar kyphosis.The original CT image data of continuously scanned spine were imported into Mimics 21.0 in DICOM format,and T11-S1 was reconstructed respectively.The established model was imported into 3-Matic software in the format of"Stl"to reconstruct the intervertebral disc,and the fibrous intervertebral disc model was obtained.The improved model was further imported into Hypermesh software,and the vertebra,nucleus pulposus,annulus fibrosus and ligament were mesh-divided.After the material properties were given,the model was imported into ABAQUS software to observe the range of motion of each vertebral body in seven different working conditions of T11-S1,and analyze the biomechanical characteristics of each segment of annulus fibrosus and nucleus pulposus. RESULTS AND CONCLUSION:(1)The range of motion of L1 vertebrae was higher than that of other vertebrae under six different working conditions:extension,forward flexion,rotation(left and right),and lateral flexion(left and right).The maximum range of motion was 2.18° during L1 vertebral flexion,and the minimum range of motion was 0.12° during L5 vertebral extension.(2)The annular fiber flexion at L2-L3 segments was greater than the extension(P<0.05),and the annular fiber flexion at L3-L4 and L4-L5 segments was less than the extension(P<0.05).The left rotation of L1-L2 annular fibers was greater than the right rotation(P<0.05).The left flexion of the annulus was greater than the right flexion in L1-L2,L2-L3,L3-L4,L4-L5 and L5-S1 segments(P<0.05).(3)The nucleus pulposus stresses of T11-L12,L1-L2,L2-L3,L3-L4 and L4-L5 segments in forward flexion were greater than in extension(P<0.05).The left rotation of T12-L1 and L3-L4 segments was smaller than the right rotation(P<0.05),and that of T11-T12,L1-L2,and L2-L3 segments was larger than the right rotation(P<0.05).The left flexion was larger than the right flexion in the T11-S1 segment.(4)It is concluded that in ankylosing spondylitis patients with lumbar kyphosis,the minimum range of motion of the vertebral body is located at the L5 vertebral body in extension.To prevent fractures,it is recommended to avoid exercise in the extension position.During the onset of lumbar kyphosis in patients with ankylosing spondylitis,the maximum stress of the annulus fibrosus and nucleus pulposus is located in the L1-L2 segment,which is fixed and will not alter with the change of body position.The late surgical treatment and correction of deformity should focus on releasing the pressure of the annulus fibrosus and nucleus pulposus in this segment to avoid the rupture of the annulus fibrosus and the injury of the nucleus pulposus.
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Objective To design an assisted patient conveying and vibration damping system to solve the problems of operator fatigue and patient bump during casualty evacuation.Methods The assisted patient conveying and vibration damping system was composed of several conveying straps and a vibration damping mechanism.The conveying straps were made up of a waist strap,two shoulder straps,a chest strap,adhesive straps and joint components,and the joint components included adjusting buckles,big buckles,small buckles,connecting buckles and hook mechanisms;the vibration damping mechanism adopted the technical form of extension handle combined with vibration absorber,in which the extension handle was made of rigid material and the vibration absorber was equipped with a scissor guiding mechanism.Tests were carried out on the system to record the operating time of the operators and to analyze the system's vibration damping characteristics.Results The system developed extended the operating time of the stretcher conveyers while reduced the vibration during casualty transport,with a maximum vibration reduction of 71.73%.Conclusion The system developed gains advantages in low vibration and low workload,and can be used for casualty conveying in poor road conditions.[Chinese Medical Equipment Journal,2024,45(1):15-24]
摘要
The structural composition and working principle of Senographe DS Digital Mammography System were introduced.The causes and elimination of 2 cases of faults of the system in exposure and artifact were proposed.References were provided for treating similar faults.[Chinese Medical Equipment Journal,2024,45(1):118-120]
摘要
Objective:To analyze the characteristics and electrogastrogram features of patients with functional dyspepsia (FD) overlapping lower gastrointestinal symptoms (LGS).Methods:The clinical data of 61 patients with FD from January 2018 to December 2020 in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. Among them, FD overlapping LGS was in 33 cases (FD overlapping LGS group), and simple FD in 28 cases (simple FD group). The manifestations of patients with FD overlapping LGS were recorded. The dyspeptic symptom score was assessed using the Rome Ⅳ criteria. Anxiety and depression status were evaluated using the hospital anxiety and depression scale (HADS), and sleep disorder was assessed using the Pittsburgh sleep quality index (PSQI). The electrogastrogram was performed, and the normal slow wave percentage (N%), bradygastria percentage (B%), tachygastria percentage (T%), arrhythmia percentage (A%), dominant frequency, dominant power and postprandial-to-fasting power ratio (PR) were recorded.Results:The most common symptom in FD patients overlapping LGS was lower abdomen distention, the incidence was 84.85% (28/33). The upper abdominal bloating score in FD overlapping LGS group was significantly higher than that in simple FD group: 7.00 (6.50, 7.00) scores vs. 5.00 (0.50, 7.00) scores, and there was statistical difference ( P<0.01); there were no statistical differences in other dyspeptic symptoms scores and total score between the two groups ( P>0.05). The incidences of depression and sleep disorder in FD overlapping LGS group were significantly higher than those in simple FD group: 42.42% (14/33) vs. 14.29% (4/28) and 69.70% (23/33) vs. 39.29% (11/28), and there were statistical differences ( χ2 = 5.77 and 5.68, P<0.05); there was no statistical difference in the incidence of anxiety between the two groups ( P>0.05). In FD overlapping LGS group, the postprandial T% in the gastric fundus and postprandial A% in the gastric body were significantly lower than those before meal: 13.79% (6.79%, 21.46%) vs. 20.69% (12.45%, 27.59%) and 3.45% (0, 6.90%) vs. 6.90% (3.45%, 13.79%), and there were statistical differences ( P<0.01). In simple FD group, the postprandial N% in the gastric fundus was significantly lower than that before meal: 55.92% (43.71%, 70.02%) vs. 69.27% (48.07%, 78.45%), and there was statistical difference ( P<0.05). In the gastric fundus, the preprandial N% in FD overlapping LGS group was significantly lower than that in simple FD group, preprandial B% and T% were significantly higher than those in simple FD group, and there were statistical differences ( P<0.01 or <0.05). In the gastric body, the preprandial N% in FD overlapping LGS group was significantly lower than that in simple FD group, and there was statistical difference ( P<0.05). In the pyloric region, the PR in FD overlapping LGS group was significantly lower than that in simple FD group, and there was statistical difference ( P<0.05). In the overall stomach, the preprandial N% in FD overlapping LGS group was significantly lower than that in simple FD group, the preprandial B% and T% were significantly higher than those in simple FD group, and there were statistical differences ( P<0.01 or <0.05). Spearman correlation analysis result showed that the disease course was not correlated with electrogastrogram parameters in patients with FD overlapping LGS ( P>0.05); the total score of dyspeptic symptoms was positively correlated with postprandial A% in the overall stomach ( r = 0.345, P<0.05), and negatively correlated with postprandial dominant frequency in the overall stomach and pyloric region ( r = -0.357 and -0.473, P<0.05 or <0.01). Conclusions:FD patients can overlap with various LGS. The patients with FD overlapping LGS have more severe dyspepsia symptoms, higher proportions of comorbid depression and sleep disorders, and more severe abnormalities in fasting proximal gastric electrical rhythm and emptying function. The severity of dyspeptic symptoms in patients with FD overlapping LGS is correlated with postprandial gastric electrical rhythm abnormalities.
摘要
Objective:To investigate effects of short-term cigarette smoke exposure combined with poly(I:C)stimulation on lung immune response and interferon expression in mice.Methods:BALB/c mice were randomly divided into 4 groups:control group,smoke group,poly(I:C)group and smoke combined poly(I:C)group.Total cell number and cell classification count of bronchoalveo-lar lavage fluid(BALF)were detected,and cell morphology was observed under ordinary light.Cytokines,chemokines,interferon and interferon stimulating genes expressions in lung tissues were detected by fluorescence quantitative PCR.Results:Compared with control group,total cell count,macrophage count and neutrophil count in smoke combined poly(I:C)group were significantly increased(P<0.05),and macrophage count was higher than that in poly(I:C)group.Macrophages of airway lavage fluid of mice in smoke combined with poly(I:C)group were larger in size,round or irregular in shape,and had more vacuoles in cytoplasm.Com-pared with control group,mRNA expressions of neutrophil chemokine CXCL1(P<0.05),CXCL2(P<0.01)and lymphocyte chemo-kine CCL2(P<0.01)in lung tissues of mice in smoke combined with poly(I:C)group were increased.IL-1β,IL-6,TNF-α mRNA expressions were significantly increased(P<0.01),IFN-β(P<0.01),IFN-γ(P<0.05),MX2(P<0.01)and IP-10(P<0.01)expre-ssions in lung tissues were significantly increased,and compared with poly(I:C)group,mRNA expressions of CXCL2(P<0.05),TNF-α(P<0.01)and IFN-β(P<0.05)in lung tissues of mice in smoke combined with poly(I:C)group were significantly increased.Conclusion:Cigarette smoke combined with poly(I:C)induces lung inflammation and expressions of interferon and interferon stimu-lating genes in mice.Cigarette exposure also increases poly(I:C)-induced acute lung inflammation and type Ⅰ interferon expression in mice.