OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy （DN）. METHODS From the perspective of healthcare service providers， a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months， a simulation period of 15 years and an annual discount rate of 5%. At the same time， one-way sensitivity analysis and probability sensitivity analysis were performed， and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan， and the accumulative utility was 8.052 4 quality-adjusted life year （QALYs）； the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan， and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value， DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio， but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients， finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.

OBJECTIVE To provide reference for safe drug use in patients with anaplastic lymphoma kinase （ALK）-positive non-small cell lung cancer （NSCLC）. METHODS Clinical pharmacists participated in the diagnosis and treatment of a patient with ALK-positive NSCLC who developed bilateral pleural effusion and hemolytic anemia after taking alectinib； regarding symptoms such as pleural effusion and hemolytic anemia in the patient， clinical pharmacists investigated the patient’s history of medication and disease， as well as potential drug interaction； to consider the correlation between the patient’s use of alectinib and the duration of pleural effusion and hemolytic anemia， clinical pharmacists suggested that clinical doctors discontinued alectinib and used reduced dose treatment after the pleural effusion improved， but the patient suffered from bilateral pleural effusion and hemolytic anemia again； after evaluating the correlation between alectinib and bilateral pleural effusion and hemolytic anemia using the Naranjo’s assessment scale， clinical pharmacists recommend permanent discontinuation of alectinib and jointly recommend replacement with ensartinib with clinical physicians. RESULTS Physicians adopted the suggestions of clinical pharmacists. The pleural effusion subsequently regressed and hemolytic anemia improved after replacing the drug. The correlation between alectinib and bilateral pleural effusion and hemolytic anemia was confirmed. CONCLUSIONS Clinical pharmacists participate in pharmaceutical monitoring of ALK-positive NSCLC patients， assist clinical doctors in developing personalized medication recommendations， and ensure the safety of patient medication.

Objective:To construct a nursing quality evaluation index system for knee ligament injury to provide a basis for standardizing the nursing practice and improving the nursing quality of knee ligament injury.Methods:Based on the three-dimensional quality structure model of "structure-process-outcome" proposed by Donabedian, the quality evaluation index system for knee ligament injury specialties was constructed through literature review, brainstorming, and Delphi expert consultation from April to June 2023.Results:Sixteen experts were included in the inquiry. The effective recovery rate of the two rounds of expert correspondence questionnaires was 16/16, the expert authority coefficient was 0.95, and the Kendell harmony coefficients of the expert correspondence were 0.116 and 0.122, respectively (both P<0.05). The final constructed knee ligament injury specialty care quality evaluation index system contained 3 primary indicators (structural quality, process quality and outcome quality), 16 secondary indicators, and 69 tertiary indicators.Conclusions:The specialized nursing quality evaluation index system for knee ligament injury constructed in this study is scientific and reliable, which can provide a basis for the evaluation and assessment of the nursing quality of knee ligament injury specialties and promote the continuous improvement of their nursing quality.

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 investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification.Methods:A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically.Results:There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant ( P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference ( P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant ( P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant ( P<0.001). Conclusions:GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

Objective To carry out rigid-body inverse dynamics modelling and analysis of a self-designed 6RSS parallel bio-inspired masticatory robot.Methods Firstly,the functions of kinematic variables including translational/rotational velocities and accelerations were derived for rigid-body inverse dynamics modelling.Secondly,the rigid-body inverse dynamics model was established with the Newton-Euler's law.Finally,the chewing motion trajectories of the oral health volunteers were tracked and numerical calculations were carried out in the case where the robot was subjected to a chewing reaction force.Results Numerical calculations showed that the driving torque and the constraint force of the robot peaked when the chewing reaction force was at its maximum.Conclusion The external force has a large impact on the inverse dynamics of the robot,and theoretical references are provided for the motion control and optimal design of the robot.[Chinese Medical Equipment Journal,2024,45(3):16-22]

The present study aims to screen and evaluate the early clinical predictors for type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI) and dementia in Hunan province. A cross-sectional study was conducted from May 2023 to October 2023 to collect data on long-term T2DM patients who settled in Hunan province and were treated in the Department of Geriatrology at Xiangya Hospital of Central South University. The patients were grouped according to the Montreal Cognitive Assessment (MoCA) scale. Basic patient information and multiple serum markers were collected, and differences between groups were compared using one-way ANOVA or Kruskal-Wallis (KW) tests. The multivariate logistic regression analysis was utilized to assess risk factors and Nomogram models were constructed. The logistic regression analysis showed that years of education and serum levels of 1, 5-AG were related factors for the progression of T2DM to T2DM with MCI, and body weight, years of education and FPN levels affected the progression of T2DM with MCI to T2DM with dementia. Based on this, two Nomogram risk prediction models were established. The area under the curve (AUC) of the Nomogram model predicting T2DM progression to T2DM combined with MCI was 0.741, and the AUC of the Nomogram model predicting T2DM combined with MCI progression to T2DM combined with dementia was 0.734. The calibration curves (DCA) of the two models in the training and validation sets were symmetrically distributed near the diagonal line, indicating that the models in the training and validation sets could match each other. In summary, body weight, years of education, and serum HDL-3, FPN, and 1, 5-AG levels are associated with the development of MCI and dementia in T2DM patients. The Nomogram models constructed based on these factors can predict the risk of MCI and dementia in T2DM patients, providing a basis for clinical decision-making.

Wilson's disease (WD) is a kind of inherited metabolic liver disease in which most patients need lifelong medication to maintain copper homeostasis in the body. Zinc is one of the most commonly used drugs for WD treatment. However, there are currently few high-quality, large-sample, and prospective clinical trials on zinc agent-treated WD. The selection and application of zinc agents are mainly based on patients' clinical phenotype, tolerance to zinc agents, and physicians' experience in treating WD. This article summarizes the application of zinc agents in WD.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.