Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Synthetic biology is a crucial tool for the development of the bio-industry and bio-economy, representing a significant aspect of new quality productive forces. As a core course for graduate students in bioengineering, Synthetic Biology plays a vital role in ensuring the supply of essential talents for the development of the bio-industry in the new era. To better serve regional economic development and provide high-level talents for China's progress in the bio-industry, we analyzed typical issues encountered in the past teaching activities, set up a multi-disciplinary teaching team, optimized the course contents, adjusted the teaching mode, and mobilized students' learning interest. With the application of scientific research project as the starting point, we guided students to think and discuss deeply through the simulation of application writing and project defense, which improved students' critical thinking and innovative thinking. With industrialization as a focus, we explored a new training model combining production, education, and research through the joint practice base of the university and enterprises introduced typical cases of biomanufacturing to encourage students to engage in scientific research. The teaching reform significantly enhances the comprehensive abilities and national sentiments of graduate students. This paper hopes to serve as a reference for colleagues engaged in teaching in this field.
Synthetic Biology/education* ; Teaching ; China ; Humans

OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis （PM）. METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group （91 cases） and a non-cured group （40 cases） based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened， and their predictive power and correlation were evaluated by univariate analysis， and multivariate Logistic regression analysis， receiver operating characteristic （ROC） curves， and correlation analysis. RESULTS Univariate analysis showed that serum creatinine， creatinine clearance rate， minimum inhibitory concentration of meropenem ≥16 μg/mL， cerebrospinal fluid red blood cell count， cerebrospinal fluid white blood cell count， cerebrospinal fluid glucose content， blood trough concentration， blood open-loop metabolite concentration/trough concentration ratio， and intrathecal injection were all correlated with efficacy （P＜0.05）. The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio， intrathecal injection， and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy （P＜0.05）. ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 （AUC＝0.647）， serum creatinine was less than 59.5 μmol/L （AUC＝0.647）， and cerebrospinal fluid glucose content was less than 3.37 mmol/L （AUC＝0.709）， the risk of treatment failure significantly increased （P＜0.05）. Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （R 2＝0.134 5， P＜0.000 1）. CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio， low serum creatinine level， lack of intrathecal injection， and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy.

Objective To summarise the best evidence for postpartum follow-up acquired from patients with gestational diabetes mellitus so as to provide an evidence-based reference for establishment of a postpartum follow-up program.Methods Literature on postpartum blood glucose follow-up in patients with gestational diabetes mellitus was retrieved from 17 major databases including BMJ Best Practice,UpToDate,Joanna Briggs Institute(JBI),International Guide Collaboration Network,National Institute for Health and Care Excellence(NICE),American Diabetes Association website,Medlive,Cochrane Library,Embase,OVID,PubMed,Web of Science,Quanfang local PubMed,CNKI,Wanfang Data,VIP,and Sinomed from the inception of databases to July 2023.The literature to be retrieved included guidelines,expert consensus,evidence summaries,systematic reviews,clinical decisions,and the original studies.Results A total of 9 articles,five practice guidelines,a systematic review,an evidence summaries,an expert consensus and a clinical decisions,were included.Totally,17 pieces of best evidence were summarised from the five aspects:postpartum blood glucose,lifestyle guidance,breastfeeding,drug treatment and health education.Conclusions The summarised best evidences can provide evidence-based references for postpartum follow-up of patients with gestational diabetes.Nursing staff in hospitals and community health centres should formulate relevant follow-up plans according to the actual postpartum conditions of patients in order to prevent the incidence of postpartum Type Ⅱ diabetes.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective: To understand the relationship between daily exercise load and physical fitness of primary school students, so as to provide relevant theoretical basis for the development of on campus physical education plans and the improvement of procedural physical health management for elementary school students. Methods: A total of 223 students from 6 classes in a primary school in Beijing were selected by a stratified random cluster sampling method from May to June 2023. The daily exercise load of the students was monitored by Polar Verity Sense heart rate armband. The duration of moderate to vigorous physical activity (MVPA) and daily Training Impulse (TRIMP) value were calculated, and the related indexes of daily exercise load were analyzed. Chi square test and univariate Logistic regression analysis were used to analyze the correlation between daily exercise load and physical fitness assessment levels, and multi factor ordinal Logistic regression analysis was used to explore the influencing factors of physical fitness assessment levels. Results: The average time spent in MVPA was (21.65±17.48) min. The TRIMP value was (361.47±124.81). The time spent in MVPA of primary school students in outdoor class, zero point sports, recess and after class PE were ( 8.86 ±8.56, 9.41±10.47, 1.97±3.12, 2.46±2.57) min, respectively. TRIMP values were (68.89±20.84, 72.83±30.27, 51.68±18.23, 19.99±5.78) in outdoor class, zero point sports, recess and after class PE, respectively. The results of univariate analysis showed that there were statistically significant differences in physical fitness levels among students with different genders, grades, and BMI ( χ 2=7.13, 19.04, 32.98, P <0.05). The duration of daily MVPA, along with TRIMP value during outdoor class, zero point sports, recess, and after PE class were all statistically significant with physical fitness levels ( OR =1.07, 1.05, 1.02, 1.03, 1.11, P <0.05). The results of multi factor ordinal Logistic regression analysis showed that the primary school grade (lower grade: OR =9.24, middle grade: OR =7.81), BMI (abnormal: OR =0.21), duration of daily MVPA in school ( OR =1.06), and TRIMP value during outdoor class ( OR =1.05) were statistically significant with physical fitness levels ( P <0.05). Conclusions There is a positive correlation between physical fitness and different grades, BMI, daily exercise load, and outdoor exercise load. Increasing daily exercise load can improve students physical health. It is suggested to tailor the school sports program to suit primary school students, increase both the intensity and duration of school daily sports, and promote procedural physical health management for elementary school students.

Background and objective Different degrees of self-transcendence exist in lung cancer patients,which can stimulate patients'self-awareness and promote them to face negative events in life positively,thus improving pa-tients'quality of life and treatment outcomes.However,there are few reports on self-transcendence in lung cancer patients in China,and the related influencing factors have not yet been clarified.This study aims to investigate the current situation of self-transcendence in lung cancer patients and explore its risk factors,so as to provide a theoretical basis for clinical intervention decision-making.Methods 243 lung cancer patients who were admitted to the Department of Lung Cancer Center of West China Hospital,Sichuan University from September 2023 to February 2024 were enrolled as the study subjects;general infor-mation questionnaire,self-transcendence scale,Herth hope scale and social support scale were used for the investigation.The influencing factors related to self-transcendence of lung cancer patients were analyzed.Results The total mean score of self-transcendence in lung cancer patients was(44.73±8.94);the total mean score of hope level was(37.60±4.98),and the total mean score of social support was(41.31±7.27).Self-transcendence was positively correlated with hope level and social support(P＜0.001,P＜0.001).Education,hope level and social support were influencing factors of self-transcendence in lung cancer pa-tients(P＜0.05,P＜0.001,P＜0.05).Conclusion Self-transcendence in lung cancer patients was at a low level and was influenced by hope level and social support.Healthcare professionals should pay attention to improving the hope level of lung cancer pa-tients,carrying out targeted psychological interventions,and at the same time guiding them to enhance the perception of social support,so as to promote the realization of self-transcendence in patients.

In recent years, the management of heart failure (HF) (including drug therapy and non-drug therapy) has made many advances, but its prevalence and mortality are still high, and the long-term prognosis is poor.It is urgent to develop new therapeutic approaches and intervention targets and explore new drugs and methods to improve the prognosis.The characteristic transformation of myocardial energy metabolism is an important marker of HF development, closely related to the mechanism of myocardial energy deficiency in the failing heart.The imbalance of glucose and fatty acid availability in cardiomyocytes, metabolic conversion from oxidative phosphorylation to glycolysis of myocardial mitochondria, uncoupling between glycolysis and glucose oxidation pathway, and fetal gene reexpression all play important roles in myocardial dysfunction and HF development.Potential therapeutic methods to reduce the severity of HF include optimizing myocardial energy substrate metabolism, enhancing mitochondrial oxidative metabolism capacity, improving myocardial mitochondrial productivity efficiency, and thereby increasing cardiac work.This paper summarizes the characteristics and molecular regulation mechanism of myocardial energy metabolism during HF and discusses the research direction of optimizing HF treatment strategy based on myocardial energy metabolism regulation.

Objective To explore the effect of evidence-based thinking oriented micro-course and case-based learning(CBL)on cultivation of clinical thinking ability of nurses who are taking the standardised nursing training in intensive care unit(ICU)so as to provide a new teaching method in the training of nurses.Methods A total of 72 nurses taking standardised nursing training in ICU of our hospital from November 2021 to October 2023 were selected as the research objects.Thirty-six of nurses who took rotation in the ICU from November 2021 to October 2022 were assigned in the control group,and other 36 nurses who took rotation in the ICU from November 2022 to October 2023 were assigned in the trial group.In the control group,CBL teaching method was adopted in the standardised nursing training,while both of evidence-based thinking oriented micro-course and CBL teaching mothed were adopted in the trial group for the standardised nursing training.The two groups were compared in terms of scores of clinical thinking ability,assessment of theory and clinical skills,as well as nurses'satisfaction with the teaching.Results After the training,nurses in the trial group exhibited significant superiority to the control group in total scores of clinical thinking ability and its three dimensions,critical thinking ability,systematic thinking ability and evidence-based thinking ability(P<0.05 for all).Furthermore,nurses in the trial group achieved significantly higher scores in theoretical assessment and assessment of clinical skills in comparison with those in the control group(P<0.05).Moreover,the trial group reported significantly higher satisfaction with both of the teaching method and learning atmosphere than those of the control group(P<0.05 for both).Conclusion Evidence-based thinking oriented micro-course and CBL teaching method can effectively improve the clinical thinking ability,theoretical knowledge and operational skills among the nurses taking standardised nursing training in ICU.