Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

ObjectiveTo observe the effect of Yangxin Tongmai Formula （养心通脉方） by midnight-noon ebb-flow administration method for rat models of premature coronary heart disease （PCHD） with blood stasis syndrome， and to explore the possible mechanism of action from the perspective of DNA methylation differential gene expression. MethodsThere were 3 SD rats in each of the blank group， model group and Yangxin Tongmai Formula group， and the rats in the model group and Yangxin Tongmai Formula group were fed with high-fat chow plus vitamin D3 by gavage plus isoproterenol hydrochloride by subcutaneous injection to construct rat models of PCHD with blood stasis syndrome. After successful modelling， rats in Yangxin Tongmai Formula group were gavaged with 18 g/（kg‧d） of Yangxin Tongmai Formula， and rats in blank group and the model group were gavaged with 4 ml/（kg‧d） of 0.9% NaCl solution， and serum samples of rats in each group were collected for DNA methylation sequencing after 3 weeks to screen for the relevant DNA methylation differentiation genes. In addition， rats with successful modelling of PCHD with blood stasis were randomly divided into model group， Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice in the heart channel period （12：00） and pericardium channel period （20：00）］， the Yangxin Tongmai Formula control group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice at 8：00 and 18：00］ and the Atorvastatin Calcium group ［atorvastatin calcium tablets solution 1.8 mg/（kg‧d） at the same intervention time as that in Yangxin Tongmai Formula control group］， and set up a blank group of 8 rats in each group. The model group and blank group were gavaged with 0.9% NaCl solution 4 ml/（kg‧d） for the same time as the Yangxin Tongmai Formula control group. After 3 weeks of gavage， the blood lipids ［including total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）］ levels of rats in each group were detected； the HE staining of myocardial tissues and thoracic aorta was used to observe the pathomorphological changes； the levels of serum inflammation indexes ［tumour necrosis factor alpha （TNF-alpha）， lipopolysaccharide （LPS）， and interleukin 10 （IL-10）］ were detected； immunoprecipitation-realtime fluorescence quantitative PCR was used to detect the relative expression of cardiac tissue screening differential genes. ResultsThe genes screened for differentially methylated regions were calmodulin 2 （Calm2）， calcium voltage-gated channel subunit α1s （Cacna1s）， and phospholipase Cβ1 （Plcb1）. Compared with the blank group， rats in the model group showed elevated levels of TC， LDL， TNF-α and LPS， and decreased levels of HDL and IL-10 （P＜0.05 or P＜0.01）； HE staining showed obvious swelling of myocardial fibres， accompanied by a large number of inflammatory cell infiltration， and thickening of the inner wall of the aortic vessels with internal wall damage， which was visible as a large number of lipid cholesterol crystals and obvious inflammatory cell infiltration. Compared with the model group， the TC， LDL， TNF-α and LPS contents of rats in the Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group， the Yangxin Tongmai Formula control group， and the atorvastatin calcium group all reduced， and the contents of HDL and IL-10 all elevated （P＜0.05）， with the improvement of myocardial tissue damage and the reduction of inflammatory infiltration， and the improvement of the damage of the inner lining of the thoracic aorta and the reduction of lipid infiltration. Compared with Yangxin Tongmai Formula control group， LDL， TNF-α and LPS contents reduced， and IL-10 contents increased in the midnight-noon ebb-flow administration method group （P＜0.05）. Compared with the model group， the relative expression of Calm2 and Plcb1 genes decreased and the relative expression of Cacna1s gene increased in Yangxin Tongmai Formula control group and the midnight-noon ebb-flow administration method group （P＜0.05）； compared with the Yangxin Tongmai Formula control group， the relative expression of Calm2 gene decreased and the relative expression of Cacna1s gene increased in the midnight-noon ebb-flow administration method group （P＜0.05）. ConclusionThe intervention of Yangxin Tongmai Formula in the heart channel period （12：00） and pericardium channel period （20：00） was more effective in improving the blood lipid level， inhibiting inflammation， and improving myocardial tissue damage in rats of PCHD with blood stasis syndrome， and Calm2 and Cacna1s genes may be the key targets of Yangxin Tongmai Formula in intervening the blood stasis syndrome of PCHD.

Objective: To establish a prediction model for high-risk cardiovascular disease (CVD) among residents aged 35 to 75 years, so as to provide the basis for improving CVD prevention and control measures. Methods: Permanent residents aged 35 to 75 years were selected from Dongcheng District, Beijing Municipality using the stratified random sampling method from 2018 to 2023. Demographic information, lifestyle, waist circumference and blood biochemical indicators were collected through questionnaire surveys, physical examinations and laboratory tests. Influencing factors for high-risk CVD among residents aged 35 to 75 years were identified using a multivariable logistic regression model, and a prediction model for high-risk CVD was established. The predictive effect was evaluated using the receiver operating characteristic (ROC) curve. Results: A total of 6 968 individuals were surveyed, including 2 821 males (40.49%) and 4 147 females (59.51%), and had a mean age of (59.92±9.33) years. There were 1 155 high-risk CVD population, with a detection rate of 16.58%. Multivariable logistic regression analysis showed that gender, age, smoking, central obesity, systolic blood pressure, fasting blood glucose, triglyceride and low-density lipoprotein cholesterol were influencing factors for high-risk CVD among residents aged 35 to 75 years (all P<0.05). The area under the ROC curve of the established prediction model was 0.849 (95%CI: 0.834-0.863), with a sensitivity of 0.693 and a specificity of 0.863, indicating good discrimination. Conclusion The model constructed by eight factors including demographic characteristics, lifestyle and blood biochemical indicators has good predictive value for high-risk CVD among residents aged 35 to 75 years.

Lactylation (Kla), a protein post-translational modification characterized by the covalent conjugation of lactyl groups to lysine residues in proteins, is widely present in living organisms. Since its discovery in 2019, it has attracted much attention for its role in regulating major pathological processes such as tumorigenesis, neurodegenerative diseases, and cardiovascular diseases. By mediating core biological processes such as signal transduction, epigenetic regulation, and metabolic homeostasis, lactylation contributes to disease progression. However, the lactylation donor lactyl-CoA has a low intracellular concentration, and the specific enzyme catalyzing lactylation is not yet clear, which has become an urgent issue in lactate research. A groundbreaking study in 2024 found that alanyl-transfer t-RNA synthetase 1/2 (AARS1/2), members of the aminoacyl-tRNA synthetase (aaRS) family, can act as protein lysine lactate transferases, modifying histones and metabolic enzymes directly with lactate as a substrate, without relying on the classical substrate lactyl-CoA, promoting a new stage in lactate research. Although exercise significantly increases lactate levels in the body and can induce changes in lactylation in multiple tissues and cells, the regulation of lactylation by exercise is not entirely consistent with lactate levels. Research has found that high-intensity exercise can induce upregulation of lactate at 37 lysine sites in 25 proteins of adipose tissue, while leading to downregulation of lactate at 27 lysine sites in 22 proteins. The level of lactate is not the only factor regulating lactylation through exercise. We speculate that the lactate transferase AARS1/2 play an important role in the process of lactylation regulated by exercise, and AARS1/2 should also be regulated by exercise. This review introduces the molecular biology characteristics, subcellular localization, and multifaceted biological functions of AARS, including its canonical roles in alanylation and editing, as well as its newly identified lactate transferase activity. We detail the discovery of AARS1/2 as lactylation catalysts and the specific process of them as lactate transferases catalyzing protein lactylation. Furthermore, we discuss the pathophysiological significance of AARS in tumorigenesis, immune dysregulation, and neuropathy, with a focus on exploring the expression regulation and possible mechanisms of AARS through exercise. The expression of AARS in skeletal muscle regulated by exercise is related to exercise time and muscle fiber type; the skeletal muscle AARS2 upregulated by long-term and high-intensity exercise catalyzes the lactylation of key metabolic enzymes such as pyruvate dehydrogenase E1 alpha subunit (PDHA1) and carnitine palmitoyltransferase 2 (CPT2), reducing exercise capacity and providing exercise protection; physiological hypoxia caused by exercise significantly reduces the ubiquitination degradation of AARS2 by inhibiting its hydroxylation, thereby maintaining high levels of AARS2 protein and exerting lactate transferase function; exercise induced lactate production can promote the translocation of AARS1 cytoplasm to the nucleus, exert lactate transferase function upon nuclear entry, regulate histone lactylation, and participate in gene expression regulation; exercise induced lactate production promotes direct interactions between AARS and star molecules such as p53 and cGAS, and is widely involved in the occurrence and development of tumors and immune diseases. Elucidating the regulatory mechanism of exercise on AARS can provide new ideas for improving metabolic diseases and promote health through exercise.

OBJECTIVE To evaluate the quality of diagnosis and treatment guidelines and expert consensuses on childhood immune thrombocytopenic purpura （ITP） published domestically and internationally， in order to provide reference for clinical practice and future guideline/expert consensus development and improvement. METHODS A systematic search was conducted across multiple databases， including PubMed， Cochrane Library， Embase， CNKI， Wanfang data， VIP， CBM； additionally， supplementary searches were carried out on websites such as Medlive， the Chinese Medical Association’s official website， and National Institute for Health and Clinical Excellence in the UK. The retrieval time ranged from the inception to September 2， 2024. Researchers who had undergone systematic training independently evaluated the methodology and report quality included in the guideline/consensus using the Appraisal of Guidelines Research and Evaluation Ⅱ （AGREE Ⅱ） and the Reporting Items for Practice Guidelines in Healthcare （RIGHT）. RESULTS A total of 11 guidelines/consensuses were included. The average scores for the six domains of AGREE Ⅱ tool respectively were “range and purpose” （[ 66.67±17.98）% ]， “participants” [58.33% （13.89%，73.61%）]， “rigor” （[ 41.81±23.85）% ]， “clarity”（[ 69.57±19.35）%]， “applicability” （[ 35.98±17.83）%]， and “independence” [27.08% （0，75.00%）]； out of 11 articles， 9 had a recommendation level of B， 2 had a recommendation level of C， and there were no A-level articles. The average reporting rates of the 7 areas in the RIGHT tool were “basic information” （[ 72.35±12.95）% ]， “background” （[ 54.55±15.40）%]，“ evidence” （[ 36.36±24.81）%]，“ recommended opinions” （[ 53.25±19.20）%]，“ review and quality assurance” [0 （0， 25.00%）]， “funding and conflict of interest statement and management” [12.50%（0，25.00%）]， and other aspects [8.33%（0， 50.00%）]. In addition， there was no statistically significant difference in the AGREE Ⅱ and RIGHT scores between the guidelines and consensuses （P＞0.05）. CONCLUSIONS The overall quality of the guidelines and consensuses included in this study is not high， with a recommended level of B or C. It is recommended that clinical decision-making prioritize referring to the relatively high-quality guideline/consensus among them. The quality of evidence in the existing traditional Chinese medicine guidelines for children with ITP needs to be improved， and there is no integrated guideline/consensus for traditional Chinese and Western medicine. It is recommended to revise or write relevant guideline/consensus according to the requirements of AGREE Ⅱ and RIGHT in various fields to guide clinical practice.

Locomotion, a fundamental motor function encompassing various forms such as swimming, walking, running, and flying, is essential for animal survival and adaptation. The mesencephalic locomotor region (MLR), located at the midbrain-hindbrain junction, is a conserved brain area critical for controlling locomotion. This review highlights recent advances in understanding the MLR’s structure and function across species, from lampreys to mammals and birds, with a particular focus on insights gained from optogenetic studies in mammals. The goal is to uncover universal strategies for MLR-mediated locomotor control. Electrical stimulation of the MLR in species such as lampreys, salamanders, cats, and mice initiates locomotion and modulates speed and patterns. For example, in lampreys, MLR stimulation induces swimming, with increased intensity or frequency enhancing propulsive force. Similarly, in salamanders, graded stimulation transitions locomotor outputs from walking to swimming. Histochemical studies reveal that effective MLR stimulation sites colocalize with cholinergic neurons, suggesting a conserved neurochemical basis for locomotion control. In mammals, the MLR comprises two key nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). Both nuclei contain glutamatergic and GABAergic neurons, with the PPN additionally housing cholinergic neurons. Optogenetic studies in mice by selectively activating glutamatergic neurons have demonstrated that the CnF and PPN play distinct roles in motor control: the CnF drives rapid escape behaviors, while the PPN regulates slower, exploratory movements. This functional specialization within the MLR allows animals to adapt their locomotion patterns and speed in response to environmental demands and behavioral objectives. Similar to findings in lampreys, the CnF and PPN in mice transmit motor commands to spinal effector circuits by modulating the activity of brainstem reticular formation neurons. However, they achieve this through distinct reticulospinal pathways, enabling the generation of specific behaviors. Further insights from monosynaptic rabies viral tracing reveal that the CnF and PPN integrate inputs from diverse brain regions to produce context-appropriate behaviors. For instance, glutamatergic neurons in the PPN receive signals from other midbrain structures, the basal ganglia, and medullary nuclei, whereas glutamatergic neurons in the CnF rarely receive inputs from the basal ganglia but instead are strongly influenced by the periaqueductal grey and inferior colliculus within the midbrain. These differential connectivity patterns underscore the specialized roles of the CnF and PPN in motor control, highlighting their unique contributions to coordinating locomotion. Birds exhibit exceptional flight capabilities, yet the avian MLR remains poorly understood. Comparative studies suggest that the pedunculopontine tegmental nucleus (PPTg) in birds is homologous to the mammalian PPN, which contains cholinergic neurons, while the intercollicular nucleus (ICo) or nucleus isthmi pars magnocellularis (ImC) may correspond to the CnF. These findings provide important clues for identifying the avian MLR and elucidating its role in flight control. However, functional validation through targeted experiments is urgently needed to confirm these hypotheses. Optogenetics and other advanced techniques in mice have greatly advanced MLR research, enabling precise manipulation of specific neuronal populations. Future studies should extend these methods to other species, particularly birds, to explore unique locomotor adaptations. Comparative analyses of MLR structure and function across species will deepen our understanding of the conserved and evolved features of motor control, revealing fundamental principles of locomotion regulation throughout evolution. By integrating findings from diverse species, we can uncover how the MLR has been adapted to meet the locomotor demands of different environments, from aquatic to aerial habitats.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Aim To preliminarily evaluate the effects of hypobaric hypoxia on organism damage in rats with post-traumatic stress disorder(PTSD),with a view to laying a foundation for drug research in plateau PTSD.Methods The rats were randomly divided into four groups,namely,the control(Control)group,the sin-gle-prolonged stress(SPS)group,the hypobaric hy-poxia(HH)group and the single-prolonged stress combined with hypobaric hypoxia(SPS+HH)group.The PTSD model was firstly constructed using the SPS method for rats in the SPS and SPS+HH groups.On the second day,rats in the HH group and SPS+HH group were placed in a low-pressure hypoxia chamber at a simulated altitude of 6000 m for 14 days.General condition,behavior,blood tests,and histomorphology were examined in order to evaluate the damage caused by low pressure hypoxia in PTSD rats.Results The body mass of rats in the SPS+HH group was signifi-cantly reduced;the feces were partly hard and lumpy,and some of them were seen to have high viscosity.Anxiety-like and depression-like behaviors were ob-served in all groups except in the control group,in which hypobaric hypoxia aggravated the behavioral ab-normalities in SPS rats.Rats in both the SPS and SPS+HH groups had coagulation dysfunction and abnor-mally increased blood viscosity,which was significantly abnormal in the SPS+HH group;erythrocytes,hemo-globin,and erythrocyte specific volume in whole blood of rats in the SPS+HH group were significantly in-creased compared with those of rats in the SPS group;and serum TP,LDH and GLU levels were abnormal in rats in the SPS+HH group.Dilated and congested blood vessels were seen in hippocampal tissue,conges-ted central veins were seen in hepatic tissue,and dilat-ed and congested liver sinusoids with mild granuloma-tous degeneration of hepatocytes were seen in rats of the SPS+HH group.Conclusion Hypobaric hypoxia exacerbates depression-like and anxiety-like behaviors in PTSD rats,as well as hematological indices and his-tomorphometric abnormalities in PTSD rats.

Aim To explore the mechanism of modified Wuzi Yanzong pill to reduce testicular toxicity of Tripterygium wilfordii by means of network pharmacolo-gy.Methods The effective chemical composition and target of modified Wuzi Yanzong Pill to reduce testicu-lar toxicity of Tripterygium wilfordii were analyzed by using multiple databases to understand the mechanism of action.Results The first five compounds of modi-fied Wuzi Yanzong pill are quercetin,sucrose,kaempferol,galactose and ellagic acid,respectively.The first five targets were TP53,SRC,EP300,MAPK3,STAT3;KEGG pathway enrichment analysis mainly concentrated in cancer pathway,lipid and atherosclero-sis,hepatitis B,apoptosis,diabetes complications AGE-RAGE signaling pathway,PI3K-Akt signaling pathway and other signaling pathways.Conclusions The ac-tive components of modified Wuzi Yanzong pill can re-duce the testicular toxicity of Tripterygium wilfordii mainly by interfering with TP53,SRC,EP300,MAPK3,STAT3 and other targets,regulating apoptosis,PI3K-Akt signaling pathway,diabetes complications AGE-RAGE signaling pathway,lipid metabolism and other pathways.

Over the past 30 years,nano-drug delivery systems(NDDS)have become a promising field of drug research.However,a poor knowledge of the in vivo process of NDDS,the limited methods of pharmacokinetic correlation,and the inability to effectively provide strong support for the construction of upstream drug as well as the evaluation of downstream pharmacology and toxicology have become the technical bottleneck for their clinical transformation.Lipid nanodrug(LND)is the most successful NDDS for industrial transformation with great biocompatibility.Taking LND as an example,this paper reviewed the delivery process and influencing factors in vivo,and summarized the regulatory mecha-nism of biological environments on drug release in vivo.Based on advanced spectroscopy and mass spectrometry techniques,the spatial and temporal distribution of the dynamic carrier particle/depolymer-ized molecule ratio and dynamic free/encapsulated drug ratio of LND in biological matrix were ana-lyzed.Finally,the existing problems and future developments in this field were summarized to provide references for the analysis of NDDS in vivo,and stimulate readers'interest in nanomedical research and development.