Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

Objective To evaluate the predictive ability and clinical application value of artificial intelligence (AI) systems in the benign and malignant differentiation and pathological type of pulmonary nodules, and to summarize clinical application experience. Methods A retrospective analysis was conducted on the clinical data of patients with pulmonary nodules admitted to the Department of Thoracic Surgery, Second Hospital of Lanzhou University, from February 2016 to February 2025. Firstly, pulmonary nodules were divided into benign and non-benign groups, and the discriminative abilities of AI systems and clinicians were compared. Subsequently, lung nodules reported as precursor glandular lesions (PGL), microinvasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) in postoperative pathological results were analyzed, comparing the efficacy of AI systems and clinicians in predicting the pathological type of pulmonary nodules. Results In the analysis of benign/non-benign pulmonary nodules, clinical data from a total of 638 patients with pulmonary nodules were included, of which there were 257 males (10 patients and 1 patient of double and triple primary lesions, respectively) and 381 females (18 patients and 1 patient of double and triple primary lesions, respectively), with a median age of 55.0 (47.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis of the two groups of variables showed that, except for nodule location, the differences in the remaining variables were statistically significant (P<0.05). Multivariate logistic regression analysis showed that age, nodule type (subsolid pulmonary nodule), average density, spicule sign, and vascular convergence sign were independent influencing factors for non-benign pulmonary nodules, among which age, nodule type (subsolid pulmonary nodule), spicule sign, and vascular convergence sign were positively correlated with non-benign pulmonary nodules, while average density was negatively correlated with the occurrence of non-benign pulmonary nodules. The area under the receiver operating characteristic curve (AUC) of the malignancy risk value given by the AI system in predicting non-benign pulmonary nodules was 0.811, slightly lower than the 0.898 predicted by clinicians. In the PGL/MIA/IAC analysis, clinical data from a total of 411 patients with pulmonary nodules were included, of which there were 149 males (8 patients of double primary lesions) and 262 females (17 patients of double primary lesions), with a median age of 56.0 (50.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis results showed that, except for gender, nodule location, and vascular convergence sign, the differences in the remaining variables among the three groups of PGL, MIA, and IAC patients were statistically significant (P<0.05). Multinomial multivariate logistic regression analysis showed that the differences between the parameters in the PGL group and the MIA group were not statistically significant (P>0.05), and the maximum diameter and average density of the nodules were statistically different between the PGL and IAC groups (P<0.05), and were positively correlated with the occurrence of IAC as independent risk factors. The average AUC value, accuracy, recall rate, and F1 score of the AI system in predicting lung nodule pathological type were 0.807, 74.3%, 73.2%, and 68.5%, respectively, all better than the clinical physicians’ prediction of lung nodule pathological type indicators (0.782, 70.9%, 66.2%, and 63.7% respectively). The AUC value of the AI system in predicting IAC was 0.853, and the sensitivity, specificity, and optimal cutoff value were 0.643, 0.943, and 50.0%, respectively. Conclusion This AI system has demonstrated high clinical value in predicting the benign and malignant nature and pathological type of lung nodules, especially in predicting lung nodule pathological type, its ability has surpassed that of clinical physicians. With the optimization of algorithms and the adequate integration of multimodal data, it can better assist clinical physicians in formulating individualized diagnostic and treatment plans for patients with lung nodules.

ObjectiveTo explore the clinical features and causative genes of short stature children with unknown etiology， providing evidence for precise clinical diagnosis and treatment. MethodsThe study recruited children with suspected but undiagnosed short stature from the pediatric endocrinology department in our hospital between January 2018 and August 2022. A retrospective analysis was performed on the clinical manifestations， laboratory test and whole exome sequencing （WES） results. Causative genes were classified and analyzed according to different pathogenic mechanisms. ResultsA total of 48 children （30 boys and 18 girls） were enrolled， aged 7.73 ± 3.97 years， with a height standard deviation score （ HtSDS） of -3.63 ± 1.67. Of the patients， 33 （68.8%） suffered from facial anomalies， 31 （64.6%） from skeletal abnormalities， 26 ［54.2%， 61.5% of whom born small for gestational age （SGA）］ from perinatal abnormalities， 24 ［50.0%， 87.5% of whom with growth hormone （GH） peak concentration below normal］ from endocrine disorders and 21（43.8%） had a family history of short stature. Laboratory tests showed that GH peak concentration following stimulation test was （9.72 ± 7.25） ng/mL， IGF-1 standard deviation score was -0.82 ± 1.42， the difference between bone age and chronological age was -0.93 ± 1.39 years. Of the 25 cases with mutant genes found by WES， 14 （56.0%） had pathogenic mutation， 6 （24.0%） likely pathogenic mutation， and 5 （20.0%） mutation of uncertain significance. Pathogenic and likely pathogenic variants were identified in 14 genes， including 10 affecting intracellular signaling pathways （PTPN11， RAF1， RIT1， ARID1B， ANKRD11， CSNK2A1， SRCAP， CUL7， SMAD4 and FAM111A） and 4 affecting extracellular matrix （ECM） components or functions （ACAN， FBN1， COL10A1 and COMP）. ConclusionsA rare monogenic disease should be considered as the possible etiology for children with severe short stature accompanied by facial anomalies， disproportionate body types， skeletal abnormalities， SGA， GH peak concentration below normal and a family history of short stature. WES played an important role in identifying the monogenic causes of short stature. This study indicated that affecting growth plate cartilage formation through intracellular signaling pathways and ECM components or functions was the main mechanism of causative genes leading to severe short stature in children. Further research may help discover and study new pathogenic variants and gene functions.

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 compare the pharmacokinetic profiles of the two teriflunomide tablets in healthy Chinese subjects under fasting and fed conditions and to evaluate their bioequivalence and safety.Methods A randomized,open,single-dose,parallel trial design was used to enroll 31 and 32 healthy Chinese male subjects in the fasting and fed groups,who were randomized to a single oral dose of 14 mg of either reference or test preparation of teriflunomide tablets.The plasma concentrations of teriflunomide were determined using liquid chromatography-tandem mass spectrometry method,and Phoenix WinNonlin 8.1 software was used to calculate pharmacokinetic parameters and perform bioequivalence analysis.Results Subjects received a single oral dose of the reference and test formulations of teriflunomide.The main pharmacokinetic parameters of teriflunomide in the fasting group were as follows:Cmax were(2.14±0.27)and(2.27±0.33)μg·mL-1,AUC0-72h were(105.70±11.20)and(107.72±11.77)μg·mL-1·h,tmax was 1.49 and 0.99 h;the main pharmacokinetic parameters of teriflunomide in the fed group were as follows:Cmaxwere(1.83±0.17)and(1.75±0.22)μg·mL-1,AUC0-72h were(102.66±9.18)and(101.57±13.01)μg·mL-1·h,tmax was 4.01 and 4.99 h.The 90％confidence intervals for the geometric means of Cmax and AUC0-72h for reference and test preparations in the fasting and fed groups were in the range of 80％to 125％.Conclusion The pharmacokinetic characteristics of the 2 formulations were similar under fasting and fed administration conditions,with good bioequivalence and safety;Postprandial administration may delay the time to peak of the drug.

Objective: To analyze the application of digital games for interventions to reduce risky sexual behavior among adolescents, so as to provide a reference for reducing adolescent risky sexual behavior. Methods: The study used PubMed, Web of Science, Cochrane Library, Scopus, Embase, China Biomedical Database, CNKI, Wanfang Database and VIP to carry out a literature search of the application of digital games for interventions aimed at reducing risky sexual behavior among adolescents covering the time period up until February 2024. Results: A total of 10 English articles were included, involving a total of 3 063 adolescents aged 10-24 years old. The publication time spanned from 2013 to 2023. The development and design of the digital games were mostly based on cognitive behavior theory and authentic decision making situations and dialogues. The game participants were divided into single party and multi party categories, mainly using virtual role playing, interactive narrative, and adventure challenges, and there were some differences in content. Digital game intervention had good feasibility and acceptability, which could improve adolescents sexual health knowledge, attitudes, self efficacy, and risk perception, so as to reduce the occurrence of risky behavior. Conclusion As an intervention aimed at reducing risky sexual behavior in adolescents, digital show has significant advantages and can serve as a new prevention and control strategy.