ObjectiveTo combine metabolomics， proteomics， and transcriptomics to analyze the biological characteristics of damp-heat toxin accumulation syndrome and damp-heat accumulation syndrome in acute gout. MethodsBlood samples were collected from 15 patients with damp-heat toxin accumulation syndrome and 15 patients with damp-heat accumulation syndrome in acute gout in clinical practice. Metabolomics technology was applied to detect serum metabolites， and an orthogonal partial sample least squares discriminant analysis model was constructed to screen for metabolites with significant intergroup changes， and enrichment pathway analysis and receiver operating characteristic （ROC） curve analysis were performed. Astral data independence acquisition （DIA） was used to detect serum proteins， perform principal component analysis and screen differential proteins， demonstrate differential ploidy by radargram， apply subcellular localisation to analyse protein sources， and finally apply weighted gene co-expression network analysis （WGCNA） to find key proteins. Transcriptome sequencing technology was also applied to detect whole blood mRNA， screen differential genes and perform WGCNA， and construct machine learning models to screen key genes. ResultsMetabolome differential analysis revealed 62 differential metabolites in positive ion mode and 26 in negative ion mode. These differential metabolites were mainly enriched in the mTOR signaling pathway and FoxO signaling pathway， with trans-3,5-dimethoxy-4-hydroxycinnamaldehyde， guanabenz， 4-aminophenyl-1-thio-beta-d-galactopyranoside showing the highest diagnostic efficacy. The proteome differential analysis found that 55 proteins up-regulated and 20 proteins down-regulated in the samples of damp-heat toxin accumulation syndrome. Notably， myelin basic protein （MBP）， transferrin （TF）， DKFZp686N02209， and apolipoprotein B （APOB） showed the most significant differences in expression. Differential proteins were mainly enriched in pathways related to fat digestion and absorption， lipid and atherosclerosis， and cholesterol metabolism. WGCNA showed the highest correlation between damp-heat toxin accumulation syndrome and the brown module， with proteins in this module primarily enriched in the hypoxia-inducible factor 1 （HIF-1） signaling pathway and lipid and atherosclerosis. Transcriptomic differential analysis identified 252 differentially expressed genes， with WGCNA indicating the highest correlation between damp-heat toxin accumulation syndrome and the midnight blue module. The random forest （RF） model was identified as the optimal machine learning model， predicting apolipoprotein B receptor （APOBR）， far upstream element-binding protein 2 （KHSRP）， POU domain class 2 transcription factor 2 （POU2F2）， EH domain-containing protein 1 （EHD1）， and family with sequence similarity 110A （FAM110A） as key genes. Integrated multi-omics analysis suggested that damp-heat toxin accumulation syndrome in the acute phase of gout is closely associated with lipid metabolism， particularly APOB. ConclusionCompared to damp-heat accumulation syndrome in the acute phase of gout， damp-heat toxin accumulation syndrome is more closely associated with lipid metabolism， particularly APOB， and lipid metabolism disorders contribute to the development of damp-heat toxin accumulation syndrome in patients with acute gout.

OBJECTIVE: To compare the effectiveness of a zero-profile three-dimensiaonal (3D)-printed microporous titanium alloy Cage and a conventional titanium plate combined with a polyether-ether-ketone (PEEK)-Cage in the treatment of single-segment cervical spondylotic myelopathy (CSM) by anterior cervical discectomy and fusion (ACDF). METHODS: The clinical data of 83 patients with single-segment CSM treated with ACDF between January 2022 and January 2023 were retrospectively analyzed, and they were divided into 3D-ZP group (35 cases, using zero-profile 3D-printed microporous titanium alloy Cage) and CP group (48 cases, using titanium plate in combination with PEEK-Cage). There was no significant difference in gender, age, disease duration, surgical intervertebral space, and preoperative Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) score, neck disability index (NDI), vertebral height at the fusion segment, Cobb angle, and other baseline data between the two groups (P>0.05). The operation time, intraoperative blood loss, hospital stay, complications, interbody fusion, and prosthesis subsidence were recorded and compared between the two groups. VAS score, NDI, and JOA score were used to evaluate the improvement of pain and function before operation, at 3 months after operation, and at last follow-up, and the vertebral height at the fusion segment and Cobb angle were measured by imaging. The degree of dysphagia was assessed by the Bazaz dysphagia scale at 1 week and at last follow-up. RESULTS: The operation was successfully completed in all the 83 patients. There was no significant difference in intraoperative blood loss and hospital stay between the two groups (P>0.05), but the operation time in the 3D-ZP group was significantly shorter than that in the CP group (P<0.05). Patients in both groups were followed up 24-35 months, with an average of 25.3 months, and there was no significant difference in the follow-up time between the two groups (P>0.05). The incidence and grade of dysphagia in CP group were significantly higher than those in 3D-ZP group at 1 week after operation and at last follow-up (P<0.05). There was no dysphagia in 3D-ZP group at last follow-up. There was no complication such as implant breakage or displacement in both groups. The intervertebral fusion rates of 3D-ZP group and CP group were 65.71% (23/35) and 60.42% (29/48) respectively at 3 months after operation, and there was no significant difference between the two groups [OR (95%CI)=1.256 (0.507, 3.109), P=0.622]. The JOA score, VAS score, and NDI significantly improved in the 3D-ZP group at 3 months and at last follow-up when compared with preoperative ones (P<0.05), but there was no significant difference between the two groups (P>0.05). There was no significant difference in the improvement rate of JOA between the two groups at last follow-up (P>0.05). At 3 months after operation and at last follow-up, the vertebral height at the fusion segment and Cobb angle significantly improved in both groups, and the two indexes in 3D-ZP group were significantly better than those in CP group (P<0.05). At last follow-up, the incidence of prosthesis subsidence in 3D-ZP group (8.57%) was significantly lower than that in CP group (29.16%) (P<0.05). CONCLUSION The application of zero-profile 3D-printed Cage and titanium plate combined with PEEK-Cage in single-segment ACDF can both reconstruct the stability of cervical spine and achieve good effectiveness. Compared with the latter, the application of the former in ACDF can shorten the operation time, reduce the incidence of prosthesis subsidence, and reduce the incidence of dysphagia.
Humans ; Spinal Fusion/instrumentation* ; Titanium ; Cervical Vertebrae/surgery* ; Diskectomy/instrumentation* ; Bone Plates ; Male ; Printing, Three-Dimensional ; Female ; Retrospective Studies ; Middle Aged ; Treatment Outcome ; Benzophenones ; Adult ; Spondylosis/surgery* ; Aged ; Polymers ; Ketones ; Polyethylene Glycols

OBJECTIVE: To evaluate the effectiveness of the single-stage anterior eccentric kyphotic distraction reduction technique (EKD-RT) for treating lower cervical dislocation with locked facet joints, assessing its reduction success rate, neurological improvement, and safety. METHODS: A retrospective analysis was conducted on 67 patients with lower cervical dislocation and locked facet joints (21 unilateral, 46 bilateral) treated between January 2015 and January 2024. There were 39 males and 28 females, with an average age of 49.5 years (range, 22-75 years). The injured segments included C _{3, 4} in 4 cases, C _{4, 5} in 13 cases, C _{5, 6} in 22 cases, and C _{6, 7} in 28 cases. The interval between injury and admission ranged from 2 hours to 2 days (mean, 5.6 hours). Preoperative Frankel grading included grade A in 9 cases, grade B in 28 cases, grade C in 17 cases, grade D in 11 cases, and grade E in 2 cases. Japanese Orthopaedic Association (JOA) score was 7.0±1.4. All patients underwent single-stage anterior cervical discectomy and fusion. Following discectomy at the dislocated level, the EKD-RT was applied to unlock and reduce the locked facet joints, followed by internal fixation. Operation time, blood loss, reduction success rate, and complications were recorded. Interbody fusion status was evaluated using Bridwell criteria. Neurological status was assessed pre- and post-operatively using Frankel grading. Spinal cord function was scored using the 17-point JOA score, and the improvement rate was calculated. RESULTS: Successful reduction of the locked facet joints achieved in all cases. The operation time was 41-85 minutes (range, 63.3 minutes), and intraoperative blood loss was 50-360 mL (range, 125.0 mL). Complications included cerebrospinal fluid leakage in 2 cases; no severe complications such as major vascular injury or recurrent laryngeal nerve injury occurred. All patients were followed up 12-24 months (mean, 17.9 months). At last follow-up, radiological examination confirmed interbody fusion in all patients, with no implant failure or migration. The Frankel grading included grade A in 3 cases, grade B in 9 cases, grade C in 13 cases, grade D in 16 cases, and grade E in 26 cases; the JOA score reached 13.7±2.3; all of which significantly improved compared to preoperative levels ( P<0.05). The improvement rate of JOA score was 66.1%±24.7%. CONCLUSION The EKD-RT is an effective surgical approach for lower cervical dislocation with locked facet joints. It enables safe and efficient reduction of the locked facet joints via a single incision, resulting in significant neurological improvement with a low complication rate.
Humans ; Male ; Middle Aged ; Female ; Cervical Vertebrae/diagnostic imaging* ; Retrospective Studies ; Adult ; Aged ; Zygapophyseal Joint/injuries* ; Joint Dislocations/diagnostic imaging* ; Treatment Outcome ; Spinal Fusion/methods* ; Young Adult ; Kyphosis/surgery*

Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer-related mortality worldwide. In recent years, metabolomics has emerged as a key systems biology approach for analyzing small-molecule metabolites in cells, tissues and organisms. It provides new strategies for early diagnosis and metabolic profiling. Additionally, metabolomics plays a crucial role in studying resistance mechanisms in lung cancer. Tumor cell metabolic reprogramming is a key driving factor in the initiation and progression of lung cancer. Metabolomics studies have revealed how lung cancer cells regulate critical pathways such as energy metabolism, lipid metabolism, and amino acid metabolism to adapt to the demands of rapid proliferation and invasive metastasis. This review summarizes the latest advances in metabolomics research in lung cancer, focusing on the characteristics of metabolic reprogramming, the identification of potential metabolic biomarkers, and the prospects of metabolomics in early diagnosis and the elucidation of resistance mechanisms in lung cancer.
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Humans ; Metabolomics/methods* ; Lung Neoplasms/pathology* ; Animals ; Biomarkers, Tumor/metabolism*

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective:To describe the distribution of fat-free mass (FFM) and fat-free mass index (FFMI) in children aged 3-17 years in China.Methods:Data were collected from National Nutrition and Health Systematic Survey in 0-18 years old children in China. By using multi-stage stratified randomized cluster sampling method, the project was conducted in 28 survey points in urban and rural areas in 14 provinces (autonomous regions and municipalities) in 7 regions in China from 2019 to 2021. FFM was measured using bioelectrical impedance meter. Finally, the body composition data of 70 853 children were included in the analysis. M ( Q1, Q3) was used to describe the gender and age specific FFM and FFMI of the children in different regions. Kruskal-Wallis H rank sum test was used to compare FFM and FFMI of boys and girls in same age group, boys in different age groups, girls in different age groups, as well as boys in same age group and girls in same age group in different regions. DSCF method was used for pairwise comparisons. Results:After the age of 11 years, the difference of FFMI between boys and girls increased year by year. The FFMI was 14.2 kg/m 2 in boys and 13.8 kg/m 2 in girls at 11 years old, the difference was significant ( χ2=135.86, P<0.001). The difference of FFMI between boys and girls exceed 1.0 kg/m 2 from 12 years old, and FFMI was 15.3 kg/m 2 in boys and 14.2 kg/m 2 in girls at 12 year old, the difference was significant ( χ2=597.27, P<0.001). The FFMI was 17.5 kg/m 2 in boys and 14.7 kg/m 2 in girls at 16 years old, the difference was significant ( χ2=2 543.60, P<0.001). The FFMI was higher in boys in northeast China, while the FFMI was lower in both boys and girls in northwest China. Conclusions:Gender specific difference was observed in the increase of FFMI with age. The FFMI was significantly higher in boys than in girls after 11 years old. It is necessary to pay attention to the problem of FFM in children in northeastern and northwestern China.

Objective:To investigate the distribution characteristics of body height, body weight and body mass index (BMI) in children aged 3-17 years in China.Methods:Data were obtained from the National Nutrition and Health Systematic Survey in 0-18 years old children in China. The study selected 70 853 children aged 3-17 years from 28 urban and rural survey sites in 14 provinces (autonomous regions and municipalities) in 7 regions of China with multi-stage stratified cluster random sampling. M ( Q1, Q3) was used to describe the region, age and gender specific body height, body weight and BMI in the children aged 3-17 years. Wilcoxon rank sum test was used to compare the body height, body weight, and BMI between boys and girls in same age group. Kruskal-Wallis H rank sum test was used to compare the body height, body weight and BMI among boys in different age groups and among girls in different age groups, as well as among boys in same age group and among girls in same age group from different regions, and DSCF method was used for further pairwise comparisons. Results:In this study, the median body height and body weight were 172.0 cm and 62.9 kg in 17-year-old boys and 160.0 cm and 53.7 kg in 17-year-old girls. The median for children's body height, body weight, and BMI in most age groups were higher in northeastern and northern China than in southern China, and the differences could be observed until age 17 years. The differences in body weight and BMI in children in northeastern and northern China were greater in Q3 than in Q1 compared with southern China. Conclusions:The body height of children aged 3-17 years continues to increase in China. Northeastern and northern China have more children with higher bodyweight, showing an obvious body weight increase trend, to which close attention needs to be paid.

Objective:To describe the distribution of fat mass (FM), fat mass percentage (FMP), and fat mass index (FMI) in children aged 3-17 years in China.Methods:Data of this study were from the National Nutrition and Health Systematic Survey in 0-18 years old children in China. A total of 70 853 children aged 3-17 years old selected from seven regions of China were included in this analysis. Body composition were measured by using bioelectrical impedance meter. The region, gender and age specific FM, FMP and FMI of the subjects were described by using M ( Q1, Q3). Kruskal-Wallis H rank sum test was used for the comparison of intergroup differences. DSCF method was used for pairwise comparisons. Results:The medians of FM, FMP and FMI were 3.0 kg, 18.3% and 2.9 kg/m 2 in boys aged 3 years and 2.9 kg, 19.0% and 2.9 kg/m 2 in girls aged 3 years, respectively. The FM increased with age and the FMP and FMI decreased with age in both boys and girls aged 3-5 years. After 11 years old, the FM, FMP and FMI decreased first and then increased in boys. From 6-17 years old, the FM, FMP and FMI increased gradually in girls. The FM, FMP and FMI were higher in girls than in boys after 12 years old (all P<0.05). The FM, FMP and FMI were relatively higher in children at the age of 6-14 in northeastern and northern China than in other regions. Conclusions:The age specific FM, FMP and FMI had different changing characteristics in boys and girls aged 3-17 years in seven regions of China. The FM, FMP and FMI also differed with region.

Objective:To analyze the relationship between body mass index (BMI) and fat mass percentage (FMP) in children aged 3-17 years in China.Methods:The BMI and FMP data of children aged 3-17 years from the National Nutrition and Health Systematic Survey in 0-18 years old children in China was analyzed. BMI- Z score/BMI and FMP were used to classify the subjects, respectively. Spearman correlation was used to analyze the correlation between BMI and FMP. The consistency between BMI- Z score/BMI and FMP in classifying the subjects was measured using Kappa coefficient. Results:The FMP of malnutrition, normal and overweight/obesity in boys was higher in age group 10-13-year than in other age groups (all P<0.001). The FMP of all nutritional status in girls increased with age (all P<0.05). The BMI of boys in all the FMP levels increased with age (all P<0.05). When the FMP of girls was 25%- or ≥30%, BMI increased with age (all P<0.001). The relationship between BMI and FMP was strong ( r=0.705, P<0.001), with r of 0.618 in boys and 0.884 in girls. The consistency between BMI- Z score/BMI and FMP in classifying the subjects was found to be moderate (Kappa=0.574, P<0.001). Conclusions:There was a strong relationship between BMI and FMP. The consistency between BMI- Z score/BMI and FMP in classifying the subjects was moderate.