Background: The magnesium depletion score (MDS), a novel clinical score, incorporates alcohol consumption, kidney disease, use of diuretics and proton pump inhibitors (PPIs) to assess magnesium levels. However, the prognostic significance of the MDS individuals with nonalcoholic fatty liver disease (NAFLD) remains uncertain. This research aimed to explore the relationship between the MDS and mortality outcomes in NAFLD patients, including all-cause mortality, cancer mortality, and cardiovascular disease (CVD) mortality. Method: Data acquired on 16,394 NAFLD patients from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 were analyzed in this cohort study. Mortality outcomes were assessed using the linked National Death Index, which included all-cause mortality, cancer mortality, and CVD mortality. Cox proportional hazards models were used to determine the hazard ratios (HRs) for mortality outcomes related to the MDS. Subgroup analyses were also performed to explore the potential modifying influences of different demographic and clinical characteristics. Result: An elevated MDS was associated with significantly higher risks of all-cause mortality (HR 1.22; 95% CI, 1.15–1.30), cancer mortality (HR 1.15; 95% CI, 1.03–1.28), and CVD mortality (HR 1.33; 95% CI, 1.18–1.51). While these associations remained consistent in many subgroups, factors such as gender, education level, and alcohol consumption influenced the link between the MDS and mortality. Conclusion: The MDS is as an innovative and feasible prognostic indicator for mortality among NAFLD patients. Incorporating the MDS into clinical practice could improve risk stratification and inform targeted interventions aimed at diminishing the risk of mortality linked to magnesium deficiency within this group.

Osteoporosis represents a major global health challenge with increasing prevalence and substantial healthcare burden. Current diagnostic approaches relying primarily on bone mineral density measurements have limitations for early disease detection and understanding pathophysiological mechanisms. We conducted comprehensive metabolomic analysis of osteoporotic cancellous bone to identify potential metabolic features and explore disease mechanisms. Hip cancellous bone samples from 18 osteoporotic patients and 18 age-matched non-osteoporotic controls were analyzed using dual-platform gas/liquid chromatography-mass spectrometry. Multivariate analysis combined with machine learning approaches identified metabolic patterns distinguishing osteoporotic from non-osteoporotic bone. Untargeted metabolomics of osteoporotic cancellous bone revealed widespread metabolic alterations. Key findings included significant reductions in amino acids (phenylalanine, glutamate, aspartate, lysine, arginine, serine, cystine), polyamines (spermidine), TCA intermediates (citrate, succinate), and purine nucleosides (adenosine, inosine, guanosine, inosine-2′-phosphate), together with decreased phospholipid precursors (phosphorylcholine, choline). In contrast, metabolites such as allantoic acid and inorganic sulfate were elevated. Pathway enrichment implicated amino acid, purine, energy, one-carbon, and phospholipid metabolism, converging on impaired osteoblast function, enhanced osteoclast activity, and oxidative stress. Statistically, inosine-2′-phosphate (AUC = 0.951) Allantoic acid (log2FC: 3.14785) and phenylalanine (log2FC: − 5.3884) showed strong discriminatory potential. This study provides the first comprehensive metabolomic profile of human osteoporotic cancellous bone, highlighting a network of metabolic disturbances that underlie dysregulated bone remodeling. These findings identify amino acid, purine, and phospholipid pathways as potential mechanistic drivers and therapeutic targets in osteoporosis. Metabolites with strong statistical significance warrant further validation and translational investigation.

China, being a densely populated nation, faces a substantial economic burden due to a high incidence of lupus nephritis (LN) cases. The concealed onset of LN has resulted in many individuals have missed the optimal timing for treatment. The aim of the research is to study the serum metabolomics of Chinese LN patients using gas chromatography (GC)/mass spectrometry (MS) and liquid chromatography (LC)/MS to identify potential diagnostic markers. Fifty LN patients and fifty normal controls, matched for Body Mass Index (BMI) and age, were selected. Serum analysis was conducted using GC/MS and LC/MS, followed by multivariate statistical analysis. Various multidimensional analyses, including principal component analysis, partial least squares discrimination analysis, and orthogonal partial least squares discrimination analysis, along with one-dimensional analyses such as t-tests, were performed. Metabolites with variable importance in projection value > 1 and a p-value < 0.05 were considered critical biomarkers for LN. Furthermore, identified biomarkers delineated relevant metabolic pathways, and a metabolic pathway map was obtained from the database. Forty-one metabolites were identified as potential LN biomarkers, primarily associated with immune regulation, energy metabolism, intestinal microbial metabolism, renal damage, and oxidative stress. The potential for diagnosing LN and other diseases through metabolomics is demonstrated. Future research should explore larger sample sizes, metabolomic comparisons across different diseases and health states, and integration of metabolomics with clinical diagnostics. Such studies will enhance the understanding of metabolomics in medical diagnosis and provide robust support for its practical application.

China, being a densely populated nation, faces a substantial economic burden due to a high incidence of lupus nephritis (LN) cases. The concealed onset of LN has resulted in many individuals have missed the optimal timing for treatment. The aim of the research is to study the serum metabolomics of Chinese LN patients using gas chromatography (GC)/mass spectrometry (MS) and liquid chromatography (LC)/MS to identify potential diagnostic markers. Fifty LN patients and fifty normal controls, matched for Body Mass Index (BMI) and age, were selected. Serum analysis was conducted using GC/MS and LC/MS, followed by multivariate statistical analysis. Various multidimensional analyses, including principal component analysis, partial least squares discrimination analysis, and orthogonal partial least squares discrimination analysis, along with one-dimensional analyses such as t-tests, were performed. Metabolites with variable importance in projection value > 1 and a p-value < 0.05 were considered critical biomarkers for LN. Furthermore, identified biomarkers delineated relevant metabolic pathways, and a metabolic pathway map was obtained from the database. Forty-one metabolites were identified as potential LN biomarkers, primarily associated with immune regulation, energy metabolism, intestinal microbial metabolism, renal damage, and oxidative stress. The potential for diagnosing LN and other diseases through metabolomics is demonstrated. Future research should explore larger sample sizes, metabolomic comparisons across different diseases and health states, and integration of metabolomics with clinical diagnostics. Such studies will enhance the understanding of metabolomics in medical diagnosis and provide robust support for its practical application.

Background The Chronic Pain Coping Inventory-42(CPCI-42) is mainly used for chronic pain management project, its original version is written in English and has been widely used in western countries. Therefore, the purpose of our study is to apply the CPCI-42 to Chinese patients and evaluate its responsiveness, reliability, and validity for Chinese patients with lumbar disc herniation (LDH). Methods Translation and adaptation were carried out in accordance with the guidelines of the American Academy of Orthopedic Surgeons Outcome Committee. A total of 133 patients who were diagnosed with LDH were included in this study. Psychometric evaluations were then performed and included score distribution, internal consistency, test–retest reliability, construct validity, and responsiveness. Results CPCI-42 is well adapted to the assessment of the cognitive and behavioral strategies of patients with LDH, and the scores of score distribution, internal consistency, test–retest reliability, construct validity, and responsiveness are excellent. Forward and reverse translation of the CPCI-42 to English from Chinese worked smoothly. Conclusion It is applicable to the assessment of quality of life of the cognitive and behavioral strategies of patients with LDH, and the scores of all indicators are excellent.

Purpose As an important public health problem, osteoporosis (OP) in China is also in an upward trend year by year. As a standard method for diagnosing OP, dual-energy X-ray absorptiometry (DXA) cannot analyze the pathological process but only see the results. It is difficult to evaluate the early diagnosis of OP. Our study was carried out through a serum metabolomic study of OP in Chinese postmenopausal women on untargeted gas chromatography (GC)/liquid chromatography (LC)–mass spectrometry (MS) to find possible diagnostic markers. Materials and Methods 50 Chinese postmenopausal women with osteoporosis and 50 age-matched women were selected as normal controls. We first used untargeted GC/LC-MS to analyze the serum of these participants and then combined it with a large number of multivariate statistical analyses to analyze the data. Finally, based on a multidimensional analysis of the metabolites, the most critical metabolites were considered to be biomarkers of OP in postmenopausal women. Further, biomarkers identified relevant metabolic pathways, followed by a map of metabolic pathways found in the database. Results We found that there may be metabolic pathway disorders like glucose metabolism, lipid metabolism, and amino acid metabolism in postmenopausal women with OP. 18 differential metabolites are considered to be potential biomarkers of OP in postmenopausal women which are a major factor in metabolism and bone physiological function. Conclusion These findings can be applied to clinical work through further validation studies. It also shows that metabonomic analysis has great potential in the application of early diagnosis and recurrence monitoring in postmenopausal OP women.

Osteosarcoma (OS) is the most common malignant bone tumour; however, the underlying mechanisms are mainly unknown. Enhancer of zeste homologue 2 (EZH2) and NOTCH pathway are important molecular signals related to carcinogenesis and tumour progression, but they are not fully understand in OS. Enhancer of zeste homologue 2, Notch3, HES1, and Nanog were detected on OS samples and statistically analysed. Expressions of these genes were investigate, and stem-like phenotype was verified in OS cells. This study found that higher EZH2 expression, Notch3 pathway, or Nanog were associated with tumour relapse and metastasis and a significantly shorter survival time. Moreover, the Notch3 pathway was activated in osteosarcoma stem cells. Enhancer of zeste homologue 2 overexpression could activate the Notch3 pathway and increase HES1 expression, leading to upregulated stem cell-related gene expression and self-renewal of OS cells. Our study demonstrates that EZH2, Notch3, and Nanog are important prognostic factors. Enhancer of zeste homologue 2 could maintain the self-renewal of OS cells, where the Notch3 pathway activation may be involved.

Chemoattractant is critical to recruitment of osteoclast precursors and stimulates tumor bone metastasis. However, the role of chemoattractant in bone metastasis of colorectal cancer (CRC) is still unclear. Histochemistry analysis and TRAP staining were utilized to detect the bone resorption and activation of osteoclasts (OCs) after administration of CCL7 neutralizing antibody or CCR1 siRNA. qRT-PCR analysis and ELISA assay were performed to detect the mRNA level and protein level of chemoattractant. BrdU assay and Tunel assay were used to detect the proliferation and apoptosis of osteoclast precursors (OCPs). The migration of OCPs was detected by Transwell assay. Western blots assay was performed to examine the protein levels of pathways regulating the expression of CCL7 or CCR1. OCPs-derived CCL7 was significantly upregulated in bone marrow after bone metastasis of CRC. Blockage of CCL7 efficiently prevented bone resorption. Administration of CCL7 promoted the migration of OCPs. Lactate promoted the expression of CCL7 through JNK pathway. In addition, CCR1 was the most important receptor of CCL7. Our study indicates the essential role of CCL7-CCR1 signaling for recruitment of OCPs in early bone metastasis of CRC. Targeting CCL7 or CCR1 could restore the bone volume, which could be a potential therapeutical target.

Excessive osteoclast differentiation and activation are closely associated with the development and progression of osteoporosis. Natural plant-derived compounds that can inhibit osteoclastogenesis are an efficient strategy for the prevention and treatment of osteoporosis. Tereticornate A (TA) is a natural terpene ester compound extracted from the leaves and branches of Eucalyptus gracilis, with antiviral, antibacterial, and anti-inflammatory activities. However, the effect of TA on osteoclastogenesis and the underlying molecular mechanism remain unclear. Based on the key role of the NF-κB pathway in the regulation of osteoclastogenesis and the observation that TA exhibits an anti-inflammatory effect by inhibiting NF-κB activity, we speculated that TA could exert anti-osteoclastogenesis activity. Herein, TA could inhibit the RANKL-induced osteoclast differentiation and formation of F-actin rings in RAW 264.7 cells. Mechanistically, TA downregulated the expression of c-Src and TRAF6, and also suppressed the RANKL-stimulated canonical RANK signaling pathways, including AKT, MAPK (p38, JNK, and ERK), and NF-κB; ultimately, downregulating the expression of NFATc1 and c-Fos, the key transcriptional factors required for the expression of genes (e.g., TRAP, cathepsin K, β-Integrin, MMP-9, ATP6V0D2, and DC-STAMP) that govern osteoclastogenesis. Our findings demonstrated that TA could effectively inhibit RANKL-induced osteoclastogenesis via the downregulation of c-Src and TRAF6 and the inhibition of RANK signaling pathways. Thus, TA could serve as a novel osteoclastogenesis inhibitor and might have beneficial effects on bone health.

Background Intracranial hemangiopericytoma is a rare disease and surgery is the mainstay treatment. Although postoperative adjuvant radiotherapy is often used, there are no reports comparing different radiotherapy techniques. The purpose of this study is to analyze the impact of post-operative radiotherapy and different radiotherapy technique on the results in patients with intracranial hemangiopericytoma (HPC). Methods We retrospectively reviewed 66 intracranial HPC patients treated between 1999 and 2019 including 29 with surgery followed by radiotherapy (11 with intensity-modulated radiotherapy (IMRT) and 18 with stereotactic radiosurgery (SRS)) and 37 with surgery alone. Chi-square test was used to compare the clinical characteristic between the groups. The Kaplan-Meier method was used to analyze overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox proportional hazards models were used to examine prognostic factors of survival. We also underwent a matched-pair analysis by using the propensity score method. Results The crude local control rates were 58.6% in the surgery plus post-operative radiotherapy group (PORT) and 67.6% in the surgery alone group ( p = 0.453). In the subgroup analysis of the PORT patients, local controls were 72.7% in the IMRT group and 50% in the SRS group ( p = 0.228). The median OS in the PORT and surgery groups were 122 months and 98 months, respectively ( p = 0.169). The median RFS was 96 months in the PORT group and 72 months in the surgery alone group ( p = 0.714). Regarding radiotherapy technique, the median OS and RFS of the SRS group were not significantly different from those in the IMRT group ( p = 0.256, 0.960). The median RFS were 112 and 72 months for pathology grade II and III patients, respectively ( p = 0.001). Propensity score matching did not change the observed results. Conclusion In this retrospective analysis, PORT did not improve the local control rates nor the survivals. The local control rates after IMRT and SRS were similar even though the IMRT technique had a much higher biological dose compared with the SRS technique.

代谢组学通过全面分析生物样品中低相对分子质量内源性代谢物,帮助了解疾病在代谢水平的发生和进展机制,可提供与疾病早期识别相关的代谢标志物信息,有助于开发疾病预测性生物标记物.目前已开展较多骨质疏松症的代谢组学研究,涉及临床诊断、治疗以及预后等方面,发现潜在生物标记物,并进一步揭示了骨质疏松症的发病机制.该文对代谢组学在骨质疏松症研究领域的应用进展作一综述,并对未来的研究方向进行展望.

Background: HMGA2 encodes a small non histone chromatin-associated protein that has no intrinsic transcriptional activity, but can modulate transcription by altering the chromatin architecture. HMGA2 was found overexpressed in a variety of epithelial and mesenchymal tumors and promoted invasion and metastasis in most malignant epithelial tumors. A recent study showed that P53 inhibited CRC progression by targeting HMGA2. However, the mechanism by which HMGA2 affect angiogenesis in CRC has not been clarified. Methods: The expression of HMGA2 was analyzed by IHC, WB and bio infomatic analysis. Cbioportal and mexpress online tools were applied to explore the CNV and methylation of HMGA2 in CRC patients. Single cell data from GEO was used to examine the specific cell type that contribute to the high HMGA2 expression in CRC. Lentivirus was used to knock down HMGA2 in CRC cells and HUVECs was used to study angiogenesis. Results: In the current study, we first detected the expression pattern of HMGA2 in CRC patients and evaluated its clinical values and CNV amplification could possibly contribute to the up regulation of HMGA2 in CRC patients. By analyzing CRC single cell data we found that HMGA2 was specifically up regulated in the colorectal epithelial cells. Furthermore, knocking down of HMGA2 suppresses angiogenesis via dual regulation of VEGF-A and SEMA3A in CRC through inactivating VEGRR2 pathway in HUVECs. Conclusions: HMGA2 might be a promising prognostic marker and target for treating advanced CRC patients.

Background To investigate the effect of lactic acid (LA) on the progression of bone metastasis from colorectal cancer (CRC) and its regulatory effects on primary CD115 (+) osteoclast (OC) precursors. Methods The BrdU assay, Annexin-V/PI assay, TRAP staining and immunofluorescence were performed to explore the effect of LA on the proliferation, apoptosis and differentiation of OC precursors in vitro and in vivo. Flow cytometry was performed to sort primary osteoclast precursors and CD4(+) T cells and to analyze the change in the expression of target proteins in osteoclast precursors. A recruitment assay was used to test how LA and Cadhein-11 regulate the recruitment of OC precursors. RT-PCR and Western blotting were performed to analyze the changes in the mRNA and protein expression of genes related to the PI3K-AKT pathway and profibrotic genes. Safranin O-fast green staining, H&E staining and TRAP staining were performed to analyze the severity of bone resorption and accumulation of osteoclasts. Results LA promoted the expression of CXCL10 and Cadherin-11 in CD115(+) precursors through the PI3K-AKT pathway. We found that CXCL10 and Cadherin-11 were regulated by the activation of CREB and mTOR, respectively. LA-induced overexpression of CXCL10 in CD115(+) precursors indirectly promoted the differentiation of osteoclast precursors through the recruitment of CD4(+) T cells, and the crosstalk between these two cells promoted bone resorption in bone metastasis from CRC. On the other hand, Cadherin-11 mediated the adhesion between osteoclast precursors and upregulated the production of specific collagens, especially Collagen 5, which facilitated fibrotic changes in the tumor microenvironment. Blockade of the PI3K-AKT pathway efficiently prevented the progression of bone metastasis caused by lactate. Conclusion LA promoted metastatic niche formation in the tumor microenvironment through the PI3K-AKT pathway. Our study provides new insight into the role of LA in the progression of bone metastasis from CRC.

Bone metastasis of colorectal cancer (CRC) cells leads to osteolysis. Aberrant activation of osteoclasts is responsible for bone resorption in tumor. In general, bone marrow-derived monocytes (BMMs) differentiate into osteoclasts, however, how CRC cells interact with BMMs and how to regulate the differentiation is elusive. We here report that CRC cells promote bone resorption in bone metastasis. Transcriptomic profiling revealed CCL3 up-regulated in MC-38 conditional medium treated BMMs. Further investigation demonstrated that CCL3 produced by BMMs facilitated cell infusion and thus promoted the osteoclastogenesis. In addition, CRC cells derived EGF stimulated the production of CCL3 in BMMs through activation of ERK/CREB pathway. Blockage of EGF or CCL3 can efficiently attenuate the osteolysis in bone metastasis of CRC.

Heterogeneity in bladder cancer results in variable clinical outcomes, posing challenges for clinical management of this malignancy. Recent studies suggest both tumor suppressive and oncogenic role of PPARγ in bladder cancer. The fuction of PPARγ signaling pathway in modulating carcinogenesis is controversial. The expression of PPARγ and association with overall survival were analyzed in patients from two cohorts. The effect of PPARγ activation on cell proliferation, cell cycle, and cell apoptosis were determined with the agonists (rosiglitazone and pioglitazone), the inverse agonist (T0070907), and the antagonist (GW9662) in Umuc-3 and 5637 bladder cancer cells. The correlation of PPARγ activation with PI3K-Akt pathway was evaluated with RNA sequencing data from the TCGA cases and 30 human bladder cancer cell lines. The effect of PPARγ activation on tumor growth was validated with subcutaneous tumor models in vivo. The effect of PPARγ activation on PI3K-Akt signaling transduction was determined with multiple assays including immunohistochemistry, flow cytometry, proteomic array, and western blotting. We showed that PPARγ was a favorable prognostic factor in patients with bladder cancer. PPARγ activation by rosiglitazone and pioglitazone markedly induced cell cycle G2 arrest and apoptosis in bladder cancer cells, which resulted in inhibition of cell proliferation in vitro and suppression of tumor growth in vivo. The underlying mechanism involved marked inhibition of PI3K-Akt pathway. This study reported the tumor-suppressive effect of PPARγ agonists in bladder cancer, suggesting that transactivation of PPARγ could be served as a potential strategy for the chemoprevention and therapeutic treatment of bladder cancer.