ObjectiveTo study the distribution of bone-specific alkaline phosphatase (BALP), type Ⅰ collagen cross-linked C-telopeptide (CTX) and tartrate-resistant acid phosphatase (TRAP)-5b in plateau area builders, and analyze the influencing factors under plateau environment. MethodsBetween April and May, 2014, using random stratified cluster sampling, we included in our study 650 blood samples from the power grid construction people in Batang County of Ganzi Autonomous Prefecture of Sichuan Province and Mangkang County of Tibet Autonomous Region with an altitude ranging from 2 600 to 4 450 meters, averaging (3 586.50±610.85) meters. We collected their fasting blood and detected their TRAP-5b, CTX and BALP by enzyme-linked immunosorbent assay method. By using SPSS 13.0, we analyzed the relationship between TRAP-5b, CTX, BALP and the influencing factors such as age, working intensity, residence time in the plateau area and altitude of the plateau. In the end, we tried to find out the main influencing factors of bone metabolic markers in the plateau environment.ResultsThe levels of CTX, BALP and TRAP-5b were the highest before the age of 20, and the average levels of them were respectively (1.04±0.38) ng/mL, (52.09±14.62) μg/L, and (4.22±1.38) U/L. With the increase of age, the levels of CTX, TRAP-5b and BALP showed a downward trend, but CTX and BALP reached the lowest level in the age group of 40 to 49 years old, and the average levels of CTX and BALP were (0.44±0.26) ng/mL and (24.77±9.89) μg/L, respectively. Then they gradually increased after the age of 50. TRAP-5b reached the lowest level in the age group of 30 to 39 years old, and the average level of TRAP-5b was (2.59±0.95) U/L. Then it gradually increased after the age of 40. The activity of CTX and BALP increased obviously with the increase of altitude. With the increase of labor intensity, BALP, TRAP-5b and CTX all increased. However, no matter what labor intensity, the bone formation marker BALP first increased and then decreased with the plateau residence time, while the bone absorption marker TRAP-5b increased after the first reduction.ConclusionsBone metabolic markers are different in different age groups. Altitude, working intensity and plateau working time have significant effects on bone metabolism markers.
Objective To explore key genes and mechanisms of depression aggravating Crohn disease. Methods In March 2023, the Public Health Genomics and Precision Health Knowledge Base and Gene Expression Omnibus database were used to identify the overlapping differentially expressed genes between Crohn disease and depression and the key genes were screened by Metascape, STRING, Cytoscape, and protein interaction network analysis. The Gene Expression Omnibus database was used to analyze the correlations between key genes and clinical pathologies such as Crohn Disease Endoscopic Index of Severity and intestinal microvilli length. Results There were 137 overlapping differentially expressed genes between Crohn disease and depression, and 25 key genes were further screened out. Among them, CREB1, FKBP5, MAPT, NTSR1, OXTR, PROK2, POMC, HTR2B, and PPARGC1A genes were significantly correlated with multiple clinical parameters. The functions of PROK2 and PROK2-related genes were mainly enriched in neutrophil and granulocyte migration, neutrophil and granulocyte chemotaxis, etc. Conclusions There are 25 key genes, especially CREB1, FKBP5, MAPT, NTSR1, OXTR, PROK2, POMC, HTR2B, and PPARGC1A, that possibly contribute to the establishment and deterioration of Crohn disease caused by depressive disorder. Among these genes, PROK2 showes the possibility of regulating immune cell (neutrophils and CD8+ T cells) infiltration.
The human gut microbiota regulates many host pathophysiological processes including metabolic, inflammatory, immune and cellular responses. In recent years, the incidence and mortality of lung cancer have increased rapidly, which is one of the biggest challenges in the field of cancer treatment today, especially in non-small cell lung cancer. Animal models and clinical studies have found that the gut microbiota of non-small cell lung cancer patients is significantly changed compared with the healthy people. The gut microbiota and metabolites can not only play a pro-cancer or tumor suppressor role by regulating immune, inflammatory responses and so on, but also be related with radiotherapy and chemotherapy of non-small cell lung cancer and the resistance of immunotherapy. Therefore, gut microbiota and related metabolites can be both potential markers for early diagnosis and prognosis in patients with non-small cell lung cancer and novel therapeutic targets for targeted drugs. This study will review the latest research progress of effect of gut microbiota on non-small cell lung cancer, and provide a new diagnosis and treatment ideas for non-small cell lung cancer.
Breast cancer is a malignant tumor with the highest morbidity and mortality in female in recent years, and it is a complex disease that affects human health. Studies have shown that dynamic network biomarkers (DNB) can effectively identify critical states at which complex diseases such as breast cancer change from a normal state to a disease state. However, the traditional DNB method requires data from multiple samples in the same disease state, which is usually unachievable in clinical diagnosis. This paper quantitatively analyzes the time series data of MCF-7 breast cancer cells and finds the DNB module of a single sample in the time series based on landscape DNB (L-DNB) method. Then, a comprehensive index is constructed to detect its early warning signals to determine the critical state of breast cancer cell differentiation. The results of this study may be of great significance for the prevention and early diagnosis of breast cancer. It is expected that this paper can provide references for the related research of breast cancer.
Objective To study the changes of receptor activator of nuclear factor-κB ligand (RANKL, an osteoclastogenesis-promoting factor) and osteoprotegerin (OPG, the decoy receptor for RANKL), oxidative stress and bone turnover markers in obstructive sleep apnea-hypopnea syndrome (OSAHS), in order to understand the potential mechanisms underlying bone loss in OSAHS patients. Methods Ninety-eight male patients with OSAHS, confirmed by polysomnography (PSG) study, were enrolled. The patients were divided into mild-moderate groups and severe groups. Forty-two male subjects who were confirmed as not having OSAHS served as the controls. The subjects’ bone mineral density (BMD) and T-score were assessed in lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Blood samples were collected from all subjects for measurement of RANKL, OPG, the bone formation marker bone-specific alkaline phosphatase (BAP), the bone resorption marker tartrate-resistant acid phosphatase-5b (TRAP-5b), total antioxidant capacity (TAOC). Twenty-eight severe OSAHS patients accepted continuous positive airway pressure (CPAP) treatment voluntarily. After 6 months, PSG was conducted, and serum RANKL, OPG, TAOC, TRAP-5b, BAP was measured after six months treatment. Results The BMD, T-score of the femoral neck and the lumbar spine were significantly lower in OSAHS patients as compared to the control group. The level of BAP was significantly decreased in the OSAHS group as compared to the control group, and there was no significant difference in TRAP-5b level between two groups. As compared with the control group, levels of OPG, TAOC and the OPG/RANKL ratio decreased significantly. None of these parameters (BMD, T-score, RANKL, OPG, TRAP-5b, BAP) showed significant difference between patients with mild-moderate and severe OSAHS group. Correlation analysis showed that the apnea hypopnea index and oxygen desaturation index were correlated with TAOC. BAP level was positively correlated with TAOC and lowest pulse oxygen saturation. The serum level of TAOC was lower in the OSAHS group after CPAP therapy, but the levels of RANKL, OPG, TRAP-5b, BAP were not different. As compared with the OSAHS group before CPAP therapy, the BMD of the femoral neck and the lumbar spine were not significant difference. Conclusions In patients with OSAHS, the oxidative stress response is enhanced, and imbalance of OPG/RANKL is shifted, which participates in the occurrence of osteoporosis. The oxidative stress injury of severe OSAHS patients was relieved after non-invasive ventilation treatment, but the effect of oxidative stress response on bone metabolism still needs further evaluation.
Ferroptosis is a unique way of cell death discovered in recent years, which involves the lethal process of iron ion accumulation and lipid peroxidation, which is obviously different from the traditional cell death pathway such as apoptosis and necrosis. For a long time, tuberculosis has been a major infectious disease in the field of global public health, which brings a serious burden to the society because of its high morbidity and mortality. The emergence of drug resistance aggravates the difficulty of treating tuberculosis, and new treatment strategies and drug targets are urgently needed. Combined with the latest research progress at home and abroad, This article will discuss the molecular mechanism of ferroptosis and pulmonary tuberculosis and the relationship between signal pathways, biomarkers and related genes, in order to provide a new perspective for the diagnosis and treatment of pulmonary tuberculosis.
Cerebral small vessel disease is a common neurological disease, including acute and non-acute categories. With the development of neuroimaging, cerebral small vessel disease has attracted substantial attention in recent years. However, the categories and concepts of cerebral small vessel disease and the related imaging markers usually confuse people. The purpose of this study was to discuss the relationships among acute and non-acute cerebral small vessel disease and the imaging markers, so as to improve the understanding of cerebral small vessel disease, and to shed light on clinical practice and research.
Objective To explore the change of serum levels of neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinases-2 (TIMP-2), and insulin-like growth factor-binding protein 7 (IGFBP-7) in the early stage of multiple trauma, and their predictive efficacy for acute kidney injury (AKI). Methods The multiple trauma patients admitted between February 2020 and July 2021 were prospectively selected, and they were divided into AKI group and non-AKI group according to whether they developed AKI within 72 h after injury. The serum levels of NGAL, TIMP-2, and IGFBP-7 measured at admission and 12, 24, and 48 h after injury, the Acute Pathophysiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ) score, intensive care unit duration, rate of renal replacement therapy, and 28-day mortality rate were compared between the two groups. Results A total of 51 patients were included, including 20 in the AKI group and 31 in the non-AKI group. The APACHE Ⅱ at admission (20.60±3.57 vs. 11.61±3.44), intensive care unit duration [(16.75±2.71) vs. (11.13±3.41) d], rate of renal replacement therapy (35.0% vs. 0.0%), and 28-day mortality rate (25.0% vs. 3.2%) in the AKI group were higher than those in the non-AKI group (P<0.05). The serum levels of NGAL and IGFBP-7 at admission and 12, 24, and 48 h after injury in the AKI group were all higher than those in the non-AKI group (P<0.05). For the prediction of AKI, the areas under receiver operating characteristic curves and 95% confidence intervals of serum NGAL, TIMP-2 and IGFBP-7 12 h after injury were 0.98 (0.96, 1.00), 0.92 (0.83, 1.00), and 0.87 (0.78, 0.97), respectively. Conclusion Serum NGAL, TIMP-2, and IGFBP-7 have high predictive efficacy for AKI secondary to multiple trauma, and continuous monitoring of serum NGAL can be used for early prediction of AKI secondary to multiple trauma.
ObjectiveEarly diagnosis of biliary atresia (BA) is crucial for improving patient prognosis. This study aimed to evaluate the accuracy of serum matrix metalloproteinase-7 (MMP-7) and gamma-glutamyl transferase (GGT) in diagnosing BA. MethodsWe conducted a comprehensive search of English-language databases (PubMed, Elsevier, Web of Science) and Chinese-language databases (CNKI, WanFang Data, VIP) for studies published from the inception of these databases up to December 30, 2024. Eligible studies included diagnostic data based on serum MMP-7 and GGT levels from children with BA and non-BA cholestasis. Results Through a systematic review and meta-analysis, a total of 24 publications encompassing 33 studies were included, covering a combined cohort of 6 879 children with cholestasis. The results of the binary diagnostic model analysis revealed that the pooled sensitivity and specificity of serum matrix metalloproteinase-7 (MMP-7) were 93% (95%CI 92 to 94) and 87% (95%CI 85 to 88), respectively. The positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) for MMP-7 were 8.63 (95%CI 5.88 to 12.66), 0.09 (95%CI 0.06 to 0.13), and 115.31 (95%CI 69.08 to 192.48), respectively. The area under the receiver operating characteristic curve (AUC) for MMP-7 was 0.9659, indicating excellent diagnostic performance. In comparison, gamma-glutamyl transferase (GGT) demonstrated a pooled sensitivity of 76% (95%CI 73 to 78) and specificity of 80% (95%CI 78 to 82). The corresponding PLR, NLR, and DOR for GGT were 3.50 (95%CI 2.77 to 4.43), 0.30 (95%CI 0.25 to 0.36), and 12.69 (95%CI 9.18 to 17.55), respectively. The AUC for GGT was calculated to be 0.849 4, reflecting moderate diagnostic accuracy. ConclusionSerum MMP-7 demonstrates higher diagnostic accuracy compared to GGT, which may significantly enhance the diagnostic efficiency for biliary atresia. However, due to its heterogeneity, further multicenter, large-sample, prospective studies that adhere strictly to experimental protocols are necessary to validate its diagnostic accuracy.
ObjectiveTo analyze the current development of researches on biomarkers for predicting the efficacy of immunotherapy in non-small cell lung cancer and to provide reference for subsequent studies. MethodsStudies on biomarkers for predicting the efficacy of immunotherapy for non-small cell lung cancer indexed in the Web of Science Core Collection from 2017 to 2021 were searched by computer. The annual distribution, journals, authors, countries, institutions, and keywords of studies were visualized and analyzed by CiteSpace. ResultsA total of 426 studies were collected, including 298 articles and 128 reviews. The average number of published studies was about 85, and increased year by year. PD-L1 expression, tumor mutational burden, tumor microenvironment and liquid biopsy were hot keywords in this field. ConclusionIn the future, combination of biomarkers in the liquid biopsy and tumor microenvironment with radiomics analysis will be the research hotspot and frontier in this field for more accurate assessment with tumor-related signatures such as lymphocytic immune status and characteristics of tumor lesions in non-small cell lung cancer patients.