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Resumen La interferencia por paraproteínas en los análisis clínicos ha sido extensamente informada a nivel mundial. Si bien se han propuesto estrategias metodológicas para evitar el informe de datos erróneos asociados a interferencias (p. ej. confirmación manual, sistema de alerta), en pocos casos se ha propuesto su detección como herramienta diagnóstica de patologías no sospechadas desde la clínica. A partir del trabajo conjunto de dos hospitales de la provincia de Buenos Aires se describió: i) la presencia de interferencia positiva de paraproteínas en la determinación de bilirrubina total con reactivos y autoanalizadores Wiener, y ii) su contribución, en un período inferior a los seis meses, a la detección de cuatro gammapatías no sospechadas (tres monoclonales). Se recomienda dar difusión de esta inferencia a nivel nacional y se propone un esquema de trabajo en laboratorio para identificar la interferencia así como un perfil mínimo de determinaciones para evaluar la existencia de gammapatías desconocidas.
Abstract Paraprotein interference in clinical biochemistry has been widely reported around the world. Methodological strategies have been proposed to avoid reporting erroneous data due to interferences (i.e. manual check, alert system); however, few cases have suggested its use as a diagnostic tool for unsuspected pathologies. Based on the joint work of two hospitals from Buenos Aires Province, the following has been described: i) the presence of positive interference of paraproteins in the assessment of total bilirubin with Wiener chemistry and autoanalizers, and ii) its contribution, in less than six months, to the diagnosis of four gammophaties previously unsuspected (three monoclonal ones). Sharing the occurrence of this interference in our country is recommended. An interference identification workflow is also propose, as well as a set of biochemical assays to evaluate the occurrence of unsuspected gammophaties.
Resumo A interferência da paraproteína na bioquímica clínica tem sido amplamente relatada em todo o mundo. Embora estratégias metodológicas para evitar a comunicação de dados errôneos associados a interferências tenham sido propostas (p. ex., verificação manual, sistema de alerta), em poucos casos sugerem seu uso como ferramenta diagnóstica para patologias não suspeitas a partir da clínica. Com base no trabalho conjunto de dois hospitais da Província de Buenos Aires, foi descrita: i) a presença de interferência positiva de paraproteínas na determinação da bilirrubina total com reagentes e autoanalisadores Wiener e ii) sua contribuição, em um período inferior aos seis meses, para o diagnóstico de quatro gamopatias não suspeitas (três monoclonais). Recomenda-se difundir essa interferência em nível nacional e se propõe um esquema de trabalho em laboratório para identificar a interferência bem como um perfil mínimo de determinações para avaliar a ocorrência de gamopatias desconhecidas.
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Diet therapy in conservative treatment of chronic kidney disease involves protein restriction, but there is not enough evidence to recommend a particular type of protein, whether animal or plant based. However, studies suggest that plant-based diets help reduce the consumption of total and animal protein, reduce the need for nephroprotective drugs, improve complications and bring advantages in terms of disease progression and patient survival. The article considers up-to-date data on the effects of this diet and observed that when low in protein, primarily vegetable and in some cases supplemented with ketoanalogues, it can result in positive clinical outcomes, such as: delay in the decrease in the glomerular filtration rate, lower concentrations of urea, reduction of serum creatinine and phosphorus concentrations, lower metabolic acidosis, higher insulin sensitivity and lower systemic inflammation. As a whole, this dietary pattern may be able to postpone the start of dialysis with less progression of renal insufficiency. Additional research is needed to better characterize this dietary pattern.
La dietoterapia en el tratamiento conservador de la enfermedad renal crónica implica la restricción de proteínas, pero aún no hay pruebas suficientes para recomendar un tipo concreto de proteínas, ya sean animales o vegetales. Sin embargo, los estudios sugieren que las dietas basadas en plantas ayudan a reducir la ingesta de proteínas totales y animales, disminuyen la necesidad de fármacos nefroprotectores, mejoran las complicaciones y presentan ventajas con respecto a la progresión de la enfermedad y la supervivencia de los pacientes. En este artículo se consideran datos actualizados sobre los efectos de esta dieta y se observa que, cuando es hipoproteica, principalmente vegetal y en algunos casos se complementa con cetoanálogos, puede dar lugar a resultados clínicos positivos, como una disminución retardada de la tasa de filtración glomerular, concentraciones más bajas de urea, concentraciones reducidas de creatinina y fósforo séricos, menor acidosis metabólica, mayor sensibilidad a la insulina y menor inflamación sistémica. En conjunto, este patrón dietético tiene el potencial de retrasar el inicio de la diálisis con una menor progresión de la insuficiencia renal. Es necesario seguir investigando para caracterizar mejor este patrón dietético.
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Objective:To explore the expression levels of serum triple domain 35 (TRIM35) and tumor necrosis factor receptor associated factor 3 (TRAF3) in patients with acute pancreatitis (AP) and their correlation with the severity and prognosis of the disease.Methods:Using a prospective research method, 93 patients with AP (observation group) were selected from July 2020 to September 2022 in Qinghai Red Cross Hospital, including 40 cases of mild acute pancreatitis (MAP), 29 cases of moderate to severe acute pancreatitis (MSAP) and 24 cases of severe acute pancreatitis (SAP). During the same period, 40 healthy individuals who underwent physical examinations were selected as healthy control group. The serum TRIM35 and TRAF3 levels were detected by real time fluorescence quantitative polymerase chain reaction (RT-qPCR). The survival status after 28 d of admission was followed up. The correlation was analyzed by Pearson method. Multivariate Logistic regression analysis was used to analyze the relationship between serum TRIM35 and TRAF3 levels and the prognosis in patients with AP. The efficacy of serum TRIM35 and TRAF3 in predicting the prognosis in patients with AP was evaluated by the receiver operating characteristics (ROC) curve.Results:The serum TRIM35 and TRAF3 levels in observation group were significantly higher than those in healthy control group (3.76 ± 1.36 vs. 1.02 ± 0.19 and 5.37 ± 2.18 vs. 1.04 ± 0.16), and there were statistical differences ( P<0.01). The serum TRIM35 and TRAF3 levels in patients with MSAP and SAP were significantly higher than those in patients with MAP (4.11 ± 1.73 and 4.96 ± 1.47 vs. 2.79 ± 1.04, 5.43 ± 2.15 and 7.01 ± 2.85 vs. 4.35 ± 1.79), the indexes in patients with SAP were significantly higher than those in patients with MSAP, and there were statistical differences ( P<0.05). The follow-up results showed that 11 cases died and 82 cases survived. The serum TRIM35 and TRAF3 levels in death patients were significantly higher than those in surviving patients (4.94 ± 1.01 vs. 3.60 ± 1.67 and 7.08 ± 1.43 vs. 5.14 ± 2.57), and there were statistical differences ( P<0.05). Pearson correlation analysis result showed that serum TRIM35 level was positive correlation with serum TRAF3 level in patients with AP ( r = 0.483, P<0.01). Multivariate Logistic regression analysis result showed that serum TRIM35 and TRAF3 levels were the independent risk factors of prognosis in patients with AP ( OR = 1.86 and 1.37, 95% CI 1.12 to 3.09 and 1.02 to 1.82, P<0.05). ROC curve analysis result showed that the area under the curve of serum TRIM35 combined with TRAF3 levels for evaluating the prognosis in patients with AP was significantly larger than serum TRIM35 and TRAF3 alone (0.85 vs. 0.81 and 0.81, Z = 0.03 and 0.04, P<0.05). The optimal cutoff values of serum TRIM35 and TRAF3 levels were 4.90 and 6.11. Conclusions:The serum TRIM35 and TRAF3 levels in patients with AP are significantly elevated, and are related to the severity of the condition. The serum TRIM35 and TRAF3 levels are independent risk of prognosis in patients with AP, and their combined detection is more valuable in evaluating the prognosis in patients with AP.
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Autophagy is an important mechanism to maintain cellular function and metabolism,whereas ab-normal autophagy can cause the advent and worsening of various diseases.N6-Methyladenosine(m6A)RNA methylation is a reversible RNA modification,which is regulated by m6A methyltransferase,m6A demethylase and m6A-binding protein.Studies have shown that autophagy-related genes promote or attenuate autophagy level dependent on the regulation of m6A,and then participate in the process of diseases.This paper reviews the progress of m6A modification regulatory enzymes and their binding proteins in regulating cell autophagy to provide reference for future researches.
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Increasing age is the most important factor for cognitive impairment.Alzheimer disease(AD)and sarcopenia are significant causes of frailty and disability in older adults.It is important to have an in-depth understanding of the relationship between sarcopenia and AD.Studies have reported that sarcopenia often disturbs the secretion of muscle factors,which may increase the risk of developing dementia.In turn,the pathological feature of dementia,such as the de-position of amyloid β-protein(Aβ),amyloid precursor protein(APP)and tau protein in peripheral neurons,may be related to a decline in muscle function.In particular,the deposition of Aβ and APP may eventually lead to movement disorders and disability.Therefore,we hypothesize that AD and sarcopenia may mutually promote each other's pathological develop-ment.This results in exacerbation of clinical and pathological damage,in which myokine and amyloid proteins play impor-tant roles.However,the interrelationship based on amyloid protein and myokine production has not been discussed in de-tail in other reviews.In this paper,we reference and discuss the studies on this topic,and review the common risk factors for sarcopenia and AD and the potential and mechanisms for mutual improvement.
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Objective:To investigate the correlation between serum ischemia modified albumin (IMA) and calmodulin (CaM) expression levels and neurological impairment in patients with cerebral small vessel disease.Methods:The clinical data of 140 patients with cerebral small vessel disease (CSVD) who received treatment at The Third People Hospital in Liaocheng between April 2020 and December 2021 were retrospectively analyzed. On admission, serum levels of CaM and IMA were measured using an enzyme-linked immunosorbent assay and an albumin-cobalt binding test. Patients' neurological function was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Patients' transient cerebral ischemia, urinary incontinence, and gait disturbance were evaluated using the National Institute of Neurological Disorders and Stroke Scale. Patients' cognitive function was evaluated using the Montreal Cognitive Assessment scale. The influential factors of serum IMA and CaM expression levels in patients with CSVD were analyzed. The factors that affect the severity of neuological imairment in patients with CSVD and their correlation with serum IMA and CaM expression levels were analyzed.Results:The gender, age, presence or absence of gait disorders, and presence or absence of urinary incontinence of patients were not correlated with serum IMA and CaM levels (all P > 0.05). The serum levels of IMA [(38.5 ± 5.3) × 103U/L, (38.5 ± 4.7) × 103U/L, (39.0 ± 4.4) × 103U/L] and CaM [(190.4 ± 34.5) μg/L, (191.2 ± 26.7) μg/L, (199.7 ± 24.8) μg/L] in patients with cognitive impairment, dizziness and vertigo, and transient cerebral ischemia were significantly higher than those in patients with normal cognitive function, patients without dizziness and vertigo, or patients without transient cerebral ischemia [(27.3 ± 4.4) × 103U/L, (21.0 ± 3.8) × 103U/L, (20.5 ± 5.1) × 103U/L, (180.6 ± 29.6) μg/L, (179.5 ± 28.6) μg/L, (168.6 ± 32.4) μg/L, t = 14.10, 24.36, 22.50, all P < 0.05]. There were significant differences in cognitive impairment (38/16/9), dizziness and vertigo (39/16/8), transient cerebral hemorrhage (35/16/9), NIHSS score [(3.6 ± 0.8) points, (7.5 ± 0.9) points, (16.2 ± 3.2) points], CaM levels [(125.3 ± 20.5) μg/L, (185.5 ± 23.6) μg/L, (237.9 ± 54.3) μg/L], and IMA levels [(21.2 ± 3.5)] × 103 U/L, [(38.5 ± 4.3) × 103 U/L, (74.9 ± 5.4) × 103 U/L] among patients with mild, moderate, and severe neurological impairment ( t = 32.87, 11.28, 12.42, 34.59, 151.73, 147.84, all P < 0.05). The results of multivariate analysis indicated that cognitive impairment ( OR = 1.578, 95% CI: 1.043-2.386), transient cerebral ischemia ( OR = 2.396, 95% CI: 1.156-4.969), dizziness and vertigo ( OR = 1.906, 95% CI: 1.086-3.345), NIHSS score ( OR = 2.171, 95% CI: 1.162-4.056), CaM level ( OR = 2.022, 95% CI: 1.268-3.224), and increased IMA levels ( OR = 2.090, 95% CI: 1.313-3.325) were independent influential factors for worsened neurological impairment (all P < 0.05). The serum levels of IMA and CaM in patients with CSVD were significantly positively correlated with the severity of neurological impairment ( r = 5.45, 8.33, both P < 0.05). Conclusion:The elevated serum levels of IMA and CaM in patients with CSVD serve as independent risk factors for neurological impairment, and these levels are positively correlated with the severity of neurological impairment.
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Objective:To study and screen the differential expression of inflammatory proteins in diabetes skin ulcers and common skin ulcers, so as to provide experimental basis for further research on anti-inflammatory and healing drug targets of diabetes skin ulcers.Methods:The tissues of 11 patients with diabetes skin ulcer, 12 patients with common skin ulcer and 11 patients with normal skin were collected from the First Hospital of Hunan University of Chinese Medicine. The levels of inflammatory protein Toll like receptor 4 (TLR4), nuclear factor κB (NF-κB), pro-inflammatory factor interferon -γ (IFN -γ), tumor necrosis factor - α (TNF -α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1β (IL-1β), macrophage chemotactic protein-1 (MCP-1), anti-inflammatory factors epidermal growth factor (EGF), interleukin-4 (IL-4), and interleukin-10 (IL-10) were detected in three groups of tissues using enzyme-linked immunosorbent assay (ELISA).Results:Compared with normal tissues, the concentrations of TLR4, NF-κB, IFN -γ, TNF -α, IL-1β, IL-6, IL-8, MCP-1 and EGF in common ulcer skin tissues and diabetes ulcer tissues were higher, and the concentrations of IL-10 were lower, with statistically significant differences (all P<0.05); Compared with the normal tissue, the concentration of IL-4 in diabetes ulcer tissue was lower, the difference was statistically significant ( P<0.05); Compared with ordinary ulcer skin tissue, the concentrations of TLR4, NF-κB and MCP-1 in diabetes ulcer tissue were higher, and the concentrations of IL-4 were lower, with statistically significant differences (all P<0.05). Conclusions:The skin ulcer in diabetes patients will have inflammatory reaction, and high glucose promotes the inflammatory reaction of skin ulcer, which may be related to the abnormal expression of TLR4, NF-κB, MCP-1 and IL-4. TLR4/NF-κB signal pathway and inflammatory factors MCP-1 and IL-4 may be the target of the inflammation regulation of diabetes skin ulcer.
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The TMEM family is widely distributed in the plasma membrane and organelle membrane, and has multiple biological functions. The TMEM family has different functions and mechanisms of action in different diseases. Recent research shows that TMEM family members play an important role in the pathogenesis of non tumor diseases, especially in cardiovascular, respiratory and nervous system diseases, such as atherosclerosis, Parkinson′s disease, depression, etc. This article reviews the mechanism of action of the TMEM family in non tumor diseases, which is of great significance for further revealing the disease mechanism and elucidating the biological functions of TMEM family members, and provides a new perspective for disease treatment strategies.
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Objective:To investigate the clinical characteristics, muscle pathological features and treatment in patients with Juvenile idiopathic inflammatory myopathy (JIIM) with positive anti-nuclear matrix protein 2 (NXP2) antibody.Methods:The clinical data of 8 IMM patients with positive anti-NXP2 antibody were collected and the clinical manifestations, auxiliary examinations, muscle pathological changes and therapeutic effects were retrospectively analyzed.Results:The ratio of male to female was 1:3. The median age of disease onset was (6.1±3.8) years. Eight cases had proximal muscle weakness, 7 had dermatomyositis-like rash, 5 had myalgia,4 had calcinosis,3 had skin ulcer, 2 had edema and 1 had abdominal pain. Five cases had elevated serum creatine kinase. Eight cases with lower limb muscle MRI showed abnormal signals in muscle, space between muscles and fat tissue, 3 cases with chest high-resolution CT (HRCT) showed interstitial lung disease. Abdominal CT of 1 case showed irregular thickening, edema and peripheral inflammatory exudation in ascending colon and proximal transverse colon. Pathological biopsy of skeletal muscle showed perifascicular atrophy, inflammatory cell infiltration in fascicular membrane and around small vessels and muscle fiber space. Edema, hyperplasia could be seen in interstitium; but dissolved necrosis, and regenerated muscle fibers were rarely seen. Treatments included glucocorticoids, immunosuppressive agents and biological agents (1 case). After 6 months of follow-up, 5 cases had good outcomes and 3 cases had poor outcomes.Conclusion:Dermatomyositis is the major clinical manifestation of idiopathic inflammatory myopathy with positive anti-NXP2 antibody.It is associated with myasthenia, calcinosis, skin ulcers and intestinal vasculitis. The pathological changes in skeletal muscle are relatively slightmild. Glucocorticoids combined with immunosuppressive agents are effective in most cases.
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Objective:To study the expression and prognostic impact of secretory carrier membrane protein 3 (SCAMP3) in hepatocellular carcinoma (HCC) and its gene set enrichment analysis.Methods:SCAMP3 expression and its prognosis were analyzed using The Cancer Genome Atlas (TCGA) database. The cancer tissue and paracancerous tissue were collected from four patients with HCC undergoing surgery in Lishui Central Hospital to detect the expression of SCAMP3. Based on TCGA database, univariate and multivariate Cox regression was performed to analyze the relevance of SCAMP3 with prognosis of HCC. Gene set enrichment analysis was utilized to clarify the biological role of SCAMP3.Results:In TCGA database, SCAMP3 expression was higher in HCC tissues than that in normal liver tissues ( Z=-8.38, P<0.001). Patients were divided into the low-expression group ( n=185) and high-expression group ( n=185) based on the median SCAMP3 expression, and the overall survival rate was lower in patients with high SCAMP3 expression. In our four patients. The expression of SCAMP3 mRNA and protein in cancer tissues was higher than that in paracancerous tissues ( t=8.55, 6.24, both P<0.001). In multivariate Cox regression analysis, the higher SCAMP3 expression was associated with a higher risk of death ( HR=1.466, 95% CI: 1.143-1.881, P<0.001). Gene set enrichment analysis in patients with high SCAMP3 expression, the coagulation cascade and three signaling pathways involving the complements, retinol metabolism, and peroxisome proliferator-activated receptor were identified. Conclusion:SCAMP3 expression elevated in HCC, patients with a higher expression of SCAMP3 might have a worse prognosis. High SCAMP3 expression is a risk factor for the survival of patients with HCC. High SCAMP3 expression is associated with the coagulation cascade and the complements, retinoid metabolism, and peroxisome proliferator-activated receptor pathways.
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Fibroblast activation protein inhibitor (FAPI) has been the focus of nuclear medicine since its introduction. With the in-depth study of FAPI tracer, its clinical application in various non-malignant diseases has also been gradually reported. Many studies have confirmed its uptake in a variety of non-malignant diseases, which indicate that FAPI tracers have good application prospects. This article reviews the latest research status and clinical application of radiolabeled FAPIs in cardiovascular diseases, rheumatic immune diseases, immunoglobulin (Ig)G4-related diseases, renal fibrosis and other non-malignant diseases at home and abroad.
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Objective:pH low insertion peptide (pHLIP)-variant 7 (var7)-fluorescein isothiocyanate (FITC) was used to explore an accurate imaging tool that targeted burn wounds to better perform burn debridement.Methods:Twelve rat models of burn wound were established and pHLIP-var7-FITC with different concentrations (0.5, 1.5 and 2.0 mg/ml) were injected from the rat tail vein for in vivo fluorescence imaging. By determining the concentration of fluorescent conjugates to the burn wound, the scope of wound injury necrosis was judged by combining pathological sections, and its residue and toxicity in important organs such as heart, liver, kidneys, and brain were detected. The Kruskal-Wallis rank sum test, Bonferroni correction method and one-way analysis of variance were used for data analysis. Results:Within 24 h, the fluorescence photons per unit area of the burn wound in the group of 0.5 mg/ml, 1.5 mg/ml and 2.0 mg/ml were 1.49(1.31, 1.65), 2.46(1.88, 2.68), 2.77 (1.94, 3.10)×10 7 p·s -1·cm -2·Sr -1, with significant differences in the overall distribution of fluorescence photons ( H=73.55, P<0.001). The fluorescence intensity was stronger in the group with higher concentration, but with no significant difference in the number of fluorescence photons between the group of 1.5 mg/ml and 2.0 mg/ml ( P=0.263, Bonferroni correction method). At 14 time points (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 7.0, 8.0, 12, 24 h), there was no significant difference in the overall mean of fluorescence photons ( F=1.04, P=0.419), and the tissue with burn necrosis seen in tissue sections was highly consistent with the fluorescence imaging region. There was no obvious fluorescence residue in the heart, liver, kidney and brain sections. Conclusion:In superficial second-degree burn tissue, pHLIP-var7-FITC can accurately target and gather on the burn wound within 24 h, showing a clear boundary between burn tissue and normal tissue, which can assist clinical surgical debridement to determine the extent of injury.
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Objective:To compare Al 18F-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04 PET/CT with 18F-FDG PET/CT in the evaluation of patients with initial gastric cancer. Methods:Twenty patients (13 males, 7 females, age: 27-77 years) with histologically proven gastric cancer were recruited prospectively between March 2021 and July 2022 in the First Affiliated Hospital of Zhengzhou University. Each patient underwent both 18F-FDG and Al 18F-NOTA-FAPI-04 PET/CT within one week. SUV max, tumor background ratio (TBR) and positive detection rate of the two methods were compared (Wilcoxon signed rank sum test, McNemar χ2 test). Results:Al 18F-NOTA-FAPI-04 showed higher SUV max and TBR than those of 18F-FDG in primary tumors (10.2(8.0, 13.7) vs 5.2(3.3, 7.7), z=-3.47, P=0.001; 7.6(5.6, 10.3) vs 2.4(1.8, 3.0), z=-3.85, P<0.001). For the detection of primary gastric cancer, the positive detection rate of Al 18F-NOTA-FAPI-04 PET/CT showed the trend of being higher than that of 18F-FDG PET/CT (95%(19/20) and 75%(15/20); χ2=2.25, P=0.125). For assessing lymph node metastasis, the detection rate of Al 18F-NOTA-FAPI-04 PET/CT was higher than that of 18F-FDG PET/CT (78.9%(101/128) vs 64.8%(83/128); χ2=13.47, P<0.001). The SUV max and TBR of Al 18F-NOTA-FAPI-04 in lymph node were higher than those of 18F-FDG (5.3(3.5, 9.2) vs 2.8(1.8, 4.7), z=-7.31, P<0.001; 4.6(2.6, 6.5) vs 1.7(1.0, 3.0), z=-8.44, P<0.001). For the detection of peritoneal carcinomatosis, Al 18F-NOTA-FAPI-04 PET/CT showed higher peritoneal cancer index (PCI), SUV max, and TBR compared to 18F-FDG PET/CT (PCI: 12.0(3.0, 29.8) vs 5.5(0.5, 17.5), z=-2.22, P=0.026; SUV max: 8.2(4.4, 12.5) vs 2.7(1.9, 4.0); z=-2.52, P=0.012; TBR: 5.1(2.9, 13.3) vs 1.1(0.9, 2.0); z=-2.52, P=0.012). Conclusion:Al 18F-NOTA-FAPI-04 PET/CT outperforms 18F-FDG PET/CT in primary and metastatic lesions of gastric cancer and might be a potential novel modality for imaging patients with gastric cancer.
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Myocardial fibrosis is an important pathological process in the development of cardiovascular diseases, which is closely related to the prognosis of patients. Activated cardiac fibroblasts (CFs) are the main effector cells, whose surface specifically overexpress fibroblast activation protein (FAP). Radionuclide-labeled FAP inhibitors (FAPIs) can specifically bind to FAP to visualize activated CFs in vivo, showing preliminary clinical application in the early diagnosis, prognosis prediction and interventional guidance of various cardiovascular diseases. This article reviews the progress of researches on the application of radionuclide-labeled FAPIs in cardiovascular diseases imaging.
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Objective To explore the analysis of the relationship of the serum levels of focal adhe-sion kinase(FAK)and fatty acid-binding protein 4(FABP4)with myocardial injury and cardiac function in elderly patients with acute myocardial infarction(AMI).Methods A total of 211 AMI patients admitted to our hospital from January 2020 to April 2023 were enrolled and assigned into the AMI group,while another 60 healthy volunteers who took routine physical examinations in our hospital during the same period served as the control group.The serum FAK and FABP4 lev-els were compared between the two groups.Multivariate logistic regression analysis was employed to identify influencing factors associated with AMI,and ROC curve was plotted to assess the pre-dictive efficacy of the serum FAK and FABP4 levels for AMI in the elderly population.Pearson correlation analysis was conducted to explore the relationship between serum FAK and FABP4 levels and myocardial injury as well as cardiac function.Results The AMI group exhibited signifi-cantly elevated serum FAK,FABP4,CK-MB,cTnⅠ and CK levels,and larger LVESD and LVEDD,but lower LVEF when compared with the control group(P＜0.05,P＜0.01).For the AMI patients,the serum FAK and FABP4 levels were positively correlated with CK-MB,cTnⅠ and CK levels,as well as LVESD and LVEDD,and negatively with LVEF(P＜0.05).Multivariate logistic regression analysis revealed that both serum levels of FAK(OR=2.872,95％CI:2.230-3.698,P=0.000)and FABP4(OR=2.667,95％CI:1.713-4.154,P=0.000)were influencing factors for AMI.ROC analysis indicated that the cut-off value of FAK level for diagnosing AMI was 25.60 pg/L,with an AUC value of 0.801(95％CI:0.750-0.852).Similarly,the cut-off value of FABP4 in the diagnosis was 23.22 pg/L,with an AUC value of 0.760(95％CI:0.707-0.812).Combined FAK and FABP4 levels yielded,with an AUC value of 0.899(95％CI:0.839-0.918).Conclusion Serum FAK and FABP4 levels are abnormally high in the elderly patients with AMI,which is closely related to myocardial injury and cardiac function.The two indicators alone or in combination can effectively predict the occurrence of AMI.
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Objective To investigate the role of Smad signaling pathway in rat model of cerebral in-farction and explore the expression of insulin-like growth factor binding protein 3(IGFBP-3)in brain tissue and its relationship with neural function.Methods Sixty healthy adult male SD rats were randomly and equally divided into model group,sham-operation group,and normal control group.The model of cerebral infarction was established by using intraluminal thread occlusion,and the rats of the sham-operation group were only given exposure of the internal carotid artery and direct suture of the incision.In 1 week after successful modeling,Modified Neurological Seve-rity Score(mNSS)was used to evaluate the neurological function.HE staining was employed to observe the histopathological changes in the brain tissues.Western blotting and RT-PCR were adopted to detect the brain expression of IGFBP-3,Smad2 and Smad4 at protein and mRNA le-vels.Spearman correlation analysis was conducted to analyze the correlation among the expression levels of IGFBP-3,Smad2,Smad4 and P21.Results HE staining displayed that obvious brain ede-ma,characterized by disordered arrangement of brain cells,increased microglia,and blurred nucleo-lus of brain cells were observed in the rats of the model group,with the area of cerebral infarct of 20.55％.The mNSS score and the protein and mRNA levels of IGFBP-3,Smad2 and Smad4 were significantly higher,but the P21 protein and mRNA levels were obviously reduced in the model group than the sham-operation group and normal control group(P＜0.05,P＜0.01).Spearman correlation analysis showed that the mRNA level of IGFBP-3 in cerebral infarction rats was posi-tively correlated with the mNSS score and mRNA expression levels of Smad2 and Smad4(r=0.568,r=0.623,r=0.597;P＜0.01),and negatively with P21 mRNA level in the brain tissue(r=-0.573;P＜0.01).Conclusion The level of IGFBP-3 is significantly increased in brain tissue of rats with cerebral infarction,and it is closely associated with neural function of these rats,which may be related to Smad signaling pathway.
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Objective:To evaluate the effect of sevoflurane on Ca 2+ transporter expression in cardiomyocytes during right ventricular remodeling in rats with pulmonary arterial hypertension. Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were divided into 4 groups ( n=6 each) by the random number table method: control group (CM group), sevoflurane group (CS group), monocrotaline group (M group) and sevoflurane + monocrotaline group (S group). Monocrotaline 60 mg/kg was intraperitoneally injected in group M and group S, and monocrotaline lysate was intraperitoneally injected in group CM. The rats in S and CS groups inhaled 2.5% sevoflurane for 1 h, twice a week, at an interval of 3 days starting from the first day after injection of monocrotaline. Pulmonary artery acceleration time and pulmonary artery ejection time were measured by transthoracic echocardiography at 6 weeks after monocrotaline injection. The chest was exposed under 3% sevoflurane anesthesia, the heart was perfused, and the pulmonary artery branch and right ventricular myocardial tissues were retained. The wall thickness of pulmonary arterioles and cross-section area of right ventricular cardiomyocytes were observed by HE staining. The expression of Ca 2+ transporter in right ventricular cardiomyocytes was detected by Western blot. Results:Compared with CM group, the ratio of pulmonary artery acceleration time to pulmonary artery ejection time was significantly decreased, the cross-section area of right ventricular cardiomyocytes was increased, the wall thickness of pulmonary arteriole was increased, the expression of type 1 sodium-calcium exchange and inositol triphosphate receptor was up-regulated, and the expression of voltage-dependent L-type calcium channel α1C subunit, type 2 ryanodine receptor, sarcoplasmic reticulum calcium pump 2α and proteinphilin-2 was down-regulated in M group ( P<0.01). Compared with group M, the ratio of pulmonary artery acceleration time to pulmonary artery ejection time was significantly increased, the cross-section area of right ventricular cardiomyocytes was decreased, the wall thickness of pulmonary arteriole was decreased, the expression of type 1 sodium-calcium exchange and inositol triphosphate receptor was down-regulated, and the expression of voltage-dependent L-type calcium channel α1C subunit, type 2 ryanodine receptor, sarcoplasmic reticulum calcium pump 2α and proteinphilin-2 was up-regulated in group S ( P<0.01). Conclusions:The mechanism by which sevoflurane improves right ventricular remodeling is related to regulating the expression of Ca 2+ transporter in cardiomyocytes of rats with pulmonary arterial hypertension.
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Objective:To evaluate the role of Ras homolog gene family member A (RhoA) in hydrogen-induced alleviation of lipopolysaccharide (LPS)-caused damage to pulmonary microvascular endothelial cell(PMVEC) barrier function in mice.Methods:PMVECs were cultured in DMEM/F12 medium containing 10% fetal bovine serum and 1% penicillin/streptomycin until 4-6 passage. These cells were divided into 6 groups ( n=36 each) using a random number table method: control group (group A), hydrogen-rich medium group (group B), LPS group (group C), LPS + hydrogen-rich medium group (group D), LPS + RhoA inhibitor C3 enzyme group (group E) and LPS + hydrogen-rich medium + RhoA agonist U-46619 group (group F). Cells were cultured within normal medium in group A, group C and group E and within hydrogen-rich medium in group B, group D and group F. LPS at a final concentration of 1 μg/ml was simultaneously added in group C, group D, group E and group F. C3 enzyme at a final concentration of 3 μg/ml was added at 2 h before addition of LPS in group E. U-46619 at a final concentration of 10 mg/ml was added at 3 h before addition of LPS in group F. The expression of vascular endothelial (VE)-cadherin and occludin was determined by Western blot at 6, 12 and 24 h after incubation with LPS. At 24 h after incubation with LPS, the release rate of LDH was measured by LDH method, cell viability was measured by MTT method, and the activity of RhoA was determined by GST pull-down method. Results:Compared with group A, the expression of VE-cadherin and occludin was significantly down-regulated at 6, 12 and 24 h of incubation, the cell viability was decreased at 24 h of incubation, and the release rate of LDH and activity of RhoA were increased in group C ( P<0.05). Compared with group C, the expression of VE-cadherin and occludin was significantly up-regulated at 6, 12 and 24 h of incubation, the cell viability was increased at 24 h of incubation, and the release rate of LDH and activity of RhoA were decreased in group D ( P<0.05). Compared with group C, the expression of VE-cadherin and occludin was significantly up-regulated at 6, 12 and 24 h of incubation, the cell viability was increased at 24 h of incubation, and the release rate of LDH and activity of RhoA were decreased in group E ( P<0.05). Compared with group D, the expression of VE-cadherin and occludin was significantly down-regulated at 6, 12 and 24 h of incubation, the cell viability was decreased at 24 h of incubation, and the release rate of LDH and activity of RhoA were increased in group F ( P<0.05). Conclusions:RhoA is involved in hydrogen-induced alleviation of LPS-caused damage to PMVEC barrier function in mice.
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Objective:To investigate the expression level of transcription factor dimerization partner 2 (TFDP2) in the placentas of women with preeclampsia, and analyze its effect on the apoptosis of trophoblast cells.Methods:Placental tissues from thirty puerperae with preeclampsia who gave birth by cesarean section in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School between January 2018 and December 2022 (preeclampsia group) and 30 healthy puerperae undergoing cesarean section during the same period (control group) were retrospectively selected. Immunohistochemistry was used to localize TFDP2 in the placental tissues. Real-time quantitative-polymerase chain reaction (qRT-PCR) and Western blot were used to detect the differences in expression of TFDP2 at mRNA and protein levels in placental tissues between the two groups. Forskolin-exposed BeWo cells were transfected with small interfering RNA (siRNA) to knockdown TFDP2 and the changes in the expression of apoptosis-related indicators, B cell lymphoma 2 (Bcl2) and Bcl2 associated X (Bax), at protein and mRNA levels were analyzed by Western blot and qRT-PCR, respectively. Besides, the change in the apoptosis level of BeWo cells was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry. Downstream signaling pathways were analyzed to understand the involved molecular mechanisms. Two independent samples t-test, Wilcoxon rank-sum test, and Chi-square test were used for statistical analysis. Results:TFDP2 was mostly localized in the syncytiotrophoblasts and the extravillous trophoblasts in the normal placentas. TFDP2 expression in the syncytiotrophoblasts was lower in the preeclampsia group than in the control group at both mRNA (0.722±0.239 vs. 1.000±0.348, t=3.61, P=0.001) and protein (0.728±0.185 vs. 1.000±0.206, t=2.41, P=0.037) levels. Comparing the group without knockdown of TFDP2, the knockdown of TFDP2 in BeWo cells elevated the Bax/Bcl2 ratio (mRNA: 1.755±0.452 vs. 1.000±0.279, t=3.48, P=0.006; protein: 3.206±0.922 vs. 1.000±0.290, t=3.95, P=0.017), and increased cell apoptosis both in number and ratio (TUNEL staining: 4.556±1.740 vs. 2.444±1.130, t=3.05, P=0.008; flow cytometry: 21.37%±1.66% vs. 12.61%±0.38%, t=8.92, P=0.001). Furthermore, following TFDP2 knockdown, a decrease in the phosphorylation activity of catalytic subunit of protein kinase A (PKAc) at the Thr197 site was observed in the cytoplasm of BeWo cells (0.466±0.035 vs. 1.000±0.075, t=11.19, P<0.001) and a reduction in the expression of β-catenin in the cell nucleus was also detected (0.250±0.093 vs. 1.000±0.269, t=4.57, P=0.010). Conclusion:The expression of TFDP2 decreased significantly in the placentas of patients with preeclampsia, which may promote the apoptosis of syncytiotrophoblasts by inhibiting the PKAc/β-catenin signaling pathway.
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Prefoldin (PFDN), a hexameric chaperone complex, is crucial for the correct folding of nascent proteins. PFDN5, a subunit of PFDN, also known as MM-1, plays an essential role in regulating cell migration and senescence. Emerging evidences suggest that PFDN-5 deletion or mutation significantly contributes to the initiation and progression of multiple cancers and the prognosis of patients. In this paper, recent researches on the biological underpinnings of PFDN-5 and its anti-cancer prospect are reviewed, aiming to provide a novel potential therapeutic target for the treatment of malignancies.