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【Objective】 To identify the risk factors of patients of bone metastatic prostate cancer with high tumor load progressed to castration resistant prostate cancer (CRPC), establish a nomogram prediction model and evaluate its consistency and accuracy. 【Methods】 A total of 164 patients diagnosed by puncture and imaging during 2012 and 2022 were included.The general characteristics were analyzed with IBM SPSS software; the variables were screened with Cox regression; the multivariate risk factors with P<0.05 were included in the nomogram prediction model.The consistency and prediction accuracy of the model were evaluated with C-index, receiver operating characteristic (ROC) curve and calibration chart. 【Results】 In univariate analysis, initial prostate-specific antigen (PSA), prostate-specific antigen density (PSAD), Gleason score, T stage, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were correlated with CRPC (P<0.05).Multivariate analysis showed that initial PSA, Gleason score, T stage, ALP and LDH were independent risk factors of CRPC (P<0.05).Based on the above five risk factors, a nomogram prediction model was constructed.The C-index was 0.801, the area under ROC curve (AUC) of 1-year progression-free survival (PFS) was 0.701 (0.608-0.794), and the AUC of 2-year PFS was 0.857 (0.767-0.947).The calibration chart showed that the prediction probability of the model was in good agreement with the actual probability. 【Conclusion】 Initial PSA, Gleason score, T stage, ALP and LDH are independent risk factors of CRPC.The predictive model may be an effective tool for the initial diagnosis of high tumor load bone metastatic prostate cancer, but more data are needed for internal and external validation.
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A 31-year-old woman infected with severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) at 33-weeks pregnant was subject to cesarean delivery due to a worsening respiratory condition. On the fourth day of illness, the patient was placed on a ventilator, with extracorporeal membrane oxygenation (ECMO) treatment initiated on the ninth day. Passive range of motion (ROM) training started on the day 33 of illness. She was weaned off ECMO on day 55 of illness and taken off of the ventilator on day 8. The tracheostomy tube was replaced with a speech cannula on day 87 of illness, at which time the patient began to complain of pain during passive ROM training. Plain X-ray photography and computed tomography (CT) showed ossification around the bilateral shoulder and hip joints, as well as on medial thighs, accompanied by an alkaline phosphatase (ALP) value of 942 U/L. She was subsequently diagnosed with heterotopic ossification, after which passive ROM training was changed to protective ROM training, in addition to treatment with indomethacin farnesyl and etidronate disodium. The patient was transferred to our hospital on day 122 of illness for the purpose of continuing rehabilitation. On day 155 of illness, ossification decreased on the medial thighs, according to CT. She was able to walk independently indoors and was discharged home on day 181 of illness. This case demonstrates the importance of checking the ALP levels and palpating the periarticular area in patients infected with SARS‑CoV‑2 before initiating passive ROM training, as well as being aware of any pain experienced during training. In the case of any abnormalities, assessing the ossification around the joints of extremities by imaging examination is a priority.
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Abstract Objective: To describe the behavior of total alkaline phosphatase (tALP) in patients with metastatic castration-resistant prostate cancer receiving radium-223 therapy, in a real-world scenario, and to describe overall survival (OS) among such patients. Materials and Methods: This was a retrospective study involving 97 patients treated between February 2017 and September 2020. Patients were stratified by the baseline tALP (normal/elevated). A tALP response was defined as a ≥ 30% reduction from baseline at week 12. For patients with elevated baseline tALP, we also evaluated treatment response as a ≥ 10% reduction in tALP after the first cycle of treatment. We defined OS as the time from the first treatment cycle to the date of death. Results: There was a significant reduction in the median tALP after each cycle of treatment (p < 0.05 for all). Data for tALP at week 12 were available for 71 of the 97 patients. Of those 71 patients, 26 (36.6%) responded. Elevated baseline tALP was observed in 47 patients, of whom 19 (40.4%) showed a response. Longer OS was observed in the patients with normal baseline tALP, in those with elevated baseline tALP that showed a response to treatment (≥ 10% reduction), and in those who received 5-6 cycles of therapy. Conclusion: The tALP may be used to predict which patients will benefit from treatment with a greater number of cycles of radium-223 therapy and will have longer OS.
Resumo Objetivo: Descrever o comportamento da fosfatase alcalina total (tALP) em pacientes com carcinoma de próstata metastático resistente a castração, submetidos a terapia com rádio-223 em um cenário do mundo real, e a sobrevida global (SG) desses pacientes. Materiais e Métodos: Estudo retrospectivo envolvento 97 pacientes, no período de fevereiro/2017 a setembro/2020. Os pacientes foram estratificados de acordo com a tALP basal (normal/elevada). A resposta à tALP foi definida como uma redução em relação à linha de base de ≥ 30% na semana-12. Para pacientes com tALP basal elevada, também foi avaliada a resposta ao tratamento como uma redução de ≥ 10% de tALP após o primeiro ciclo. A SG foi definida como o tempo entre o primeiro ciclo e a data do óbito. Resultados: A redução da tALP média após cada ciclo foi significativa (p < 0,05). A tALP na semana 12 estava disponível para 71 dos 97 pacientes. Desses 71 pacientes, 26 (36,6%) responderam. Dezenove (40,4%) dos 47 pacientes com tALP elevada apresentaram resposta. Foi observada uma SG mais longa nos pacientes com tALP basal normal, nos pacientes com tALP basal elevada que apresentaram resposta ao tratamento (redução de ≥ 10%) e nos pacientes que receberam 5-6 ciclos. Conclusão: A tALP pode ser usada para prever parte dos pacientes que se beneficiarão do tratamento com um maior número de ciclos e uma SG mais longa.
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Berberine is a phytocompound from plants viz. Phellodendri cortex and Coptis rhizome, used to treat a variety of diseases. It is effective in preventing osteoporosis, but it is less effective than drugs currently used in clinical practice. In this study, we used a novel berberine derivative, WJCPR11, to promote osteoblast differentiation and to investigate its use in the prevention and treatment of osteoporosis. WJCPR11 at a safe concentration without toxicity increased alkaline phosphatase (ALP) activity induced by bone morphogenetic protein 2 (BMP2) dose-dependently. The mRNA expression of ALP, osteocalcin (OC), runt-related transcription factor 2 (Runx2), and osterix was increased, with the ALP level increasing the most. In addition, the protein abundance of bone sialoprotein (BSP), collagen, type I, alpha 1, Runx2, and osterix were also increased. Moreover, the transcriptional activity of ALP, BSP, and OC was increased by WJCPR11, with OC showing the most significant increase. The results indicate that osteoblast differentiation is promoted by WJCPR11, and it could play a role in the prevention of osteoporosis.
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Objective:To study the changes and influencing factors of serum alkaline phosphatase (ALP) levels in patients with hyperthyroidism before and after antithyroid drug treapy.Methods:Using the case-control study, a total of 241 hyperthyroidism patients who visited the Department of Endocrinology, Linfen People's Hospital from January 2019 to January 2022 were selected and included in the hyperthyroidism group; and 241 individuals with normal thyroid function who underwent health examinations during the same period were selected as the control group. Basic information such as gender, age, history of underlying diseases, and history of drug use from all subjects were collected. Fasting venous blood samples of all subjects the next day and patients in the hyperthyroidism group after 6 months of antithyroid drug therapy were collected for testing of thyroid function indicators [serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid stimulating hormone (TSH), thyroid stimulating hormone receptor antibody (TRAb), anti thyroid peroxidase antibody (TPOAb), anti thyroglobulin antibody (TgAb)] and liver function indicators [serum ALP, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), γ-glutamyl transpeptidase (GGT), and total protein (TP)]. The influencing factors of serum ALP were analyzed. Results:The levels of serum FT 3, FT 4, TRAb, TPOAb, and TgAb in patients with hyperthyroidism were significantly higher than those in the control group ( Z = - 18.94, - 18.78, - 10.62, - 10.39, - 10.33, P < 0.001), while TSH level was significantly lower than that in the control group ( Z = - 19.32, P < 0.001). There were 141, 34, 28, 14, and 8 cases of elevated serum ALP, ALT, AST, GGT, and TBIL levels in the hyperthyroidism group, accounting for 58.51%, 14.11%, 11.62%, 5.81%, and 3.32%, respectively. Among 141 patients with elevated serum ALP level, 104 had only elevated ALP level, while 37 had one or more abnormalities in ALT, AST, GGT, and TBIL. The serum levels of ALP, ALT, AST, GGT, and TBIL in patients with hyperthyroidism were higher than those in the control group ( Z = - 14.83, - 5.10, - 2.57, - 3.30, - 12.36, P < 0.001), and the TP level was lower than that in the control group ( Z = - 4.01, P < 0.001). After 6 months of antithyroid drug therapy, the levels of serum FT 3, FT 4, TSH, ALP, ALT, AST, GGT, and TBIL in patients with hyperthyroidism were statistically significant compared to before treatment ( Z = - 18.48, - 18.69, - 18.07, - 12.79, - 6.21, - 5.71, - 3.99, - 2.95, P < 0.001). There was no statistically significant difference in serum ALP level between the hyperthyroidism group and the control group ( Z = - 1.56, P = 0.118). Spearman correlation analysis showed that serum ALP level in patients with hyperthyroidism were positively correlated with FT 3, FT 4, and TRAb levels ( r = 0.54, 0.59, 0.36, P < 0.001), and negatively correlated with TSH level ( r = - 0.50, P < 0.001). The results of logistic regression analysis showed that elevated of serum FT 4, GGT levels, and decresed of TSH level were independent risk factors for elevated serum ALP level ( OR = 1.38, 1.04, 0.28, P < 0.05). Conclusion:Antithyroid drug therapy can improve the abnormal elevation of serum ALP level in patients with hyperthyroidism, and FT 4, GGT, and TSH levels are independent influencing factors.
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Objective To observe and analyze functional areas of the cerebral cortex in C57BL/6 mice of various ages.Methods Improved alkaline phosphatase staining was used to reveal the microvascular morphology of the cerebral cortex in C57BL/6 mice,including the motor cortex(primary and secondary motor cortex),sensory cortex(primary and secondary somatosensory cortex),visual cortex(primary and secondary visual cortex),and auditory cortex(primary and secondary auditory cortex),olfactory cortex(extrarhinal and entorhinal cortex).Images were captured under an OLYMPUS BX51 microscope with Image-Pro Plus 5.1 software.The microvascular length density(Lv),microvascular surface area density(Sv),and microvascular volume density(Vv)were analyzed by Image-Pro Plus 5.1 software.Results Expression of alkaline phosphatase was abundant in cerebral cortical microvessels of adult and elderly mice,and slightly expressed in juvenile mice,but not in lactating mice.Pial blood vessels enter the cortex in T shape,Y shape,large arc,and small arc four manners.Lv,Sv and Vv in different parts of the same aged mice showed a decreasing trend in motor,sensory,visual,auditory and olfactory cortexes,and the microvascular density of Lv,Sv and Vv in motor and sensory cortexes was statistically significant compared with the olfactory cortex(P<0.05).The vascular density in all functional areas in elderly mice was lower than that in adult mice,but no statistical significance was found(P>0.05).Conclusions The expression of alkaline phosphatase in microvessels in functional areas of the cerebral cortex in C57BL/6 mice increases with age and reached its peak value in adulthood.The microvascular architecture in the brain provides morphological parameters to establish cerebrovascular disease models.
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Objective:To investigate the influencing factors of survival benefit of patients after radical cystectomy and its correlation with preoperative albumin-to-alkaline phosphatase ratio (AAPR).Methods:The clinical data of 116 patients after radical cystectomy were retrospectively analyzed from January 2011 to January 2020 in Handan First Hospital. The influencing factors of survival benefit of patients after radical cystectomy were analyzed and the correlation between preoperative AAPR and overall survival time were evaluated. Kaplan-Meier method was used for survival analysis, and Log-rank test was used for comparison between groups. Cox proportional regression model was used to analyze the influencing factors of survival and prognosis and the correlation with preoperative AAPR. Trend Chi-square test was used to evaluate the level of preoperative AAPR.Results:Univariate Cox regression analysis showed that age, tumor diameter, pT stage, pN stage, histopathological grade, hydronephrosis, postoperative adjuvant chemotherapy and preoperative AAPR level were related to the overall survival time of patients after radical cystectomy( P<0.05). Multivariate Cox regression analysis showed that in calibration model Ⅰ and Ⅱ, the risk of death in high AAPR group was 0.351 and 0.433 times higher than low AAPR group( P<0.05). The risk of death decreased to 85.9% and 84.6% for every one unit increase of preoperative AAPR. The overall survival time of patients with high AARP level were significantly longer than patients with low and medium AARP level( P<0.05). Conclusion:The survival benefit of patients after radical cystectomy was independently related to the preoperative AAPR level; the higher the preoperative AAPR level, the longer the overall survival time.
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Objective:To explore the clinical characteristics of patients with colchicine poisoning, and analyze the risk factors affecting the prognosis of colchicine poisoning and its value in the prognostic assessment.Methods:Patients with colchicine poisoning admitted to the Emergency Intensive Care Unit of the First Affiliated Hospital of Wenzhou Medical University from December 2017 to October 2022 were retrospectively included and divided into the survival group and death group according to the 14-d outcome. The general conditions of the two groups of patients were compared, and the clinical characteristics of patients with colchicine poisoning were analyzed. The differences of laboratory indexes, electrocardiogram, cardiac ultrasound and other clinical indexes during the first admission of patients between the two groups were compared, and their value in the prognosis evaluation of patients with colchicine poisoning was explored.Results:There were 41 patients with colchicine poisoning, aged 15-85 years, including 35 males and 6 females. There were 27 patients (65.9%) in the survival group and 14 patients (34.1%) in the death group, including accumulative poisoning (58.7%) and suicide poisoning (41.3%). The main clinical manifestations of patients with colchicine poisoning were gastrointestinal symptoms (82.93%), multiple organ dysfunction (78.05%), infectious fever (73.17%), myocardial damage (48.78%), coagulation dysfunction (46.34%), and bone marrow suppression (41.46%). Intestinal obstruction (19.51%) and rhabdomyolysis (2.44%) occurred in some patients. Multivariate Logistic regression analysis showed that the increase in absolute value of QTc interval ( OR=1.028, 95% CI: 1.000~1.056, P<0.05), lactic acid ( OR=1.599, 95% CI: 1.088~2.350, P<0.05), prothrombin time ( OR=1.205, 95% CI: 1.002~1.450, P<0.05), D-dimer ( OR=1.242, 95% CI: 1.089~1.417, P<0.05), and alkaline phosphatase ( OR=1.013, 95% CI: 1.002~1.024, P<0.05) were the risk factors for the prognosis of patients with colchicine poisoning. The decrease in the absolute value of ADL score ( OR=0.947, 95% CI: 0.909~0.988, P<0.05) and indirect bilirubin ( OR=0.756, 95% CI: 0.572~0.999, P<0.05) were the protective factors for the prognosis of patients with colchicine poisoning. D-dimer (AUC=0.913), lactic acid (AUC= 0.875) and alkaline phosphatase (AUC=0.770) had predictive value for the prognosis of patients with colchicine poisoning, and their cut-off values were 8.965 mg/L, 4.05 mmol/L and 230.5 U/L, respectively. Conclusions:The patients with colchicine poisoning have multiple organ dysfunction on admission, and are in a critical condition. The early levels of D-dimer, lactic acid and alkaline phosphatase could effectively predict the prognosis of patients with colchicine poisoning.
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Objective:To investigate the clinical characteristics of drug-induced liver injury and provide a theoretical basis for the prevention and treatment of drug-induced liver injury.Methods:The clinical data of 202 patients with complete information on drug-induced liver injury who received treatment in First Hospital of Shanxi Medical University from November 2018 to November 2021 were collected. The information including gender, age, type and name of drugs taken or exposed, clinical characteristics, autoantibodies, and liver function was statistically analyzed.Results:Among the 202 patients with drug-induced liver injury, 77 patients (38.1%) were male and 125 patients (61.9%) were female. Age distribution was mainly at > 40-60 years. There were 141 cases (69.8%) of hepatocellular type, 27 cases (13.4%) of cholestatic type, and 34 cases (16.8%) of mixed type. There were statistically significant differences in alanine aminotransferase, aspartate aminotransferase, γ-glutamine transferase, alkaline phosphatase, prothrombin time, international standardized ratio, and prothrombin activity between different clinical types ( H = 91.43, 58.65, 9.25, 32.69, 9.56, 8.19, 9.40, all P < 0.05). Among the 202 patients with drug-induced liver injury, severe liver injury occurred in the largest proportion of cases (40.6%). There was no significant difference in the disease severity between different clinical types ( P = 0.789). The top three types of drugs causing liver injury were traditional Chinese medicine [52.0% (105/202)], antineoplastic drugs [6.4% (13/202)], and antipsychotics [5.9% (12/202)]. The detection rate of autoantibodies in 202 patients with drug-induced liver injury was 29.7% (60/202). Conclusion:Drug-induced liver injury lacks specificity in clinical manifestations. A wide variety of drugs can cause liver injury. Clinicians should strengthen liver function monitoring in key populations. The proportion of patients with mixed-type liver failure is high, which should be taken seriously. When patients with drug-induced liver injury are positive for liver disease-related antibodies, clinicians should be vigilant about the possibility of drug-induced liver injury.
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Objective:To systematically evaluate the effects of protein restriction, low-sodium diet and alkaline diet on renal outcomes, the rate of change in estimated glomerular filtration rate (eGFR) and all-cause mortality in chronic kidney disease (CKD) patients.Methods:Three main databases, Ovid, EMBASE and the Cochrane Library database, were searched for randomized controlled trials about the effects of protein restriction, alkaline diet, low-sodium diet in chronic kidney disease. The primary outcome was renal composite endpoint events, the annual rate of change in eGFR and all-cause mortality. Renal composite endpoint events was defined as >25% or 50% decrease from baseline in eGFR, doubling of serum creatinine, or the development of end-stage renal diseaseas during follow-up.The studies were selected according to inclusion and exclusion criteria and assessed for quality using Jadad Scale. Two investigators were chosen to search, extract and evaluate the data independently. Software Stata 16.0 and RevMan 5.4 were used for meta-analysis.Results:A total of 34 studies with 5 589 participants were included. Protein restriction ( RR = 0.78, 95% CI: 0.64 to 0.96, P < 0.001), alkaline diet ( RR = 0.64, 95% CI: 0.43 to 0.98, P < 0.001) and low-sodium diet ( RR = 0.45, 95% CI: 0.28 to 0.73, P < 0.01) reduced the risk of renal composite outcomes. Protein restriction ( MD = 1.85, 95% CI: 0.77 to 2.93, P = 0.001), alkaline diet ( MD = 1.45, 95% CI: 0.53 to 2.37, P < 0.001) and low-sodium diet ( MD = 1.84, 95% CI: 1.06 to 2.63, P < 0.001) also decreased the rate of delince in eGFR. But these dietary patterns did not show a clear beneficial effect for all-cause mortality ( RR = 1.15, 95% CI: 0.76 to 1.73, P = 0.167 for protein restriction, RR = 0.96, 95% CI: 0.31 to 3.02, P = 0.546 for alkaline diet and RR = 0.82, 95% CI: 0.48 to 1.40, P = 0.057 for low-sodium diet). Conclusion:The three dietary interventions may decline the rate of renal function exacerbation and decrease the risk of unfavourable renal outcomes in CKD patients, while have no clear beneficial effect on all-cause mortality.
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UiO-66 (University of Oslo 66) is a kind of promising material that can improve the release and bioavailability of poorly water-soluble bioactive compounds of traditional Chinese medicine. However, the loading of quercetin in raw UiO-66 was not ideal. In this study, UiO-66-BH (UiO-66-blend-heating) was obtained by heating UiO-66 and KOH solution following blended them. UiO-66-BH maintained the outline of octahedral structure of UiO-66 but with obvious rough and uneven pores on the surface. UiO-66-BH had good adsorption of quercetin with saturation adsorption was 138.92 mg·g-1, the adsorption process belonged to single molecular layer adsorption and was controlled by chemisorption. UiO-66-BH can control the release of quercetin in simulated gastrointestinal fluid, and the drug concentration was significantly higher than that of free quercetin after long-term release (36% vs 9%). Compared with quercetin, the ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) ammonium salt) radical scavenging activity of UiO-66-BH@quercetin drug delivery system decreased, while the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity remained almost unchanged. The drug delivery system showed a strong antioxidant effect similar to quercetin. The findings indicated that UiO-66-BH could control release of quercetin and was expected to be used as a drug carrier material for some insoluble active components of traditional Chinese medicine such as quercetin.
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Background@#Vascular calcification is an important non-conventional for cardiovascular disease (CVD) in chronic kidney disease (CKD) patients with chronic hemodialysis (HD). Abdominal aortic calcification (AAC) is reported as an independent predictor for cardiovascular morbidity and mortality. Bone-specific Alkali Phosphatase (bALP) and Alkali Phosphatase (ALP) enzymes are produced and released when changes or disorders of bone and mineral metabolism occur. Given biomarker studies such as bALP and ALP which are more often associated with patient mortality, more research will be needed to assess whether these bALP and ALP biomarkers have a linear distribution of relationships with vascular calcification.@*Objective@#This study aimed to evaluate the serum biomarker to predict calcification and further can be one of diagnosis modality of calcification in hemodialysis patients.@*Methods@#A total of 75 chronic HD CKD patients were included in the study. bALP and ALP serum levels were measured with ELISA, as well as AAC measured by lateral abdominal radiographs (X-Ray).@*Results@#bALP and ALP are positively correlated with AAC scores (p value <0.001 and 0.045). Multivariate logistic regression analysis shows that history of diabetes, bALP levels, and parathyroid hormone (PTH) levels are independent risk factors for AAC in chronic HD CKD patients. Receiver Operating Characteristic (ROC) shows the area under the curve (AUC) of bALP and ALP for AAC prediction are 0.882 (95% CI: 0.801-0.962; p value: <0.001) and 0.634 (95% CI: 0.509-0.760; p value: 0.045).@*Conclusion@#ALP and especially bALP serum correlate closely with vascular calcification in chronic HD CKD patients accompanied by a superior diagnostic value of bALP biomarkers when compared to ALP.
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【Objective】 To investigate the relationship between preoperative albumin-to-alkaline phosphatase ratio (AAPR) and postoperative recurrence of localized penile cancer (T1-3N0M0). 【Methods】 Clinical data of patients with limited penile cancer admitted to our hospital during Jan.2012 and Jan.2017 were collected to compare the differences in age, body mass index (BMI), AAPR, hypertension, diabetes mellitus, tumor diameter, postoperative pathological grading and staging between the postoperative recurrence group and the non-recurrence group. 【Results】 The differences in AAPR(P=0.001), WHO/ISUP pathological grading(P=0.018), and pathological stage(P=0.012)between the recurrence and non-recurrence groups were statistically significant. Cox regression results showed that AAPR was an independent risk factor for recurrence (P=0.041). Survival curve results showed that patients in the high and low AAPR groups had an inverse relationship with recurrence-free survival (P=0.028). 【Conclusion】 Preoperative AAPR is an independent risk factor for recurrence after surgery for limited penile cancer and is associated with recurrence-free survival. As AAPR increases, the incidence of recurrence decreases and progression-free survival increases.
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【Objective】 To observe the role of liver/bone/kidney alkaline phosphatase gene (ALPL) in liver regeneration following 70% hepatectomy (partial hepatectomy, PH). 【Methods】 A knock-out mouse model (ALPL+/-) was established, and a 70% hepatectomy was performed. Changes in liver weight and liver function were measured at PH 1 day, PH 3 day, and PH 7 day (PH1d、PH3d、PH7d) after surgery. In addition, cell proliferation, hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) were performed by Western blotting, immunofluorescence staining, and enzyme linked immunosorbent assay. 【Results】 ALPL knockout mice at PH7d exhibited a lower ratio of liver/total body weight than normal control mice. An analysis of liver function showed no significant difference between the ALPL knockout group and the WT (ALPL+/+) group when the ALPL gene was deleted. While Ki67 staining and PCNA analysis indicated that liver cell proliferation was decreased in ALPL+/- mice at PH1d and increased at PH7d compared to that in ALPL+/+group. Additionally, knockouts of ALPL decreased serum and liver HGF and VEGF levels at PH1d compared to WT controls, but increased at PH7d. 【Conclusion】 The knockout of ALPL leads to a delayed liver regeneration following hepatectomy, which provides theoretical support for exploring the mechanisms underlying liver regeneration after hepatectomy.
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Objective To establish a scoring system based on the preoperative serum levels of alpha-fetoprotein (AFP) and alkaline phosphatase (ALP), and to investigate its value in predicting the prognosis of patients with resectable hepatocellular carcinoma (HCC). Methods A retrospective analysis was performed for 154 HCC patients who underwent hepatectomy as the initial treatment in Tianjin First Central Hospital from January 2016 to August 2019. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off values of serum AFP and ALP; the Kaplan-Meier curve and the log-rank test were used for survival analysis to evaluate the relationship between the AFP-ALP score and disease-free survival (DFS); univariate and multivariate Cox regression analyses were used to identify the independent prognostic factors for HCC patients. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. Results The ROC curve analysis showed that serum AFP had an optimal cut-off value of 250.0 ng/mL and an area under the ROC curve (AUC) of 0.674 (95% confidence interval [ CI ]: 0.580-0.767) in predicting DFS, while serum ALP had an optimal cut-off value of 95.5 U/L and an AUC of 0.745 (95% CI : 0.652-0.838). The survival analysis showed that high preoperative serum levels of AFP (≥250.0 ng/mL) and ALP (≥95.5 U/L) were significantly associated with the poor prognosis of HCC patients ( P < 0.001). Based on the AFP-ALP score, all HCC patients were further divided into 0-point group (AFP < 250.0 ng/mL and ALP < 95.5 U/L), 1-point group (AFP≥250.0 ng/mL, ALP < 95.5 U/L; or AFP < 250.0 ng/mL, ALP ≥95.5 U/L), and 2-point group (AFP≥250.0 ng/mL and ALP≥95.5 U/L). The survival curves showed that the 0-, 1-, and 2-point groups had a median DFS of 60.0 (56.7-67.3) months, 20.0 (1.4-36.6) months, and 13.0(7.9-18.0) months, respectively, and there were significant survival differences between the three groups ( P < 0.05). Serum AFP-ALP score (1 point vs 0 point: hazard ratio [ HR ]=4.060, 95% confidence interval [ CI ]: 2.050-8.039, P < 0.001; 2 points vs 0 point: HR =4.583, 95% CI : 2.385-8.805, P < 0.001) was an independent prognostic factor for HCC patients. Conclusion The scoring system based on the serum levels of AFP and ALP can effectively identify HCC patients with poor prognosis, and therefore, it might be used as a simple and reliable tool for prognostic assessment in the clinical treatment of HCC.
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ObjectiveTo explore the pretreatment methods to promote the enzymatic digestion and extraction of active ingredients from Magnoliae Officinalis Cortex dregs（MOCD）， and to provide a reference basis for the utilization of resource components in MOCD. MethodLiquid chromatography-mass spectrometry（LC-MS） was used for qualitative analysis of resource components in MOCD with an Agilent C18 reversed-phase column（3.0 mm×100 mm， 2.7 µm） at the flow rate of 0.4 mL·min-1， the mobile phase was water（A）-acetonitrile（B） for gradient elution（0-3 min， 25%-48%B； 3-6 min， 48%-59%B； 6-10 min， 59%-80%B； 10-20 min， 80%-90%B； 20-25 min， 90%B）， electrospray ionization（ESI） was employed with negative ion mode scanning and scanning range of m/z 50-1 200. A high performance liquid chromatography（HPLC）， which refered to the determination in the 2020 edition of Chinese Pharmacopoeia， was used for quantitative analysis of resource components in MOCD. Four kinds of pretreatment agents were used to separate the resource components from MOCD， and the mechanism of different pretreatment agents was investigated by field emission scanning electron microscopy（FESEM）， X-ray powder diffraction（XRD） and Fourier transform infrared spectroscopy（FT-IR）. ResultMagnolol， honokiol and lignocellulose were identified as the main resource components of MOCD by qualitative and quantitative analysis. Under the conditions of 1% NaOH， reaction temperature at 80 ℃ and reaction time of 60 min， the concentration of reducing sugar produced by the enzymatic hydrolysis was 32.18 g·L-1， which was 79.8% higher than that of the untreated MOCD. After adding tween-80， the enzymatic hydrolysis time was reduced to 1/3 of the original time， the concentration of reducing sugar was increased by 102.0%. And the total recovery of magnolol and honokiol in the pretreatment solution was 69.23%. ConclusionMagnolol， honokiol and lignocellulosic components in MOCD are valuable for development and utilization， the combination of alkaline pretreatment and tween-80 can realize the recovery and utilization of these three resource components， which can provide a new idea for comprehensive utilization of resource components in MOCD.
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Objective @# To investigate the effect of erythropoietin producing hepatocyte kinase receptor ligand B2-erythropoietin producing hepatocyte kinase receptor B4 (EphrinB2/EphB4) on the osteogenic differentiation of MC3T3-E1 cells in a hypoxic environment to provide experimental evidence for hypoxia regulation of osteoblast differentiation.@*Methods @# Control groups and cobalt chloride (CoCl2)-induced hypoxia groups were set up first. qRT-PCR was used to detect the mRNA expression of the osteogenic markers alkaline phosphatase (ALP), collogen1 (COL I), runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN). ALP staining was used to detect the activity of cell alkaline phosphatase after osteogenic induction. The mRNA and protein expression levels of hypoxia inducible factor-1α (HIF-1α), EphrinB2 and EphB4 in the two groups were detected via qRT-PCR and Western blot. Then, the CoCl2 + inhibitor group was established. NVP-BHG712, an EphB4 phosphorylation inhibitor, was added to this group to prevent EphrinB2 from binding to EphB4 and producing signals. qRT-PCR and Western blot were used to detect the mRNA and protein expression of osteogenic markers, including ALP, RUNX2, COL I, and OCN. ALP staining and Alizarin red S staining were used to measure osteoblast differentiation and mineralization. @*Results @# Compared with the control group, the mRNA expression of the osteogenic differentiation markers ALP, RUNX2, COL-1, and OCN in MC3T3-E1 cells increased, and ALP activity and mineralization were enhanced under CoCl2-induced hypoxia in vitro (P<0.05). Additionally, the expression of HIF-1α, EphrinB2 and EphB4 was upregulated at the mRNA and protein levels under hypoxia (P<0.05). When NVP-BHG712 was used to block the connection between EphrinB2 and EphB4, the expression of osteogenic markers and ALP activity and mineralization were decreased (P<0.05).@*Conclusion@#EphrinB2/EphB4 can promote osteogenic differentiation of MC3T3-E1 cells and increase the expression of osteogenic markers and tissue mineralization in a hypoxic environment.
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ABSTRACT Hypophosphatasia (HPP) is an inherited disease caused by a low activity of tissue-nonspecific alkaline phosphatase, a hydrolase that removes phosphate groups from many molecules. Decreased alkaline phosphatase activity leads to the accumulation of three main metabolites, i.e., pyridoxal 5'-phosphate (PLP), inorganic pyrophosphate (PPi), and phosphoethanolamine. Impairment in PLP dephosphorylation induces seizures, while PPi accumulation inhibits bone mineralization. Clinically, HPP has a wide spectrum of presentations, ranging from neonatal death to an apparent lack of symptoms. This disease is classified into six subtypes according to the age at onset of first signs or symptoms. The clinical manifestations of the disease include rickets-like bone changes, bone demineralization, fragility fractures, reduced muscular strength, chest deformity, pulmonary hypoplasia, nephrolithiasis, nephrocalcinosis, and chondrocalcinosis. Treatment of HPP consists of enzyme replacement therapy. Before this therapy was approved, treatment was palliative and associated with high morbidity and mortality. Asfotase alfa has changed the prognosis of the disease by reducing bone deformity and improving bone mineralization, lung function, and muscle weakness, among other benefits. In adults, teriparatide and anti-sclerostin antibody have been used off-label in selected cases, demonstrating benefit in accelerating fracture healing and in concomitant treatment of osteoporosis. This review summarizes the main aspects of HPP and identifies the particularities of the disease in adult patients.
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ABSTRACT Objective To assess the predictive value of preoperative serum laboratory test results for identifying choledocholithiasis and reduce the use of cholangioresonance and its inherent costs. Methods Patients aged 21-69 years who underwent preoperative cholangioresonance examination at our institute were included. Patients with a history of fluctuating jaundice or biliary pancreatitis, bile duct dilatation on ultrasonography, and elevated levels of canalicular enzymes (alkaline phosphatase >100U/L and gamma-glutamyl transferase >50U/L) underwent cholangioresonance-guided surgery. Cases of choledocholithiasis confirmed by cholangioresonance were compared with those without choledocholithiasis. Serum laboratory data were evaluated and the diagnostic capabilities of these examinations were analyzed. Results A total of 104 patients were included. For detecting choledocholithiasis using alkaline phosphatase, the cut-off point was 78U/L, sensitivity was 97.6% (95%CI: 87.4-99.9), and specificity was 72.6% (95%CI: 59.8-83.1). In the binary logistic regression analysis, age (OR= 0.92; 95%CI: 0.86-0.98) and alkaline phosphatase level (OR= 1.02; 95%CI: 1.01-1.05) were selected for the final model. Conclusion Serum alkaline phosphatase levels may aid preoperative diagnosis of asymptomatic choledocholithiasis. After a global clinical assessment of the patient, serum laboratory findings may contribute to a reduction in cholangioresonance-related heathcare costs.
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Objetivo: Este estudo objetivou avaliar o potencial proliferativo e de diferenciação das células tronco da papila cultivadas conjuntamente com fibrina rica em plaquetas (PRF) preparados sob dois protocolos de centrifugação distintos. Material e Métodos: Protocolos padrão e avançado de PRF foram utilizados. As células foram divididas em 4 grupos: controle negativo, controle positivo, padrão (L-PRF) e avançado (A-PRF). A contagem de células e ensaio de viabilidade foram realizados para verificar a capacidade proliferativa. Coloração vermelho de alizarina S, atividade de fosfatase alcalina e imunofluorescência para o receptor ativador do fator nuclear kappa-B (RANKL) foram utilizados para avaliar o potencial osteogênico e de diferenciação celular. Resultados: Ambos os tipos de PRF aumentaram o número de células, viabilidade celular sem toxicidade o que refletiu no aumento da proliferação e diferenciação de acordo com os testes realizados. Conclusão: O grupo A-PRF aumentou significativamente a proliferação e diferenciação comparado com o grupo L-PRF.(AU)
Objectives: The present work was designed to evaluate the proliferation and differentiation potential of stem cells from the apical papilla (SCAP) seeded along with platelet rich fibrin (PRF) scaffolds prepared under two different centrifugation protocols. Materials and Methods: Standard and advanced PRF protocols were used. Cells were divided into 4 groups: negative control, positive control, standard (L-PRF) and advanced (A-PRF) groups. Cell count and cell viability assays were carried out to assess the proliferation capacity. Alizarin red S (ARS) stain, Alkaline phosphatase (ALP) activity and Receptor activator of nuclear factor-kappa B ligand (RANKL) immunofluorescence staining were used to evaluate the osteogenic potential in the differentiated cells. Results:Both types of platelet rich fibrin increased the cell count, cell viability with no cytotoxicity that was reflected on increased proliferation and differentiation in terms of the performed tests. Conclusion: A-PRF group showed significant increase in proliferation and differentiation potentials compared to L-PRF group