[Clinical characteristics and prognosis analysis of gastric cancer patients with bone metastasis].

Objectives: To investigate the clinical characteristics and prognosis of bone metastasis of gastric cancer, analyze the influencing factors of bone metastasis and the effects of different treatment methods, and provide a basis for early detection and treatment optimization of bone metastasis of gastric cancer. Methods: A total of 142 gastric cancer patients with bone metastasis admitted to the First Hospital of Lanzhou University from January 2011 to December 2021 were enrolled, including 60 cases of simple bone metastasis and 82 cases of bone metastasis combined with extraosseous metastasis. 142 patients with stage Ⅲgastric cancer without distant metastasis and 142 gastric cancer patients with visceral metastasis admitted to this hospital during the same period were also enrolled for comparison. Logistic regression analysis was used to determine the influencing factors of bone metastasis, and the Cox proportional hazards regression model was used to evaluate the influencing factors of overall survival (OS) of patients with bone metastasis. Results: Among the 142 patients with bone metastasis, poorly differentiated adenocarcinoma was the main type (123 cases), and 45 patients had simultaneous bone metastasis. Rib metastasis (100 cases), spine metastasis (88 cases), and pelvis metastasis (84 cases) were more common. A total of 110 patients had multiple bone metastasis, and 82 patients had extraosseous metastasis. Results of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extraosseous metastasis group were compared. There were significant differences in age, degree of differentiation, Borrmann type, alkaline phosphatase, lactate dehydrogenase, serum calcium, alanine aminotransferase, aspartate aminotransferase, creatine kinase isoenzyme, lymphocyte, hemoglobin, platelet, CEA, CA19-9, and CA724 (all P<0.05). Multivariate logistic regression analysis showed that Borrmann type was an independent protective factor of bone metastasis of gastric cancer (type 3: OR=0.07, 95%CI: 0.01-0.64, P=0.018). Alkaline phosphatase (OR=2.54, 95% CI: 1.07-6.01, P=0.034), serum calcium (OR=2.71, 95% CI: 1.15-6.41, P=0.023), creatine kinase isoenzyme (OR=16.33, 95% CI: 1.83-145.58, P=0.012), platelet (OR=10.08, 95% CI:1.89-53.85, P=0.007), and CA19-9 (OR=2.40, 95% CI: 1.14-5.05, P=0.021) were independent risk factors of bone metastasis of gastric cancer. The median OS of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extrabony group were 47, 13, 18, and 6 months, respectively, and the difference was statistically significant (P<0.001). The median OS of patients with bone metastasis only who underwent primary tumor surgery was 33 months, better than 6 months of patients without surgery (P=0.048). Multivariate Cox regression analysis showed that extraosseous metastasis (HR=2.45, 95% CI: 1.56-3.85, P<0.001) and decreased hemoglobin (HR=1.54, 95%CI: 1.02-2.34, P=0.042) were independent risk factors of OS of gastric cancer patients with bone metastasis. Conclusions: The prognosis of gastric cancer patients with bone metastasis alone is significantly better than that of other stage Ⅳ patients. For such patients, surgery on the primary site combined with chemotherapy after full evaluation may prolong the survival time.

Changes in the concentration of bone turnover markers in men after maximum intensity exercise.

Background: Physical activity is an important factor in modelling the remodelling and metabolism of bone tissue. The aim of the study was to evaluate the changes in indices demonstrating bone turnover in men under the influence of maximum-intensity exercise. Methods: The study involved 33 men aged 20-25, divided into two groups: experimental (n = 15) and control (n = 18). People training medium- and long-distance running were assigned to the experimental group, and non-training individuals to the control. Selected somatic, physiological and biochemical indices were measured. The level of aerobic fitness was determined using a progressively increasing graded test (treadmill test for subjective fatigue). Blood samples for determinations were taken before the test and 60 minutes after its completion. The concentration of selected bone turnover markers was assessed: bone fraction of alkaline phosphatase (b-ALP), osteoclacin (OC), N-terminal cross-linked telopeptide of the alpha chain of type I collagen (NTx1), N-terminal propeptide of type I progolagen (PINP), osteoprotegerin (OPG). In addition, the concentration of 25(OH)D3 prior to the stress test was determined. Additionally, pre and post exercise, the concentration of lactates in the capillary blood was determined. Results: When comparing the two groups, significant statistical differences were found for the mean level of: 25(OH)D3 (p = 0.025), b-ALP (p < 0.001), OC (p = 0.004) and PINP (p = 0.029) prior to the test. On the other hand, within individual groups, between the values pre and post the stress test, there were statistically significant differences for the average level of: b-ALP (p < 0.001), NTx1 (p < 0.001), OPG (p = 0.001) and PINP (p = 0.002). Conclusion: A single-session maximum physical effort can become an effective tool to initiate positive changes in bone turnover markers.

Light microscopic morphology of blood cells of non-descript indigenous Zoar chicken of Mizoram, India.

Identifying and analysing distinct blood cells is crucial for the diagnosis and treatment of diseases in the field of biomedicine. The present study was undertaken to study the cytomorphological and cytochemical characteristics of the blood cells of Zoar, a non-descript indigenous breed of chicken extensively reared under backyard poultry farming in Mizoram, India. For this study, 2 mL of blood samples were aseptically collected from the wings veins of 12 chickens and were processed for light microscopic study under standard protocols. The matured erythrocytes were elliptical, while the immature erythrocytes appeared oval. The heterophils were positive for SBB (SBB), Periodic Acid Schiff (PAS), acid phosphatase, alkaline phosphatase and Arylsulphatase while the eosinophils were positive for SBB, PAS, alkaline phosphatase, cytochrome oxidase and peroxidase. The basophils of were positive for toluidine blue while the thrombocytes were positive for PAS. These cytochemical and cytoenzymatic staining properties plays a very important role in diagnosis, differentiation, and classification of leukaemias.

Metastatic Melanoma of the Common Bile Duct Presented with Dyspepsia.

Malignant melanoma (MM) is an aggressive tumor that can metastasize to any organ, but biliary tract metastasis is scarce. We describe a very rare case of MM metastasis to the common bile duct (CBD), presented with only dyspeptic symptoms. The patient had mildly elevated alkaline phosphatase and gamma-glutamyl transferase levels. Magnetic resonance cholangiopancreatography demonstrated a dilated common bile duct with a distal stricture. The MM diagnosis was established with the ampulla of Vater biopsy specimens obtained by endoscopic retrograde cholangiopancreatography (ERCP), and the patient's symptoms were resolved after biliary stenting. Both primary CBD cancer and other cancer types like MM that metastasize to CBD can cause obstruction and can be manifested only by dyspeptic symptoms. MM metastasis to CBD can cause obstruction manifested only by dyspeptic symptoms without obstructive jaundice. ERCP can be employed as a promising option for treatment and diagnosis. New-onset dyspeptic symptoms in patients with a history of MM should be investigated thoroughly, especially in the context of biliary metastasis.

Limited prognostic role of routine serum markers (AP, CEA, LDH and NSE) in oligorecurrent prostate cancer patients undergoing PSMA-radioguided surgery.

INTRODUCTION: We evaluated the prognostic role of pre-salvage prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) serum levels of alkaline phosphatase (AP), carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), and neuron-specific enolase (NSE). MATERIALS AND METHODS: Patients who consecutively underwent PSMA-RGS for prostate cancer (PCa) oligorecurrence between January 2019 and January 2022 were selected. Biomarkers were assessed one day before surgery. Cox regression and logistic regression models tested the relationship between biochemical recurrence-free survival (BFS), 6- and 12-month biochemical recurrence (BCR), and several independent variables, including biomarkers. RESULTS: 153 consecutive patients were analyzed. In the univariable Cox regression analysis, none of the biomarkers achieved predictor status (AP: hazard ratio [HR] = 1.03, 95% CI 0.99, 1.01; p = 0.19; CEA: HR = 1.73, 95% CI 0.94, 1.21; p = 0.34; LDH: HR = 1.01, 95% CI 1.00, 1.01; p = 0.05; NSE: HR = 1.02, 95% CI 0.98, 1.06; p = 0.39). The only independent predictor of BFS was the number of positive lesions on PSMA PET (HR = 1.17, 95% CI 1.02, 1.30; p = 0.03). The number of positive lesions was confirmed as independent predictor for BCR within 6 and 12 months (BCR < 6 months: odds ratio [OR] = 1.1, 95% CI 1.0, 1.3; p = 0.04; BCR < 12 months: OR = 1.1, 95% CI 1.0, 1.3; p = 0.04). CONCLUSION: The assessment of AP, CEA, LDH, and NSE before salvage PSMA-RGS showed no prognostic impact. Further studies are needed to identify possible predictors that will optimize patient selection for salvage PSMA-RGS.

[Correlation between CRAB Symptoms and Antioxidant Enzyme Activity in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the relationship between clinical indicators of CRAB symptoms and antioxidant enzyme activity in patients with multiple myeloma (MM). METHODS: The activity of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in the bone marrow supernatants of 44 patients with MM and 12 patients with non-malignant hematological diseases was detected by colorimetric assay, and then the differences in the activity of antioxidant enzymes between the two groups were compared. Furthermore, the relationship between the activity of antioxidant enzymes in the MM group and the levels of serum calcium, serum creatinine (Scr), hemoglobin (Hb), alkaline phosphatase (ALP) as well as bone lesions were analyzed. RESULTS: The antioxidant enzyme activity was lower in MM patients compared with the control group (P < 0.05). When the concentrations of serum calcium and ALP were higher than the normal levels, Hb was lower than 85 g/L, and there were multiple bone lesions, the activity of CAT, SOD and GPX was significantly declined (P < 0.05); When the concentration of Scr≥177 µmol/L, the activity of GPX was significantly declined (P < 0.05). Regression analyses showed that CAT, SOD and GPX were negatively correlated with serum calcium (r =-0.538, r =-0.456, r =-0.431), Scr (r =-0.342, r =-0.384, r =-0.463), and ALP (r =-0.551, r =-0.572, r =-0.482). CONCLUSION: The activity of antioxidant enzymes, including CAT, SOD and GPX, were decreased in patients with MM and they were negatively correlated with some clinical indicators of CRAB symptoms (such as serum calcium, Scr, and ALP), which suggests that promoting the activity of antioxidant enzymes may be beneficial to treat the CRAB symptoms of the patients with MM.

Elevated alkaline phosphatase independently predicts early postoperative complications in noninfectious revision total shoulder arthroplasty.

PURPOSE: This study investigates the association between preoperative serum alkaline phosphatase levels and 30 day postoperative complications following noninfectious revision total shoulder arthroplasty (TSA). We hypothesize that elevated alkaline phosphatase levels are significantly associated with an increased 30 day postoperative complication rate. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients who underwent noninfectious revision TSA from 2015 to 2022. The study population was divided into two groups based on preoperative serum alkaline phosphatase: normal (44-147 IU/L) and elevated (> 147 IU/L). Logistic regression analysis was conducted to investigate the relationship between elevated alkaline phosphatase levels and postoperative complications. RESULTS: Compared to normal levels, elevated alkaline phosphatase was independently associated with a significantly greater likelihood of experiencing any complications (odds ratio [OR] 2.54, 95% confidence interval [CI] 1.41-4.55; P = .002), sepsis (OR 9.96, 95% CI 1.67-59.29; P = .012), blood transfusions (OR 3.77, 95% CI 1.48-9.61; P = .005), readmission (OR 3.65, 95% CI 1.48-9.01; P = .005), and length of stay > 2 days (OR 2.37, 95% CI 1.31-4.30; P = .004). CONCLUSIONS: Elevated preoperative alkaline phosphatase was associated with a greater rate of early postoperative complications following noninfectious revision TSA. LEVEL OF EVIDENCE: Level III; Retrospective Cohort Comparison; Prognosis Study.

Assessment of clinical chemistry and hematological parameters in female Sprague-Dawley rats following a 7-day oral exposure to three different species of Echinacea.

Echinacea has grown in popularity due to its broad therapeutic benefits. Despite its popularity, comprehensive safety evaluations for three medicinal species are limited. In this study, female Sprague-Dawley rats received oral doses (0, 25, 50, 100, 200 mg/kg/d) of 75% (v/v) ethanol extract from the aerial parts of 9 Echinacea samples of three species - Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida - over a 7-day period. Blood and serum samples, collected twenty-four hours post the final dose, were analyzed for hematology and clinical chemistry parameters. The results revealed varied effects across the tested samples, with many parameters showing no discernible impacts at administered doses. Subtle alterations were observed in parameters such as relative liver weight, alkaline phosphatase (ALP), and platelet count. Parameters like relative spleen weight, alanine transaminase (ALT), glucose, urea, hematocrit, hemoglobin, and RBC count exhibited effects in only one out of the nine samples tested. These findings emphasize the heterogeneity in the effects of Echinacea. While the results suggest that Echinacea samples might be considered relatively safe, potential clinical implications warrant caution and underscore the importance of extended testing. A comprehensive toxicity profile assessment remains paramount to conclusively ascertain the safety of three Echinacea species.

Predictors of bone mineral density in patients receiving glucocorticoid replacement for Addison's disease.

PURPOSE: Patients receiving long-term glucocorticoid (GC) treatment are at risk of osteoporosis, while bone effects of substitution doses in Addison's disease (AD) remain equivocal. The project was aimed to evaluate serum bone turnover markers (BTMs): osteocalcin, type I procollagen N-terminal propeptide (PINP), collagen C-terminal telopeptide (CTX), sclerostin, DKK-1 protein, and alkaline phosphatase (ALP) in relation to bone mineral density (BMD) during GC replacement. METHODS: Serum BTMs and hormones were assessed in 80 patients with AD (22 males, 25 pre- and 33 postmenopausal females) on hydrocortisone (HC) substitution for ≥3 years. Densitometry with dual-energy X-ray absorptiometry covered the lumbar spine (LS) and femoral neck (FN). RESULTS: Among BTMs, only PINP levels were altered in AD. BMD Z-scores remained negative except for FN in males. Considering T-scores, osteopenia was found in LS in 45.5% males, 24% young and 42.4% postmenopausal females, while osteoporosis in 9.0%, 4.0% and 21.1%, respectively. Lumbar BMD correlated positively with body mass (p = 0.0001) and serum DHEA-S (p = 9.899 × 10-6). Negative correlation was detected with HC dose/day/kg (p = 0.0320), cumulative HC dose (p = 0.0030), patient's age (p = 1.038 × 10-5), disease duration (p = 0.0004), ALP activity (p = 0.0041) and CTX level (p = 0.0105). However, only age, body mass, ALP, serum CTX, and sclerostin remained independent predictors of LS BMD. CONCLUSION: Standard HC substitution does not considerably accelerate BMD loss in AD patients and their serum BTMs: CTX, osteocalcin, sclerostin, DKK-1, and ALP activity remain within the reference ranges. Independent predictors of low lumbar spine BMD, especially ALP activity, serum CTX and sclerostin, might be monitored during GC substitution.

Effect of vitamin D supplementation or fortification on bone turnover markers in women: a systematic review and meta-analysis.

Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomised clinical trials reported changes in bone resorption markers (serum C-terminal telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP) and procollagen type-1 intact N-terminal propeptide (P1NP)) following vitamin D administration in women (aged ≥ 18 years) were considered. Mean differences (MD) and their respective 95 % CI were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: -0·038, n 22) and OC (MD: -0·610, n 24) with high heterogeneity and uNTX (MD: -8·188, n 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600 µg/d and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.

The Influence of the Preoperative Albumin to Alkaline Phosphatase Ratio on Overall Survival in Post-Radical Surgery for Colorectal Cancer and the Construction of a Nomogram Prediction Model.

PURPOSE: The albumin to alkaline phosphatase ratio (AAPR) is a newly developed blood biomarker that has been reported to have prognostic value in several types of cancers. The aim of this study was to investigate the predictive value of AAPR in overall survival after radical colon cancer surgery in patients with stage I-III colorectal cancer (CRC). METHODS: The clinical data of 221 eligible patients with stage I ∼ III CRC were retrospectively analyzed. A series of survival analyses were performed to assess the prognostic value of AAPR. Univariate and multifactorial Cox analyses were performed to identify independent risk factors. Columnar graph prediction models were further constructed based on independent risk factors such as AAPR, and their predictive properties were validated. RESULTS: The optimal cutoff value of preoperative AAPR for postoperative overall survival (OS) in patients undergoing laparoscopic radical CRC was .495 as shown by univariate and multifactorial Cox regression analysis. The factors of age ≤65 years, Tumor-Node-Metastasis (TNM) stage I-II, tumor grading (high/medium differentiation), CEA ≤5, and AAPR ≥.495 were associated with better OS (P < .05). CONCLUSIONS: Preoperative AAPR level was a good predictor of postoperative survival in patients undergoing laparoscopic radical CRC surgery, and AAPR <.495 was an independent risk factor for decreased postoperative OS.

Total alkaline phosphatase levels by gestational age in a large sample of pregnant women.

INTRODUCTION: Total alkaline phosphatase (tALP) levels rise physiologically in maternal serum during pregnancy, and excessively so in certain conditions. However, current reference values are dated, nonlinear, and based on small samples. Factors related to variation in tALP remain unexplained. Thus, our goals in this study were to establish a physiological development curve for tALP within low-risk pregnancies and to evaluate the factors influencing tALP values. METHODS: This was a single-center, retrospective, observational study. All patients who delivered a live singleton infant at our center from January 1, 2011 to May 31, 2019, and had a tALP assay during pregnancy, were included regardless of the gestational age at which the assay was conducted. RESULTS: A total of 2415 pregnancies were included. Median tALP decreased during the first trimester, it increased slightly during the second trimester, and then increased sharply during the third trimester. Factors associated with a significant increase in tALP were chronic histiocytic intervillositis, cholestasis, multiple pregnancies, liver disease, preeclampsia, smoking, and low weight for gestational age. Conversely, gestational diabetes was associated with a discrete decrease in tALP. DISCUSSION: Our large sample allowed establishment of tALP reference curves based on gestational age. To interpret these results more thoroughly, factors that influence tALP rates should be further scrutinized.

Changes in bone turnover markers in adolescents with gastroesophageal reflux disease treated with lansoprazole.

Background: Proton pump inhibitors (PPIs) have been suggested to lead to bone resorption, while the effects of PPIs on the bone mineral metabolism in children has received only limited attention in literature to date. The present study investigates whether lansoprazole alters bone turnover markers in adolescents with gastroesophageal reflux disease (GERD). Patients and methods: Included in the study were adolescents aged 16-18 with GERD and a healthy volunteers group. The GERD patient group was treated with lansoprazole 30 mg once daily for eight weeks. The serum calcium, phosphorus, magnesium, alkaline phosphatase (ALP), parathormone (PTH), 25 (OH) vitamin D, osteocalcin and urinary calcium, creatinine, deoxypyridinoline (DPD), collagen type-1 crosslinked C-telopeptide (CTX) and collagen type-1 crosslinked N-telopeptide (NTX) of both groups were studied before and after the end of the treatment. Results: A comparison of the 30 patients with GERD and the 30 volunteers revealed no significant difference in the serum calcium, phosphorus, magnesium, ALP, urinary calcium/creatinine ratio, 25 (OH) vitamin D and PTH levels measured before and after the lansoprazole treatment, while the osteocalcin, DPD, CTX and NTX values were found to be higher after treatment when compared to those at pre- treatment. Conclusions: The results of this study reveal that eight weeks of treatment with 30 mg lansoprazole daily increased the bone turnover markers of CTX, NTX, DPD and osteocalcin in adolescents aged 16-18.

Icariin attenuates thioacetamide­induced bone loss via the RANKL­p38/ERK­NFAT signaling pathway.

There is an increasing incidence of destructive bone disease caused by osteoclast proliferation. This is characterized by reduced bone mass and imbalance of bone homeostasis. Icariin (ICA), a flavonoid compound isolated from Epimedium, has anti­osteoporosis activity and inhibits the formation of osteoclasts and bone resorption. The purpose of the present study was to investigate the protective effect of ICA on osteoclastic differentiation induced by thioacetamide (TAA) and its possible mechanism in Sprague Dawley (SD) rats. In the present study, SD rats were intraperitoneally injected with TAA (300 mg/kg) for the bone loss model, treated with ICA (600 mg/kg, intragastric gavage) in the ICA group and TAA+ICA group for treatment of bone loss for 6 weeks. Indexes associated with bone metabolism, such as alkaline phosphatase, N­terminal telopeptide of type­I collagen (NTX­I), calcium (Ca), phosphorus (P) and magnesium (Mg) in the serum, were detected. Osteoclast differentiation of femoral tissues was detected by hematoxylin and eosin and tartrate­resistant acid phosphatase staining. The femoral bone mass was evaluated using a three­point bending test and micro computed tomography. Western blotting was used to detect the expression levels of osteoclast­related proteins in each group. In the rats treated with TAA, the serum concentrations of Ca, P and Mg were decreased, the serum concentration of NTX­I was increased, osteoclast differentiation of the femur was increased, femur bone stress and bone mass were decreased and the bone loss and osteoclast formation were reduced after ICA treatment. In addition, ICA inhibited the protein expression of receptor activator of nuclear factor κ­Β ligand (RANKL), receptor activator of nuclear factor κ­B (RANK), p38, ERK, c­Fos and nuclear factor of activated T cells 1 (NFATc1) in the femur of rats treated with TAA. The results suggested that ICA may inhibit osteoclast differentiation by downregulating the RANKL­p38/ERK­NFAT signaling pathway and prevent TAA­induced bone loss. The results are helpful to understand the mechanism of osteoclast differentiation induced by TAA, as well as the antiresorptive activity and molecular mechanism of ICA, and to provide new ideas for the treatment of osteolytic diseases.

Clinical, biochemical and genetic findings in adult patients with chronic hypophosphatasemia.

PURPOSE: The study aimed to define the clinical, biochemical and genetic features of adult patients with osteopenia/osteoporosis and/or bone fragility and low serum alkaline phosphatase (sALP). METHODS: Twenty-two patients with at least two sALP values below the reference range were retrospectively enrolled after exclusion of secondary causes. Data about clinical features, mineral and bone markers, serum pyridoxal-5'-phosphate (PLP), urine phosphoethanolamine (PEA), lumbar and femur bone densitometry, and column X-ray were collected. Peripheral blood DNA of each participant was analyzed to detect ALPL gene anomalies. RESULTS: Pathogenic ALPL variants (pALPL) occurred in 23% and benign variants in 36% of patients (bALPL), while nine patients harbored wild-type alleles (wtALPL). Fragility fractures and dental anomalies were more frequent in patients harboring pALPL and bALPL than in wtALPL patients. Of note, wtALPL patients comprised women treated with tamoxifen for hormone-sensitive breast cancer. Mineral and bone markers were similar in the three groups. Mean urine PEA levels were significantly higher in patients harboring pALPL than those detected in patients harboring bALPL and wtALPL; by contrast, serum PLP levels were similar in the three groups. A 6-points score, considering clinical and biochemical features, was predictive of pALPL detection [P = 0.060, OR 1.92 (95% CI 0.972, 3.794)], and more significantly of pALPL or bALPL [P = 0.025, OR 14.33 (95% CI 1.401, 14.605)]. CONCLUSION: In osteopenic/osteoporotic patients, single clinical or biochemical factors did not distinguish hypophosphatasemic patients harboring pALPL or bALPL from those harboring wtALPL. Occurrence of multiple clinical and biochemical features is predictive of ALPL anomalies, and, therefore, they should be carefully identified. Tamoxifen emerged as a hypophosphatasemic drug.

Prognostic Value of ALP and LDH in Periampullary Carcinoma Patients Undergoing Surgery.

OBJECTIVE: Conversion of normal cells to cancer cells is often accompanied by abnormal synthesis of serum enzymes. Both alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) have been reported to have prognostic value in a variety of malignancies. The aim of this study was to investigate the effect of preoperative serum ALP and LDH levels on the prognosis of patients with periampullary carcinoma who underwent pancreatoduodenectomy (PD). METHODS: According to the preoperative ALP or LDH values, 856 cancer patients receiving PD treatment from January 2001 to January 2019 were divided into high-ALP group and low-ALP group or high-LDH group and low-LDH group. Statistical analysis was carried out to study the differences between the high-ALP and low-ALP groups or the high-LDH and low-LDH groups. Furthermore, the possibility of preoperative ALP or LDH as prognostic factor of periampullary carcinoma was investigated. RESULTS: In both the high-ALP and the high-LDH groups, the prognosis of patients with periampullary carcinoma who underwent PD was worse than that of the low-ALP and low- LDH group. Even through risk factor analysis, it was found that preoperative ALP and LDH could be independent prognostic factor for patients with periampullary carcinoma who underwent PD. CONCLUSION: Preoperative ALP or LDH is an independent risk factor for periampullary carcinoma.

The Novel Bone Alkaline Phosphatase Isoform B1x Is Associated with Improved 5-Year Survival in Chronic Kidney Disease.

Circulating alkaline phosphatase (ALP) is an independent cardiovascular risk marker. Serum bone ALP (BALP) isoforms indicate bone turnover and comprise approximately 50% of total circulating ALP. In chronic kidney disease (CKD), mortality is highest in patients with increased ALP and BALP and low bone turnover. However, not all low bone turnover states are associated with increased mortality. Chronic inflammation and oxidative stress, features of protein energy wasting syndrome, induce cardiovascular BALP activity and fibro-calcification, while bone turnover is suppressed. Circulating BALP isoform B1x is associated with low ALP and low bone turnover and has been exclusively detected in CKD. We investigated the association of serum B1x with survival, abdominal aortic calcification (AAC) score, and aortic pulse wave velocity (PWV) in CKD. Serum ALP, BALP isoforms, parathyroid hormone (PTH), PWV, and AAC were measured repeatedly over 2 years in 68 prevalent dialysis patients. Mortality was assessed after 5 years. B1x was detected in 53 patients. A competing risk analysis revealed an association of B1x with improved 5-year survival; whereas, baseline PWV, but not AAC score, predicted mortality. However, PWV improved in 26 patients (53%), and B1x was associated with variation of PWV over time (p = 0.03). Patients with B1x had lower PTH and total ALP, suggesting an association with lower bone turnover. In conclusion, B1x is associated with time-varying PWV, lower circulating ALP, and improved survival in CKD, and thus may be an indicator of a reduced cardiovascular risk profile among patients with low bone turnover.

Serum Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Level in Patients with Hepatocellular Carcinoma.

OBJECTIVE: To evaluate the clinical value of carcinoembryonic-antigen-related cell-adhesion molecule 1 (CEACAM1) in predicting the severity of hepatocellular carcinoma(HCC). METHODS: We evaluated 40 healthy subjects and 40 HCC patients by collecting venous blood for the comparison. Serum CEACAM1 was detected using the Human CEACAM1 ELISA Kit. Other laboratory chemistries were analyzed by standard methods. RESULTS: The serum level of CEACAM1 was not different between HCC patients and healthy subjects (p=0.0069). There was a correlation between serum CEACAM1 level and total bilirubin, and direct bilirubin. There was also a statistically significant difference among serum CEACAM1 levels stratified by BCLC staging and MELD score at the cut-point of 18. Lower platelet count, higher levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were observed in HCC patients. CONCLUSION: An increase of serum CEACAM1 level was associated with cholestasis. The role of this molecule in HCC diagnosis was unclear. However, serum CAECAM1 may be useful to predict the severity in HCC patients.

Mokko Lactone Attenuates Doxorubicin-Induced Hepatotoxicity in Rats: Emphasis on Sirt-1/FOXO1/NF-κB Axis.

Doxorubicin (DOX), a common chemotherapeutic agent, suffers serious adverse effects including hepatotoxicity. Mokko lactone (ML) is a guainolide sesquiterpene with promising biological activities. The study aimed to evaluate the protection offered by ML against hepatotoxicity induced by DOX in rats. Our data indicated ML exhibited protective effects as evidenced by ameliorating the rise in serum activities of alanine transaminase, aspartate transaminase and alkaline phosphatase. This was confirmed histologically as ML prevented DOX-induced pathological alteration in liver architecture. Further, ML administration significantly prevented malondialdehyde accumulation, glutathione depletion and superoxide dismutase and catalase exhaustion. Antioxidant action of ML was associated with enhanced expression of the nuclear translocation of NF-E2-related factor 2 (Nrf2) and a lower expression of forkhead box protein O1 (FOXO1). Also, ML showed potent anti-inflammatory activities highlighted by decreased expression of interleukin 6, tumor necrosis factor α and nuclear factor κB (NF-κB). The anti-apoptotic effects of ML were associated with decreased Bax and enhanced Bcl-2 mRNA expression in liver tissues. ML caused a significant up-regulation in the expression of silent information regulator 1 (Sirt-1). Therefore, it can be concluded that ML prevents liver injury caused by DOX. This could partially be due to the ML regulatory activities on Sirt-1/FOXO1/NF-κB axis.

Clinical Characteristics and Management of Patients With McCune-Albright Syndrome With GH Excess and Precocious Puberty: A Case Series and Literature Review.

Background: McCune-Albright syndrome is a rare disorder characterized by fibrous dysplasia, café au lait skin spots, and hyperfunctioning endocrinopathies. The coexistence of precocious puberty and growth hormone excess in McCune-Albright syndrome is rare. Both conditions can manifest as accelerated growth, and treatments can be more challenging for such patients. This study aimed to describe the clinical manifestations of combined GH excess and PP in the context of McCune-Albright syndrome and analyze the clinical features and treatments of these patients. Method: Clinical data from 60 McCune-Albright syndrome patients from Peking Union Medical College Hospital were obtained. The demographic characteristics, growth hormone, insulin-like growth factor-1, prolactin, alkaline phosphatase, and sex hormone levels; growth velocity; and bone age data were obtained. The growth velocity Z-score, bone age over chronological age ratio, and predicted adult height Z-score were calculated before and after treatment. Published studies and case reports were systemically searched, and data on demographic, clinical, and biochemical characteristics and treatment outcomes were obtained. Results: We reviewed seven patients among 60 McCune-Albright syndrome patients at Peking Union Medical College Hospital (5 female) and 39 patients (25 female) from the published literature. Six of the seven patients from Peking Union Medical College Hospital and half of the patients from the published studies were pediatric patients. These patients had increased growth velocity Z-scores and bone age over chronological age ratios. After good control of both conditions, the growth velocity Z-score and bone age over chronological age ratio decreased significantly, and the predicted adult height Z-score increased. The final heights and predicted adult height Z-scores were not impaired in patients with gigantism. All the patients had craniofacial fibrous dysplasia associated with optic and otologic complications. Conclusion: McCune-Albright syndrome with growth hormone excess and precocious puberty is more common in girls. Patients have accelerated linear growth and advanced skeletal age, and early and good control of both conditions leads to a reduced growth velocity and stabilized bone age. The predicted adult and final heights are not negatively affected when growth hormone excess is diagnosed in pediatric patients.