Correlation analysis of peripheral platelet markers and disease phenotypes in Alzheimer's disease.

INTRODUCTION: Platelets serve as the primary peripheral reservoir of amyloid beta (Aß). However, there is limited research on platelet markers in routine blood examinations, particularly with regard to the large platelet ratio (P-LCR) in Alzheimer's disease (AD). METHODS: This study included 512 AD patients and 205 healthy controls (HCs). Platelet markers and apolipoprotein E (APOE) 4 status were assessed in all participants. RESULTS: The study revealed that P-LCR was significantly elevated in AD patients compared to HCs. In AD patients carrying APOE4, P-LCR significantly negatively correlated with Montreal Cognitive Assessment scores. There was an observed increasing trend in the rate of change in P-LCR with disease progression. Binary logistic regression analysis indicated that P-LCR may constitute a risk factor for AD, after adjusting for age, sex, APOE4, and body mass index. DISCUSSION: P-LCR is associated with disease severity in AD patients carrying APOE4. P-LCR may be a promising marker to reflect platelet activity in AD patients. HIGHLIGHTS: P-LCR significantly negatively correlated with MoCA scores in AD patients with APOE4. The rate of change in P-LCR showed an increasing trend with disease progression. P-LCR may be a risk factor for AD.

Effects of Lactobacillus fermentum HY01 on the quality characteristics and storage stability of yak yogurt.

Lactobacillus fermentum HY01 is a probiotic strain screened from traditional yak yogurt, which can effectively relieve enteritis and constipation. This study aimed to evaluate the effects of HY01 as an adjunct starter on the quality and storage of yak yogurt. A total of 36 main volatile flavor substances were detected in all samples. In particular, more aldehydes, esters, and alcohols were detected in yak yogurt prepared by mixed fermentation of L. fermentum HY01 and starter MY105 (including Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus). The rheological results showed that the yak yogurt prepared by mixed fermentation of L. fermentum HY01 and starter MY105 had higher apparent viscosity and lower tan δ value compared with compared with traditional yak yogurt, yak yogurt with only L. fermentum HY01, and cow yogurt with L. fermentum HY01 and starter MY105. Meanwhile, the conjugated linoleic acid in the yak yogurt prepared by mixed fermentation of L. fermentum HY01 and starter was significantly higher than those in the HY01 group or the yogurt starter group alone. After 28 d of storage at 4°C, the number of HY01 in the yak yogurt prepared by mixed fermentation of L. fermentum HY01 and starter was still higher than 107 cfu/mL, its acidity was lower than 110°T, and its syneresis was the lowest. The results indicated that L. fermentum HY01 could improve the flavor, texture, and storage properties of yak yogurt.

Expression of eosinophil in peripheral blood of patients with COVID-19 and its clinical significance.

AIMS: To investigate the eosinophil cell (EC) expression in peripheral blood of patients infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) and its clinical significance of diagnosis and prognosis. METHODS: 95 patients, whose nucleic acid test of SARS-CoV-2 was positive to make a definite diagnosis of COVID-19, were selected as the study group. They were admitted at the Chengdu Public Health Clinical Medical Center from January 21 to March 2, 2020. Another 95 healthy subjects and 95 non-infectious fever patients during the same period were selected as the control group. The BC-6900 blood cell analyzer was used to continuously observe and detect ECs in 95 patients with COVID-19 and the control group. The differences in expression levels of ECs in peripheral blood were analyzed. RESULTS: ECs were significantly decreased in 95 (75.8%) COVID-19 patients (P < .01). The absolute EC count IQR was 0.01 × 109/L (0 × 109/L - 0.04 × 109/L), and the EC percentage IQR was 0.3% (0.1% - 0.8%). As the patients' condition improved, the ECs returned to normal, but for those without improvement, ECs continued to decline. CONCLUSIONS: ECs decreased remarkably in patients with COVID-19, and gradually returned to normal after the improvement of the patients' condition, while EC continued to decrease in patients without improvement. It is suggested that ECs have certain clinical significance in the diagnosis and prognosis of COVID-19, and may be a useful index in the early warning of acute infectious diseases.

Long-term survival of femoral neck fracture patients aged over ninety years: Arthroplasty compared with nonoperative treatment.

BACKGROUND: The aging of the Chinese population is expected to lead to an increase in nonagenarians and centenarians. The mortality rate in nonagenarian hip fracture patients is equivalent to the mortality rate in the average population at 5 years after injury. It is imperative to evaluate 5-year mortality in this small but very challenging subgroup of patients to optimize patient management. The primary purpose of the current retrospective study was to compare five-year survival in patients aged over 90 years who received arthroplasty or nonoperative treatment for femoral neck fracture during a 16-year period. METHODS: From January 1998 to December 2014, all consecutive nonagenarian and centenarian patients with femoral neck fracture admitted to our hospital were included in the evaluation. The primary outcome was defined as thirty-day, 1-year, 3-year, and 5-year mortality after injury. Survival analysis was performed with the Kaplan-Meier method. Using the log-rank test, stratified analyses were performed to compare differences in the overall cumulative mortality and mortality at three time points (1 year, 3 years, and 5 years) after injury and differences in survival distributions. RESULTS: Over the 16-year study period, the arthroplasty group and the nonoperative treatment group included 33 and 53 patients, respectively. The long-term survival probability of the arthroplasty group was significantly higher than that of the nonoperative treatment group (p = 0.002). The survival time of the arthroplasty group was significantly higher than that of the nonoperative treatment group (median (P75-P25) = 53 (59) versus median (P75-P25) = 22 (52), p = 0.001). The mortality differences, except for 30-day mortality, at five time points (1, 2, 3, 4, and 5 years) between the nonoperative group and arthroplasty group were significant. The stratified analyses of overall cumulative mortality and mortality at three time points (1, 3, and 5 years) after injury demonstrated that the nonoperative treatment group had significantly higher cumulative mortality than the arthroplasty group. CONCLUSIONS: Our study demonstrates that arthroplasty is more likely to improve long-term survival in femoral neck fracture patients aged over 90 years than nonoperative treatment. It can be expected that nearly half of patients will survive more than 5 years after surgery.

[Effects of Danqi Capsule on Platelet Function in Healthy People].

OBJECTIVES: To study the effects of Danqi Capsule on platelet function in healthy people. METHODS: Sixteen healthy volunteer were divided into low dose (4 capsules/time, 3 times/d) and high dose group (6 capsules/time, 3 times/d), and received Danqi Capsule by orally administration for 2 weeks. The venous blood were collect at 3 time points: one week before taking Danqi Capsule (control), one week after taking Danqi Capsule (1 week), two week after taking Danqi Capsule (2 weeks). Blood samples were used for the measurements of conventional coagulation examination, complete blood count, liver and kidney function test, platelet aggregation test, the plasma levels of P-selectin and von Willebrand factor (vWF) , and maximum aggregation (MA). RESULTS: In both dosage group, Danqi capsule(1 week/2 weeks) administration showed no difference in conventional coagulation examination, complete blood count, liver and kidney function test, or the plasma level of vWF ( P>0.05), but showed difference (decreased) in platelet aggregation test and the plasma level of P-selectin (vs. control, P<0.05). CONCLUSIONS: Danqi Capsule inhibits platelet activation and platelet aggregation, but not affects the plasma level of vWF, the coagulation function or the hepatorenal function in normal subjects.

Mannitol-adenine-phosphate: a novel solution for intraoperative blood salvage.

BACKGROUND: Intraoperative blood salvage (IBS) procedures include washing with normal saline (NS), which may deplete red blood cell (RBC) nutrients. The mannitol-adenine-phosphate (MAP) solution, commonly used for RBC preservation, provides glycolytic substrates; therefore, MAP should be a better solution than NS in IBS. In this study, we determined whether using MAP could reduce washing-associated RBC damage and destruction. STUDY DESIGN AND METHODS: Adenine nucleotide contents, RBC morphology, and plasma free hemoglobin (PF-Hb) level of RBCs treated with NS or MAP solution were compared under three conditions: (1) 4-hour preservation of fresh blood from healthy volunteers, (2) collection from the shed blood of patients, and 3) incubation of the collected shed blood with plasma. RESULTS: Adenine nucleotide level and RBC elongation index were greater and PF-Hb level was lower in MAP groups than NS groups (p < 0.05) after preservation and incubation. In NS, RBCs lost their deformability and became stomatocytes, and even RBC "ghosts" 48 hours after incubation, while they remained normal in MAP solution. CONCLUSION: The MAP solution helps preserve RBC morphology and function, and reduces hemolysis, possibly due to improved energy production. Therefore, MAP should replace NS during IBS.

Long-term leukocyte filtration should be avoided during extracorporeal circulation.

Filtration during extracorporeal circulation (ECC) not only removes but also activates leukocytes; therefore, long-term leukocyte filtration may cause adverse effects. In the present study, we tested this hypothesis by priming ECC with 300 mL of canine blood and examining filtration effects in 3 groups (n = 6 each) during 60 min ECC. In the control group (Group C) blood was filtrated with an arterial filter for 60 min; in long-term (Group L) and short-term (Group S) groups, blood was filtrated with a leukocyte filter for 60 and 5 min. We found that about 90% of leukocytes were removed after 5 min of filtration in both Groups L and S. Although leukocyte count continued to reduce, mean fluorescent intensities of CD11/CD18, free hemoglobin, and neutrophil elastase increased in Group L and were higher than those in Groups C and S at 60 min. Leukocyte rupture, cytoplasmic leakage, and circulating naked nuclei were also found in Group L. The data support our hypothesis that long-term filtration can induce inflammation and lead to leukocyte destruction.

A mathematical algorithm to harmonize measurements for thyroid-stimulating hormone between instruments.

BACKGROUND: Thyroid-stimulating hormone (TSH) is measured differently between diagnostic units using different devices, which makes cross-comparisons challenging. Here, we have developed a mathematical algorithm to harmonize TSH measurements between 2 instruments, the Abbott ISR2000 and the Siemens ADVIA Centaur XP. METHODS: Applying the principle of the maximum allowable error between the standard curve and real signal values, the minimum number of comparison samples required for TSH hormone detection was calculated for both instruments. Next, a mathematical algorithm describing the relationship between TSH standard curves from both instruments was established. The algorithm was then tested on sample measurements from both instruments, with signals transformed to Siemens ADVIA Centuar XP-type data. Finally, test results were assessed where the relative error was 1/2 TEa). After algorithmic transformation, the average percentage error was reduced to 7.93% (<1/2 TEa). CONCLUSIONS: Our algorithm enables TSH measurements across different instruments to be comparable, and provides a method to harmonize TSH data between laboratories that utilize different instrumentation.

Isolation of circulating exosomes and identification of exosomal PD-L1 for predicting immunotherapy response.

Exosomes, a subgroup of extracellular vesicles secreted by multiple cells, have great potential as cancer biomarkers in clinical applications. However, enrichment and detection of exosomes from complex media remain a huge challenge due to their small size. Herein, we used iodixanol density gradient centrifugation for the isolation and purification of exosomes and label-free detection of exosomal PD-L1 using a biochip based on surface plasmon resonance (SPR-ExoPD-L1). The obtained exosomes are lipid-bilayer vesicles and the classical exosome markers CD9, CD63 and CD81 are highly enriched. Besides, PD-L1 is specifically expressed on exosomes instead of non-vesicular components or large extracellular vesicles. Compared with enzyme-linked immunosorbent assays, the SPR-ExoPD-L1 assay could better distinguish exosomes derived from melanoma cells with different levels of PD-L1. Accurate measurement of exosomal PD-L1 could provide critical clinical information for cancer diagnosis and personalized immunotherapy of cancer.

Design, synthesis and biological evaluation of 3-aryl-7-hydroxy scopoletin derivatives as autophagy activators against tumorigenesis.

A natural product scopoletin, which also contains an ortho-substituted phenolic structure in its skeleton, was found in some medicinal plants. In this study, to develop scopoletin-based autophagy activators, various aryl substitutes were introduced at the 3-positon or 4-position of scopoletin skeleton with the ortho-substituted phenolic structure retained. A total of twenty-three derivatives were synthesized, evaluated for their antiproliferation activity against four cancer cells (MCF-7, HeLa, PC3, and MGC803), and discussed for their structure-activity relationships (SARs). Among these derivatives, 5c was the most potent compound with an excellent improvement of antiproliferation activity against PC3 and MGC803 cells compared to the parental scopoletin. 5c displayed up to 17.9- and 5.7-fold improvement of antiproliferation activities against PC3 and MGC803 cells compared to 5-FU (IC50 = 0.14 µM vs IC50 = 2.50 µM, IC50 = 1.02 µM vs IC50 = 5.81 µM), respectively. Moreover, 5c showed excellent selectivity between cancer cells and one normal cell (GES-1). Further mechanism investigations confirmed that 5c inhibited PC3 and MGC803 cell proliferation via inducing autophagy. Interestingly, 5c also induced mitochondria-mediated apoptosis in PC3 cells but not in MGC803 cells. Moreover, 5c possessed the ability to suppress colony formation and migration of PC3 and MGC803 cells. In addition, 5c arrested the cell cycle at the G2/M phase of PC3 cells.

Combining initial chest CT with clinical variables in differentiating coronavirus disease 2019 (COVID-19) pneumonia from influenza pneumonia.

Coronavirus disease 2019 (COVID-19) has spread in more than 100 countries and regions around the world, raising grave global concerns. COVID-19 has a similar pattern of infection, clinical symptoms, and chest imaging findings to influenza pneumonia. In this retrospective study, we analysed clinical and chest CT data of 24 patients with COVID-19 and 79 patients with influenza pneumonia. Univariate analysis demonstrated that the temperature, systolic pressure, cough and sputum production could distinguish COVID-19 from influenza pneumonia. The diagnostic sensitivity and specificity for the clinical features are 0.783 and 0.747, and the AUC value is 0.819. Univariate analysis demonstrates that nine CT features, central-peripheral distribution, superior-inferior distribution, anterior-posterior distribution, patches of GGO, GGO nodule, vascular enlargement in GGO, air bronchogram, bronchiectasis within focus, interlobular septal thickening, could distinguish COVID-19 from influenza pneumonia. The diagnostic sensitivity and specificity for the CT features are 0.750 and 0.962, and the AUC value is 0.927. Finally, a multivariate logistic regression model combined the variables from the clinical variables and CT features models was made. The combined model contained six features: systolic blood pressure, sputum production, vascular enlargement in the GGO, GGO nodule, central-peripheral distribution and bronchiectasis within focus. The diagnostic sensitivity and specificity for the combined features are 0.87 and 0.96, and the AUC value is 0.961. In conclusion, some CT features or clinical variables can differentiate COVID-19 from influenza pneumonia. Moreover, CT features combined with clinical variables had higher diagnostic performance.

Platelet-leukocyte aggregate is associated with adverse events after surgical intervention for rheumatic heart disease.

Platelet-leukocyte aggregate (PLA) is implicated in the etiology of both vascular lesions and cardiovascular events. This prospective cohort study aimed to examine the prognostic value of PLA for major adverse cardiac and cerebrovascular events (MACCE) and perioperative adverse events (AEs) in patients with rheumatic heart disease undergoing surgical intervention by Cox proportional hazard regression and logistic regression. A total of 244 patients were included, of whom 7 were lost to follow-up. Among the analyzed 237 subjects who completed 3-year follow-up, 30 experienced MACCE and 38 experienced perioperative AEs. Preoperative PLA was higher in subjects who developed MACCE (13.32%) than in those who did not (8.69%, p = 0.040). In multivariate regression, elevated PLA was associated with increased MACCE (hazard ratio 1.51 for each quartile, 95% CI 1.07-2.13; p = 0.020), and perioperative AEs (odds ratio 1.61, 95% CI 1.14-2.26; p = 0.007). The optimal PLA cut-off for predicting MACCE was 6.8%. Subjects with PLA > 6.8% had a higher prevalence of MACCE (17.1% vs. 5.5%, p = 0.009) and perioperative AEs (19.9% vs. 8.6%, p = 0.018). Kaplan-Meier analysis showed shorter MACCE-free survival in patients with PLA > 6.8% (p = 0.007, log rank). Elevated preoperative PLA is associated with increased MACCE and perioperative AEs in patients with rheumatic valve disease undergoing surgical intervention.

Protective effects of hyperoside (quercetin-3-o-galactoside) to PC12 cells against cytotoxicity induced by hydrogen peroxide and tert-butyl hydroperoxide.

Reactive oxygen species are believed to play a very significant role in the pathogenesis of several diseases including Alzheimer's disease and Parkinson's disease. It is reported that the crucial balance between reactive oxygen species generation and antioxidant defense is regarded as a force in a wide variety of chronic diseases. In this paper, PC12 cells were used to study the antioxidative effect of hyperoside. The results indicated that hyperoside could effectively protect PC12 cells against cytotoxicity induced by hydrogen peroxide and tert-butyl hydroperoxide at 160 microg/ml and 100 microg/ml, respectively. The study also showed that hyperoside was no harmful within the tested concentration range and could easily enter into the PC12 cells. With the increasing concentration of hyperoside, cytotoxicity induced by hydrogen peroxide and tert-butyl hydroperoxide was significantly attenuated and the corresponding extracellular lactate dehydrogenase levels decreased concurrently by pretreatment with hyperoside. The results were proved by flow cytometric detection of apoptotic cells. All the above results showed hyperoside could efficiently prevent the PC12 cells from shrinking and turning against apoptosis induced by hydrogen peroxide and tert-butyl hydroperoxide.

Is there a role of TNFR1 in acute lung injury cases associated with extracorporeal circulation?

The signaling pathway for tumor necrosis factor-α (TNF-α) and its receptors is up-regulated during extracorporeal circulation (ECC), and recruits blood neutrophil into the lung tissue, which results in acute lung injury (ALI). In this study, we evaluated the role of tumor necrosis factor receptor 1 (TNFR1) in ECC-induced ALI by blocking TNF-α binding to TNFR1 with CAY10500. Anesthetized Sprague-Dawley (SD) rats were pretreated intravenously with phosphate buffered saline (PBS) or vehicle (0.3 ml ethanol IV) or CAY10500, and then underwent ECC for 2 h. The oxygenation index (OI) and pulmonary inflammation were assessed after ECC. OI was significantly decreased, while TNF-α and neutrophil in bronchoalveolar lavage fluid (BALF) and plasma TNF-α increased after ECC. Pretreatment of CAY10500 decreased plasma TNF-α level, but did not decrease TNF-α levels and neutrophil counts in BALF or improve OI. Lung histopathology showed significant alveolar congestion, infiltration of the leukocytes in the airspace, and increased thickness of the alveolar wall in all ECC-treated groups. CAY10500 pretreatment slightly reduced leukocyte infiltration in lungs, but did not change the wet/dry ratio in the lung tissue. Blocking TNF-α binding to TNFR1 by CAY10500 intravenously slightly mitigates pulmonary inflammation, but cannot improve the pulmonary function, indicating the limited role of TNFR1 pathway in circulating inflammatory cell in ECC-induced ALI.

Tyrosinase inhibitory effects and inhibition mechanisms of nobiletin and hesperidin from citrus peel crude extracts.

The inhibitory effects of nobiletin and hesperidin from citrus peel crude extracts on tyrosinase diphenolase activity have been evaluated. IC50 of nobiletin and hesperidin were 1.49 mM and 16.08 mM, respectively and their inhibition mechanisms are competitive type with inhibition constant (Ki) 2.82 mM and noncompetitive type with Ki 9.16 mM, respectively. Crude extracts from citrus peel (C. unshiu Marc.) were extracted with 95% ethanol and fractionated by petroleum ether (PCPE). The ethanol phase (ECPE) was further desorbed from macroporous adsorption resin (FGRE). Their IC50 values were 8.09 mg/mL, 7.53 mg/mL and 4.80 mg/mL, respectively. Their inhibition of melanogenesis in B16 mouse melanoma cells was also evaluated. FGRE showed a significant inhibition (42.48% at 31.25 microg/mL, p < 0.01) while hesperidin showed almost no inhibition. Nobiletin and PCPE gave efficacious antiproliferation effects on the B16 mouse melanoma cell with IC50 values 88.6 microM and 62.96 microg/mL, respectively, through the MTT test. Hesperidin and other crude extracts showed very low cytotoxity to the B16 cell.

Tyrosinase inhibitory effects and inhibition mechanisms of nobiletin and hesperidin from citrus peel crude extracts.

The inhibitory effects of nobiletin and hesperidin from citrus peel crude extracts on tyrosinase diphenolase activity are evaluated. IC50 of nobiletin and hesperidin is 1.49 mM and 16.08mM, respectively and their inhibition mechanism is competitive type with Ki = 2.82 mM and noncompetitive with Ki = 9.16 mM, respectively. Crude extracts from citrus peel (C. unshiu Marc.) were extracted with 95% ethanol and fractionated by petroleum ether (PCPE). The ethanol phase (ECPE) was further desorbed from macroporous adsorption resin (FGRE). Their IC50 values were 8.09 mg/mL, 7.53 mg/mL and 4.80 mg/mL, respectively. Their inhibition on melanogenesis in B16 mouse melanoma cells was also evaluated. FGRE showed a significant inhibition (42.5% at 31.25 microg/mL, p < 0.01) while hesperidin showed almost no inhibition. Nobiletin and PCPE give efficacious antiproliferation effects on B16 mouse melanoma cell with IC50 values 88.6 microM and 62.96 microg/mL, respectively, by the MTT test. Hesperidin and other crude extracts showed very low cytotoxity to the B16 cell.

Citrus flavonoids in fruit and traditional Chinese medicinal food ingredients in China.

Flavonoids-enriched tissues of citrus such as peel, immature fruit and flower are consumed as culinary seasonings, tea ingredients in China for centuries. This HPLC quantitative study on the five citrus flavonoids, naringin, hesperidin, neohesperidin, sinensetin and nobiletin on a wide range of Chinese citrus fruits and several Traditional Chinese Medicinal food ingredients in East China, revealed a great diversity in flavonoid composition. Huyou peel (C. paradisi cv. Changshanhuyou) was found to be the best naringin (3.25%) and neohesperidin (2.76%) source; C. aurantium, a major ingredient of several citrus-related TCM, is also a suitable source of naringin and neohesperidin, and a good juice source for flavanone glycosides; the peel of Wenzhoumiju (C. unshiu) is one of the richest local species in hesperidin (up to 6.25%); Zaoju (C. subcompressa) has the highest content of nobiletin (0.59%), a polymethoxylated flavone. LC-ES-MS analysis of Zanthoxylum genus for flavonoids revealed for the first time the presence of significant amounts (0.74%) of hesperidin in the root of Liangmianzhen (Z. nitidum (Roxb.) DC), a relative of Sichuan pepper, which is a spice widely used in China.