Practical application of the patient data-based quality control method: the potassium example.

Introduction: Internal quality control (IQC) is a core pillar of laboratory quality control strategies. Internal quality control commercial materials lack the same characteristics as patient samples and IQC contributes to the costs of laboratory testing. Patient data-based quality control (PDB-QC) may be a valuable supplement to IQC; the smaller the biological variation, the stronger the ability to detect errors. Using the potassium concentration in serum as an example study compared error detection effectiveness between PDB-QC and IQC. Materials and methods: Serum potassium concentrations were measured by using an indirect ion-selective electrode method. For the training database, 23,772 patient-generated data and 366 IQC data from April 2022 to September 2022 were used; 15,351 patient-generated data and 246 IQC data from October 2022 to January 2023 were used as the testing database. For both PDB-QC and IQC, average values and standard deviations were calculated, and z-score charts were plotted for comparison purposes. Results: Five systematic and three random errors were detected using IQC. Nine systematic errors but no random errors were detected in PDB-QC. The PDB-QC showed systematic error warnings earlier than the IQC. Conclusions: The daily average value of patient-generated data was superior to IQC in terms of the efficiency and timeliness of detecting systematic errors but inferior to IQC in detecting random errors.

Strengthening implementation research on social prescribing in mental healthcare for older adults in Western Pacific Region.

Aging population grows faster and has great demand for mental healthcare in the Western Pacific Region. Within the continuum of holistic care framework, mental healthcare for older adults is conceptualized to promote people's mental wellbeing, the "positive" states of mental health. As social determinants accounts much for mental health outcomes, addressing these factors may benefit older adults mental wellbeing in natural settings. Social prescribing, emerged as an innovative approach linking medical and social care, has been observed to potentially benefit mental wellbeing of older adults. However, it remained uncertain how to successfully implement social prescribing schemes in realistic world, such as community. In this viewpoint, we discuss three key elements, i.e., stakeholders, contextual factors, and outcome measures, that might facilitate identification of appropriate implementation strategies. Besides, we argue that implementation research needs to be strengthened and supported, aiming to accumulate evidence for scaling up social prescribing schemes to promote older adults mental wellbeing in the population level. We also provide directions for future implementation research on social prescribing for mental healthcare among older adults in the Western Pacific Region.

Wolfberry water extract attenuates blue light-emitting diode damage to ARPE-19 cells and mouse retina by activating the NRF2 signaling pathway.

The wolfberry is believed to improve eyesight in traditional Chinese medicine. Soaking wolfberry in thermos cups has become a common health-preserving practice. The object of this paper was to research the protective effects of wolfberry water extract (WWE) on oxidative injury induced by blue light-emitting diodes (LEDs) in ARPE-19 cells and C57BL/6J mice. Wolfberry water extract significantly increased cell viability, reduced ROS production, stabilized mitochondrial membrane potential, and inhibited apoptosis in blue LED-induced cells (P < 0.05). The protective effects of WWE against blue LED-induced cytotoxicity and ROS accumulation in cells were abolished by transfection with Nrf2 siRNA. In blue LED-exposed C57BL/6J mice, WWE treatment markedly increased the amplitudes of electroretinogram (ERG) waves a and b, increased the thickness of retinal outer nuclear layer (ONL), activated endogenous antioxidant enzymes, and decreased MDA levels in the retina and lens. WWE also promoted NRF2 translocation and the expression of the downstream genes Ho-1, Nqo1, Gclc, and Gclm in the retina. The protection of WWE in ERG a and b wave amplitudes and ROS levels were abrogated in Nrf2 knockout mice. These results suggested that WWE has beneficial effects on retinal injury induced by blue LED, and mechanisms of action at least partly via the NRF2 signaling pathway.

Purple sweet potato anthocyanin extract regulates redox state related to gut microbiota homeostasis in obese mice.

This study explored the advantageous effects of purple sweet potato anthocyanin extract (PSPAE) on redox state in obese mice. The normal chow diet (NCD) group, high-fat/cholesterol diet (HCD) group, and three groups based on HCD and added with low, middle, and high dose of PSPAE (PAL, PAM, and PAH) were raised for 12 weeks. High dose of PSPAE treatment decreased the elevations of the body weight by 24.7%, serum total cholesterol by 48.3%, serum triglyceride by 42.4%, and elevated serum activities of glutathione peroxidase by 53.3%, superoxide dismutase by 57.8%, catalase by 75.4%, decreased serum contents of malondialdehyde by 27.1% and lipopolysaccharides by 40.5%, as well as increased caecal total short-chain fatty acid by 2.05-fold. Additionally, PSPAE depressed toll-like receptor 4 (TLR-4), nuclear factor kappa-B (NF-κB), interleukin 6, tumor necrosis factor α, and preserved nuclear factor erythroid-2-related factor 2 (Nrf2) gene expression. Similarly, the protein expression of Nrf2 was enhanced, while TLR-4 and p-NF-κB/NF-κB were depressed by PSPAE treatment. Moreover, PSPAE administration promoted the protection of intestinal barrier function and rebuilt gut microbiota homeostasis by blooming g_Akkermansia, g_Bifidobacterium, and g_Lactobacillus. Furthermore, antibiotic interference experiments showed that the gut microbiota was indispensable for preserving the redox state of PSPAE. These results suggested that PSPAE administration could be an opportunity for improving HCD-induced obesity and the redox state related to gut dysbiosis. PRACTICAL APPLICATION: Purple sweet potato anthocyanin has diverse pharmacological properties. It is applicable for individuals to consume extracts (as pills or other forms) from raw purple sweet potato if they want to improve obesity or redox state.

Apple phlorizin attenuates oxidative stress in Drosophila melanogaster.

Apple phlorizin has a lot of applications owing to its antioxidant and hepatoprotective properties. This study explored the antioxidant effects and life span-prolonging activity of apple phlorizin in Drosophila melanogaster. Treatment with apple phlorizin was found to significantly extend the life span and ameliorate the age-related decline of locomotor function. This life span-extending activity was associated with the increased activity of superoxide dismutase, catalase, mRNA expression of glutamate-cysteine ligase catalytic subunit, cap-n-collar (cnc, homologue of mammalian Nrf2 gene), Keap1, and deacetylase sir2, as well as the downregulation of methuselah. Computational analysis suggested phlorizin could work as a Nrf2 activator and exert its biological activities by interfering with the Keap1 and Nrf2 binding. Therefore, it was concluded that the antioxidant and anti-aging effects of phlorizin might, at least in part, be mediated through the cooperation with the endogenous stress defense system. PRACTICAL APPLICATIONS: Phlorizin, from apple peel, has been used as a nutrient for over 100 years. To date, despite extensive research on phlorizin, a report on its effect on the antioxidant system in fruit flies is yet lacking. This report demonstrates that phlorizin can exert a protective effect on antioxidant issues and prolong life in fruit flies, which is valuable in the rational utilization of phlorizin in functional foods.

Dietary wood pulp-derived sterols modulation of cholesterol metabolism and gut microbiota in high-fat-diet-fed hamsters.

Evidence indicates that wood pulp-derived sterols (WS) have beneficial effects on cardiovascular diseases. The present study aimed to (i) investigate the serum cholesterol-lowering activity of dietary WS and (ii) investigate the effects of dietary WS on the balance of gut microbiota in hamsters fed with a high-fat diet. Thirty-six hamsters were divided into four groups fed on a normal chow diet (NCD), a high-fat diet (HFD), or HFD plus 0.1% or 0.5% wood pulp-derived sterols (WSL, WSH), respectively, for 6 weeks. Levels of serum total cholesterol, triglyceride, HDL-C, non-HDL-C, and non-HDL-C/HDL-C ratio in hamsters fed the NCD were originally 120.4 mg dL-1, 235.8 mg dL-1, 71.7 mg dL-1, 48.7 mg dL-1 and 0.68 mg dL-1, which were elevated by being fed the HFD to 187.7 mg dL-1, 389.5 mg dL-1, 92.3 mg dL-1, 95.3 mg dL-1 and 1.03 mg dL-1, and alleviated completely by being fed the WSH. The excretion of total fecal neutral sterols was dose-dependently increased with the amounts of dietary WS. Furthermore, dietary supplementation with WS modulated the relative abundance of gut microbiota compared with the HFD group. Spearman's correlation analysis revealed that Bacteroides, Allobaculum, Coprobacillus, Lactobacillus, Akkermansia, Coprococcus, and Oscillospira were correlated negatively with most of the serum metabolic parameters and cholesterol metabolic parameters, whereas Desulfovibrio was positively correlated with most of the lipid metabolism-associated parameters. Taken together, dietary supplementation with WS was found to have cholesterol-lowering activity, in part mediated by modulating the gut microbiota in a positive way and regulating the cholesterol absorption and metabolism-related genes.

Rosemary Extract-Mediated Lifespan Extension and Attenuated Oxidative Damage in Drosophila melanogaster Fed on High-Fat Diet.

Rosemary extract has a potent antioxidant activity and is widely used in the food industry. In this study, the lifespan prolonging and antioxidant activity of rosemary extract was evaluated by high-fat-induced oxidative damage in Drosophila melanogaster. The results revealed that the lifespan and climbing ability of fruit flies was enhanced significantly by feeding rosemary extract. Furthermore, feeding with rosemary extract significantly increased the enzyme activity of superoxide dismutase (SOD) and catalase (CAT), and significantly decreased the level of malonaldehyde. The gene expression of SOD, CAT, and nuclear factor erythroid-2 related factor 2 was enhanced and that for methuselah was significantly reduced. The comet assay showed that high-fat diet-induced DNA lesion was significantly reduced in larvae treated with the rosemary extract. Our results suggest that feeding with rosemary extract is effective to the extended lifespan in fruit flies by strengthening of the resistance to high-fat-induced oxidative stress and by stimulating, at least in part, the endogenous antioxidant response.

Epimedium polysaccharide and propolis flavone can synergistically inhibit the cellular infectivity of NDV and improve the curative effect of ND in chicken.

Four prescriptions, epimedium flavone plus propolis flavone (EF-PF), epimedium flavone plus propolis extracts (EF-PE), epimedium polysaccharide plus propolis flavone (EP-PF) and epimedium polysaccharide plus propolis extracts (EP-PE), were prepared and their antiviral effects were compared. In test in vitro, the four prescriptions within safety concentration scope and Newcastle disease virus (NDV) were added into cultured chick embryo fibroblast (CEF) in three modes, pre-, post-adding drug and simultaneous-adding drug and virus after being mixed, the cellular A(570) values were determined by MTT method and the highest virus inhibitory rates were calculated to compare the antiviral activity of four prescriptions. In test in vivo, three hundred 21-day-old chickens were randomly divided into 6 groups and challenged with NDV except for blank control group. After 24h the chickens in four prescription groups were injected with corresponding drugs respectively, in virus control and blank control groups, with physiological saline, once a day for three successive days. On days 3, 7 and 14 after challenge, the serum antibody titer was determined. On day 15 after challenge, the mortality, morbidity and cure rate in every group were counted. The results showed that the most of A(570) values in EP-PF group were numberly or significantly larger than those of the corresponding virus control group and the highest virus inhibitory rates of EP-PF at optimal concentration group were the highest among four prescription groups in three drug-adding modes, which confirmed that EP-PF could significantly inhibit the infectivity of NDV to CEF, its action was stronger than those of other three prescriptions; in EP-PF group, the antibody titers and cure rate were the highest and the mortality and morbidity were lowest presenting numberly or significantly differences in comparison with other three prescription groups. These results indicated that epimedium polysaccharide and propolis flavone possessed synergistical action, EP-PF prescription could significantly inhibit the cellular infectivity of NDV, improve the curative effect of ND in chicken and would be expected to exploit into a new-type antiviral drug.

Hepatic sinusoidal obstruction syndrome associated with consumption of Gynura segetum.

BACKGROUND & AIMS: One major cause of hepatic sinusoidal obstruction syndrome (HSOS) is the intake of pyrrolizidine alkaloid (PA)-containing products. Over 8000 PA-induced HSOS cases have been reported worldwide and at least 51 among them were suspected to be attributed to exposure to the Chinese medicine 'Tusanqi'. PA-induced hepatotoxicity involves cytochrome P450-mediated metabolic activation of PAs to electrophilic pyrrolic metabolites which react with macromolecules, such as proteins. However, no studies have found such protein adduction in HSOS patients. We report one HSOS case confirmed by liver biopsy, where the patient claimed taking 'Tusanqi' as self-medication. METHODS: The herb was analyzed by HPLC-MS, and its induced hepatotoxicity in rats was assessed by monitoring the alteration of serum ALT level and liver morphology. Blood pyrrole-protein adducts were determined by UPLC-MS. RESULTS: The herb the patient consumed was identified as Gynura segetum, an erroneous substitute of non-PA-containing Sedum aizoon, called 'Tusanqi'. Hepatotoxic PAs senecionine and seneciphylline were detected in G. segetum. In the PA-exposed patient, serum pyrrole-protein adducts were detected by a newly developed analytical approach. The animal study showed a good correlation of liver injury with the ingestion of G. segetum. CONCLUSIONS: For the first time, serum pyrrole-protein adducts were unequivocally detected in a PA-induced HSOS patient, and such adducts show a potential to be developed as a biomarker for the assessment of PA-induced HSOS. Similar to the well-known case of aristolochic acid-poisoning, the observed HSOS was confirmed to arise from the consumption of PA-containing G. segetum, an erroneous substitute of non-PA-containing S. aizoon.

[Chinese medicinal monomer and compound for 60Co-gamma-induced spermatogenic disturbance in mice].

OBJECTIVE: To explore the effects of the monomer and compound of the Chinese herbal drugs resveratrol, lycium barbarum polysaccharide (LBP) and icariin on 60Co-gamma-induced spermatogenic disturbance in mice based on the theory of modern Chinese medicine. METHODS: A total of 105 male Kunming mice were randomly divided into seven groups, with 15 in each. Group A were normally raised and Groups B, C, D, E, F and G irradiated by 60Co-gamma 6 Gy followed by 60Co-gamma 4 Gy at the interval of 7 days. A week later, Groups C, D, E, F and G received intragastrically the suspension of resveratrol, resveratrol + LBP, resveratrol + icariin, resveratrol + LBP + icariin and resveratrol + LBP + icariin + L-carnitine, respectively, at the dose of 80 mg/(kg x d) for 60 days. The general condition, physical signs and body weight changes of the mice were recorded, and 24 hours after the intragastric medication, their testes were harvested to obtain the testicular weight and indexes, the levels of FSH, LH, T and E2 determined by ELISA, the T/E2 ratio calculated, and the histology of the testis tissues observed under the microscope. RESULTS: The testicular indexes of the mice were decreased by radiation-induced damage, but restored to some extent after intragastric medication, especially in Groups E, F and G. The levels of FSH, LH and T were obviously improved by LBP. The T level and testis weight were increased by Icariin. The level of T/E2 was elevated in Groups E, F and G. The best results were achieved in Group F, which exhibited almost complete recovery from reproductive endocrine disorder and spermatogenic damage. CONCLUSION: The Chinese medicinal monomer is effective for 60Co-gamma-induced spermatogenic disturbance in mice, and the compound suspension of resveratrol + LBP + icariin produces the best result.

Further insight into the impact of sodium selenite on selenoenzymes: high-dose selenite enhances hepatic thioredoxin reductase 1 activity as a consequence of liver injury.

Selenium (Se) at supranutritional levels can enhance the activity of glutathione S-transferase (GST), whose gene is a target of nuclear factor erythroid-2 related factor 2 (Nrf2). Recent studies indicated that the thioredoxin reductase 1 (TrxR1) gene could also be targeted by Nrf2. Thus, high-dose Se may stimulate TrxR1 provided it enhances GST activity. Indeed, one study found that Se at supranutritional levels transiently increased hepatic TrxR1 activity. However, another study reported that supranutritional Se had no such effect on hepatic TrxR1 activity. In view of this discrepancy, the present research investigated whether high-dose Se has any impact on hepatic TrxR1. Moreover, we investigated whether Se preferentially activates GST over TrxR1. We observed that when sodium selenite (SS) caused liver injury, both hepatic TrxR1 activity and hepatic GST activity increased. Further experiments indicated that SS increased hepatic GST activity at either toxic or high but non-toxic dose levels; however, increase in hepatic TrxR1 activity occurred only at toxic levels, suggesting that enhanced TrxR1 activity correlates with liver injury. To corroborate this, we showed that hepatotoxic agents, thioacetamide or carbon tetrachloride, caused marked increases in hepatic TrxR1 activity. In conclusion, high-dose SS indeed can enhance hepatic TrxR1 activity, but only on the condition that it causes liver injury. High-dose SS affects hepatic GST more readily than hepatic TrxR1. Thus, the cancer-preventive mechanism of Se at non-toxic supranutritional levels relies more on its modulation of GST rather than TrxR1, at least in liver tissue.

Thioacetamide-induced cirrhosis in selenium-adequate mice displays rapid and persistent abnormity of hepatic selenoenzymes which are mute to selenium supplementation.

Selenium reduction in cirrhosis is frequently reported. The known beneficial effect of selenium supplementation on cirrhosis is probably obtained from nutritionally selenium-deficient subjects. Whether selenium supplementation truly improves cirrhosis in general needs additional experimental investigation. Thioacetamide was used to induce cirrhosis in selenium-adequate and -deficient mice. Selenoenzyme activity and selenium content were measured and the influence of selenium supplementation was evaluated. In Se-adequate mice, thioacetamide-mediated rapid onset of hepatic oxidative stress resulted in an increase in thioredoxin reductase activity and a decrease in both glutathione peroxidase activity and selenium content. The inverse activity of selenoenzymes (i.e. TrxR activity goes up and GPx activity goes down) was persistent and mute to selenium supplementation during the progress of cirrhosis; accordingly, cirrhosis was not improved by selenium supplementation in any period. On the other hand, selenium supplementation to selenium-deficient mice always more efficiently increased hepatic glutathione peroxidase activity and selenium content compared with those treated with thioacetamide, indicating that thioacetamide impairs the liver bioavailability of selenium. Although thioacetamide profoundly affects hepatic selenium status in selenium-adequate mice, selenium supplementation does not modify the changes. Selenium supplementation to cirrhotic subjects with a background of nutritional selenium deficiency can improve selenium status but cannot restore hepatic glutathione peroxidase and selenium to normal levels.

Elemental selenium at nano size possesses lower toxicity without compromising the fundamental effect on selenoenzymes: comparison with selenomethionine in mice.

Glutathione peroxidase and thioredoxin reductase are major selenoenzymes through which selenium exerts powerful antioxidant effects. Selenium also elicits pro-oxidant effects at toxic levels. The antioxidant and pro-oxidant effects, or bioavailability and toxicity, of selenium depend on its chemical form. Selenomethionine is considered to be the most appropriate supplemental form due to its excellent bioavailability and lower toxicity compared to various selenium compounds. The present studies reveal that, compared with selenomethionine, elemental selenium at nano size (Nano-Se) possesses equal efficacy in increasing the activities of glutathione peroxidase and thioredoxin reductase but has much lower toxicity as indicated by median lethal dose, acute liver injury, and short-term toxicity. Our results suggest that Nano-Se can serve as an antioxidant with reduced risk of selenium toxicity.

Comparison of short-term toxicity between Nano-Se and selenite in mice.

We previously reported that, as compared with selenite, nano red elemental selenium (Nano-Se) had lower acute toxicity in mice and similar bioavailability in terms of up-regulating seleno-enzymes. The short-term toxicity of both selenite and Nano-Se in mice was further compared in this study. At an oral dose of 6 mg/kg bw per day administered for consecutive 12 days, selenite and Nano-Se completely and partially suppressed mice growth respectively. Abnormal liver function was more pronounced with selenite treatment than Nano-Se as indicated by the increase of both alanine aminotransferase and aspartate aminotransferase in serum. Selenite inhibited liver catalase and superoxide dismutase activities, whereas, Nano-Se did not affect these two antioxidant enzymes. Selenite increased the malondialdehyde content of liver, but Nano-Se decreased it. Both Se forms had similar effects on depletion of reduced glutathione and up-regulated glutathione peroxidase. Nano-Se was more potent than selenite in the induction of glutathione S-transferase. At oral doses of 2 or 4 mg/kg bw per day for consecutive 15 days, selenite was more active than Nano-Se in supressing growth, deleting reduced glutathione, and inhibiting superoxide dismutase activities. Taken together, these results indicate that over a short-term, a high-dose of selenite caused more pronounced oxidative stress, greater liver injury, and prominent retardation of growth as compared to Nano-Se.

Nano red elemental selenium has no size effect in the induction of seleno-enzymes in both cultured cells and mice.

We previous reported that a nano red elemental selenium (Nano-Se) in the range from 20 approximately 60 nm had similar bioavailability to sodium selenite (BioFactors 15 (2001) 27). We recently found that Nano-Se with different size had marked difference in scavenging an array of free radicals in vitro, the smaller the particle, the better scavenging activity (Free Radic. Biol. Med. 35 (2003) 805). In order to examine whether there is a size effect of Nano-Se in the induction of Se-dependent enzymes, a range of Nano-Se (5 approximately 200 nm) have been prepared based on the control of elemental Se atom aggregation. The sizes of Nano-Se particles were inversely correlated with protein levels in the redox system of selenite and glutathione. Different sizes of red elemental Se were prepared by adding varying amount of bovine serum albumin (BSA). Three different sizes of Nano-Se (5 approximately 15 nm, 20 approximately 60 nm, and 80 approximately 200 nm) have been chosen for the comparison of biological activity in terms of the induction of seleno-enzyme activities. Results showed that there was no significant size effect of Nano-Se from 5 to 200 nm in the induction of glutathione peroxidase (GPx), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and thioredoxin reductase-1 (TrxR-1) in human hepatoma HepG2 cells and the livers of mice.