Associations of liver dysfunction with incident dementia, cognition, and brain structure: A prospective cohort study of 431 699 adults.

The relationship between liver dysfunction and dementia has been researched extensively but remains poorly understood. In this study, we investigate the longitudinal and cross-sectional associations between liver function and liver diseases and risk of incident dementia, impaired cognition, and brain structure abnormalities using Cox proportion hazard model and linear regression model. 431 699 participants with a mean of 8.65 (standard deviation [SD] 2.61) years of follow-up were included from the UK Biobank; 5542 all-cause dementia (ACD), 2427 Alzheimer's disease (AD), and 1282 vascular dementia (VaD) cases were documented. We observed that per SD decreases in alanine transaminase (ALT; hazard ratio [HR], 0.917; PFDR <0.001) and per SD increases in aspartate aminotransferase (AST; HR, 1.048; PFDR = 0.010), AST to ALT ratio (HR, 1.195; PFDR <0.001), gamma-glutamyl transpeptidase (GGT; HR, 1.066; PFDR <0.001), alcoholic liver disease (ALD; HR, 2.872; PFDR <0.001), and fibrosis and cirrhosis of liver (HR, 2.285; PFDR = 0.002), being significantly associated with a higher risk of incident ACD. Restricted cubic spline models identified a strong U-shaped association between Alb and AST and incident ACD (Pnonlinear <0.05). Worse cognition was positively correlated with AST, AST to ALT ratio, direct bilirubin (DBil), and GGT; negatively correlated with ALT, Alb, and total bilirubin (TBil); and ALD and fibrosis and cirrhosis of liver (PFDR <0.05). Moreover, changes in ALT, GGT, AST to ALT ratio, and ALD were significantly associated with altered cortical and subcortical regions, including hippocampus, amygdala, thalamus, pallidum, and fusiform (PFDR <0.05). In sensitivity analysis, metabolic dysfunction-associated steatotic liver disease (MASLD) was associated with the risk of ACD and brain subcortical changes. Our findings provide substantial evidence that liver dysfunction may be an important factor for incident dementia. Early intervention in the unhealthy liver may help prevent cognitive impairment and dementia incidence.

Associations between liver function and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in non-demented adults: The CABLE study.

Liver function has been suggested as a possible factor in the progression of Alzheimer's disease (AD) development. However, the association between liver function and cerebrospinal fluid (CSF) levels of AD biomarkers remains unclear. In this study, we analyzed the data from 1687 adults without dementia from the Chinese Alzheimer's Biomarker and LifestylE study to investigate differences in liver function between pathological and clinical AD groups, as defined by the 2018 National Institute on Aging-Alzheimer's Association Research Framework. We also examined the linear relationship between liver function, CSF AD biomarkers, and cognition using linear regression models. Furthermore, mediation analyses were applied to explore the potential mediation effects of AD pathological biomarkers on cognition. Our findings indicated that, with AD pathological and clinical progression, the concentrations of total protein (TP), globulin (GLO), and aspartate aminotransferase/alanine transaminase (ALT) increased, while albumin/globulin (A/G), adenosine deaminase, alpha-L-fucosidase, albumin, prealbumin, ALT, and glutamate dehydrogenase (GLDH) concentrations decreased. Furthermore, we also identified significant relationships between TP (ß = -0.115, pFDR < 0.001), GLO (ß = -0.184, pFDR < 0.001), and A/G (ß = 0.182, pFDR < 0.001) and CSF ß-amyloid1-42 (Aß1-42 ) (and its related CSF AD biomarkers). Moreover, after 10 000 bootstrapped iterations, we identified a potential mechanism by which TP and GLDH may affect cognition by mediating CSF AD biomarkers, with mediation effect sizes ranging from 3.91% to 16.44%. Overall, our results suggested that abnormal liver function might be involved in the clinical and pathological progression of AD. Amyloid and tau pathologies also might partially mediate the relationship between liver function and cognition. Future research is needed to fully understand the underlying mechanisms and causality to develop an approach to AD prevention and treatment approach.

Amyloid pathology mediates the associations between plasma fibrinogen and cognition in non-demented adults.

Though previous studies revealed the potential associations of elevated levels of plasma fibrinogen with dementia, there is still limited understanding regarding the influence of Alzheimer's disease (AD) biomarkers on these associations. We sought to investigate the interrelationships among fibrinogen, cerebrospinal fluid (CSF) AD biomarkers, and cognition in non-demented adults. We included 1996 non-demented adults from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study and 337 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The associations of fibrinogen with AD biomarkers and cognition were explored using multiple linear regression models. The mediation analyses with 10 000 bootstrapped iterations were conducted to explore the mediating effects of AD biomarkers on cognition. In addition, interaction analyses and subgroup analyses were conducted to assess the influence of covariates on the relationships between fibrinogen and AD biomarkers. Participants exhibiting low Aß42 were designated as A+, while those demonstrating high phosphorylated tau (P-tau) and total tau (Tau) were labeled as T+ and N+, respectively. Individuals with normal measures of Aß42 and P-tau were categorized as the A-T- group, and those with abnormal levels of both Aß42 and P-tau were grouped under A+T+. Fibrinogen was higher in the A+ subgroup compared to that in the A- subgroup (p = 0.026). Fibrinogen was higher in the A+T+ subgroup compared to that in the A-T- subgroup (p = 0.011). Higher fibrinogen was associated with worse cognition and Aß pathology (all p < 0.05). Additionally, the associations between fibrinogen and cognition were partially mediated by Aß pathology (mediation proportion range 8%-28%). Interaction analyses and subgroup analyses showed that age and ApoE ε4 affect the relationships between fibrinogen and Aß pathology. Fibrinogen was associated with both cognition and Aß pathology. Aß pathology may be a critical mediator for impacts of fibrinogen on cognition.

IFITM3 reduces infectious bursal disease virus proliferation by regulating interferon expression.

Interferon-inducible transmembrane protein 3 (IFITM3), a member of the interferon-stimulating factor (ISG) family, has various antiviral functions. Infectious bursal disease virus (IBDV) mainly invades the bursa of Fabricius in chickens, causing a reduction in their immunity and resulting in death from secondary infections. Our previous study found that IBDV infection promotes the expression of chicken IFITM3. However, the role of chicken IFITM3 in IBDV infection remains unknown. To explore this role, the overexpression vector for IFITM3 was constructed and transfected into HD-11 and DF-1 cells. The results showed that the overexpression of IFITM3 significantly reduced IBDV proliferation. While the IBDV proliferation increased when IFITM3 was inhibited by using siRNA. To further explore the mechanism by which IFITM3 reduces IBDV proliferation, the effects of IFITM3 on interferon (IFN) were investigated. Transfecting the constructed IFITM3 vectors into HD-11 and DF-1 cells demonstrated that IFITM3 promoted the expression of IFN-α, IFN-ß, and IFN-γ. To investigate the mechanism by which IFITM3 regulates IFN expression, the effects of IFITM3 on IFN production were explored. The results showed that the IKB gene mainly affected the regulatory effects of IFITM3 on IFN. Taken together, IFITM3 may reduce viral proliferation by regulating changes in IFNs, and this process may involve a positive feedback effect of IFITM3 on IFN. IKB plays an important role in the regulation of IFN effects by IFITM3.

On finding natural antibiotics based on TCM formulae.

CONTEXT: Novel kinds of antibiotics are needed to combat the emergence of antibacterial resistance. Natural products (NPs) have shown potential as antibiotic candidates. Current experimental methods are not yet capable of exploring the massive, redundant, and noise-involved chemical space of NPs. In silico approaches are needed to select NPs as antibiotic candidates. OBJECTIVE: This study screens out NPs with antibacterial efficacy guided by both TCM and modern medicine and constructed a dataset aiming to serve the new antibiotic design. METHOD: A knowledge-based network is proposed in this study involving NPs, herbs, the concepts of TCM, and the treatment protocols (or etiologies) of infectious in modern medicine. Using this network, the NPs candidates are screened out and compose the dataset. Feature selection of machine learning approaches is conducted to evaluate the constructed dataset and statistically validate the im- portance of all NPs candidates for different antibiotics by a classification task. RESULTS: The extensive experiments prove the constructed dataset reaches a convincing classification performance with a 0.9421 weighted accuracy, 0.9324 recall, and 0.9409 precision. The further visu- alizations of sample importance prove the comprehensive evaluation for model interpretation based on medical value considerations.

A population-based cohort of drug exposures and adverse pregnancy outcomes in China (DEEP): rationale, design, and baseline characteristics.

The DEEP cohort is the first population-based cohort of pregnant population in China that longitudinally documented drug uses throughout the pregnancy life course and adverse pregnancy outcomes. The main goal of the study aims to monitor and evaluate the safety of drug use through the pregnancy life course in the Chinese setting. The DEEP cohort is developed primarily based on the population-based data platforms in Xiamen, a municipal city of 5 million population in southeast China. Based on these data platforms, we developed a pregnancy database that documented health care services and outcomes in the maternal and other departments. For identifying drug uses, we developed a drug prescription database using electronic healthcare records documented in the platforms across the primary, secondary and tertiary hospitals. By linking these two databases, we developed the DEEP cohort. All the pregnant women and their offspring in Xiamen are provided with health care and followed up according to standard protocols, and the primary adverse outcomes - congenital malformations - are collected using a standardized Case Report Form. From January 2013 to December 2021, the DEEP cohort included 564,740 pregnancies among 470,137 mothers, and documented 526,276 live births, 14,090 miscarriages and 6,058 fetal deaths/stillbirths and 25,723 continuing pregnancies. In total, 13,284,982 prescriptions were documented, in which 2,096 chemicals drugs, 163 biological products, 847 Chinese patent medicines and 655 herbal medicines were prescribed. The overall incidence rate of congenital malformations was 2.0% (10,444/526,276), while there were 25,526 (4.9%) preterm births and 25,605 (4.9%) live births with low birth weight.

Anti-synthase syndrome associated with SARS-Cov-2 infection.

BACKGROUND: Anti-synthetase syndrome (AS) is a rare autoimmune idiopathic inflammatory myopathy (IIM) with diverse manifestations, including arthritis, interstitial lung disease (ILD), Raynaud's phenomenon, unexplained persistent fever, and mechanic's hands. CASE PRESENTATION: We present the case of a 72-year-old woman, previously healthy, who was admitted to our hospital for treatment of cough and rapid breathing. The patient had elevated white blood cells and C-reactive protein, and tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). She was initially diagnosed with community-acquired pneumonia and received tamoxifen for anti-infection treatment, but her dystonia worsened. She eventually required non-invasive ventilator support, tested positive for SARS-Cov-2 again, and started antiviral therapy, corticosteroids to reduce alveolar effusion, anticoagulation, and other treatments. However, her condition continued to deteriorate, with the lowest oxygenation index reaching only 80mmHg. Ultimately, she underwent tracheal intubation and mechanical ventilation. Chest CT revealed rapid progressive interstitial changes in her lungs, and her hands showed noticeable fraternization changes. At this point, we suspected that the novel coronavirus infection might be associated with autoimmune diseases. The patient's autoimmune antibody spectrum showed positive results for anti-recombinant RO-52 antibody and myositis-specific antibody anti-alanyl tRNA synthetase (anti-PL-12). The patient was treated with dexamethasone sodium phosphate for anti-inflammatory and anti-fibrotic effects. After successful extubation, the patient was discharged with only oral prednisone tablets at a dose of 30 mg. CONCLUSIONS: This case presents an early diagnosis and successful treatment of anti-synthetase syndrome combined with SARS-Cov-2 infection, emphasizing the importance of comprehensive physical examination. Additionally, it highlights the rapid progression of interstitial lung disease under SARS-Cov-2 infection, which is often difficult to distinguish on imaging. In cases where treatment for SARS-Cov-2 infection is ineffective, early screening for autoimmune diseases is recommended. As there is currently no standardized method for treating AS-ILD, the successful treatment of this case provides a reference for clinical research on anti-synthetase syndrome in the later stage.

The combination of allantoin, bisabolol, D-panthenol and dipotassium glycyrrhizinate mitigates UVB-induced PGE2 synthesis by keratinocytes.

OBJECTIVE: Erythema, characterized by the redness of the skin, is a common skin reaction triggered by various endogenous and exogenous factors. This response is often a result of the activation of underlying inflammatory mechanisms within the skin. The objective of this study is to investigate the potential benefits of applying a combination of skincare ingredients, namely allantoin, bisabolol, D-panthenol and dipotassium glycyrrhizinate (AB5D), in the modulation of inflammatory factors associated with erythema. Additionally, the study aims to elucidate the mechanisms by which these ingredients exert their combined actions to alleviate erythema-associated inflammation. METHODS: Human epidermal keratinocytes were exposed to UVB and subsequently treated with AB5D. Transcriptomics profiling was performed to analyse the dose-response effect of AB5D treatment on keratinocytes. The quantitation of inflammatory mediators, including PGE2 , IL-1α, IL-6, IL-8, IL-1RA and TNFα, was performed on cultured media. Additionally, the oxygen radical absorbance capacity (ORAC) assay was carried out to evaluate the total antioxidant capacity of both individual ingredients and the AB5D combination. To assess the in-vitro antioxidant effects of AB5D against UVB-induced oxidative stress in hTERT keratinocytes, real-time quantitation of mitochondrial superoxide was measured through live-cell imaging. RESULTS: The application of AB5D to UVB-exposed keratinocytes downregulated gene sets associated with inflammatory responses, highlighting the anti-inflammatory properties of AB5D. Specifically, AB5D effectively reduced the production of PGE2 , leading to the downregulation of inflammatory cytokines. Moreover, our findings indicate that AB5D exhibits antioxidative capabilities, functioning as both an antioxidant agent and a regulator of antioxidant enzyme expression to counteract the detrimental effects of cellular oxidative stress. CONCLUSION: We demonstrated that AB5D can reduce UVB-induced PGE2 , IL-1α, IL-6, IL-8, IL-1RA and TNFα as well as mitochondrial superoxide. These findings suggest that AB5D may alleviate erythema by modulating inflammation via PGE2 and through antioxidation mechanisms.

L'érythème, caractérisé par une rougeur sur la peau, est une réaction cutanée fréquente déclenchée par divers facteurs endogènes et exogènes. Il s'agit d'une réponse qui résulte souvent de l'activation des mécanismes inflammatoires sous-jacents dans la peau. OBJECTIF: cette étude vise à étudier les bénéfices potentiels de l'application d'une association d'ingrédients de soins cutanés, à savoir l'allantoïne, le bisabolol, le D-panthénol et le glycyrrhizinate dipotassique (AB5D) dans la modulation des facteurs inflammatoires associés à l'érythème. En outre, l'étude vise à élucider les mécanismes par lesquels ces ingrédients exercent leurs actions combinées pour soulager l'inflammation associée à l'érythème. MÉTHODES: les kératinocytes épidermiques humains ont été exposés aux UVB et traités par la suite par AB5D. Un profilage transcriptomique a été effectué pour analyser l'effet dose-réponse du traitement par AB5D sur les kératinocytes. La quantification des médiateurs inflammatoires, y compris PGE2, IL-1α, IL-6, IL-8, IL-1RA et TNFα, a été effectuée sur des milieux de culture. En outre, le dosage de la capacité d'absorption des radicaux oxygénés (Oxygen Radical Absorbance Capacity, ORAC) a été effectué pour évaluer la capacité antioxydante totale des deux ingrédients individuels et de l'association AB5D. Pour évaluer les effets antioxydants in vitro de l'AB5D contre le stress oxydatif induit par les UVB dans les kératinocytes hTERT, on a mesuré la quantification en temps réel du superoxyde mitochondrial par des tests d'imagerie des cellules vivantes. RÉSULTATS: l'application de l'AB5D aux ensembles de gènes régulés à la baisse exposés aux kératinocytes UVB associés à des réponses inflammatoires, a mis en évidence les propriétés anti-inflammatoires de l'AB5D. Plus précisément, l'AB5D a efficacement réduit la production de PGE2, entraînant une régulation négative des cytokines inflammatoires. En outre, nos résultats indiquent que l'AB5D présente des capacités antioxydantes. Il fonctionne à la fois comme un agent antioxydant et comme un régulateur de l'expression enzymatique antioxydante pour contrer les effets néfastes du stress oxydatif cellulaire. CONCLUSION: nous avons montré que l'AB5D pouvait réduire la PGE2 induite par les UVB, l'IL-1α, l'IL-6, IL-8, IL-1RA et le TNFα, ainsi que le superoxyde mitochondrial. Ces résultats suggèrent que l'AB5D pourrait soulager l'érythème en modulant l'inflammation via la PGE2 et via des mécanismes d'antioxydation.

Effect of sugar reduction on sensory characteristics of dried fish mince product.

BACKGROUND: Excessive sugar consumption has been linked to type 2 diabetes, obesity and other diseases. Therefore, it is indispensable to reduce sugar of food. However, the sensory characteristics of food are affected after sugar reduction (SR). Currently, SR has been reported in drinks, jams, candies, and other fruit related or sweet foods; but salty or protein related foods have not been explored, therefore there is a big gap that needs to be filled. RESULTS: Sensory scores of initial sweetness and sweetness reduced by 0.26 and 0.12 in 10% SR dried fish mince product compared with control, and there was a small difference between 25% SR (3.33) and 40% SR (3.09) samples. It also showed that 10% SR sample had a small reduction in sweetness value and free sugar content by 3.5% (0.42/11.9) and 7.8% (2.12/27.06) compared with control; while values in 25% SR sample decreased sharply but were not much different from 40% SR sample. Electronic nose results showed that SR had a small effect on odor. Texture analysis showed that texture properties of 25% SR sample were significantly different from control. CONCLUSIONS: Dried fish mince product with below 10% SR had a small difference on the sensory characteristics and there was a big change when SR was more than 20%. Dried fish mince product with 25% SR and 40% SR had no significant difference. SR had a small effect on odor, but had a great effect on texture properties, especially over 20% SR. © 2023 Society of Chemical Industry.

Kinetics and mechanisms of thermal deterioration in silver carp (Hypophthalmichtys molitrix) surimi gel quality under high-temperature sterilization.

BACKGROUND: The gelation properties of surimi gel under various high temperatures (115, 118, and 121 °C) and sterilization intensities (F0 values of 3-7 min) were systematically investigated. A kinetic model detailed quality changes during heat treatment through mathematical analysis, elucidating mechanisms for gel quality degradation. RESULTS: Increased sterilization intensity significantly reduced the quality characteristics of surimi gel. Compared to the gel without sterilization treatment, when the sterilization intensity was increased to 7 min, the gel strength of the groups treated at 115 °C, 118 °C, and 121 °C decreased by 68.35%, 51.4%, and 51.71%, respectively, and the water-holding capacity decreased by 24.87%, 16.85%, and 22.5%, respectively. The hardness, chewiness, and whiteness of the gel also significantly decreased, and the changes in these indicators all conformed to a first-order kinetic model. Activation energy of 291.52 kJ mol-1 highlighted gel strength as the least heat-resistant. At equivalent sterilization intensities, 115 °C exhibited the poorest gel quality, followed by 121 °C, with 118 °C showing relatively better gel quality. Increased T22 and decreased PT22 suggested heightened water mobility and transition of immobilized water within the gel into free water. Protein degradation, weakened disulfide bonds and hydrophobic interaction, and protein conformation changes collectively led to a rough and incoherent gel network structure with large fissures, as verified by the results of scanning electron microscopy. Correlation analysis indicated potential for precise control over surimi gel quality by modulating physicochemical attributes. CONCLUSION: The outcomes may be beneficial to improve the production and quality control of ready-to-eat surimi-based products. © 2024 Society of Chemical Industry.

Study on the effect and mechanism of chicken breast on the gel properties of silver carp (Hypophthalmichtys molitrix) surimi.

BACKGROUND: Adding appropriate exogenous substances is an effective means to improve the quality of freshwater fish surimi. The present study investigated the effects of chicken breast on the gel properties of mixed minced meat products. RESULTS: With the increase in the proportion of chicken breast, the breaking force of mixed gels gradually increased. When the addition ratio was 30:70, the gel strength of mixed gels had the highest strength of 759.00 g cm-1 and also the highest water holding capacity of 87.36%. Compared with surimi gels (0:100), the hardness, adhesiveness and chewiness of mixed gels were significantly improved. The increase in the proportion of chicken breast increased the thermal stability of the mixed sol and improved the rheological properties of the mixed sol. When the proportion was 40:60, the area of immobile water (A22 ) in the mixed gel increased significantly, and the highest A22 was 3463.24. The hydrophobic interactions and disulfide bonds in the mixed gel were significantly increased as a result of the addition of chicken breast. The results of microstructure, electrophoresis and Raman spectroscopy indicated that the addition of chicken breast promoted the cross-linking of the proteins in mixed gels, which facilitated the transformation of the protein secondary structure from α-helical to ß-folded structure, thus forming a more uniform and orderly network structure. CONCLUSION: These results suggest that improving the gel properties of silver carp surimi by use of chicken breast has practical implications for the development of new blended products for surimi processing. © 2023 Society of Chemical Industry.

[Comparison of initiation of antihypertensive therapy strategies for primary prevention of cardiovascular diseases in Chinese population: A decision-analytic Markov modelling study].

OBJECTIVE: To evaluate the health benefits and intervention efficiency of different strategies of initiating antihypertensive therapy for the primary prevention of cardiovascular diseases in a community-based Chinese population from the Chinese electronic health records research in Yinzhou (CHERRY) study. METHODS: A decision-analytic Markov model was used to simulate and compare different antihypertensive initiation strategies, including: Strategy 1, initiation of antihypertensive therapy for Chinese adults with systolic blood pressure (SBP) ≥140 mmHg (2020 Chinese guideline on the primary prevention of cardiovascular diseases); Strategy 2, initiation of antihypertensive therapy for Chinese adults with SBP ≥130 mmHg; Strategy 3, initiation of antihypertensive therapy for Chinese adults with SBP≥140 mmHg, or with SBP between 130 and 140 mmHg and at high risk of cardiovascular diseases (2017 American College of Cardiology/American Heart Association guideline for the prevention, detection, evaluation, and management of high blood pressure in adults); Strategy 4, initiation of antihypertensive therapy for Chinese adults with SBP≥160 mmHg, or with SBP between 140 and 160 mmHg and at high risk of cardiovascular diseases (2019 United Kingdom National Institute for Health and Care Excellence guideline for the hypertension in adults: Diagnosis and management). The high 10-year cardiovascular risk was defined as the predicted risk over 10% based on the 2019 World Health Organization cardiovascular disease risk charts. Different strategies were simulated by the Markov model for ten years (cycles), with parameters mainly from the CHERRY study or published literature. After ten cycles of simulation, the numbers of quality-adjusted life years (QALY), cardiovascular events and all-cause deaths were calculated to evaluate the health benefits of each strategy, and the numbers needed to treat (NNT) for each cardiovascular event or all-cause death could be prevented were calculated to assess the intervention efficiency. One-way sensitivity analysis on the uncertainty of incidence rates of cardiovascular disease and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. RESULTS: A total of 213 987 Chinese adults aged 35-79 years without cardiovascular diseases were included. Compared with strategy 1, the number of cardiovascular events that could be prevented in strategy 2 increased by 666 (95% UI: 334-975), while the NNT per cardiovascular event prevented increased by 10 (95% UI: 7-20). In contrast to strategy 1, the number of cardiovascular events that could be prevented in strategy 3 increased by 388 (95% UI: 194-569), and the NNT per cardiovascular event prevented decreased by 6 (95% UI: 4-12), suggesting that strategy 3 had better health benefits and intervention efficiency. Compared to strategy 1, although the number of cardiovascular events that could be prevented decreased by 193 (95% UI: 98-281) in strategy 4, the NNT per cardiovascular event prevented decreased by 18 (95% UI: 13-37) with better efficiency. The results were consistent in the sensitivity analyses. CONCLUSION: When initiating antihypertensive therapy in an economically developed area of China, the strategy combined with cardiovascular risk assessment is more efficient than those purely based on the SBP threshold. The cardiovascular risk assessment strategy with different SBP thresholds is suggested to balance health benefits and intervention efficiency in diverse populations.

Effects of Cuisine-Based Chinese Heart-Healthy Diet in Lowering Blood Pressure Among Adults in China: Multicenter, Single-Blind, Randomized, Parallel Controlled Feeding Trial.

BACKGROUND: More than one-fifth of the world's population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation. METHODS: A multicenter, patient- and outcome assessor-blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mm Hg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines (Shangdong, Huaiyang, Cantonese, Szechuan). After a 7-day run-in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine-based Chinese heart-healthy diet for another 28 days. The primary outcome was SBP, and secondary outcomes included diastolic blood pressure and food preference score. Linear regression models were used to estimate the intervention effects and adjustments for the center. The incremental cost per 1 mm Hg reduction in SBP was also calculated. RESULTS: A total of 265 participants were randomized (135 on the Chinese heart-healthy diet and 130 on the control diet), with 52% women, mean age of 56.5±9.8 years, and mean SBP and diastolic blood pressure of 139.4±8.3 and 88.1±8.0 mm Hg, respectively, at baseline. The change in SBP and diastolic blood pressure from baseline to the end of the study in the control group was -5.0 (95% CI, -6.5 to -3.5) mm Hg and -2.8 (95% CI, -3.7 to -1.9) mm Hg, respectively. The net difference of change between the 2 groups in SBP and diastolic blood pressure were -10.0 (95% CI, -12.1 to -7.9) mm Hg and -3.8 (95% CI, -5.0 to -2.5) mm Hg, respectively. The effect size did not differ among cuisines (P for interaction=0.173). The mean food preference score was 9.5 (with 10 the best preferred) at baseline, and the net change during intervention was 0.1 (95% CI, -0.1 to 0.2; P=0.558). The incremental cost-effectiveness ratio per 1 mm Hg SBP reduction was CNY 0.4 (USD 0.06) per day. No difference in the number of adverse events was found between the 2 groups (P=0.259), and none of the adverse events was associated with the intervention. CONCLUSIONS: The Chinese heart-healthy diet is effective, palatable, and cost-effective in reducing blood pressure in Chinese adults with high blood pressure, with a clinically significant effect applicable across major Chinese cuisine cultures. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03882645.

Experience with 2 years' intervention to progressively reduce salt supply to kitchens in elderly care facilities-challenges and further research: post hoc analysis of the DECIDE-Salt randomized clinical trial.

BACKGROUND: Progressive reduction of sodium intake is an attractive approach for addressing excessive salt intake, but evidence for this strategy in real practice is limited. We aimed to determine the feasibility, effectiveness, and safety of a progressive sodium intake reduction intervention in real-world setting. METHODS: We randomized 48 residential elderly care facilities in China, with 1612 participants aged 55 years and older, to either progressive reduction (PR, 24 facilities) or no reduction (NR, 24 facilities) of the supply of study salt to the kitchens of these facilities for 2 years. The primary efficacy outcome was systolic blood pressure (SBP) at any scheduled follow-up visit. Secondary efficacy outcomes included diastolic blood pressure (DBP) at any scheduled follow-up visit, and major adverse cardiovascular events (comprising non-fatal stroke, non-fatal myocardial infarction, hospitalized non-fatal heart failure, or vascular death) and total mortality. The perception of food saltiness, the addition of out-of-study salt in meals, and 24-h urinary sodium excretion were used as process indicators. RESULTS: Pre-specified analysis per randomization found no effect of the intervention on the 2-year overall mean systolic and diastolic blood pressure (SBP, DBP) and any other outcomes. However, post hoc analysis showed that the intervention effect on blood pressure varied over multiple follow-up visits (p for interaction < 0.046) and presented favorable differences at the 24-month visit (SBP = - 3.0 mmHg, 95%CI = - 5.6, - 0.5; p = 0.020; DBP = - 2.0 mmHg, 95%CI - 3.4, - 0.63; p = 0.004). The effect on 24-h sodium was non-significant (- 8.4 mmol, 95%CI = - 21.8 to 4.9, p = 0.216), though fewer participants with NR than with PR reported food tasting bland (odds ratio 0.46; 95%CI 0.29 to 0.73; p = 0.001). Reporting of bland food taste and other process measures indicated that intervention delivery and adherence were not fully achieved as designed. CONCLUSIONS: The experience of this real-world study demonstrated that achieving acceptability and sustainability of the progressive sodium intake reduction strategy among older adults was challenging, but it has shown potential for effectiveness in these and potentially other residential settings if the lessons of DECIDE-Salt are applied in further studies. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03290716).

The collectin subfamily member 11 (Ca-Colec11) from Qihe crucian carp (Carassius auratus) agglutinates and inhibits Aeromonas hydrophila and Staphylococcus aureus.

The collectin subfamily member 11 (Colec11), plays an important role in innate immunity as a pattern recognition molecule. In the present study, a colec11 homolog was identified and characterised from Qihe crucian carp, namely, Ca-colec11. The full-length cDNA of Ca-colec11 was composed of 1129 bp, with a 99 bp 5'-untranslated region (UTR), 816 bp open reading frame (ORF) encoding a 271-aa protein and 214 bp 3'-UTR with a polyadenylation signal sequence (aataaa) and a poly(A) tail. The deduced amino acid sequence of Ca-Colec11 contained a si gnal peptide, collagen domain, neck region and carbohydrate-recognition domain (CRD), which had four conserved cysteine residues (Cys170-Cys256 and Cys242-Cys264) and an EPN/WND motif required for carbohydrate-binding specificity. Tissue expression profile analysis by quantitative real-time polymerase chain reaction (RT-qPCR) showed that Ca-colec11 was ubiquitously distributed in the tested tissues and highly expressed in the liver. The gene expression levels of Ca-colec11 were evidently up-regulated in the liver, spleen, kidney and head kidney after infection with A. hydrophila and S. aureus. The recombinant Ca-Colec11 (rCa-Colec11) purified from Escherichia coli BL21 (DE3) could agglutinate A. hydrophila and S. aureus, and it possessed haemagglutination activity against rabbit erythrocytes, which was inhibited by various carbohydrates, including d-Mannose, N-Acetyl-d-mannosamine, l-Fucose, d-Glucose, N-Acetyl-d-glucosamine, d-Galactose, LPS and PGN. Furthermore, rCa-Colec11 could inhibit the growth of A. hydrophila and S. aureus. These findings collectively demonstrated that Ca-Colec11, as a PRR, could play a role in the immune defence of Qihe crucian carp.

National incidence and mortality of hospitalized sepsis in China.

BACKGROUND: Sepsis is a leading cause of preventable death around the world. Population-based estimation of sepsis incidence is lacking in China. In this study, we aimed to estimate the population-based incidence and geographic variation of hospitalized sepsis in China. METHODS: We retrospectively identified hospitalized sepsis from the nationwide National Data Center for Medical Service (NDCMS) and the National Mortality Surveillance System (NMSS) by ICD-10 codes for the period from 2017 to 2019. In-hospital sepsis case fatality and mortality rate were calculated to extrapolate the national incidence of hospitalized sepsis. The geographic distribution of hospitalized sepsis incidence was examined using Global Moran's Index. RESULTS: We identified 9,455,279 patients with 10,682,625 implicit-coded sepsis admissions in NDCMS and 806,728 sepsis-related deaths in NMSS. We estimated that the annual standardized incidence of hospitalized sepsis was 328.25 (95% CI 315.41-341.09), 359.26 (95% CI 345.4-373.12) and 421.85 (95% CI 406.65-437.05) cases per 100,000 in 2017, 2018 and 2019, respectively. We observed 8.7% of the incidences occurred among neonates less than 1 year old, 11.7% among children aged 1-9 years, and 57.5% among elderly older than 65 years. Significant spatial autocorrelation for incidence of hospitalized sepsis was observed across China (Moran's Index 0.42, p = 0.001; 0.45, p = 0.001; 0.26, p = 0.011 for 2017, 2018, 2019, respectively). Higher number of hospital bed supply and higher disposable income per capita were significantly associated with a higher incidence of hospitalized sepsis. CONCLUSION: Our study showed a greater burden of sepsis hospitalizations than previous estimated. The geographical disparities suggested more efforts were needed in prevention of sepsis.

Higher Prevalence of Generalized Pustular Psoriasis in Asia? A Population-Based Study Using Claim Data in China and a Systematic Review.

BACKGROUND: Few studies have reported the burden of generalized pustular psoriasis (GPP), a severe and potentially life-threatening skin disease, especially at a national level. OBJECTIVES: The aim of this study is to estimate the nationwide burden of GPP in China and make a systemic review of the published data. METHODS: We conducted a population-based study using Urban Basic Medical Insurance in China from 2012 to 2016. GPP cases were identified by primary diagnoses including the international classification of Diseases codes (ICD-10: L40.1 and ICD-9: 694.3). A systematic review was conducted using relevant databases up to January 2022. RESULTS: The crude prevalence and incidence of GPP in 2016 were 1.403 (95% confidence interval [CI]: 1.115-1.691) and 0.629 (95% CI: 0.483-0.775) per 100,000 person-years, respectively. The rates were higher in males than in females for both prevalence (1.429 vs. 1.135) and incidence (0.635 vs. 0.520). The prevalence and incidence showed a bimodal age distribution, with the first peak occurring in the 0- to 3-year age-group and the second peak occurring in the 30- to 39-year age-group. The per capita total cost per year for 1 patient with GPP was 609.26 (± 45.77) US dollars. Seven studies were identified in a systematic review, according to which the prevalence (per 100,000) of GPP tended to be higher in Asian countries (0.746-8.178 in Japan and 12.230 in Korea) than in France (0.176), Sweden (6.25), and Brazil (0.7). CONCLUSIONS: This is the largest study concerning the disease burden of GPP, and in this study, the prevalence seemed to be higher in Asia. Although the direct economic burden of GPP did not seem high during the study period, the future usage of biologics and the humanistic burden should also be considered for policy-related decision-making.

Association between serum lipoprotein(a) and mildly reduced eGFR: a cross-sectional study.

Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease (CVD) and aortic stenosis. However, the data on the relationship between Lp(a) and mildly reduced estimated glomerular filtration rate (eGFR) has been disputed. This study was conducted to assess the relationship between Lp(a) concentrations and mildly reduced eGFR in healthy subjects.This community-based, cross-sectional study enrolled 1,064 volunteers aged ≥ 40 years who lived in Yonghong Community, Zhonglou District, Changzhou, China, between December 2016 and December 2017. A mildly reduced eGFR was defined as eGFR between 60 and 90 mL/min/1.73m2. A standardized questionnaire and biochemical measurements were used to gather information about participants. The serum concentration of Lp(a) was determined using the latex-enhanced immunoturbidimetric test. Of the total study population, 34.8% (n = 370) were men, and the mean age was 66.8 ± 8.5 years. A significant association existed between Lp(a) levels and the risk of mildly reduced eGFR. Individuals with the highest tertile of Lp(a) had higher odds of mildly reduced eGFR after adjusting for various confounders (adjusted odds ratio [OR]: 1.80, 95% confidence interval [CI]: 1.24-2.60, P = 0.0025) compared to those with the lowest tertile of Lp(a). Multivariable logistic regression of studies in which Lp(a) was presented as continuous variables showed consistent results (adjusted OR: 1.23 for 1-SD increment of Ln-Lp(a), 95% CI: 1.05-1.43). Subgroup analyses showed that study characteristics such as age, sex, obesity, diabetes, and hypertension status did not significantly affect the association (P for all interactions > 0.05). These results suggest that higher serum Lp(a) level was an independent risk factor for mildly reduced eGFR.

Associations of the A/T/N profiles in PET, CSF, and plasma biomarkers with Alzheimer's disease neuropathology at autopsy.

INTRODUCTION: To examine the extent to which positron emission tomography (PET)-, cerebrospinal fluid (CSF)-, and plasma-related amyloid-ß/tau/neurodegeneration (A/T/N) biomarkers are associated with Alzheimer's disease (AD) neuropathology at autopsy. METHODS: A total of 100 participants who respectively underwent antemortem biomarker measurements and postmortem neuropathology were included in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We examined the associations of PET-, CSF-, and plasma-related A/T/N biomarkers in combinations or alone with AD neuropathological changes (ADNC). RESULTS: PET- and CSF-related A/T/N biomarkers in combination showed high concordance with the ADNC stage and alone showed high accuracy in discriminating autopsy-confirmed AD. However, the plasma-related A/T/N biomarkers alone showed better discriminative performance only when combined with apolipoprotein E (APO)E ε4 genotype. DISCUSSION: This study supports that PET- and CSF-related A/T/N profiles can be used to predict accurately the stages of AD neuropathology. For diagnostic settings, PET-, CSF-, and plasma-related A/T/N biomarkers are all useful diagnostic tools to detect the presence of AD neuropathology. HIGHLIGHTS: PET- and CSF-related A/T/N biomarkers in combination can accurately predict the specific stages of AD neuropathology. PET- and CSF-related A/T/N biomarkers alone may serve as a precise diagnostic tool for detecting AD neuropathology at autopsy. Plasma-related A/T/N biomarkers may need combined risk factors when used as a diagnostic tool. Aß PET and CSF p-tau181/Aß42 were most consistent with Aß pathology, while tau PET and CSF p-tau181/Aß42 were most consistent with tau pathology.

Differences between ante mortem Alzheimer's disease biomarkers in predicting neuropathology at autopsy.

INTRODUCTION: This study aimed to assess whether biomarkers related to amyloid, tau, and neurodegeneration can accurately predict Alzheimer's disease (AD) neuropathology at autopsy in early and late clinical stages. METHODS: We included 100 participants who had ante mortem biomarker measurements and underwent post mortem neuropathological examination. Based on ante mortem clinical diagnosis, participants were divided into non-dementia and dementia, as early or late clinical stages. RESULTS: Amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) amyloid beta (Aß)42/phosphorylated tau (p-tau)181 showed excellent performance in differentiating autopsy-confirmed AD and predicting the risk of neuropathological changes in early and late clinical stages. However, CSF Aß42 performed better in the early clinical stage, while CSF p-tau181, CSF t-tau, and plasma p-tau181 performed better in the late clinical stage. DISCUSSION: Our findings provide important clinical information that, if using PET, CSF, and plasma biomarkers to detect AD pathology, researchers must consider their differential performances at different clinical stages of AD. HIGHLIGHTS: Amyloid PET and CSF Aß42/p-tau181 were the most promising candidate biomarkers for predicting AD pathology. CSF Aß42 can serve as a candidate predictive biomarker in the early clinical stage of AD. CSF p-tau181, CSF t-tau, and plasma p-tau181 can serve as candidate predictive biomarkers in the late clinical stage of AD. Combining APOE ε4 genotypes can significantly improve the predictive accuracy of AD-related biomarkers for AD pathology.