Efficacy and safety of trastuzumab deruxtecan in patients with solid tumors: a systematic review and meta-analysis of 3 randomized controlled trials.

Trastuzumab deruxtecan (T-DXd, DS-8201) is a targeted antibody-drug conjugate that specifically targets human epidermal growth factor receptor 2 (HER2). In 2019, it was approved by the US Food and Drug Administration for the treatment of HER2-positive breast cancer. However, ongoing research is exploring its potential efficacy in other solid tumors, such as non-small-cell lung cancer and colorectal cancer, as well as in tumors with low HER2 levels. It is important to examine the safety and effectiveness of trastuzumab deruxtecan in these various types of solid tumors, as some studies have raised concerns about potential serious adverse events associated with its use. In this meta-analysis, we conducted a comprehensive search of PubMed, EMBASE, Cochrane Library, and Web of Science to identify randomized controlled trials (RCTs) that evaluated the efficacy and safety of trastuzumab deruxtecan in solid tumors. We used RevMan 5.4 software to perform a meta-analysis, calculating odds ratios (OR), risk ratios (RR), and weighted mean differences (WMD) with 95% confidence intervals (CIs). After an exhaustive search, we identified three articles that met our inclusion criteria, which included a total of 1268 patients. The results of the meta-analysis showed that the treatment group had significantly higher overall survival (WMD=5.12, 95% CI (2.79, 7.44), P<0.0001), progression-free survival (WMD=3.45, 95% CI (0.8, 6.1), P=0.01), overall response rate (OR=6.49, 95% CI (4.90, 8.58), P<0.00001), and disease control rate (OR=4.68, 95% CI (2.78, 7.89), P<0.00001), TRAEs (RR=6.93, 95% CI (2.06, 23.25), P=0.002). However, there was no significant difference in TRAEs≥3 (RR=1.08, 95% CI (0.75, 1.56), P=0.68) between the trials. Based on the available evidence, trastuzumab deruxtecan appears to be an effective and safe treatment option for HER2-positive solid tumors. Although the number of studies included in this analysis is limited, ongoing trials are being conducted, further evaluating its potential in various solid tumors. The results of these trials will enhance our understanding of trastuzumab deruxtecan and potentially expand its applications, bringing hope to more patients with solid tumors.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), somatic and fatigue symptoms in cardiovascular diseases comorbid major depressive disorder (MDD): A randomized controlled trial.

INTRODUCTION: Cardiovascular diseases (CVDs) and major depressive disorder (MDD) are the two most disabling diseases. Patients with CVDs comorbid depression had somatic and fatigue symptoms and were associated with chronic inflammation and omega-3 polyunsaturated fatty acid (n-3 PUFA) deficits. However, there have been limited studies on the effects of n-3 PUFAs on somatic and fatigue symptoms in patients with CVDs comorbid MDD. METHOD: Forty patients with CVDs comorbid MDD (58% males, mean age of 60 ± 9 years) were enrolled and randomised to receive either n-3 PUFAs (2 g of eicosapentaenoic acid [EPA] and 1 g of docosahexaenoic acid[DHA] per day) or placebo in a 12-week double-blind clinical trial. We assessed the somatic symptoms with Neurotoxicity Rating Scale (NRS) and fatigue symptoms with Fatigue Scale at baseline, weeks 1, 2, 4, 8 and 12, as well as blood levels of Brain-Derived Neurotrophic Factor (BDNF), inflammatory biomarkers and PUFAs, at the baseline and week 12. RESULTS: The n-3 PUFAs group had a greater reduction in Fatigue scores than the placebo group at Week 4 (p =.042), while there were no differences in the changes of NRS scores. N-3 PUFAs group also had a greater increase in EPA (p =.001) and a greater decrease in total n-6 PUFAs (p =.030). Moreover, in the subgroup analyses in the younger age group (age < 55), the n-3 PUFAs group had a greater reduction on NRS total scores at Week 12 (p =.012) and NRS Somatic scores at Week 2 (p =.010), Week 8 (p =.027), Week 12 (p =.012) than the placebo group. In addition, the pre- and post-treatment changes of EPA and total n-3 PUFAs levels were negatively associated with the changes of NRS scores at Weeks 2, 4, and 8 (all p <.05), and the changes of BDNF levels were negatively associated with NRS scores at Weeks 8 and 12 (both p <.05) in the younger age group. In the older age group (age ≥ 55), there were a lesser reduction on NRS scores at Weeks 1, 2 and 4 (all p <.05), but a greater reduction on Fatigue score at Week 4 (p =.026), compared to the placebo group. There was no significant correlation between the changes of blood BDNF, inflammation, PUFAs and NRS and Fatigue scores in general and in the older age group. CONCLUSION: Overall, n-3 PUFAs improved the fatigue symptoms in patients with CVDs comorbid MDD and the general somatic symptoms in specific subpopulation of younger age patients, and perhaps via the interplay between BDNF and EPA. Our findings provide promising rationales for future studies to investigate the treatment effects of omega-3 fatty acids on fatigue and somatic symptoms of chronic mental and medical diseases.

Data mining-based analysis on medication rules of Chinese herbal medicine treating headache with blood stasis syndrome.

Objective: The incidence of headaches with blood stasis syndrome has increased. Herein, we used scientific, statistical methods to explore the medication rules of Chinese herbal medicines (CHMs) to treat headaches with blood stasis syndrome and provide a scientific and reliable theoretical basis for clinical treatment. Methods: First, we retrieved studies related to CHMs used to treat headaches with blood stasis syndrome from the VIP, CNKI, Wanfang, and PubMed databases. We used Excel 2013 to establish a database and SPSS Modeler 18.0 and SPSS 25.0 to conduct frequency, association rule, and cluster analyses. Results: Based on the screening criteria, we retrieved 126 CHM prescriptions for headaches with blood stasis syndrome involving 149 herbs. The top three high-frequency herbs were Chuanxiong Rhizoma (Chuanxiong), Angelica Sinensis Radix (Danggui), and Carthami Flos (Honghua). Blood-activating and stasis-eliminating herbs were the most frequently used herb efficacy categories. The liver meridian represented the most frequently used herb meridian tropism. The properties and taste of herbs were mainly warm and bitter, respectively. We obtained 21 association rules and five new clusters. The Chuanxiong Rhizoma (Chuanxiong) and Angelica Sinensis Radix (Danggui) herb pair had the strongest correlation. Conclusion: We analyzed published CHM prescriptions for headaches with blood stasis syndrome and eliminated factors that did not reach an agreement, such as herb dosage. We used different data mining and analysis methods to ensure that the method and process were scientific and the conclusion was reliable, comprising a valuable reference for selecting herbs for the clinical treatment of headaches with blood stasis syndrome. The Xuefu Zhuyu Decoction (XFZYD) was the primary CHM prescription for headaches with blood stasis syndrome. Xiaoyao San (XYS) and Buyang Huanwu Decoction (BYHWD) might also be clinical references for treatment selection. Meridian-inducing and insect herbs might be used according to syndromes.

Determination of D-serine and D-alanine Tissue Levels in the Prefrontal Cortex and Hippocampus of Rats After a Single Dose of Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, with Potential Antipsychotic and Antidepressant Properties.

The effects of the N-methyl-D-aspartate receptor activators D-serine, D-alanine, and sarcosine against schizophrenia and depression are promising. Nevertheless, high doses of D-serine and sarcosine are associated with undesirable nephrotoxicity or worsened prostatic cancer. Thus, alternatives are needed. DAAO inhibition can increase D-serine as well as D-alanine and protect against D-serine-induced nephrotoxicity. Although several DAAO inhibitors improve the symptoms of schizophrenia and depression, they can increase the plasma levels but not brain levels of D-serine. The mechanism of action of DAAO inhibitors remains unclear. We investigated the effects of the DAAO inhibitor sodium benzoate on the prefrontal cortex and hippocampal level of D-alanine as known another substrate with antipsychotic and antidepressant properties and other NMDAR-related amino acids, such as, L-alanine, D-serine, L-serine, D-glutamate, L-glutamate, and glycine levels. Our results indicate that sodium benzoate exerts antipsychotic and antidepressant-like effects without changing the D-serine levels in the brain prefrontal cortex (PFC) and hippocampus. Moreover, D-alanine levels in the PFC and hippocampus did not change. Despite these negative findings regarding the effects of D-amino acids in the PFC and hippocampus, sodium benzoate exhibited antipsychotic and antidepressant-like effects. Thus, the therapeutic effects of sodium benzoate are independent of D-serine or D-alanine levels. In conclusion, sodium benzoate may be effective among patients with schizophrenia or depression; however, the mechanisms of actions remain to be elucidated.

A novel l-rhamnose-binding lectin participates in defending against bacterial infection in zebrafish.

l-rhamnose-binding lectin (RBL), which is a class of animal lectins independent of Ca2+, can specifically bind l-rhamnose or d-galactose. Although several lectins in zebrafish have been reported, their functional mechanisms have not been fully uncovered. In this study, we discovered a novel l-rhamnose binding lectin (DrRBL) and studied its innate immune function. The DrRBL protein contains only one carbohydrate-recognition domain (CRD), which includes two strictly conserved motifs, "YGR" and "DPC". DrRBL was detected in all tested tissues and was present at high levels in the spleen, hepatopancreas and skin. After Aeromonas hydrophila challenge, the DrRBL mRNA level was significantly upregulated. Additionally, DrRBL was secreted into the extracellular matrix. Recombinant DrRBL (rDrRBL) could significantly inhibit the growth of gram-positive/negative bacteria, bind to several bacteria and cause obvious agglutination. The rDrRBL protein could combine with polysaccharides, such as PGN and LPS, rather than LTA. A more detailed study showed that rDrRBL could combine with monosaccharides, such as mannose, rhamnose and glucose, which are important components of PGN and LPS. However, rDrRBL could not bind to ribitol, which is an important component of LTA. The DrRBL deletion mutants, DrRBLΔ144-150 and DrRBLΔ198-200, were also constructed. DrRBLΔ144-150 ("ANYGRTD" deficient) showed weak bacterial inhibiting ability. However, DrRBLΔ198-200 ("DPC" deficient) showed weak agglutination ability. These results suggest that the "DPC" domain is important for agglutination. The conserved domain "ANYGRTD" is essential for inhibiting bacterial growth.

A C-type lectin containing two carbohydrate recognition domains participates in the antibacterial response by regulating the JNK pathway and promoting phagocytosis.

C-type lectins (CTLs) are important immune-related molecules in crustaceans. However, the immunologic mechanism by which CTLs eliminate invading pathogens is still unclear. In this study, we studied the antimicrobial mechanism of a CTL containing two carbohydrate recognition domains (DClec). After Aeromonas hydrophila challenge, several antimicrobial peptides (ALF1, ALF4, ALF5 and lys-i2) were upregulated. The transcript levels of ALF1, ALF4 and ALF5 were downregulated after A. hydrophila challenge in groups with DClec interference or inhibition compared with the control group. Similar results were obtained after c-Jun N-terminal kinase (JNK) interference. This finding indicates that DClec might regulate the JNK signalling pathway and subsequently adjust antimicrobial peptide (AMP) expression. Additionally, we found that DClec was secreted into the hemolymph. Recombinant protein DClec (rDClec) agglutinated gram-positive or gram-negative bacteria. Both rDClec and the native DClec in hemolymph bound to different bacteria. In this process, Ca2+ promoted the rDClec bacterial binding ability. After DClec interference, the phagocytosis ability of hemocytes was lower than that of the control group. Therefore, DClec can facilitate bacterial elimination by promoting AMPs expression and hemocyte phagocytosis.

Artificial neural network-genetic algorithm-based optimization of aerobic composting process parameters of Ganoderma lucidum residue.

The rapid development of traditional Chinese medicine enterprises has put forward higher requirements for the resource utilization of traditional Chinese medicine residues (TCMR). Aerobic composting of TCMR to prepare bio-organic fertilizer is an effective resource utilization method. In this study, a back-propagation artificial neural network (BPNN) model using composting factors as inputs (C/N, initial moisture content, type of inoculant, composting days) and the humic acid content as the output was constructed based on the orthogonal test data. BPNN-GA (a genetic algorithm) was used for extreme value optimization, and the optimal composting process parameter combination was obtained and verified. The results show that the combination of orthogonal testing and BPNN can effectively establish the relationship between the composting process parameters and humic acid content. The R2 value was 0. 9064. The optimized parameter combination is as follows: C/N,37.42; moisture content,69.76%; bacteria,no; and composting time,50 d.

The potential of immature poken (Citrus reticulata) extract in the weight management, lipid and glucose metabolism.

OBJECTIVES: The prevalence of obesity was increasing globally, with nearly half a billion of the world's population now considered to be overweight or obese. The immature poken (Citrus reticulata) was a good source of flavonoids and phenolic acids, which may exert an anti-obesity effect. However, the current efficacy in clinical trials was still unclear. Thus, the object of this study was to explore whether immature poken had an anti-obesity effect in the clinical trial. METHODS: In this study, we identified nine major compounds from immature poken extract (IPE), and most compounds significantly decreased the lipid accumulation in adipocytes. In addition, 20 subjects with body mass index (BMI) ≥ 24 or body fat > 30 were recruited and randomly allocated to placebo and experimental (IPE) groups for 6 week intervention and 2 week follow-up. RESULTS: In comparison with the baseline results (week 0), the body weight, body fat, and waist circumference at week 6 in the IPE group were significantly decreased by 1.49 kg, 0.33%, 2.1 cm. Moreover, in blood biochemical analysis, total cholesterol (TC), triglyceride (TG), fasting blood sugar (FBS), and insulin levels at week 6 in IPE group were also decreased by 3.6, 4.6, 2.1 (mg/dL), and 2.9 (µU/mL), respectively. CONCLUSIONS: The finding showed that immature poken had important roles in fat metabolism by suppressing adipogenesis, and immature poken may provide new weight loss strategies for obese people.

[Development and analysis of clinical prediction model of acupuncture and moxibustion treatment for stroke at recovery stage].

OBJECTIVE: To develop the clinical prediction model of therapeutic effect in treatment with acupuncture and moxibustion for the patients with stroke at recovery stage under different conditions so as to provide a tool for predicting the therapeutic effect of acupuncture and moxibustion. METHODS: A total of 1410 patients with stroke at recovery stage were collected from the Third Affiliated Hospital of Zhejiang Chinese Medical University from 2012 to 2019. The relevant data were extracted, i.e. sex, age, time of onset, neurological functional deficit score (NFDS) and acupuncture and moxibustion therapy. The difference of NFDS before and after treatment was adopted to evaluate the therapeutic effect in the patients. Using SPSS26.0 software and CART decision tree analysis, the clinical prediction model was developed. RESULTS: The key variables in the prediction model of therapeutic effect in the patients with stroke at recovery stage under different conditions included age, time of onset, hypertension, cardiac disease, diabetes, TCM diagnosis, hemoglobin (HB), serum homocysteine (HCY) and acupuncture and moxibustion therapy. There were 12 main rules generated by the decision tree model, including 8 rules for predicting the improvements of therapeutic effect and 4 rules for predicting the absence of improvements (i.e. no change and deterioration). The accuracy rates of the model training set and test set were 80.0% and 72.8% respectively, the area under curve (AUC) of ROC was 0.797 and the model identification and classification results were satisfactory. CONCLUSION: The clinical prediction model developed by CART decision tree analysis is high in accuracy for the prediction of the therapeutic effect in the patients with stroke at recovery stage under different conditions. Based on the therapeutic effect predicted in the hospital visit, the physicians may adopt the corresponding regimens of acupuncture and moxibustion therapy in patients.

Plasma d-glutamate levels for detecting mild cognitive impairment and Alzheimer's disease: Machine learning approaches.

BACKGROUND: d-glutamate, which is involved in N-methyl-d-aspartate receptor modulation, may be associated with cognitive ageing. AIMS: This study aimed to use peripheral plasma d-glutamate levels to differentiate patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) from healthy individuals and to evaluate its prediction ability using machine learning. METHODS: Overall, 31 healthy controls, 21 patients with MCI and 133 patients with AD were recruited. Serum d-glutamate levels were measured using high-performance liquid chromatography (HPLC). Cognitive deficit severity was assessed using the Clinical Dementia Rating scale and the Mini-Mental Status Examination (MMSE). We employed four machine learning algorithms (support vector machine, logistic regression, random forest and naïve Bayes) to build an optimal predictive model to distinguish patients with MCI or AD from healthy controls. RESULTS: The MCI and AD groups had lower plasma d-glutamate levels (1097.79 ± 283.99 and 785.10 ± 720.06 ng/mL, respectively) compared to healthy controls (1620.08 ± 548.80 ng/mL). The naïve Bayes model and random forest model appeared to be the best models for determining MCI and AD susceptibility, respectively (area under the receiver operating characteristic curve: 0.8207 and 0.7900; sensitivity: 0.8438 and 0.6997; and specificity: 0.8158 and 0.9188, respectively). The total MMSE score was positively correlated with d-glutamate levels (r = 0.368, p < 0.001). Multivariate regression analysis indicated that d-glutamate levels were significantly associated with the total MMSE score (B = 0.003, 95% confidence interval 0.002-0.005, p < 0.001). CONCLUSIONS: Peripheral plasma d-glutamate levels were associated with cognitive impairment and may therefore be a suitable peripheral biomarker for detecting MCI and AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing MCI and AD in outpatient clinics.

[Assessing fractional vegetation cover changes and ecological quality of the Wuyi Mountain National Nature Reserve based on remote sensing spatial information]. / 基于遥感空间信息的武夷山国家级自然保护区植被覆盖度变化与生态质量评估.

The Wuyi Mountain National Nature Reserve (WYS), established in 1979, is the largest and most intact subtropical forest ecosystem in southeastern China. No study has assessed the vegetation coverage change along with its ecological effect after the protection of the reserve for almost 40 years. In this study, the NDVI data of Landsat Image was corrected using the NDVI data of MODIS, the fractional vegetation cover (FVC) and the remote sensing based ecological index (RSEI) were calculated to assess the change of FVC and ecological quality in WYS with five Landsat images representing a period from 1979 to 2017. The results showed that after protection for nearly 40 years the FVC of the reserve had been significantly increased from 73.6% in 1979 to 89.5% in 2017, which consequently improved ecological quality from 0.801 in 1988 to 0.823 in 2017. In 2017, the area with the good and excellent ecological quality grades accounted for 98.7% of the total. Spatially, the ecologically-improved areas mainly distributed in the northeast core area and the center of the southwest core area. The ecologically-declined areas mostly occurred along roadsides and peaks. Vertically, the highest FVC and ecological quality areas distributed in the elevations between 1300-1900 m. In general, the improvement of FVC and ecological quality in the Wuyi Mountain National Nature Reserve was due largely to the effective policies and the successful protection by local government and people, except for some special year that may be affected mainly by climate conditions.

Precision Medicine of Sodium Benzoate for the Treatment of Behavioral and Psychological Symptoms of Dementia (BPSD).

OBJECTIVE: Behavioral and psychological symptoms of dementia (BPSD) are associated with poorer prognosis of dementia. A 24-week study demonstrated that sodium benzoate, a D-amino acid oxidase (DAAO) inhibitor, surpassed placebo in improving cognitive function in early-phase Alzheimer's disease; however, benzoate did not excel placebo in another 6-week study on BPSD. The current study examined whether the precision medicine approach was able to identify specific individuals with BPSD who could benefit from benzoate treatment. METHODS: In the randomized, double-blind, placebo-controlled, 6-week trial, 97 patients with BPSD were allocated to receive 250-1500 mg/day of sodium benzoate or placebo. Cognitive function was measured by the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and behavioral and psychological symptoms were mainly measured by Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). DAAO level, amino acids (L-serine, D-serine, L-alanine, and D-alanine, glycine), and two antioxidants (catalase, superoxide dismutase) were assayed in peripheral blood. RESULTS: After benzoate treatment, DAAO inhibition was correlated with ADAS-cog decrease (p = 0.034), while baseline DAAO level was correlated with baseline BEHAVE-AD score. Multiple linear regression analyses showed that cognitive improvement after benzoate treatment was correlated with DAAO decrease, female gender, younger age, BMI, baseline BPSD severity, and antipsychotic use. CONCLUSION: The finding suggests that sodium benzoate may have potential to benefit cognitive function in a fraction of BPSD patients after 6 weeks of treatment. Of note, the precision medicine approach may be helpful for identifying individuals who could respond to benzoate. More studies are warranted to confirm the preliminary findings. TRIAL REGISTRATION: The trial was registered online (https://clinicaltrials.gov/ct2/show/NCT02103673).

Omega-3 polyunsaturated fatty acids in cardiovascular diseases comorbid major depressive disorder - Results from a randomized controlled trial.

INTRODUCTION: Cardiovascular diseases (CVDs) and major depressive disorder (MDD) will be the two most disabling diseases by 2030. Patients with CVDs comorbid depression had lower levels of total omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (DHA), and a higher omega-6 to omega-3 ratio. However, there have been limited studies on the effects n-3 PUFAs on MDD in patients with CVDs. METHOD: We have enrolled a total of 59 patients (64% males, mean age of 61.5 ±â€¯9.0 years and mean education of 10.2 ±â€¯4.2 years) with CVDs comorbid MDD. They were randomized into either receiving n-3 PUFAs (2 g per day of eicosapentaenoic acid (EPA) and 1 g of DHA) or placebo for 12 weeks. We assessed depression symptom severity with Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI), as well as blood fatty acid levels, electrocardiogram and blood biochemistry, at the baseline and at the endpoint. RESULTS: There were no differences between the n-3 PUFAs and placebo group in the changes of HAMD and BDI total scores, while PUFAs group had a greater reduction in HAMD Cognition subscale scores than the placebo group at week 8 (p < 0.05). Moreover, subgroup analyses found that the n-3 group had a greater reduction of HAMD Core subscale scores than the placebo group at the end of week 12 (p < 0.05) for the very severe DEP group (HAMD ≥ 23). CONCLUSION: Overall, n-3 PUFAs did not show a beneficial effect on depressive symptoms when compared with placebo. However, when stratified with depression severity, n-3 PUFAs supplementation improved core depression symptoms in the very severe MDD group. N-3 PUFAs supplementation may provide a treatment option for a subpopulation of patients with CVDs comorbid MDD.

Flavivirus Cross-Reactivity to Dengue Nonstructural Protein 1 Antigen Detection Assays.

Dengue virus (DENV) and Zika virus (ZIKV) are flaviviruses of public health relevance. Both viruses circulate in the same endemic settings and acute infections generally manifest similar symptoms. This highlights the importance of accurate diagnosis for clinical management and outbreak control. One of the commonly used acute diagnostic markers for flaviviruses is nonstructural protein 1 (NS1). However, false positives due to antigenic cross-reactivity have been reported between DENV and ZIKV infections when using DENV NS1 antigen (NS1 Ag) detection assays in acute cases. Therefore, we investigated the lowest detectable virus titres and cross-reactivity of three commercial dengue NS1 Ag rapid assays and two ELISAs for different flaviviruses. Our results showed that substantially high viral titres of ZIKV, Kunjin virus (KUNV) and yellow fever virus (YFV) are required to give false-positive results when using DENV NS1 rapid detection assays. Commercial DENV NS1 ELISAs did not react with ZIKV and YFV. In comparison, tested assays detected DENV at a significantly low virus titre. Given the relatively low viral loads reported in clinical samples, our findings suggest that commercially available dengue NS1 Ag detection assays are less likely to generate false-positive results among clinical samples in areas where multiple flaviviruses cocirculate.

High-dose eicosapentaenoic acid (EPA) improves attention and vigilance in children and adolescents with attention deficit hyperactivity disorder (ADHD) and low endogenous EPA levels.

No studies have examined the relationship between endogenous polyunsaturated fatty acids (PUFAs) levels and treatment response to PUFAs. We conducted a 12-week, double-blind, placebo-controlled trial comparing the effects of high-dose eicosapentaenoic acid (EPA, 1.2 g) and placebo on cognitive function (continuous performance test) in n = 92 youth (age 6-18-years-old) with Attention Deficit Hyperactivity Disorder (ADHD). Blood erythrocytes PUFAs were measured before and after treatment, to examine the effects of baseline endogenous EPA levels on treatment response and the effects of EPA treatment on PUFAs levels. Secondary measures included other ADHD symptoms, emotional symptoms, and levels of plasma high-sensitivity c-reactive protein (hs-CRP) and brain-derived neurotrophic factor (BDNF). Overall, EPA group improved more than placebo group on focused attention (variability, Effect size (ES) = 0.38, p = 0.041); moreover, within youth with the lowest baseline endogenous EPA levels, EPA group improved more than placebo group in another measure of focused attention (hit reaction time, HRT, ES = 0.89, p = 0.015) and in vigilance (HRT interstimulus interval changes, HRTISIC, ES = 0.83, p = 0.036). Interestingly, EPA group improved less than placebo group in impulsivity (commission errors), both overall and in youth with the highest baseline EPA levels, who also showed less improvement in other ADHD and emotional symptoms. EPA increased blood erythrocytes EPA by 1.6-fold but not DHA levels, and did not affect hs-CRP and BDNF plasma levels. In conclusion, EPA treatment improves cognitive symptoms in ADHD youth, especially if they have a low baseline endogenous EPA level, while youth with high EPA levels may be negatively affected by this treatment.

pLG72 levels increase in early phase of Alzheimer's disease but decrease in late phase.

pLG72, named as D-amino acid oxidase activator (although it is not an activator of D-amino acid oxidase demonstrated by later studies), in mitochondria has been regarded as an important modulator of D-amino acid oxidase that can regulate the N-methyl-D-aspartate receptor (NMDAR). Both oxidative stress in mitochondria and NMDAR neurotransmission play essential roles in the process of neurodegenerative dementia. The aim of the study was to investigate whether pLG72 levels changed with the severity of neurodegenerative dementia. We enrolled 376 individuals as the overall cohort, consisting of five groups: healthy elderly, amnestic mild cognitive impairment [MCI], mild Alzheimer's disease [AD], moderate AD, and severe AD. pLG72 levels in plasma were measured using Western blotting. The severity of cognitive deficit was principally evaluated by Clinical Dementia Rating Scale. A gender- and age- matched cohort was selected to elucidate the effects of gender and age. pLG72 levels increased in the MCI and mild AD groups when compared to the healthy group. However, pLG72 levels in the moderate and severe AD groups were lower than those in the mild AD group. D-serine level and D- to total serine ratio were significantly different among the five groups. L-serine levels were correlated with the pLG72 levels. The results in the gender- and age- matched cohort were similar to those of the overall cohort. The finding supports the hypothesis of NMDAR hypofunction in early-phase dementia and NMDAR hyperfunction in late-phase dementia. Further studies are warranted to test whether pLG72 could reflect the function of NMDAR.

D-glutamate, D-serine, and D-alanine differ in their roles in cognitive decline in patients with Alzheimer's disease or mild cognitive impairment.

BACKGROUND: D-amino acids have been recognized as bioactive substances in humans. d-Serine and D-alanine are co-agonists of N-methyl-d-aspartate receptors. Glutamate has been suggested to be involved in the pathophysiology of Alzheimer's disease (AD). This study aimed to explore the roles of amino acids, particularly D-amino acids, in cognitive decline among patients with AD or mild cognitive impairment (MCI). METHODS: We enrolled 144 patients: 20 amnestic MCI, 85 mild AD, 25 moderate AD, and 14 severe AD. Serum levels of amino acids were measured by high performance liquid chromatography and confirmed by D-amino acid oxidase assay. The cognitive function was mainly evaluated by Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog). RESULTS: ADAS-cog total scores were positively correlated with d-serine (r = 0.186, p = 0.026) and D-/Total- serine ratio (r = 0.191, p = 0.022). ADAS-cog behavior scores were negatively correlated with D-glutamate (r = -0.177, p = 0.034) and L-glutamate (r = -0.250, p = 0.003), but positively correlated with D-alanine (r = 0.236, p = 0.005) and D-/Total- alanine ratio (r = 0.252, p = 0.002). Among the 11 tasks of ADAS-cog, D-glutamate and d-serine were correlated with different items respectively, noteworthily in the opposite direction. CONCLUSION: This is the first study suggesting that D-amino acids in blood may be correlated with ADAS-cog in different items and in the opposite direction. Lower D-glutamate and higher D-alanine levels may predict more behavioral symptoms. In summary, D-glutamate, d-serine and D-alanine play different and characteristic roles in AD. Further longitudinal studies are warranted to elucidate the function and interaction of D-amino acids in specific cognitive domains as well as various phases of dementia.

Dietary Profiles, Nutritional Biochemistry Status, and Attention-Deficit/Hyperactivity Disorder: Path Analysis for a Case-Control Study.

This study aims to investigate dietary and nutritional biochemistry profiles of attention-deficit/hyperactivity disorder (ADHD) and to explore their potential relationship by path analysis. We enrolled 216 children with ADHD and 216 age-, height- and gender-matched controls from 31 elementary schools in Taiwan. Dietary intake of the participants was assessed using a food frequency questionnaire (FFQ). Fasting blood samples were collected to determine the serum levels of multiple nutritional markers. Moreover, we employed a structural equation model (SEM) to link diet, nutritional markers and ADHD. Compared to healthy control, ADHD children had significantly lower serum levels of vitamin B12, folate, vitamin B6, ferritin concentration, and monounsaturated fatty acids (MUFA), but higher levels of serum saturated fatty acids (SFA), n-6/n-3 fatty acid ratio, and inorganic phosphorous concentration. Children with ADHD had more intake of nutrient-poor foods such as high sugar and high fat foods, and had less intake of vegetable, fruit, protein-rich foods than their counterpart. SEM analysis showed that the poor nutritional biochemistry profiles linked the association between unhealthy dietary patterns and ADHD. In conclusion, an unhealthy dietary pattern may be a predecessor of the poor nutritional biochemistry status, and managing diet and nutrition conditions should be considered to improve ADHD symptoms in children.

Association between Interleukin-6 Levels and Perioperative Fatigue in Gastric Adenocarcinoma Patients.

BACKGROUND: Gastric adenocarcinoma (GA), one of the most common gastrointestinal cancers worldwide, is often accompanied by cancer cachexia in the advanced stage owing to malnutrition and cancer-related symptoms. Although resection is the most effective curative procedure for GA patients, it may cause perioperative fatigue, worsening the extent of cancer cachexia. Although the relationship between cytokines and cancer fatigue has been evaluated, it is unclear which cytokines are associated with fatigue in GA patients. Therefore, this study aimed to investigate whether the changes in cytokine levels were associated with the perioperative changes in fatigue amongst GA patients. METHODS: We included GA patients undergoing gastric surgery in a single academic medical center between June 2017 and December 2018. Fatigue-related questionnaires, serum cytokine levels (interferon-gamma, interleukin (IL)-1, IL-2, IL-5, IL-6, IL-12 p70, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor), and biochemistry profiles (albumin, prealbumin, C-reactive protein, and white blood cell counts) were assessed at three time points (preoperative day 0 (POD 0), post-operative day 1 (POD 1), and postoperative day 7 (POD 7)). We used the Brief Fatigue Inventory-Taiwan Form to assess the extent of fatigue. The change in fatigue scores among the three time points, as an independent variable, was adjusted for clinicopathologic characteristics, malnutrition risk, and cancer stages. RESULTS: A total of 34 patients were included for analysis, including 12 female and 22 male patients. The mean age was 68.9 years. The mean score for fatigue on POD 0, POD 1, and POD 7 was 1.7, 6.2, and 3.6, respectively, with significant differences among the three time points (P < 0.001). Among the cytokines, only IL-6 was significantly elevated from POD 0 to POD 1. In the regression model, the change in IL-6 levels between POD 0 and POD 1 (coefficients = 0.01 for every 1 pg/mL increment; 95% confidence interval: 0.01-0.02; P = 0.037) and high malnutrition risk (coefficients = 2.80; 95% confidence interval: 1.45-3.52; P = 0.041) were significantly associated with changes in fatigue scores. CONCLUSIONS: The perioperative changes in plasma IL-6 levels are positively associated with changes in the fatigue scores of GA patients undergoing gastric surgery. Targeting the IL-6 signaling cascade or new fatigue-targeting medications may attenuate perioperative fatigue, and further clinical studies should be designed to validate this hypothesis.