A composite gel formed by konjac glucomannan together with Nano-CF obtained by FeCl3-citric acid hydrolysis as a potential fat substitute.

This study aims to fabricate composite gels using nano citrus fiber (Nano-CF) derived from the hydrolysis process of citric acid (CA) with FeCl3, with a simultaneous exploration of its potential as an substitute to fats. Investigation of varying FeCl3 concentrations (0.01 to 0.03 mmol/g of CA) revealed a significant enhancement in the water-holding and oil-retention capacity of the Nano-CF. The meticulous synthesis of the composite gels involved integrating nano citrus fibers with konjac glucomannan (KGM) through high-speed shearing, followed by a comprehensive evaluation of its microstructure and physicochemical attributes. Increasing the Nano-CF concentration within the gels led to a synergistic interaction with KGM, resulting in enhanced viscosity, improved thermal stability, and restricted water molecule mobility within the system. The gels initially displayed reduced firmness, resilience, and adhesive characteristics, followed by subsequent improvement. When the ratio of Nano-CF to KGM was 0.5:1, the composite gels exhibited texture parameters, viscosity, and viscoelastic stability comparable to whipped animal cream formulations. These findings provide a new idea for the application of Nano-CF/KGM composite gels in whipped cream.

Family analysis and literature study of hereditary hypophosphatemic rickets with hypercalciuria.

BACKGROUND: Hereditary hypophosphatemia rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder characterised by reduced renal phosphate reabsorption leading to hypophosphataemia, rickets and bone pain. Here, we present a case of HHRH in a Chinese boy. CASE PRESENTATION: We report a 11-year-old female proband, who was admitted to our hospital with bilateral genuvarum deformity and short stature. Computed Tomography (CT) showed kidney stones, blood tests showed hypophosphatemia, For a clear diagnosis, we employed high-throughput sequencing technology to screen for variants. Our gene sequencing approach encompassed whole exome sequencing, detection of exon and intron junction regions, and examination of a 20 bp region of adjacent introns. Flanking sequences are defined as ±50 bp upstream and downstream of the 5' and 3' ends of the coding region.The raw sequence data were compared to the known gene sequence data in publicly available sequence data bases using Burrows-Wheeler Aligner software (BWA, 0.7.12-r1039), and the pathogenic variant sites were annotated using Annovar. Subsequently, the suspected pathogenic variants were classified according to ACMG's gene variation classification system. Simultaneously, unreported or clinically ambiguous pathogenic variants were predicted and annotated based on population databases. Any suspected pathogenic variants identified through this analysis were then validated using Sanger sequencing technology. At last, the proband and her affected sister carried pathogenic homozygous variant in the geneSLC34A3(exon 13, c.1402C > T; p.R468W). Their parents were both heterozygous carriers of the variant. Genetic testing revealed that the patient has anLRP5(exon 18, c.3917C > T; p.A1306V) variant of Uncertain significance, which is a rare homozygous variant. CONCLUSION: This case report aims to raise awareness of the presenting characteristics of HHRH. The paper describes a unique case involving variants in both theSLC34A3andLRP5genes, which are inherited in an autosomal recessive manner. This combination of gene variants has not been previously reported in the literature. It is uncertain whether the presence of these two mutated genes in the same individual will result in more severe clinical symptoms. This report shows that an accurate diagnosis is critical, and with early diagnosis and correct treatment, patients will have a better prognosis.

Design, characterization and digestibility of ß-carotene-loaded emulsion system stabilized by whey protein with chitosan and potato starch addition.

The physicochemical properties and gastrointestinal fate of ß-carotene-loaded emulsions and emulsion gels were examined. The emulsion was emulsified by whey protein isolate and incorporated with chitosan, then the emulsion gels were produced by gelatinizing potato starch in the aqueous phase. The rheology properties, water distribution, and microstructure of emulsions and emulsion gels were modulated by chitosan combination. A standardized INFOGEST method was employed to track the gastrointestinal fate of emulsion systems. Significant changes in droplet size, zeta-potential, and aggregation state were detected during in vitro digestion, including simulated oral, stomach, and small intestine phases. The presence of chitosan led to a significantly reduced free fatty acids release in emulsion, whereas a slightly increasing released amount in the emulsion gel. ß-carotene bioaccessibility was significantly improved by hydrogel formation and chitosan addition. These results could be used to formulate advanced emulsion systems to improve the gastrointestinal fate of hydrophobic nutraceuticals.

Bidirectional association between hypothyroidism and myasthenia gravis: a Mendelian randomized study.

OBJECTIVES: Although observational studies have suggested a link between hypothyroidism and myasthenia gravis (MG), a causal relationship has not been established. We aimed to investigate the causal association using a two-sample Mendelian randomization (MR) study. METHODS: Using summary statistics from genome-wide association studies involving 494,577 and 38,243 individuals, single-nucleotide polymorphisms exhibiting no linkage disequilibrium (r2 ≤ 0.001) and displaying significant differences (p ≤ 5 × 10-8) were selected for hypothyroidism and MG. To assess the potential causality relationship between hypothyroidism and MG, MR analysis was conducted using inverse variance weighted (IVW), weighted median method, and MR-Egger. The MR-Egger regression, heterogeneity test, pleiotropy test, and leave-one-out sensitivity test were employed to examine sensitivity analyses. In addition, validation datasets were used to validate the relevant results. RESULTS: Genetic liability to hypothyroidism was positively associated with MG (IVW, OR: 1.36, 95% CI: 1.17-1.58, p = 7.53 × 10-05; weighted median, OR: 1.19, 95% CI: 0.70-2.02, p = 0.522; MR-Egger, OR: 1.19, 95% CI: 0.98-1.45, p = 0.080). Among the three MR methods, the correlation between hypothyroidism and MG genetic prediction was consistent. The independent validation set (IVW, OR: 466.47, 95% CI: 4.70 -46,285.95, p = 0.01) further supported this. Additionally, bidirectional studies showed that using IVW, there was no reverse causality (OR: 1.104, 95%CI: 0.96-1.27, p = 0.170). DISCUSSION: This MR study showed that hypothyroidism can increase the risk of MG. Further investigation into the underlying mechanisms of this potential causality is warranted to offer novel therapeutic options for MG in the future.

A Diagnostic Model for Parkinson's Disease Based on Anoikis-Related Genes.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, and its pathological mechanisms are thought to be closely linked to apoptosis. Anoikis, a specific type of apoptosis, has recently been suggested to play a role in the progression of Parkinson's disease; however, the underlying mechanisms are not well understood. To explore the potential mechanisms involved in PD, we selected genes from the GSE28894 dataset and compared their expression in PD patients and healthy controls to identify differentially expressed genes (DEGs), and selected anoikis-related genes (ANRGs) from the DEGs. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression approach and multivariate logistic regression highlighted five key genes-GSK3B, PCNA, CDC42, DAPK2, and SRC-as biomarker candidates. Subsequently, we developed a nomogram model incorporating these 5 genes along with age and sex to predict and diagnose PD. To evaluate the model's coherence, clinical applicability, and distinguishability, we utilized receiver operating characteristic (ROC) curves, the C-index, and calibration curves and validated it in both the GSE20295 dataset and our center's external clinical data. In addition, we confirmed the differential expression of the 5 model genes in human blood samples through qRT-PCR and Western blotting. Our constructed anoikis-related PD diagnostic model exhibits satisfactory predictive accuracy and offers novel insights into both diagnosis and treatment strategies for Parkinson's disease while facilitating its implementation in clinical practice.

The lipid digestion behavior of oil-in-water emulsions stabilized by different particle-sized insoluble dietary fiber from citrus peel.

In this study, oil-in-water emulsions stabilized by insoluble dietary fibre from citrus peel (CIDF) exhibited an obviously delayed lipid digestion property through gastrointestinal tract (GIT) model. Our results suggested that the rate and extent of lipid digestion greatly relied on particle sizes and concentrations of CIDF, and the inhibition effect of lipolysis was markedly enhanced with decreasing particle sizes and increasing CIDF levels. Furthermore, compared with Tween80-stabilized emulsion, the maximum inhibition extent of lipolysis was 38.77% for CIDF400-stabilized one at 0.4 wt% concentration. Effects of CIDFs on lipid digestion was mainly due to the formation of protective layers around oil droplets, further blocking the entry of lipase to the internal lipids, and/or attributed to the increasing viscosity of emulsions caused by CIDFs, finally limiting the transportation of some substances in the simulated small intestine digestion. Our research would provide useful references for the application of CIDF-stabilized emulsions in low-calorie food.

In-situ label-free temperature-compensated DNA hybridization detection with a fiber-optic interferometer and a fiber Bragg grating for microfluidic chip.

We demonstrated a temperature-compensated optofluidic DNA biosensor available for microfluidic chip. The optofluidic sensor was composed of an interferometer and a fiber Bragg grating (FBG) by femtosecond laser direct writing micro/nano processing technology. The sensing arm of the interferometer was suspended on the inner wall of the microchannel and could directly interact with the microfluid. With the immobilization of the single stranded probe DNA (pDNA), this optofluidic biosensor could achieve specific detection of single stranded complementary DNA (scDNA). The experimental results indicated that a linear response within 50 nM and the detection limit of 1.87 nM were achieved. In addition, the optofluidic biosensor could simultaneously monitor temperature to avoid temperature fluctuations interfering with the DNA hybridization detection process. And, the optofluidic detection channel could achieve fast sample replacement within 10 s at a flow rate of 2 µL/min and sample consumption only required nanoliters. This optofluidic DNA biosensor had the advantages of label-free, good specificity, dual parameter detection, low sample consumption, fast response, and easy repeatable preparation, which was of great significance for the field of DNA hybridization research and solving the temperature sensitivity problem of biosensors and had good prospects in biological analysis.

Development of gene model combined with machine learning technology to predict for advanced atherosclerotic plaques.

BACKGROUND: Atherosclerosis, as a major cause of stroke, is responsible for a quarter of deaths worldwide. In particular, rupture of late-stage plaques in large vessels such as the carotid artery can lead to serious cardiovascular disease. The aim of our study was to establish a genetic model combined with machining leaning techniques to screen out gene signatures and predict for advanced atherosclerosis plaques. METHODS: The microarray dataset GSE28829 and GSE43292 which were publicly obtained from the Gene Expression Omnibus database were utilized to screen for potential predictive genes. Differentially expressed genes (DEGs) were identified by using the "limma" R package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG) analyses of these DEGs were performed by Metascape. Later, Random Forest (RF) algorithm was applied to further screen out top-30 genes which contribute the most. The expression data of top 30-DEGs were converted into a "Gene Score". Finally, we developed a model based on artificial neural network (ANN) to predict advanced atherosclerotic plaques. The model later was validated in an independent test dataset GSE104140. RESULTS: A total of 176 DEGs were identified in the training datasets. GO and KEGG enrichment analysis revealed that these genes were enriched in leukocyte-mediated immune response, cytokine- cytokine interactions, and immunoinflammatory signaling. Further, top-30 genes (including 25 upregulated and 5 downregulated DEGs) were screened as predictors by RF algorithm. The predictive model was developed with a significantly predictive value (AUC = 0.913) in the training datasets, and was validated with an independent dataset GSE104140 (AUC = 0.827). CONCLUSION: In present study, our prediction model was established and showed satisfactory predictive power in both training and test datasets. In addition, this is the first study adopted bioinformatics methods combined with machine learning techniques (RF and ANN) to explore and predict for the advanced atherosclerotic plaques. However, further investigations were needed to verify the screened DEGs and predictive effectiveness of this model.

M6A-Related Long Non-Coding RNA Displays Utility in Predicting Prognosis, Portraying the Tumor Immune Microenvironment and Guiding Immunotherapy in Pancreatic Ductal Adenocarcinoma.

N6-methyladenosine (m6A) lncRNA plays a pivotal role in cancer. However, little is known about its role in pancreatic ductal adenocarcinoma (PDAC) and its tumor immune microenvironment (TIME). Based on The Cancer Genome Atlas (TCGA) cohort, m6A-related lncRNAs (m6A-lncRNA) with prognostic value were filtered using Pearson analysis and univariate Cox regression analysis. Distinct m6A-lncRNA subtypes were divided using unsupervised consensus clustering. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to establish an m6A-lncRNA-based risk score signature. The CIBERSORT and ESTIMATE algorithms were employed to analyze the TIME. The expression pattern of TRAF3IP2-AS1 was examined using qRT-PCR. The influence of TRAF3IP2-AS1 knockdown on cell proliferation was estimated by performing CCK8, EdU and colony-formation assays. Flow cytometry was applied to measure the effect of TRAF3IP2-AS1 knockdown on cell cycle and apoptosis. The in vivo anti-tumor effect of TRAF3IP2-AS1 was validated in a tumor-bearing mouse model. Two m6A-lncRNA subtypes with different TIME features were clarified. A risk score signature was constructed as a prognostic predictor based on m6A-lncRNAs. The risk score also correlated with TIME characterization, which facilitated immunotherapy. Finally, the m6A-lncRNA TRAF3IP2-AS1 was proved to be a tumor suppressor in PDAC. We comprehensively demonstrated m6A-lncRNAs to be useful tools for prognosis prediction, TIME depiction and immunotherapeutic guidance in PDAC.

Parkinson's Disease Gene Biomarkers Screened by the LASSO and SVM Algorithms.

Parkinson's disease (PD) is a common progressive neurodegenerative disorder. Various evidence has revealed the possible penetration of peripheral immune cells in the substantia nigra, which may be essential for PD. Our study uses machine learning (ML) to screen for potential PD genetic biomarkers. Gene expression profiles were screened from the Gene Expression Omnibus (GEO). Differential expression genes (DEGs) were selected for the enrichment analysis. A protein-protein interaction (PPI) network was built with the STRING database (Search Tool for the Retrieval of Interacting Genes), and two ML approaches, namely least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE), were employed to identify candidate genes. The external validation dataset further tested the expression degree and diagnostic value of candidate biomarkers. To assess the validity of the diagnosis, we determined the receiver operating characteristic (ROC) curve. A convolution tool was employed to evaluate the composition of immune cells by CIBERSORT, and we performed correlation analyses on the basis of the training dataset. Twenty-seven DEGs were screened in the PD and control samples. Our results from the enrichment analysis showed a close association with inflammatory and immune-associated diseases. Both the LASSO and SVM algorithms screened eight and six characteristic genes. AGTR1, GBE1, TPBG, and HSPA6 are overlapping hub genes strongly related to PD. Our results of the area under the ROC (AUC), including AGTR1 (AUC = 0.933), GBE1 (AUC = 0.967), TPBG (AUC = 0.767), and HSPA6 (AUC = 0.633), suggested that these genes have good diagnostic value, and these genes were significantly associated with the degree of immune cell infiltration. AGTR1, GBE1, TPBG, and HSPA6 were identified as potential biomarkers in the diagnosis of PD and provide a novel viewpoint for further study on PD immune mechanism and therapy.

Association between plasma trimethylamine-N-oxide and cognitive impairment in patients with transient ischemic attack.

BACKGROUND: There is increasing evidence for the association of trimethylamine-N-oxide (TMAO) with cognitive impairment after minor stroke or transient ischemic attack (TIA). However, how TMAO affects cognitive function in TIA patients has seldom been studied. METHODS: A total of 310 TIA participants were retrospectively collected from our stroke register between January 2020 and July 2021. Plasma TMAO was measured by liquid chromatography‒mass spectrometry at baseline. Cognitive performance was assessed by neuropsychological evaluation at 3 months after TIA onset. RESULTS: A total of 310 patients were included (mean age, 74 years; male, 160 [51.6%]; mean ABCD2 score, 2.6). TMAO was positively associated with cognitive impairment after TIA (aOR, 1.423; 95% CI, 1.125-2.561). The highest quartile of TMAO was related to an almost 2-fold increased risk of cognitive decline compared to the lowest quartile. Furthermore, executive and memory function were more susceptible to impairment after TIA in groups with higher levels of TMAO. Mediation analysis revealed that the overall mediated effect was-0.347 (p < 0.001), and the intermediary effect of CRP was-0.108. CONCLUSION: Plasma TMAO at baseline was independently associated with cognitive impairment at the 3-month follow-up after TIA. In addition, the inflammatory marker CRP may serve as an important mediator in this relationship. Our study may provide some insights into anti-inflammatory therapy to improve the cognitive trajectory of TIA patients with high TMAO levels.

A novel angiogenic effect of PCSK9- regulated genes.

BACKGROUND: Since the discovery of the Proprotein Convertase Subtilisin/Kexin Type 9(PCSK9) gene has been involved in regulating low-density lipoprotein metabolism and cardiovascular disease (CVD), many therapeutic strategies directly targeting PCSK9 have been introduced. PCSK9 gain of function (GoF) mutations are associated with autosomal dominant hypercholesterolemia (ADH) and premature atherosclerosis. In contrast, PCSK9 loss of function (LOF) mutations have cardioprotective effects and can lead to familial hypo cholesterol in some instances. However, its potential impacts beyond the typical effects on lipid metabolism have not been elucidated. Therefore the study aimed to identify and verify PCSK9's possible effects beyond its traditional role in lipid metabolism. METHODS: The S127R is a PCSK9 gain of function mutation. Firstly, We used the data of the gene expression Omnibus(GEO) database to identify the differentially expressed genes between S127R mutation carriers and ordinary people. Secondly, the identification and analysis of significant genes were performed with various bioinformatics programs. Thirdly, to verify the possible effect and the potential pathways of PCSK9 on angiogenesis, we constructed PCSK9 low and high expression models by transfecting PCSK9-siRNA (small interfering RNA) and PCSK9-plasmid complex into human umbilical vein endothelial cells (HUVECs), respectively. Furthermore, Wound-Healing Assay and Capillary tube formation assay were applied to measure the effect of PCSK9 on angiogenesis. Fourthly, the expression level of VEGFR2 and the significant genes between PCSK9 low and high expression models were verified by quantitative real-time PCR. All data were analysed by GraphPad Prism 8 software. RESULTS: 88 DEGs were identified, including 45 up-regulated and 43 down-regulated DEGs. Furthermore, we identified the six genes (MMP9, CASP3, EGR1, NGFR, LEFTY1 and NODAL) as significantly different genes between PCSK9-S127R and Control hiPSC. Further, we found that these significant difference genes were mainly associated with angiogenesis after enrichment analysis. To verify the possible effect of PCSK9 on angiogenesis, we constructed low and high-expression PCSK9 models by transfecting siRNA and PCSK9-plasmid complex into human umbilical vein endothelial cells (HUVECs), respectively. The tubule formation test and Wound healing assays showed that overexpression of PCSK9 had an inhibitory effect on angiogenesis, which could be reversed by decreasing the expression of PCSK9. Moreover, bioinformatics analysis indicated that the six hub genes (MMP9, CASP3, EGR1, NGFR, LEFTY1 and NODAL) might play a vital role in the biological function of PCSK9 in angiogenesis. Real-time quantitative PCR was applied to clarify the expression profiles of these critical genes in overexpression/knockdown PCSK9. Finally, the expression levels of MMP9, Caspase3, LEFTY1, and NODAL were suppressed by overexpression of PCSK9 and could be alleviated by PCSK9 knockdown. Otherwise, EGR1 had the opposite expression trend, and there was no specific trend of NGFR after repeated experiments. CONCLUSION: PCSK9 might play an essential role in angiogenesis, unlike its typical role in lipid metabolism, and MMP9, Caspase3, LEFTY1, NODAL, and EGR1 may be involved in the regulation of angiogenesis as critical genes.

Characteristics of composite gels composed of citrus insoluble nanofiber and amylose and their potential to be used as fat replacers.

Here, we prepared novel composite gels composed of citrus insoluble nanofiber and amylose, and examined their potential to be used as fat replacers and inhibit lipid digestion. We further evaluated the effect of different nanofiber/amylose ratios on the texture, thermal stability, water distribution, microstructure and lipid digestion of the composite gels. The addition of nanofiber improved the hardness, gumminess, viscoelasticity, thermal stability, and water-holding capacity of the composite gels, as well as strengthen their interpenetrating three-dimensional network. The gel prepared at a nanofiber/amylose ratio of 1:4 could provide an oral sensory perception similar to that of cream and therefore can be used as a potential fat replacer. Moreover, the emulsion stabilized by nanofiber/amylose could well inhibit lipid digestion, and the nanofiber/amylose ratio of 1:4 could achieve the minimum release amount of free fatty acids (55.81%). These findings provide a reference for the development of potential fat replacers.

Effect of particle size on composition, physicochemical, functional, and structural properties of insoluble dietary fiber concentrate from citrus peel.

To investigate the composition, physicochemical, functional, and structural properties of citrus insoluble dietary fiber concentrate from citrus peel affected by different particle sizes, citrus insoluble dietary fiber concentrate was modified by coarse crush and superfine grinding treatments. The results showed that the contents of hemicellulose and lignin significantly decrease and a significant increase in cellulose and insoluble dietary fiber contents with the reduction in particle size. In addition, the markedly decreased particle size and obviously microstructural changes of citrus insoluble dietary fiber concentrate powder were observed. The color value of citrus insoluble dietary fiber concentrate was observably improved, crystallinity and thermal stability of modified fiber slightly increase with the decrease in particle size, which is due to the partial elimination of hemicellulose and lignin after the treatments. However, water holding capacity, water swelling capacity, and oil holding capacity were found to be lower with the reduction in particle size, which might be attributed to the fact that superfine grinding treatment destroyed the structure integrity, thus causing some soluble components to break away from the cellulose backbone, or due to aggregation of smaller granules. The present study suggested that decreasing the particle size could effectively change some properties of citrus insoluble dietary fiber concentrate, which will provide new perspectives for the application of citrus insoluble dietary fiber concentrate in food products.

Effects of different particle-sized insoluble dietary fibre from citrus peel on adsorption and activity inhibition of pancreatic lipase.

Insoluble dietary fibre from citrus peels (CIDF) was found to have adsorption and inhibitory effect on the activity of pancreatic lipase (PL). CIDF-400 exhibited the greatest adsorption and activity inhibition effect on PL. The fluorescence quenching spectra indicated that CIDF could quench PL through a dynamic quenching process induced by the electrostatic interactions with only one binding site between them. The synchronous fluorescence and three-dimensional fluorescence spectra showed that CIDF might combine with PL to induce the increase in hydrophobicity and the reduction in polarity of tyrosine (Tyr) and tryptophan (Try) residues, which further led to the conformational alternations of PL. Moreover, circular dichroism (CD) showed that CIDF altered the secondary structure of PL, decreased α-helical structure content, and increased ß-sheet structure content, potentially resulting in PL structure opening and its active site exposure. This study provides new perspectives for the application of CIDFs produced from agricultural waste in regulating lipid metabolism.

The influence of unexpected early termination of intravenous rt-PA treatment on clinical outcome in acute ischemic stroke patients.

INTRODUCTION: This study aimed to explore the impact of unexpected early termination during intravenous thrombolysis on clinical prognosis in patients with acute ischemic stroke (AIS). METHODS: Patients who received intravenous thrombolysis were divided into an early termination group and a normal treatment group. The causes of unexpected termination were analyzed, and the prognosis was compared between the groups. RESULTS: The main causes of early termination of thrombolytic therapy included subjective wishes of family members (11.8%, 4) and persistently elevated blood pressure (14.7%, 5). The effective rate of thrombolytic therapy in the early termination group was significantly lower than that in the normal treatment group (P < 0.05). The rate of early neurological deterioration in the early termination group was significantly higher than that in the normal treatment group (P < 0.05). There was no significant difference in the incidence of symptomatic intracranial hemorrhage after thrombolysis between the two groups (P > 0.05). The average mRS score of the early termination group was significantly higher than that of the normal treatment group (P < 0.05). Multivariate analysis indicated that early termination of thrombolytic therapy and cumulative dosage of rt-PA before termination were the main factors affecting the 3-month prognosis. CONCLUSION: Subjective wishes of family members and persistently elevated blood pressure may be the main causes of early termination of thrombolysis, and the 3-month prognosis of patients could be adversely affected by early termination of thrombolytic therapy and cumulative dosage of rt-PA. Certain measures, such as popularizing thrombolytic health education and optimizing blood pressure management before and during thrombolysis, may be helpful for the normal operation of intravenous thrombolysis.

Neglected vitamin K deficiency causing coagulation dysfunction in an older patient with pneumonia: a case report.

BACKGROUND: The development of coagulation disorders can be dangerous and fatal in the older people, especially those with multiple medical conditions. Vitamin K-dependent coagulation disorders are easily overlooked when anticoagulant drugs are not used and the patient shows no signs of bleeding. CASE PRESENTATION: We report a case of a 71-year-old male suffering from pulmonary infection with severe coagulation disorder without bleeding symptoms. He also had a history of Parkinson's disease, Alzheimer's disease and cardiac insufficiency. Coagulation tests were normal at the time of admission, prothrombin time (PT) is 13.9 (normal, 9.5-13.1) seconds and the activated partial thromboplastin time (APTT) is 30.2 (normal, 25.1-36.5) seconds. But it turned severely abnormal after 20 days (PT: 136.1 s, APTT: 54.8 s). However, no anticoagulants such as warfarin was used and no bleeding symptoms were observed. Subsequent mixing studies with normal plasma showed a decrease in prothrombin times. Vitamin K deficiency was thought to be the cause of coagulation disorders considering long-term antibiotic therapy, especially cephalosporins, inadequate diet and abnormal liver function. After supplementation with 20 mg of vitamin K, coagulation dysfunction was rescued the next day and serious consequences were effectively prevented. CONCLUSIONS: Overall, timely vitamin K supplementation with antimicrobials that affect vitamin K metabolism requires clinician attention, especially in older patients who are multimorbid, frail or nutritionally compromised, and are admitted to hospital because of an infection that needs antimicrobial therapy are at risk of clotting disorders due to abnormal vitamin K metabolism secondary to altered gut flora, which can exacerbate existing nutritional deficiencies.

Targeting gut-brain axis through scalp-abdominal electroacupuncture in Parkinson's disease.

BACKGROUND: Evidence suggests that the pathogenesis of Parkinson's disease (PD) is initiated in the gut rather than in the brain. Thus, targeting the gut in early stages may have the potential to halt disease progression and alleviate symptoms. Various acupuncture techniques have been used to treat patients with PD and have shown promising results. However, previous acupuncture techniques focused on the brain and motor symptoms. We aimed to determine if targeting PD patients' gut-brain axis through electroacupuncture could be an effective, safe, and low-cost therapeutic option for management of non-motor and motor symptoms. METHODS: Thirty patients with mild to moderate PD were randomised into an intervention (n = 15) and a control group (n = 15). The intervention group received electroacupuncture twice a week for 30 min based on conventional drug treatment for 8 weeks. Conventional drug treatment was continued in the control group. The primary outcomes were changes in the score of clinical scales including the Non-motor Symptom Rating Scale (NMSS), PD Sleep Scale (PDSS), Bristol Stool Function Scale (BSFS), and Patient Associated Constipation and Quality of Life Scale (PAC-QOL). The secondary outcomes were the Unified PD Rating Scale (UPDRS) and Modified Hoehn-Yahr Staging Scale scores. Stool samples from the intervention group were collected before and after the procedure and were sent for gene sequencing. Adverse effects and personal impressions of the patients were noted during the course of the trial. RESULT: An 8-week course of scalp-abdominal electroacupuncture treatment was effective in improving the NMSS, PDSS, and UPDRS scores in patients with PD. Further, there was statistical significance in the two subdomains of NMSS, namely sleep/fatigue and miscellaneous, further implying the efficacy of acupuncture on sleep disturbance. However, although the current acupuncture treatment was gut targeted, it had no effect on BSFS or PAC-QOL. Apart from improved UPDRS motor scores and activities of daily living scores, acupuncture had no significant impact on scores of mentation, behaviour, mood, and therapy complications. Acupuncture did not alter the Hoehn and Yahr stage. Significant alterations in gut bacterial composition were detected in nine taxa at the genus level. The relative abundances of the genera Bacteroides and Parasutterella were significantly increased after the intervention, whereas the abundances of the genera Dialister, Hungatella, Barnesiella, Megasphaera, Allisonella, Intestinimon, and Moryella were significantly lower. CONCLUSION: An 8-week scalp-abdominal electroacupuncture treatment may be a complementary and alternative vehicle for PD patients. We detected nine taxa at the genus level which were significantly altered after treatment, emphasising the role of the gut-brain axis in the process.

Association between Cognitive Decline and Altered Cerebral Perfusion in Adults with Moyamoya Disease after Revascularization.

INTRODUCTION: Certain studies have observed that patients with moyamoya disease (MMD) have cognitive decline after revascularization. Thus, this study analyzed the relationship between cognitive decline and altered cerebral perfusion after revascularization. METHODS: Here, 313 adult patients with MMD underwent single unilateral revascularization. First, cognitive function was scored using a Mini-Mental Scale (MMSE) and Montreal cognitive function scale (MoCA) before and 3 months after the operation (superficial temporal artery-middle cerebral artery anastomosis with encephalo-myo-synangiosis). Then, computed tomography perfusion was performed before and 1 week after the operation to assess the cerebral perfusion. RESULTS: Our data showed that cognitive function decreased in 55 cases (17.6%) after revascularization. Furthermore, the incidence of cerebral hyperperfusion (CHP) was significantly higher in the cognitive decline group (49/55) than in the cognitive nondecline group (89.1% vs. 5.4%, p < 0.001). Results also showed that although all 55 patients had postoperative cognitive decline, 47 experienced relative cerebral blood flow (CBF) decrease at a relatively distant area of the anastomosis compared with that before the operation, which was significantly higher than in patients without cognitive decline (85.5% vs. 1.94%, p < 0.001). In addition, 41 patients had a simultaneous occurrence of local CHP and paradoxical CBF decrease at a relatively distant anastomosis area, which indicated the incident of watershed shift (WS). As observed, WS occurred in 74.5% of patients with cognitive decline, significantly higher than in patients without cognitive decline (74.5% vs. 0%, p < 0.0001). Through multiple logistic regression analysis, WS was also observed to be a strong independent risk factor for predicting postoperative cognitive decline 3 months after revascularization (odds ratio 17.780, 95% confidence interval 1.668-18.564; p = 0.017). CONCLUSION: Therefore, cognitive decline in patients with MMD after revascularization is related to WS, leading to an uneven distribution of CBF.

The neuroprotective effects of paeoniflorin against MPP+-induced damage to dopaminergic neurons via the Akt/Nrf2/GPX4 pathway.

Paeoniflorin (PF), a water-soluble monoterpene glycoside extracted from the root of Paeonia lactiflora Pall, has been shown to exert neuroprotective effects against neurodegenerative diseases such as Parkinson's disease (PD). However, its underlying mechanisms remain unknown. Our results showed that at certain concentrations, PF alleviated 1-methyl-4-phenylpyridinium (MPP+)-induced morphological damage and inhibited neuronal ferroptosis. Moreover, our research indicated that the neuroprotective effect of PF could be partially blocked by ML385 (a nuclear factor erythroid-2-related factor 2 (Nrf2) inhibitor) and LY29400 (an Akt inhibitor). These findings suggest that PF protects against MPP+-induced neurotoxicity by preventing ferroptosis via activation of the Akt/Nrf2/Gpx4 pathway in vitro.