Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Penicillium oxalicum strain can be isolated from the Bletilla striata (Thunb.) Reichb. f. tubers.Its solid-state fermentation products are concentrated by percolation extraction. Separation and purification have been conducted to the ethyl acetate extracts by preparative HPLC.Based on the use of spectrometry, we have determined 17 known compounds, 12,13-dihydroxy-fumitremorgin C (1), pseurotin A (2), tyrosol (3), cyclo-(L-Pro-L-Val) (4), cis-4-hydroxy-8-O-methylmellein (5), uracil (6), cyclo-(L-Pro-L-Ala) (7), 1,2,3,4-tetrahydro-4-hydroxy-4-quinolin carboxylic acid (8), cyclo-(Gly-L-Pro) (9), 2’-deoxyuridine (10), 1-(β-D-ribofuranosyl)thymine (11), cyclo-(L-Val-Gly) (12), 2’-deoxythymidine (13), cyclo-(Gly-D-Phe) (14), cyclo-L-(4-hydroxyprolinyl)-D-leucine (15), cyclo-(L)-4-hydroxy-Pro-(L)-Phe (16), uridine (17). Here, we report compounds 1–3, 5, 7–8, 11–12, 14–17 are first found and isolated from this endophyte.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

OBJECTIVE: To observe the influence of acupuncture on microcirculation perfusion of the pericardium meridian and heart in acute myocardial ischemia (AMI) rats and evaluate whether acupuncture can simultaneously affect the meridians and corresponding viscera. Additionally, acupoints at different meridians were compared and whether they exert the same effects was discussed. METHODS: Totally 32 Sprague-Dawley rats were subjected to left anterior descending (LAD) ligation to develop an AMI model. Rats were divided into 4 groups, including AMI, acupuncture Neiguan (PC 6), Lieque (LU 7) and Qiansanli (LI 10) groups (n=8). Eight rats received only thoracotomy (sham-operated group). The rats in the acupuncture groups received manual acupuncture at PC 6, LU 7 and LI 10 acupoints for 15 min, respectively. The microcirculation perfusion of pericardium meridian and heart was monitored by laser speckle perfusion imager (LSPI) before, during and after acupuncture manipulation for 15 min. Subsequently, the perfusion unit (PU) was calculated and analyzed by PSI System. RESULTS: After LAD, compared to pre-acupuncture stage, the heart microcirculation perfusion (HMP) in the AMI group decreased continuously at during-acupuncture (P>0.05) and post-acupuncture stages (P<0.05), and the pericardium meridian microcirculation perfusion (PMP) showed no significant differences at 3 stages (P>0.05). Compared to pre-acupuncture stage, the PMP and HMP in PC 6 group significantly increased during acupuncture manipulation (both P<0.05), and PMP decreased obviously after acupuncture (P<0.05). The PMP in the LU 7 and LI 10 groups were slightly elevated (both P>0.05); however, they were significantly reduced after acupuncture manipulation (both P<0.05). Additionally, HMP of LI 10 group was decreased significantly during acupuncture, especially compared to pre-acupuncture stage (P<0.05). CONCLUSIONS Acupuncture at PC 6 obviously increased the PMP and HMP in AMI rats, and the effects were superior to at LU 7 and LI 10 acupoints. It was further confirmed that acupuncture promoted qi and blood circulation, indicating that acupoint specificity exists and features a meridian-propagated effect.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Electroacupuncture ; Meridians ; Microcirculation ; Myocardial Ischemia ; Perfusion ; Pericardium ; Rats ; Rats, Sprague-Dawley

ObjectiveTo investigate the virologic response to direct-acting antiviral (DAA) therapy and the changes in liver stiffness measurement (LSM), fibrosis-4 (FIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) after treatment in chronic hepatitis C (CHC) patients with different alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at baseline in a real-world setting. MethodsCHC patients who attended the outpatient service of Department of Infectious Diseases, Peking University First Hospital, from December 2017 to May 2020 were enrolled, and virologic response rate was calculated. The Wilcoxon rank-sum test was used to compare LSM, FIB-4, and APRI between groups at baseline and at 12 weeks after treatment, and the chi-square test was used for comparison of categorical data between groups. ResultsA total of 48 CHC patients were enrolled, among whom 33.3% had abnormal ALT or AST at baseline. Among these patients, the virologic response rate was 85.4% at week 4 of treatment and 100% at the end of treatment and at 12, 24, and 48 weeks after treatment, and there were significant changes from baseline to 12 weeks after treatment in LSM ［6.1 (51-12.4) kPa vs 8.6 (5.7-16.9) kPa, Z=-1.676, P=0.043］ and APRI ［0.24(0.19-0.48) vs 0.42(0.23-1.17), Z=-2.050, P=0027］. From baseline to 12 weeks after treatment, the patients with abnormal ALT or AST at baseline had significant changes in LSM ［89(5.6-13.1) kPa vs 14.4(8.0-28.2) kPa, Z=-1.679, P=0.047］ and APRI ［0.44(0.25-0.50) vs 1.29(0.99-2.09), Z=-3.427, P=0.001］. ConclusionCHC patients achieve a high sustained virologic response rate after DAA therapy, and the patients with abnormal ALT or AST at baseline tend to have more significant improvements in LSM and APRI than those without such abnormality.

Objective:To explore the absorption and transport properties of flavanomarein in the Madin-Darby canine kidney(MDCK) monolayer cell model. Method:Methyl thiazolyl tetrazolium(MTT) assay was used to investigate the toxicity of flavanomarein in MDCK cells. The resistance value of MDCK monolayer cell model was detected by Millicell-ERS-2 cell resistometer. The effects of mass concentration of flavanomarein,administration time,sodium-glucose cotransporter(SGLTs) inhibitor and glucose transporter 2(GLUT2) inhibitor on the transmembrane transport of flavanomarein were investigated. The concentration of flavanomarein was determined by UPLC-MS/MS, and the apparent permeability coefficient(Papp) and the efflux ratio(ER) were calculated. Result:When the concentration of flavanomarein was 5.625-120 mg·L^-1, there was no significant toxic effect on MDCK cells. The transport of flavanomarein in MDCK monolayer cell model was time-dependent and concentration-dependent. The Papp values of flavanomarein were basically between 1×10^-6 cm·s^-1 to 10×10^-6 cm·s^-1. Compared with the blank group, the phlorizin group significantly reduced the transport of flavanomarein on the MDCK monolayer cell model at 60 min and 90 min. Conclusion:Flavanomarein is a moderately absorbed drug in the intestine, its transmembrane transport mechanism is dominated by passive transport along with active transport. SGLTs may be involved in mediating the transport of flavanomarein on the MDCK monolayer cell model.