Objective:To compare the enrichment effects of ultrafiltration, polyethylene glycol (PEG) precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution on viruses in drinking water.Methods:Using phage MS2 as the target virus, three different concentrations of drinking water samples were prepared, and the samples were enriched by ultrafiltration 1, ultrafiltration 2, PEG precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution method, respectively. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to quantify MS2 nucleic acid in pre and post concentrated samples and the recovery rates of MS2 in samples with high, medium and low concentrations were compared among the five methods.Results:Comparing the MS2 enrichment recovery rates of individual enrichment method in water samples of different concentrations, ultrafiltration method 1, PEG precipitation method, aluminum salt precipitation method, and membrane adsorption-elution method were not affected by the sample concentration, and the differences of the recovery rates for the three concentration water samples among the four methods were not statistically significant ( P>0.05). The MS2 enrichment recovery rates of the five enrichment methods were significantly different in all concentration samples ( P<0.05). The recovery rates of ultrafiltration method 1 were higher in all three concentration samples, followed by aluminum salt precipitation and anionic membrane adsorption-elution, PEG precipitation were higher in high concentration samples, but lower in low and medium concentration samples, and the recovery rates of ultrafiltration method 2 were the lowest in all three concentration samples. Comparing the Ct values of MS2 in the enriched samples by five methods, the Ct values of ultrafiltration method 1 were the smallest in the three concentration water samples. There was no statistically significant difference in MS2 Ct values among the five enrichment methods in the medium and high concentration water samples ( P>0.05). In low concentration simulated water samples, only the difference of MS2 Ct value between ultrafiltration method 1 and ultrafiltration method 2 was statistically significant ( Z=16.000, P=0.016). Conclusions:Considering the operation simplicity, operation time and virus recovery rate after enrichment, ultrafiltration was the most effective method for virus enrichment in drinking water.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, causing dementia and affecting millions of individuals. One prominent characteristic in the brains of AD patients is glucose hypometabolism. In the context of galactose metabolism, intracellular glucose levels are heightened. Galactose mutarotase (GALM) plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion of β-D-galactose into α-D-galactose (α-D-G). The latter is then converted into glucose-6-phosphate, improving glucose metabolism levels. However, the involvement of GALM in AD progression is still unclear. In the present study, we found that the expression of GALM was significantly increased in AD patients and model mice. Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein (APP) and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), β-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and Aβ deposition by increasing the maturation of ADAM10, although it did not alter the expression of BACE1 and PS1. Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation (LTP) and spatial learning and memory in AD model mice. Importantly, direct α-D-G (20 mg/kg, i.p.) also inhibited Aβ deposition by increasing the maturation of ADAM10, thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, our results indicate that GALM shifts APP processing towards α-cleavage, preventing Aβ generation by increasing the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and α-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
Animals ; ADAM10 Protein/metabolism* ; Alzheimer Disease/pathology* ; Amyloid Precursor Protein Secretases/metabolism* ; Disease Models, Animal ; Humans ; Mice ; Amyloid beta-Peptides/metabolism* ; Male ; Mice, Transgenic ; Membrane Proteins/metabolism* ; Cognitive Dysfunction/pathology* ; Mice, Inbred C57BL ; Amyloid beta-Protein Precursor/metabolism* ; Female ; Hippocampus/metabolism* ; Long-Term Potentiation/physiology*

Objective To develop a method of pulsed direct current electrospray ionization mass spectrometry(pulsed-dc-ESI-MS)for rapid detection of 4 kinds of amphetamines in saliva.Methods Saliva samples were adjusted to optimal pH using NaOH,followed by protein precipitation with anhydrous magnesium sulfate and liquid-liquid extraction with ethyl acetate.The supernatant was then analyzed via pulsed-dc-ESI-MS.Results The limits of detection were 0.01～0.5 ng/mL and the limits of quantitative were 1.0～5.0 ng/mL.In addition,in the concentration range,4 amphetamines have good linear relationships,the correlation coefficients(R2)were all greater than 0.999,the recoveries of 97.21%～104.70%and the relative standard deviations(RSDs)were less than 10%.Conclusion The method has the advantages of simple operation,fast detection,high sensitivity,selectivity and good stability.It can be used for on-site rapid detection of amphetamines in saliva.

Objective:To compare the enrichment effects of ultrafiltration, polyethylene glycol (PEG) precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution on viruses in drinking water.Methods:Using phage MS2 as the target virus, three different concentrations of drinking water samples were prepared, and the samples were enriched by ultrafiltration 1, ultrafiltration 2, PEG precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution method, respectively. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to quantify MS2 nucleic acid in pre and post concentrated samples and the recovery rates of MS2 in samples with high, medium and low concentrations were compared among the five methods.Results:Comparing the MS2 enrichment recovery rates of individual enrichment method in water samples of different concentrations, ultrafiltration method 1, PEG precipitation method, aluminum salt precipitation method, and membrane adsorption-elution method were not affected by the sample concentration, and the differences of the recovery rates for the three concentration water samples among the four methods were not statistically significant ( P>0.05). The MS2 enrichment recovery rates of the five enrichment methods were significantly different in all concentration samples ( P<0.05). The recovery rates of ultrafiltration method 1 were higher in all three concentration samples, followed by aluminum salt precipitation and anionic membrane adsorption-elution, PEG precipitation were higher in high concentration samples, but lower in low and medium concentration samples, and the recovery rates of ultrafiltration method 2 were the lowest in all three concentration samples. Comparing the Ct values of MS2 in the enriched samples by five methods, the Ct values of ultrafiltration method 1 were the smallest in the three concentration water samples. There was no statistically significant difference in MS2 Ct values among the five enrichment methods in the medium and high concentration water samples ( P>0.05). In low concentration simulated water samples, only the difference of MS2 Ct value between ultrafiltration method 1 and ultrafiltration method 2 was statistically significant ( Z=16.000, P=0.016). Conclusions:Considering the operation simplicity, operation time and virus recovery rate after enrichment, ultrafiltration was the most effective method for virus enrichment in drinking water.

Objective To develop a method of pulsed direct current electrospray ionization mass spectrometry(pulsed-dc-ESI-MS)for rapid detection of 4 kinds of amphetamines in saliva.Methods Saliva samples were adjusted to optimal pH using NaOH,followed by protein precipitation with anhydrous magnesium sulfate and liquid-liquid extraction with ethyl acetate.The supernatant was then analyzed via pulsed-dc-ESI-MS.Results The limits of detection were 0.01～0.5 ng/mL and the limits of quantitative were 1.0～5.0 ng/mL.In addition,in the concentration range,4 amphetamines have good linear relationships,the correlation coefficients(R2)were all greater than 0.999,the recoveries of 97.21%～104.70%and the relative standard deviations(RSDs)were less than 10%.Conclusion The method has the advantages of simple operation,fast detection,high sensitivity,selectivity and good stability.It can be used for on-site rapid detection of amphetamines in saliva.

Objective:To explore the influencing factors and pathways of home-based exercise rehabilitation compliance in patients after percutaneous coronary intervention (PCI), so as to provide theoretical basis for formulating targeted intervention program.Methods:From July 2022 to February 2023, convenience sampling was used to select 220 patients who underwent PCI at Yantai Yuhuangding Hospital affiliated with Qingdao Medical College, Qingdao University as the study subject. A survey was conducted on patients using the General Information Questionnaires, Self-Efficacy for Exercise Scale, Illness Perception and Behavior Questionnaire in Patients with Coronary Heart Disease after PCI, Social Support Rating Scale, and Exercise Rehabilitation Compliance Follow-up Scale.Results:A total of 220 questionnaires were distributed, and 215 valid questionnaires were collected, with an effective response rate of 97.73% (215/220). The Exercise Rehabilitation Compliance Follow-up Scale in 215 patients after PCI was (11.35±3.85). The mediating effect of exercise self-efficacy between social support and exercise compliance was 0.150 [95% CI (0.055, 0.167), P<0.01], and the mediating effect of disease cognition between social support and exercise compliance after PCI was 0.065 [95% CI (0.016, 0.090), P<0.05]. The direct effect of social support on exercise compliance was 0.238 [95% CI (0.064, 0.278), P<0.01], and the indirect effect was 0.215 [95% CI (0.083, 0.233), P<0.05], and the mediating effect accounted for 47.46% of the total effect. Conclusions:Social support can directly or indirectly affect the compliance of patients with home-based exercise rehabilitation through the mediating effect of exercise self-efficacy and post PCI disease cognition. Medical and nursing staff can improve patient exercise self-efficacy and disease cognition by constructing intervention strategies based on social support, thereby enhancing home-based exercise rehabilitation compliance.

Objective:To explore the level of physical activity of Chinese adults with haemophilia and its related factors so as to provide a reference for their comprehensive management.Methods:The daily physical activity of adults with haemophilia was surveyed using the International Physical Activity Questionnaire (IPAQ). A total of 110 questionnaires were eligible for analysis at last. The results were compared with published data from other societies using independent sample t-tests and chi squared tests. Spearman correlation analysis and multivariate logistic regression analysis were applied to explore factors related to the subjects′ physical activity levels.Results:Fully 30.9% of the subjects claimed to maintain a high level of physical activity. This was significantly different from the distribution of physical activity observed in Japan (12.4%), Ireland (50.9%) and the United Kingdom (43.1%). According to the Spearman correlation analysis, the number of joints affected, anxiety, and depression are all significantly related to the level of physical activity among such adults. Multivariate logistic regression analysis showed that depression was an independent factor affecting the patients′ level of physical activities.Conclusion:Chinese and Japanese adults with hemophilia have relatively low levels of physical activity, possibly influenced by depression.

Objective:To investigate the expression and clinical significance of microRNA-124(miR-124)and microRNA-1976(miR-1976)in the serum of patients with Parkinson's disease(PD).Methods:A total of 58 patients with PD were selected from September 2020 to June 2022 and categorized as the PD group.The Unified Parkinson's Disease Rating Scale(UPDRS)score was used to divide the PD patients into two groups: those with a UPDRS score≤60(25 patients)and those with a UPDRS score >60(33 patients). The Hoehn-Yahr grading scale was used to grade the PD patients.Additionally, 30 healthy individuals who had undergone a physical examination during the same period were selected as the control group.After collecting the subjects' serum, we performed real-time fluorescent quantitative PCR(qRT-PCR)to detect the expressions of miR-124 and miR-1976 in the serum.Logistic regression analysis was employed to analyze the influencing factors, and the diagnostic significance of serum miR-124 and miR-1976 in PD patients was evaluated using the receiver operating characteristic(ROC)curve.To predict the target genes of miR-1976, we utilized several software including TargetScan and Mirtarbase.Results:Compared to the control group, the PD group showed a significant down-regulation of serum miR-124 expression[(1.49±0.36) vs.(1.02±0.32)]( t=8.85, P<0.001), while miR-1976 expression was sharply up-regulated[(0.98±0.30) vs.(1.33±0.37)]( t=6.92, P<0.001). The low expression of serum miR-124 and the overexpression of miR-1976 were identified as independent risk factors for PD( OR>1, P<0.05). The Hoehn-Yahr rating of PD patients with a UPDRS score above 60 was higher than that of patients with a UPDRS score below 60[(3.42 ± 0.73) vs.(2.16 ± 0.42)]( t=3.05, P<0.05). However, there was no significant difference in serum miR-124 and miR-1976 expression between groups with different UPDRS scores[miR-124: (1.09±0.26) vs.(0.98±0.38)( t=0.89, P>0.05); miR-1976: (1.42±0.43) vs.(1.23±0.68)( t=0.62, P>0.05)]. The ROC analysis results demonstrated that miR-124 and miR-1976 had area under the curve(AUC)values of 0.832 and 0.797, respectively, in diagnosing PD.The corresponding cutoff values were 1.205 and 1.196, respectively.The sensitivity for miR-124 was 74.1%, while for miR-1976 it was 51.8%.The specificity for miR-124 was 77.8%, and for miR-1976 it was 90.1%.When both miR-124 and miR-1976 were combined in the diagnosis of PD, the AUC was 0.912, with a sensitivity of 76.4% and a specificity of 93.2%.Furthermore, it was found that miR-1976 targeted the PINK1 gene, suggesting its potential as a target gene in PD. Conclusions:The expression of miR-124 was found to be decreased in PD patients, while the expression of miR-1976 was increased.Both miR-124 and miR-1976 showed some reference value in PD diagnosis, and their combined diagnostic value was higher.This suggests that further study on their significance is warranted.However, it should be noted that the expressions of miR-124 and miR-1976 were not found to be correlated with the UPDRS score of PD patients.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.