Evaluation of serum neurofilament light chain and glial fibrillary acidic protein in the diagnosis of Alzheimer's disease.

Purpose: This study aimed to evaluate the use of serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in the diagnosis of Alzheimer's disease (AD) and the differential diagnosis between AD and mild cognitive impairment (MCI). Methods: From September 2021 to October 2022, we collected venous blood from patients and healthy individuals who visited our hospital's Neurology Department, and we isolated serum to detect NfL and GFAP using direct chemiluminescence. The results were analyzed using one-way analysis of variance (ANOVA) analysis and receiver operating characteristic (ROC) curves. Results: Pairwise comparisons among the three groups showed that compared with the health checkup (HC) group, serum NfL and GFAP were increased in both AD and MCI (PNfL < 0.05, PGFAP < 0.01). There were significant differences in GFAP between MCI and AD groups, and the level in AD group was higher (p < 0.01), while there was no difference in NfL. Both serum NfL and serum GFAP levels can independently diagnose AD (p < 0.01). The ROC curve showed that GFAP had a higher diagnostic efficacy, with an area under the ROC curve (AUC) of 0.928. The cut-off values of the two serum markers for the diagnosis of AD were NfL > 40.09 pg./mL and GFAP >31.40 pg./mL. Sensitivity and specificity for NfL in the diagnosis of AD were 59.6 and 76.2%, respectively, and for GFAP, they were 90.4 and 82.1%, respectively. The combined diagnosis of GFAP and NfL improved the diagnostic efficiency (AUC = 0.931, sensitivity = 78.8%, specificity = 92.3%). The cut-off value of GFAP for the differential diagnosis of MCI and AD was 46.05 pg./mL. Conclusion: Both serum NfL and serum GFAP can be used as biomarkers for the diagnosis of AD. Serum GFAP has better diagnostic efficacy and can distinguish AD from MCI. A combined diagnosis can improve diagnostic specificity.

The presumable effects of hydroxychloroquine and its metabolites in the treatment of systemic lupus erythematosus.

OBJECTIVE: Hydroxychloroquine (HCQ) is an essential drug in the treatment of systemic lupus erythematosus (SLE). This study aimed to detect the concentrations of HCQ and its metabolites from peripheral blood of SLE patients and to investigate the relationship between those concentrations and SLE disease activity. METHODS: 176 SLE patients treated with HCQ were enrolled in this study. The concentrations of HCQ and its metabolites in their peripheral blood were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Patients' disease activity was evaluated with the systemic lupus erythematosus disease activity index (SLEDAI). The variables between different concentrations or treatments were statistically analyzed. Linear regression was employed to explore relationships between the concentrations of HCQ and its metabolites with the disease activity. RESULTS: The SLEDAI was lower in patients with higher concentrations of HCQ, desethylhydroxychloroquine (DHCQ), and desethylchloroquine (DCQ) (P = 0.024, P = 0.018, and P = 0.003, respectively). There were no significant differences in SLEDAI and the concentrations of HCQ and its metabolites among groups with different treatments (P > 0.05). After adjusting age, gender, disease duration, HCQ dose adjusted to actual body weight, and glucocorticoid (GC) dose, the SLEDAI was negatively correlated with the concentrations of HCQ, DHCQ, DCQ and bisdesethylchloroquine (BDCQ) (P = 0.007, P = 0.011, P = 0.029, and P = 0.008, respectively). After grouping analysis, in patients treated with HCQ and GC, the SLEDAI was negatively correlated with concentrations of HCQ, DHCQ and BDCQ (P = 0.011, P = 0.035, and P = 0.036, respectively). CONCLUSIONS: The concentrations of HCQ and metabolites were correlated with the SLE disease activity after adjusting possible confounding factors, indicating that HCQ and its metabolites might play certain immunoregulatory roles in SLE treatment. Moreover, GC might have a synergistic effect with HCQ. It is helpful in clinical management and follow-up to monitor the concentrations of HCQ and its metabolites in SLE patients.

Bis-iodine-labeled Curcumin as a Potential CT Imaging Agent for ß-amyloid Plaques in the Brain.

BACKGROUND: Alzheimer's disease (AD) is one of the most common causes of dementia, affecting many old people. OBJECTIVES: By designing and synthesizing intracerebral imaging probes, we tried to provide a new solution for the early diagnosis of AD. METHODS: We designed and synthesized bis-iodine-labeled curcumin, and verified its performance through in vivo and in vitro experiments. RESULTS: In this study, bis-iodine-labeled curcumin (7, BICUR) was synthesized. In the in vitro mass spectrum binding assay, Kd values of BICUR with Aß1-40 and Aß1-42 aggregates were 46.29 nM and 64.29 nM, respectively. Aß plaques in AD brain adjacent sections were positively stained by BICUR, which was similar to some other curcumin derivatives. The Log P value of BICUR was 1.45. In the biodistribution experiment, BICUR showed the highest initial brain uptake (5.87% compared to the blood concentration) two minutes after the tail vein injection and rapid clearance from the mouse brain. In the acute toxicity experiment, BICUR showed low toxicity, and the LD50 was >100 mg/kg. Moreover, BICUR showed a high stability in vitro (86.68% unchanged BICUR after incubation for 120min in mouse brain homogenate). Besides, BICUR produced an enhanced CT imaging effect that could be sensitively detected in vitro, but it also showed an obvious differentiation from surrounding tissues after intracerebral injection. CONCLUSION: All results suggested that BICUR could probably act as a targeted CT imaging agent for Aß plaques in the brain.

Multi-fluorine labeled indanone derivatives as potential MRI imaging probes for ß-Amyloid plaques.

In order to realize the early diagnosis of Alzheimer's disease (AD), we designed and synthesized a series of multi-fluorine labeled indanone derivatives based on indanone which could target ß-amyloid (Aß). Through the in vitro staining experiment and affinity experiment, we selected 7d out, and then evaluated it through other in vivo and in vitro experiments. The staining of AD human brain adjacent sections revealed that compound 7d could bind to Aß plaques with high affinity. In the in vitro binding assay, 7d showed a balanced affinity with Aß1-40 (Kd = 367 ± 13) and Aß1-42 (Kd = 384 ± 56). Also, 7d exhibited a low toxicity (LD50 > 50 mg/kg) and an excellent ability to pass through the blood-brain barrier (Log p = 3.87). The biodistribution experiment in mice showed that 7d reached the highest brain uptake after 1 h of tail vein injection and cleared after 24 h. A low concentration of 7d (1.875 mg/ml) showed a strong imaging ability (19F-weighted mode), and the imaging capability increased with the increasing of concentration. All the results showed that 7d could provide a feasible solution for the early diagnosis of AD under non-radioactive condition.

Combined diagnosis of QF-PCR and CNV-Seq in fetal chromosomal abnormalities: A new perspective on prenatal diagnosis.

OBJECTIVE: This study aimed to evaluate the effect of QF-PCR and CNV-seq in diagnosing prenatal fetal chromosomal aberrations, explore the advantages and necessity of multimethod joint diagnosis. METHODS: We chose pregnant women with the indication of fetal chromosome examination in our hospital last year, collected 657 cases of amniotic fluid for QF-PCR and CNV-seq analyzes. RESULTS: While detecting aneuploidy, the coincidence rate of QF-PCR and CNV-seq was 100% (56/56). For all 46 chromosomes, 523 cases (79.60%, 523/657) coincided precisely, 128 cases (19.48%, 128/657) showed abnormality with CNV-seq, 8 cases (1.22%, 8/657) revealed abnormality by QF-PCR. In serological Down's syndrome screening, 328 cases showed a high risk of trisomy 21, of which CNV-seq and QF-PCR were consistent in 4 cases (1.22%, 4/328), CNV-seq found 87 cases of CNVs in 78 samples except for chromosomal aneuploidy abnormalities, among these, 18 cases (20.69%, 18/87) were polymorphic, 7 cases (8.05%, 7/87) might cause disease, 13 cases (14.94%, 13/87) caused disease explicitly, 21 cases (24.14%, 21/87) were possibly benign, 17 cases (19.54%, 17/87) were explicitly benign, and the classification of 11 cases (12.64%, 11/87) was unclear. CONCLUSION: QF-PCR and CNV-seq were highly consistent in diagnosing chromosomal aneuploidy. The high risk of serological Down's screening might not only due to the aneuploidy of chromosomes 21, 18, and NTD, but also the microdeletion or microduplication of all 46 chromosomes. So using CNV-seq combined with QF-PCR could effectively reduce the risk of missed diagnosis.

Melatonin binds with high affinity and specificity to beta-amyloid: LC-MS provides insight into Alzheimer's disease treatment.

To study the potential relationship between melatonin and beta-amyloid (Abeta), we established a liquid chromatography-mass spectrometry (LC-MS) method to quantitatively analyze melatonin, deuterated isotopes (melatonin-D4), and internal standard 6-iodo-2-(4'-dimethylamino-) phenyl-imidazo(1,2) pyridine (IMPY) under positive (+) mode. The gradient elution was set to 6 min, and the corresponding peak time of melatonin and its isotope melatonin-D4 was 3.14 min, while the peak time for the internal standard IMPY was 3.24 min. Next, we established and optimized the molecule receptor saturation binding assay based on LC-MS to determine the melatonin affinity for beta-amyloid (Abeta). Melatonin showed a high and specific binding for Abeta. The corresponding equilibrium dissociation constant (Kd) of melatonin with Abeta 1-40 and Abeta 1-42 was 814.37 ± 36.62 and 628.33 ± 13.57 nmol·L-1 ; besides, the Kd of melatonin with mixed plaques (1-40 and 1-42) was 461.13 ± 45.37 nmol·L-1 . The results may suggest the potential mechanism of action of MT on Abeta and provide a theoretical basis for the improvement of MT treatment of Alzheimer's disease.

Application Value of Triton X-100 to Modified Hodge Test and Carbapenem Inactivation Method in the Detection of Acinetobacter baumannii Carbapenemase.

AIM: To compare the sensitivity and specificity before and after the addition of Triton X-100 in the modified Hodge test (MHT) and carbapenem inactivation method (CIM) for the detection of carbapenemase in Acinetobacter baumannii. MATERIALS AND METHODS: A total of 135 isolates of A. baumannii (83 carbapenem-resistant and 52 carbapenem-sensitive) were selected and the carbapenemase genotypes were detected using PCR. Carbapenemase phenotypes were tested using the MHT, Triton-MHT (THT), CIM, modified CIM (mCIM), and Triton-CIM (TCIM). Different concentrations (0.05, 0.1, 0.25, and 0.5% v/v) of Triton X-100 were used in the TCIM. RESULTS: The sensitivity was determined to be 59.03% (MHT), 100% (THT), 6.02% (CIM), 8.43% (mCIM), 71.08% (TCIM 0.05%), 100% (TCIM 0.1%), 97.59% (TCIM 0.25%), and 96.38% (TCIM 0.5%) in 83 carbapenemase-producing isolates, and the specificity for each of these methods was 100%. CONCLUSION: The addition of Triton X-100 while using the MHT and CIM could significantly improve the sensitivity in the detection of A. baumannii carbapenemase with a specificity of 100%. A concentration of 0.1% v/v Triton X-100 showed the best results in TCIM.

Human papillomavirus infection and follow-up on positive results in 7222 female samples obtained from 2016 to 2019 in Hefei, China.

BACKGROUND: Human papillomavirus (HPV) infection rates in women vary regionally. This study analyzed HPV infection in women of different age groups in Hefei, China, performed follow-up on positive cases, and discussed infection prognoses. METHODS: Samples (7,222) of exfoliated cervical cells were collected in Hefei and tested with an HPV assay kit against 27 HPV genotypes. Statistical software was used to analyze the data. RESULTS: The total positive rate of infection was 17.13% (1,068 women), and the 51-60-year age group had the highest HPV infection rate (19.82%). There were statistically significant differences between rates in the 21-30 and 31-40 (P = 0.002), 21-30 and 41-50 (P = 0.0003), 21-30 and 51-60 (P = 0.00003), and 51-60 and >60 age groups (P = 0.046). High-risk infection (15.67%) and single infection (13.01%) were the main types of HPV infection. The dominant genotypes of high-risk infection were HPV 52 (2.42%), HPV 16 (2.01%), HPV 53 (1.43%), HPV 58 (1.32%) and HPV 66 (1.01%). We conducted follow-up on cases in 69 of 94 women who had a history of 1-4 years of positive infection, and in 18 (seven treated, 11 untreated) patients, infection status turned negative (26.09%). Seventeen of the fifty-one women whose infections did not turn negative received treatment. Persistent infection was predominantly observed in high-risk genotypes (56 of 69). CONCLUSIONS: The results recommend that women in Hefei improve health awareness and receive a 9-valent vaccine. Additionally, women with persistent infections should consult a gynecologist to prevent cervical lesions.