Objective To explore the correlation of progesterone and expression of extrasynaptic δ-subunits containing γ-aminobutyric acid type A receptors (δGABA

To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer's disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aβ42, Aβ42/Aβ40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aβ42, Aβ42/Aβ40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.

There is no doubt that the traditional Chinese medicine(TCM) is effective, practical and scientific after it was used for thousands of years. However, the mechanisms of action of many TCM are still unclear because of their multi-component, multi-target and multi-level features, which hinder the modernization and internationalization of the TCM. Proteomics is to analyze the composition and activity of intracellular proteins which are changing dynamically from a holistic perspective. It is consistent with the holistic and dynamic views of the TCM and brings about the hope of clarifying the mechanism of action of the TCM. In recent years, great progress has been made in the application of proteomics to determine the mechanism of the TCM. This article introduced the core technologies of proteomics and systematically summarized the applications of proteomics in the study of the mechanism of the Chinese medicinal formulae, single Chinese medicine and monomeric compounds from the TCM to provide innovative ideas and methods for reference.

BACKGROUND: Even though estrogen can prevent secondary spinal cord injury, exert a neuroprotective role, and inhibit apoptosis in mesenchymal stem cells in vitro,little is reported on the combined use of estrogen and bone marrow mesenchymal stem cells(BMSCs)in the treatment of spinal cord injury. OBJECTIVE: To investigate the effects and mechanism of s intramuscular injection of estradiol combined with BMSCs in the treatment of spinal cord injury. METHODS: One hundred and forty-four Sprague-Dawley rats were randomly divided into four groups: combined group, BMSCs group, estradiol group and control group. After the establishment of spinal cord injury model, the rats were given intramuscular injection of estradiol 250 μg/kg estradiol combined with 6×106BMSCs (60 μL), BMSCs, estradiol or PBS in different groups, respectively. After transplantation, related indicators were detected. RESULTS AND CONCLUSION: At 1 and 4 weeks after modeling, the behavioral scores in the combined group were significantly higher than those in the other three groups (P < 0.05). At 3 and 7 days after transplantation, superoxide dismutase levels in the combined group were significantly higher than those in the other three groups, but the malondialdehyde levels were lowest in the combined group (P < 0.05). At 3 and 7 days after transplantation, the apoptotic rate in the spinal cord tissues was significantly lower in the combined group than the other three groups (P < 0.05). To conclude, estradiol can alleviate secondary cell apoptosis and inhibit oxidative stress after spinal cord injury, which contributes to the spinal motor function recovery after BMSCs transplantation.

OBJECTIVES: To explore the identification method of full sibling between two males with microdeletion and mutation of Y chromosome. METHODS: DNA were extracted from two samples. The type testing of Y-STR and autosomal STR were performed. Full sibling between two individuals was calculated by IBS, ITO and discriminant functions methods. RESULTS: There were 2 loci mutations existed in 33 Y-STR loci and one of the two samples had 19 loci deletions. The IBS of two samples was 53 and greater than the threshold which was 42; FSI was 1.36×10¹⁶ and far greater than 19. The discriminant function of full sibling-unrelated individual D_FS2 was greater than D_R2, which meant the two individuals tend to be full sibling. CONCLUSIONS The methods of IBS, ITO and discriminant functions of full sibling-unrelated individual can be used comprehensively to provide more reliable expert opinion in microdeletion and mutation of Y chromosome in full sibling identification.
Alleles ; Chromosome Aberrations ; Chromosomes, Human, Y/genetics* ; Discriminant Analysis ; Forensic Genetics ; Humans ; Male ; Polymerase Chain Reaction ; Sequence Deletion ; Siblings

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.
Antibodies, Monoclonal ; pharmacokinetics ; Cytotoxins ; pharmacokinetics ; Humans ; Immunoconjugates ; pharmacokinetics ; Neoplasms ; drug therapy

The eye is a highly protected organ , which makes it a formida-ble task to develop an effective drug delivery approach for ocular disea-ses.Transport of drugs applied by traditional dosage forms such as topical and intravitreal routes of administration is severely restricted to the eye , especially to the posterior segment areas.During the past decades , great progress has been made in ocular drug delivery systems facilitated by new technologies such as microemulsion , nanosuspension , nanoparticle , lipo-some, niosome, dendrimer, contact lens, intraocular implants, ionto-phoresis and microneedle , et al.In this review , recent developments of ocular drug delivery systems are summarized.

Alzheimer′s disease ( AD ) is a common neurodegenerative disorder that causes progressive memory and cognitive impairment and ul-timately leads to death of patients.Aggregation of amyloid β-peptide ( Aβ) is a central event in AD pathogenesis, which is based onβ-sheet formation of Aβpeptides.β-Sheet breaker peptides are oligopeptides that can prevent and/or reverse β-sheet formation and thus represent a promising class of candidates for treatment of AD. This review is to summarize the progress of β-Sheet breaker peptides made in the past few decades.

Objective To determine whether the combination of traditional risk factors and quantitative coronary angiography (QCA) assessment could provide accurate prognostic information on a population-based study including 1137 adults with subclinical artherosclerosis and with coronary risk factors. Methods Participants underwent coronary angiography examination before the minimal stenotic diameters, segment diameters, percent stenosis, plaque areas. Other parameters were analyzed by the computer-assisted Coronary Angiography Analysis System. The Framingham Risk Score for each participant was assessed. During the 1 year follow-up period, all kinds of endpoint cardiovascular events were screened. Endpoint events were defined as death from coronary heart disease, nonfatal myocardial infarction (MI) or unstable angina pectoris. Results During the 1 year of follow-up period, a total of 124 participants developed an endpoint event, which was significantly associated with the Framingham Risk Score, calcium of plaques and the plaque areas (all Ps＜0.05).The QCA score incorporated with the QCA parameters was related to the endpoint events. The Framingham Risk Score was combined with QCA score through logistic regression for prediction of end-point events. Data from the ROC analysis showed the accuracy of this prediction algorithm was superior to the accuracy when variables themselves were used. The event-free survival rate was inferior to the control group in participates under high risk, when being screened with this prediction algorithm (P＜0.05). Conclusion The risk of cardiovascular attack in subclinical artherosclerosis individual seemed to be associated with the Framingham Risk Score, calcium of plaques and the plaque areas. When the traditional risk factors (the Framingham Risk Score) were combined with QCA, the new method could provide more prognostic information on those adults with subclinical artherosclerosis.

Objective To observe the diagnostic value of non-invasive 128-slice computed tomography coronary angiography(CTA)in comparison with invasive coronary angiography.Methods 128-slice CTA and invasive coronary angiography were performed in 78 unselected consecutive patients(63 patients with suspected coronary artery disease and 15 patients with previous coronary stenting,56 males,mean age 61±10 years)and ＞50% reduction of minimal lumen diameter was defined as significant coronary stenosis.Results Fifty-eight out of 879 segments(7%)from CTA were not assessable because of irreguldr rhythm,vessel calcification or tachycardia.Compared with invasive coronary angiography,segmentbased analysis from the 821 segments showed the sensitivity by CTA was 87%,specificity 97%,PPV 83% and NPV 97%.Four out of 22 stents implanted in 15 patients were not assessable by CTA because of poor image quality.Compared with invasive coronary angiography,the sensitivity of diagnosing in-stent restenosis by CTA was 100%,specificity 77%,PPV 63% and NPV 100% for the remaining 18 stents-Conclusions One hundred and twenty-eight-slice CTA has a high accuracy for detecting coronary artery disease and instent restenosis after coronary stenting and could be considered as a valuable noninvasive technique for screening coronary artery disease in suspected patients.