The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer's disease (AD) research. Here, we present PI4AD, a computational medicine framework that integrates multi-omics data, systems biology, and artificial neural networks for therapeutic discovery. This framework leverages multi-omic and network evidence to deliver three core functionalities: clinical target prioritisation; self-organising prioritisation map construction, distinguishing AD-specific targets from those linked to neuropsychiatric disorders; and pathway crosstalk-informed therapeutic discovery. PI4AD successfully recovers clinically validated targets like APP and ESR1, confirming its prioritisation efficacy. Its artificial neural network component identifies disease-specific molecular signatures, while pathway crosstalk analysis reveals critical nodal genes (e.g., HRAS and MAPK1), drug repurposing candidates, and clinically relevant network modules. By validating targets, elucidating disease-specific therapeutic potentials, and exploring crosstalk mechanisms, PI4AD bridges genetic insights with pathway-level biology, establishing a systems genetics foundation for rational therapeutic development. Importantly, its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation-provides a strategy to disrupt AD progression, complementing conventional amyloid/tau-focused paradigms, with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.

The association of Zika virus (ZIKV) infection with microcephaly has raised alarm worldwide. Their causal link has been confirmed in different animal models infected by ZIKV. However, the molecular mechanisms underlying ZIKV pathogenesis are far from clear. Hence, we performed global gene expression analysis of ZIKV-infected mouse brains to unveil the biolog-ical and molecular networks underpinning microcephaly. We found significant dysregulation of the sub-networks associated with brain development, immune response, cell death, microglial cell acti-vation, and autophagy amongst others. We provided detailed analysis of the related complicated gene networks and the links between them. Additionally, we analyzed the signaling pathways that were likely to be involved. This report provides systemic insights into not only the pathogenesis, but also a path to the development of prophylactic and therapeutic strategies against ZIKV infection.

Objective To explore the feasibility and evaluate the teaching effect of case-based multidisciplinary team teaching mode in clinical practice teaching of gynecology.Method According to different grade,120 students were divided into experimental group and control group (60 students per group).The teaching content contained three malignant tumor cases,which were cervical cancer,endometrial cancer and ovarian cancer.The course needed 12 periods totally.The experimental group received multidisciplinary team (MDT) teaching mode,and the control group received traditional lecture-based learning teaching mode (LBL).Teaching effect evaluation and test scores would be analyzed at the end of teaching.SPSS19.0 was used for t test and chi-square test.Results Our results showed that the theory test scores,practical skills test scores,the paperwork scores and the total scores of the students in MDT group were significantly higher than those in the traditional group (P＜0.05).At the same time,the students' self-evaluation scores in the ability of information retrieval,acquisition,understanding,comprehensive and the ability of self-learning,learning interest,enthusiasm and teamwork were significantly higher than the traditional group (P＜0.05).Conclusion MDT teaching mode is feasible,which can improve teaching effect and students' quality,and is worthy of advocating and popularization.

Objective To determine the effects of intrauterine growth retardation(IUGR) caused by malnutrition during pregnancy on the lung structure and expression of Clara cell protein (CCSP) and interferon (IFN)-γ in the fetal lungs,and to explore their relation ship with pulmonary disease.Methods Fetal rats from maternal protein-malnutrition dams were studied on day 20(term 21.5 day).The lung pathology was examined by means of Hematoxylin and eosin(HE) stain.Plasma was collected to determine the CCSP and IFN-γ concentration.Lungs were harvested to measure the expression of CCSP and IFN-γ mRNA by using fluorescent quantization reverse transcription (RT)-PCR and the levels of CCSP and IFN-γ protein were assessed by using enzyme-linked immunosorbent assay.Results Malnutrition fetus body weight significantly less compared to control group,so did the lung weight.However,lung weight,expressed as a percentage of body weight between the 2 groups was not different.The IUGR group had significantly decreased alveolar number manifested by lower radial alveolar count,and significantly increased mean linear intercept of alveoli.Both the CCSP mRNA expression and protein level in lung of IUGR rats were decreased compared with control rats (all P ＜ 0.05).A decline in plasma CCSP protein concentration was also noted compared with control group (P ＜0.05).Furthermore,IUGR group fetus showed lower IFN-γ levels both in circulation and in the lung tissue (all P ＜ 0.05).Conclusions Intrauterine malnutrition significantly alters lung structure and cytokine IFN-γ level,and the latter may further inhibit the transcription of CCSP gene.These alterations may contribute to both early and late postnatal respiratory morbidity.

As one of the first resident standardized training bases, department of ophthalmology of Shanghai Ruijin Hospital participated in this reform process from 2010. Relevant rules and regulations (training management system , training scheme implementation system and evaluation system ) were strictly obeyed. When new problems emerged, under the guidance of department in charge, a series of regimens were formulated and improved gradually by Ophthalmology Professional Committee of Shanghai Resident Standardized Training Department. Based on reviewing and summarizing the work in the last 3 years, some thoughts and suggestions on the resident standardized training in future were put forward ,in-cluding how to better solve the“heavily used, lightly cultured” problem, the“disregarding medical ethics establishment”problem, the“disregarding assessment of teachers”problem and the“disregard-ing obtaining employment”problem.

Objective To investigate the effect of pigment epithelium-derived factor (PEDF) on rat retinal Müller cells under high glucose conditions. Methods Müller cells cultured in 25 mmoL/L glncose were incubated with 100 ng/ml PEDF or 10 ng/ml interleukin-1β(IL-1β) for 24 h. The expression of IL-1β or PEDF in Müller cells was measured by indirect immunofluorescence, Western blot or realtime RT-PCR. The survival of Müller cells was detected by MTT assay. Results Under high glucose conditions, expression of IL-1β or PEDF was decreased after treated with 100 ng/ml PEDF or 10 ng/ml IL-1β for 24 hours by the methods of immunocytochemistry, Western blot or realtime PCR (P ＜ 0.05). Activity of Müller cells was increased significantly by PEDF (0.48±0.09 vs 0.64±0.17, P＜0.05). Conclusion In mimic diabetic conditions, PEDF decreases expression of IL-1β in rat retinal Müller cells and enhances the cell activity. To some degree, PEDF may block the process of inflammation in diabetic retinopathy.

Objective To study the expression and relationship of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in epithe-lial ovarian carcinoma. Methods Immunohistochemical staining S-P methods was used to detect the expression of OPN and MMP-9 in the samples of 60 epithelial ovarian carcinoma,20 benign ovarian tumor,20 borderline ovarian tumor and 10 normal ovarian tissue. Results The expression level of OPN and MMP-9 in epithelial ovarian carcinoma(109.86±21.51) were significantly higher than those in borderline ovarian tumor(45.81±8.93),benign ovarian tumor(11.86±3.01) and normal ovarian tissue(5.32±2.74). The expression level of OPN and MMP-9 related to the tumor grading,tumor stage and lymph node metastasis,while had no relationship with histological grading. There was significant positive correlation between OPN and MMP-9 in epithelial ovarian carcinoma (r = 0.80,P < 0.05). Conclusion The increased expression of OPN and MMP-9 may play an important role in the process of carcinogenesis, progression and differentiation of epithelial ovari-an carcinoma. OPN and MMP-9 may be a useful targets for treatment of ovarian carcinoma.