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.

Objective: To explore the association between single nucleotide polymorphism rs12632942 in SCN10A exon and oxaliplatin-induced peripheral neuropathy (OXLIPN) in colorectal cancer (CRC) patients receiving chemotherapy. Methods:Atotal of 319 cases of blood samples from CRC patients receiving chemotherapy regimen with Oxaliplatin (OXL) were collected from the Second Affiliated Hospital of Guangzhou Medical University, the Second Affiliated Hospital of Nanchang University, and Guangzhou Baiyun District Hospital of Chinese Medicine during January 2011 and June 2013. DNAwas routinely extracted, and PCR amplification was performed to analyze the genotype of rs12632942; and OXLIPN of patients was also evaluated. The association between rs12632942 genotype and OXLIPN was analyzed by χ2 test and multivariate logistic regression model. Results: The genotypes of rs12632942 of 319 CRC patients:AAof 134 cases,AG of 156 cases and GG of 29 cases; and the genotype distribution of rs12632942 was in accordance with Hardy-Weinberg equiliberum (P>0.05). χ2 test showed that rs12632942AG+GG genotype was associated with Ⅱ-Ⅳ degree OXLIPN (P<0.01). Multivariate logistic regression model showed that rs12632942 AG + GG genotype was an independent risk factor for Ⅱ-Ⅳ degree OXLIPN（OR=2.044； 95%CI=1.231-3.392; P<0.01） . Conclusion: Colorectal cancer patients with SCN10A exon polymorphism rs12632942AG + GG genotype were susceptible to Ⅱ-Ⅳ degree OXLIPN.

Objective: By investigating the genotype and evolutionary variation of hantavirus (HV) in Tiantai county, a national surveillance site for hemorrhagic fever with renal syndrome (HFRS) was set in Zhejiang province, from 2011 to 2018, to reveal the molecular epidemiological characteristics of hantavirus (HV) in Tiantai. Methods: Total RNA was extracted from ultrasound treated HV antigen- positive rat lung samples in Tiantai from 2011 to 2018. After cDNA was prepared, nested PCR was used to amplify partial sequence of M fragments by using specific primers of HV. The sequences of HV in Tiantai from 2011 to 2018 were compared with other known HV sequences in order to identify the genotype and analyze the evolution and variation of the virus. Results: In 67 HV antigen-positive lung specimens, 31 were positive in nested PCR amplification with type-specific primers, including 30 Hantaan virus (HTNV) positive samples, 1 Seoul virus (SEOV) positive sample, and all the 31 samples were from Apodemus agrarius. The phylogenetic tree based on partial M segment was divided into monophyletic group, 30 strains were distributed in HTNV group and 1 was in SEOV group. The HTNV strain Tiantai T2018-130 was independently in one branch, sharing 84.8%-87.9% homology with other strains both at home and abroad, including 29 strains in HTNV group in Tiantai. The other 29 HTNV strains in Tiantai showed closer relationship. The SEOV strain T2016-31 from Apodemus agrarius showed closer relationship with previous strains of SEOV, Tiantai ZT71, ZT10 and Z37 strains of Wenzhou, Zhejiang province. Conclusions HTNV, the main genotype of HV in Tiantai of Zhejiang province, showed obvious geographic clustering, but the strain T2018-130 was distinct from the others in Tiantai. Meanwhile, by sequence analysis, we confirmed that The SEOV strain T2016-31 existed in in Apodemus agrarius, indicating there was a phenomenon of "spillover" between virus and host in SEOV evolution.

Objective: To learn the population,virus status and viral types of hantavirus（HV）hosts in Tiantai County of Zhejiang Province from 2011 to 2018,and to provide evidence for hemorrhagic fever with renal syndrome（HFRS）control. Methods: Rodents in Tiantai County were captured by night trapping method. After the species and age of rodents were identified,the composition of rodent species,dominant species and density of rodents were analyzed. The lungs and blood of rodents were sampled to detect the antigen and antibody of HV by immunofluorescence method. The HV antigen-positive lung samples were detected by RT-PCR with specific primers of HV S fragment,then HV was isolated and identified by inoculating Vero-E6 cells. Results: The average rodent density in Tiantai County from 2011 to 2018 was 4.44%. The rodent density in the field and residential areas were 4.94% and 2.23%,respectively. Ten species of rodents were identified,with Apodemus agrarius dominant in the field and Rattus norvegicus in the residential areas. Sixty-seven lung samples were HV antigen positive（4.13%）,one from Rattus norvegicus and the other sixty-six from Apodemus agrarius. Seventy-nine blood samples were HV antibody positive（4.86%）,all from Apodemus agrarius. Thirty-four HV antigen-positive lung samples were positive（50.75%）after RT-PCR amplification. Twenty-two strains of virus were isolated and all of them were from Apodemus agrarius,including twenty-one strains of Hantaan type（HTN）and one strain of Seoul type（SEO）. Conclusion In Tiantai County,Apodemus agrarius is the main source of HFRS infection;the main epidemic type of HV is HTN and SEO is first found in Apodemus agrarius.

Based on the reported IDO1 inhibitor U-3i,11 phenylsulfonamide derivatives were designed and syn-thesized by adopting bioisosterism and molecular docking technology.The inhibitory activities of the target compounds against IDO1 were determined by the HeLa cell-based kynurenine assay.The results demonstrated that most compounds showed different degrees of inhibitory effects on IDO1.Among them,compounds 3b and 3e displayed the most potent activity and could reverse IDO1-mediated immune suppression,which might be worth of further investigation.

Objective S gene of hantavirus(HV) was expressed in insect cells by genetic engineering technology.The expression product of S gene was used as antigen to detect anti-HV specific antibody IgG in serum.Methods Gene encoding NP of the strain HV-Z10 was amplified by PCR and then its eukaryotic expression system rBAC-Z 10S-TN was constructed by using the routine genetic engineering method.SDS-PAGE was applied to measure the expression of rNP.Ion-exchange plus Ni-NTA-affinity chromatography was performed to purify the recombinant product.Indirect immuno-fluorescence assay (IFA) was used to determine the specific immune-reactivity of rNP.WB assay was established to detect the serum samples from 95 confirmed HFRS patients.Parameters related to the outcomes of detection were compared with the routine HV-IgG IFA method.Results rBAC-Z10S-TN was able to express rNP with high efficiency.The purified rNP only showed a single protein fragment in the gel after SDS-PAGE.HV IgG could efficiently recognize rNP and hybridize with the recombinant protein.97.67％ of the serum samples from the HFRS patients were positive confirmed by WB.Conclusions We successfully constructed a high efficient prokaryotic expression system of NP encoding gene from hantavirus strain HV-Z10.WB assay which was established in this study could be used as a new serological test for HFRS diagnosis,thanks to the simplicity,safety,sensitivity and specificity of this method.

Objective To investigate the effects of electroacupuncture at Sanyinjiao (SP6) and Yinlingquan (SP9) on muscle repair in the gastrocnemius muscle damaged rats and its possible mechanism. Methods 30 male Sprague-Dawley rats were randomly divided into blank group (n=10), model group (n=10) and electroacupuncture group (n=10). The latter 2 groups were modeled with gastrocnemius muscle crush injury. The electroacupuncture group received electroacupuncture at Sanyinjiao and Yinlingquan for 14 days. Their gastrocnemius was observed with HE staining, and the expressions of basic fibroblast growth factor (bFGF) and insulin-like growth factor-1 (IGF-1) in gastroc-nemius tissues and the serum were determined with immunochemical assay and enzyme-linked immunosorbent assay (ELISA). Results Compared with the model group, there was less damage in the electroacupuncture group, with more expression of bFGF and IGF-1 in tis-sues (P<0.01) and serum (P<0.05). Conclusion Electroacupuncture can promote muscle repair after gastrocnemius muscle damage in rats, which may be related to the increase of the bFGF and IGF-1 expression in gastrocnemius tissue and serum.

Objective To study the efficacy of low-dose daytime ambulatory peritoneal dialysis (DAPD) and low-dose CAPD in diabetic end-stage renal disease (ESRD) patients with better residual renal function (RRF). Methods Forty stable diabetic ESRD patients with better RRF (rGFR ≥ 5 ml/min and urine volume ≥ 750 ml/d) were enrolled. They were randomly divided into two groups: low-dose DAPD group (n=20) and low-dose CAPD group (n=20). DAPD group received three 1.5 L to 2 L daily exchanges with a nocturnal empty belly, dwelling for 3 to 4 hours. CAPD group received three 1.5 L to 2 L daily exchange or four 1.5 L daily exchange regimens and dwelled during the night. At the beginning of the study and 6 months later, total weekly Kt/V and Ccr (peritoneal+renal), rGFR were calculated. Meanwhile 24-hour urinary protein,serum albumin (Alb), hemoglobin (Hb), fasting plasma glucose, glycosylated hemoglobin and insulin dosage were measured. Nutritional status was assessed by SGA. Results Thirty-five patients fulfilled the study. There were no significant differences between two groups in age, gender, BMI,PD time, D/Pcr, etc. At the end of the 6th month, the insulin dose[(33.6±10.9) U/d] and 24-hour dialysate protein [(11.13t4.95) g] in CAPD group were significantly higher as compared to DAPD group [(20.6±6.2) U/d, P＜0.05 and (5.66±2.88) g, P＜0.01 respectively]. Alb in CAPD group [(29.7±4.2) g/L] was significantly lower than that in DAPD group [(36.5 ±3.9) g/L, P＜0.05].While the net ultrafiltration [(554±187) ml vs (309±177) ml], 24-hour urine volume [(1090±361)ml vs (750±258) ml] and rGFR [(8.21±2.40) ml/min vs (4.88±2.11) ml/min] in DAPD group were all significantly higher than those in CAPD group (all P＜0.05). Conclusion For the diabetic ESRD patients with better RRF, the low-dose DAPD regimen is more effective to control plasma glucose, improve nutritional status and protect RRF than the low-dose CAPD.

Objective To study the therapeutic effect and possible adverse effects of tribendimidine enteric coated tablets in the treatment of infections due to hookworms, Ascaris lumbricoides, Trichuris trichiura, Enterobius vermicularis. Methods According to the standard clinical trial design and protocol, pearsons infected with hookworms, Ascaris lumbricoides, Trichuris trichiura, or Enterobius vermicularis respectively, were treated with tribendimidine enteric coated tablets in four counties of Guangdong and Jiangsu Provinces, albendazole was used as control. Results For hookworm infection, the curative rate (eggs negative in the faeces) were 89^5%(85/95) and 70^6%(60/85) with tribendimidine (400 mg) and albendazole(400 mg) respectively; for Ascaris infection, 97^4%(114/117) and 98^9%(91/92) with tribendimidine(300 mg) and albendazole(400 mg) respectively; for Trichuris infection,33^3%(25/75) and 56^1%(23/41) with tribendimidine(400 mg/day for 3 days) and albendazole(400 mg/day for 3 days) respectively; for Enterobius infection in children, 74^1%(60/81) and 93^0%(40/43) with tribendimidine(200 mg) and albendazole(200 mg) respectively. No considerable side effect was found. Conclusion Tribendimidine is highly active in the treatment of hookworm, Ascaris lumbricoides infections, free of major adverse effect and easy to administer. It is more effective than albendazole for the infection of Necator americanus.