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.

BACKGROUND:Anterior subtotal corpectomy,decompression and fusion is a conventional method to treat cervical degenerative diseases.A titanium cage is an important implant to maintain the stability of the cervical spine after subtotal corpectomy.In recent years,many patients have complications such as titanium cage sinking,which are highly controversial. OBJECTIVE:To investigate the internal biomechanical relationship between the tilt angle of the titanium cage and postoperative titanium cage subsidence after anterior subtotal cervical corpectomy,decompression and fusion. METHODS:A three-dimensional finite element model of the C4-C6 segment was established by CT images of a normal human cervical spine,in which the anterior subtotal resection,decompression and fusion of the C5 vertebral body were simulated,and titanium cages with different tilt angles(-6° to-1° negative angle,that is,the front edge of titanium cage is shorter than the rear edge of titanium cage;1° to 6° positive angle,that is,the front edge of titanium cage is longer than the rear edge of titanium cage)were placed.After setting the boundary conditions,preloads of 50,100 and 150 N were applied respectively on the C4 vertebral body.The stress value of each contact point between the titanium cage and C4 lower-end plate and C6 lower-end plate(seven stress contact points on the contact surface of titanium mesh)was recorded and statistical analysis was conducted. RESULTS AND CONCLUSION:(1)The tilt angles of the titanium cage of the positive angle group and negative angle group under 50,100 and 150 N stress respectively were found by Mann Whitn test,with P<0.05,which was statistically significant.The dispersion coefficients of the positive angle group were smaller than those of the negative angle group under 50,100 and 150 N stress conditions.(2)Under 50,100 and 150 N stress conditions,the Wilcoxon sign rank test in the positive angle group of titanium cage tilt angle found that when the angle was set to 1° to 5°,the difference was not statistically significant(P>0.05).However,when the tilt angle of the titanium cage was set to 6°,the difference was statistically significant(P<0.05).(3)Under 50,100 and 150 N stress conditions,the Wilcoxon sign rank test in the negative angle group of titanium cage tilt angle found that when the tilt angle was set to-1° to-6°,the difference was not statistically significant(P>0.05).(4)It is concluded that in the sagittal position,the titanium cage with a positive tilt angle is more stable than with a negative tilt angle,which is more suitable for clinical use.The tilt angle of the titanium cage is relatively stable in the range of 1° to 5°.When the tilt angle is 6°,the stability starts to decline,which is easy to cause complications of titanium cage sinking after surgery.It is more suitable to select the titanium cage with a tilt angle of 1° to 5° according to the clinical situation during surgery to improve the efficacy.

Objective To investigate the efficacy and safety of hypofractionated thoracic radiotherapy combined with EP chemotherapy in the treatment of limited-stage small-cell lung cancer (LS-SCLC). Methods A total of 117 patients with LS-SCLC were enrolled and randomly divided into test group (n=59) and control group (n=58). Patients in the experiment group were given hypofractionated thoracic radiotherapy combined with EP chemotherapy, while patients in the control group were given hyperfractionation radiotherapy combined with EP chemotherapy. Objective response rate (ORR), 2-year overall survival (OS), 2-year progression free survival (PFS), and immune cell level were used to evaluate clinical efficacy. We compared the incidence of side effects between the two groups. Results After the treatment, the ORR of patients in the test group was higher than that in the control group (P > 0.05). The mean OS and PFS of patients in the test group were significantly longer than those in the control group (P < 0.05). The levels of CD3⁺, CD4⁺, CD4⁺/CD8⁺, and NK cells in the test group were significantly higher, whereas the levels of CD8⁺ were significantly lower than those in the control group (P < 0.05). The incidence of radiation pneumonitis, radiation esophagitis, and severe dermatitis in the test group was significantly lower than that in the control group (P < 0.05). Conclusion Hypofractionated radiotherapy combined with EP chemotherapy for treatment of LS-SCLC can effectively improve the anticancer efficacy and patient survival, reduce the damage to the body's immune function, and alleviate adverse reaction of radiotherapy.

Objective To establish a rational drug use model of PIVAS and promote the rational drug use in clinical practices by enhancing the quality of prescription review by pharmacists. Methods The PIVAS physician orders received from 2014 to 2021 were extracted through the hospital information management (HIS) system. The types of irrational physician orders were statistically analyzed, the improvements were made by the method of quality control circle (QCC). Results The model of PIVAS rational drug use formed a standardized process. The proficiency of physician order review was improved. From 2014 to 2021, the number and proportion of unreasonable physician orders in PIVAS decreased year by year. Every type of unreasonable physician orders was improved year by year. Conclusion The professional and technical levels of pharmacist for physician order review at our hospital were improved by the model of PIVAS rational drug use. The quality of pharmaceutical service was significantly improved which ensured the safety of patients' medication.

Objective:To analyze the medication rules in the ancient book Pu Ji Fang for the external treatment of acne based on data mining method. Methods:By screening out the methods of treating acne externally in Pu Ji Fang and establishing a standardized medical record database, this paper adopted the web version of Ancient and Modern Medical Record Cloud Platform to calculate the frequency, properties, flavors, and meridians of those medicines, and conduct cluster analysis by using IBM SPSS Modeler 18.0 software to analyze the association rules. Results:A total of 87 prescriptions were selected, including 164 kinds of Chinese materia medica, among which. Radix Angelicae, Ligusticum Wallichii, Rhizoma Typhoni and lead powder are frequently appeared. The properties of those medicines are mainly warm, cold and mild; the flavors of those medicines are mainly spicy, acrid, sweet and bitter, and the meridians mainly belongs to lung, spleen, stomach and liver meridians. The medical pair and group with the strongest associationion are Ligusticum Wallichii- Radix Angelicae and Rhizoma Typhonii- Radix Angelicae- Ligusticum Wallichii. Those freuently appeared medicines could be grouped into three categories. The paste dosage that was frequently appeared has strong correlation with tallow, mercury and lead powder, while the powder dosage that was frequenctly appeared has strong correlation with Angelica Dahurica, Radix Saponicae, Gleditsia sinensis, Radices Ligustici Sinensis and Ligusticum Wallichii. Conclusions:The application of data mining method could preliminarily reveal the medication rules of Pu Ji Fang for the external treatment of acne. The main treatment method is XinSanFaYue. The three categories of Chinese materia medica are used to treat the syndrome of asthenic habitus attacked by exogenous pathogenic factors, exterior attacked by wind heat and hot blood stasis respectively, showing the rules of treating acne externally before Ming Dynasty and providing references for the clinical treatment of acne.

Objective:To collect and analyze the evaluation index of infertility treated by Traditional Chinese Medicine (TCM), which will lay a foundation for the establishment of the core index and evaluation index system of TCM treating infertility.Methods:By retriving the published literatures of randomized controlled trials of infertility treated by TCM in the database of CNKI, VIP, Wanfang, SinoMed, PubMed and Cochrane Library from January 1, 2011 to December 31, 2020, and after the screening according to the creteria of inclusion and exclusion, this paper analyzed the normal indexes of infertility and the pathogenic indexes of TCM.Results:A total of 95 RCTs were included, including 9 069 patients aged between 20-39 years old. The average sample size of each RCT study was 95, involving 78 evaluation criteria. The highest frequency of use was the total effective rate, etiological-index analysis found that the general indicators of infertility such as the total effective rate, pregnancy rate, TCM syndrome scores,and common etiological factors such as LH, FSH are the characteristic indicators.Conclusion:There are many problems in the evaluation indexes of clinical trials of treating infertility by TCM, such as great differences in number and not standardized usage. It is necessary to carry out research on the construction of core indicator and evaluation indicator systems of infertility according to different etiologies.

Objective:This meta-analysis was conducted to systematically evaluate the short-term efficacy and safety of indocyanine green fluorescence imaging guided laparoscopic liver tumor resection (FIGLTR).Methods:A systematic search was made for the literature on indocyanine green fluorescence image-guided laparoscopic hepatectomy in randomized, semi-randomized controlled trials and observational studies, and manually search published materials and conference papers in Chinese and English and trace references included in the literature. The retrieval period was up to September 2021. The quality of included studies was evaluated, then the meta-analysis was conducted using Review Manager 5.1 software.Results:Ten studies were included with 803 patients, including 341 in the FIGLTR group and 462 in the non-FIGLTR group. Meta results showed that: Compared to the traditional resection group, indocyanine green fluorescence imaging can significantly shorten the operative time ( MD=-22.61, 95% CI: -34.20--11.03, P<0.001), reduce intraoperative bleeding ( MD=-49.17, 95% CI: -84.99--13.36, P<0.01), shorter hospital stay ( MD=-0.89, 95% CI: -7.72--0.06, P<0.05), Improve the removal rate of R 0 edge ( OR=8.80, 95% CI: 1.96-39.44, P<0.05) and reduce the incidence of postoperative complications ( OR=0.55, 95% CI: 0.34-0.87, P<0.05) of laparoscopic liver tumor resection. There were no differences found in portal block time and transfusion rate. Conclusion:Indocyanine green fluorescence imaging technology provides a new way for safe and accurate laparoscopic resection of liver tumors.

Objective:To explore the effects of rs6354 polymorphism of 5-HTT gene and family factors on the adaptability of Mongolian school-age children.Methods:The adaptability of 453 primary school students was assessed based on the middle childhood temperament questionnaire(MCTQ). The polymorphism of 5-HTT gene rs6354 was determined by improved multiple ligase detection reaction(iMLDR) technology. SPSS18.0 statistical software was used for data processing and analysis.Results:(1) The adaptability scores of children with GG/GT and TT genotype at rs6354 locus of 5-HTT gene were(2.88±0.73) and(3.03±0.76). (2) Univariate analysis showed that the adaptability scores of Mongolian school-age children were significantly different among different education levels of their parents (father F=2.580, P=0.037; mother F=3.245, P=0.012). (3) Multiple regression analysis showed that mother's educational level( B=-0.079, P=0.010) and rs6354 polymorphism( B=0.165, P=0.041) were inflencing factors of the adaptability score of Mongolian school-age children. (4) Logistic regression analysis showed that father's education level was a significant impact factor of the adaptive level of Mongolian school-age children( B=0.453, P<0.05, OR=1.573, 95% CI=1.023-2.417). Conclusion:rs6354 polymorphism is weakly correlated with children's adaptability, and the education level of parents, especially fathers, may be an important factor affecting the adaptability of Mongolian school-age children.

ObjectiveTo investigate the efficacy and safety of CalliSpheres microsphere-transcatheter arterial chemoembolization (CSM-TACE) versus conventional transcatheter arterial chemoembolization (cTACE) in the treatment of hepatocellular carcinoma (HCC) through a meta-analysis. MethodsPubMed, Web of Science, Cochrane Library, CNKI, Wanfang Data, and VIP were searched for all Chinese and English articles on the application of CSM-TACE and cTACE in HCC published up to the end of October, 2020. After quality assessment was performed for the articles included, RevMan 5.3 software provided by Cochrane Library was used for analysis. ResultsA total of 15 studies were included, with 1535 patients in total. This meta-analysis showed that compared with the patients receiving cTACE, the patients receiving CSM-TACE had significantly higher 1-year overall survival rate (odds ratio ［OR］=2.26, 95% confidence interval ［CI］: 1.63-3.13, P＜0.000 01), 2-year overall survival rate (OR=1.73, 95%CI: 1.20-2.50, P=0.003), and 2-year progression-free survival rate (OR=1.60, 95%CI: 1.05-2.43, P=0.03). In terms of safety, compared with the patients receiving cTACE, the patients receiving CSM-TACE had significantly lower incidence rates of postoperative vomiting (OR=0.65, 95%CI: 0.46-0.92, P=0.01), bone marrow suppression (OR=0.17, 95%CI: 0.05-0.54, P=0.003), and neutropenia (OR=0.18, 95%CI: 0.07-045, P=0.000 3), while there were no significant differences between the two groups of patients in postoperative pyrexia, abdominal pain, and ascites (all P＞0.05). ConclusionCSM-TACE has significant advantages in improving 1- and 2-year overall survival rates and 2-year progression-free survival rates and can significantly reduce the incidence rates of postoperative vomiting, bone marrow suppression, and neutropenia. Therefore, CSM-TACE is a safe and effective treatment method.

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.