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.

OBJECTIVES: This study investigates independent risk factors for postoperative internal fixation device infection in patients with maxillofacial fractures and proposes an early warning model based on the synthetic minority over-sampling technique (SMOTE) algorithm. METHODS: A total of 1 104 patients who underwent surgical treatment for maxillofacial fractures at Oral and Maxillofacial Surgery Department, Affiliated Hospital of Nantong University from January 2021 to December 2024 were retrospectively analyzed. The patients were divided into two groups based on the presence of postoperative internal fixation device infection: the infection group (27 cases) and non-infection group (1 077 cases). Clinical data from both groups were collected and subjected to statistical analysis. Univariate and binary Logistic regression analysis were used to identify risk factors for postoperative internal fixation device infection in maxillofacial fractures. Subsequently, a Logistic regression model was established, and the dataset was improved based on the SMOTE algorithm to construct an early warning model with the improved dataset. The prediction performance of the models was compared and validated. RESULTS: Among the 1 104 patients who underwent surgical treatment for maxillofacial fractures, 27 cases of postoperative internal fixation device infections were identified, corresponding to an infection rate of 2.45% (27/1 104). Age, diabetes history, fracture severity, and oral hygiene status were all identified as risk factors for postoperative internal fixation device infections in maxillofacial fractures (all P<0.05). The prediction model based on the original data (P1). The prediction model based on the SMOTE algorithm (P2). Receiver operating characteristic (ROC) curve analysis shows that the area under curve (AUC) for the P2 model was 0.882, the P1 model was 0.861, indicating the superior predictive performance of the P2 model. The DeLong test results show that the difference in AUC between the two models was statistically significant (P<0.05). CONCLUSIONS Age, diabetes history, postoperative fracture severity, and oral hygiene status are all risk factors for infections associated with internal fixation devices after maxillofacial fracture surgery. The proposed early warning model demonstrated good predictive performance. Medical professionals can utilize this model to effectively intervene and anticipate infections related to internal fixation devices after maxillofacial fracture surgery.
Humans ; Algorithms ; Retrospective Studies ; Male ; Female ; Fracture Fixation, Internal/instrumentation* ; Risk Factors ; Middle Aged ; Adult ; Logistic Models ; Surgical Wound Infection/epidemiology* ; Aged ; Internal Fixators/adverse effects* ; Maxillofacial Injuries/surgery* ; Adolescent

Objective To observe the therapeutic effect and mechanism of allicin on uremic-induced myocardial injury in rats.Methods Twenty-four rats were randomly divided into sham-operated group,model group,and low-,and high-dose allicin groups,with six rats in each group.Except for the sham-operated group,the uremic-induced myocardial injury model was constructed using the 5/6 nephrectomy method in all other groups of rats.After successful modeling,corresponding interventions were carried outed.At the end of the intervention,the renal function of rats was observed,the cardiac mass index was calculated,the levels of serum high-sensitive cardiac troponinⅠ(hs-cTnI)and creatine kinase isoenzyme(CK-MB)were detected by enzyme-linked immunosorbent assay(ELISA),the pathological changes of rat cardiac tissues were observed by hematoxylin-eosin(HE)staining,the changes of autophagosomes and autolysosomes were observed by transmission electron microscopy,and the protein expressions of PTEN-induced putative kinase 1(PINK1)and E3 ubiquitin protein ligase(Parkin)in myocardial tissues were detected by Western Blot.Results Compared with the sham-operated group,the serum creatinine(SCr),blood urine nitrogen(BUN),cardiac mass index,CK-MB and hs-cTnI in rats in the model group were elevated(P<0.05),the pathological damage of cardiac tissues were obvious,and the autophagosomes and autolysosomes were decreased,and PINK1 and Parkin protein expressions in myocardial tissues were decreased(P<0.05);compared with the model group,SCr,BUN,cardiac mass index,CK-MB and hs-cTnI in allicin low-and hogh-dose groups were decreased,the changes of pathological damage of cardiac tissues were relieved,the autophagosomes and autolysosomes were increased,and PINK1 and Parkin protein expressions in myocardial tissues were increased(P<0.05).Conclusion Allicin can reduce myocardial injury in uremic rats,and its mechanism may be related to the up-regulation of PINK1/Parkin-mediated mitochondrial autophagy.

Myocardial injury is the leading cause of death in uremic patients.PINK 1/Parkin-mediated mitochondrial autophagy is involved in the progression of myocardial injury.In recent years,pathogenic turbidity has been gradually accepted as a representative of a new type of toxic pathogens by the researchers of traditional Chinese medicine(TCM).This paper sorts out literature about pathogenic turbidity,analyzes the etiological and pathogenic characteristics of pathogenic turbidity,and suggests that the pathogenesis of uremia-induced myocardial injury can be more comprehensively clarified from the perspective of healthy-qi deficiency resulting in latent pathogenic turbidity.In the patients with uremia,the down-regulation of PINK1/Parkin causes the weakening of mitochondrial autophagy,which leads to the elevation of levels of reactive oxygen species(ROS)and inflammatory factors,and eventually causes the injury of myocardial cell.The above pathogenic mechanism is similar to the process of traditional Chinese medicine(TCM)in which the deficiency of the healthy-qi(in particular kidney deficiency)results in the production of the pathogenic turbidity(showing as dampness,blood stasis,phlegm,toxin and so on)and then causes the pathogenic turbidity hide in vessels and collaterals and gradually injure the heart vessels,and eventually results in the deficiency of heart vessels.The mitochondrial autophagy mechanism mediated by the PINK1/Parkin pathway is suitalbe for explaining the TCM pathogenesis of uremia-induced myocardial injury,characterized by healthy-qi deficiency resulting in latent pathogenic turbidity,and also is suitable for interpretating the principle of supporting healthy-qi to eliminate pathogenic turbidity for treating uremia-induced myocardial injury.Under the guidance of the theory of health y-qi deficiency and turbid pathogens in TCM,the development of specific PINK 1/Parkin agonists may expand the approach for the treatment of uremia-induced myocardial injury.

Objective To investigate the compatibility between antiepileptic active pharmaceutical ingredient(API)levetiracetam and binder polyethylene glycol 6000,and provide a basis for evaluating and ensuring the safety of drugs.Methods Levetiracetam and polyethylene glycol 6000 from different producers were mixed in a certain proportion,and placed under different conditions according to the test method of stability influencing factors.The compatibility of levetiracetam and polyethylene glycol 6000 was analyzed by differential scanning calorimetry and HPLC,respectively,and the thermal variations,changes of levetiracetam appearance and related substances were investigated.Results After being placed under high humidity(relative humidity of 90％)and light(4 500 Lx)for 10 days,the compatibility between API and pharmaceutical excipients was proved good,while under the conditions of high temperature of 50℃ and 60℃,polyethylene glycol 6000 interacted with levetiracetam,resulting in the growth of levetiracetam related substances including impurity A and total amount of impurities,along with the production of two unknown impurities.Polyethylene glycol 6000 from different producers and different batches had different effects on the related substances of levetiracetam.Conclusion There is a risk of compatibility between levetiracetam and polyethylene glycol 6000 under elevated temperatures,and it is recommended that preparation producers optimize product prescriptions and improve the quality and safety of drugs.

AIM:To investigate the effect of circular RNA MYO9A-006(circMYO9A_006)on hypertrophic phenotype of cardiomyocytes and the underlying mechanism.METHODS:The effect of adenovirus-mediated overexpres-sion of circMYO9A_006 on the expression of hypertrophy-related proteins,including β-myosin heavy chain(β-MHC),skeletal muscle actin alpha 1(ACTA1)and atrial natriuretic peptide(ANP),was evaluated in neonatal mouse ventricular cardiomyocytes(NMVCs).Moreover,a neonatal rat ventricular cardiomyocyte(NRVC)model of phenylephrine(PE)-in-duced hypertrophy was established.The effect of circMYO9A_006 overexpression on NRVC size was ascertained using Phalloidin-iFluor 647 staining method.Dual-luciferase reporter assay was employed to measure the activity of potential in-ternal ribosome entry sites(IRES)in circMYO9A_006.The translation and intracellular location of the circMYO9A_006-translated protein,MYO9A-208aa,were verified using Western blot.To investigate the role of MYO9A-208aa in the ef-fect of circMYO9A_006 on the cardiomyocyte hypertrophic phenotype,we prepared and used the following adenoviruses:the recombinant circMYO9A_006-ORF adenovirus to express MYO9A-208aa,the recombinant circMYO9A_006-ATG-mut adenovirus that does not express MYO9A-208aa,the recombinant circMYO9A_006 adenovirus,and the adenovirus vector control.These were then employed to infect NRVCs.RESULTS:Successful adenovirus-mediated overexpression of circMYO9A_006 was observed in NMVCs.The increased expression of circMYO9A_006 notably reduced the expres-sion of hypertrophy-related proteins in NMVCs(P<0.01).Concurrently,overexpression of circMYO9A_006 substantially reduced the expression of hypertrophy-associated proteins and diminished the size of PE-induced NRVCs(P<0.05).Dual-luciferase reporter assay identified the activity of 2 IRES in circMYO9A_006.Western blot results indicated that circ-MYO9A_006 could produce the MYO9A-208aa protein with an anticipated molecular weight of 28 kD in NRVCs,primari-ly found in the cytoplasm.Elevated expression of both circMYO9A_006 and MYO9A-208aa consistently reduced the ex-pression of hypertrophy-associated proteins(P<0.01),and counteracted the enlarged size of PE-induced NRVCs(P<0.05).However,increased expression of circMYO9A_006-ATG-mut did not counteract the PE-induced hypertrophic phe-notype of NRVCs.CONCLUSION:circMYO9A_006 attenuates the hypertrophic phenotype of cardiomyocytes by synthe-sizing the MYO9A-208aa protein.

Purpose/Significance To analyze the influencing factors of user satisfaction on mobile medical platform,and to put for-ward suggestions to improve the quality of medical service and user satisfaction.Method/Process Taking the evaluation texts of users from eight tertiary hospitals in Guangxi in the online mobile medical service platform of haodf.com as the research object,the paper uses the software of ROST content mining system to filter meaningless words,carries out emotional analysis,word frequency statistical analysis and co-occurrence matrix semantic network analysis.Result/Conclusion The degree of satisfaction and recognition of users to the mo-bile medical service platform is high.From the perspective of influencing factors and departments,it puts forward some suggestions on how to improve the satisfaction of mobile medical service users.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To observe the clinical efficacy of auricular needle-embedding therapy for treating primary insomnia. Methods:A total of 63 patients were randomly divided into a conventional acupuncture group and an auricular needle-embedding group.The conventional acupuncture group received acupuncture at meridian points,while the auricular needle-embedding group received acupuncture at auricular points.Treatments were given once a day for 6 consecutive days,followed by a 1-day break,as a course of treatment.Both groups were treated for 2 courses.Before treatment,and after 1 course and 2 courses of treatment,the Pittsburgh sleep quality index(PSQI)score was assessed,and the efficacy was evaluated. Results:The cured and markedly effective rate and total effective rate of the auricular needle-embedding group were higher than those of the conventional acupuncture group,but there was no significant difference between the two groups(P>0.05).After 1 course of treatment,the PSQI global score and the scores of subjective sleep quality,sleep latency,sleep duration,habitual sleep efficiency,and daytime dysfunction of both groups decreased compared with those before treatment(P<0.01);there was no statistical significance in comparing the PSQI global score and individual component scores between the two groups(P>0.05).After 2 courses of treatment,the PSQI global score and the scores of sleep latency and habitual sleep efficiency of the auricular needle-embedding group decreased compared with those after 1 course of treatment(P<0.01 or P<0.05),while only the score of sleep latency of the conventional acupuncture group decreased compared with that after 1 course of treatment(P<0.05);the PSQI global score and the scores of subjective sleep quality and sleep latency of the auricular needle-embedding group were lower than those of the conventional acupuncture group(P<0.05). Conclusion:Both therapies can improve insomnia.Compared to conventional acupuncture,auricular needle-embedding therapy demonstrates a therapeutic advantage in improving sleep latency and sleep quality,making it worthy of clinical promotion.

Objective:To establish a high performance liquid chromatography method for the simultaneous determination of dimethyl oxalate (DMO) and diethyl oxalate (DEO) in workplace air.Methods:From January 2022 to January 2023, air samples were collected by silica gel tubes, desorbed by acetonitrile, separated by C18 chromatographic column, detected by photo-array detector, and retention time was used to characterize and peak area was used to quantify at 210 nm wavelength.Results:The linear relationships of DMO and DEO were good, r>0.999. The detection limits of DMO and DEO were 0.39 and 0.52 μg/ml, respectively. The quantitative limit was 1.28 μg/ml for DMO and 1.72 μg/ml for DEO. Average desorption efficiency for DMO was 82.40%-92.72%, and DEO was 94.13%-97.69%. The intra-assay precision of DMO was 1.87%-6.18%, and DEO was 2.25%-3.31%. Inter-assay precision of DMO was 3.29%-5.73%, and DEO was 1.38%-2.94%. Average sampling efficiencies were 100% for both DMO and DEO. Breakthrough capacity of DMO was 37.61 mg (200 mg solid adsorbent), DEO was >28.11 mg (200 mg solid adsorbent). Samples should be stored at 4 ℃ for at least 7 days. Conclusion:This method is easy to operate and has strong practicability. All indicators meet the requirements of the specification, and it is suitable for the simultaneous determination of DMO and DEO in the workplace air.