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

Background Previous studies have demonstrated that the vagus nerve stimulation improves upper limb function in patients with stroke sequelae(six month-two years).This study aimed to investigate whether the auricular intradermal acupuncture(AIA)acted on the auricular branch of the vagus nerve can facilitate the recovery of upper limb motor function and expedite the effects and characteristics of rehabilitation processes in flaccid phase after stroke in Phase Brunnstrom Ⅰ.Methods This study utilized a randomized controlled single-blinded clinical design.Patients with ischemic stroke in Phase Brunnstrom Ⅰ were randomly assigned to the auricular intradermal acupuncture(AIA)group(AIA,standard rehabilitation,conventional acupuncture)or the sham auricular intradermal acupuncture(sham AIA)group(the sham AIA,standard rehabilitation,conventional acupuncture)for 6 days of 1 week(6 times).Primary outcome measures:Brunnstrom(Ueda Assessment),Fugl-Meyer assessment of the upper extremity(FMA-UE)and its subtype score(FMA-UEFS,FMA-UEES),Wolf motor function test scale(WMFT).Secondary outcome measures:Upper limb active range of joint motion(AROM),manual muscle test(MMT)of upper limb muscles,Barthel index(BI).Results Of the 332 patients who were screened,70 patients met the criteria and were recruited.There were 35 patients in the AIA group,1 patient was fall off,34 patients were actually completed;35 patients in the sham AIA group had no falling off case.Primary outcome measures:The upper Ueda assessment of the AIA group were better than those of the sham AIA group after treatment on days 3 and 6(P<0.05,P<0.001,respectively).The FMA-UEFS score on days 6 of the AIA group were significantly better than those of the sham AIA group(P<0.05).FMA-UEES of the AIA group was more associated with FMA-UE than FMA-UEFS with FMA-UE after treatment on day 6(FMA-UEFS:r=0.728,P<0.001;FMA-UEES:r=0.744,P<0.001).After 3 days and 6 days of treatment,the AIA group of the WMFT were significantly improved in the sham AIA group(P<0.05,P<0.001,respectively).Secondary outcome measures:AROM:After 6 days of treatment,the AIA group of shoulder abduction were more improved than in the sham AIA group(P<0.05).MMT:The muscle strength of elbow flexion,and elbow extension muscle improved more in the AIA group than in the sham AIA group(P<0.05).Barthel index(BI):After 6 days of treatment,there was a significant improvement in the group compared with before treatment(P<0.05),but no difference compared with the group(P>0.05).Conclusions AIA combined with conventional rehabilitation and acupuncture,can effectively improve the upper limb motor function of patients with post-ischemic stroke flaccid hemiplegia and accelerates the rehabilitation process of upper limb motor function.Clinical Trial Registration The study protocol is registered withhttp://www.chictr.org.cn(accession number:ChiCTR2200058141).

Objective To systematically summarize the real experiences of the patients with totally implanted venous access ports(TIVAP)over the survival period of port-carrying,and provide references for formulation of the targeted health management programs.Methods A systematic search was conducted on databases of PubMed,Web of Science,Cochrane Library,CINAHL,Embase,PsycNET,China National Knowledge Infrastructure(CNKI),SinoMed,Wanfang Data base,and Vip for a qualitative study on the life experiences,needs,and feelings of patients with implanted infusion ports.The search period spanned from the inception of the databases to 3rd August,2024.Results A total of 14 studies were included,in 12 categories extracted from 38 research findings.Four synthesised results were further summarised,they were:impact on individual physical and mental health,impact on home life,challenges and needs in self-management and self-coping strategies of patients.Conclusion The implantation of TIVAP can produce both positive and negative experiences to the treatment as well as the life of patients.Healthcare professionals should be aware of the differences in emotion,cognition,need and personal coping strategy among the patients,hence to take effective measures to optimise the port-carrying experience of the patients,enhance the self-management enthusiasm and improve the quality of life of patients.

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.

Background Previous studies have demonstrated that the vagus nerve stimulation improves upper limb function in patients with stroke sequelae(six month-two years).This study aimed to investigate whether the auricular intradermal acupuncture(AIA)acted on the auricular branch of the vagus nerve can facilitate the recovery of upper limb motor function and expedite the effects and characteristics of rehabilitation processes in flaccid phase after stroke in Phase Brunnstrom Ⅰ.Methods This study utilized a randomized controlled single-blinded clinical design.Patients with ischemic stroke in Phase Brunnstrom Ⅰ were randomly assigned to the auricular intradermal acupuncture(AIA)group(AIA,standard rehabilitation,conventional acupuncture)or the sham auricular intradermal acupuncture(sham AIA)group(the sham AIA,standard rehabilitation,conventional acupuncture)for 6 days of 1 week(6 times).Primary outcome measures:Brunnstrom(Ueda Assessment),Fugl-Meyer assessment of the upper extremity(FMA-UE)and its subtype score(FMA-UEFS,FMA-UEES),Wolf motor function test scale(WMFT).Secondary outcome measures:Upper limb active range of joint motion(AROM),manual muscle test(MMT)of upper limb muscles,Barthel index(BI).Results Of the 332 patients who were screened,70 patients met the criteria and were recruited.There were 35 patients in the AIA group,1 patient was fall off,34 patients were actually completed;35 patients in the sham AIA group had no falling off case.Primary outcome measures:The upper Ueda assessment of the AIA group were better than those of the sham AIA group after treatment on days 3 and 6(P<0.05,P<0.001,respectively).The FMA-UEFS score on days 6 of the AIA group were significantly better than those of the sham AIA group(P<0.05).FMA-UEES of the AIA group was more associated with FMA-UE than FMA-UEFS with FMA-UE after treatment on day 6(FMA-UEFS:r=0.728,P<0.001;FMA-UEES:r=0.744,P<0.001).After 3 days and 6 days of treatment,the AIA group of the WMFT were significantly improved in the sham AIA group(P<0.05,P<0.001,respectively).Secondary outcome measures:AROM:After 6 days of treatment,the AIA group of shoulder abduction were more improved than in the sham AIA group(P<0.05).MMT:The muscle strength of elbow flexion,and elbow extension muscle improved more in the AIA group than in the sham AIA group(P<0.05).Barthel index(BI):After 6 days of treatment,there was a significant improvement in the group compared with before treatment(P<0.05),but no difference compared with the group(P>0.05).Conclusions AIA combined with conventional rehabilitation and acupuncture,can effectively improve the upper limb motor function of patients with post-ischemic stroke flaccid hemiplegia and accelerates the rehabilitation process of upper limb motor function.Clinical Trial Registration The study protocol is registered withhttp://www.chictr.org.cn(accession number:ChiCTR2200058141).

Objective To systematically summarize the real experiences of the patients with totally implanted venous access ports(TIVAP)over the survival period of port-carrying,and provide references for formulation of the targeted health management programs.Methods A systematic search was conducted on databases of PubMed,Web of Science,Cochrane Library,CINAHL,Embase,PsycNET,China National Knowledge Infrastructure(CNKI),SinoMed,Wanfang Data base,and Vip for a qualitative study on the life experiences,needs,and feelings of patients with implanted infusion ports.The search period spanned from the inception of the databases to 3rd August,2024.Results A total of 14 studies were included,in 12 categories extracted from 38 research findings.Four synthesised results were further summarised,they were:impact on individual physical and mental health,impact on home life,challenges and needs in self-management and self-coping strategies of patients.Conclusion The implantation of TIVAP can produce both positive and negative experiences to the treatment as well as the life of patients.Healthcare professionals should be aware of the differences in emotion,cognition,need and personal coping strategy among the patients,hence to take effective measures to optimise the port-carrying experience of the patients,enhance the self-management enthusiasm and improve the quality of life of patients.

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.

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.