Adverse drug reactions （ADRs） refer to harmful or unintended reactions unrelated to the intended purpose of medication administration， which can lead to various issues such as accelerated disease progression and prolonged hospitalization. Traditional ADRs monitoring systems （such as spontaneous reporting systems） suffer from limitations such as low reporting rates and inconsistent data quality， which hinder the early prevention and control of ADRs. With the rapid development of information technology， machine learning has emerged as a powerful tool for management and decision-making of ADRs by leveraging its strengths in feature extraction and dynamic temporal pattern analysis. By reviewing relevant literature at home and abroad in recent years， this paper summarizes the progress in the application of machine learning for ADRs prediction. It is found that machine learning has gradually been applied to the early warning and risk prediction of ADRs in target organs such as the kidneys， liver， heart and bone marrow （such as acute kidney injury， drug-induced liver injury， and so on）. Although machine learning demonstrates significant application potential in the field of ADRs prediction， it still faces limitations such as inadequate quality control of clinical data， lack of standardized criteria for model performance evaluation， insufficient model interpretability and difficulties in clinical translation. In the future， the development trend of machine learning in the field of ADRs prediction should follow a “technology-validation-integration” pathway to systematically promote the practical implementation of models.

The connotation of "treat heat with cold" and "disperse fire constraint" differs， and under the guidance of these two principles， there are variations in the selection of acupoints， choice of needles， and manipulation techniques in clinical acupuncture. "Treat heat with cold" is used to clear and drain heat pathogens， while "disperse fire constraint" focuses on diffusing and dissipating fire from constraint. When both fire constraint and internal heat coexist， treatment should combine both "dispersing the fire" and "cooling the heat". In clinical acupuncture， for clearing heat and draining heat pathogens， acupoints on Governor vessel （督脉） and Yangming （阳明经） channel are commonly selected， with Jing-well points， Ying-spring points and He-sea points. To diffuse and dissipate fire constraint， acupoints on the Taiyang （太阳） and Shaoyang （少阳） channels are usually chosen， with Jing-river points and Ashi points as the primary options. In terms of needle choice， for heat syndrome， filiform needles， three-edged needles， and cupping are often used for clearing heat and resolving toxins； for fire constraint syndrome， moxibustion and fire needles are employed to expel fire from the body. Regarding manipulation techniques， draining method can be used in both conditions， with heat syndrome requiring shallow needling and quick removal， while fire constraint syndrome requiring deeper and longer retention of needles， having an emphasis on hand pressure coordination and smooth qi flow. In clinical practice， it is essential to distinguish the presence of "constraint" and the depth of the disease location to appropriately combine "dispersing fire" and "cooling heat".

ObjectiveTo explore the visual attention distribution across different lateral facial profiles and analyze the influence of observer gender and professional background on aesthetic evaluation， providing an aesthetic basis for the design of clinical orthodontic treatment. MethodsEye-tracking technology was employed to record the gaze paths of 136 subjects （orthodontists， non-orthodontic dentists， and non-medical professionals） when evaluating three types of male and female lateral profiles （convex， straight， and concave）. A questionnaire survey was conducted using a visual analog scale （VAS）. Data differences and the consistency between eye-tracking and questionnaire results were analyzed through t-tests， analysis of variance （ANOVA）， and Kappa coefficient analysis. ResultsThe questionnaire scores for straight profiles were significantly higher than those for convex and concave profiles （P<0.05）. Eye-tracking revealed that subjects primarily focused on the eye and nasal regions （P<0.001）， followed by the mouth. However， orthodontists showed no significant difference in attention between the mouth and eye-nasal areas （P>0.05）. Additionally， gender differences were notable. Female observers prioritized the mouth （P<0.05）， while male observers paid later attention to the oral-buccal region. The forehead and chin rapidly attracted attention during the initial evaluation phase， particularly in female concave profiles （P<0.05）. Eye-tracking data demonstrated high consistency with questionnaire results （κ=0.868）. ConclusionThis study， utilizing eye-tracking technology， finds that the eye and nasal regions are the core focus areas for aesthetic evaluation of lateral profiles. Gender differences result in distinct gaze preferences （males emphasize the nose， while females emphasize the eyes）， whereas orthodontists focus more on the lips and forehead. As aesthetic baselines， the forehead and chin， with their profile characteristics， should be prioritized in treatment. This research provides a basis for developing personalized orthodontic plans and establishing aesthetic consensus between clinicians and patients.

ObjectiveTo investigate the effects of atorvastatin （ATV） on the proliferation and differentiation of rat bone marrow mesenchymal stem cells （BMSCs）， periodontal ligament stem cells （PDLSCs）， and dental pulp stem cells （DPSCs） in vitro， and to validate the regulatory effect of ATV on periodontal bone formation and tooth movement using a rat orthodontic tooth movement （OTM） model. MethodsThe effects of ATV on the proliferation and osteogenic/odontogenic differentiation of rat BMSCs， PDLSCs， and DPSCs were assessed in vitro. CCK-8 assay was used to detect the proliferation of the three types of cells. Alkaline phosphatase （ALP） staining and Alizarin Red staining were employed to evaluate osteogenic differentiation capacity. Western blot was used to detect the expression of osteogenesis-related proteins ［collagen type I （COL-I）， Runt-related transcription factor 2 （Runx2）， bone morphogenetic protein-2 （BMP-2）， osteocalcin （OCN）］ and the odontogenesis-related protein dentin sialophosphoprotein （DSPP） in BMSCs， PDLSCs and DPSCs. An OTM rat model was established， with rats randomly assigned to an ATV gavage group and a control group. The ATV gavage group received daily oral administration of ATV at a dose of 20 mg/kg， while the control group received an equal volume of solvent by gavage. Tooth movement distance was measured via Micro-CT on days 7， 14， and 21. Histomorphology of periodontal tissues was observed using Hematoxylin and Eosin （HE） staining and Masson staining. The gene and protein expression levels of osteogenic markers （BMP-2， Runx2， OCN） on the tension side of the first molar were detected by qRT-PCR and immunohistochemistry， respectively. ResultsATV at concentrations of 1×10⁻⁶ mol/L and 1×10⁻⁷ mol/L significantly promoted the proliferation and osteogenic/odontogenic differentiation of BMSCs， PDLSCs， and DPSCs， manifested as enhanced ALP activity， increased mineralized nodule formation， and up-regulated expression of osteogenic/odontogenic proteins COL-I， Runx2， BMP-2， OCN， and DSPP （P<0.001）. In the OTM model， compared with the control group， the ATV gavage group showed a significant reduction in tooth movement distance （P<0.05）， enhanced osteogenic activity in periodontal tissues， and significantly increased gene （P<0.001） and protein （P<0.05） expression of BMP-2， Runx2， and OCN on the tension side of the first molar. ConclusionATV enhances periodontal osteogenesis by promoting osteogenic/dentinogenic differentiation， thus inhibiting tooth movement.

Hepatic sinusoidal capillarization is the first event in the process of fibrogenesis， and inhibiting hepatic sinusoidal capillarization can effectively improve the pathological process of liver fibrosis. Various studies have shown that traditional Chinese medicine can significantly inhibit hepatic sinusoidal capillarization. This article systematically reviews the effective constituents， monomers， and compound prescriptions of traditional Chinese medicine， summarizes their mechanism of action in inhibiting hepatic sinusoidal capillarization， and analyzes the theoretical core of traditional Chinese medicine in inhibiting hepatic sinusoidal capillarization from the perspective of traditional Chinese medicine， in order to provide ideas and literature support for the treatment of liver fibrosis.

Objective To investigate the mechanism of long non-coding RNA(LncRNA)FUT8-AS1 on diabetic ischemia-reperfusion injury by regulating growth differentiation factor 15(GDF15).Methods Male SD rats were randomly divided into Sham group,cerebral ischemia-reperfusion injury(MCAO/R)group,diabetic cerebral ischemia-reperfusion injury(DM-MCAO/R)group,DM-MCAO/R+sh NC group,and DM-MCAO/R+sh FUT8-AS1 group.TTC staining was used to assess the size of cerebral infarction.Tunel staining was selected to evaluate the apoptosis of neurons in brain tissue.Nissl staining was used to assess the number of neurons in brain tissue.The expression of LncRNA FUT8-AS1,GDF15 mRNA in Willis arterial loop and internal carotid artery tissues were detected by qRT-PCR.The expression of α-SMA,eNOS,p-eNOS,GDF15 protein in Willis arterial loop and internal carotid artery was detected by Western blot.The rat brain microvascular endothelial cells were divided into control(Con)group,OGD/R group,HG-OGD/R group,HG-OGD/R+sh NC group,HG-OGD/R+sh FUT8-AS1 group,HG-OGD/R+sh FUT8-AS1+oe NC group,and HG-OGD/R+sh FUT8-AS1+oe GDF15 group.MTT assay was used to detect cell viability.Lactate dehydrogenase(LDH)assay was used to detect cell damage.The expression ofα-smooth muscle actin(α-SMA),endothelial nitric oxide synthase(eNOS),p-eNOS protein was detected by Western blot.Results Compared with the Sham group,the percentage of cerebral infarction,the number of Tunel-positive cells,the FUT8-AS1 and mRNA expression of GDF15 and the expression of GDF-15 protein increased(P<0.05),and the expression of α-SMA,eNOS,p-eNOS proteins decreased in the MCAO/R group(P<0.05),and the number of neurons in the hippocampus decreased,the morphology was shrunk,and the color was dark in the MCAO/R group.Compared with the MCAO/R group,the percentage of cerebral infarction,the number of Tunel-positive cells,the FUT8-AS1 and mRNA expression of GDF15 and the expression of GDF-15 protein increased(P<0.05),and the expression of α-SMA,eNOS,p-eNOS proteins decreased in the DM-MCAO/R group(P<0.05),and the number of neurons in the hippocampus decreased in the DM-MCAO/R group.Compared with the DM-MCAO/R+sh NC group,the percentage of cerebral infarction,the number of Tunel-positive cells,the FUT8-AS1 and mRNA expression of GDF15 and the expression of GDF-15 protein decreased(P<0.05),and the expression of α-SMA,eNOS,p-eNOS proteins increased in the DM-MCAO/R+sh FUT8-AS1 group(P<0.05),and the number of neurons in the hippocampus increased in the DM-MCAO/R+sh FUT8-AS1 group.Compared with the Con group,the LDH release,FUT8-AS1 expression,GDF15 mRNA and protein expression increased(P<0.05),and the cell activity,α-SMA,eNOS,and p-eNOS protein expressions decreased in the OGD/R group(P<0.05).Compared with the OGD/R group,the LDH release,FUT8-AS1 expression,GDF15 mRNA and protein expression increased(P<0.05),and the cell activity,α-SMA,eNOS,and p-eNOS protein expressions decreased in the HG-OGD/R group(P<0.05).Compared with the HG-OGD/R+sh NC group,the LDH release,FUT8-AS1 expression,GDF15 mRNA and protein expression decreased(P<0.05),and the cell activity,α-SMA,eNOS,and p-eNOS protein expressions increased in the HG-OGD/R+sh FUT8-AS1 group(P<0.05).Compared with the HG-OGD/R+sh NC group,the LDH release,GDF15 mRNA and protein expression increased(P<0.05),and the cell activity decreased in the HG-OGD/R+oe GDF15 group(P<0.05).Compared with the HG-OGD/R+sh FUT8-AS1+oe NC group,the expression of α-SMA,eNOS,p-eNOS proteins decreased in the HG-OGD/R+sh FUT8-AS1+oe GDF15 group(P<0.05).Conclusions LncRNA FUT8-AS1 may exacerbate diabetic cerebral ischemia-reperfusion injury by regulating GDF15.

Objective Explore the clinical and molecular genetic characteristics of children with epilepsy as the first symptom caused by mutations in the ATPase Na+/K+transporting subunit alpha-3(ATP1A3)gene.Methods Clinical data of 853 epilepsy patients who visited the Department of Pediatric Neurology at Northwest Women's and Children's Hospital from November 2021 to December 2023 were retrospectively collected.Among them,3 cases were diagnosed with ATP1A3 gene mutations.Next-generation sequencing(NGS)techniques was used to perform whole exome sequencing analysis on serum samples from ATP1A3 gene mutation patients,and Sanger sequencing method was used for mutation verification.Results The ATP1A3 gene mutation sites in three patients were c.2401(exo n17)G>A,c.1103C>T and c.2542+1G>A,all of which presented with epilepsy as the initial symptom,mainly manifested as seizures and loss of consciousness.Imaging examination shows no abnormalities or slight widening of the subarachnoid space in both frontal and temporal regions,with background slow waves appearing in the electroencephalogram.Seizure were relieved after treatment with antiepileptic drugs.Conclusion The heterozygous mutations c.1103C>T and c.2542+1G>A at the ATP1A3 gene locus are novel pathogenic variations in epilepsy,and further confirm that the c.2401(exon17)G>A heterozygous mutation can cause epilepsy symptoms in patients.The clinical phenotype of ATP1A3 gene mutation includes typical alternating hemiplegia and muscle tone disorders,as well as seizures and developmental delay.

Objective To systematically analyze the changes in clinical indicators including blood leukocytes and neutrophils,liver and kidney functions,coagulation function,lipids,and levels of thyroid hormones and antibodies in Graves'ophthalmopathy(GO)patients who had undergone effective treatment with tocilizumab(TCZ)and to explore their clinical significance.Methods Eighty-five patients with moderately or severely active GO who were effectively treated with TCZ were enrolled.Early morning fasting blood was collected and tested for routine blood,biochemical routine,coagulation function,thyroid hormone and antibodies,and basic information such as gender,age,duration of the disease,history of smoking,comorbidities,and medications were also collected from all patients,so changes in the clinical indicators before and after the treatment could be analyzed and correlation analyses could be carried out.Results Patients with moderately to severely active GO treated with TCZ showed a significant decrease in absolute blood leukocyte and neutrophil values compared with before,and a significant decrease in liver function(alanine transaminase,aspartate aminotransferase,creatinine),cholesterol(total cholesterol,high-density lipoprotein and low-density lipoprotein)levels were significantly higher than before,and concentrations of coagulation parameters[prothrombin time,activated partial thromboplastin time,fibrinogen(FIB)and D-dimer]were significantly decreased.The concentrations of thyroid hormone and thyroid-stimulating hormone levels increased significantly,and the antibody titer of thyrotropin receptor antibody(TRAB)was significantly down-regulated after treatment.TRAB levels were significantly correlated with FIB before treatment.Conclusion Thyroid function and antibody levels improved after TCZ treatment in patients with moderately to severely active GO,but blood leukocytes,liver function and coagulation function changed significantly compared with before.The results of this study confirm the therapeutic effect of TCZ on immune disorders in GO ophthalmopathy,while underscoring the importance of monitoring potential adverse effects in clinical treatment.

Objective To evaluate the application value of stereotactic robotic surgery driven by a multi scenario AI system in the elderly with severe hypoperfusion in the internal capsule area and minor HTH.Methods A retrospective analysis was conducted on 101 minor HTH patients com-plicated with severe hypoperfusion in the internal capsule area identified by an AI diagnostic sys-tem in our department from January to October 2024.Among them,48 cases who underwent ster-eotactic robotic drainage with AI system support were assigned into the study group,and 53 cases of conventional drug treatment were into the control group.The general clinical data were com-pared between the two group.Improvement rate of rCBF 14 d after treatment,effective rate 90 d after treatment,favorable prognosis rate,and incidence of shunt dependent hydrocephalus were compared between the two groups to evaluate the application value of AI-assisted stereotactic ro-botic surgery in these patients.Results The study group had significantly higher improvement rate of rCBF 14 d after treatment,better effective rate and larger ratio of favorable prognosis 90 d after treatment when compared with the control group(60.4％vs 39.6％,P＜0.05;62.5％vs 41.5％,P＜0.05;64.6％vs 43.4％,P＜0.05).Conclusion Stereotactic robotic assisted drainage driven by multi scenario AI system can significantly improve the prognosis of the elderly minor HTH patients complicated with severe hypoperfusion in the internal capsule area.

Objective To explore the feasibility and safety of non-anticoagulation veno-venous extracorporeal membrane oxygenation(VV-ECMO)in patients with severe chest trauma.Methods A retrospective cohort study method was used.A total of 19 patients with severe chest trauma who received VV-ECMO with a delayed anticoagulation strategy at Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2018 to October 2021 were included in the delayed anticoagulation group,and 20 patients with severe chest trauma who received VV-ECMO with a non-anticoagulation strategy from November 2021 to October 2024 were included in the non-anticoagulation group.The overall clinical characteristics of the patients were statistically analyzed,including gender,age,injury severity score(ISS),acute physiology and chronic health evaluationⅡ(APACHEⅡ),reason for VV-ECMO,use of vasoactive drugs,oxygenation index(PaO2/FiO2),and interval from injury to VV-ECMO.The primary outcomes were hemorrhagic and thrombotic complications.The secondary outcomes were blood transfusion during VV-ECMO,VV-ECMO time,mechanical ventilation time,intensive care unit(ICU)length of stay,and 28-day mortality.Results There was no significant difference in gender,age,ISS score,APACHEⅡscore,reason for VV-ECMO,use of vasoactive drugs,PaO2/FiO2,and interval from injury to VV-ECMO between the non-anticoagulation group and the delayed anticoagulation group.There was no significant difference in overall incidence of hemorrhagic and thrombotic between the two groups[incidence of hemorrhagic complications:15.0%(3/20)vs.31.6%(6/19),incidence of thrombotic:15.0%(3/20)vs.5.3%(1/19),both P>0.05].The infusion rate of 4 or more paked red blood cell(PRBC)within 24 hours during VV-ECMO in the non-anticoagulation group was significantly lower than that in the delayed anticoagulation group[5.0%(1/20)vs.31.6%(6/19),P<0.05].The amount of PRBC and platelet transfusion and the time on VV-ECMO in the non-anticoagulation group during VV-ECMO were significantly lower than those in the delayed anticoagulation group[PRBC(U):5.8±3.8 vs.8.1±3.1,platelets(U):1(0,1)vs.2(1,3),time on VV-ECMO(hours):71.55±24.37 vs.114.21±34.08,all P<0.05].There were no statistically significant differences in the amount of plasma and cryoprecipitate transfusion during VV-ECMO,mechanical ventilation time,ICU hospitalization time,and 28-day mortality between the two groups.Conclusion For patients with severe chest trauma receiving VV-ECMO withholding routine systemic anticoagulation did not result in thrombotic complications or higher mortality and required less PRBC and platelet transfusions.Non-anticoagulant VV-ECMO is safe and feasible for patients with severe chest trauma with high risk of bleeding.