Abstract:Objective To develop and validate a prediction model for the intraoperative wedge effect during proxi-mal femoral nail antirotation(PFNA)fixation in patients with intertrochanteric femoral fractures.Methods A total of 597 patients with intertrochanteric femoral fractures were retrospectively enrolled.The occurrence of wedge effect was de-termined based on postoperative radiographic criteria(a reduction in the neck-shaft angle by≥4° compared to the contra-lateral side and lateral displacement of the femoral shaft by≥7 mm).Admission-related clinical data were collected.Least absolute shrinkage and selection operator(LASSO)regression was used to screen predictive variables,and multi-variable Logistic regression analysis was performed to identify independent influencing factors and to construct a nomo-gram prediction model.Internal validation was conducted using the bootstrap resampling method(1,000 repetitions).The concordance index(C-index),area under the receiver operating characteristic curve(AUC),and Brier score were calculated,and calibration curves and decision curve analysis were plotted to evaluate the discrimination,calibration,and clinical applicability of the model.Results Intraoperative wedge effect occurred in 83 patients(13.9%)and did not occur in 514 patients(86.1%).Involvement of the greater trochanter(OR=18.022,95%CI:8.546-38.005),lat-eral wall fracture(OR=9.431,95%CI:4.703-18.910),body mass index(BMI)>24 kg/m²(OR=8.670,95%CI:4.228-17.778),and bone mineral density(BMD)T-score≤-2.5(OR=9.236,95%CI:4.548-18.755)were identi-fied as risk factors for the wedge effect(all P<0.05).In contrast,absence of lesser trochanter displacement(OR=0.386,95%CI:0.205-0.730)was a protective factor(P<0.05).The nomogram model constructed based on these fac-tors yielded an area under the receiver operating characteristic curve(AUC)of 0.922(95%CI:0.895-0.950),with a corrected C-index of 0.918 and a Brier score of 0.070.The calibration curve showed close agreement with the ideal ref-erence line,and decision curve analysis demonstrated that the model provided a net clinical benefit within a threshold probability range of 0.05-0.50.Conclusions Greater trochanter involvement,lateral wall fracture,BMI>24 kg/m²,and BMD T-score≤-2.5 are risk factors for the intraoperative wedge effect,while absence of lesser trochanter displace-ment is a protective factor.The prediction model incorporating these factors exhibits favorable discrimination,calibration,and clinical utility.

Abstract:Objective To investigate the effect of circadian rhythm disruption caused by light pollution on bone mi-croarchitecture in mice and its underlying mechanism of action.Methods Twelve mice were divided into four groups(n=3 per group)using a random number table:the normal circadian rhythm group,the model group,the melatonin interven-tion group,and the rhythm recovery group.Mice in the normal circadian rhythm group were maintained under a standard 12-hour light-dark cycle(12 h light:12 h darkness)throughout the experimental period.Mice in the remaining groups were exposed to an extended photoperiod(15 h light:9 h darkness)to simulate light pollution and induce circadian rhythm dis-ruption.Mice in the melatonin intervention group received daily oral administration of melatonin at a dose of 10 mg/(kg·d)concomitantly with the modeling phase.Mice in the rhythm recovery group were returned to the standard 12-hour light-dark cycle after 8 weeks of prolonged light exposure and were then maintained under these conditions for an additional 8 weeks.At the conclusion of the 16-week study,femoral specimens were collected.Bone microarchitectural parameters,including bone volume fraction,trabecular thickness,and trabecular number,were assessed using high-resolution micro-computed tomography.Osteoclast density was calculated via Tartrate-resistant acid phosphatase(TRAP)staining.Pearson correla-tion analysis was performed to assess the relationships between osteoclast density and bone microarchitecture parame-ters.Results Compared with the normal rhythm group,the model group exhibited significantly lower bone volume frac-tion(BV/TV),reduced trabecular thickness(Tb.Th),decreased trabecular number(Tb.N),and elevated osteoclast den-sity(all P<0.05).No statistically significant differences were observed in BV/TV,Tb.Th,Tb.N,or osteoclast density be-tween the model group and the melatonin intervention group(all P>0.05).In contrast,the rhythm recovery group showed significantly higher BV/TV,greater Tb.Th,increased Tb.N,and lower osteoclast density(all P<0.05).Furthermore,os-teoclast density was negatively correlated with BV/TV,Tb.N,and Tb.Th(r=-0.669,-0.826,and-0.857,respective-ly;all P<0.05).Conclusions Long-term exposure to light pollution impairs bone microarchitecture in mice,potentially mediated by aberrantly increased osteoclast activity.Although exogenous melatonin does not effectively mitigate this patho-logical process,optimizing ambient light conditions may represent a viable strategy for preserving skeletal health.

Abstract:Objective To investigate the predictive value of preoperative serum monocyte chemotactic protein-1(MCP-1),plasminogen activator inhibitor-1(PAI-1)levels,and fingertip tactile function for postoperative delirium(POD)in elderly patients with hip fractures undergoing hip arthroplasty.Methods A prospective cohort of 220 elderly hip fracture patients undergoing hip arthroplasty was enrolled.Fasting venous blood was collected one day preoperatively.Serum MCP-1 and PAI-1 levels were measured using enzyme-linked immunosorbent assay(ELISA).Concurrently,bilater-al fingertip tactile function was assessed using the Semmes-Weinstein monofilament test.Postoperative delirium was evalu-ated at seven days post-surgery using the Confusion Scale.Clinical perioperative data were compared between elderly hip replacement patients with and without POD.Multivariate Logistic regression analysis identified independent risk factors for POD.Receiver operating characteristic(ROC)curves evaluated the predictive efficacy of preoperative serum MCP-1,pre-operative serum PAI-1,and fingertip tactile function,both individually and in combination,for POD.Internal validation was performed using 1,000 bootstrap resamples,with curve analysis assessing the clinical net benefit of predictive mod-els.Results Among 220 elderly hip replacement patients,45 developed POD,yielding an incidence rate of 20.45%.Elderly patients with POD exhibited higher age,ASA physical status,transfusion rates,intraoperative blood loss,intraop-erative fluid administration,and preoperative serum MCP-1 and PAI-1 levels than those without POD,while albumin lev-els were lower(all P<0.05).Multivariate Logistic regression analysis revealed that increased age,ASA physical status classification Ⅲ-Ⅳ,increased intraoperative fluid administration,elevated preoperative serum MCP-1,elevated preopera-tive serum PAI-1,and worsened fingertip tactile sensation grade were all independent risk factors for POD in elderly hip re-placement patients(all P<0.05).ROC curve analysis revealed that the areas under the curve(AUCs)of preoperative se-rum MCP-1,PAI-1 levels,and fingertip tactile function individually in predicting POD in elderly hip replacement patients were 0.809,0.799,and 0.787,respectively.The combined prediction of POD using all three indicators yielded an AUC of 0.938.Bootstrap internal validation revealed a C-statistic of 0.938(95%CI:0.933-0.943)for the combined model.Decision curve analysis revealed that within the threshold probability range of 0.15 to 0.98,the combined model demon-strated greater net benefit than any single indicator.Conclusions Elevated preoperative serum MCP-1 and PAI-1 lev-els,along with increased fingertip tactile function grading,are independent risk factors for POD in elderly hip replacement patients.The combined use of these three indicators exhibits high predictive value for POD in this patient population.

Abstract:Objective To explore the ultrasonic manifestations of abnormally thickened placenta and its rela-tionship with pregnancy outcomes,providing imaging evidence for prenatal identification of high-risk pregnancies.Methods Eighty singleton pregnant women who underwent prenatal ultrasound examination and had their placental thickness status clearly defined were retrospectively selected.The subjects were divided into the control group(28 cases),placental thickening group(24 cases),and abnormally thickened placenta group(28 cases)based on the pla-cental thickness measured in the first ultrasound.Ultrasonic indicators[fetal growth restriction(FGR),placental thick-ness,and placental morphological features(whether combined with placental spherical changes or other placental morpho-logical abnormalities),fetal hemodynamics(abnormal blood flow spectra of the umbilical artery and middle cerebral ar-tery)],delivery outcomes[delivery mode(cesarean section or vaginal delivery),placental abruption,induction of labor or other fetal loss],neonatal outcomes[abnormal neonatal Apgar score,low birth weight or preterm birth],and placental pathological indicators[placental villous infarction,placental chorioamnionitis(including chorioamnionitis)]were com-pared among the groups.For outcome indicators with a small number of cases,only descriptive analysis was conducted.Results The incidence of FGR and placental spherical changes in the abnormally thickened placenta group was higher than that in the control group and the placental thickening group,and the incidence of placental spherical changes in the placental thickening group was higher than that in the control group(all P<0.05);abnormal blood flow spectra were only observed in the abnormally thickened placenta group.The cesarean section rate and placental abruption rate in the abnor-mally thickened placenta group were higher than those in the control group and the placental thickening group,and the ce-sarean section rate and placental abruption rate in the placental thickening group were higher than those in the control group(all P<0.05);induction of labor or other fetal loss was only observed in the abnormally thickened placenta group.The incidence of abnormal neonatal Apgar score in the abnormally thickened placenta group was higher than that in the con-trol group and the placental thickening group,and the incidence of abnormal neonatal Apgar score in the placental thicken-ing group was higher than that in the control group(all P<0.05);low birth weight or preterm infants were only observed in the abnormally thickened placenta group.The incidence of placental villous infarction or placental chorioamnionitis in the abnormally thickened placenta group was higher than that in the control group and the placental thickening group,and the incidence of placental villous infarction or placental chorioamnionitis in the placental thickening group was higher than that in the control group(all P<0.05).Conclusion Abnormally thickened placenta,especially when combined with spheri-cal changes,is associated with an increased risk of fetal growth restriction,adverse delivery and neonatal outcomes,and placental pathological abnormalities.

Abstract:Insomnia is a common sleep disorder primarily characterized by difficulties in sleep initiation and mainte-nance,and its occurrence and development are closely associated with circadian rhythm disruption.As a representative formula in traditional Chinese medicine for guiding yang into yin,Banxia Shumi decoction has demonstrated certain thera-peutic effects in improving insomnia.Banxia Shumi decoction can ameliorate sleep-wake rhythm disturbances by regulat-ing the rhythmic expression of core clock genes such as circadian locomotor output cycles kaput(CLOCK),brain and mus-cle ARNT-like 1(BMAL1),period(PER),and cryptochrome(CRY).Simultaneously,it restores the central excitatory-inhibitory balance by modulating multiple neurotransmitter systems,including melatonin,γ-aminobutyric acid(GABA),glutamate,serotonin,dopamine,norepinephrine,and orexin.Additionally,it suppresses the overactivation of the hypo-thalamic-pituitary-adrenal(HPA)axis and improves abnormalities in the circadian rhythm of inflammatory factors,thereby synergistically enhancing sleep architecture and sleep homeostasis.The mechanism by which Banxia Shumi decoction im-proves insomnia through multi-target and multi-pathway regulation of the circadian rhythm network aligns with the theoreti-cal connotation of traditional Chinese medicine in harmonizing yin and yang and guiding yang into yin.This provides a the-oretical reference for mechanistic research and clinical applications of traditional Chinese medicine in the prevention and treatment of insomnia.

Abstract:Objective To explore the potential mechanism of the Chinese herbal pair Danggui(Angelica sinensis Radix)-Chuanxiong(Ligusticum chuanxiong)in treatment of ischemic stroke(IS)based on network pharmacology and to provide theoretical basis for its clinical application.Methods The active ingredients of the Chinese herbal pair Danggui-Chuanxiong and their corresponding target genes were screened using the Traditional Chinese Medicine Systems Pharmacol-ogy Database and Analysis Platform(TCMSP).The target genes were standardized via the UniProt database.Disease-relat-ed target genes for IS were retrieved from the GeneCards,OMIM,and CTD databases.The intersection of the drug target genes and the disease target genes was obtained as the potential therapeutic targets of the Chinese herbal pair Danggui-Ch-uanxiong for IS.A protein-protein interaction(PPI)network and a drug-compound-intersection target-disease network were constructed based on the intersection target genes.The core target genes and the main active ingredients of the Chi-nese herbal pair Danggui-Chuanxiong for the treatment of IS were screened using these networks.Subsequently,Gene On-tology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the core target genes.Finally,molecular docking was employed to validate the binding affinity between the main active ingredients and the core target genes.Results A total of 8 active ingredients of the Chinese herbal pair Danggui-Chuanxiong,66 related target genes were identified,and 10,458 disease-related target genes for IS were ob-tained.The intersection revealed 55 overlapping target genes.Topological analysis of the PPI network identified core tar-get genes such as the c-Jun proto-oncogene(JUN),heat shock protein 90β(HSP90AB1),Caspase-3(CASP3),B-cell lymphoma 2(BCL2),and estrogen receptor 1(ESR1).Analysis of the drug-compound-intersection target-disease network screened out main active ingredients including β-sitosterol,myricetin,stigmasterol,senkyunolide,and ligustrazine.The GO enrichment analysis results showed that the core target genes were primarily involved in biological processes such as the regulation of neuronal apoptosis,modulation of postsynaptic membrane potential,and the nuclear receptor-mediated steroid hormone signaling pathway.The KEGG pathway enrichment analysis results indicated that the core target genes were significantly enriched in pathways such as neuroactive ligand-receptor interaction,and lipid and atherosclerosis.The molecular docking results demonstrated that the main active ingredients of the Chinese herbal pair Danggui-Chuanx-iong exhibited good binding affinities with the core target genes in the treatment of IS,with calculated binding energies all below-5.0 kcal/mol.Conclusions The Chinese herbal pair Danggui-Chuanxiong may exert multi-target and multi-pathway neuroprotective effects by utilizing various active ingredients such as β-sitosterol,myricetin,and stigmasterol to act on key targets including JUN,HSP90AB1,and CASP3.This synergistic action regulates related signaling pathways involving neuroactive ligand-receptor interactions,lipid metabolism,oxidative stress,inflammatory response,and neuro-nal apoptosis.

Abstract:Objective To develop and validate a prognostic model for children with spastic cerebral palsy who un-dergo selective posterior rhizotomy(SPR).Methods A total of 145 children with spastic cerebral palsy who underwent SPR were retrospectively enrolled.These patients were divided into the training set(n=102)and validation set(n=43)at a ratio of 7:3.The Ashworth scale was employed to assess the lower-limb muscle tone of patients before and after surgery.A decrease of≥1 level in lower-limb muscle tone after surgery was regarded as a favorable prognosis,whereas a decrease of<1 level was considered an unfavorable prognosis.Relevant data of chilren were collected.Univariate and multivariate Logistic regression analyses were used in the training set to screen independent risk factors,and we constructed a nomo-gram prediction model.In the validation set,the model was internally validated using the Bootstrap method with 1,000 resamplings.Its discrimination,goodness-of-fit,calibration,and clinical utility were assessed using the receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test,calibration curve,and decision curve analysis.Results Among the 102 patients in the training set,54 had a favorable prognosis and 48 had an unfavorable prognosis.Among the 43 cere-bral palsy patients in the validation set,28 had a favorable prognosis and 15 had an unfavorable prognosis.Older age(OR=1.269,95%CI:1.098-1.466,P<0.05),Gross Motor Function Classification System(GMFCS)grade Ⅳ-Ⅴ(OR=3.984,95%CI:1.423-11.152,P<0.05),and the inability to sit independently(OR=3.970,95%CI:1.275-12.359,P<0.05)were identified as independent risk factors for the unfavorable prognosis in patients with spastic cerebral palsy.Based on the analysis of influencing factors,the regression equation of the model was obtained as logit(P)=-3.336+0.238×age+1.382×GMFCS grading+1.379×sitting independently.The AUC of the training-set prediction model was 0.801(95%CI:0.712-0.889),and the AUC of the validation-set prediction model was 0.785(95%CI:0.646-0.923).There was no statistically significant difference between the actual probability of an unfavorable prognosis and the predicted probability(χ2=9.182,df=8,P=0.327),indicating a good goodness-of-fit.The calibration plot also demon-strated a high degree of consistency between the predicted model and clinical observations.The model predicted that the probability of an unfavorable prognosis(i.e.,threshold probability)in patients with spastic cerebral palsy ranged from 19%to 96%,both of which were higher than the two extreme lines.Conclusions Older age,GMFCS grade Ⅳ-Ⅴ,and the inability to sit independently are independent risk factors for the unfavorable prognosis in SPR.The risk prediction model constructed based on these risk factors exhibits good discrimination,calibration,and clinical practical value.

Abstract:Objective To investigate the clinical efficacy of the Jingjin(muscle region of the meridian,sinew/ten-don/fascia)acupuncture therapy combined with intermittent θ-burst transcranial magnetic stimulation(iTBS)on increased hand muscle tone in stroke patients during the spastic phase.Methods Sixty patients in the spastic phase after stroke were selected and divided into three groups using a random number table,with 20 in each:the conventional group,the iT-BS group,and the combined group.Patients in all groups received conventional rehabilitation training.In addition,pa-tients in the iTBS group received iTBS treatment on the primary motor cortex of the affected side,and patients in the com-bined group received Jingjin acupuncture therapy in addition to the iTBS treatment.Assessments were conducted before treatment(T0),immediately after treatment(T1),and during short-term follow-up(T2)using the Modified Ashworth Scale(MAS)to evaluate hand muscle tone,the Fugl-Meyer Assessment Upper Extremity(FMA-UE)to evaluate upper limb motor function,the Modified Barthel Index(MBI)to assess activities of daily living,and motor evoked potentials(MEP)to evaluate the functional status of central motor pathways and changes in cortical excitability.Results Compared with those at T0 in the same group,the MEP values,FMA-UE scores,and MBI scores of all groups at T1 and T2 increased,while MAS scores decreased(all P<0.05).At T1 and T2,the MEP values,FMA-UE scores,and MBI scores of the combined group and iTBS group were higher than those of the conventional group,while MAS scores were lower than those of the con-ventional group;moreover,the MEP values,FMA-UE scores,and MBI scores of the combined group were higher than those of the iTBS group,and MAS scores were lower than those of the iTBS group(all P<0.05).There were no statistically significant differences in any indicators among the groups at the T0 time point(all P>0.05).Conclusion The Jingjin acupuncture combined with iTBS can effectively reduce hand muscle tone in patients during the spastic phase of stroke,and improve hand motor function and daily living abilities;its underlying mechanism may be associated with the facilitation of functional recovery in the central motor pathway and the restoration of cerebral cortex excitability on the affected side.

Abstract:Objective To investigate whether a moderate elevation of serum potassium exerts neuroprotective effects in the rat models with cerebral ischemia-reperfusion injury(CIRI)by modulating the Ca²⁺/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)/Caspase-3 signaling pathway.Methods Ninety-six Sprague-Dawley(SD)rats were assigned into four groups(n=24 per group)using a random number table method:the sham-operated group(Sham group),the model group,the high-dose potassium chloride group(HD group),and the low-dose potassium chloride group(LD group),re-spectively.The CIRI models were established by inducing middle cerebral artery occlusion(MCAO)using the intralumi-nal filament technique.After 90 minutes of occlusion,the filament was withdrawn to restore cerebral blood flow,thereby achieving reperfusion.In the Sham group,only vascular dissection was performed.At the onset of reperfusion,rats in the HD,LD,and model groups were administered an equal volume(3.2 mL/kg)of 2.5%potassium chloride solution(equiva-lent KCl dose:80 mg/kg),1.25%potassium chloride solution(equivalent KCl dose:40 mg/kg),and normal saline(0.9%NaCl),respectively,via intravenous injection into the internal jugular vein.After 24 hours,rats were sacrificed,and brain tissues were collected.TTC staining was used to observe the pathological changes and measure infarct volume.TUNEL staining was applied to assess neuronal apoptosis,and commercial kits were employed to determine K⁺ and Ca²⁺ lev-els.The expression levels of proteins associated with the calcium signaling pathway CaMKⅡ,its phosphorylated form at Thr-286/287(p-CaMKⅡ-Thr-286/287),as well as the apoptosis-related proteins B-cell lymphoma 2(Bcl-2),Bcl-2-as-sociated X protein(Bax),and cleaved Caspase-3(Cleaved-Caspase-3)were detected by Western blotting.Results In the model group,large pale infarct areas were observed in the brain tissues.Compared with the model group,both the LD and HD groups showed a reduction in the infarct area,with the HD group exhibiting a more significant decrease than the LD group.Compared with the Sham group,the model group exhibited a significantly larger cerebral infarct volume percent-age,a higher rate of neuronal apoptosis,a decreased concentration of K⁺ and an increased concentration of Ca²⁺ in the brain tissues.Furthermore,the protein expression levels of CaMKⅡ,p-CaMKⅡ-Thr-286/287,Bax,and Cleaved-Cas-pase-3 were significantly up-regulated,while the expression of Bcl-2 was down-regulated in the model group(all P<0.05).Compared with the model group,the HD group showed a significantly lower percentage of cerebral infarct volume,a reduced rate of neuronal apoptosis,an increased concentration of K⁺ and a decreased concentration of Ca²⁺ in the brain tissues.Furthermore,the protein expression levels of CaMKII,p-CaMKⅡ,Bax,and Cleaved-Caspase-3 were significant-ly down-regulated,while the expression of Bcl-2 was up-regulated in the HD group(all P<0.05).In the LD group,the brain tissue K⁺ concentration and Bcl-2 protein expression were significantly higher than those in the model group(both P<0.05).Conclusion The administration of a moderately elevated dose of potassium chloride to CIRI rats,at a tolerable level,may increase serum potassium,reduce intracellular calcium concentration,inhibit the Ca²⁺/CaMKⅡ/Caspase-3 signaling pathway,consequently decrease neuronal apoptosis,and exert a neuroprotective effect.

Abstract:Objective To investigate the application effect of portable isokinetic training on lower-limb functional re-habilitation in patients with early post-stroke hemiplegia.Methods Eighty patients with early post-stroke hemiplegia(onset≤3 months)were prospectively enrolled and randomly assigned(random number table)into the control group(n=40)and isokinetic training group(n=40).Patients in the control group received conventional comprehensive rehabilita-tion.In addition to conventional rehabilitation,patients in the isokinetic training group underwent bedside knee flexion-ex-tension training using a portable isokinetic muscle strength training system.Assessments were performed before interven-tion and after 4 weeks,including muscle tone of the paretic lower limb[modified Ashworth scale(MAS)],muscle strength of the paretic lower limb[peak torque(PT)and total work(TW)at an angular velocity of 60°/s],motor function[Fugl-Meyer Assessment(FMA)],balance function[Berg Balance Scale(BBS)],and walking ability[Holden's Func-tional Ambulation Category(FAC)].Results Before intervention,no significant difference was found in the MAS grade of the paretic lower limb between these two groups(P>0.05).After intervention,the isokinetic training group showed low-er MAS grade than the control group(P<0.05).Before intervention,there were no significant differences in PT or TW of the paretic extensors or flexors between these two groups(all P>0.05).After intervention,PT and TW of both extensors and flexors increased in both groups in comparison with the baseline,and all strength indices were higher in the isokinetic training group than in the control group(all P<0.05).Before intervention,there were no significant differences in FMA and BBS scores or FAC grades between groups(all P>0.05).After intervention,FMA and BBS scores and FAC grades in-creased in both groups compared with the baseline,and the isokinetic training group achieved higher FMA and BBS scores and higher FAC grades than the control group(all P<0.05).Conclusion Adding portable isokinetic strength training to conventional comprehensive rehabilitation in the early stage after stroke may further reduce muscle tone and improve mus-cle strength of the paretic lower limb,thereby facilitating recovery of motor,balance,and walking abilities.

Abstract:Objective To investigate the clinical characteristics,imaging features,and key diagnostic and thera-peutic considerations of midbrain infarction presenting with ophthalmoplegia as the initial manifestation,thereby enhanc-ing clinicians'ability to recognise this uncommon presentation.Methods A retrospective analysis was conducted on the clinical data of two patients with acute mesencephalic lacunar infarction presenting with ophthalmoplegia.The data includ-ed medical history,neurological examination,imaging studies,diagnostic and therapeutic processes,and follow-up out-comes,supplemented by relevant literature review.Results Both patients presented with ophthalmoplegia symptoms such as diplopia in the early stages,without significant additional neurological signs.Case 1 presented with typical anteri-or nucleus-interstitial ophthalmoplegia;imaging revealed acute lacunar infarction in the paramedian midbrain region,sug-gesting involvement of the left medial longitudinal fasciculus.Case 2 exhibited hypoglossal oculomotor palsy;imaging dem-onstrated acute punctate infarction adjacent to the midbrain aqueduct,indicating involvement of structures related to the superior branch of the oculomotor nerve.Both patients had risk factors for cerebrovascular events,including diabetes melli-tus.Diffusion-weighted imaging(DWI)on cranial magnetic resonance imaging(MRI)demonstrated lesions in the early phase,with some sequences showing atypical patterns.Following standardised antiplatelet therapy,lipid-lowering treat-ment,and risk factor management,follow-up revealed complete resolution of ocular muscle paralysis symptoms in both cas-es,with favourable outcomes.Conclusions Interstitial and subnuclear ophthalmoplegia represent uncommon initial pre-sentations of midbrain infarction.Early integration of neurological examination with cranial MRI and DWI facilitates defini-tive diagnosis and guides standardised management,thereby improving patient outcomes.

Abstract:Objective To investigate the influence of melatonin receptor 1B(MTNR1B)gene polymorphisms at loci rs10830963,rs3781637,and rs3781638 in pregnant women on neonatal pregnancy outcomes.Methods A prospective cohort study was adopted.Using cluster sampling,268 pregnant women with adverse neonatal pregnancy outcomes(pre-term birth,low birth weight,and macrosomia)were selected as the adverse outcome group,and 268 pregnant women with healthy neonates during the same period were selected as the favorable outcome group.Baseline data of both groups were collected.Peripheral blood samples were taken and MTNR1B gene polymorphism was detected using improved multiplex li-gation detection reaction technology.The multivariate Logistic regression model was used to analyze the influence of MT-NR1B gene polymorphisms in pregnant women on adverse neonatal pregnancy outcomes.Multiplicative interaction terms were introduced to assess their interaction with gestational diabetes mellitus(GDM).Results There were significant dif-ferences in the genotype and allele frequencies of MTNR1B rs3781637 between the two groups(both P<0.05).After ad-justing for confounding factors including maternal age,pre-pregnancy BMI,gestational weight gain,history of abortion,history of embryonic arrest,co-morbid GDM,and premature rupture of membranes,analysis of the rs3781637 locus showed that in the dominant model,the pregnant women carrying the CT/TT genotype had a lower risk of adverse neonatal pregnancy outcomes than those carrying the CC genotype(OR=0.852,95%CI:0.731-0.995,P<0.05);in the reces-sive model,the pregnant women carrying the TT genotype had a lower risk than those carrying the CC/CT genotype(OR=0.635,95%CI:0.528-0.765,P<0.05).Stratified analysis results showed that for MTNR1B gene rs3781637 site,the risk of adverse neonatal pregnancy outcomes was lower in participants without GDM than in those with GDM across the CT genotype(OR=0.321,95%CI:0.114-0.902),TT genotype(OR=0.682,95%CI:0.363-0.986),T allele(OR=0.265,95%CI:0.117-0.600),and recessive model of TT genotype(OR=0.270;95%CI:0.109-0.669)(all P<0.05).Testing of multiplicative interaction terms revealed that there was a multiplicative interaction between MTNR1B gene rs3781637 site polymorphism and GDM in the TT genotype(OR=0.253,95%CI:0.081-0.782),T allele(OR=0.452,95%CI:0.223-0.923),dominant model of CT/TT genotype(OR=0.423,95%CI:0.192-0.946)and reces-sive model of CC/CT and TT genotypes(OR=0.342,0.263;95%CI:0.172-0.683,0.102-0.673)(all P<0.05).Conclusions Maternal MTNR1B gene polymorphism at locus rs3781637 is an influencing factor for neonatal pregnancy outcomes,with the T allele and TT genotype potentially acting as protective factors.This protective effect exhibits a multi-plicative interaction with GDM status.

Abstract:Objective To investigate the clinical characteristics,key diagnostic points,therapeutic strategies,and postoperative management of recurrent giant endometrial polyps,and to improve clinical awareness of this rare condition.Methods We retrospectively analyzed the clinical data of one patient with recurrent giant endometrial polyp,including medical history,imaging findings,laboratory examination results,surgical approach,pathological characteristics,and postoperative follow-up.We also reviewed the relevant literature.Results We encountered a 27-year-old female patient with a history of multiple endometrial polyp recurrences who presented with pelvic mass and irregular vaginal bleeding.Ul-trasonography and pelvic magnetic resonance imaging(MRI)revealed a huge intrauterine space-occupying lesion,with im-aging manifestations similar to gestational trophoblastic disease.Preoperative serum human chorionic gonadotropin(hCG)was mildly elevated and carbohydrate antigen 125(CA125)was significantly increased.Exploratory laparotomy confirmed the lesion origin,and postoperative pathological examination verified the diagnosis of giant endometrial polyp.After sur-gery,the patient received hormonal regulation therapy combined with gonadotropin-releasing hormone agonist(GnRHa)pretreatment,followed by placement of a levonorgestrel-releasing intrauterine system(LNG-IUS)for long-term manage-ment.We observed no obvious recurrence during follow-up.Conclusions Recurrent giant endometrial polyps are clini-cally rare entities with complex imaging manifestations,which can easily be confused with gestational trophoblastic disease and endometrial malignant lesions.Accurate diagnosis requires comprehensive judgment based on medical history,labora-tory examination,imaging studies,and pathological results.Considering the risks of recurrence and potential malignant transformation,clinicians should establish individualized long-term follow-up and management strategies on the basis of standardized treatment.

Abstract:Objective To investigate the efficacy of low-frequency repetitive transcranial magnetic stimulation(LF-rTMS)combined with transauricular auricular vagus nerve stimulation(taVNS)in improving upper limb function in pa-tients with intracerebral haemorrhage.Methods Sixty patients with hemiplegia due to intracerebral haemorrhage were randomly divided into the LF-rTMS group and the combined therapy group,with 30 in each.Patients in both groups re-ceived standard pharmacological and rehabilitation therapy.Patients in the LF-rTMS group additionally underwent LF-rT-MS targeting the contralateral primary motor cortex,while patients in the combined therapy group concurrently received taVNS alongside LF-rTMS.The treatment cycle lasted four weeks.Upper limb motor function was assessed pre-and post-treatment using the Fugl-Meyer Upper Limb Scale(FMA-UE)and the Hong Kong edition of Functional Test for the Hemi-plegic Upper Extremity(FTHUE-HK).Near-infrared brain functional imaging was employed to measure changes in cere-bral tissue oxyhaemoglobin(HbO₂)concentration to evaluate the cortical functional activation levels.Results Pre-treat-ment FMA-UE and FTHUE-HK scores showed no statistically significant differences between groups(all P>0.05).After treatment,the LF-rTMS group exhibited higher FMA-UE scores,while the combined therapy group demonstrated higher FMA-UE and FTHUE-HK scores in comparison with the pre-treatment levels(both P<0.05).Furthermore,the combined therapy group achieved significantly higher FMA-UE and FTHUE-HK scores than the LF-rTMS group(both P<0.05).Pre-treatment cerebral tissue HbO₂ concentrations showed no statistically significant differences between groups(P>0.05).Af-ter treatment,HbO₂ concentrations increased in both groups in comparison with the baseline,with the combined therapy group exhibiting higher levels than the LF-rTMS group(both P<0.05).Conclusion LF-rTMS combined with taVNS may effectively improve upper limb motor function in patients with intracerebral haemorrhage by enhancing cortical func-tional activation levels.

Abstract:Objective To compare the clinical efficacy and safety of argatroban and tirofiban in the treatment of pa-tients with progressive cerebral infarction(PCI).Methods Eighty patients with PCI were enrolled in this study and were divided into the argatroban group and the tirofiban group(40 cases per group)using a random number table method.Patients in the argatroban group were immediately administered argatroban injection upon admission.For the first 2 days,60 mg of argatroban injection was diluted in 500 mL of 0.9%sodium chloride injection for intravenous infusion,with the infusion duration lasting no less than 24 h per day.For the subsequent 5 days,the dosage was adjusted to 20 mg of argatro-ban injection diluted in 100 mL of 0.9%sodium chloride injection,and the infusion duration was set at no less than 3 h per day.Patients in the tirofiban group were treated with tirofiban injection immediately after admission,with a single dose regimen of 12.5 mg of tirofiban injection diluted in 250 mL of 0.9%sodium chloride injection for a continuous intravenous infusion of 48 h.Both groups received combined basic therapy starting from the 3rd day of treatment.The National Insti-tutes of Health Stroke Scale(NIHSS)was adopted to evaluate the degree of neurological deficit before treatment and on the 14th day after treatment initiation.A 3-month follow-up was conducted,and the modified Rankin Scale(mRS)score was used to assess the patients'prognosis.Routine blood tests,liver and kidney function tests,and coagulation function pa-rameters were measured in both groups before and after treatment.Additionally,the incidence of severe bleeding events and drug-related adverse reactions were recorded throughout the treatment period and the 3-month follow-up.Results After 14 days of treatment,the NIHSS scores of both groups were significantly lower than those before treatment(both P<0.05),and the NIHSS score of the tirofiban group was lower than that of the argatroban group(P<0.05).During 3 months of follow-up,the mRS scores of both groups significantly decreased in comparison with those before treatment(both P<0.05),and the mRS score of the tirofiban group was lower than that of the argatroban group(P<0.05).At 3 months of fol-low-up,the proportion of functional independence in the tirofiban group was higher than that in the argatroban group(P<0.05),while there was no statistically significant difference in the proportion of severe disability between the two groups(P>0.05).Before and after treatment,the blood routine,liver and kidney function,and coagulation function indexes of both groups were normal.During the treatment period and within 3 months of follow-up,no severe bleeding events such as symptomatic intracerebral hemorrhage,gastrointestinal bleeding,or gingival bleeding occurred in either group;only 1 pa-tient in each group developed mild subcutaneous ecchymosis,which resolved spontaneously without special treatment.Conclusions Both argatroban and tirofiban can effectively improve the neurological deficit and long-term prognosis of pa-tients with PCI in the early treatment,with good safety and no increased risk of bleeding.Tirofiban has more advantages in promoting neurological function recovery and improving prognosis.

Abstract:Objective To investigate the value of multimodal magnetic resonance imaging(MRI)combining diffusion-weighted imaging(DWI),T2* relaxation time quantitative imaging(T2* mapping),and susceptibility-weighted imaging(SWI)in the differential diagnosis of prostate cancer(PCa)and benign prostatic hyperplasia(BPH).Methods Thirty-five pa-tients with PCa were retrospectively enrolled as the PCa group,and 45 patients with BPH were enrolled as the BPH group.All patients underwent conventional prostate MRI,DWI,T2* mapping,and SWI.The apparent diffusion coefficient(ADC)value,T2* value,and the number of calcifications and microhemorrhages were obtained.Differences in these pa-rameters between the two groups were compared.A multivariate Logistic regression model was constructed to develop a combined diagnostic model.Receiver operating characteristic(ROC)curves were plotted to evaluate the diagnostic effi-cacy of each individual parameter and the combined models.Results The ADC and T2* values in the PCa group were sig-nificantly lower than those in the BPH group,while the number of microhemorrhages was significantly larger in the PCa group(all P<0.05).No statistically significant difference was found in the number of calcifications between the two groups(P>0.05).Single-parameter diagnostic models based on ADC value,T2* value,and the number of microhemorrhages yielded areas under the ROC curve(AUCs)of 0.930,0.866,and 0.661,respectively.The combined model incorporat-ing ADC and T2* values and the combined model incorporating ADC value,T2* value,and the number of microhemor-rhages,both constructed using multivariate Logistic regression analysis,achieved an AUC of 0.961.The AUCs of both combined models were superior to those of the individual ADC value model and the individual T2* value model(both P<0.05).Conclusions Multimodal MRI combining DWI,T2* mapping,and SWI can improve differentiation between PCa and BPH.The combined application of DWI and T2* mapping demonstrates high diagnostic value.

Abstract:Objective To investigate whether low expression of neural epidermal growth factor-like 1(NELL1)in-fluences the malignant biological behavior of glioblastoma(GBM)cells through the focal adhesion kinase(FAK)signaling pathway.Methods Human astrocytes(SVGP12 cells)and human GBM cells(A172,U251 cells)were cultured.West-ern blotting was used to detect NELL1 protein expression in different cell types for cell selection.The selected experimen-tal cells were randomly divided into the negative control group,NELL1-knockdown group 1,and NELL1-knockdown group 2.These groups were infected with negative control lentivirus or NELL1-interfering lentiviral particles(Sh1,Sh2),respec-tively.Knockdown efficiency was verified by quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting.Cell proliferation was assessed by colony formation assay and CCK-8 assay.The apoptosis was detected by Annex-in V-APC/PI double staining.Cell migration was evaluated by Transwell assay.The expression of phosphorylated FAK(p-FAK)and epithelial-mesenchymal transition(EMT)-related proteins(E-cadherin,N-cadherin,and Snail)was measured by Western blotting.Results Compared with SVGP12 cells,the relative expression of NELL1 protein was higher in both A172 and U251 cells(both P<0.05).Because NELL1 expression was lower in A172 cells than in U251 cells,A172 cells were selected for subsequent experiments to ensure scientific rigor.Compared with the negative control group,the relative expression levels of NELL1 mRNA and protein were lower(both P<0.05),the number of colonies formed was smaller(both P<0.05),the optical density(OD)values at 24,48,and 72 hours of culture were lower(all P<0.05),the apopto-sis rates were higher(both P<0.05),the number of transmembrane cells was smaller(both P<0.05),and the protein ex-pression of p-FAK,E-cadherin,N-cadherin,and Snail was lower in the NELL1-knockdown groups 1 and 2(all P<0.05).Conclusion Knockdown of NELL1 may inhibit the proliferation and migration of GBM cells and induce apoptosis,poten-tially by regulating the FAK signaling pathway to promote EMT.

Abstract:Autism spectrum disorder(ASD)is a type of neurodevelopmental disorders that onset in childhood,and its neurobiological mechanisms have not been fully elucidated.Magnetic resonance imaging(MRI)technology,due to its non-invasive nature and multi-parameter advantages,has played an important role in revealing brain structure,white mat-ter connectivity,functional networks,and neurochemical abnormalities in children with ASD.In the MRI studies of chil-dren with ASD,structural MRI and diffusion tensor imaging studies involve abnormalities in multiple brain regions'struc-tures and white matter microstructures,suggesting gender dependence and developmental dynamics;magnetic resonance spectroscopy studies focus on abnormal changes in metabolites related to excitatory and inhibitory neurotransmission;blood oxygen level-dependent functional MRI studies mainly revolve around functional connectivity patterns and their plas-ticity characteristics.In recent years,the application of multimodal MRI fusion and artificial intelligence methods in the identification of ASD neuro-subtypes and auxiliary diagnosis has been increasing,but its clinical promotion is still affected by factors such as result heterogeneity,insufficient sample representativeness,and limited methodological standardiza-tion.In-depth research on the multimodal MRI characteristics of children with ASD can provide objective evidence for fur-ther understanding its neurobiological basis and optimizing clinical assessment.

Abstract:Objective To investigate the mechanism by which resveratrol(Res)attenuates oxygen-glucose depriva-tion/reperfusion(OGD/R)-induced injury in primary cortical neurons based on silent information regulator1/forkhead box O1(SIRT1/FOXO1)signaling pathway.Methods We cultured primary cortical neurons in vitro and established the OGD/R injury models.After intervening with different concentrations of Res,neuronal viability was detected using the CCK-8 assay to screen the optimal experimental concentration of Res.The OGD/R-induced neuronal models were random-ly divided into three groups:OGD/R group,OGD/R+Res group,and OGD/R+Res+SIRT1 inhibitor EX527 group(OGD/R+Res+EX527 group),respectively;meanwhile,some normal primary cortical neurons were assigned as the control group(Norm group).We treated the OGD/R+Res group with the optimal concentration of Res,while the OGD/R+Res+EX527 group was administered the optimal concentration of Res combined with 25 μmol/L EX527 for 24-hour incubation.Corti-cal neuronal viability was determined via the CCK-8 assay.Quantitative real-time polymerase chain reaction(qRT-PCR)was applied to detect the mRNA expression levels of silent information regulator 1(SIRT1)and autophagy-associated gene microtubule-associated protein light chain 3(LC3).We performed Western blotting to measure the protein expression lev-els of SIRT1/forkhead box O1(FOXO1)signaling pathway-related proteins and autophagy-associated marker proteins(LC3-Ⅱ/LC3-Ⅰ ratio,p62),and immunofluorescence staining was used to observe the formation of autophagosomes(re-flected by LC3-positive cells).Results Based on the neuronal viability results,we selected 20 μmol/L as the optimal experimental concentration of Res.Compared with the Norm group,the mRNA expression levels of IRT1 and LC3 in the OGD/R group were slightly higher,but no statistically significant differences were found(both P>0.05).Compared with the OGD/R group,the mRNA expression levels of SIRT1 and LC3 increased in the OGD/R+Res group(both P<0.05),whereas the OGD/R+Res+EX527 group exhibited significantly lower mRNA expression levels of these two genes than those in the OGD/R+Res group(both P<0.05).Compared with the Norm group,the OGD/R group had significantly higher pro-tein expression levels of SIRT1 and FOXO1 as well as an elevated LC3-Ⅱ/LC3-Ⅰ ratio(all P<0.05),while the protein expression of p62 significantly decreased(P<0.05).Compared with the OGD/R group,the SIRT1 protein expression and LC3-Ⅱ/LC3-Ⅰ ratio were higher in the OGD/R+Res group(both P<0.05),and the protein expression levels of FOXO1 and p62 were significantly down-regulated(both P<0.05).Compared with the OGD/R+Res group,the OGD/R+Res+EX527 group showed significantly lower SIRT1 protein expression and LC3-Ⅱ/LC3-Ⅰ ratio(both P<0.05),along with significantly higher protein expression levels of FOXO1 and p62(both P<0.05).Additionally,a significantly higher pro-portion of LC3-positive cells was found in the OGD/R group than in the Norm group(P<0.05).We observed a significant-ly higher proportion of LC3-positive cells in the OGD/R+Res group than in the OGD/R group(P<0.05),while the propor-tion of LC3-positive cells in the OGD/R+Res+EX527 group was significantly lower than that in the OGD/R+Res group(P<0.05).Conclusion Res may alleviate OGD/R-induced primary cortical neuronal damage by promoting autophagy through activating the SIRT1/FOXO1 signaling pathway.

Abstract:Central nervous system(CNS)disorders are multifactorial diseases characterized by progressive neuronal loss and synaptic dysfunction,with highly complex pathogenic mechanisms.Zuogui pill,a classical traditional Chinese medicine formula that nourishes yin,tonifies the kidney,and replenishes essence and marrow,is traditionally used for syn-dromes associated with true yin deficiency.Accumulating evidence suggests that Zuogui pill exerts neuroprotective and neurorestorative effects in CNS disorders through multi-target and multi-pathway mechanisms.In Alzheimer's disease(AD),Zuogui pill has been reported to modulate disease pathology by inhibiting the production and aggregation of β-amy-loid(Aβ),attenuating neuroinflammation,suppressing neuronal apoptosis,reducing oxidative stress,and regulating epi-genetic modifications.In ischemic stroke(IS),its protective effects are associated with the attenuation of oxidative stress and neuroinflammation,the promotion of neurotrophic factor secretion,and the enhancement of neurogenesis and angiogen-esis,thereby facilitating neural and vascular repair.In multiple sclerosis(MS),Zuogui pill may alleviate disease progres-sion by modulating immune and inflammatory responses and by inhibiting signaling pathways that restrict axonal regenera-tion.Collectively,elucidating the molecular and cellular mechanisms underlying the therapeutic effects of Zuogui pills in CNS disorders may provide a theoretical framework for further mechanistic investigations and support its clinical promotion.