Abstract:Objective To screen the core target genes of Xiaoyin granules for psoriasis treatment and to explore its potential mechanism based on network pharmacology and bioinformatics.Methods Potential active ingredients and tar-get genes of Xiaoyin granules were screened using the TCM Systems Pharmacology Database and Analysis Platform(TC-MSP).Psoriasis-related target genes were retrieved from the GeneCards database.The intersection of these two sets was identified as common target genes.These common targets were uploaded to the STRING database to construct a protein-pro-tein interaction(PPI)network.Topological analysis was performed with Cytoscape software to screen for core target genes.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses for the core targets were conducted via the Metascape platform.Differentially expressed genes(DEGs)between psoriatic lesions and normal skin were screened from the Gene Expression Omnibus(GEO)database.The intersection of these DEGs with the drug targets was taken to further identify key core target genes.Results A total of 197 active ingre-dients and 241 target genes of Xiaoyin granules were identified.There were 4,024 psoriasis-related target genes.Their in-tersection yielded 124 common target genes.PPI network analysis identified eight genes as core targets,including fatty ac-id binding protein 5(FABP5),serine/threonine kinase 1(AKT1),and prostaglandin-endoperoxide synthase 2(PTGS2).GO and KEGG enrichment analyses indicated that these core targets were primarily involved in regulating inflammatory re-sponse,immune response,and signaling pathways such as phosphatidylinositol 3-kinase(PI3K)-AKT,interleukin-17(IL-17),and lipid and atherosclerosis.GEO analysis identified 90 DEGs.Their intersection with the drug targets yielded FABP5 as the key core target gene.Conclusions The core target gene of Xiaoyin granules in treating psoriasis is FABP5.Its therapeutic effect is likely achieved through a synergistic mechanism involving multiple ingredients,targets,and pathways.

Abstract:Peripheral nerve block,as an important analgesic method within the framework of enhanced recovery after surgery,is widely used in perioperative analgesia management due to its definite analgesic effect and ability to reduce opi-oid consumption.However,as the effect of nerve block subsides,some patients may experience a sudden and severe exac-erbation of pain that significantly exceeds the expected postoperative pain level,known as rebound pain after peripheral nerve block,which seriously affects analgesic efficacy and postoperative rehabilitation.The occurrence of rebound pain is influenced by multiple factors,including individual patient characteristics,surgical and anesthetic methods,as well as psychological and cognitive states.Its pathophysiological mechanisms involve various processes such as central sensitiza-tion,alterations in peripheral nerve excitability,inflammatory cascade reactions,microglial activation,and nerve injury related to local anesthetics and the procedure itself.Given these mechanisms,significant research progress has been achieved in recent years in optimizing local anesthetics and adjuvants,improving nerve block techniques,implementing multimodal perioperative analgesia strategies,and strengthening preoperative education and management of high-risk popu-lations.In-depth research on the risk factors,pathophysiological mechanisms,and prevention and treatment strategies of rebound pain after peripheral nerve block can provide a reference for the clinical optimization of perioperative pain manage-ment and reducing the risk of rebound pain after peripheral nerve block.

Abstract:Objective To observe the clinical efficacy of high-frequency repetitive transcranial magnetic stimulation combined with language training based on mirror neuron theory in the treatment of articulation disorders in Parkinson's dis-ease.Methods A total of 106 patients with dysarthria caused by Parkinson's disease were selected,and then were ran-domly divided into the observation group and control group,with 53 cases in each.Patients in the control group were given language training based on the mirror neuron theory,while patients in the observation group were treated with high-frequen-cy repetitive transcranial magnetic stimulation on the basis of the treatment method of the control group.Both groups were treated for 30 days.The clinical efficacy after treatment was compared between the two groups,including pre-and post-treatment scores of the Frenchay Dysarthria Assessment(FDA),Grade-Roughness-Breathiness-Asthenia-Strain(GRBAS)scale,and Voice Handicap Index(VHI)questionnaire;voice function indicators such as maximum phonation time(MPT),maximum counting ability(MCA),contact quotient perturbation(CQP),and intensity;vocal fold vibration regu-larity indicators including fundamental frequency perturbation(Jitter),normalized noise energy(NNE),and harmonic-to-noise ratio(HNR);brain injury markers including serum α-synuclein(α-syn),neurofilament light chain(NF-L),and amyloid β-peptide 1-42(Aβ1-42);as well as treatment safety.Results The total effective rate of the observation group was 96.15%,which was higher than that(80.39%)of the control group(P<0.05).After treatment,the FDA score,GRBAS score,VHI score,MPT,MCA,CQP,intensity,Jitter,NNE,HNR and the levels of serum α-syn,NF-L and Aβ1-42 in both groups were improved compared with those before treatment,and the indexes were better in the observation group than in the control group(all P<0.05).There was no statistically significant difference in the total incidence of adverse reac-tions between the two groups during the treatment period(P>0.05).Conclusions High-frequency repetitive transcrani-al magnetic stimulation combined with language training based on mirror neuron theory has a significant therapeutic effect on dysarthria in Parkinson's disease.It can improve patients'clinical symptoms,voice function,and vocal fold vibration regularity,alleviate brain injury,and has good safety.

Abstract:Mirror visual feedback(MVF)therapy,a multimodal rehabilitation technique based on neuroplasticity the-ory,has seen its clinical application expand to multiple fields,including cerebral palsy,autism spectrum disorder,chron-ic pain(phantom limb pain,post-mastectomy shoulder-arm pain),and peripheral nerve injuries(peripheral facial paraly-sis,carpal tunnel syndrome),demonstrating significant cross-disease potential.By providing the correct visual-proprio-ceptive matching,MVF helps correct disease-induced interhemispheric inhibitory imbalance or sensorimotor integration ab-normalities,thereby promoting synaptic remodeling and cortical reorganization conducive to functional compensation.Ear-ly intervention during the acute or subacute stage of disease,combined with treatment of adequate intensity and duration(e.g.,multiple sessions per week over several weeks),is crucial for achieving optimal outcomes.Meanwhile,the syner-gistic effect of MVF with techniques such as repetitive transcranial magnetic stimulation and task-oriented training provides insights into overcoming the limitations of single therapeutic approaches.

Abstract:Based on a three-dimensional stem cell culture system,organoid technology recapitulates key processes of human brain development and exhibits distinct advantages in in vitro modeling of neurological tumors,traumatic brain inju-ry,neurodegenerative diseases[Alzheimer's disease(AD),Parkinson's disease(PD)],stroke,and neurodevelopmen-tal disorders(microcephaly,autism spectrum disorder).Currently,brain organoids derived from induced pluripotent stem cells not only highly preserve patient-specific genetic backgrounds but also replicate disease-related cellular heterogeneity and microenvironment features,providing a powerful technical basis for mechanistic investigations,drug screening,and personalized therapeutic strategies.In regenerative medicine,transplantation studies have confirmed the capacity of brain organoids to integrate with host neural circuits and promote functional recovery,revealing promising and broad clinical ap-plication potential.However,challenges such as insufficient vascularization,limited model maturity,incomplete standard-ization,and ethical considerations remain.Through interdisciplinary innovation,brain organoid technology is expected to drive paradigm shifts in neuroscience research and serve as a core driver for the advancement of precision medicine.

Abstract:Objective To investigate the predictive value of serum neuronal injury biomarkers combined with Glasgow Coma Scale-pupil(GCS-P)score on the prognosis of patients with traumatic brain injury(TBI).Methods A to-tal of 234 TBI patients were enrolled.Their prognosis at 28 days after admission was assessed using the Glasgow Outcome Scale.Prognosis-related data on admission were collected.Serum levels of neuronal injury biomarkers,including phos-phorylated tau181(p-tau181),neurofilament light chain(NfL),ubiquitin carboxyl-terminal hydrolase L1(UCH-L1),gli-al fibrillary acidic protein(GFAP),and S-100 calcium-binding protein B(S-100B),were measured using enzyme-linked immunosorbent assay.The GCS-P score was calculated based on the Glasgow Coma Scale(GCS)score and the Pupil(P)score.The least absolute shrinkage and selection operator(LASSO)regression was used to screen factors influencing the prognosis of TBI patients.Subsequently,multivariate Logistic regression analysis was performed to analyze the impact of serum neuronal injury biomarkers and the GCS-P score on TBI patient prognosis.Receiver operating characteristic(ROC)curves were plotted,and the area under the curve(AUC)was used to analyze the predictive value of the combination of se-rum neuronal injury biomarkers and the GCS-P score.Results Among the 234 TBI patients,93 cases(39.74%)had an unfavorable prognosis at 28 days,while 141 cases(60.26%)had a favorable prognosis.Brain herniation(OR=8.328,95%CI:2.941-23.577),midline shift≥5 mm(OR=2.918,95%CI:1.177-7.232),and elevated levels of p-tau181(OR=1.453,95%CI:1.225-1.722),NfL(OR=1.039,95%CI:1.020-1.057),UCH-L1(OR=1.026,95%CI:1.008-1.043),GFAP(OR=1.042,95%CI:1.006-1.079),and S-100B(OR=1.102,95%CI:1.039-1.170)were identified as independent risk factors for the poor prognosis in TBI patients(all P<0.05).An increased GCS-P score(OR=0.808,95%CI:0.716-0.913)was an independent protective factor(P<0.05).The probability of predicting prognosis in TBI patients by combining serum neuronal injury biomarkers with the GCS-P score was fitted using Logistic regression:Logit(P)=-4.534+0.317×p-tau181+0.036×NfL+0.025×UCH-L1+0.041×GFAP+0.098×S-100B-0.237×GCS-P score.The AUCs for predicting the poor prognosis in TBI patients using p-tau181,NfL,UCH-L1,GFAP,S-100B,GCS-P score alone,and the combination of them were 0.740,0.714,0.678,0.648,0.682,0.756,and 0.919,respectively.The AUC of the combined prediction was significantly greater than that of each individual indicator(Z=5.693,5.962,6.778,7.289,6.917,5.660,respectively;all P<0.05).Conclusions TBI patients with elevat-ed serum levels of neuronal injury biomarkers(p-tau181,NfL,UCH-L1,GFAP,S-100B)and a decreased GCS-P score tend to have an unfavorable prognosis.The combination of these indicators demonstrates high predictive value for the prog-nosis of TBI patients.

Abstract:Objective To investigate factors influencing mortality within 90 days after successful recanalization fol-lowing endovascular thrombectomy(EVT)in patients with acute ischemic stroke due to large vessel occlusion(AIS-LVO).Methods A retrospective cohort of 449 AIS-LVO patients undergoing EVT with successful recanalisation of the occluded vessel was enrolled.Clinical outcomes were determined by modified Rankin scale(mRS)scores at 90 days after surgery,and we divided patients as the deceased(mRS=6)or the surviving(mRS<6).Baseline demographic characteris-tics,clinical status,laboratory parameters,perioperative factors,and postoperative complications were compared between groups.Multivariate Logistic regression analyzed factors influencing 90-day mortality following successful EVT recanalisa-tion.Results Among 449 AIS-LVO patients,88 died within 90 days postoperatively,yielding a mortality rate of 19.6%.AIS-LVO patients who died within 90 days after successful EVT recanalisation exhibited significantly higher age,NIHSS scores,D-dimer levels,fasting blood glucose levels,and higher proportions of prior stroke history,atrial fibrilla-tion,posterior circulation occlusion,stroke-associated pneumonia,stress-induced peptic ulcer,acute heart failure,acute renal failure,symptomatic intracranial haemorrhage,and cerebral herniation than the survivors(all P<0.05).Mul-tivariate Logistic regression analysis revealed that age,fasting blood glucose,posterior circulation occlusion,stroke-asso-ciated pneumonia,stress-induced peptic ulcer,acute renal failure,symptomatic intracranial haemorrhage,and cerebral herniation were independent influencing factors for 90-day mortality after successful recanalisation following EVT in AIS-LVO patients(all P<0.05).Conclusions Multiple factors influence mortality within 90 days after successful recanali-sation following EVT in AIS-LVO patients.Advanced age,elevated fasting blood glucose,posterior circulation occlu-sion,and multiple perioperative complications are identified as independent risk factors for 90-day mortality in this popu-lation.

Abstract:Objective To investigate the protective effects of Huangzhu Qingnao granules(HZQNG)against cere-bral ischemia-reperfusion injury in rats subjected to middle cerebral artery occlusion/reperfusion(MCAO/R)and to ex-plore the underlying mechanism.Methods In vivo experiment,Wistar rats were randomly divided into the sham group,model group,butylphthalide group,and low-,medium-,and high-dose HZQNG groups,with 10 in each.Neurological deficits were evaluated using the Zea-Longa score.Histopathological changes,infarct area,blood-brain barrier(BBB)ul-trastructure,and apoptosis were assessed.Oxidative stress indices[reactive oxygen species(ROS),malondialdehyde(MDA),and superoxide dismutase(SOD)],serum inflammatory cytokines(IL-1β and IL-18),and the expression levels of thioredoxin-interacting protein(TXNIP),NOD-,LRR-and pyrin domain-containing protein 3(NLRP3),apoptosis-as-sociated speck-like protein containing a CARD(ASC),Caspase-1,and Gasdermin D(GSDMD)were measured.The in-teraction between TXNIP and NLRP3 was examined by co-immunoprecipitation.In vitro experiment,BV2 microglial cells were assigned into the normal group,model group,NLRP3 inhibitor group,and low-,medium-,and high-dose HZQNG groups.Cell viability was assessed using CCK-8.TXNIP-NLRP3 interaction was analyzed by co-immunoprecipitation,and the expression of TXNIP,NLRP3,ASC,Caspase-1 and GSDMD proteins was detected by Western blotting.Results In vivo experiment:The Zea-Longa neurological function score,the percentage of cerebral infarct area,the rate of neuronal apoptosis,the levels of ROS and MDA in the brain tissues,serum levels of IL-18 and IL-1β,as well as the protein expres-sion levels of TXNIP,NLRP3,ASC,Caspase-1,and GSDMD in the brain tissues,were as follows:model group>low-dose HZQNG group>medium-dose HZQNG group>butylphthalide group>high-dose HZQNG group>sham group(all P<0.05).In contrast,the SOD activity in the brain tissues followed the reverse order:sham group>high-dose HZQNG group>butylphthalide group>medium-dose HZQNG group>low-dose HZQNG group>model group(all P<0.05).HE staining results showed that the brain tissue structure in the sham group was essentially normal,while the model group ex-hibited disordered neuronal arrangement and significant structural damage.The pathological changes in the brain tissues were alleviated in the low-,medium-,and high-dose HZQNG groups,as well as in the butylphthalide group.Transmission electron microscopy revealed severe damage to the ultrastructure of the BBB in the cerebral cortex of the model group,whereas HZQNG intervention mitigated the extent of ultrastructural damage to the BBB.Co-immunoprecipitation confirmed the interaction between TXNIP and NLRP3 in rat brain tissues.Conclusion HZQNG ameliorates cerebral ischemia-re-perfusion injury in MCAO/R rats.The protective effects may be associated with alleviation of oxidative stress and inhibi-tion of the TXNIP/NLRP3/Caspase-1/GSDMD pathway-mediated inflammatory response and pyroptosis,thereby reducing BBB injury and promoting neurological recovery.

Abstract:Objective To evaluate the effect of remimazolam on the early postoperative cognitive function of frail el-derly patients under general anesthesia.Methods A total of 80 frail elderly patients undergoing total knee arthroplasty were divided into the remimazolam group(group R)and propofol group(group P)using the random number table,with 40 cases in each group.Both groups underwent the operation under general anesthesia.In the remimazolam group,anesthesia was induced and maintained using remimazolam,whereas in the propofol group,induction and maintenance were achieved with propofol.Perioperative early cognitive function was assessed using the Mini-Mental State Examination(MMSE)at 1 day before surgery and at 1,3,and 7 days after surgery.Heart rate(HR),mean arterial pressure(MAP),and the bispectral index(BIS)were recorded at baseline(T1),loss of consciousness(T2),5 minutes after laryngeal mask inser-tion(T3),30 minutes after surgery initiation(T4),return of consciousness(T5),and laryngeal mask removal(T6).Venous blood was collected at 1 day before surgery and at 6 and 24 h after surgery to measure serum levels of interleukin-6(IL-6)and C-reactive protein(CRP).Additionally,the following data were recorded:anesthesia induction time,re-covery time,laryngeal mask removal time,and the occurrence of perioperative adverse events.Results MMSE scores were significantly higher in the remimazolam group than in the propofol group on both postoperative day 1 and day 3(both P<0.05).In the remimazolam group,HR at T2 and T3 as well as MAP at T2,T3 and T4 were significantly higher than those in the propofol group.Both HR and MAP in the remimazolam group were significantly lower than those of the propo-fol group at T5 and T6(both P<0.05).The remimazolam group showed significantly higher BIS values at T2,T3,T4,and T6,and significantly lower serum levels of IL-6 and CRP at 6 and 24 h postoperatively than the propofol group(all P<0.05).Anesthesia induction time was significantly longer in the remimazolam group than in the propofol group(P<0.05).However,no statistically significant differences in the recovery time or laryngeal mask removal time were ob-served between the two groups(both P>0.05).Following Bonferroni correction,no statistically significant difference in the adverse event rate was found between these two groups(P>0.01).Conclusion The use of remimazolam for general anesthesia in frail elderly patients is associated with less impact on early postoperative cognitive function and this may be related to its ability to stabilize blood hemodynamics and electroencephalographic activity,as well as to reduce the level of inflammatory response.

Abstract:Objective To observe the 1-year clinical outcome of percutaneous transforaminal endoscopic discectomy in patients with thoracic disc herniation(TDH).Methods A retrospective analysis was conducted on 8 patients with TDH,all of whom underwent percutaneous transforaminal endoscopic discectomy and completed a 1-year follow-up.Preop-eratively and at 1 day,7 days,1 month,3 months,6 months,and 1 year postoperatively,the visual analogue scale(VAS)was used to assess pain of the thoracic and dorsal regions as well as lower extremities,the Oswestry Disability In-dex(ODI)to evaluate thoracic spinal function,and the Japanese Orthopaedic Association(JOA)score to assess neurologi-cal function.The JOA improvement rate was calculated to evaluate therapeutic efficacy,and complications and reoperation cases during surgery and follow-up were recorded.Results All 8 patients underwent uneventful surgeries,with an aver-age operation time of(119.0±12.9)minutes and a hospital stay of 6.5(6-7)days.Compared with the preoperative val-ues,the VAS scores,ODI,and JOA scores at all postoperative time points were significantly improved(all P<0.05).The excellent and good rates at 3,6,and 12 months postoperatively were 75%,100%,and 100%,respectively.No complica-tions such as dural tear,nerve injury,or infection occurred during surgery and within 1 year of follow-up.Additionally,there were no cases of thoracic spinal instability,adjacent segment degeneration,or reoperations.Conclusions Percuta-neous transforaminal endoscopic discectomy significantly alleviated preoperative pain in patients with TDH and improved spinal function.The therapeutic effect tended to be stable at 6 months after the operation.No complications occurred intra-operatively or during the 1-year follow-up period,and no revision surgery was necessary.

Abstract:Objective To observe the application effect of closed-loop target-controlled infusion of propofol in an-esthesia for percutaneous balloon compression of the trigeminal ganglion.Methods Sixty-three patients with trigeminal neuralgia(TN)undergoing percutaneous balloon compression were prospectively selected and were randomly divided into the observation group(n=32)and control group(n=31).Both groups received target-controlled infusion(TCI)of propofol during balloon compression,with a target bispectral index of 50-60.In the observation group,the target concentration of propofol was automatically adjusted by a closed-loop system,while in the control group,it was manually adjusted by anes-thesiologists according to vital signs.Blood pressure and pulse were recorded at admission to the operating room(T0),loss of consciousness(T1),start of surgery(T2),balloon compression(T3),and end of surgery(T4).Visual analogue scale(VAS)scores were assessed before surgery and 1 day after surgery.Intraoperative propofol dosage,postoperative awakening time,balloon compression time,and balloon inflation volume were recorded and compared between the two groups.Results Compared with T0,blood pressure increased significantly and pulse rate decreased significantly at T1 and T2 in the observation group(both P<0.05),while similar changes were observed at T1,T2,and T3 in the control group(all P<0.05).At T1,T2,and T3,blood pressure was significantly lower,and pulse rate was significantly higher in the observation group than in the control group(all P<0.05).One day after surgery,VAS scores were significantly lower than those before surgery in both groups,and the score in the observation group was significantly lower than that in the con-trol group(all P<0.05).The intraoperative propofol dosage was significantly lower,and postoperative awakening time was significantly shorter in the observation group than in the control group(both P<0.05).In addition,balloon compression time and balloon inflation volume were significantly lower in the observation group than in the control group(both P<0.05).Conclusion Closed-loop target-controlled infusion of propofol can effectively maintain intraoperative hemody-namic stability in patients with TN undergoing percutaneous balloon compression,reduce anesthetic consumption,shorten postoperative awakening time,alleviate early postoperative pain,and improve surgical efficiency by optimizing balloon compression parameters.

Abstract:Objective To construct a nomogram prediction model of ischemic stroke(AIS)complicated with early-onset epilepsy based on quantitative electroencephalogram(EEG)parameters,and to internally validate its efficacy.Methods This retrospective study included 357 patients with AIS.The diagnosis of AIS complicated with early-onset ep-ilepsy was determined according to the 2017 International League Against Epilepsy diagnostic criteria.Relevant data were collected.All patients underwent quantitative EEG examination,with parameters including the frequencies of α,β,δ,and θ waves,and the calculated δ/θ(DTR),δ/α(DAR),and(δ+θ)/(α+β)(DTABR).Univariate and multivariate Logistic regression analyses were used to examine the impact of quantitative EEG parameters on the occurrence of early-on-set epilepsy in AIS patients,and a nomogram prediction model was constructed accordingly.Internal validation was per-formed using the Bootstrap method with 1,000 resamples.Calibration curves,receiver operating characteristic(ROC)curves,and decision curve analysis(DCA)were applied to evaluate the model's calibration,discrimination,and clini-cal application value.Results Among the 357 AIS patients,106 developed early-onset epilepsy,while 251 did not.High θ wave frequency(OR=1.185,95%CI:1.038-3.173),high DTABR(OR=2.061,95%CI:1.118-3.798),se-vere neurological deficit(OR=1.664,95%CI:1.169-2.367),and cortical lesion location(OR=1.406,95%CI:1.083-1.825)were independent risk factors for early-onset epilepsy in AIS patients(all P<0.05).The prediction model was formulated based on Logistic regression.The calibration curve of the model aligned well with the ideal curve,with a mean absolute error of 0.001.The area under the ROC curve was 0.861(95%CI:0.815-0.893).DCA indicated that the model provided clinical net benefit across a wide range of threshold probabilities.Conclusions Quantitative EEG parameters θ wave and DTABR are influential factors for early-onset epilepsy in AIS patients.The nomogram prediction model constructed based on these parameters demonstrates high calibration,good discriminatory ability,and significant clinical utility value.

Abstract:Objective To explore the clinical value of probe-based confocal laser endomicroscopy(pCLE)as an ad-junct to medical thoracoscopy in the diagnosis of pleural diseases,and to provide evidence for the precise diagnosis of early pleural lesions.Methods The diagnostic and therapeutic processes of two patients with pleural effusion of unknown etiol-ogy accompanied by abnormally elevated tumor markers were retrospectively analyzed.Both patients first underwent con-ventional medical thoracoscopy.Subsequently,pCLE was introduced through the working channel of the medical thoraco-scope to perform real-time,in vivo histological-level observation of suspicious pleural areas.Targeted pleural cytological examination and biopsy were then performed at sites showing abnormalities on pCLE.Results Conventional medical tho-racoscopy revealed no obvious pleural abnormalities in either patient,and appropriate biopsy sites could not be clearly identified.In contrast,pCLE detected clusters of atypical cells in both cases.In Case 1,intraoperative pleural effusion cy-tology revealed clusters of atypical glandular epithelial cells.In Case 2,pleural biopsy guided by pCLE demonstrated a ma-lignant epithelial tumor.Ultimately,both patients were pathologically confirmed to have lung adenocarcinoma.The histo-pathological findings were highly consistent with the intraoperative pCLE observations in both cases.Conclusions The pCLE enables real-time,in vivo histological-level visualization of the pleura and can effectively identify early,subtle pleu-ral lesions.It provides precise targeting guidance for pleural biopsy during medical thoracoscopy,compensates for the diag-nostic limitations of conventional medical thoracoscopy,and has important clinical value in improving the diagnostic rate of early pleural diseases.

Abstract:Acute respiratory distress syndrome(ARDS)is a critical clinical syndrome characterized by diffuse lung injury and severe pulmonary dysfunction.It has a complex pathophysiology,a high mortality rate,and lacks specific thera-peutic interventions.Hypoxia-inducible factor-1α(HIF-1α)is a key transcription factor mediating cellular responses to hypoxia and is considered to play a pivotal role in the initiation,progression,and prognosis of ARDS.Under combined hy-poxic and inflammatory stimuli,HIF-1α is markedly up-regulated,promoting the release of proinflammatory cytokines and aberrant activation of immune cells,thereby exacerbating pulmonary inflammation.Concurrently,HIF-1α aggravates lung tissue injury by regulating macrophage polarization,neutrophil function,and T-lymphocyte differentiation.HIF-1α also fa-cilitates metabolic reprogramming by enhancing glycolysis and lactate production,inducing oxidative stress and amplifying inflammatory responses,which in turn promotes apoptosis of alveolar epithelial and endothelial cells and disrupts the alveo-lar-capillary barrier.In addition,HIF-1α accelerates the progression of pulmonary fibrosis by promoting fibroblast activa-tion,epithelial-mesenchymal transition,and M2 macrophage polarization.A comprehensive understanding of the mecha-nisms by which HIF-1α contributes to ARDS pathogenesis will provide a theoretical basis for elucidating the pathological foundations of ARDS and for the development of novel therapeutic strategies.

Abstract:Objective To analyze the predictive value of the admission neutrophil-percentage-to-albumin ratio(NPAR)for poor prognosis in patients with heart failure(HF)due to dilated cardiomyopathy(DCM)based on propensity score matching(PSM).Methods A total of 220 patients with HF due to DCM admitted from January 2022 to June 2024 were retrospectively selected.Relevant clinical data were collected upon admission.Neutrophil percentage was measured using an automated hematology analyzer,and albumin levels were determined using the bromocresol green method,with NPAR calculated as their ratio.During the one-year follow-up,poor prognosis was defined as the occurrence of rehospital-ization for HF,malignant arrhythmia,cardiac death,or all-cause death.A 1:1 PSM was applied to patients with different prognoses to obtain a sample with balanced intergroup variables.Multivariate Logistic regression analysis was used to iden-tify independent risk factors for poor prognosis in patients with HF due to DCM.The predictive values of N-terminal pro-B-type natriuretic peptide(NT-proBNP)and NPAR for poor prognosis were assessed using receiver operating characteristic(ROC)curve.Results Among 220 patients,82 patients experienced poor prognosis,with an incidence of 37.3%.Af-ter PSM,78 matched pairs of patients with balanced baseline characteristics were obtained.Following PSM,patients with poor prognosis showed significantly lower left ventricular ejection fraction and albumin levels,and significantly higher neu-trophil percentage,NT-proBNP,troponin I,C-reactive protein,and NPAR than patients with good prognosis(all P<0.05).Multivariate Logistic regression analysis revealed that elevated NT-proBNP and elevated NPAR were independent risk factors for poor prognosis in patients with HF due to DCM(all P<0.05).ROC curve analysis demonstrated that the ar-ea under the curve(AUC)of NPAR in predicting poor prognosis was 0.781,which was higher than the AUCs of neutrophil percentage(0.699)and albumin(0.716)alone(both P<0.05).The combined prediction of NT-proBNP and NPAR achieved an AUC of 0.850,which was higher than the AUCs of NT-proBNP(0.746)or NPAR(0.781)alone(both P<0.05).Conclusions Elevated admission NPAR is an independent risk factor for poor prognosis in patients with HF due to DCM and holds predictive value for patient prognosis.Furthermore,combining NPAR with NT-proBNP further enhanc-es the predictive value for poor prognosis in these patients.

Abstract:Objective To analyze the influencing factors for symptomatic radiation pneumonitis(SRP)in patients with non-small-cell lung cancer(NSCLC)after radiotherapy and to construct a predictive model.Methods A total of 364 NSCLC patients who underwent radiotherapy were retrospectively selected and divided into the SRP group(90 cases)and non-SRP group(274 cases)based on the occurrence of SRP within 6 months after radiotherapy.Clinical data of the two groups were collected and compared,including basic information such as gender,age,smoking history,alcohol histo-ry,comorbid diabetes,comorbid hypertension,pathological type,tumor location,TNM stage,performance status score,combined chemotherapy,combined immunotherapy,combined targeted therapy,radiotherapy mode,prognostic nutrition-al index(PNI),neutrophil-to-lymphocyte ratio(NLR),as well as radiotherapy-related data such as radiation dose,tumor target volume,lymph node target volume,planning target volume,left lung volume,right lung volume,total lung vol-ume,percentage of total lung volume receiving a specific dose[lung V5,V10,V20,V30,V40,V50,and V60],and mean lung dose(MLD).Multivariate unconditional Logistic regression analysis was used to identify independent influencing factors for SRP in NSCLC patients after radiotherapy,and a nomogram model was constructed.The predictive perfor-mance of the model was evaluated using the receiver operating characteristic(ROC)curve,C-index,calibration curve,and decision curve analysis.Results The SRP group had higher age,higher proportion of combined chemotherapy,high-er NLR,higher lung V5,V10,V20,V30,and higher MLD than the non-SRP group(all P<0.05),while the PNI was lower in the SRP group(P<0.05).Multivariate unconditional Logistic regression analysis showed that increased age,combined che-motherapy,increased lung V5,increased MLD,and elevated NLR were independent risk factors for SRP in NSCLC patients after radiotherapy,while elevated PNI was an independent protective factor(all P<0.05).The nomogram model construct-ed based on these factors had a C-index of 0.919(95%CI:0.916-0.923).The calibration curve closely aligned with the ideal curve,and the decision curve analysis showed a wide range of net benefits.The ROC curve demonstrated that the ar-ea under the curve(AUC)of the nomogram model for predicting SRP in NSCLC patients after radiotherapy was 0.919(95%CI:0.887-0.945),with the sensitivity and specificity of 0.8556 and 0.8504,respectively.Conclusions Age,combined chemotherapy,lung V5,MLD,NLR,and PNI are independent influencing factors for SRP in NSCLC patients after radiotherapy.The nomogram model constructed based on these factors can effectively predict the risk of SRP in NSCLC patients after radiotherapy,with high discriminative ability,consistency,and clinical applicability.

Abstract:Objective To observe the diagnostic efficacy of serum C-reactive protein(CRP)and interleukin-6(IL-6)in chronic obstructive pulmonary disease(COPD)complicated with sarcopenia.Methods Totally 130 patients with COPD were divided into two groups based on the presence of sarcopenia:the COPD group(59 cases)and the COPD with sarcopenia group(71 cases).Serum CRP was detected by latex-enhanced immunoturbidimetry in both groups and serum IL-6 by ELISA.The receiver operating characteristic(ROC)curve was drawn to evaluate the diagnostic efficacy of serum CRP and IL-6 levels in COPD complicated with sarcopenia.Results The serum CRP and IL-6 levels in the COPD group were(3.03±2.43)mg/L and(2.44±1.60)pg/mL,respectively,and they were(32.23±25.17)mg/L and(10.24±8.75)pg/mL in the COPD complicated with sarcopenia group,respectively;there were statistically significant differences between these two groups(all P<0.05).The area under the curve of serum CRP level in diagnosing COPD with sarcopenia was 0.944(95%CI:0.900-0.987).When the cut-off value was 10.85 mg/L,the sensitivity and specificity of serum CRP level in diagnosing COPD with sarcopenia were 0.873 and 0.983,respectively.The area under the curve of serum IL-6 level in diagnosing COPD with sarcopenia was 0.816(95%CI:0.743-0.889).When the cut-off value was 6.98 pg/mL,the sensitivity and specificity of serum IL-6 level in diagnosing COPD with sarcopenia were 0.761 and 0.864,respective-ly.The area under the curve of serum CRP combined with IL-6 for the diagnosis of COPD with sarcopenia was 0.952(95%CI:0.913-0.991);the sensitivity and specificity for the diagnosis of COPD with sarcopenia were 0.897 and 0.905,re-spectively.Conclusion Serum CRP and IL-6 levels increase in patients with COPD complicated with sarcopenia;detec-tion of serum CRP and IL-6 levels is helpful in the diagnosis of COPD complicated with sarcopenia and has a high diagnos-tic efficacy.

Abstract:Objective To construct a tri-specific T-cell engager(TriTE-3-19-1)capable of simultaneously targeting human CD3,CD19,and PD-L1,and to evaluate its ability to mediate T-cell-specific killing of CD19⁺PD-L1⁺ lymphoma cells.Methods The lentiviral expression vector pLentiR.SV40-TriTE-3-19-1 was constructed using molecular cloning technique,transiently transfected into 293T cells,and the culture supernatant was collected and purified to obtain the tri-specific T-cell engager TriTE-3-19-1.ELISA was used to detect the binding activity of TriTE-3-19-1 to Jurkat(CD3⁺),Ra-ji(CD19⁺),3T3/PD-L1(PD-L1⁺),and Raji-PD-L1(CD19⁺PD-L1⁺)cells.LDH release assay was performed to assess the killing ability of T cells mediated by different concentrations of TriTE-3-19-1 against target cells(CD19⁺,PD-L1⁺,and CD19⁺PD-L1⁺ cells).Blocking experiments targeting the anti-PD-L1 domain were conducted to observe changes in the kill-ing ability of TriTE-3-19-1 against CD19⁺PD-L1⁺ cells,and ELISA was used to measure the levels of cytokines interleukin-2(IL-2),interferon-γ(IFN-γ),and tumor necrosis factor-α(TNF-α).Results The lentiviral expression vector pLen-ti R.SV40-TriTE-3-19-1 was successfully constructed.The purified tri-specific T-cell engager TriTE-3-19-1 showed an ex-pected band at approximately 84 kDa in its monomeric form.The binding activity of TriTE-3-19-1 to Jurkat(CD3⁺),Raji(CD19⁺),3T3/PD-L1(PD-L1⁺),and Raji-PD-L1(CD19⁺PD-L1⁺)cells exhibited typical dose-response relationships.As the concentration of TriTE-3-19-1 increased,the killing effect of T cells on CD19⁺,PD-L1⁺,and CD19⁺PD-L1⁺ cells showed a dose-dependent enhancement(all P<0.05).Moreover,the T-cell-mediated killing of CD19⁺PD-L1⁺ cells was significantly stronger than that of CD19⁺ cells or PD-L1⁺ cells(all P<0.05).When the anti-PD-L1 domain of TriTE-3-19-1 was blocked,its ability to mediate T-cell killing of Raji-PD-L1(CD19⁺PD-L1⁺)cells was reduced(P<0.05),and the ex-pression levels of cytokines IL-2,IFN-γ,and TNF-α also decreased(all P<0.05).Conclusion The tri-specific T-cell engager TriTE-3-19-1 was successfully constructed,demonstrating binding to CD3⁺,CD19⁺,PD-L1⁺,and CD19⁺PD-L1⁺cells,and effectively mediating T-cell killing of CD19⁺PD-L1⁺ lymphoma cells.

Abstract:Objective To investigate the risk factors for pneumonia complicated with plastic bronchitis(PB)in chil-dren,to construct a decision tree prediction model,and to evaluate its clinical predictive performance,providing a refer-ence for early identification of PB.Methods A total of 533 children diagnosed with pneumonia were retrospectively en-rolled as the training cohort,and an additional 103 children were collected as a same-center temporal external validation cohort.PB was diagnosed when bronchial casts were observed by bronchoscopy.Forty-seven multidimensional clinical variables were collected,including general characteristics,clinical manifestations,physical signs,imaging findings,and laboratory indicators.Univariate analysis,Spearman rank correlation analysis,and multivariate Logistic regression were used to identify independent risk factors for PB.Based on these factors,a decision tree prediction model was constructed.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curves.Internal vali-dation was performed using the Bootstrap method with 1,000 resamples.Model calibration was assessed by the Hosmer-Lemeshow test,and clinical utility was evaluated by decision curve analysis(DCA).Results Among the 533 children with pneumonia,126 cases(23.64%)developed PB.Multivariate Logistic regression analysis showed that higher maxi-mum body temperature,higher neutrophil percentage,elevated D-dimer,decreased albumin,increased immunoglobulin A,increased immunoglobulin E,elevated serum ferritin,consolidation involving≥2/3 of a lung lobe,and pleural effusion were independent risk factors for PB(all P<0.05).A five-layer decision tree model was constructed based on these inde-pendent risk factors.In internal validation,the area under the ROC curve(AUC)was 0.860,indicating good discrimina-tive ability;the Hosmer-Lemeshow test demonstrated good calibration(P>0.05),and DCA showed a positive net clinical benefit across a wide range of threshold probabilities(8%-100%).In external validation,the model also exhibited good discrimination(AUC=0.926)and calibration(both P>0.05),with favorable net clinical benefit over threshold probabili-ties of 9%-100%.Conclusion The decision tree prediction model for plastic bronchitis constructed based on indepen-dent risk factors derived from multidimensional clinical indicators demonstrates good predictive performance and may pro-vide a useful reference for early identification of PB in children with pneumonia.

Abstract:Objective To observe the effect of circular RNA SORBS2(circSORBS2)on myocardial injury in septic mice and to explore its mechanism.Methods Forty-eight SPF C57BL/6J male mice were randomly divided into Sham group,model group,sh-NC group and sh-circSORBS2 group,with 12 mice in each group.The mice in the model group,sh-NC group and sh-circSORBS2 group were treated with cecal ligation(CLP)to construct the mouse models of sepsis-in-duced myocardial injury.Mice in the sh-NC group and sh-circSORBS2 group were intravenously injected with sh-NC(neg-ative control)or sh-circSORBS2(silencing circSORBS2 expression)adeno-associated virus vector particles one week be-fore CLP.In the Sham group,only laparotomy and abdominal closure were performed without ligation and puncture of the cecum,and no tail vein injection was performed.After the mouse models were completed,the survival rate,myocardial histopathology,cardiac function indexes[left ventricular systolic pressure(LVSP),maximum rate of left ventricular pres-sure increase(+dp/dtmax),maximum rate of left ventricular pressure decrease(-dp/dtmax),left ventricular end-diastolic pressure(LVEDP),creatine kinase isoenzyme MB(CK-MB),and cardiac troponin I(cTnI)],myocardial tissue inflam-matory factors[tumor necrosis factor(TNF)-α and interleukin-6(IL-6)],myocardial tissue pyroptosis-related factors[NOD-like receptor hot protein domain-related protein 3(NLRP3),caspase-1(Caspase-1),IL-1β,and Gasdermin D(GSDMD)],and the relative expression levels of circRBSSO2,miR-21-3 p,and Sma/MAD-related protein 7(SMAD7)mRNA in the myocardial tissues of mice in each group were observed and compared.The targeting relationship of circ-SORBS2,miR-21-3 p and SMAD7 was predicted by starBase target gene prediction website,and verified by luciferase re-porter gene experiment.Results Compared with the Sham group,the survival rate,LVSP,+dp/dtmax,and miR-21-3p decreased,while LVEDP,-dp/dtmax,cTnI,CK-MB,TNF-α,IL-6,NLRP3,Caspase-1,IL-1β,GSDMD,circSORBS2,and SMAD7 mRNA increased(all P<0.05),and myocardial necrosis occurred in the model group.Compared with the sh-NC group,the survival rate,LVSP,+dp/dtmax,and miR-21-3p increased,while LVEDP,-dp/dtmax,cTnI,CK-MB,TNF-α,IL-6,NLRP3,Caspase-1,IL-1β,GSDMD,circSORBS2,and SMAD7 mRNA decreased(all P<0.05),and the degree of myocardial injury was alleviated in the sh-circSORBS2 group.The results of the dual-luciferase reporter gene assay showed that circSORBS2 targetedly regulated miR-21-3p,and miR-21-3p regulated SMAD7.Conclusion Inhibition of circSORBS2 expression can alleviate myocardial injury in septic mice,and the mechanism may be related to circSORBS2 relieving the inhibition of SMAD7 by adsorbing miR-21-3p.