To develop an multimodal interpretable model that integrates whole slide images(WSI) and clinical features, and to validate its efficacy in predicting pathological complete response(pCR) in lung cancer patients following neoadjuvant therapy.

ObjectiveTo investigate the potential therapeutic effects of Dengzhan Shengmai capsules （DZSM） on myocardial fibrosis after myocardial infarction and decipher the underlying molecular mechanisms by virtue of network robustness algorithm. MethodsA rat model of myocardial infarction was established by ligating the left anterior descending coronary artery. Successfully modeled Sprague-Dawley rats were randomly allocated into a model group， an enalapril group（3.15 mg·kg^-1）， and high- and low-dose DZSM groups（226.8，113.4 mg·kg^-1）. In addition， a sham group was set up. After four consecutive weeks of intervention， the cardiac function was assessed via echocardiography， and myocardial collagen deposition was observed through Sirius red staining. The key regulatory pathways of DZSM were analyzed by the network robustness algorithm. Enzyme-linked immunosorbent assay （ELISA） and immunofluorescence assay were employed to validate the mechanisms. ResultsCompared with the sham group， the model group exhibited decreased left ventricular ejection fraction （LVEF%） and fractional shortening （FS%） （P<0.01） and increased myocardial collagen volume fraction （CVF%） （P<0.01）. Compared with the model group， high-dose DZSM and enalapril improved LVEF% and FS% （P<0.01）. Both high- and low-dose DZSM reduced the CVF% （P<0.05， P<0.05，）. Network analysis indicated that DZSM exerted its effects by regulating neutrophil infiltration and related inflammatory pathways. Experimental validation showed that DZSM significantly reduced the protein levels of nuclear factor （NF）-κB， Janus kinase 2 （JAK2）， and signal transduction activator and transducer 3 （STAT3） in the cardiac tissue， as well as the levels of chemokine （C-X-C motif） ligand 1 （CXCL1）， interleukin （IL）-1β， neutrophil elastase-DNA complex （NE-DNA）， and myeloperoxidase-DNA complex （MPO-DNA） in the plasma. ConclusionDZSM may ameliorate myocardial fibrosis by inhibiting neutrophil infiltration and extracellular trap formation and regulating the NF-κB/JAK2/STAT3 signaling pathway.

AIM: To compare the efficacy of highly aspherical lenslets(HAL), defocus incorporated multiple segments(DIMS), and single-vision spectacle lenses(SVL)in slowing myopia progression in children and adolescents.

METHODS: In this retrospective cohort study, myopic children and adolescents aged 6-16 y who were prescribed spectacle lenses at the hospital between January 2023 and June 2023 were included. Participants were divided into the HAL, DIMS, and SVL groups according to the correction modality voluntarily selected by participants and their guardians. The follow-up duration was 12 mo. After 12 mo of wear, changes from baseline in sphere, cylinder, spherical equivalent(SE), axial length(AL), flat corneal curvature(K1), steep corneal curvature(K2), mean corneal curvature, and binocular visual function \〖binocular cross-cylinder(BCC), negative/positive relative accommodation(NRA/PRA)\〗 were compared among the three groups after 12-month spectacle wear. Three groups were further stratified by age into age≤10 y and age>10 y subgroups to explore the effect of age on myopia control efficacy of defocus lenses.

RESULTS: A total of 159 myopic participants(159 eyes; only the right eye was included for each subject)were enrolled. In the HAL group(55 participants), there were 24 males and 31 females, with a mean age of 10.07±2.14 y. The DIMS group consisted of 60 participants(33 males, 27 females), with a mean age of 10.02±1.88 y. The SVL group included 44 participants(21 males, 23 females), with a mean age of 10.59±1.93 y. There were no significant differences in K1, K2, mean corneal curvature, NRA, BCC, and PRA among the three groups after 12-month spectacle wear(all P>0.05). There were statistically significant differences in the changes in sphere, SE, and AL(all P<0.05). The changes in sphere, cylinder, SE, and AL in the HAL and DIMS groups were significantly lower than those in the SVL group(all P<0.0167). The DIMS group showed a significantly smaller cylinder progression than the SVL group(P<0.0167). In participants aged≤10 y, the change in spherical power in the HAL group was significantly smaller than those in the DIMS group and SVL group after 12-month spectacle wear(all P<0.0167). The change in cylindrical power in the DIMS group was smaller than that in the SVL group(all P<0.0167). Among participants aged>10 y, the changes in spherical power, SE, and AL in both the HAL group and DIMS group were significantly smaller than those in the SVL group after 12-month spectacle wear(all P<0.0167).

CONCLUSION: Both HAL and DIMS lenses can effectively slow the progression of refractive error and AL elongation in children and adolescents, without significant adverse effects on binocular visual function. Among children≤10 y, HAL lenses yield superior spherical power control, whereas DIMS lenses provide better astigmatism control than SVL.

Objective:To explore the characteristics of the brain functional networks in children with spastic cerebral palsy (SCP) while at rest and to correlate them with motor functioning.Methods:Thirty-six children with SCP were enrolled as the SCP group, while thirty-four age-matched healthy children were recruited as the control group (the HC group). Functional near-infrared spectroscopy was used to detect changes in the concentration of oxygenated hemoglobin in the children′s cerebral cortex while at rest. The left prefrontal cortex (LPFC), right prefrontal cortex (RPFC), left motor cortex (LMC), and right motor cortex (RMC) were selected as regions of interest. Phase locking values (PLVs) were used to evaluate the strength of functional connectivity (FC) among these brain regions, and graph theory methods were applied to analyze the topological properties of the brain networks. Motor functioning was assessed using the gross motor function measure (GMFM).Results:The analyses of FC strength revealed that the SCP group had significantly weaker FC among all of the regions of interest while at rest compared to the HC group. Their PLVs for LPFC-RPFC, LPFC-RMC, RPFC-RMC and LMC-RMC connectivity were all significantly smaller. Graph theory analysis showed that the SCP group had significantly lower global efficiency (GE) and smaller clustering coefficients (CCs) and network density (D), while their characteristic path lengths were significantly longer. According to the correlation analysis, the PLVs for LMC-RMC connections in the SCP group were positively correlated with their scores on dimensions D and E of the GMFM ( r=0.496 and r=0.579 respectively). GE ( r=0.587 and r=0.642) and CC ( r=0.318 and r=0.759) showed similar significant positive correlations with GMFM dimensions D and E. Conclusions:At rest, the functional networks in the brains of children with SCP exhibit abnormalities closely associated with their motor dysfunction.

Druggability evaluation is one of the core processes in new drug development, yet the inaccuracy and high cost of existing in vitro liver models have been a major technical bottleneck, leading to an increasing demand from the pharmaceutical industry for reliable in vitro liver models to enhance the efficiency of new drug research and development. Traditional animal models and in vitro 2D culture models have their limitations in simulating in vivo physiological and pathological conditions, making it challenging to accurately predict drug efficacy and safety. With the advancement of microfluidic technology, in vitro cell culture, and biosensor technology, liver-on-a-chip (LOC) has garnered increasing attention in the field of new drug development in recent years, and is expected to become a powerful tool for addressing the challenges in druggability evaluation. While introducing the construction technology of LOC, this article mainly summarizes the research and application of existing LOC from the perspectives of disease model construction, drug metabolism research, and drug safety evaluation. Furthermore, it analyzes the role of LOC in druggability evaluation and discusses the current challenges and prospects in this field.

Objective To investigate the factors influencing the efficacy of intravesical Bacille Calmette-Guérin(BCG)instillation after transurethral resection of bladder tumor(TURBT)in patients with intermediate-and high-risk non-muscle invasive bladder cancer(NMIBC),and to construct a prediction model for recurrence after BCG treatment.Methods A retrospective cohort study was conducted on the subjected patients diagnosed with intermediate-and high-risk NMIBC undergoing TURBT followed by standard BCG instillation.The 110 patients treated in Department of Urology of Army Medical Center of PLA from January 2018 to December 2023 were assigned into a training set,while the 52 patients treated at Department of Urology of General Hospital of Central Theater Command from January 2015 to December 2020 were into an external validation set.A total of 17 variables were included and analyzed.Univariate and multivariate Cox regression analyses were performed to identify factors associated with recurrence after BCG instillation,and nomograms were plotted to predict 1-year,3-year,and 5-year recurrence-free survival(RFS).Calibration curve,decision curve analysis(DCA),and receiver operating characteristic(ROC)curve analysis were conducted for internal and external validation to evaluate the predictive performance and clinical utility of the model.Results In the training set,26 patients(23.64%)experienced recurrence during the follow-up period,with a median RFS of 32.00(18.00～50.50)months.Univariate Cox regression analysis suggested that platelet count,eosinophil to lymphocyte ratio(ELR),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),systemic immune inflammation(SII)index,and neutrophil-monocyte to lymphocyte ratio(NMLR),pathological T1 stage(pT1)tumor and hemoglobin,albumin,lymphocyte,and platelet(HALP)score were potential factors influencing recurrence after BCG instillation.Multivariate Cox regression analysis identified high HALP score(HR=0.185,95%CI:0.046～0.736,P=0.017)as an independent protective factor,while high ELR(HR=3.599,95%CI:1.505～8.608,P=0.004)and pT1 stage(HR=3.240,95%CI:1.191～8.818,P=0.021)were independent risk factors for recurrence.Based on this,a nomogram prediction model was constructed.The calibration curves demonstrated good agreement between predicted and actual 1-,3-,and 5-year recurrence risks.Decision curve analysis indicated clinical utility across a wide threshold probability range.In the training set,the model showed strong predictive performance for 1-(AUC=0.842),3-(AUC=0.847),and 5-year(AUC=0.887)recurrence risks,which was further validated in the external cohort.Conclusion Higher HALP score prior to BCG instillation therapy is a protective factor against tumor recurrence,while higher ELR and pT1 stage are risk factors.Our nomogram prediction model based on HALP score,ELR and pathological T stage,can identify individuals at high risk of recurrence after BCG instillation therapy.

Objective To investigate the expression of NOP16 nucleolar protein(HSPC111)and triple do-main protein 2(TRIM2)in colorectal cancer(CRC),as well as their clinicopathological characteristics and prognostic evaluation value.Methods A total of 110 CRC patients admitted to SUN Simiao Hospital,Beijing University of Traditional Chinese Medicine from February 2018 to February 2019 were selected as the research subjects.The expressions of HSPC111 and TRIM2 in tissues were detected by immunohistochemistry.The survival curves of the HSPC111 and TRIM2 positive and negative groups were plotted by Kaplan-Meier sur-vival analysis.The COX regression model was used to analyze the risk factors influencing the prognosis of CRC patients.A nomogram model for the prognosis of CRC was constructed,and the accuracy of the model was analyzed using the prognostic calibration curve.Results The positive rates of HSPC111 and TRIM2 in CRC cancer tissues were higher than those in the adjacent groups,and the differences were statistically signifi-cant(P＜0.001).The positive rates of HSPC111 and TRIM2 in CRC cancer tissues with TNM stage Ⅲ and lymph node metastasis increased,and the difference was statistically significant(P＜0.001).The 5-year sur-vival rate of CRC patients in the HSPC111 positive group was lower than that in the negative group(Log-rank x2=10.121,P=0.001).The 5-year survival rate of CRC patients TRIM2 positive group was lower than that in the negative group(Log-rank x2=13.620,P＜0.001).Positive HSPC111,positive TRIM2,TNM stage Ⅲand lymph node metastasis were risk factors affecting the prognosis of CRC patients.The consistency index of the Nomogram prediction model based on HSPC111,TRIM2,TNM staging and lymph node metastasis was 0.846(95％CI:0.822-0.870)and the predicted value was close to the actual value,with good discrimination.Conclusion The increased expression of HSPC111 and TRIM2 in CRC is involved in promoting the progres-sion of CRC.Nomogram prediction models based on HSPC111,TRIM2,TNM staging and lymph node metas-tasis are helpful for evaluating the prognosis of CRC.

PANoptosis is a novel mode of cell death that intelligently initiates signaling pathways by forming PANoptosome.It can promote the development of retinopathy and nephropathy by regulating the inflammatory response and cell death triggered by hyperglycemia.It activates inflammasome release and plays a role in Alzheimer's disease(AD)and osteoarthritis.Similarly,PANoptosis can promote cochlear aging by damaging mitochondria,changing immune response and inducing inflammatory response,aiming to provide new thera-peutic ideas for the disease.

Objective To investigate the association between the TyG index,its modified variants,and the risk of developing colorectal cancer(CRC).Methods This study included a total of 93,177 participants from the 2006 Kailuan Group health examination cohort.Participants were categorized into four quartiles(Q1-Q4)according to their TyG and modified TyG indices.Follow-up began at the baseline examination,with incident CRC as the primary outcome.Participants were censored at the time of CRC diagnosis,death,or the end of the study,whichever occurred first.The dose-response relationship between TyG and its modified indices and the risk of CRC was evalu-ated using restricted cubic splines(RCS)in conjunction with Cox proportional hazards regression models,yielding hazard ratios(HRs)and 95%confidence intervals(CIs).To compare the strength of associations between TyG and its modified versions(TyG-BMI,TyG-WC,TyG-WHR,TyG-WHtR,TyG-WWI)and CRC risk,HRs for CRC per one standard deviation increase in each index were calculated and compared.Results Both the TyG index and its modified variants demonstrated a significant dose-response relationship with the risk of CRC incidence.Specifically,for the TyG index,each 1-standard deviation(SD)increase was associated with a 1.17-fold(95%CI:1.09～1.27)higher risk of CRC.Compared with the first quartile(Q1),the third quartile(Q3)and fourth quartile(Q4)exhibited a 1.25-fold(95%CI:1.01～1.55)and 1.26-fold(95%CI:1.01～1.57)increased risk,respectively.For TyG-BMI,each 1-SD increase was linked to a 1.20-fold(95%CI:1.07～1.35)elevated CRC risk.Compared with Q1,Q3 and Q4 showed a 1.32-fold(95%CI:1.06～1.64)and 1.51-fold(95%CI:1.21～1.88)increase,respectively.Regarding TyG-WC,each 1-SD increment was associated with a 1.22-fold(95%CI:1.13～1.32)higher CRC risk,with Q3 and Q4 showing a 1.35-fold(95%CI:1.08～1.70)and 1.56-fold(95%CI:1.24～1.96)increased risk compared to Q1.For TyG-WHtR,each 1-SD increase was associated with a 1.24-fold(95%CI:1.08-1.42)higher CRC risk.Compared with Q1,Q2,Q3,and Q4 demonstrated a 1.31-fold(95%CI:1.03～1.66),1.55-fold(95%CI:1.23～1.95),and 1.60-fold(95%CI:1.27～2.02)increase,respectively.In the case of TyG-WHR,each 1-SD increase was associated with a 1.19-fold(95%CI:1.10～1.29)higher CRC risk,with Q4 showing a 1.42-fold(95%CI:1.14～1.77)increased risk compared to Q1.Finally,for TyG-WWI,each 1-SD increase was associated with a 1.22-fold(95%CI:1.13～1.32)elevated CRC risk,with both Q3 and Q4 showing a 1.58-fold increase(Q3:95%CI:1.26～1.98;Q4:95%CI:1.25～1.99).Stratified analyses by sex and age consistently revealed significant associations between the TyG index and its modified variants and CRC risk.Furthermore,these indices were independently associated with the incidence of both colon cancer and rectal cancer.Conclusions(1)Elevated levels of the TyG index and its modified variants are independent risk factors for CRC.(2)Both the TyG index and its modified forms demonstrate a significant dose-response association with the incidence of CRC.(3)Among the modified TyG indices,TyG-WWI,TyG-WHtR,TyG-BMI,TyG-WC,and TyG-WHR showed stronger correlations with CRC risk compared to the original TyG index.