AIM:To study the protective effect of transient receptor potential vanilic acid subtype 1(TRPV1)agonist capsaicin(CAP)on traumatic blood loss shock rats,and to further explore its possible mechanism by network pharmacology.METHODS:Forty-five SD rats were divided into 5 groups by random number table method:normal group,shock group,lactated Ringer's solution(LR)group,CAP pretreatment(single administration before shock)group,CAP pre-final administration(twice administration before and after shock)group,with 9 rats in each group for survival observation.Then 32 SD rats were divided into 4 groups according to the results of survival experiment:normal group,shock group,LR group,CAP pre-final administration group,with 8 rats in each group for blood pressure,hemodynamics,arterial blood gas,vascular reactivi-ty and hepaticand renal blood flow.At the same time,the potential mechanism of CAP in the treat-ment of traumatic hemorrhagic shock was investi-gated by network pharmacology.Furthermore,ap-ply the dataset to validate and analyse the diagnos-tic value of the hub genes.RESULTS:Rats in shock group died within hours of the completion of the shock model,and the mean survival time was 1.25(0.42,6.21)h.LR resuscitation could improve the survival of rats to some extent.The survival rate and survival time of rats in the CAP pretreatment group were slightly increased as compared with the LR group,while twice administration of CAP be-fore and after shock(CAP pre-final administration)resulted in better outcomes than LR resuscitation alone.Further results indicated that CAP pre-final administration significantly reduced the blood lac-tic acid level,improved the vasoconstrictive and di-astolic reactivity,and increased the liver and kidney blood flow of shock rats as compared with LR group.The improvement of hemodynamics and blood gas indexes in CAP group was slightly higher than LR group,but there was no statistical signifi-cance.A total of 37 genes related to CAP anti-trau-matic hemorrhage shock were obtained by net-work pharmacology.KEGG enrichment analysis showed that the Ca ion signaling pathway and Ras signaling pathway were significantly enriched.Vali-dation of the dataset showed that the expression levels of CXCR4,NF-kB1,GFPA and NTF3 hub gene were significantly different in the normal and shock groups,and that CXCR4 has a high diagnostic value for traumatic haemorrhagic shock.CONCLUSIONS:CAP,the TRPV1 agonist,significantly improved vas-cular function,increased organ blood flow,and cor-rected the lactic acidosis in rats with traumatic hemorrhagic shock,thus markedly improved the survival outcomes.The mechanism may be related to Ca ion signal pathway and Ras signal pathway.CXCR4,NF-kB1,GFPA and NTF3 may be having an important role in it.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Recently,diffusion models have emerged as a promising paradigm for molecular design and optimization.However,most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geom-etries,with limited research on molecular sequence diffusion models.The International Union of Pure and Applied Chemistry(IUPAC)names are more akin to chemical natural language than the simplified molecular input line entry system(SMILES)for organic compounds.In this work,we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language(SMILES)and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language.We propose DiffIUPAC,a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings.Evaluation results demonstrate that our model out-performs existing methods and successfully captures the semantic rules of both chemical languages.Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints.Additionally,to illustrate the model's applicability in drug design,we conducted case studies in functional group editing,analogue design and linker design.

Objective To target at the NKG2A-HLA-E inhibitory axis,a pluripotent stem cell(iPSC)-derived geneti-cally engineered natural killer cells(NK cells)with NKG2A knockout(NKG2A KO-iNK)were prepared and then their tumor-killing efficacy was evaluated in vitro.Methods NKG2A was knocked out in iPSCs using gene-editing technology.These cells were then differentiated into NKG2A KO-iNK cells.Surface markers at each differentiation stage were analyzed by flow cytometry.Western blot confirmed NKG2A knockout,and flow cytometry assessed expres-sion of activating receptors(NKG2D)and natural cytotoxicity receptors(NKp30,NKp44,NKp46)in NKG2A KO-iNK cells.Cytotoxic activity against tumor cell lines with varying human leukocyte antigen E(HLA-E)expression level was evaluated via lactate dehydrogenase(LDH)release assay.Results Co-transfection of iPSCs with Cas9 pro-tein and three small-guide RNAs(sgRNAs)targeting at exons 1 and 2 of the KLRC1 gene(encoding NKG2A)suc-cessfully generated monoclonal NKG2A-knockout iPSCs(NKG2A KO-iPSCs)with a single T-base insertion in exon 1.During iPSC differentiation into NK cells,CD34 expression reached 30％-50％at the embryoid body(EB)stage(day 8),while CD56 and CD 16 expression exceeded 80％by day 28.Western blot confirmed complete NKG2A knockout in NKG2A KO-iNK cells.Flow cytometry revealed comparable expression level of activating receptor NKG2D and cytotox-icity receptors(NKp30,NKp44,NKp46)between NKG2A KO-iNK and wild-type iNK(WT-iNK)cells.The LDH assay results indicated that the cytotoxic activity of NKG2A KO-iNK cells against the HLA-E highly-expressed B-cell precursor leukemia cell line Nalm6 cells was significantly higher than that of WT-iNK cells,while there was no signif-icant difference between them and human myeloma cell line H929 cells with low HLA-E expression and human hepa-tocellular carcinoma cell line HepG2 cells with almost no HLA-E expression.Interferon-γ(IFN-γ)pretreatment up regulated HLA-E expression in Nalm6 cells,further amplifying NKG2A KO-iNK-mediated cytotoxicity.Conclusions By disrupting the NKG2A-HLA-E inhibitory axis,NKG2A KO-iNK cells exhibit markedly enhanced in vitro cytotoxic-ity against HLA-E-high tumor cells.This result highlights their potential function as a novel adoptive cell therapy strategy for cancers reliant on HLA-E-mediated immune evasion.

Recently, diffusion models have emerged as a promising paradigm for molecular design and optimization. However, most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geometries, with limited research on molecular sequence diffusion models. The International Union of Pure and Applied Chemistry (IUPAC) names are more akin to chemical natural language than the Simplified Molecular Input Line Entry System (SMILES) for organic compounds. In this work, we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language (SMILES) and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language. We propose DiffIUPAC, a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings. Evaluation results demonstrate that our model outperforms existing methods and successfully captures the semantic rules of both chemical languages. Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints. Additionally, to illustrate the model's applicability in drug design, we conducted case studies in functional group editing, analogue design and linker design.

Objective To observe the value of multi-sequence magnetic resonance imaging(MRI)radiomics in predicting the efficacy of concurrent chemoradiotherapy(CCRT)in locally advanced cervical squamous cell carcinoma(CSCC)patients.Methods Clinical data of 100 CSCC patients underwent CCRT treatment were selected.In order to better validate the performance of the model,patients were randomly divided into the training set(70 cases)and the validation set(30 cases)in a 7∶3 ratio.According to the efficacy criteria for solid tumors,patients were divided into the complete response(CR)group(n=16)and the partial response(PR)group(n=14).Examination images of cross-sectional DWI,T2WI and enhanced T1WI were collected from all patients before treatment.ITK-SNAP software package combined with three sequences were used to outline ROI,and the open source software PyRadiomics was used to extract image omics features.For MRI omics features,the minimum redundancy maximum correlation(mRMR)algorithm was used to analyze and screen out the first 30 main features,and then the minimum absolute contraction and selection method(Lasso)based on 10-fold cross-validation was used to reduce dimensionality to screen the non-zero coefficient features.According to the weighting coefficient of Lasso-Logistic regression model in the training set,patient omics labels were calculated.Logistic regression analysis was used to construct a prediction model based on DWI,T2WI and T1WI sequence prediction models and multiple sequenomics labels.Receiver operating characteristic(ROC)curves evaluated the predictive value of each omics model for CCRT treatment in patients with locally advanced CSCC.Results There were 38 cases in the CR group and 32 cases in the PR group in the training set.There were 16 cases in the CR group and 14 cases in the PR group in the validation set.There were no significant differences in patient age,FIGO stage,differentiation degree,maximum lesion diameter and menstrual status between the CR group and the PR group in the training and validation sets.A total of 851 imaging features were extracted from the ROI target area.After the first 30 features were retained by mRMR algorithm,3 CR-related features were selected from the 851 imaging omics features of each individual sequence by Lasso algorithm and 10-fold cross-validation.Eight CR related features were selected from 2 553 features after the combination of the three sequences.ROC curve results showed that in the training set and validation set,the AUC of multiple sequences combined to predict the therapeutic effect of CCRT in patients with locally advanced CSCC was 0.971 and 0.946,respectively,which was higher than that of T1WI,T2WI and DWI single sequence prediction(training set Z=2.683,2.046,2.817,P＜0.05;verification set Z=2.075,2.117,2.005,P＜0.05).Conclusion The multi sequence MRI radiomics model has high predictive value for the efficacy of CCRT treatment in locally advanced CSCC patients.

Objective:To study the effect of anthocyanins(C3G)on cuproptosis in chronic epileptic rats.Methods:Chronic epileptic rat model was induced by pentatetrazol(PTZ),and 90 SD rats were randomly divided into control group,PTZ group,elesclomol(ELC)group,tetrathiomolybdate(TTM)group,C3G group and ELC+C3G group.The grade,latency and frequency of seizures were recorded in each group.electroencephalogram(EEG)was used to detect abnormal electrical discharge in the brain.The action potential of hippocampal neurons was measured by patch-clamp technique.The contents of glutathione(GSH)and cuprous ions(Cu+)in hippocampus were determined by kit.Neuron damage in hippocampus was evaluated by Nissl staining.The expression of ferredoxin1(FDX1)and lipoic acid synthase(LIAS)in hippocampus was analyzed by immunohistochemistry and Western blot.Results:Compared with the control group,the rats in the PTZ group exhibited epileptic-like seizures,suggesting that the modeling was successful.Com-pared with other epileptic groups,the ELC group showed increased seizure grade,more abnormal discharges,shortened latency period,enhanced neuronal excitability,decreased Nissl particles,elevated Cu+levels,decreased GSH levels,and increased expressions of FDX1 and LIAS.The reverse was observed in C3G group(P＜0.05).Neuron damage in ELC+C3G group was less severe than that in ELC group,but more than that in PTZ group(P＜0.05).Neuron dam-age in TTM group was less severe than that in PTZ group,but more severe than that in C3G group(P＜0.05).Conclusion:cuproptosis exists in hippocampus of rats with chronic epilepsy,and the C3G can significantly inhibit cu-proptosis and alleviate the occurrence and development of chronic epilepsy.

Objective:To study the effect of anthocyanins(C3G)on cuproptosis in chronic epileptic rats.Methods:Chronic epileptic rat model was induced by pentatetrazol(PTZ),and 90 SD rats were randomly divided into control group,PTZ group,elesclomol(ELC)group,tetrathiomolybdate(TTM)group,C3G group and ELC+C3G group.The grade,latency and frequency of seizures were recorded in each group.electroencephalogram(EEG)was used to detect abnormal electrical discharge in the brain.The action potential of hippocampal neurons was measured by patch-clamp technique.The contents of glutathione(GSH)and cuprous ions(Cu+)in hippocampus were determined by kit.Neuron damage in hippocampus was evaluated by Nissl staining.The expression of ferredoxin1(FDX1)and lipoic acid synthase(LIAS)in hippocampus was analyzed by immunohistochemistry and Western blot.Results:Compared with the control group,the rats in the PTZ group exhibited epileptic-like seizures,suggesting that the modeling was successful.Com-pared with other epileptic groups,the ELC group showed increased seizure grade,more abnormal discharges,shortened latency period,enhanced neuronal excitability,decreased Nissl particles,elevated Cu+levels,decreased GSH levels,and increased expressions of FDX1 and LIAS.The reverse was observed in C3G group(P＜0.05).Neuron damage in ELC+C3G group was less severe than that in ELC group,but more than that in PTZ group(P＜0.05).Neuron dam-age in TTM group was less severe than that in PTZ group,but more severe than that in C3G group(P＜0.05).Conclusion:cuproptosis exists in hippocampus of rats with chronic epilepsy,and the C3G can significantly inhibit cu-proptosis and alleviate the occurrence and development of chronic epilepsy.

AIM:To study the protective effect of transient receptor potential vanilic acid subtype 1(TRPV1)agonist capsaicin(CAP)on traumatic blood loss shock rats,and to further explore its possible mechanism by network pharmacology.METHODS:Forty-five SD rats were divided into 5 groups by random number table method:normal group,shock group,lactated Ringer's solution(LR)group,CAP pretreatment(single administration before shock)group,CAP pre-final administration(twice administration before and after shock)group,with 9 rats in each group for survival observation.Then 32 SD rats were divided into 4 groups according to the results of survival experiment:normal group,shock group,LR group,CAP pre-final administration group,with 8 rats in each group for blood pressure,hemodynamics,arterial blood gas,vascular reactivi-ty and hepaticand renal blood flow.At the same time,the potential mechanism of CAP in the treat-ment of traumatic hemorrhagic shock was investi-gated by network pharmacology.Furthermore,ap-ply the dataset to validate and analyse the diagnos-tic value of the hub genes.RESULTS:Rats in shock group died within hours of the completion of the shock model,and the mean survival time was 1.25(0.42,6.21)h.LR resuscitation could improve the survival of rats to some extent.The survival rate and survival time of rats in the CAP pretreatment group were slightly increased as compared with the LR group,while twice administration of CAP be-fore and after shock(CAP pre-final administration)resulted in better outcomes than LR resuscitation alone.Further results indicated that CAP pre-final administration significantly reduced the blood lac-tic acid level,improved the vasoconstrictive and di-astolic reactivity,and increased the liver and kidney blood flow of shock rats as compared with LR group.The improvement of hemodynamics and blood gas indexes in CAP group was slightly higher than LR group,but there was no statistical signifi-cance.A total of 37 genes related to CAP anti-trau-matic hemorrhage shock were obtained by net-work pharmacology.KEGG enrichment analysis showed that the Ca ion signaling pathway and Ras signaling pathway were significantly enriched.Vali-dation of the dataset showed that the expression levels of CXCR4,NF-kB1,GFPA and NTF3 hub gene were significantly different in the normal and shock groups,and that CXCR4 has a high diagnostic value for traumatic haemorrhagic shock.CONCLUSIONS:CAP,the TRPV1 agonist,significantly improved vas-cular function,increased organ blood flow,and cor-rected the lactic acidosis in rats with traumatic hemorrhagic shock,thus markedly improved the survival outcomes.The mechanism may be related to Ca ion signal pathway and Ras signal pathway.CXCR4,NF-kB1,GFPA and NTF3 may be having an important role in it.