ObjectiveTo investigate the application value of a multimodal model integrating radiomics features， deep learning features， and clinical structured data in predicting severe acute pancreatitis （SAP）， and to provide more accurate tools for the early identification of SAP in clinical practice. MethodsThe patients with acute pancreatitis （AP） who attended The First Affiliated Hospital of Soochow University， Jintan Hospital Affiliated to Jiangsu University， and Suzhou Yongding Hospital from January 1， 2017 to December 31， 2023 were included. Related data were collected， including demographic information， previous medical history， etiology， laboratory test data， and systemic inflammatory response syndrome （SIRS） within 24 hours after admission， as well as imaging data within 72 hours after admission， while related scores were calculated， including Ranson score， modified CT severity index （MCTSI）， bedside index for severity in acute pancreatitis （BISAP）， and systemic inflammatory response syndrome， albumin， blood urea nitrogen and pleural effusion （SABP） score. The model was constructed in the following process： （1） three-dimensional CT images were used to extract and identify radiomics features， and a radiomics classification model was established based on the extreme gradient Boost （XGBoost） algorithm； （2） U-Net is used to perform semantic segmentation of three-dimensional CT images， and then the results of segmentation were imported into 3D ResNet50 to construct a deep learning classification model； （3） the predicted values of the above two models were integrated with clinical structured data to establish a multimodal model based on the XGBoost algorithm. The variable importance plot and local interpretability plot were used to perform visual interpretation of the model. The independent samples t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test or Fisher’s exact test was used for comparison of categorical data between groups. The receiver operating characteristic （ROC） curve was plotted for each model and existing scoring systems， and the area under the ROC curve （AUC） was calculated to assess their performance； the Delong test was used for comparison of AUC. ResultsA total of 609 patients who met the criteria were included， among whom 114 （18.7%） developed SAP. In this study， the data of 426 patients from The First Affiliated Hospital of Soochow University was used as the training set， and the data of 183 patients from Jintan Hospital Affiliated to Jiangsu University and Suzhou Yongding Hospital were used as the independent test set. The multimodal model had an AUC of 0.914 in the test set， which was significantly higher than the AUC of traditional scoring systems such as MCTSI （AUC=0.827）， Ranson score （AUC=0.675）， BISAP （AUC=0.791）， and SABP score （AUC=0.648）； in addition， the multimodal model showed a significant improvement in performance compared with the radiomics classification model （AUC=0.739） and the deep learning classification model （AUC=0.685） （the Delong test： Z=-3.23， -4.83， -3.48， -4.92， -4.31， and -4.59， all P <0.01）. The top 10 variables in terms of importance in the multimodal model were pleural effusion， predicted value of the deep learning model， predicted value of the radiomics model， triglycerides， calcium ions， SIRS， white blood cell count， age， platelets， and C-reactive protein， suggesting that the above variables had significant contributions to the performance of the model in predicting SAP. ConclusionBased on structured data， radiomic features， and deep learning features， this study constructs a multicenter prediction model for SAP based on the XGBoost algorithm， which has a better predictive performance than existing traditional scoring systems and unimodal models.

A micro gas chromatographic column with mesoporous surface micro column array prepared by anodization method was proposed.A porous support layer with a characteristic pore size of about 30 nm inside the chromatographic column was prepared in situ using anodization method,and a uniform alumina stationary phase was deposited on the mesoporous support layer using atom layer deposition(ALD)technique.The existence of a mesoporous support layer increased surface area of the chromatographic column,thereby increasing the total amount of stationary phase loading and enhancing column capacity,which facilitated chromatographic separation.The test results showed that the porous support layer significantly reduced the longitudinal molecular diffusion and mass transfer resistance of the micro gas chromatographic column,and significantly increased the number of theoretical plates(n-nonane increased by 290.2%).Furthermore,column efficiency of the chromatographic column was less affected by flow rate,which was conducive to rapid separation of heavy hydrocarbon mixtures.

Neonatal jaundice is commonly seen in early postnatal days，and is partly caused by hemolysis. It has been found that hemolytic jaundice in neonates is often accompanied with myocardial injury，which may pose a threat to their health. However，the pathogenic mechanism remains unclear. This review focuses on the potential mechanisms of myocardial injury associated with hemolytic jaundice，particularly highlighting the role of carboxyhemoglobin（COHb）as a potential contributor. Emerging evidence suggests that COHb，a hemolytic metabolite，can cause myocardial injury through mechanisms such as influencing oxygen metabolism and exerting cytotoxic effects，particularly in neonates who are susceptible to hypoxia. The review aims to summarize the latest research progress in this field，to facilitate early prediction，early detection，and timely intervention for hemolytic jaundice accompanied with myocardial injury，while providing novel therapeutic strategies and targets.

Wound repair and infection have long posed significant challenges in clinical medicine.Am-phibians,adapting to complex environments through long-term natural selection,have evolved skin sys-tems with remarkable abilities to resist external damage and promote rapid wound healing,making them an important source for discovering candidate molecules for wound healing.In this study,a novel peptide composed of 22 amino acids,with the sequence"VGKAGLETAACKATNSCFNIDW"and a molecular weight of 2299.6 D,was screened from the cDNA library of Odorrana tormota and named PN-VW22.The peptide was synthesized by solid-phase synthesis,and its effects on cell proliferation were evaluated using the CCK-8 assay and scratch wound healing assay in human keratinocytes(HaCaT)and mouse em-bryonic fibroblasts(NIH3T3).Antibacterial activity was assessed by determining the minimum inhibitory concentration(MIC).Results showed that PN-VW22 at various concentrations had no significant effect on the cell viability in NIH3T3 cells(P＞0.05),but significantly enhanced HaCaT cell viability at 0.5μmol/L(P＜0.001).Meanwhile,PN-VW22 induced cell proliferation and promoted wound healing in HaCaT cells,with a healing rate of 64.44％after 24 h incubation at 0.5 μmol/L.Furthermore,PN-VW22 exhibited antibacterial activity against Staphylococcus aureus with an MIC value of 13.92 μmol/L.In sum,this study identified PN-VW22 as a novel bifunctional peptide with both wound repair and anti-infective properties,providing a new toxin peptide template for the development of wound healing drugs.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Aim To investigate the mechanism of Guanxinning injection regulating cardiac immune mi-croenvironment to improve myocardial infarction in mice.Methods In this study,MI model was estab-lished by permanent ligation of left anterior descending coronary artery in mice.The mice were divided into five groups:sham operation group,model group,Guanxinning injection low dose group,Guanxinning in-jection high dose group and positive drug captopril group.Hearts were weighed,heart tissues were collect-ed,and Masson staining was used for pathological anal-ysis of heart tissues;immunofluorescence staining was used to detect apoptosis and CCL21 expression in the infarct border zone;flow cytometry was used to detect the proportion of immune cells in myocardial ischemia tissues and lymph nodes;PCR was used to detect CCL21 expression in heart and in vitro human lymphat-ic endothelial cells(HLEC).Results Compared with the model group,the low and high dose groups of Guanxinning injection significantly improved cardiac hypertrophy.Apoptosis in the border zone of myocardi-al infarction was reduced in the low and high dose groups of Guanxinning injection and captopril group.Compared with the model group,the proportion of leu-kocytes in the infarct border zone was dreduced and the proportion of CD4+T cells,Treg cells,and CD8+T cells in the mediastinal lymph nodes and infarct border zone of the heart was regulated in the low and high dose groups of Guanxinning injection;CCL21 secretion by the heart and lymphatic vessels increased.Conclu-sions Guanxinning injection can significantly improve cardiac hypertrophy and fibrosis in MI mice,reduce ap-optosis in the infarct border zone,and play a role in an-ti-myocardial ischemia injury by promoting CCL21 ex-pression in lymphatic vessels to regulate the proportion of mediastinal lymph nodes and cardiac T cells after myocardial infarction.

Objective To explore the biological characteristics associated with different subtypes and the response to immunotherapy by integrating multiomics analysis and artificial neural networks(ANN)to delineate the precise molecular subtypes of adrenocortical carcinoma(ACC)and establish a prognostic prediction model,in order to provide reference for the accurate prognosis assessment and individualized treatment of ACC.Methods The multiomics data of 44 Chinese ACC patients admitted to the Department of Urology,West China Hospital of Sichuan University during Jan.1,2012 and Dec.31,2022 were integrated,including genomic,transcriptomic and clinical features.Ten different clustering algorithms were employed for consensus clustering to identify robust molecular subtypes.The results were then incorporated into an ANN model to construct an ANN-driven prognostic index(ANPI)for patient stratification and survival prediction.Results Three distinct molecular subtypes(cancer subtypes,CS1-3)with significantly different prognoses were identified,among which CS1 exhibited the poorest survival outcomes.A set of 20 core genes was selected to form the basis of the ANPI model.ANPI effectively stratified patients into high-and low-risk groups:patients in the low-ANPI group had significantly better overall survival and exhibited"hot tumor"immune phenotypes,suggesting greater benefits from immunotherapy.In contrast,high-ANPI patients had worse prognoses and displayed"cold tumor"characteristics with weaker immunotherapy responses.Conclusion Our integrative multiomics analysis illustrated the molecular landscape of ACC in the Chinese population and uncovered the key immune-related features linked to clinical outcomes.The ANPI model demonstrated strong performance in prognostic prediction and immunotherapy response assessment,offering a valuable tool for precision oncology and clinical decision-making.

Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

Human NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavoenzyme expressed at high levels in multiple solid tumors, making it an attractive target for anticancer drugs. Bioactivatable drugs targeting NQO1, such as β-lapachone (β-lap), are currently in clinical trials for the treatment of cancer. β-Lap selectively kills NQO1-positive (NQO1⁺) cancer cells by inducing reactive oxygen species (ROS) via catalytic activation of NQO1. In this study, we demonstrated that cryptotanshinone (CTS), a naturally occurring compound, induces NQO1-dependent necrosis without affecting NQO1 activity. CTS selectively kills NQO1⁺ cancer cells by inducing NQO1-dependent necrosis. Interestingly, CTS directly binds to NQO1 but does not activate its catalytic activity. In addition, CTS enables activation of JNK1/2 and PARP, accumulation of iron and Ca²⁺, and depletion of ATP and NAD⁺. Furthermore, CTS selectively suppressed tumor growth in the NQO1⁺ xenograft models, which was reversed by NQO1 inhibitor and NQO1 shRNA. In conclusion, CTS induces NQO1-dependent necrosis via the JNK1/2/iron/PARP/NAD⁺/Ca²⁺ signaling pathway. This study demonstrates the non-enzymatic function of NQO1 in inducing cell death and provides new avenues for the design and development of NQO1-targeted anticancer drugs.

Objective Evaluate the effects of different solvent extracts from Jujing Pills on improving retinal damage in kidney Yang deficiency aging mice and explore the underlying mechanism.Methods A composite modeling method of subcutaneous injection of D-galactose and hind limb injection of hydrocortisone was used to establish a kidney Yang deficiency type aging mouse model,and various solvent extract of Jujing Pills were given for intervention treatment.The improvement effect of different solvent extracts of Jujing Pills on aging mice with kidney Yang deficiency was evaluated by observing physical signs,measuring serum oxidative stress marker levels,and cyclic nucleotide levels.Optical coherence tomography(OCT)was used to detect the condition of the mouse retina,HE staining was used to detect the degree of retinal cell damage,TUNEL staining was used to detect retinal cell apoptosis,assay kit was used to detect oxidative stress factor expression,enzyme-linked immunosorbent assay was used to detect the expression of ciliary neurotrophic factor(CNTF),brain-derived neurotrophic factor(BDNF),and nerve growth factor(NGF)in the mouse eyeball,and Western blotting(WB)was used to quantitatively analyze the expression levels of apoptosis and neurotrophic pathway related proteins in the mouse retina tissue.Results Compared with the control group,the model group mice showed slow weight gain,reduced activity,decreased expression of antioxidant factors such as superoxide dismutase(SOD)and glutathione(GSH)in serum(P<0.01),and decreased cAMP/cGMP ratio(P<0.01).Different solvent extracts of Jujing Pills significantly increased the expression of antioxidant factors such as SOD and GSH(P<0.05),reduced the production of oxidative product malondialdehyde(MDA)(P<0.01),and increased the cAMP/cGMP ratio(P<0.01);Significantly increased the retinal thickness of model mice(P<0.01),improved retinal damage and inhibited retinal cell apoptosis(P<0.01),and significantly downregulated the ratio expression levels of Cleaved Caspase-3 and Caspase-3(P<0.01);The expression of CNTF,BDNF,and NGF was upregulated by water extracted medicinal residue alcohol extract,water extracted alcohol sediment,and total extract(P<0.01).The phosphorylation levels of CREB and ERK in the eyeball were significantly upregulated by water extracted medicinal residue alcohol extract and total extract(P<0.05).Conclusion Different solvent extracts of Jujing Pills can exert different pharmacological effects on improving retinal damage in aging mice with kidney yang deficiency model.Its mechanism of action is related to improving retinal apoptosis caused by oxidative stress and increasing the expression of nutritional factors.