ObjectiveTo explore the effect and mechanism of Jianpi Xiaoai prescription （JPXA） in ameliorating the 5-fluorouracil （5-FU） resistance of colon cancer. MethodsA HCT116/5-FU resistant cell line was established. Different concentrations （10%， 15%， 20%） of JPXA-containing serum and drug-free serum were used for intervention， and 10% fetal bovine serum （10% FBS）， fibroblast growth factor receptor （FGFR） inhibitor （AZD4547）， and recombinant fibroblast growth factor 2 （FGF2） were set as the control groups. Sensitive HCT116 cells were used in the FGF2 group， while HCT116/5-FU cells were used in other groups. Drug resistance， the level of FGF2 in the cell culture medium， the mRNA level of FGF2 in cells， and the protein levels of FGF2/FGFR and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） were determined. The drug-resistant cells were transplanted into the axilla of nude mice to establish a tumor model. The modeled mice were allocated into model， JPXA （15 g·kg^-1）， 5-FU （0.02 g·kg^-1）， JPXA+5-FU （15 g·kg^-1+0.02 g·kg^-1）， AZD4547 （0.012 5 g·kg^-1）， and AZD4547+5-FU （0.012 5 g·kg^-1+0.02 g·kg^-1） groups. The tumor growth and the protein levels of FGF/FGFR and PI3K/Akt in each group were observed. ResultsThe survival rate of HCT116/5-FU cells decreased in all the JPXA groups with different concentrations. The cell survival rate was decreased most obviously in the 20% JPXA group. The level of FGF2 in the cell culture medium and the mRNA level of FGF2 in cells of each JXPA group decreased， and the decrease was the most significant in the 20% group （P<0.01）. HCT116/5-FU cells showed up-regulated protein levels of FGF2 and phosphorylated fibroblast growth factor receptor 1 （p-FGFR1）， but down-regulated protein level of FGFR1 （P<0.01）. JPXA down-regulated the expression of FGF2 and p-FGFR1 and up-regulated the expression of FGFR1 （P<0.05）. In addition， JPXA down-regulated the expression levels of phosphorylated protein kinase B （p-Akt） and phosphorylated mammalian target of rapamycin （p-mTOR）， while up-regulating the expression levels of Akt and Bcl-2-asociated death promoter （Bad） （P<0.05）. Animal experiments showed that the JPXA combined with 5-FU significantly inhibited the growth of drug-resistant tumors， reduced the protein levels of FGF2， p-FGFR1， phosphorylated phosphatidylinositol-3-kinase （p-PI3K）， p-Akt， and p-mTOR， and increased the expression of Bad. It indicated that JPXA can inhibit the FGF2/FGFR1 signaling in colon cancer and regulate PI3K/Akt and downstream signaling pathways. ConclusionJPXA can ameliorate the chemotherapy resistance of colon cancer through down-regulating FGF2 expression and inhibiting the activation of the PI3K/Akt signaling pathway.

Vascular endothelial growth factor (VEGF) inhibitors are drugs that target and inhibit tumor angiogenesis. By blocking the signaling pathway of VEGF and its receptor, they suppress tumor proliferation and play a crucial role in tumor treatment. However, their side effects, such as hypertension, proteinuria, hand-foot skin reactions, and myelosuppression, during treatment seriously affect patients' treatment compliance and quality of life. The development of intervention strategies for the side effects of VEGF inhibitors is of great importance for tumor treatment. This article reviews the clinical characteristics and toxic mechanisms of common side effects caused by VEGF inhibitors during tumor treatment and summarizes intervention strategies that combine traditional Chinese and Western medicines. Drug dosages were precisely monitored and adjusted to achieve antitumor treatment. Patients' discomfort symptoms are improved through prescriptions that act by tonifying qi and promoting blood circulation, strengthening the spleen, and tonifying the kidney. The combination of traditional Chinese and Western medicines is used to treat patients, thus providing a safe and effective treatment plan for patients with cancer.

ObjectiveTo systematically screen and validate key immunogenic cell death （ICD）-related genes that play important roles in primary sjögren’s syndrome （pSS） using multi-omics data. MethodsGene expression profiles of pSS patients and healthy controls （GSE66795， 131pSS patients/29 healthy controls） were obtained from the Gene Expression Omnibus （GEO） database. Candidate genes were selected by intersecting these profiles with known ICD core gene sets and pSS-related targets. The CIBERSORT algorithm was used to analyze immune cell infiltration characteristics. Validation of gene expression was performed using transcriptomic data from sorted CD8⁺ T cell subsets （GSE93683）. Finally， labial gland tissues and peripheral blood samples from 10 pSS patients and 4 healthy controls were collected， and key genes were experimentally validated by reverse transcription quantitative polymerase chain reaction （RT-qPCR）. ResultsSeven intersecting genes from the ICD-differentially expressed genes （DEGs）-pSS intersection were identified ［caspase 1 （CASP1）， forkhead box P3 （FOXP3）， interferon-gamma （IFNG）， myeloid differentiation primary response 88 （MYD88）， toll-like receptor 7 （TLR7）， DExD/H-box helicase 58 （DDX58）， and interferon induced helicase C domain 1 （IFIH1）］. Immune infiltration analysis showed that in pSS labial gland tissues， the proportions of naïve B cells and dendritic cells significantly increased， while the proportions of resting NK cells and M0 macrophages decreased （P<0.05）. Transcriptomic data of CD8⁺T cell subsets indicated that IFIH1 expression was significantly elevated in central memory CD8⁺T cells （P<0.05）. RT-qPCR experimental validation revealed that DDX58， IFIH1， and CASP1 were significantly upregulated in both peripheral blood leukocytes and labial gland tissues of pSS patients （all P<0.05）， whereas IFNG expression increased in peripheral blood but decreased in labial gland tissues （P<0.05）. ConclusionThis study identified and confirmed DDX58， IFIH1， CASP1， and IFNG as key ICD-related genes in pSS through a combination of bioinformatics and experimental validation， providing new candidate targets for further understanding the immunopathological mechanisms of pSS.

Purpose To investigate the functional connectivity(FC)pattern between the bilateral lower limb sensorimotor cortex(LSM)and the whole brain in type 2 diabetic peripheral neuropathy(DPN).Materials and Methods A total of 44 DPN patients and 43 healthy controls admitted to Shaanxi Provincial People's Hospital from February 2021 to December 2022 were enrolled prospectively and underwent neuropsychological assessment and resting-state fMRI scans.Using bilateral LSM as the regions of interest,the differences of bilateral LSM and whole brain FC between DPN patients and healthy controls were compared.FC in different brain areas were extracted and correlated with clinical/neuropsychological scores.Results Compared with healthy controls,DPN patients had reduced FC of the LSM with the right cerebellar lobule Ⅵ,the right lateral occipitotemporal cortex,the bilateral rostral prefrontal cortex and the bilateral anterior cingulate gyrus.The FC between LSM and right cerebellar Ⅵ in DPN patients were significantly negatively correlated with fasting blood glucose(r=-0.490,P=0.001).The FC between LSM and bilateral anterior cingulate gyrus in DPN patients were significantly positively correlated with Montreal cognitive assessment scores(r=0.479,P=0.001).Conclusion Abnormal FC between LSM and multiple brain regions,suggesting that DPN may have extensive effects on brain regions that maintain motion and motor control function in type 2 diabetes mellitus patients.

Purpose To investigate the functional connectivity(FC)pattern between the bilateral lower limb sensorimotor cortex(LSM)and the whole brain in type 2 diabetic peripheral neuropathy(DPN).Materials and Methods A total of 44 DPN patients and 43 healthy controls admitted to Shaanxi Provincial People's Hospital from February 2021 to December 2022 were enrolled prospectively and underwent neuropsychological assessment and resting-state fMRI scans.Using bilateral LSM as the regions of interest,the differences of bilateral LSM and whole brain FC between DPN patients and healthy controls were compared.FC in different brain areas were extracted and correlated with clinical/neuropsychological scores.Results Compared with healthy controls,DPN patients had reduced FC of the LSM with the right cerebellar lobule Ⅵ,the right lateral occipitotemporal cortex,the bilateral rostral prefrontal cortex and the bilateral anterior cingulate gyrus.The FC between LSM and right cerebellar Ⅵ in DPN patients were significantly negatively correlated with fasting blood glucose(r=-0.490,P=0.001).The FC between LSM and bilateral anterior cingulate gyrus in DPN patients were significantly positively correlated with Montreal cognitive assessment scores(r=0.479,P=0.001).Conclusion Abnormal FC between LSM and multiple brain regions,suggesting that DPN may have extensive effects on brain regions that maintain motion and motor control function in type 2 diabetes mellitus patients.

AIM:A strain was isolated and identified as the H3N8 subtype of the avian influenza virus from a sick chicken at a farm in Yangjiang,Guangdong Province,named A/chicken/Yangjiang/552/2023(abbreviated as YJ/552).The aim of this research is to determine its genetic evolution,biological properties and pathogenicity in hamsters.This study may provide a theoretical strategy for preventing and treating the H3N8 subtype avian influenza virus-induced epidemic.METHODS:A strain of H3N8 avian influenza virus from chickens was characterised by phylogenetic analy-sis,antigenic diversity,receptor-binding specificity,neuraminidase activity,replication,and transmission in hamsters and a systematic pathological analysis was conducted.RESULTS:This novel avian influenza virus was generated through complex recombination of Eurasian avian H3 genes,North American avian N8 genes and six internal genes of H9N2 sub-type AIV.The cleavage site of the outer protein,HA,was PEKQTR↓GLF,which is characteristic of the low pathogenic avian influenza virus.The HA gene of YJ/552 exhibited the highest nucleotide homology with A/China/ZMD-22-2/2022(H3N8)at 99.09%,while the NA gene showed the highest homology with A/chicken/Dongguan/879/2022(H3N8)at 99.01%.This strain preferentially binds to avian-type receptors and could bind to human-type receptors.This virus could effectively replicate in the trachea and lungs of inoculated and contact hamsters.CONCLUSION:YJ/552 is a recombi-nant H3N8 avian influenza virus replicated in the upper respiratory system and transmitted in hamsters.This study pro-vides data support for the early warning and prevention of H3 subtype avian influenza viruses.

Objective Piperazine derivatives are a group of emerging psychoactive substances with excitatory and hallucinogenic effects on the central nervous system.This study established a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)screening method for the detection of 40 piperazine compounds in urine.Methods A 200 μL urine sample(spiked with an internal standard at 1 ng/mL)was subjected to liquid-liquid extraction with ethyl acetate.After nitrogen evaporation,the residue was redissolved in 200 μL methanol and injected for analysis.Separation was performed on a Waters Acquity UPLC? HSS T3 column(100 mm × 2.1 mm,1.8 μm).The mobile phase consisted of(A)20 mmol/L ammonium acetate buffer containing 0.1％formic acid and 5％acetonitrile,and(B)acetonitrile.Gradient elution was applied,and detection was carried out in multiple reaction monitoring(MRM)mode.Quantification was achieved using an internal standard calibration curve.Results The 40 piperazine substances demonstrated good linearity within the range of 1-50 ng/mL,with correlation coefficients of 0.995-0.998.The extraction recovery ranged from 51.51％to 104.1％.Intra-day precision was below 5％,while inter-day precision ranged from 1.61％to 10.17％.Accuracy was between-7.84％and 8.77％.The limits of detection were 0.2-1 ng/mL,and the limit of quantification was 1 ng/mL.Conclusion The proposed method requires only a small sample volume,exhibits high sensitivity,selectivity,and stability,and offers short run times.It is suitable for the qualitative and quantitative determination of piperazine derivatives in urine in forensic toxicology practice.

Objective:To investigate the efficacy and safety of dupilumab in the treatment of elderly patients (≥ 60 years old) with atopic dermatitis (AD), with particular attention paid to rare adverse reactions.Methods:A single-center retrospective analysis was conducted on data collected from 281 elderly AD patients who received the standard regimen of dupilumab at the Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2020 to May 2024. Clinical characteristics such as gender, disease duration, skin lesion manifestations, and itch severity were analyzed. Changes in skin lesions and itch severity, as well as related adverse events were recorded during the follow-up period of 0 - 16 weeks. The efficacy and safety of dupilumab in the treatment of elderly AD patients were evaluated.Results:Among the 281 elderly AD patients, 214 were males (76.16%) and 67 were females (23.84%), with the age being 71.13 ± 7.91 years and the age at onset being 59.92 ± 15.72 years. The disease duration ( M[ IQR]) was 5.00 (13.00) years. After standard-regimen dupilumab treatment, the improvement rates of clinical outcome indicators SCORing Atopic Dermatitis (SCORAD) and pruritus numerical rating scale (NRS) scores gradually increased. At week 16, the improvement rates of SCORAD and NRS scores ( M[ IQR]) reached the maxima of 72.37% (23.89%) and 75.00% (29.72%), respectively. The overall incidence of adverse events was relatively low, with only 16 patients (6.05%) reporting adverse events. Common adverse reactions such as conjunctivitis (2 cases, 0.71%) and facial erythema (1 case, 0.36%) were mild and well-tolerated. Phenotype switching occurred in 10 cases (3.56%) . Conclusion:Dupilumab was an effective and safe treatment for elderly AD, but phenotype switching may occur.

Microvascular invasion is one of the critical factors influencing the prognosis of patients with hepatocellular carcinoma.Accurate preoperative prediction for its occurrence holds pivotal significance for the formulation of clinical individualized treatment decisions.Traditional diagnosis primarily relies on the evaluation of postoperative histopathological results,which exhibits a certain degree of lag.However,the emergence of radiomics features and biomarkers offers new insights for the preoperative prediction of mi-crovascular invasion.The preoperative prediction model based on radiomics and biomarkers is capable of precisely analyzing and efficiently predicting the occurrence risk of microvascular invasion from both macro-scopic imaging features and microscopic molecular levels,thereby providing multi-dimensional and precise scientific evidence for clinical decision-making.

Aim To investigates whether sphingosine-1-phosphate(S1P)regulates the expression of mitochon-drial calcium uniporter(MCU)via the sphingosine-1-phosphate receptor/proline-rich tyrosine kinase 2(S1PR/Pyk2)sig-naling pathway,thereby reducing oxidative stress-induced mitochondrial damage and inhibiting mitochondria-related apopto-sis.Methods Human umbilical vein endothelial cells(HUVEC)were subjected to oxidative damage using hydrogen peroxide(H2O2)as a model.Different concentrations of S1P were applied to the oxidative damaged HUVEC.Addi-tionally,the S1PR1 agonist SEW2871,the S1PR1 inhibitor W146,and the Pyk2 inhibitor PF-562271 were used to explore the specific mechanism of S1P action.Results S1P treatment significantly alleviated oxidative damage in HUVEC and was accompanied by an increase in S1PR1 expression(P<0.05),while S1PR3 expression remained unchanged.Mean-while,the expression levels of Pyk2 and MCU decreased(P<0.05).SEW2871 further reduced mitochondrial damage,whereas W146 exacerbated it(P<0.05).Furthermore,the application of the Pyk2 inhibitor PF-562271 also reduced H2O2-induced mitochondrial damage(P<0.05),further confirming the role of Pyk2 in this process.Conclusion S1P reduces H2O2-induced mitochondrial damage and inhibits mitochondria-related apoptosis in HUVEC by suppressing Pyk2 expression via S1PR1.