ObjectiveTo explore the value of a multimodal MRI-based radiomics nomogram for differentiating human epidermal growth factor receptor-2 （HER-2） negative breast cancer molecular subtypes.MethodsA retrospective analysis was conducted on 190 patients with HER-2 negative breast cancer who underwent multimodal MRI examination， and the patients were divided into two molecular subtype groups： a HER-2 low expression group （n=108） and a HER-2 zero expression group （n=82）. The cases were randomly stratified and sampled at a ratio of 7∶3 and divided into a training set of 133 cases and a testing set of 57 cases. The clinical and radiological features of the patients were collected， the radiomics features based on T2-weighted imaging （T2WI）， diffusion-weighted imaging （DWI）， and dynamic contrast-enhanced （DCE）-MRI were extracted， and the clinical-radiological model， unimodal radiomics model， multimodal radiomics model， and combined model were constructed respectively. Then the nomogram combined multimodal radiomics signature （radsocre） with clinical-radiological features was used to construct a visualized predictive model， and the area under the curve （AUC） was used to compare the effectiveness of different models in distinguishing HER-2 low expression and zero expression subtypes.ResultsA significant difference in radscore was demonstrated between the HER-2 low and HER-2 zero expression groups in both the training （P<0.000 1） and testing sets （P<0.01）. The AUC of the multimodal radiomics model in the training set and the testing set were 0.914 and 0.836， respectively， which was superior to any unimodal radiomics model. The nomogram demonstrated great diagnostic efficacy （AUC=0.930 in training set； AUC=0.865 in testing set）.ConclusionA multimodal MRI-based nomogram incorporating radsocre and clinical-radiological features can accurately distinguish the subtypes of HER-2 negative breast cancer.

ObjectiveTo investigate the effect of Zishen Huoxue Formula （ZSXHF） on molecular-targeted therapy-associated proteinuria in patients with primary liver cancer （PLC）， to assess the efficacy of ZSXHF in the treatment of molecular-targeted therapy-associated proteinuria， and to provide a basis for clinical medication. MethodsA retrospective cohort study was conducted among the PLC patients with molecular-targeted therapy-associated proteinuria who were diagnosed and treated in The Department of Hepatology of Chinese PLA General Hospital， from January 1， 2022 to July 1， 2025. With ZSXHF treatment as the exposure factor， the patients with a cumulative treatment duration of ≥9 weeks were enrolled as traditional Chinese medicine （TCM） group， while those without TCM treatment were enrolled as control group. Propensity score matching was performed for the two groups at a ratio of 1∶1 based on sex， age， 24-hour urinary protein， blood urea nitrogen， and serum creatinine. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. Univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for promoting the improvement of targeted-therapy-associated proteinuria. ResultsA total of 137 PLC patients with targeted-therapy-associated proteinuria were enrolled， with 34 patients in the TCM group and 103 in the control group. After follow-up for 6 months， the TCM group had a significant improvement in urinary protein grade compared with the control group （χ²=9.261， P=0.016）. There were 25 patients in each group after propensity score matching， and after follow-up for 6 months， there were significant differences between the two groups in urinary protein grade （χ²=15.689， P<0.001） and 24-hour urinary protein （Z=-3.075， P=0.002）. After cumulative treatment with ZSXHF for ≥9 weeks， the TCM group had a significantly greater change in 24-hour urinary protein from baseline compared with the control group （t=-2.514， P=0.016）， while there were no significant differences in the changes in liver and renal function after ZSXHF intervention between the two groups （all P>0.05）. The multivariate Logistic regression analysis showed that ZSXHF treatment （odds ratio=2.901， 95% confidence interval： 1.135 — 7.417， P=0.026） was an independent influencing factor for improvement in molecular-targeted therapy-associated proteinuria. ConclusionZSHXF can effectively alleviate molecular-targeted therapy-associated proteinuria in PLC patients with a favorable safety profile， which provides a new reference for TCM prevention and treatment of molecular-targeted therapy-associated adverse reactions in PLC patients.

ObjectiveTo evaluate the clinical efficacy of Fuzheng Huaji Formula （扶正化积方） for chronic hepatitis B to reduce the incidence of liver cirrhosis and hepatocellular carcinoma. MethodsA retrospective cohort study was conducted， collecting medical records of 118 patients with chronic hepatitis B and 234 patients with hepatitis B-related cirrhosis who visited the hospital between January 1， 2014， and December 31， 2018. The use of Fuzheng Huaji Formula was designated as the exposure factor. Patients receiving antiviral treatment for hepatitis B without concurrent Fuzheng Huaji Formula therapy were included in the western medicine group， while those receiving antiviral treatment combined with Fuzheng Huaji Formula for a cumulative treatment lasting longer than 3 months were included in the combined treatment group. The follow-up observation period was five years. Kaplan-Meier survival analysis was used to assess the cumulative incidence of cirrhosis in patients with chronic hepatitis B and the cumulative incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis. Univariate and multivariate Cox regression analyses were employed to examine the factors influencing the occurrence of cirrhosis and hepatocellular carcinoma. ResultsAmong patients with chronic hepatitis B， there were 55 cases in the combined treatment group and 63 cases in the western medicine group； among patients with hepatitis B-related cirrhosis， there were 110 cases in the combined treatment group and 124 cases in the western medicine group. Five-year follow-up outcomes for chronic hepatitis B patients showed that the cumulative incidence of cirrhosis was 5.45% （3/55） in the combined treatment group and 17.46% （11/63） in the western medicine group， with a statistically significant difference between groups （Z = 2.003， P = 0.045）. Five-year follow-up outcomes for hepatitis B-related cirrhosis patients showed that the cumulative incidence of hepatocellular carcinoma was 8.18% （9/110） in the combined treatment group and 22.58% （28/124） in the western medicine group， also showing a statistically significant difference （Z = 3.007， P = 0.003）. Univariate and multivariate Cox regression analyses indicated that treatment with Fuzheng Huaji Formula is an independent protective factor in preventing the progression of chronic hepatitis B to cirrhosis and the progression of hepatitis B-related cirrhosis to hepatocellular carcinoma （P＜0.05）. ConclusionCombining Fuzheng Huaji Formula with antiviral therapy for hepatitis B can effectively intervene in the disease progression of chronic hepatitis B， reducing the incidence of cirrhosis and hepatocellular carcinoma.

Objective To observe changes of white matter function in adolescent smoker(AS)with resting-state functional MRI(rs-fMRI)fractional amplitude of low-frequency fluctuation(fALFF)technique.Methods Forty-five adolescents(AS group)and 45 control subjects(control group)were prospectively enrolled,and brain rs-fMRI were acquired.Brain regions with fALFF being different between groups were observed,and the correlations with clinical indicators were analyzed.Results Compared with that in control group,fALFF of the right superior longitudinal fasciculus significantly elevated in AS group(FDR correct Q＜0.05),in which the peak of the cluster was positively correlated with score of Fagerstr?m test for nicotine dependence(FTND)(r=0.294,P=0.049).Conclusion White matter function changed in AS,presenting as significantly increased fALFF in right superior longitudinal fasciculus,which was positively correlated with nicotine dependence.

Objective To explore the diagnostic value of amide proton transfer weighted imaging(APTWI)in conjunction with prostate-specific antigen density(PSAD)for detecting clinically significant prostate cancer(csPCa)within prostate imaging reporting and data system(PI-RADS)v2.13-5 grade lesions.Methods A retrospective analysis was conducted on the clinical and imaging data of 88 patients diagnosed with PI-RADS 3-5 grade prostate lesions.There were 59 patients with prostate cancer(PCa)and 29 with benign prostate lesion(BPL).The PCa group was divided into csPCa group(44 cases)and clinically insignificant prostate cancer(ciPCa)group(15 cases)according to Gleason score(GS).Spearman rank correlation analysis was used to analyze the correlation between APTWI-related parameters and GS in PCa.Comparative analyses were conducted to identify statistical discrepancies in APTWI and prostate-specific antigen(PSA)-related parameters across various groups.Subsequently,both solitary and combined diagnostic models were developed,and the receiver operating characteristic(ROC)curve were utilized to evaluate the diagnostic efficacy.Results APTmax and APTmean were moderately positively correlated with GS(r=0.683,r=0.705,respectively),and APTmin was weakly positively correlated with GS(r=0.547).APTWI and PSA-related parameters were significantly higher in the PCa group than in the BPL group,and APTmin had the highest efficacy in diagnosing PCa[area under the curve(AUC)=0.855].APTWI and PSA-related parameters differed among the BPL,ciPCa and csPCa groups(P＜0.05).Among the groups,statistically significant differences were observed in each parameter of APTWI and PSA-related indices between the BPL group and the csPCa group,as well as between the ciPCa group and the csPCa group(P＜0.05).In contrast,only APTmin and PSAD exhibited significant differ-ences between the BPL group and the ciPCa group(P＜0.05).The results of the combined diagnosis showed that APTmin+PSAD had the highest diagnostic efficacy for diagnosing PCa(AUC=0.899),and APTmean+PSAD had the highest diagnostic efficacy for diagnosing csPCa(AUC=0.838).Conclusion In PI-RADS 3-5 grade prostate lesions,APTWI and PSA-related parameters are statisti-cally different in the BPL,ciPCa,and csPCa groups.Notably,the combination of APTmean and PSAD exhibit the highest diagnostic efficacy for csPCa.

Cholangiocarcinoma,as a malignant tumor with strong invasiveness and poor prognosis,has a complex metastasis mechanism,and urgently needs in-depth research.Circulating tumor cells(CTC),as the key cell type for tumor cells to shed from the primary site and enter the bloodstream,have significant research significance.In recent years,studies have found that the invasive pseudopodia of CTC play a significant role in the migration and invasion of tumor cells.Among them,in terms of signal transduction pathways,the Rho family GTPases(RhoA,Rac1,Cdc42)work in coordination to regulate the contractility of the pseudofoot,the branching polymerization and orientation of actin,and the phosphoinositide3-kinase/protein kinase B(PI3K/AKT)pathway promotes the assembly of actin and cross-communicates with the Rho family by activating AKT.At the molecular mechanism level,long non-coding RNAs regulate the expression of pseudopolypod-related genes by adsorbing miRNAs and other means.Matrix metalloproteinase(MMP)degrades the extracellular matrix(ECM)to form an invasion positive feedback.In terms of the microenvironment,cancer-associated fibroblast(CAF)and the cytokines such as transforming growth factor-β(TGF-β)secreted by macrophages,epidermal growth factor(EGF),and interleukin-6(IL-6)activate pseudopodia to form signal transduction pathways.ECM hardness and fiber arrangement affect the extension direction of pseudopodia through mechanical force conduction.This article conducted a comprehensive analysis of the biological characteristics of CTC,the formation mechanism of invasive pseudopodia in cholangiocarcinoma,the metastatic features of cholangiocarcinoma cells and their clinical significance,as well as the role of CTC in the metastatic process of cholangiocarcinoma,in order to summarize the existing research results,explore potential therapeutic targets and future research directions,and provide new ideas for the clinical treatment of cholangiocarcinoma.

Cholangiocarcinoma,as a malignant tumor with strong invasiveness and poor prognosis,has a complex metastasis mechanism,and urgently needs in-depth research.Circulating tumor cells(CTC),as the key cell type for tumor cells to shed from the primary site and enter the bloodstream,have significant research significance.In recent years,studies have found that the invasive pseudopodia of CTC play a significant role in the migration and invasion of tumor cells.Among them,in terms of signal transduction pathways,the Rho family GTPases(RhoA,Rac1,Cdc42)work in coordination to regulate the contractility of the pseudofoot,the branching polymerization and orientation of actin,and the phosphoinositide3-kinase/protein kinase B(PI3K/AKT)pathway promotes the assembly of actin and cross-communicates with the Rho family by activating AKT.At the molecular mechanism level,long non-coding RNAs regulate the expression of pseudopolypod-related genes by adsorbing miRNAs and other means.Matrix metalloproteinase(MMP)degrades the extracellular matrix(ECM)to form an invasion positive feedback.In terms of the microenvironment,cancer-associated fibroblast(CAF)and the cytokines such as transforming growth factor-β(TGF-β)secreted by macrophages,epidermal growth factor(EGF),and interleukin-6(IL-6)activate pseudopodia to form signal transduction pathways.ECM hardness and fiber arrangement affect the extension direction of pseudopodia through mechanical force conduction.This article conducted a comprehensive analysis of the biological characteristics of CTC,the formation mechanism of invasive pseudopodia in cholangiocarcinoma,the metastatic features of cholangiocarcinoma cells and their clinical significance,as well as the role of CTC in the metastatic process of cholangiocarcinoma,in order to summarize the existing research results,explore potential therapeutic targets and future research directions,and provide new ideas for the clinical treatment of cholangiocarcinoma.

Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Primary liver cancer is one of the most common malignant tumors of the digestive system， and the “inflammation-to-cancer transformation” （ICT） of chronic hepatitis is the core pathological process of the progression of chronic hepatitis to liver cancer. Persistent and uncontrolled liver inflammation in patients with chronic hepatitis often leads to repeated liver tissue damage and repair， which gradually develops into liver fibrosis and cirrhosis， eventually leading to malignant transformation through the mechanisms such as gene mutation and microenvironment imbalance. ICT in chronic hepatitis is the key link between chronic hepatitis and liver cancer， and its dynamic evolution involves various pathogenic factors such as dampness， heat， deficiency， toxin， and stasis； among which damp-heat and vital energy deficiency are the initiating factors for ICT of chronic hepatitis， while intermingled stasis and toxin are the key pathological products that promote malignant transformation. Based on the concept of preventive treatment， traditional Chinese medicine can effectively delay and even block the ICT of chronic hepatitis by regulating inflammation， metabolism， and abnormal cell proliferation through multiple targets， which provides important strategies and research directions for the prevention and treatment of liver cancer.