Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Diabetic kidney disease （DKD） stands as one of the most prevalent microvascular complications of diabetes，noted for its concealed onset and tendency to evolve into end-stage renal disease，profoundly impacting patients' life expectancy and quality of life. Epithelial-to-mesenchymal transition （EMT） is a central pathological process in the initiation and progression of DKD，facilitating disease advancement and renal fibrosis，thus representing a crucial focus of research into the pathological mechanisms of DKD. EMT is driven by the abnormal activation of signaling pathways，including transforming growth factor-β （TGF-β）/Smad，secreted glycoprotein/β-catenin，Notch，tumor necrosis factor-α （TNF-α）/nuclear factor-κB （NF-κB），and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR），leading to renal cellular injury and subsequently accelerating renal fibrosis and the progression of DKD. Traditional Chinese medicine （TCM），characterized by its multi-target and multi-pathway therapeutic approach，demonstrates unique advantages in addressing DKD and EMT. Recent research has shown that active ingredients in TCM，including glycosides，flavonoids，and polyphenols，as well as TCM formulas，can precisely target these relevant signaling pathways，effectively inhibiting cellular injury in DKD and intervening in the EMT process. These findings not only underscore the potential of TCM monomers and formulas in treating DKD and EMT but also pave new directions for research in this field within TCM. This paper systematically reviewed the signaling pathways associated with EMT and provided an in-depth analysis of the research achievements and underlying mechanisms of TCM monomers and formulas in treating DKD and intervening in EMT，aiming to offer new insights and directions for TCM in the treatment of DKD and research on EMT，thereby further promoting the modernization and development of TCM.

Objective To observe the impact of sublingual nitroglycerin(NTG)on imaging quality of non-contrast MR coronary angiography(NMRCA).Methods Thirty patients with suspected coronary heart disease(CHD)who would undergo coronary angiography(CAG)examination were prospectively collected.NMRCA images were acquired before and after sublingual NTG.Clinical meaningful stenosis was defined as CAG showed luminal stenosis ≥50％.Then imaging quality scores,diameters and display length of coronary arteries,as well as the impact of NTG on diagnostic performances of NMRCA for coronary artery stenosis were compared between images before and after administration of NTG.Results After administration of NTG,image quality of left main(LM)-left anterior descending artery(LAD)and left circumflex artery(LCX),as well as the proximal,mid and distal segments of LAD and distal segment of LCX significantly improved(all P＜0.05).No significant difference of visible coronary artery length was noticed before and after administration of NTG(all P＞0.05).After administration of NTG,diameter of right coronary artery(RCA),LM-LAD and LCX increased(all P＜0.05),with dilation rate of 16.23％(13.57％,19.17％),17.52％(12.69％,21.11％)and 14.30％(7.62％,23.22％),respectively,while the sensitivity,specificity,accuracy and negative predictive value of NMRCA for diagnosing coronary artery stenosis improved(all P＜0.05).Conclusion Sublingual NTG could improve imaging quality of NMRCA and increase its efficacy for diagnosing coronary artery stenosis.

Objective To detect the expression of cytochrome c oxidase assembly factor 6(COA6)in breast cancer,study its clinical significance,and analyze the effect of COA6 on immune infiltration in breast cancer.Methods Differential genes were screened by the whole transcriptome sequencing and the expression of COA6 was explored with TCGA(The Cancer Genome Atlas Program)database.The tissues of 125 breast cancer and adjacent tissues were stained by immunohistochemistry to detect COA6 protein expression and analyze the correlation with clinical features.The COA6 mRNA and protein expression in breast cancer cells and tissues were determined by qRT-PCR and Western blot,respectively.The TIMER(Tumor Immune Estimation Resource)database was used to analyze the correlation between high COA6 gene expression and immune cell infiltration.Results The positive expression rate of COA6 in breast cancer tissues was 88％(110/125),which was higher than that of paracarinoma tissues(7.2％,9/125)(P＜0.05)and was positively correlated with tumor size and histological grade.In fresh breast cancer tissues,COA6 protein expression was significantly higher than that in adjacent tissues.Both COA6 mRNA and protein expression were significantly increased in the breast cancer cell lines.COA6 was positively cor-related with the infiltration of helper T cells,NK cells,CD8+T cells,M1 type macrophages,regulatory T cells,dendritic cells,and memory CD4+T cells in the tumor microenvironment.Conclusions The expression level of COA6 is increased in breast cancer and is positively correlated with tumor immune infiltration,which provides a po-tential therapeutic target for breast cancer treatment.

OBJECTIVE To establish a visualized loop-mediated isothermal amplification(LAMP)for rapid detec-tion of Klebsiella pneumoniae and evaluate the sensitivity and specificity of the detection method.METHODS To-tally4 specific LAMP primers were designed by targeting to rcsA gene of the K.pneumoniae.The reaction condi-tions(temperature,time)and the parameters of the reaction system were optimized,the reaction was made visu-alized by using chimeric fluorescent dye SYBR Green Ⅰ.The optimal reactions conditions and reaction systems were determined based on the results of visualization and agarose gel electrophoresis.The optimized conditions and systems were used to test the sensitivity by diluting DNA template on a 10-fold gradient,meanwhile,the specifici-ty of the method was evaluated by detecting K.pneumoniae and other ten species of common bacteria and fungi.RESULTS The optimal reaction temperature was 63 ℃ after the optimization,with the reaction time 35 min;the concentration of buffer solution in the reaction system was determined as 0.8×,with the concentration of magne-sium ion 8 mmol/L,the concentration of dNTPs 1.4 mmol/L,the ratio of internal to external primers 6∶1,the concentration of Bst DNA polymerase 0.32 U/μl,the concentration of betaine 0.75 mmol/L.For the test of sensi-tivity,the method could detect the template with the concentration of 1.5 ng/μl.For the test of specificity,only the detection of K.pneumoniae could display positive visualized result and positive electrophoretic band.CONCLUSIONS The visualized LAMP with high specificity and sensitivity for rapid detection of K.pneumoniae is successfully established,facilitating the observation of the detection result without the use of precise instruments.It is suitable for the detection in grass-root laboratories after successful preliminary application in clinical detection.

OBJECTIVE To establish a visualized loop-mediated isothermal amplification(LAMP)for rapid detec-tion of Klebsiella pneumoniae and evaluate the sensitivity and specificity of the detection method.METHODS To-tally4 specific LAMP primers were designed by targeting to rcsA gene of the K.pneumoniae.The reaction condi-tions(temperature,time)and the parameters of the reaction system were optimized,the reaction was made visu-alized by using chimeric fluorescent dye SYBR Green Ⅰ.The optimal reactions conditions and reaction systems were determined based on the results of visualization and agarose gel electrophoresis.The optimized conditions and systems were used to test the sensitivity by diluting DNA template on a 10-fold gradient,meanwhile,the specifici-ty of the method was evaluated by detecting K.pneumoniae and other ten species of common bacteria and fungi.RESULTS The optimal reaction temperature was 63 ℃ after the optimization,with the reaction time 35 min;the concentration of buffer solution in the reaction system was determined as 0.8×,with the concentration of magne-sium ion 8 mmol/L,the concentration of dNTPs 1.4 mmol/L,the ratio of internal to external primers 6∶1,the concentration of Bst DNA polymerase 0.32 U/μl,the concentration of betaine 0.75 mmol/L.For the test of sensi-tivity,the method could detect the template with the concentration of 1.5 ng/μl.For the test of specificity,only the detection of K.pneumoniae could display positive visualized result and positive electrophoretic band.CONCLUSIONS The visualized LAMP with high specificity and sensitivity for rapid detection of K.pneumoniae is successfully established,facilitating the observation of the detection result without the use of precise instruments.It is suitable for the detection in grass-root laboratories after successful preliminary application in clinical detection.

Objective To observe the impact of sublingual nitroglycerin(NTG)on imaging quality of non-contrast MR coronary angiography(NMRCA).Methods Thirty patients with suspected coronary heart disease(CHD)who would undergo coronary angiography(CAG)examination were prospectively collected.NMRCA images were acquired before and after sublingual NTG.Clinical meaningful stenosis was defined as CAG showed luminal stenosis ≥50％.Then imaging quality scores,diameters and display length of coronary arteries,as well as the impact of NTG on diagnostic performances of NMRCA for coronary artery stenosis were compared between images before and after administration of NTG.Results After administration of NTG,image quality of left main(LM)-left anterior descending artery(LAD)and left circumflex artery(LCX),as well as the proximal,mid and distal segments of LAD and distal segment of LCX significantly improved(all P＜0.05).No significant difference of visible coronary artery length was noticed before and after administration of NTG(all P＞0.05).After administration of NTG,diameter of right coronary artery(RCA),LM-LAD and LCX increased(all P＜0.05),with dilation rate of 16.23％(13.57％,19.17％),17.52％(12.69％,21.11％)and 14.30％(7.62％,23.22％),respectively,while the sensitivity,specificity,accuracy and negative predictive value of NMRCA for diagnosing coronary artery stenosis improved(all P＜0.05).Conclusion Sublingual NTG could improve imaging quality of NMRCA and increase its efficacy for diagnosing coronary artery stenosis.

Objective:To explore the optimal acceleration factor and feasibility of the compressed SENSE (CS) technique in non-contrast MR coronary angiography (NMRCA) for clinical practice.Methods:The image data of completed coronary CTA and 3.0 T NMRCA sequence in 31 patients with suspected coronary heart disease were prospectively recruited at Fuyang People′s Hospital from August 2021 to November 2021. NMRCA sequences included conventional SENSE2 sequence and CS sequences with acceleration factors of 4, 5, and 6, respectively. The subjective scores of image quality and the objective scores, the contrast ratios between assessed coronaries and myocardium (CMCR) were compared among the 4 groups using the Friedman and Wilcoxon rank sum test.Results:Compared with the conventional SENSE2 [(343±46)s], the scan time of CS4 (269±36), CS5 (214±29) and CS6 (178±26) s were shortened by 21.5%, 37.5% and 48.0%, respectively. There was a good consistency between the subjective scores of the four groups (Kappa=0.769, 95% Cl 0.738-0.800). There was no significant difference in subjective score and CMCR value between CS4 and SENSE2 ( P>0.05). The coronary artery segments of CS5 and CS6 were significantly different from SENSE2 group ( P<0.05). Conclusions:For 3.0 T NMRCA, CS technology shows high feasibility. The CS4 can reduce imaging time while ensuring high-quality coronary arterial images, which has a well-established clinical application value for NMRCA.

Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention, which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6 (Ce6), hydrophilic chemotherapeutic drug berberrubine (BBR) and matrix metalloproteinase-2 (MMP-2) response peptide (PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6 (BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine (PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively, we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect.

Objective:To study the effect of Sanjie Xiaoliu Recipe on transplanted tumors in breast cancer mice through in vivo experiments, in order to explore the efficacy and mechanism of Sanjie Xiaoliu Recipe on breast cancer patients. Methods:45 BaL B/c female mice were selected to establish the transplanted tumor model of breast cancer. All the transplanted tumor models of breast cancer mice were randomly divided into five groups: the control group (intragastric administration of normal saline), the low, medium and high dose group of Sanjie Xiaoliu Recipe (intragastric administration of different doses of Sanjie Xiaoliu Decoction), and the paclitaxel group (intraperitoneal injection of paclitaxel). After 24 days of continuous administration, the diet and activities of mice were observed; the body weight, weight and volume changes of transplanted tumor mice were recorded, and the tumor inhibition rate was calculated. Western blot was used to detect the expression of epithelial mesenchymal transformation related proteins (E-cadherin, N-cadherin, Vimentin) in the transplanted tumor tissues of mice in each group.Results:(1) The food intake and activity status of mice treated with Sanjie Xiaoliu Recipe were less affected by the transplanted tumor of breast cancer. (2) The volume and weight of transplanted tumor in the treat groups were smaller than those in the control group (all P<0.01), and the volume of transplanted tumor in the middle dose group of Sanjie Xiaoliu Recipe was smaller than that in the low dose group ( P<0.05). The tumor inhibition rates among the treatment groups were: Sanjie Xiaoliu Recipe medium dose group 52.4%, paclitaxel group 40.3%, Sanjie Xiaoliu Recipe low dose group 39.5%, Sanjie Xiaoliu Recipe high dose group 34.1%. (3) The results of Western blot showed that the expression level of E-cadherin in the transplanted tumor tissue of the treat groups was higher than that in the control group, and the expression levels of N-cadherin and Vimentin were lower than that in the control group, with statistically significant difference (all P<0.05). Conclusions:The Sanjie Xiaoliu Recipe can improve the weakness and reduced consumption of breast cancer mice, which can inhibit the tumor mass growth in mice to a certain extent. Its mechanism may be that Sanjie Xiaoliu Recipe can inhibit the epithelial mesenchymal transformation of breast cancer and the invasion and metastasis of breast cancer.