The mechanism and targeted intervention of the HIF-1 pathway in improving atherosclerotic heart's sensitivity to ischemic postconditioning.

BACKGROUND: IPoC possesses a preventive effect against IR injury in healthy myocardium, but IPoC's protective effect on atherosclerotic myocardium is controversial. The current investigation aims to determine whether IPoC remains protective in atherosclerotic myocardium subjected to ischemia-reperfusion (IR) injury; to explore the specific mechanisms by which IPoC exerts cardioprotection; to explore whether HIF-1 upregulation combined with IPoC could further the provide cardioprotection; and to gaze at the specific mechanism whereby combined treatment expert the cardioprotection. METHODS: ApoE-/- mice fed with a high-fat diet (HFD) were used to develop a model of atherosclerosis. The myocardial IR model was induced by occlusion of the left anterior descending (LAD) artery for 45 min, followed by reperfusion for 120 min. The protection of IPoC in both healthy and atherosclerotic myocardium was evaluated by measuring oxidative stress, apoptosis, infarct size, pathology, mitochondrial dysfunction and morphology of myocardium. The specific mechanism by which IPoC exerts cardioprotection in healthy and atherosclerotic myocardium was observed by measuring the expression of proteins involved in HIF-1, APMK and RISK pathways. The effect of HIF-1α overexpression on the cardioprotection by IPoC was observed by intravenous AAV9 -HIF-1α injection. RESULTS: In healthy ischemic myocardium, IPoC exerted myocardial protective effects (antioxidant, anti-apoptosis, and improved mitochondrial function) through the activation of HIF-1, AMPK and RISK pathways. In atherosclerotic ischemic myocardium, IPoC exerted cardioprotection only through the activation of HIF-1 pathway; however, HIF-1 overexpression combined IPoC restored the activation of AMPK and RISK pathways, thereby further alleviating the myocardial IR injury. CONCLUSIONS: In the atherosclerotic state, the HIF-1 pathway is the intrinsic mechanism by which IPoC exerts cardioprotective effects. The combination of HIF-1 upregulation and IPoC has a significant effect in reducing myocardial injury, which is worth being promoted and advocated. In addition, HIF-1-AMPK and HIF-1-RISK may be two endogenous cardioprotective signalling pathways with great value, which deserve to be thoroughly investigated in the future.

An Interpretable Multitask Framework BiLAT Enables Accurate Prediction of Cyclin-Dependent Protein Kinase Inhibitors.

The cyclin-dependent protein kinases (CDKs) are protein-serine/threonine kinases with crucial effects on the regulation of cell cycle and transcription. CDKs can be a hallmark of cancer since their excessive expression could lead to impaired cell proliferation. However, the selectivity profile of most developed CDK inhibitors is not enough, which have hindered the therapeutic use of CDK inhibitors. In this study, we propose a multitask deep learning framework called BiLAT based on SMILES representation for the prediction of the inhibitory activity of molecules on eight CDK subtypes (CDK1, 2, 4-9). The framework is mainly composed of an improved bidirectional long short-term memory module BiLSTM and the encode layer of the Transformer framework. Additionally, the data enhancement method of SMILES enumeration is applied to improve the performance of the model. Compared with baseline predictive models based on three conventional machine learning methods and two multitask deep learning algorithms, BiLAT achieves the best performance with the highest average AUC, ACC, F1-score, and MCC values of 0.938, 0.894, 0.911, and 0.715 for the test set. Moreover, we constructed a targeted external data set CDK-Dec for the CDK family, which mainly contains bait values screened by 3D similarity with active compounds. This dataset was utilized in the subsequent evaluation of our model. It is worth mentioning that the BiLAT model is interpretable and can be used by chemists to design and synthesize compounds with improved activity. To further verify the generalization ability of the multitask BiLAT model, we also conducted another evaluation on three public datasets (Tox21, ClinTox, and SIDER). Compared with several currently popular models, BiLAT shows the best performance on two datasets. These results indicate that BiLAT is an effective tool for accelerating drug discovery.

FSDscore: An Effective Target-focused Scoring Criterion for Virtual Screening.

Improving screening efficiency is one of the most challenging tasks of virtual screening (VS). In this work, we propose an effective target-focused scoring criterion for VS and apply it to the screening of a specific target scaffold replacement library constructed by enumeration of suitable substitution fragments and R-groups of known ligands. This criterion is based on both ligand- and structure-based scoring methods, which includes feature maps, 3D shape similarity, and the pairwise distance information between proteins and ligands (FSDscore). It is precisely due to the hybrid advantages of ligand- and structure-based approaches that FSDscore performs far better on the validation dataset than other scoring methods. We apply FSDscore to the VS of different kinase targets, MERTK (Mer tyrosine kinase) and ABL1 (tyrosine-protein kinase ABL1) in order to avoid occasionality. Finally, a VS case study shows the potential and effectiveness of our scoring criterion in drug discovery and molecular dynamics simulation further verifies its powerful ability.

Research on Circuit Breaker Operating Mechanism Fault Diagnosis Method Combining Global-Local Feature Extraction and KELM.

In response to the lack of generality in feature extraction using modal decomposition methods and the susceptibility of diagnostic performance to parameter selection in traditional mechanical fault diagnosis of high-voltage circuit breaker operating mechanisms, this paper proposes a Global-Local feature extraction method based on Generalized S-Transform (S-Translate) combined with Gray Level Co-Occurrence Matrix (GLCM) and complemented by Maximum Relevance and Minimum Redundancy (mRMR) feature selection. The GL (Global-Local)-mRMR-KELM fault diagnosis model is proposed, which employs the Kernel Extreme Learning Machine (KELM). In this model, the original time-frequency domain features and the time-frequency features of the Generalized S-Transform matrix of vibration signals under different states of the circuit breaker are first extracted as global features. Then, the GLCM is obtained to extract texture features as local features. Finally, the mRMR and KELM are comprehensively applied to perform feature selection and classification on the dataset, thereby accomplishing the fault diagnosis of the circuit breaker's operating mechanism. In this study, the 72.5 kV SF6 circuit breaker operating mechanism is taken as the research object, and three types of mechanical faults are simulated to obtain a vibration signal. Experimental results verify the effectiveness of the proposed GL-mRMR-KELM model, achieving a diagnostic accuracy of 96%. This research provides a feasible approach for the fault diagnosis of circuit breaker operating mechanisms.

KID: A Kinase-Focused Interaction Database and Its Application in the Construction of Kinase-Focused Molecule Databases.

Protein kinases are important drug targets for the treatment of several diseases. The interaction between kinases and ligands is vital in the process of small-molecule kinase inhibitor (SMKI) design. In this study, we propose a method to extract fragments and amino acid residues from crystal structures for kinase-ligand interactions. In addition, core fragments that interact with the important hinge region of kinases were extracted along with their decorations. Based on the superimposed structural data of kinases from the kinase-ligand interaction fingerprint and structure database, we obtained two libraries, namely, a hinge-unfocused fragment-amino acid pair library (FAP Lib) that contains 6672 pairs of fragments and corresponding amino-acids, and a hinge-focused hinge binder library (HB Lib) of 3560 pairs of hinge-binding scaffolds with their corresponding decorations. These two libraries constitute a kinase-focused interaction database (KID). In depth analysis was conducted on KID to explore important characteristics of fragments in the design of SMKIs. With KID, we built two kinase-focused molecule databases, one called Recomb_DB, which contains 1,72,346 molecules generated through fragment recombination based on the FAP Lib, and another called RsdHB_DB, which contains 93,030 molecules generated based on our HB Lib using molecular generation methods. Compared with five databases both commercial and non-commercial, these two databases both ranked top 3 in scaffold diversity, top 4 in molecule fingerprint diversity, and are more focused on the chemical space of kinase inhibitors. Hence, KID presents a useful addition to existing databases for the exploration of novel SMKIs.

Household Groups' Land Use Decisions Investigation Based on Perspective of Livelihood Heterogeneity in Sichuan Province, China.

Land use decision-making is a vital livelihood strategy associated with the rational collocation of livelihood asset endowments by rural households. Based on the perspective of livelihood heterogeneity, this paper collected the data from 540 farm households in 27 villages in three Sichuan Province counties to identify the land use decision-making characteristics of the household groups. A land use decision-making framework (LUDF) based on the sustainable livelihood framework (SLF) was established and dynamic and dual indicators were developed to divide the sample into six household groups. The household livelihood capital, livelihood strategies, and livelihood diversity were then analyzed at the regional and household group level, and the land use decisions of these household groups were explored, from which the following was found. (1) Overall livelihood capital in the study area was low, and except for human assets, there were few other assets, with households in the survey areas being more inclined to engage in non-farming livelihood activities; however, households in Nanjiang and Qionglai had greater livelihood activities choices than Luxian. (2) The LL-type household was the chief household group; the household group distribution in Qionglai was well-proportioned but uneven in Nanjiang and Luxian; and the HL-type, ML-type, and LL-type household livelihood strategy choices were polarized. (3) Most households were involved in land self-cultivation, followed by land transfer-in, land transfer-out, and land abandonment households. Specifically, there were more households that cultivated fragmented landholdings than specialized households with large-scale landholdings, the land transfer rate was relatively low, the transfer-in land area was far greater than the transfer-out land areas, and a small number of households that had abandoned their land were still involved in agricultural production. (4) There were obvious discordant human-land relationships and inefficient land uses in the study area. Based on these findings, relevant policy recommendations are given to improve farm household livelihood capital, optimize livelihood strategies, and assist in land use decision-making.

Research on the Influence of Informal Employment on Residents' Happiness in China: Empirical Analysis Based on CLDS Data.

The influence of informal employment on residents' happiness has gained wide attention around the world. However, few studies focus on this topic in China. Using the 2016 wave of the China Labor Force Dynamics Survey (CLDS) data, we examined the effect of informal employment and its mechanisms on residents' happiness in China. Our study shows there is a significant negative correlation between informal employment and residents' happiness in China. Moreover, the correlation between informal employment and residents' happiness is stronger for residents who are female, migrating, and with a rural household registration. In addition, we investigated possible mechanisms of the effect, including individual income, social respect, unemployment expectations, and social security, and found that informal employment reduces the happiness of residents by widening the gap in unemployment probability and social insurance level among residents.

Age, male sex, higher posterior tibial slope, deep sulcus sign, bone bruises on the lateral femoral condyle, and concomitant medial meniscal tears are risk factors for lateral meniscal posterior root tears: a systematic review and meta-analysis.

PURPOSE: Lateral meniscus posterior root tears (LMPRTs) are commonly found in patients with anterior cruciate ligament (ACL) injuries. However, risk factors for LMPRTs are not well known. This study was designed to systematically review the available evidence regarding risk factors associated with LMPRTs. METHODS: The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched for papers containing the key words "lateral meniscus posterior root tears", "LMPRTs" and "risk factor". Inclusion screening, data extraction, and quality assessment of the included articles were conducted independently by two authors. Statistical analysis was conducted to determine risk factors for LMPRTs. RESULT: Seventeen studies with a total sample size of 6, 589 patients were identified. The pooled prevalence of LMPRTs was 9.6% (range, 5.1-33.8%) for ACL injury. Significant risk factors included a patient age of < 30 [OR = 1.4, 95% CI (1.07, 1.84), p = 0.01], male sex [OR = 1.50, 95% CI (1.24,1.81), p = 0.01], higher body mass index (BMI) [MD = 0.45, 95% CI (0.13, 0.76), p < 0.01], higher lateral posterior tibial slope (LPTS) [MD = 2.22, 95% CI (1.37, 3.07), p < 0.01], deep sulcus sign [OR = 5.76, 95% CI (1.35, 24.52), p < 0.01] and bone bruises on lateral femoral condyle [OR = 4.88, 95% CI (1.27, 18.77), p < 0.01], lateral meniscal extrusion > 1 mm [OR = 5.56, 95% CI (1.52, 20.29), p < 0.01] and > 3 mm [OR = 12.91 95% CI (1.28, 130.01), p < 0.01], medial meniscal tears [OR = 1.40, 95% CI (1.12, 1.75), p < 0.01], and medial ramp lesions [OR = 2.29, 95% CI (1.35, 3.89), p < 0.01]. CONCLUSION: Age below 30, male, higher BMI, higher LPTS, deep sulcus sign, bone bruises on lateral femoral condyle, lateral meniscal extrusion, medial meniscal tear, and medial ramp lesion are risk factors for LMPRTs. LEVEL OF EVIDENCE: Level IV.

Drug repositioning: Progress and challenges in drug discovery for various diseases.

Compared with traditional de novo drug discovery, drug repurposing has become an attractive drug discovery strategy due to its low-cost and high efficiency. Through a comprehensive analysis of the candidates that have been identified with drug repositioning potentials, it is found that although some drugs do not show obvious advantages in the original indications, they may exert more obvious effects in other diseases. In addition, some drugs have a synergistic effect to exert better clinical efficacy if used in combination. Particularly, it has been confirmed that drug repositioning has benefits and values on the current public health emergency such as the COVID-19 pandemic, which proved the great potential of drug repositioning. In this review, we systematically reviewed a series of representative drugs that have been repositioned for different diseases and illustrated successful cases in each disease. Especially, the mechanism of action for the representative drugs in new indications were explicitly explored for each disease, we hope this review can provide important insights for follow-up research.

Effective Reaction-Based De Novo Strategy for Kinase Targets: A Case Study on MERTK Inhibitors.

Reaction-based de novo design is the computational generation of novel molecular structures by linking building blocks using reaction vectors derived from chemistry knowledge. In this work, we first adopted a recurrent neural network (RNN) model to generate three groups of building blocks with different functional groups and then constructed an in silico target-focused combinatorial library based on chemical reaction rules. Mer tyrosine kinase (MERTK) was used as a study case. Combined with a scaffold enrichment analysis, 15 novel MERTK inhibitors covering four scaffolds were achieved. Among them, compound 5a obtained an IC50 value of 53.4 nM against MERTK without any further optimization. The efficiency of hit identification could be significantly improved by shrinking the compound library with the fragment iterative optimization strategy and enriching the dominant scaffold in the hinge region. We hope that this strategy can provide new insights for accelerating the drug discovery process.

Minimum distance quantile regression for spatial autoregressive panel data models with fixed effects.

This paper considers the quantile regression model with individual fixed effects for spatial panel data. Efficient minimum distance quantile regression estimators based on instrumental variable (IV) method are proposed for parameter estimation. The proposed estimator is computational fast compared with the IV-FEQR estimator proposed by Dai et al. (2020). Asymptotic properties of the proposed estimators are also established. Simulations are conducted to study the performance of the proposed method. Finally, we illustrate our methodologies using a cigarettes demand data set.

Quantile regression for general spatial panel data models with fixed effects.

This paper considers the quantile regression model with both individual fixed effect and time period effect for general spatial panel data. Fixed effects quantile regression estimators based on instrumental variable method will be proposed. Asymptotic properties of the proposed estimators will be developed. Simulations are conducted to study the performance of the proposed method. We will illustrate our methodologies using a cigarettes demand data set.

[Pseudoangiosarcomatous squamous cell carcinoma of the penis: a case report with clinicopathological and human papilloma virus analyses].

OBJECTIVE: To further understand the clinicopathological, ultrastructural and molecular features of penile pseudoangiosarcomatous squamous cell carcinoma (PASCC), and improve its diagnosis and treatment. METHODS: A 47-year-old male patient with penile PASCC was reported and the relevant literature reviewed. The main clinical manifestations of the patient were a typical surface ulceration with hemorrhage and purulent secretion with a foul smell, a papillary mass about 5.0 cm x 5.0 cm x 4.0 cm for 1 year on the foreskin of the penis, and 3 enlarged bilateral inguinal lymph nodes. CT scanning showed no enlarged lymph nodes in the abdomen and pelvis, and X-ray examination revealed no abnormality in the chest. RESULTS: The diagnosis was established by biopsy. Partial penectomy and bilateral inguinal lymphadenectomy (T2N2M0) were performed, followed by adjuvant pelvic radiotherapy. Two months later, total penectomy was necessitated by penile flap necrosis and local recurrence. Eleven months after the first surgery, the patient died of extensive metastasis to the pelvis and lungs. Under the light microsope, the tumor was mainly composed of vessel-like lacunar reticularis spindle cells and a few local squamous cancer cells. Careful examination revealed some focal areas with evident transition from squamous nests to the more acantholytic areas extending towards the pseudoangiosarcomatous spaces. Pathogenetically, it appeared to be the variant of acantholytic squamous cell carcinoma. Immunohistochemically, most tumor cells were strongly positive for keratin (AE1/AE3) and focally positive for EMA, with the typical squamous cells focally positive for 34betaE12 and vimentin. The vessels that proliferated in the tumor were decorated by CD31, CD34 and factor VIII-related antigens, but the tumor cells were negative for HMB45, SMA, Desmin and CEA. HPV DNA (HPVpan, HPV6B/11, HPV16/18, HPV31/33) was not detected by in situ hybridization in the primary and metastatic tumors. CONCLUSION: PASCC is a specific and extremely rare subtype of penile SCC with dramatic similarity to angiosarcoma under the microscope, with poor prognosis. Its diagnosis depends on histopathological, immunohistochemical and ultrastructural studies. Such a presentation underscores the importance of timely consultation, early diagnosis and prompt treatment.

Direct visualization of reversible switching of micropatterned polyelectrolyte brushes on gold surfaces using laser scanning confocal microscopy.

We apply confocal fluorescence microscopy for real time studies of reversible conformational changes of poly(methacryloyloxyethyl phosphate) (PMEP) brushes chemically grafted onto gold substrates. Oregon green 488 fluorophores chemically attached onto the PMEP polymers were used as reporters for probing the conformational changes. Use of a specially designed liquid flow microchamber allowed dynamic imaging of the brushes under varying environmental conditions. The fluorescence intensities exhibited fully reversible brightness changes on alternation of the solution in the chamber between water and KCl. This reversible quenching behavior is consistent with a conformational change between an extended and a collapsed brush configuration. The fluorescence quenching behavior of the brushes was found to be dependent on ion concentration as well as polymer grafting density and was caused by nonradiative energy transfer to the polymer scaffold and the gold substrate.

Fluorescence intensity and lifetime imaging of free and micellar-encapsulated doxorubicin in living cells.

Frequency domain fluorescence lifetime imaging microscopy (FLIM) has been used in combination with laser scanning confocal microscopy to study the cellular uptake behavior of the antitumor drug doxorubicin (DOX) and micellar-encapsulated DOX (PLyAd-DOX). The endocytosis uptake process of PLyAd-DOX was monitored over 72 hours using confocal microscopy, with a maximum fluorescence recorded at incubation periods around 24 hours. The micellar structure was not found to release the encapsulated DOX during the time course of imaging. FLIM revealed single lifetime distributions of PLyAd-DOX during accumulation in the cytoplasm. The free DOX in contrast was observed both in the cytoplasm and the nuclear domain of the cell, showing bimodal lifetime distributions. There was a marked dependence of the measured free-DOX lifetime on concentration within the cell, in contrast to reference experiments in aqueous solution, where no such dependence was found. The results suggest the formation of macromolecular structures inside the living cells.

[Expression of epithelial-cadherin, CD44v6 and connexin43 in hepatocellular carcinoma].

OBJECTIVE: To study the expression of epithelial-cadherin (E-cad), CD44v6 and Cx43 in hepatocellular carcinoma (HCC) and its relationship with sex and age of patients, as well as tumor histopathologic grades. METHODS: Double immunofluorescent staining and laser scanning confocal microscopy was used to study the expression of E-cad, CD44v6 and Cx43 in 30 cases of normal liver tissue, 25 cases of benign hepatic lesions and 38 cases of HCC. In the HCC group, correlation of antigen expression with sex and age of patients and tumor histopathologic grades was studied by T-test. RESULTS: Significant decrease in expression of E-cad and Cx43 was noted in HCC group, as compared to normal liver tissue and benign hepatic lesion (P<0.05). On the other hand, CD44v6 expression was higher in HCC group than in the other two groups (P<0.05). In HCC group, the expression of E-cad and Cx43 did not correlate with sex, age and histopathologic grades (P>0.05). However, CD44v6 expression positively correlated with higher tumor histopathologic grades (P<0.05) but not sex and age of patients (P>0.05). In HCC group, the expression of E-cad positively correlated with that of Cx43, while the expression of CD44v6 negatively correlated with that of E-cad and Cx43. CONCLUSIONS: Tumor immunophenotype alters during development and progression of HCC. Low expression of E-cad and Cx43 and high expression of CD44v6 may be related to aggressive clinical behavior of HCC, moreover, high expression of CD44v6 correlated with high tumor grades. Detection of E-cad, CD44v6 and Cx43 expression may thus be useful in predicting prognosis of HCC.

[Expression of integrin-linked kinase in prostate cancer and its significance].

OBJECTIVE: To investigate the expression of integrin-linked kinase (ILK) in primary prostate cancer and its clinical significance. METHODS: The expression of ILK was analysed in 50 prostate cancer and 16 benign prostatic hyperplasia samples by immunohistochemical staining. RESULTS: The positive percentage of ILK was 46.0% (23/50) in primary prostate cancer. The higher the grade and the clinical stage of the tumor, the lower the expression of ILK. The positive percentages of ILK were 9.1% (1/11) in the well differentiated type, 56.4% (22/39) in the moderately and poorly differentiated type (chi2 = 12.28, P < 0.01), 24.0% (6/25) in the well and moderately differentiated type, 68.0% (17/25) in the poorly differentiated type (chi2 = 9.74, P < 0.01), 22.6% (7/31) at the A + B stage and 84.0% (16/19) at the C + D stage (chi2 = 11.8, P < 0.01). But in benign prostatic hyperplasia, it was only 6.2% (1/16), significantly lower than in primary prostate cancer (46.0%) (chi2 = 8.27, P < 0.01). CONCLUSION: The abnormal expression of ILK plays an important role in the development of primary prostate cancer, and the detection of ILK may be useful for the judgement of tumor development and prognosis.

Pathological characteristics of gastric leiomyoblastoma.

AIM: To determine the pathological characteristics of gastric leiomyoblastoma. METHODS: All tissues were obtained during surgery or gastroscopy. Tissue specimens for examination by light microscope were 1 cm x 1 cm x 1 cm in size, fixed in 40 g/L neutral buffered formaldehyde, embedded in paraffin, and stained with hematoxylin and eosin. The fresh tissues obtained for electron microscopy were 1 mm x 1 mm x 1 mm in size, and fixed in phosphate buffered 30 g/L glutaraldehyde, postfixed in 10 g/L osmium tetroxide and dehydrated in graded alcohol, embebbed in Epon 812. Ultrathin sections of 50 nm were stained with uranyl acetate and lead citrate and examined under a JEM-2000 EX transmission electron microscope. RESULTS: The most important histopathological feature of leiomyoblastoma was the predominance of large, rounded or polygonal cells with characteristic perinuclear clear zone in cytoplasms. The tumor cells arranged in patch, cell junction or junctional complex could be found occasionally between cells under electron microscope. Most of the neoplastic cytoplasms were filled with myofilaments, dense bodies, and dense patches. Rough endoplasmic reticulum dilatated as lakes, and large quantities of protein secretions of intermediate electron density were found in the dilated cisternae. Intracisternal segregation could also be found. The nuclei were round or oval, and anomalous nuclei were found in part of cells. CONCLUSION: The diagnosis of gastric leiomyoblastoma can be confirmed by electron microscopy. The clear appearance of tumor cells is due to the dilation of rough endoplasmic reticulum, not fat droplets, glycogens or mucus in cytoplasm.

Expressions of chromogranin A and cathepsin D in human primary hepatocellular carcinoma.

AIM:To determine the expression and clinical significance of chromogranin A and cathepsin D in hepatocellular carcinoma (HCC).METHODS:Double immunofluorescence stain-ing techniques combined with laser confocal scanning microscopy (LSCM) was used to investigate chromogranin A and cathepsin D expressions in 85 HCC patients.RESULTS:Cathepsin D was expressed in 3 normal liver tissues, while in HCC the staining showed regional variation and the fraction of strongly stained cells increased as the tumors became less differentiated and usually clinically more malignant.Cells which showed strong positivity for cathepsin D were present in 71/85(83.5%) cases. Strong expression of cathepsin D in cancer cells was related to histopathological features. They were more common in grade 3-4 (26/28, 92.9%) and grade 2 (46/53, 86.8%) tumors than in grade 1 tumors (1/4, 25.0%)(P <0.01). No significant correlation was found between age and cathepsin D expression. In patients with positive cathepsin D reaction, the mean age was 52.1± 2.8 years (range 32-68 years) and in the group with negative reaction, the mean age was 51.3± 4.5 years (range 28-71 years). No obvious relationship was observed between CgA expression in cancer cells and the histopathological features. The CgA positive rate was 75.0% (3/4) in grade 1, 71.7% (38/53) in grade 2,and 71.4% (20/28) in grade 3-4(P >0.05) tumors. The coexpression of CgA and cathepsin D was found by double labeled immunofluorescence staining techniques. The processing of cathepsin D was disturbed in HCC cells and accumulated in the cells.Cathepsin D had proteolytic activity and autocrine mitogenic effect, suggesting their functions in invasion. These findings demonstrated that the expression of cathepsin D in HCC had prognostic value.CONCLUSION:Chromogranin A and cathepsin D are expressed in a high proportion of HCC and the existence of cathepsin D in HCC might be related to processing of CgA. This is clearly a subject for further studies because of its potential clinical applications.