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1.
PeerJ ; 12: e17619, 2024.
Article in English | MEDLINE | ID: mdl-38952980

ABSTRACT

Background: Andrographolide (Andro), an extract of Andrographis paniculate (Burm.f.) Wall. ex Nees (Acanthaceae), possesses diverse biologically active properties. However, the precise mechanisms and effects of Andro on pancreatic cancer (PC) remain unclear. Methods: The cytotoxic potential of Andro and underlying mechanism towards PC cells was investigated through in vitro experiments and a xenograft mouse model. PC cells were first subjected to varying concentrations of Andro. The reactive oxygen species (ROS) was assessed using flow cytometry and DCFH-DA staining. The apoptosis rate was detected by flow cytometry. Additionally, western blot was applied to evaluate the expression levels of cleaved-caspase-3, DJ-1, LC3-I, LC3-II, and p62. To further elucidate the involvement of ROS accumulation and autophagy, we employed N-acetylcysteine as a scavenger of ROS and 3-Methyladenine as an inhibitor of autophagy. Results: Andro demonstrated potent anti-proliferative effects on PC cells and induced apoptosis, both in vitro and in vivo. The cytotoxicity of Andro on PC cells was counteracted by DJ-1 overexpression. The reduction in DJ-1 expression caused by Andro led to ROS accumulation, subsequently inhibiting the growth of PC cells. Furthermore, Andro stimulated cytoprotective autophagy, thus weakening the antitumor effect. Pharmacological blockade of autophagy further enhanced the antitumor efficacy of Andro. Conclusion: Our study indicated that ROS accumulation induced by the DJ-1 reduction played a key role in Andro-mediated PC cell inhibition. Furthermore, the protective autophagy induced by the Andro in PC cells is a mechanism that needs to be addressed in future studies.


Subject(s)
Apoptosis , Autophagy , Diterpenes , Pancreatic Neoplasms , Protein Deglycase DJ-1 , Reactive Oxygen Species , Reactive Oxygen Species/metabolism , Diterpenes/pharmacology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , Autophagy/drug effects , Protein Deglycase DJ-1/metabolism , Protein Deglycase DJ-1/genetics , Animals , Humans , Mice , Cell Line, Tumor , Apoptosis/drug effects , Xenograft Model Antitumor Assays , Mice, Nude
2.
J Clin Transl Hepatol ; 12(3): 266-277, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38426196

ABSTRACT

Background and Aims: Targeted therapy and immunotherapy have emerged as treatment options for hepatocellular carcinoma (HCC) in recent years. The significance of serine and glycine metabolism in various cancers is widely acknowledged. This study aims to investigate their correlation with the prognosis and tumor immune microenvironment (TIME) of HCC. Methods: Based on the public database, different subtypes were identified by cluster analysis, and the prognostic model was constructed through regression analysis. The gene expression omnibus (GEO) data set was used as the validation set to verify the performance of the model. The survival curve evaluated prognostic ability. CIBERSORT was used to evaluate the level of immune cell infiltration, and maftools analyzed the mutations. DsigDB screened small molecule compounds related to prognostic genes. Results: HCC was found to have two distinct subtypes. Subsequently, we constructed a risk score prognostic model through regression analysis based on serine and glycine metabolism-related genes (SGMGs). A nomogram was constructed based on risk scores and other clinical factors. HCC patients with a higher risk score showed a poor prognosis, and there were significant differences in immune cell infiltration between the high- and low-risk groups. In addition, three potential drugs associated with prognostic genes, streptozocin, norfloxacin, and hydrocotarnine, were identified. Conclusions: This study investigated the expression patterns of SGMGs and their relationship with tumor characteristics, resulting in the development of a novel model for predicting the prognosis of HCC patients. The study provides a reference for clinical prognosis prediction and treatment of HCC patients.

3.
Phytomedicine ; 126: 155402, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38350242

ABSTRACT

BACKGROUND: Vasculogenic mimicry (VM) is an angiogenesis-independent process that potentially contributes to the poor clinical outcome of anti-angiogenesis therapy in multiple malignant cancers, including pancreatic adenocarcinoma (PAAD). Several studies have shown that ginsenoside Rg3, a bioactive component of ginseng, holds considerable potential for cancer treatment. Our previous work has proved that Rg3 can inhibit VM formation in PAAD. However, its underlying mechanism remains unclear. PURPOSE: To explore the underlying mechanism by which Rg3 affects VM formation in PAAD. METHODS: We first investigated the effects of Rg3 on the cellular phenotypes of two PAAD cell lines (SW-1990 and PCI-35), and the expression of EMT- and stemness-related proteins. SW-1990 cells were adopted to construct xenograft models, and the anti-tumor effects of Rg3 in vivo were validated. Subsequently, we isolated the exosomes from the two PAAD cell lines with Rg3 treatment or not, and explored whether Rg3 regulated VM via PAAD cell-derived exosomes. MiRNA sequencing, clinical analysis, and rescue experiments were performed to investigate whether and which miRNA was involved. Subsequently, the target gene of miRNA was predicted using the miRDB website (https://mirdb.org/), and rescue experiments were further conducted to validate those in vitro and in vivo. RESULTS: Rg3 indeed exhibited excellent anti-tumor effects both in vitro and in vivo, with inhibitory effects on EMT and stemness of PAAD cells. More interestingly, Rg3-treated PAAD cell-derived exosomes suppressed the tube-forming ability of HUVEC and PAAD cells, with a decrease in stemness-related protein expression, indicating that Rg3 inhibited both angiogenesis and VM processes. Subsequently, we found that Rg3 induced the up-regulation of miR-204 in PAAD cell-derived exosomes, and miR-204 alone inhibited tube and sphere formation abilities of PAAD cells like exosomes. Specifically, miR-204 down-regulated DVL3 expression, which was involved in regulating cancer cell stemness, and ultimately affected VM. The in vivo experiments further indicated that Rg3-treated SW-1990 cell-derived exosome-inhibited tumor growth, VM formation, and stemness-related protein expression can be abrogated by DVL3 overexpression. CONCLUSION: Ginsenoside Rg3 increased the PAAD cell-derived exosomal miR-204 levels, which subsequently inhibited its target genes DVL3 expression in the receptor PAAD cells, and the down-regulated DVL3 broke stemness maintenance, ultimately suppressing VM formation of PAAD. Our findings revealed a novel mechanism by which Rg3 exerted its anti-tumor activity in PAAD via inhibiting VM, and provided a promising strategy to make up for the deficiency of anti-angiogenesis therapy in cancer.


Subject(s)
Adenocarcinoma , Ginsenosides , MicroRNAs , Pancreatic Neoplasms , Percutaneous Coronary Intervention , Humans , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Cell Line, Tumor , MicroRNAs/genetics , Cell Proliferation , Neovascularization, Pathologic/drug therapy , Gene Expression Regulation, Neoplastic , Dishevelled Proteins/genetics
4.
Org Lett ; 25(39): 7132-7136, 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37751201

ABSTRACT

Herein is developed a base-promoted approach for the synthesis of C2-substituted indoles and N-fused polycyclic indoles via 5-endo-dig cyclization of 2-alkynyl anilines, followed by a 1,3'-acyl migration or a dearomatizing Michael addition process. A range of N-H free indoles and 8,9-dihydropyrido[1,2-a]indol-6(7H)-one scaffolds were synthesized in good to excellent yields with broad scope.

5.
Am J Transl Res ; 14(6): 3610-3637, 2022.
Article in English | MEDLINE | ID: mdl-35836899

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of tumor-related death. MicroRNAs (miRNAs) belong to a subfamily of functional non-coding RNAs (ncRNAs) and are essential regulators of tumorigenesis. They affect tumor-related therapeutic response, tumor metastasis, and clinical outcomes of several human malignant tumors. However, the prognostic value of miRNAs and their role in the tumor immune microenvironment (TIME) of HCC have not been clarified. MATERIALS AND METHODS: Raw RNA-sequencing data (mRNA and miRNA) and clinicopathological characteristics of HCC samples were downloaded from the TCGA-GDC database. The Perl programming language, R software, Cytoscape software, and several online databases were used to clarify the clinical significance and biological functions of miRNAs and their target genes in HCC. RESULTS: A total of 424 mRNA-sequencing samples and 425 miRNA-sequencing samples were obtained from the TCGA database. There were 344 HCC cases with complete information in the TCGA dataset and they were randomly categorized into two subgroups. Six miRNAs were identified as independent prognostic biomarkers for HCC patients by univariate and multivariate Cox regression analysis. The constructed prognostic signature, which contains these six miRNAs, was significantly correlated with overall survival (OS). In addition, this prognostic signature is superior to single miRNA in predicting short-term prognosis of HCC patients. We also found that the prognostic signature was significantly associated with tumor-related immune cell infiltration, TIME, and immunotherapeutic response. Furthermore, a total of 4568 potential target genes of six miRNAs were identified. The miRNA-mRNA co-expression network, protein-protein interaction (PPI) network, and functional and pathway enrichment analysis demonstrated that these miRNA-related target genes have important biological effects during the initiation and progression of HCC. CONCLUSIONS: This study demonstrates that the miRNA signature can accurately predict the prognosis of HCC patients and provide a basis for novel immunotherapy treatments.

6.
Front Oncol ; 11: 711402, 2021.
Article in English | MEDLINE | ID: mdl-34497764

ABSTRACT

BACKGROUND: Pancreatic cancer is one of the principal causes of tumor-related death worldwide. CXC chemokines, a subfamily of functional chemotactic peptides, affect the initiation of tumor cells and clinical outcomes in several human malignant tumors. However, the specific biological functions and clinical significance of CXC chemokines in pancreatic cancer have not been clarified. METHODS: Bioinformatics analysis tools and databases, including ONCOMINE, GEPIA2, the Human Protein Atlas, DAVID, GeneMANIA, cBioPortal, STRING, DGidb, MethSurv, TRRUST, SurvExpress, SurvivalMeth, and TIMER, were utilized to clarify the clinical significance and biological functions of CXC chemokine in pancreatic cancer. RESULTS: Except for CXCL11/12, the transcriptional levels of other CXC chemokines in PAAD tissues were significantly elevated, and the expression level of CXCL16 was the highest among these CXC chemokines. Our findings also suggested that all of the CXC chemokines were linked to tumor-immune dysfunction involving the abundance of immune cell infiltration, and the Cox proportional hazard model confirmed that dendritic and CXCL3/5/7/8/11/17 were significantly associated with the clinical outcome of PAAD patients. Furthermore, increasing expressions of CXCL5/9/10/11/17 were related to unfavorable overall survival (OS), and only CXCL17 was a prognostic factor for disease-free survival (DFS) in PAAD patients. The expression pattern and prognostic power of CXC chemokines were further validated in the independent GSE62452 dataset. For the prognostic value of single CpG of DNA methylation of CXC chemokines in patients with PAAD, we identified 3 CpGs of CXCL1, 2 CpGs of CXCL2, 2 CpGs of CXCL3, 3 CpGs of CXCL4, 10 CpGs of CXCL5, 1 CpG of CXCL6, 1 CpG of CXCL7, 3 CpGs of CXCL12, 3 CpGs of CXCL14, and 5 CpGs of CXCL17 that were significantly associated with prognosis in PAAD patients. Moreover, the prognostic value of CXC chemokine signature in PAAD was explored and tested in two independent cohort, and results indicated that the patients in the low-risk group had a better OS compared with the high-risk group. Survival analysis of the DNA methylation of CXC chemokine signature demonstrated that PAAD patients in the high-risk group had longer survival times. CONCLUSIONS: These findings reveal the novel insights into CXC chemokine expression and their biological functions in the pancreatic cancers, which might serve as accurate prognostic biomarkers and suitable immunotherapeutic targets for patients with pancreatic cancer.

7.
World J Clin Cases ; 9(22): 6418-6427, 2021 Aug 06.
Article in English | MEDLINE | ID: mdl-34435007

ABSTRACT

BACKGROUND: Pancreatic inflammatory myofibroblastic tumor (IMT) is a relatively rare disease that is often confused with pancreatic cancer or pancreatic neuroendocrine tumors. The histological features of IMTs show that tissue from this type of tumor contains an intermingling of fibroblast and myofibroblast proliferation, accompanied by a varying degree of inflammatory cell infiltration. CASE SUMMARY: The management of an IMT occurring at the neck of the pancreas is presented in this paper. A 66-year-old female patient was diagnosed with a pancreatic neck mass after a series of tests. The patient underwent enucleation of the pancreatic neck tumor after a pathological diagnosis of IMT. Previous research on the clinical features, pathological diagnosis and treatment of pancreatic IMTs was reviewed. Compared with previous reports, this is a unique case of enucleation of a pancreatic IMT. CONCLUSION: The enucleation of pancreatic IMTs may be a safe and efficient surgical method for managing such tumors with a better prognosis. Further cases are required to explore surgical measures for pancreatic IMTs.

8.
Signal Transduct Target Ther ; 6(1): 153, 2021 04 23.
Article in English | MEDLINE | ID: mdl-33888679

ABSTRACT

The extracellular matrix (ECM) is one of the major components of tumors that plays multiple crucial roles, including mechanical support, modulation of the microenvironment, and a source of signaling molecules. The quantity and cross-linking status of ECM components are major factors determining tissue stiffness. During tumorigenesis, the interplay between cancer cells and the tumor microenvironment (TME) often results in the stiffness of the ECM, leading to aberrant mechanotransduction and further malignant transformation. Therefore, a comprehensive understanding of ECM dysregulation in the TME would contribute to the discovery of promising therapeutic targets for cancer treatment. Herein, we summarized the knowledge concerning the following: (1) major ECM constituents and their functions in both normal and malignant conditions; (2) the interplay between cancer cells and the ECM in the TME; (3) key receptors for mechanotransduction and their alteration during carcinogenesis; and (4) the current therapeutic strategies targeting aberrant ECM for cancer treatment.


Subject(s)
Carcinogenesis/genetics , Extracellular Matrix/genetics , Neoplasms/genetics , Tumor Microenvironment/genetics , Humans , Neoplasms/pathology , Neoplasms/therapy
9.
Medicine (Baltimore) ; 100(12): e25320, 2021 Mar 26.
Article in English | MEDLINE | ID: mdl-33761734

ABSTRACT

ABSTRACT: To investigate the expression pattern and diagnostic performance of matrix metalloproteinase 28 (MMP28) in pancreatic cancer (PC).The RNA-seq data of PC and normal pancreas tissue were acquired from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression. Clinical information of PC that included prognostic data was obtained from TCGA. Later, Fisher exact test was applied for comparison of different clinicopathological features between high and low expression of MMP28 in PC. Afterwards, Kaplan-Meier survival analysis and Cox analysis (univariate and multivariate analysis) were used to explore the prognostic performance of MMP28 in PC cohort. Finally, gene set enrichment analysis (GSEA) revealed the potential signaling pathways related to high expression of MMP28 in PC.Upregulation of MMP28 was identified in PC tissue compared to normal pancreas tissue (P < .001). Overexpression of MMP28 was related to histological grade (P < .001), M classification (P = .014), and survival status (P = .028). Kaplan-Meier survival analysis revealed that high level of MMP28 implied unfavorable prognosis in PC (P = .002). Multivariate analysis confirmed that MMP28 was an independent risk factor in PC (hazard rate = 1.308, P = .018). Our GSEA analysis found that signaling pathways including glycolysis, p53 pathway, notch signaling, estrogen response late, cholesterol homeostasis, estrogen response early, mitotic spindle, and transforming growth factor beta signaling were enriched in the group with higher MMP28 expression.High expression of MMP28 could be identified in PC, which also served as an independent risk element for PC.


Subject(s)
Matrix Metalloproteinases, Secreted/metabolism , Pancreatic Neoplasms , Biomarkers, Tumor/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Prognosis , Proportional Hazards Models , Risk Assessment , Risk Factors , Signal Transduction , Up-Regulation
10.
Infect Dis Immun ; 1(1): 36-42, 2021 Apr.
Article in English | MEDLINE | ID: mdl-38630102

ABSTRACT

Background: Pre-existing liver disease is a risk factor for the worse prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to evaluate whether chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) affect the expression of viral receptor angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in the liver. Methods: Twelve pairs of matched liver tissues of HCC and para-carcinoma were collected from the First Affiliated Hospital of Zhejiang University School of Medicine. And 20 liver biopsies from CHB patients were collected from Peking University People's Hospital. The expression of ACE2 and TMRPSS2 were detected using immunofluorescence staining, western blot, and RT-qPCR. The effects of hepatitis B virus (HBV) replication or interferon on ACE2 and TMPRSS2 expression were tested in hepatic cell lines. Results: The mRNA expression of TMPRSS2 in HCC tissues was six-fold higher than that of para-carcinoma tissues (P = 0.002), whereas that of ACE2 was not statistically different between HCC and para-carcinoma tissues. Hepatocellular ACE2 expression was detected in 35% (7/20) of CHB patients and mostly distributed in the inflammatory areas. However, there was no difference in TMPRSS2 expression between areas with or without inflammation. IFN-α2b slightly induced ACE2 expression (2.4-fold, P = 0.033) in HepG2 cells but not in Huh-7, QSG-7701, and L-02 cells. IFN-α2b did not affect TMPRSS2 expression in these cell lines. In addition, HBV replication did not alter ACE2 expression in HepAD38 cells. Conclusions: Although HBV replication does not directly affect the expression of ACE2 and TMPRSS2, intrahepatic inflammation and carcinogenesis may increase their expression in some patients, which, in turn, may facilitate SARS-CoV-2 infection in hepatocytes.

11.
Front Med (Lausanne) ; 7: 556, 2020.
Article in English | MEDLINE | ID: mdl-33072775

ABSTRACT

As the most prevalent type of mRNA modification in mammals, N6-methyladenosine (m6A) is involved in various biological processes. Accumulating studies have indicated that the deregulation of m6A RNA modification is linked to cancer and other diseases. However, its implications in hepatocellular carcinoma (HCC) remain poorly characterized. Herein, we sought to investigate the expression pattern of 13 key regulators for m6A RNA modification and to evaluate their prognostic value in HCC. First, we systematically analyzed data from The Cancer Genome Atlas (TCGA) database pertaining to patient clinical information and mRNA gene expression data. We found that 11 out of 13 key regulators for m6A RNA modification showed significantly higher expression levels in HCC. Subsequently, we identified two subgroups (clusters 1 and 2) via consensus clustering based on the expression of 13 m6A RNA methylation regulators. Cluster 2 had a worse prognosis and was also significantly correlated with higher histological grade and pathological stage when compared with cluster 1. Moreover, cluster 2 was remarkedly enriched for cancer-related pathways. We further constructed a robust risk signature of five regulators for m6A RNA modification. Further analysis indicated that this risk signature could be an independent prognostic factor for HCC, and the prognostic relevance of this five-gene risk signature was successfully validated using the Gene Expression Omnibus (GEO) dataset. Finally, we established a novel prognostic nomogram on the basis of age, gender, histological grade, pathological stage, and risk score to precisely predict the prognosis of patients with HCC. In summary, we herein uncovered the vital role of regulators for m6A RNA modification in HCC and developed a risk signature as a promising prognostic marker in HCC patients.

12.
Medicine (Baltimore) ; 99(30): e21120, 2020 Jul 24.
Article in English | MEDLINE | ID: mdl-32791686

ABSTRACT

INTRODUCTION: Pancreaticoduodenectomy (PD) has been widely applied as a standard surgical procedure to treat periampullary diseases. The placement of a pancreaticojejunal anastomotic stent is considered an effective and safe method for preventing pancreatic fistula after PD. Recently, the role of pancreaticojejunal anastomotic stents has been challenged, as gradually increasing complications have been observed. Stent-related small bowel perforation has only occurred in 2 cases as long-term complications but has not been reported to occur within 1 week after surgery. PATIENT CONCERNS: Here, we report the case of a 71-year-old female patient complaining of painless jaundice who underwent PD with a pancreaticojejunal anastomotic stent for a duodenal papillary adenocarcinoma (T4N1M0). Four days after surgery, she had a sudden rise in temperature, high white blood cell count, significantly elevated C-reactive protein and 400 ml green-brown drainage fluid. Enhanced computed tomography showed hydrops abdominis. DIAGNOSIS: Small bowel perforation caused by stent migration was considered first. INTERVENTIONS: An emergency exploratory laparotomy was performed. We located the pancreaticojejunal anastomotic stent, which extended 2 cm from the small bowel, and sutured the jejunum hole after cutting away the protruding part of the stent. OUTCOMES: The patient recovered smoothly and was discharged on the 7th day after the second surgery. After more than 12 months of follow-up, the patient is doing well and is free of any symptoms related to the procedure. CONCLUSION: We caution that stent-related complications can occur when perioperative patients suffer from unexplained or sudden changes in vital signs after PD. In addition, the function of the pancreaticojejunal anastomotic stent needs to be reevaluated by future studies.


Subject(s)
Intestinal Perforation/etiology , Jejunal Diseases/etiology , Prosthesis Failure/adverse effects , Stents/adverse effects , Aged , Female , Humans , Pancreaticoduodenectomy/adverse effects , Pancreaticojejunostomy/adverse effects , Postoperative Complications/etiology
13.
Front Oncol ; 10: 887, 2020.
Article in English | MEDLINE | ID: mdl-32676450

ABSTRACT

Background: To compare the predictive power between radiomics and non-radiomics (conventional imaging and functional imaging methods) for preoperative evaluation of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods: Comprehensive publications were screened in PubMed, Embase, and Cochrane Library. Studies focusing on the discrimination values of imaging methods, including radiomics and non-radiomics methods, for MVI evaluation were included in our meta-analysis. Results: Thirty-three imaging studies with 5,462 cases, focusing on preoperative evaluation of MVI status in HCC, were included. The sensitivity and specificity of MVI prediction in HCC were 0.78 [95% confidence interval (CI): 0.75-0.80; I 2 = 70.7%] and 0.78 (95% CI: 0.76-0.81; I 2 = 0.0%) for radiomics, respectively, and were 0.73 (95% CI: 0.71-0.75; I 2 = 83.7%) and 0.82 (95% CI: 0.80-0.83; I 2 = 86.5%) for non-radiomics, respectively. The areas under the receiver operation curves for radiomics and non-radiomics to predict MVI status in HCC were 0.8550 and 0.8601, respectively, showing no significant difference. Conclusion: The imaging method is feasible to predict the MVI state of HCC. Radiomics method based on medical image data is a promising application in clinical practice and can provide quantifiable image features. With the help of these features, highly consistent prediction performance will be achieved in anticipation.

14.
Am J Gastroenterol ; 113(11): 1660-1668, 2018 11.
Article in English | MEDLINE | ID: mdl-30353056

ABSTRACT

BACKGROUND: The current upper limits of normal (ULN) for serum alanine aminotransferase (ALT) are increasingly challenged. We aimed to re-evaluate the ULN for ALT and assess the potential impact on the classification of natural course of chronic hepatitis B virus (HBV) infection in children. METHODS: Laboratory data obtained from three hospitals in China were retrospectively analysed. In total, 2054 children with chronic HBV infection and 8149 healthy children at age ≤18 years were included in the study. RESULTS: Age-specific and gender-specific ULNs for ALT, at averages of 30 U/L for boys and 24 U/L for girls, were calculated from the data of healthy children. Using the revised ULNs vs. the current ULNs (40-50 U/L), 31-60% vs. 9-17% of the 2054 HBV-infected children had an abnormal result as seen in their ALT baseline analysis, and the highest abnormality rate was seen in the infants. Data of 516 HBV-infected children were applied for the classification of clinical phase, 28.8% vs. 19.8% of the children were classified into the phases of hepatitis B e antigen (HBeAg-)positive/negative hepatitis. During a median follow-up of 62 months, 39 of 153 children underwent HBeAg seroconversion, whereas 3 of them had persistently "normal" ALT, according to the current ULN. CONCLUSIONS: The revision of ULN for ALT in children substantially impacts the classification of the natural course of chronic HBV infection. Mild ALT fluctuation is common during the stage childhood, suggesting a need to rethink the current conceptions of immune tolerance and natural course of chronic HBV infection in the children.


Subject(s)
Alanine Transaminase/standards , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/diagnosis , Adolescent , Age Factors , Alanine Transaminase/blood , Child , Child, Preschool , China , Female , Hepatitis B e Antigens/blood , Hepatitis B e Antigens/isolation & purification , Hepatitis B virus/immunology , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/immunology , Hepatitis B, Chronic/virology , Humans , Infant , Liver Function Tests/methods , Liver Function Tests/standards , Male , Reference Values , Retrospective Studies , Sex Factors
15.
Medicine (Baltimore) ; 97(29): e11487, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30024526

ABSTRACT

RATIONALE: Neuroendocrine carcinoma (NEC) arising from the extrahepatic biliary tracts (EHBTs) is rare, and thus its management and prognosis remain poorly clarified. We herein describe a case of NEC in the perihilar EHBTs, and review the literature, together with a comparison between NECs in the perihilar and distal EHBTs, to elucidate the management strategy and oncological outcome of this rare entity. PATIENT CONCERNS: A 62-year-old Chinese male was admitted with complaints of painless jaundice. Imaging studies revealed a 2-cm mass in the hepatic hilum, regional lymph node involvement, and severe stenosis at the junction of the common hepatic ducts. DIAGNOSES: The histopathological examination of the resected specimen demonstrated small tumor cells with round hperchromatic nuclei and scant cytoplasm. A detailed immunohistochemical analysis showed that the tumor was strongly positive for synaptophysin, CD56 and chromogranin A, with a Ki-67 labeling index greater than 80%. These results led to a diagnosis of NEC in the perihilar bile duct. INTERVENTIONS: The patient underwent surgical resection including a left hemihepatectomy, cholecystectomy, lymphadenectomy and Roux-en-Y hepaticojejunostomy. OUTCOMES: During the two months of follow-up, repeated imaging studies indicated tumor recurrence in the liver. The patient died 6 months after surgery. LESSONS: NEC in the EHBTs is extremely challenging to diagnose preoperatively because of mimicking other bile duct cancers. The prognosis of this disease entity is dismal, and most patients die within 2 years after diagnosis. Subtyping of NECs into perihilar NECs and distal NECs is beneficial for clinical applications, including guiding therapy selection and predicting survival.


Subject(s)
Bile Duct Neoplasms/pathology , Bile Ducts, Extrahepatic/pathology , Carcinoma, Neuroendocrine/diagnosis , Anastomosis, Roux-en-Y/methods , Bile Duct Neoplasms/surgery , Bile Ducts, Extrahepatic/surgery , Carcinoma, Neuroendocrine/surgery , Cholecystectomy/methods , Fatal Outcome , Hepatectomy/methods , Humans , Liver/pathology , Liver/surgery , Lymph Node Excision/methods , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Recurrence, Local , Tomography, X-Ray Computed
16.
Medicine (Baltimore) ; 97(2): e9499, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29480839

ABSTRACT

RATIONALE: Currently, percutaneous catheter drainage (PCD) is regarded as the first-line treatment modality of pyogenic liver abscess. Severe complications associated with PCD were uncommon. Hepatic rupture is an uncommon but life-threatening liver trauma with high mortality. Its management is challenging because a delay in the diagnosis may lead to fatal hemorrhagic shock. To our knowledge, PCD-associated hepatic rupture has never been reported. PATIENT CONCERNS: We report herein a rare case of PCD-associated hepatic rupture. Its clinical courses and our therapeutic approaches are presented. Moreover, the clinical significance, underlying causes, and current views on severe liver trauma management will be discussed briefly. DIAGNOSES: A diabetic patient suffering from fever and malaise was diagnosed with a pyogenic liver abscess. PCD was performed because intravenous antibiotics were ineffective. The patient developed a liver rupture following PCD, with clinical and imaging confirmation but without further progression. INTERVENTIONS: Surgical repair and vascular intervention were both inappropriate. As a result, medical treatments with supportive care were adopted and were found to be effective. OUTCOMES: The patient's condition improved gradually, with stabilized imaging and laboratory performance. He recovered uneventfully during follow-ups. LESSONS: Hepatic rupture should be listed as an extremely rare but severe complication of PCD. Immediate suspicion and effective intervention may avoid an unfavorable consequence.


Subject(s)
Catheters , Drainage , Liver Abscess, Pyogenic/therapy , Liver/injuries , Rupture/etiology , Aged , Diabetes Complications/diagnostic imaging , Drainage/instrumentation , Humans , Liver/diagnostic imaging , Liver Abscess, Pyogenic/complications , Liver Abscess, Pyogenic/diagnostic imaging , Male
17.
Medicine (Baltimore) ; 96(43): e8351, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29069015

ABSTRACT

Contrast-enhanced magnetic resonance imaging (MRI) characteristics of small-diameter mass-forming intrahepatic cholangiocarcinomas (ICCs) (diameter ≤3 cm) are still unclear.This study focused on imaging findings of small mass-forming ICCs. The MRI findings for small-diameter mass-forming ICCs were summarized, and the enhancement features of small ICC nodules with different diameters [2 groups were defined: a smaller nodule group (ICC diameter <2 cm) and a larger nodule group (ICC diameter >2 cm)] were compared on contrast-enhanced MRI.In our study, there were 41 small ICC nodules in 41 patients, including 30 men and 11 women (average age, 56 years). The nodules were characterized by peripheral hyperintense in the arterial phase on contrast-enhanced MRI. In the different diameter groups, peripheral hyperintense was the most common in the larger nodule group (56% vs 12%, P < .05) and hypointense was more common in the smaller nodule group (25% vs 0%, P < .05) in the arterial phase on contrast-enhanced MRI. Smaller nodules mainly showed progressive enhancement, whereas larger nodules mainly showed peripheral continuous enhancement (56% vs 6%, P < .05).The small-diameter mass-forming ICC nodules mainly show peripheral continuous enhancement on contrast-enhanced MRI; however, those with diameters <2 cm commonly show progressive enhancement.


Subject(s)
Bile Duct Neoplasms/diagnostic imaging , Cholangiocarcinoma/diagnostic imaging , Contrast Media , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Adult , Bile Ducts, Intrahepatic/diagnostic imaging , Diagnosis, Differential , Female , Humans , Liver/diagnostic imaging , Male , Middle Aged , Radiologists , Retrospective Studies
18.
Medicine (Baltimore) ; 96(41): e8297, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29019904

ABSTRACT

RATIONALE: Inflammatory myofibroblastic tumors (IMTs) are rare neoplastic lesions with benign tendency. Even more rare are IMTs from the greater omentum (GO-IMT). A GO-IMT is easily misdiagnosed as other malignant tumors before operation; thus, clinicians need to be familiar with its imaging findings. Here, we report the imaging findings of a GO-IMT patient presenting with a pelvic mass. PATIENT CONCERNS: Ultrasound of the IMT in the pelvic cavity showed a hypoechoic mass. A computed tomography (CT) scan showed a nearly circular soft tissue mass with a clear border and heterogeneous density, and the surrounding tissues were pushed and compressed. Contrast-enhanced CT showed severe persistent enhancement in the lesion edges and mural nodules, but not in the central necrosis. DIAGNOSES: Histopathology and immunohistochemistry confirmed that the mass was a GO-IMT. INTERVENTIONS: The tumor was resected after preoperative preparation. OUTCOMES: No recurrence or metastasis was found during a short-term follow-up. LESSONS: The GO-IMT is an inferior epigastric mass in the periphery of the bowel, and is usually well-demarcated without calcification or lymphadenopathy. Contrast-enhanced CT showed a heterogeneous hypervascular mass where the center necrosis, the edge of the tumor, and the mural nodules can be partially reinforced.


Subject(s)
Dissection/methods , Laparoscopy/methods , Lymph Nodes , Neoplasms, Muscle Tissue , Omentum/pathology , Peritoneal Neoplasms , Adult , Female , Humans , Hyperplasia , Inflammation/etiology , Lymph Node Excision/methods , Lymph Nodes/pathology , Lymph Nodes/surgery , Neoplasms, Muscle Tissue/pathology , Neoplasms, Muscle Tissue/physiopathology , Neoplasms, Muscle Tissue/surgery , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/physiopathology , Peritoneal Neoplasms/surgery , Tomography, X-Ray Computed/methods , Treatment Outcome
19.
BMC Complement Altern Med ; 17(1): 467, 2017 Sep 21.
Article in English | MEDLINE | ID: mdl-28934950

ABSTRACT

BACKGROUND: Although various treatments for breast cancer related lymphedema exist, there is still a need for a more effective and convenient approach. Pilot studies and our clinical observations suggested that acupuncture may be a potential option. This study aims to verify the effectiveness of acupuncture on BCRL and evaluate its safety using a rigorously designed trial. METHODS/DESIGN: Women who are clinically diagnosed as unilateral BCRL, with a 10% to 40% increase in volume compared to the unaffected arm, will be recruited. Following baseline assessment, participants will be randomized to either the real acupuncture group or sham-acupuncture group at a ratio of 1:1, and given a standard real acupuncture or sham-acupuncture treatment accordingly on both arms followed by the same usual care of decongestive therapy. Volume measurements of both arms will be performed for every participant after each treatment. Data collected at baseline and the last session will be used to calculate the primary outcome and secondary outcomes. Other data will be exploited for interim analyses and trial monitoring. The primary outcome is the absolute reduced limb volume ratio. Secondary outcomes are incidence of adverse events and change in quality of life. A t test or non-parameter test will be used to compare the difference between two groups, and assess the overall effectiveness of acupuncture using the SPSS software (version 12). DISCUSSION: This study will help expand our knowledge about the effectiveness of acupuncture on BCRL, and how acupuncture might be used in the management of this condition. Acupuncture may be a promising complement or alternative to conventional lymphedema treatment methods, if its effectiveness is confirmed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02803736 (Registered on October 31, 2016).


Subject(s)
Acupuncture Therapy , Breast Cancer Lymphedema/therapy , Acupuncture Points , Female , Humans , Multicenter Studies as Topic , Quality of Life , Randomized Controlled Trials as Topic , Treatment Outcome
20.
Medicine (Baltimore) ; 96(50): e9192, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29390333

ABSTRACT

RATIONALE: Hemangioma of the liver is a benign hepatic tumor, more common in women than in men, which is typically asymptomatic, solitary, and incidentally discovered. Atypical hemangioma is a variant of hepatic hemangioma with atypical imaging finding features on CT and MRI that can be confused with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and mixed hepatocellular cholangiocarcinoma (HCC-CC). PATIENT CONCERNS: We report a case of atypical hepatic hemangioma mimicking HCC-CC: A 59-year-old man was referred to our hospital for a hepatic lesion that was 4.7×3.6 cm in size and located in segments 2 and 3 of the liver. Serum alpha-fetoprotein (AFP) level increased from 17.03 ng/mL to 374.9 ng/mL. The patient was positive for hepatitis B. DIAGNOSES: Atypical hepatic hemangioma. INTERVENTIONS: US, CT, MRI and Tc-99m RBC liver scans were performed. Dynamic contrast-enhanced MRI showed no uptake in the corresponding area during the arterial phase, peripheral nodular enhancement during the portal phase and delayed phase, and hypo-intensity in the central area. An initial diagnosis of HCC-CC was offered based on the history and imaging findings. Finally, percutaneous liver biopsy (PLB) was offered to the patient. Histopathologic examination of the liver lesions revealed nodular cirrhosis and atypical hyperplasia of liver cells with cavernous hemangioma, where numerous old Schistosoma japonicum eggs were found. OUTCOMES: Accurate diagnosis of the patient obviated the need for surgery. The patient's recovery after liver puncture was uneventful, and he was discharged on the seventh post-operative day. LESSONS: In some cases, accurate preoperative imaging of focal hepatic lesions is essential but insufficient for diagnosis. PLB and histopathological examination are important, especially in patients with suspected malignancy.


Subject(s)
Hemangioma/diagnosis , Liver Neoplasms/diagnosis , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/diagnosis , Cholangiocarcinoma/diagnosis , Diagnosis, Differential , Diagnostic Imaging , Hemangioma/pathology , Hemangioma/therapy , Humans , Image-Guided Biopsy , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Male , Middle Aged , Punctures
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