Therapeutic effect of transplantation of bone marrow mesenchymal stem cells co-cultured with bone marrow M2 macrophages on a rat model of liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSCM2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl4）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSCM2. The rats were given subcutaneous injection of CCl4 for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSCM2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl4. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSCM2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSCM2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSCM2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSCM2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSCM2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSCM2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl4/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

Role of Takeda G protein-coupled receptor-5 in non-viral liver diseases / 临床肝胆病杂志

Non-viral liver diseases mainly include nonalcoholic fatty liver disease, alcoholic liver disease, autoimmune liver disease, and cholestatic liver disease, and the prevalence rate of non-viral liver diseases tends to increase in recent years. Takeda G protein-coupled receptor-5 (TGR5) belongs to the G protein-coupled receptor superfamily and is activated by primary and secondary bile acids. TGR5 plays an important regulatory role in bile acid homeostasis, basal metabolism, energy balance, and alleviation of inflammatory response and is a potential therapeutic target for many diseases. An increasing number of evidence has shown that TGR5 exerts a protective effect on the liver by improving bile acid and glycolipid metabolism in liver, alleviating liver inflammation, and reducing liver steatosis. This article reviews the recent advances in the basic research on TGR5 in the field of non-viral liver diseases, so as to facilitate the development of the research on TGR5.

Role of GDC-0449 in a rat model of liver fibrosis induced by carbon tetrachloride combined with 2-acetylaminofluorene / 临床肝胆病杂志

Objective To investigate the intervention effect of GDC-0449, a hedgehog signaling pathway inhibitor, on rats with liver fibrosis induced by carbon tetrachloride (CCl 4 ) combined with 2-acetylaminofluorene (2-AAF). Methods A total of 18 female Fisher344 rats were randomly divided into normal group, CCl 4 /2-AAF group, and GDC-0449 group, with 6 rats in each group. The rats in the CCl 4 /2-AAF group and the GDC-0449 group were given subcutaneously injected 30% CCl 4 -olive oil solution at a dose of 2 mL/kg twice a week for 6 weeks to induce liver fibrosis; since week 7, in addition to the injection of CCl 4 -olive oil solution, the rats in these two groups were given 2-AAF (100 mg/kg/d) by gavage, and the rats in the GDC-0449 group were given GDC-0449 (25 mg/kg/d) by gavage, while those in the normal group were given an equal volume of olive oil solution by injection and normal saline by gavage. All rats were sacrificed at the end of week 9, and related samples were collected. HE staining and sirius red (SR) staining were used to observe the changes in liver histopathology and collagen deposition, and the semi-quantitative analysis of SR-positive area and Ishak score were used to evaluate fibrosis degree; the alkaline hydrolysis method was used to measure the level of hydroxyproline (Hyp) in liver tissue; immunohistochemistry, Western blot, and qRT-PCR were used to measure the expression of α-smooth muscle actin (α-SMA), type Ⅰ collagen (Col-Ⅰ), type Ⅳ collagen (Col-Ⅳ), cytokeratin 19 (CK19), cytokeratin 7 (CK7), the epithelial cell adhesion molecule Epcam, and the hedgehog signaling pathway in liver tissue; double immunofluorescence staining was used to observe the colocalization of CK19 and the oval cell marker OV6. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the normal group, the CCl 4 /2-AAF group had marked inflammatory cell aggregation and collagen deposition in liver tissue, with the formation of a pseudolobular structure, as well as significant increases in Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Col-Ⅰ, Col-Ⅳ, Epcam, CK19, CK7, the transmembrane transporter Smoothened (Smo), Hedgehog ligand Desert Hedgehog (Dhh), the Indian Hedgehog membrane-binding receptor Patched (Ptch2), and glioma-related oncogenes Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed that CK19-positive cells also expressed OV6 in the liver tissue of rats in the CCl 4 /2-AAF group, with a significant increase compared with the normal group. Compared with the CCl 4 /2-AAF group, the GDC-0449 group had significant reductions in inflammatory cell aggregation and collagen deposition in liver tissue, Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Epcam, CK19, CK7, Smo, Ptch2, Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed a significant reduction in the number of cells with co-expression of OV6 and CK19 in liver tissue. Conclusion The Hedgehog signaling pathway inhibitor GDC-0449 can significantly inhibit the progression of liver fibrosis induced by CCl 4 /2-AAF in rats, possibly by inhibiting hepatic stellate cell activation, collagen deposition, activation and proliferation of hepatic progenitor cells, and differentiation of hepatic progenitor cells into biliary epithelial cells.

Study on the relationship between lymphovascular invasion and non-sentinel lymph node metastasis in early-stage breast cancer with positive sentinel lymph node / 肿瘤研究与临床

Objective:To explore the relationship between lymphovascular invasion and non-sentinel lymph node (NSLN) metastasis in early-stage invasive breast cancer with positive sentinel lymph node (SLN) and its significance.Methods:The clinicopathological data of 79 patients with stage cT 1-2N 0M 0 invasive breast cancer who had positive SLN by biopsy and underwent axillary lymph node dissection (ALND) from January 2015 to February 2021 in the Central Hospital of Wuhan were retrospectively analyzed. The correlation between patients' clinicopathological characteristics and NSLN metastasis was analyzed. Results:Among 79 patients, 58 patients (73.4%) underwent total mastectomy, 61 patients (77.2%) were Luminal type, 38 patients (48.1%) had lymphovascular invasion, 64 patients (81.0%) had 1-2 positive SLN, and 42 patients (53.2%) with NSLN metastasis were found after ALND. Univariate analysis showed that the proportions of patients with lymphovascular invasion diagnosed by immunohistochemistry [86.8% (33/38) vs. 51.2% (21/41)], Ki-67 positive index>30% [60.5% (23/38) vs. 36.6% (15/41)], positive human epidermal growth factor receptor 2 [36.8% (14/38) vs. 14.6% (6/41)], and elevated lymph node pathological staging [57.9% (22/38) vs. 31.7% (13/41)] in the lymphovascular invasion group were higher than those in the non-lymphovascular invasion group (all P < 0.05). Multivariate logistic regression analysis showed that lymphovascular invasion was an independent risk factor for NSLN metastasis ( OR = 2.935, 95% CI 1.081-7.970, P = 0.035). Conclusions:Lymphovascular invasion is an independent risk factor for NSLN metastasis in SLN-positive stage cT 1-2N 0M 0 invasive breast cancer. It may help to guide the decision-making of local axillary treatment, so as to avoid over or under treatment.

Efficacy observation of anaplastic lymphoma kinase-tyrosine kinase inhibitors in treatment of inflammatory myofibroblastic tumor / 肿瘤研究与临床

Objective:To investigate the efficacy of anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKI) in treatment of inflammatory myofibroblastic tumor (IMT).Methods:The clinicopathological data of one recurrent abdominal IMT patient in Renmin Hospital of Wuhan University in 2018 were retrospectively analyzed. The clinicopathological and molecular characteristics, ALK-TKI treatment efficacy and prognosis of 41 patients with IMT reported in the literature from January 2010 to August 2020 were systematically reviewed.Results:This patient with abdominal IMT in Renmin Hospital of Wuhan University was a 27-year-old female who relapsed 2 months after surgery. Chemotherapy combined with bevacizumab was ineffective. After oral administration of crizotinib, the condition resolved after 1 month, and complete remission (CR) was achieved after 29 months. The median age of onset of 41 IMT cases reported in the literature was 22 years old (0-61 years old), of which 32 cases (78.0%) had multiple organ involvement, all of which had recurrence or metastasis. There were 38 cases of ALK mutation and 3 cases of TFG-ROS1 fusion gene-positive. Thirty-four patients treated with crizotinib in the first-line treatment of ALK-TKI, and the median resistance time of crizotinib was 8 months (2-48 months). The total clinical benefit rate of ALK-TKI was 85.3% (29/34), and 20 patients achieved CR. The median time for the first CR was 11 months (4-36 months), and the median duration time of medication for CR patients was 19.5 months (2-60 months). The median progression-free survival (PFS) time of 24 patients who underwent surgery and/or chemotherapy and radiotherapy was 4 months (1-45 months); after progression, ALK-TKI treatment was performed, and the median PFS time was 14 months (3-62 months).Conclusions:IMT is a true neoplasm with characteristics of recurrence and metastasis. Reasonable combination of ALK-TKI with surgery, radiotherapy and chemotherapy can improve the prognosis of IMT patients.

Effect of polarized bone marrow-derived macrophage transplantation on the progression of CCl / 临床肝胆病杂志

Objective To investigate the effect of polarized bone marrow-derived macrophage (BMDM) transplantation on the progression of CCl 4 -induced liver fibrosis in rats. Methods Rat BMDMs were isolated and induced to differentiate into M1 phenotype (M1-BMDM) by lipopolysaccharide (5 ng/mL) or M2 phenotype (M2-BMDM) by the supernatant of L929 cells. A rat model of liver fibrosis was established by subcutaneous injection of 30% CCl 4 for 6 weeks, and at week 7, the model rats were randomly divided into model control group (M group), M1-BMDM group, and M2-BMDM group and were given a single injection of normal saline, M1-BMDM, and M2-BMDM, respectively, via the caudal vein, and subcutaneous injection of 30% CCl 4 was given until the end of week 9. Related indices were observed, including liver function, liver histopathology, hydroxyproline (Hyp) content in liver tissue, hepatic stellate cell activation, liver fibrosis, and expression of inflammatory cytokines. The continuous data were expressed as mean±standard deviation; an analysis of variance was used for comparison between multiple groups, and the SNK- q test was used for further comparison between two groups. Results Compared with the M group, both M1-BMDM and M2-BMDM significantly inhibited liver inflammation and liver fibrosis progression and significantly reduced serum alanine aminotransferase and aspartate aminotransferase activities ( P < 0.01) and Hyp content in liver tissue ( P < 0.05). M1-BMDM and M2-BMDM significantly inhibited the activation of hepatic stellate cells and significantly reduced the mRNA expression levels of TGF-β, Col1A1, and Col4 (all P < 0.05). Both M1-BMDM and M2-BMDM significantly increased the expression level of CD163 protein in liver tissue ( P < 0.01), and the M2-BMDM group had a significantly higher level than the M1-BMDM group ( P < 0.05); both M1-BMDM and M2-BMDM significantly reduced the mRNA expression levels of MMP-2 and TIMP-1 in liver tissue ( P < 0.05) and significantly increased the mRNA expression level of MMP-13 ( P < 0.01); in addition, M2-BMDM significantly reduced the expression level of CD68 protein in liver tissue ( P < 0.01). Both M1-BMDM and M2-BMDM significantly increased the mRNA expression levels of IL-6 and IL-10 and the protein expression level of albumin in liver tissue (all P < 0.05), and the above indices in the M2-BMDM group were significantly higher than those in the M1-BMDM group (all P < 0.05). Conclusion Both M1-BMDM and M2-BMDM can effectively inhibit the progression of CCl 4 -induced liver fibrosis in rats, possibly by inhibiting the activation of hepatic stellate cells and promoting the activation of anti-inflammatory macrophages. Moreover, M2-BMDM can also inhibit the activation of pro-inflammatory macrophages and thus has a better comprehensive intervention effect than M1-BMDM.

Research advances in the clinical and basic research on Fuzheng Huayu prescription in treatment of chronic liver diseases / 临床肝胆病杂志

Fuzheng Huayu prescription is developed by Shanghai University of Traditional Chinese Medicine and has the functions of promoting blood circulation, removing blood stasis, nourishing essence, and tonifying the liver, and it is an effective empirical prescription for the treatment of chronic liver diseases including chronic viral hepatitis, nonalcoholic fatty liver disease, liver fibrosis, liver cirrhosis, and liver cancer. This prescription has been used in clinical practice for many years and has a marked clinical effect in alleviating clinical symptoms and improving liver fibrosis and complications. In recent years, many scholars have conducted in-depth studies on the clinical effect and mechanism of action of Fuzheng Huayu prescription in the treatment of chronic liver diseases and achieved satisfactory results. This article summarizes related research findings in order to provide a reference for subsequent studies.

Clinical analysis of non-small cell lung cancer patients with leptomeningeal metastasis / 肿瘤研究与临床

Objective:To investigate the treatment, safety and prognosis of advanced non-small cell lung cancer patients with leptomeningeal metastasis and performance status score more than 3.Methods:The clinical data of 6 NSCLC patients with leptomeningeal metastasis admitted to the People's Hospital of Wuhan University from November 2016 to September 2018 were analyzed retrospectively. The curative effect and adverse reactions were observed, and the prognosis was analyzed.Results:There were 5 females and 1 male among 6 patients. The median age was 57 years old (46-74 years old). All 6 patients were diagnosed as stage Ⅳ lung adenocarcinoma. There were 3 patients with epidermal growth factor receptor (EGFR) exon 21 mutation, 2 patients with exon 19 mutation and one with anaplastic lymphoma kinase (ALK) fusion mutation. The time window of leptomeningeal metastasis occurred after the progression of adenocarcinoma of lung: 3 cases was more than 12 months, the other 3 cases was less than 12 months, and the average was 20.3 month. Performance status score was more than 3 when leptomeningeal metastasis occurred. The brain magnetic resonance imaging of 6 patients showed linear enhancement of leptomeningeal, cancer cells were found in cerebrospinal fluid in one case, 4 cases were treated with a combination of bevacizumab and EGFR-tyrosine kinase inhibitor (EGFR-TKI), 1 case was treated with oral administration of EGFR-TKI, 1 case was treated with oral administration of EGFR-TKI combined with temozolomide. The median overall survival (mOS) was 9 months (2-13 months), and the median progression free survival was 6 months (2-11 months).Conclusion:Lung adenocarcinoma may be prone to leptomeningeal metastasis; for NSCLC patients with leptomeningeal metastasis and performance status score more than 3, a combination of EGFR-TKI and bevacizumab has good tolerance, high safety and considerable curative effect.

Cutaneous intravascular large B-cell lymphoma in China: report of 30 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics and prognosis of patients with cutaneous intravascular large B-cell lymphoma (IVLBCL).Methods:The data of 30 cutaneous IVLBCL published between January 1989 and May 2019 in China were systematically reviewed. The clinical manifestation, biochemical and imaging characteristics and diagnostic features of patients were summarized, and then the survival of different groups was also analyzed.Results:The median onset age was 61.5 years old (25.0-83.0 years old), and there were 22 (73.3%) females. All 30 patients presented with cutaneous lesions. Initial symptoms showed cutaneous lesions in 16 (53.3%) patients; and B symptom, respiratory symptoms or central nervous system (CNS) occurred in 14 (46.7%) patients with late cutaneous lesions. Cutaneous lesions were heterogeneous, and 76.7% (23/30) lesions located in lower abdomen and proximal limbs. And 76.2% (16/21) were positive in image examination, and 78.3% (18/23) had two or more extranodal organs invasion. The median time from onset to visit was 2.5 months (0.4-24.0 months), and clinical misdiagnosis rate was 56.7%(17/30). All IVLBCL patients were confirmed by biopsy, including 6 cases (27.3%, 6/22) of bone marrow involvement, 1 case (3.3%) of hemophagocytic syndrome-associated variant, and 29 cases (96.7%) of classical variant. Finally, 81.8% (18/22) patients received anthracycline-based combined chemotherapy. Compared with non-chemotherapy group, the median OS time of chemotherapy group was prolonged [11.0 months (2.0-60.0 months) vs. 2.0 months (0.7-24.0 months), P = 0.002]. Patients with CNS symptoms had shorter median OS time compared with patients without CNS symptoms [2.0 months (0.7-6.0 months) vs. 11.0 months (1.0-60.0 months), P < 0.01]. The median OS time in the group of cutaneous lesions as initial symptom combined with other symptoms was longer than that in group of late cutaneous lesions and other symptoms as initial symptom [unreached (2.0-60.0 months) vs. 3.0 months (1.5-24.0 months), P = 0.032]. Conclusions:Cutaneous IVLBCL is a rare disease with atypical clinical characteristics in China. Prompt attention and biopsy in time will be helpful for early diagnosis. Accompanied with CNS symptoms suggests poor prognosis; and timely chemotherapy can improve the prognosis of the patients.

Clinical study of salvage strategy for patients with locally recurrent esophageal cancer after definitive radiochemotherapy / 中华放射肿瘤学杂志

Objective@#To investigate the salvage strategy and efficacy for patients with locally recurrent esophageal squamous cell carcinoma after definitive radiochemotherapy.@*Methods@#A total of 126 patients who met the inclusion criteria were enrolled in this study and divided into the salvage surgery, salvage radiochemotherapy and best supportive care.@*Results@#Fifty-eight of 126 patients received salvage esophagectomy, 52 underwent salvage radiochemotherapy and the remaining 16 patients received best supportive care. The 1-, 3-, 5-year overall survival rates of patients receiving salvage therapy were 51%, 16% and 4% for the three groups, whereas all patients in the best supportive care group died within 12.0 months (P<0.001). The 1-, 3-, 5-year survival rates in the salvage surgery and salvage radiochemotherapy groups were 48%, 20% and 7%, and 51%, 11% and 3%, respectively (P=0.473). Multivariate analysis by Cox proportional hazard model showed that T staging of recurrent tumors and salvage regimen were the independent prognostic factors in patients with locally recurrent esophageal cancer (both P<0.001). Postoperative infection occurred in 16% of the patients in the salvage surgery group, and the incidence of esophagotracheal fistula and mediastinoesophageal fistula was 10% and 6% in the salvage radiochemotherapy group.@*Conclusions@#A survival benefit can be elicited by salvage surgery or salvage radiochemotherapy in patients with locally recurrent esophageal cancer after definitive radiochemotherapy. Nevertheless, extensive attention should be paid to the management of postoperative complications in clinical practice.

Effect of various cells on the activation of hepatic stellate cells in liver microenvironment / 临床肝胆病杂志

Liver fibrosis is a dynamic pathological process characterized by excessive deposition of extracellular matrix (ECM) or hyperplasia of scar tissue. The activation of hepatic stellate cells (HSCs) is generally considered the central link in the formation of liver fibrosis. HSC activation is regulated by various factors in liver microenvironment, including physical and chemical stimulations and intercellular interactions. Intrinsic cells and immune cells in the liver and HSCs together establish a complex regulatory system to regulate HSC activation and regression. This article introduces the regulatory effect of the cells in liver microenvironment on HSC activation, in order to expand thinking for the research on new diagnosis and treatment methods for liver fibrosis.

Mechanism of Astragaloside prevents cholestatic liver fibrosis through inhibition of Notch signaling activation / 中华肝脏病杂志

Objective@#The Notch signaling pathway is closely related to biliary fibrosis. Previous studies have shown that Astragaloside (AS) can prevent the progression of cholestatic liver fibrosis. The purpose of this study is to observe the effect of AS on the regulation of Notch signaling pathway in biliary fibrosis.@*Methods@#Cholestatic liver fibrosis was established by common bile duct ligation (BDL) in rats. Two weeks after BDL, the rats were randomly divided into a model group (i.e., BDL), an Astragalosides group (AS), and a sorafenib (SORA) positive control group and treated for 3 weeks. Bile duct proliferation and liver fibrosis were determined by tissue staining. Protein and gene expression were determined by immunostaining, immunoblotting and RT-PCR, respectively. Activation of the Notch signaling pathway was evaluated by analyzing expressions of Notch-1, -2, -3, -4, Jagged (JAG)1, Delta like (DLL)-1, -3, -4, Hes1, Numb and RBP-Jκ. Statistical analysis of variance analysis, q test, P < 0.05 showed that the difference was statistically significant.@*Results@#(1) AS significantly reduced the deposition of collagen and the Hyp content of liver tissue (500.15 ± 86.10 vs. 625.72 ± 105.62, P = 0.031), and inhibited the activation of hepatic stellate cells. (2) AS significantly decreased the protein and mRNA expressions of transforming growth factor (TGF)-β1 (1.02±0.15 vs. 1.89±0.36, P = 0.007; 1.17±0.18 vs. 1.68±0.29, P = 0.013, respectively) and α-smooth muscle actin (α-SMA, 0.41±0.11 vs. 0.72±0.16, P = 0.003; 1.71±0.57 vs. 2.68±0.46, P = 0.008, respectively) compared with BDL group. In contrast, AS significantly enhanced expression of the Smad 7 protein compared with the BDL group (0.72±0.008 vs. 0.33±0.001, P = 0.005). AS also reduced biliary epithelial cell proliferation. AS reduced the mRNA levels of CK7, CK8 and CK18 (1.31±0.39 vs. 2.63±0.82, P = 0.009; 0.71±0.09 vs. 0.87±0.08, P = 0.031; 2.56±0.32 vs. 3.41±0.39, P = 0.010, respectively) and reduced the positive areas of CK19 and OV6 (62 337.17±21 873.38 vs. 22 5472.67±26 933.63, P = 0.000; 92 237.43±15 894.11 vs. 171 298.13±61 761.37, P = 0.000, respectively). (3) The mRNA expression of Notch-2, -3, -4 and JAG1 were significantly reduced in the AS group compared to the BDL group (1.07±0.19 vs. 1.51±0.28, P = 0.044; 0.99±0.24 vs. 1.18±0.10, P = 0.043; 1.36±0.42 vs. 3.40±0.44, P = 0.048; 2.62±0.43 vs. 3.73±0.83, P = 0.046, respectively). In contrast, the mRNA level of Numb was clearly enhanced after AS treatment (0.90±0.05 vs. 0.75±0.11, P = 0.019). In addition, consistent with the mRNA levels, the protein expressions of Notch-2, -3, -4 and JAG1 were reduced significantly (1.27±0.18 vs. 1.71±0.26, P = 0.004; 0.99±0.11 vs. 4.38±0.60, P = 0.001; 1.76±0.32 vs. 4.01±0.74, P = 0.002; 1.62±0.33 vs. 2.74±0.63, P = 0.002) and the Numb protein level was increased significantly (1.50±0.15 vs. 0.85±0.11, P = 0.001) in AS group compared with BDL group.@*Conclusion@#AS may prevent cholestatic liver fibrosis via inhibition of the Notch signaling pathway, thereby inhibiting the abnormal proliferation of biliary epithelial cells. Results indicate that AS may be a potential treatment for cholestatic liver disease.

Notch signaling pathway participates in the differentiation of hepatic progenitor cells into bile duct epithelial cells and progression of hepatic fibrosis in cholestatic liver fibrosis rat / 中华病理学杂志

Objective@#To investigate differentiation direction of hepatic progenitor cells (HPCs) in cholestatic liver fibrosis (CLF), and the role of Notch signaling pathway in the differentiation of HPCs.@*Methods@#A CLF rat model was established by bile duct ligation (BDL) followed by monitoring changes of Notch signal pathway and the cellular origin of proliferating cholangiocytes. After intraperitoneal injection of DAPT (a Notch signaling inhibitor) after bile duct ligation, the progress of liver fibrosis and the proliferation of cholangiocytes after inhibition of the Notch pathway were analyzed.@*Results@#Data showed that bile duct proliferation gradually increased along with inflammatory cell infiltration and proliferating bile duct cells surrounded by abundant collagen in the BDL group. Immunostaining confirmed markedly increased expression of CK19, OV6, Sox9 and EpCAM. In addition, RT-PCR results showed that Notch signaling pathway was activated significantly. Once the Notch signaling pathway was inhibited by DAPT, bile duct proliferation markedly suppressed along with significantly decreased the mRNA expression of CK19, OV6, Sox9 and EpCAM, compared with BDL group [(10.2±0.7) vs. (22.3±0.8), (7.6±1.5) vs. (18.1±3.7), (1.4±0.4) vs. (4.1±1.1), (1.3±0.3) vs. (5.0±1.4), respectively, P<0.01]. Moreover, liver fibrosis was also reduced significantly.@*Conclusion@#Notch signaling activation is required for HPCs differentiation into cholangiocytes in CLF and inhibition of the Notch signaling pathway may offer a therapeutic option for treating CLF.

Application of high-fluorescence body fluid cell mode on the platform Sysmex XE-5000 automated blood analyzer in diagnosis of meningeal carcinomatosis / 国际检验医学杂志

Objective To evaluate the performance of high-fluorescence body fluid cell (HF-BF)mode on the platform Sysmex XE-5000 automated blood analyzer,and analyse its clinical application value in diagnosis of meningeal carcinomatosis.Methods E-valuated the performance of HF-BF by using precision test and methodology comparison test.Retrospectively analyzed 295 test re-sults of cerebrospinal fluid in Zhongshan Hospital Affiliated to Xiamen University from June 2010 to September 2012.Results HF-BF on the platform Sysmex XE-5000 automated blood analyzer had high precision,and exhibited a good consistency with cytolgical examination.The percentage of high-fluorescence body fluid cell(HF-BF%)in the meningeal carcinomatosis group was higher than that in other cerebral diseases groups,had statistically significant differences (P < 0.05 ).The cut-off value for HF-BF% was 4.3%,while the area under a receiver operating characteristic (ROC)curve (AUC)was 0.933,the sensitivity was 95.2%,and the specificity was 92.7%.When HF-BF% was over 4.3%,it was more likely to detect tumor cell in cerebrospinal fluid cytology.Con-clusion HF-BF is an effective reference index for the early diagnosis of meningeal carcinomatosis and has significant clinical appli-cation value.

Effects of Chinese herbal medicine Xiaopi Pill in preventing rats from dimethylnitrosamine-induced liver fibrosis / 中西医结合学报

To explore the intervention effects of Xiaopi Pill (XPW), a compound traditional Chinese herbal medicine, on the development progress of dimethylnitrosamine (DMN)-induced liver fibrosis in rats.