1.The effects of TGF-β1 and Smad2 on liver fibrosis of biliary atresia
Meiyun DING ; Jianghua ZHAN ; Li ZHAO ; Linsheng ZHAO ; Aihua ZHANG
Tianjin Medical Journal 2016;44(7):810-813
Objective To investigate the expression and function of transforming growth factor (TGF)-β1 and Smad2 in liver fibrosis of biliary atresia (BA). Methods Liver biopsy specimens were collected from autopsy (normal group, n=5), congenital biliary dilatation (CBD group, n=10), BA patients underwent Kasai procedure (early hepatic fibrosis group, n=19) and liver transplantation (transplantation group, n=11). The first three groups were collected from January 2010 to July 2014 in Tianjin Children’s Hospital, and the last group was collected from January 2013 to January 2014 in Tianjin First Central Hospital. The hematoxylin and eosin (HE) stain were used to observe the degree of liver fibrosis of four groups. Immunohistochemistry (IHC) was used to observe expressions of TGF-β1 and Smad2 in liver tissues of these samples. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to test the quantitative mRNA of TGF-β1 and Smad2 in these samples. Results Results of HE showed that no fibrosis in autopsy group, mild fiber cell hyperplasia in CBD group, severe fibrosis in Kasai group and significant pseudolobule in transplantation group. Results of IHC showed that TGF-β1 was expressed in the cytoplasm of hepatocytes, bile duct cells, lymphocytes and neutrophils. The average optical density of TGF-β1 was the highest in Kasai group compared with that of other three groups (P < 0.05). There was no significant difference in Smad2 expression in cytoplasm of hepatocytes, bile duct cells and lymphocytes between four groups (P>0.05). Results of qRT-PCR showed that both TGF-β1 mRNA and Smad2 mRNA were the highest in early hepatic fibrosis group than those of CBD group and transplantation group (P<0.017). Conclusion In early stage of BA, TGF-β1 and Smad2 promote liver fibrosis until the formation of P-P,P-C desmosome structure. However, with BA fibrosis becomes more serious, the pro-fibrogenic function of TGF-β1 and Smad2 becomes less.
2.Values of histopathological assessment grading score in differential diagnosis of extrahepatic biliary atresia
Li ZHAO ; Xiaoli HU ; Linsheng ZHAO ; Lanyun SONG ; Jianghua ZHAN
Chinese Journal of Clinical and Experimental Pathology 2015;(10):1102-1106
Purpose To study the values of liver histopathological assessment grading score in differential diagnosis between biliary atresia ( BA) and infantile hepatitis ( IHS) . Methods Thirty four cases of BA and sixteen cases of IHS were analyzed retrospectively, which were diagnosed by biopsy. A hepatic histopathological assessment grading score was developed. This consisted of eight features such as cholestasis, hepatocellular damage, bile duct proliferation, portal edema, portal inflammation, portal fibrosis, extramedullary hemopoiesis and multinucleated giant hepatocytes. The total scores were 24 points. All the cases were assessed one by one. Results The total scores of BA were significantly higher than that of IHS (P<0. 001). The frequencies of bile duct proliferation, portal fibrosis and portal edema were significantly higher in BA than that in IHS group, while the frequency of multinucleated giant hepatocytes was significantly higher in IHS than that in BA group. Conclusions This scoring system is helpful in differentiating BA from IHS.
3.Effects of ACTH combined with Huaiqihuang on rat hypothalamic pituitary adrenal axis
Wenhong WANG ; Bili ZHANG ; Yan LIU ; Yan LIU ; Linsheng ZHAO
Tianjin Medical Journal 2016;44(7):857-860
Objective To investigate the effects of adrenocorticotropic hormone (ACTH)combined with Huaiqihuang on hypothalamic pituitary adrenal (HPA) in rats. Methods Fifty rats were randomly divided into five groups according to the random number table method:normal control group (group A), prednisone group (group B), Huaiqihuang group (group C), ACTH group (group D) and combined treatment group (group E) with 10 rats in each group. Rats in group B, C, D and E were gavaged by acetic acid prednisone water solution 12.5 mg/(kg · d) for 4 weeks to establish HPA axis suppression model. Group A was given distilled water 10 mL/(kg·d) as control. Rats in group C and E were gavaged with Huaiqihuang 5 g/(kg·d) 30 minutes after intragastric administration of prednisone acetate. At the third week of the experiment, group D and E were subcutaneous injected with ACTH 200 μg/(kg·d). The serum cortisol levels were measured respectively at the start of the ex?periment, 2 weeks and 4 weeks of experiment. Animals were sacrificed at the end of the experiment, and then weights of the pituitary, adrenal glands and the viscera index were calculated. The pathological changes of the pituitary and adrenal glands were observed by HE stainning. Results After 2 weeks, the serum cortisol levels were significantly lower in group B, C, D and E than those of group A (P<0.05), suggesting that the model was successful. After 4 weeks, the serum cortisol levels were significantly higher in group C, D and E than those of group B (P<0.05), and between the treatment group the value was group E>group D>group C (P<0.05). At the same time, the weights of pituitary and adrenal gland and the viscera in?dex were higher in the three groups than those of B group (P<0.05). The HE staining showed that there were no significant changes in the distal part of the pituitary gland in five groups. The adrenal cortex zona was thinning and the structure was dis?ordered in group B. There were different degrees of hyperplasia in group C, group D, and group E, which was the most obvi?ous in group E. Conclusion ACTH combined with Huaiqihuang can promote adrenal cortex zona hyperplasia and cortisol secretion, which reduces the glucocorticoid induced inhibition of HPA axis in rats.
4.Mutation analysis on DACT1 gene in children with neural tube defects in northern Chinese Han population
Yulian FANG ; Linsheng ZHAO ; Ruiping ZHANG ; Xiufang ZHI ; Yizheng WANG ; Lirong CAO ; Chunquan CAI
Tianjin Medical Journal 2017;45(3):297-300
Objective To investigate the correlation between neural tube defects (NTDs) and DACT1 gene, and provide the basic data for disease diagnosis and genetic counseling. Methods Blood samples were obtained from 163 NTDs patients and 480 unrelated healthy individuals. Mutation detection of DACT1 gene and DNA direct sequencing was carried out by PCR amplification. Bioinformatics analysis of these mutated loci was performed. Results Six mutations were found in NTDs patients, including 4 missense mutations (p.R45W, p.D142G, p.N356K and p.V702G). But these mutations were not found in 480 healthy individuals. Three mutated amino acid residues (p.45R, p.142D and p.356N) were highly conservative in evolution, and the mutated carriers were female patients, and suffered from anencephaly. Conclusion DACT1 gene mutation may be a risk factor of NTDs in Han population of northern China.
5.Distribution of androgen receptor and estrogen receptor in penis skin of patients with hypospadias
Linsheng ZHAO ; Ziying CHEN ; Haihua XU ; Rongrong LANG ; Xiaoli HU ; Guodong XU
Tianjin Medical Journal 2016;44(12):1504-1506
Objective To characterize the expressions of androgen receptor (AR) and estrogen receptor (ER) in penis skin of patients with congenital hypospadias. Methods Dorsal prepuce, ventral prepuce, and urethral plate were harvested from 30 patients with congenital hypospadias. The expressions of AR and ER in epidermal cells and dermal fibroblasts were assessed respectively by automated immunohistochemistry. Image Pro plus 6.0 was used to analyze the optical density (OD) value of AR and ER in different parts of epidermal cells and dermal fibroblasts. Results AR and ER were located mainly in nucleis of the squamous basal cells and prickle cells, and were also found in nucleis of subcutaneous fibroblast cells. The expression of AR was lower in epidermis of urethral plate than that of dorsal prepuce and ventral prepuce (P<0.05), but no significant difference was detected in dermal fibroblasts. The expression of ER was higher in epidermis of dorsal prepuce than that of urethral plate and ventral prepuce (P<0.05). The dermal expression of ER in fibroblast cells was increased successively in dorsal prepuce, ventral prepuce and urethral plate (P<0.05). Conclusion Lower expression of AR in urethral plate may contribute the development of hypospadias. Disorder of ER in dermal fibroblast cells of prepuce may play an important role in hypospadias.
6.The effects of ACTH and Huaiqihuang on the treatment of recurrence nephrotic syndrome in children
Wenhong WANG ; Bili ZHANG ; Yan LIU ; Yan LIU ; Linsheng ZHAO ; Lixiao YANG
Tianjin Medical Journal 2017;45(1):54-57
Objective To observe the effects and safety of adrenocorticotropic hormone (ACTH) combined with Huaiqihuang on frequent relapse nephrotic syndrome (FRNS) in children. Methods Fifty-five child patients with FRNS were divided into control group, which was given glucocorticoid (GC) to maintain the treatment (group A, n=10), Huaiqihuang group (group B, n=17), ACTH group (group C, n=14) and ACTH combined with Huaiqihuang group (combined treatment group, group D, n=14). Continuous treatment was for 12 months. The GC treatment doses, the levels of basal secretion of adrenal cortex and adrenal cortex reserve were recorded at 6-month and 12-month respectively. And the recurrence rate and adverse reactions were observed in four groups. Results After 6-month treatment, the doses of GC were significantly lower in group C and group D than those in group A and group B (P<0.05). The levels of basal secretion of adrenal cortex were increased in turn in group A~D (P<0.05). After 12-month treatment, the doses of GC were significantly decreased in group C and group D than those in group A and group B, while the level of basal secretion of adrenal cortex and adrenal cortex reserve were increased (P<0.05). There were no significant differences in the doses of GC between group C and group D (P>0.05). After treatment for 6 months and 12 months, the recurrence rates of nephrotic syndrome were significantly lower in group C and group D than those of group A and group B (P<0.05). Conclusion The simple application of ACTH and the combination of Huaiqihuang can relieve the inhibition of long-term using GC on hypothalamic pituitary adrenal axis in FRNS patients.
7.Precursor T-lymphoblastic lymphoma of the breast: one case report and reviews of literature
Xiaofan LIU ; Yaozhong ZHAO ; Yafei WANG ; Ying WANG ; Dehui ZOU ; Linsheng QIAN ; Lugui QIU
Journal of Leukemia & Lymphoma 2008;17(2):110-113
Objective To improve the recognition of precursor T- lymphoblastic lymphoma (T-LBL)of the breast. Methods One case of breast T- LBL was reported, the development of breast non-Hodgkin lymphoma and T-LBL presenting as breast masses was reviewed. Results One case of breast T-LBL was diagnosed, the patient with a high leukocyte count, breast mass and peripheral lymph nodes was treated with Hyper-CVAD regimen after active therapy and achieved complete remission (CR). Followed by maintenance therapy with Hyper-CVAD regimen for three times, disease free survival had been obtained five month.Conclusion Lymphoma of the brest is a rare malignancy. T-LBL is a highly aggressive disease with adverse prognosis, it is very uncommon for presenting as lymphoma of breast. Initiation of intensive muhiagent chemotherapy can improve the free survival and the prognosis.
8.Establishment of liver IL-6 reporter mouse model by hydrodynamic gene transfection
Cong MA ; Yulong ZHANG ; Qianqian ZHOU ; Man ZHAO ; Xiaohui WANG ; Xinquan JIANG ; Linsheng ZHAN
Military Medical Sciences 2017;41(4):269-272,277
Objective To construct a mouse model for real-time,noninvasive and specific monitoring of inflammation activation in hepatic tissues.Methods An inflammation reporter gene was targeted to the liver by hydrodynamic gene delivery technology.Bioluminescence imaging was used to detect the firefly luciferase(Fluc) expression in the mouse liver after inflammatory stimulation.Besides,the relevance between the light intensity and inflammation level was also intensively investigated.Results pIL-6-Fluc was successfully delivered to the liver.The hydrodynamic gene delivery could cause a transient liver injury that could return normal in 5 to 7 days.The expression of pIL-6-Fluc could be induced by lipopolysaccharides(LPS) treatment with an about (46.80±13.35) fold increase at the peak value,which was significantly higher than that detected by ELISA [(4.09±0.96)fold].Conclusion An inflammation reporter mouse model is constructed in this study by hydrodynamic gene transfection,allowing noninvasive monitoring of inflammation activation specifically in hepatic tissues.The reporter model is capable of monitoring inflammation activation with a sensitivity higher than that of ELISA.
9.Severe pulmonary complication after bortezomib treatment for multiple myeloma: two cases report with literature review
Yafei WANG ; Lugui QIU ; Dehui ZOU ; Ying WANG ; Shuhui DENG ; Yuan LI ; Yan XU ; Linsheng QIAN ; Yaozhong ZHAO
Journal of Leukemia & Lymphoma 2008;17(2):100-102
Objective To report two cases of severe pulmonary complication after bortezomib treatment for multiple myeloma. Methods Two cases of severe pulmonary complication after bortezomib treatment patients with relapsed multiple myeloma wereas discussed with review of literature. Results Two relapsed MM patients were treated with bortezomib and thalidomide or dexametbasone. Cough, dyspnea, fever and hypoxia developed after completion of bortezomib. Chest X-ray revealed bilateral pulmonary infiltrates,but infection was not identified with sputum cultures, and broad-spectrum antibiotics were ineffective.Conclusion Severe pulmonary injury was rare complication in patients receiving treatment for multiple myeloma, however, it was a life-threatening disorder. Prophylaxis corticosteroids maybe effective. Although corticosteroids are effective, but the mechanism of lung injury associated with bortezomib is unclear, and further evaluation of this potential toxicity is appropriate.
10.Investigation of long-term follow-up results of 135 patients with chronic myeloid leukemia receiving imatinib
Keshu ZHOU ; Cuicui WANG ; Yaozhong ZHAO ; Lijie XING ; Linsheng QIAN ; Zhen YU ; Junyuan QI ; Jianxiang WANG ; Lugui QIU
Journal of Leukemia & Lymphoma 2010;19(11):646-650
Objective To evaluate the efficacy and safety of imatinib in chronic myeloid leukemia (CML) patients and analyse the factors affecting the survival. Methods 135 CML patients receiving imatinib were evaluated for hematologic, cytogenetic, and molecular responses and adverse events. Results The median follow-up was 20 (range 3-67) months. The rate of cumulative complete hematological response (CHR), major cytogenetic response (MCyR), complete cytogenetic response( CCyR ) and complete molecular response (CMoR) in chronic phase CML patients were 97.9 %, 78.3 %, 72.2 % and 35.1%, respectively.These rates were significantly higher in chronic phase than in accelerated phase and blastic phase (P <0.001).The rate of CCyR in low-risk patients was significantly higher than high-risk patients (P =0.048). The estimated overall survival (OS) rate at 1, 3 and 5 year for chronic phase patients were (97.8±1.5) %, (95.2±2.4) % and (91.9±3.2) %, respectively. The estimated progression-free (PFS) survival rate at 1, 3 and 5 year were (92.6±2.7) %, (85.5±3.7) % and (81.3±4.3) %, respectively. The OS rate for accelerated phase patients at 6, 12 and 24 month were (93.8±6.1) %, (72.5±11.8) % and (64.5±12.9) %, the PFS rate were (92.3±7.4) %,(64.5±14.7) %, (53.7±15.7) %, respectively. The OS rate for blastic phase patients at 6, 12 and 19 month were (86.4±7.3) %, (45.4±11.4) %, (19.4±9.8) %, the PFS rate were (70.1±12.6) %, (37.6±15.6) % and (18.8±15.4) %, respectively. The OS and PFS of patients in chronic phase who achieved CCyR or CMoR were better than patients only achieved CHR (P ≤0.001). Multivariate analysis for survival of chronic phase patients indicated that imatinib resistance was the unfavourable factor for PFS (P =0.000, RR =46.744) and OS(P =0.007, RR =20.270). The non-hematological toxicity of imatinib was slight and tolerable, severe hematological toxicity was the major reason for dose reduction or drug discontinuation. Conclusion The efficacy of imatinib in chronic phase CML patients is significantly superior to which in accelerated phase and blastic phase; Achieving CCyR even CMoR is the most important thing for longer survival, iinatinib resistance is the major problem in the treatment with imatinib.