1.Intestinal absorption of forsythoside A by rat circulation in situ.
Wei ZHOU ; Liuqing DI ; Xiaolin BI ; Letian CHEN ; Qiu DU
Acta Pharmaceutica Sinica 2010;45(11):1373-8
This study is to investigate the effects of concentration, intestinal section, pH, paracellular route, substrate/inhibitor of enzyme (CYP3A) and proteins (P-gp, MRP2, SGL1) on the absorption of forsythoside A. The absorption of three concentrations (2.6, 5.2, and 10.4 microg x mL(-1)) of forsythoside A in different intestinal segments was studied with phenol red as the marker by rat circulation in situ. The results showed that the residue of forsythoside A with different concentrations had little significant difference from that obtained after perfusing via duodenum, jejunum, ileum and colon, which indicated that the absorption of forsythoside A was passive diffusion and had no difference in different segments of rat intestine. The residue of forsythoside A increased to 466.160 and 463.429 microg respectively when cyclosporine (4 microg x mL(-1)) or midazolam (50 micromol x L(-1)) was added to the circulation fluid, which showed significant difference compared to the control group (P < 0.05). Moreover, the residue of forsythoside A showed a tendency of increase with the increase of cyclosporine or midazolam. When digoxin (50 micromol x L(-1)) or EDTA (10 microg x mL(-1)) was added to the circulation fluid, the residue of forsythoside A decreased to 325.110 and 369.888 microg respectively, which showed significant difference as compared to the control group (P < 0.05). Besides, the residue of forsythoside A showed a tendency of reduction with the increase of digoxin or EDTA. However, there is no significant change in the absorption of forsythoside A when the different concentrations of mannitol were added to the circulation fluid. The results above indicated that the absorption of forsythoside A was mainly passive diffusion and involved paracellular route at the same time. In addition, the substrates of P-gp or CYP3A had dose-dependent effect on the absorption of forsythoside A.
2.Expression and significance of metallothionein in liver transplantation for patients with benign end-stage liver diseases
Letian WANG ; Shan SHAN ; Hong WANG ; Hong CHEN
Chinese Journal of Organ Transplantation 2013;34(7):415-418
Objective To investigate the expression of metallothionein (MT) in 113 specimens of liver transplantation for patients with benign end-stage liver diseases and 10 normal liver specimens,and analyze their clinical significance and prognostic value.Method 113 specimens of liver transplantation for patients with benign end-stage liver diseases and 10 normal liver specimens were included in this study.MT in these specimens was detected by using immunohistochemistry.Cox regression model was used to analyze the multi-factors for the prognosis.Results MT levels were lower in specimens of liver transplantation for patients with benign end-stage liver diseases than in normal liver specimens.MT levels were higher in specimens of HCV-related cirrhosis than in those of autoimmune hepatic (AIH) cirrhosis,but there was no significant difference among all other groups.Conclusion MT expression level in AIH cirrhosis tissue is higher than in HCV-related cirrhosis tissue.MT is the independent influencing factor for survival following liver transplantation in patients with benign end-stage liver diseases.
3.Study on the value of salivary gland ultrasonography in Sj(o)gren's syndrome
Mingzhu ZHOU ; Shuju SONG ; Letian CHEN ; Xi LIU ; Ting DUAN
Chinese Journal of Rheumatology 2016;20(5):317-320
Objective To clarify the diagnostic value of salivary gland ultrasonography in Sj(o)gren's syndrome (SS),and its correlation with the disease activity index and important organs involvement were analyzed.Methods A total of 116 patients with SS were involved,including 71 cases of primary SS and 45cases of secondary SS.Ultrasonography examination of major salivary glands was conducted for these patients,at the same time the clinical data including inflammatory parameters,the immunological parameter and the involved systems were collected.Ultrasonography examination was conducted in 49 cases as the control group.Use t test,x2test and analysis of variance for statistical analysis.Results The positive rate of salivary gland uhrasonography in SS (56/116,48.3%) was significantly higher than that of the normal control groups (1/49,2.0%),(The chi-square value was 32.57,P<0.05),the sensitivity of salivary gland ultrasonography in primary SS (62.0%) was obviously higher than secondary SS (27%),(The Chi-square value was 13.75,P<0.01).The specificity of salivary gland ultrasonography was 98%.The scores of salivary gland ultrasonography had shown positive correlation with the erythrocyte sedimentation rate,the levels of Immunoglobulin (Ig)G,and RF(r=0.234,0.353,0.176;P=0.002,0.000,0.013),and negative correlation with the white blood cell count (r=-0.292,P=0.000).Conclusion Salivary gland ultra-sonography provides additional evidence for the diagnosis of SS,particularly in primary SS groups.The scores of ultrasonography are correlated with inflammatory biomarkers,indicating that salivary gland ultrasonography is related to disease activity.
4.Establishment and significance of research-based clinical liver transplantation specimen bank for hepatocellular carcinoma
Qing ZHANG ; Yuwen HAO ; Yang YUE ; Hong CHEN ; Letian WANG ; Xinguo CHEN ; Zhongyang SHEN
Chinese Journal of Tissue Engineering Research 2014;(49):7985-7989
BACKGROUND:The establishment of a standardized clinical liver transplantation specimen bank is the primary condition for scientific research in this field, which can help to provide a qualified sample resource platform for research. OBJECTIVE:To primarily establish biological specimen bank of hepatocelular carcinoma for liver transplantation, to explore the standardized procedures of specimen colection, processing and preservation of hepatocelular carcinoma for liver transplantation, and to establish the sound and comprehensive information management system of clinical information of colected specimens. METHODS: In accordance with standardized procedures to establish biological specimen banks, the operational processes and quality control system were formulated. Liver tissue and blood samples of hepatocelular carcinoma recipients undergoing liver transplantation were regularly colected, managed and stored. Simultaneously, liver tissue and blood samples of benign liver disease in liver transplant recipients and of healthy donor were colected as controls. A systematic management was conducted in colected specimens and corresponding clinical information. RESULTS AND CONCLUSION:From August 2009, tissue and blood samples of 501 cases of receipts and donors undergoing liver transplantation with complete clinical information were colected from the specimen bank, including 203 hepatocelular carcinoma specimens, 214 benign liver disease specimens and 84 healthy donor specimens. These specimens included tumor tissue, adjacent tissues and distal non-cancerous tissue specimens, totaly 1 773. A total of 45 specimens were randomly selected for quality monitoring. The colected specimens had a high quality. Specimen information data computer management system was developed. This study initialy established a standardized research-based clinical transplantation specimen bank, which is helpful to elevate sample quality and has a good manipuility.
5.Application of liver grafts from HBsAg positive donors in liver transplantation for hepatocellular carcinoma beyond UCSF Criteria
Xinguo CHEN ; Zhongyang SHEN ; Yujian NIU ; Shan SHAN ; Letian WANG ; Li LI ; Jun LI
Chinese Journal of Organ Transplantation 2013;34(9):528-531
Objective To evaluate the outcomes of liver transplant recipients who received liver grafts from HBsAg positive donors in patients with hepatocellular carcinoma beyond UCSF (University of California,San Francisco) Criteria.Method The medical records of patients who underwent HBsAg-positive donor liver transplantation for hepatocellular carcinoma beyond UCSF Criteria from October 2008 to December 2012 at our hospital were analyzed retrospectively,including the existence status of HBV,graft function,tumor recurrence,and the survival after transplantation.Result A total of 20 patients were enrolled in the study.One patient lost follow-up while the remaining 19 patients had complete follow-up data.All the patients were followed up until June 2013,with a median follow-up duration of 12 months (range 2-57 months).One patient died from postoperative abdominal bleeding and multiple organ failure at post-transplantative day 21.Five patients survived up to now,including 4 cases with disease-free survival,who has been surviving for 57,35,26 and 12 months respectively.The remaining all 14 patients died from tumor recurrence at different time points after transplantation.Entecavir was used alone in 19 patients and Entecavir combined with Adefovir dipivoxilalone were used as anti-HBV therapy in the recipients.At posttransplant day 45,all the recipients were positive for serum HBsAg and negative for serum HBVDNA,and the liver enzymatic criteria,coagulation criteria and the serum bilirubin restored to normal levels or within twice the upper limit of normal levels.Throughout the follow-up period,recipients were all positive for serum HBsAg,but there was no recurrence of hepatitis B.The 1-,2-,3-and 4-year cumulative survival rate was 48.0%,35.0%,18.7% and 18.7% respectively.Conclusion The HBsAg positive liver may be used as a donor in liver transplantation and the graft probably works well after the operation.Liver transplantation may prolong the survival and improve the quality of life,even achieve long-term disease-free survival in patients with hepatocellular carcinoma beyond UCSF Criteria.The use of nucleotide analogue only,instead of combination with hepatitis B immune globulin,can also bring HBV well under control in liver transplant recipients with HBsAg positive donors.
6.Impact of sirolimus and tacrolimus on the tumor recurrence after liver transplantation due to HCC beyond milan criteria: randomized controlled clinical trial
Yujian NIU ; Yu LIU ; Letian WANG ; Sha MAO ; Li LI ; Zhaojie GUAN ; Xinguo CHEN
Chinese Journal of Organ Transplantation 2014;35(2):99-102
Objective To compare the impact of the sirolimus and tacrolimus on the tumor recurrence after liver transplantation due to HCC beyond Milan criteria.Method Sixty-one liver transplantation recipients due to HCC beyond Milan criteria,between Jan.2008 and Apri.2012,were randomized,with the informed consent,into two different immunosuppression groups: sirolimus group (n=30) and tacrolimus group (n=31).In tacrolimus group,tacrolimus was used as the basic immunosuppressant,methylprednisolone was discontinued within one month postoperatively,and mycophenolate mofetil was used within the dosage of 1.5 g/d accordingly.In sirolimus group,the immunosuppresive scheme was the same as that of the tacrolimus group within postoperative one month,and from that,tacrolimus was transferred to sirolimus.No antineoplastic agents were given before tumor recurrence.The tumor recurrence rate and the survival rate of the recipients were compared between the two groups.Result The median follow-up duration was 35.2 months (10.3~ 60.2).The tumor recurrence rate at postoperative year 1,2,3 and 4 in the sirolimus group (13.3%,36.7%,43.3% and 53.3%) was significantly lower than that in the tacrolimus group (38.7%,67.7%,74.2% and 77.4%),P < 0.05 for all.The one-year survival rate in the recipients postoperation had no significant difference between sirolimus group and tacrolimus group (90.0% vs.87.1%,P=0.438).The 2-,3-and 4-year survival rate in the recipients was significantly higher in the sirolimus group (53.3%,33.3% and 20.0%) than that in the tacrolimus group (41.9%,22.6% and 9.7%),P < 0.05 for all.The liver function and renal function of the recipients at the postoperative year 1,2,3 and 4 showed no significant difference between the two groups,P>0.05.Conclusion In comparison with tacrolimus,sirolimus could significantly reduce the tumor recurrence rate and increase the survival rate for the liver transplant recipients due to HCC beyond Milan criteria.
7.Diagnosis and Curative Effect of Tuberculosis in Solid Organ Transplantation Patients
Hong CHEN ; Hang LIU ; Qing ZHANG ; Letian WAMG ; Yan TIAN ; Xu WANG
Chinese Journal of Nosocomiology 2009;0(14):-
OBJECTIVE To investigate the clinical feature,diagnosis and treatment of tuberculosis in post-solid organ transplantation patients.METHODS The clinical data of 11 patients with tuberculosis post-solid organ transplantation were analyzed retrospectively,in which eight cases were the patients with post-liver transplantation,two cases were the patients with post-kidney transplantation and one patient with post-liver and kidney transplantation.The diaghosis were based on the case history,pathogenic,image and the consequence of diagnostic therapy against tuberculosis were observed.RESULTS Infection rate of tuberculosis after liver transplantation,kidney transplantation and combined liver and kidney transplantation were 0.92%,1.10% and 7.14%,respectively.The three cases suffered from acute miliary tuberculosis.One case suffered from exudative pulmonary tuberculosis.One case suffered from tuberculosis pleuritis.One case suffered from lymph node tuberculosis.One case suffered from tuberculosis of lumber spine complicating exudative pulmonary tuberculosis.Four cases were not found lesion in their body.Each patient was adopted with individual treatment.The following up were 83 day to 1080 day.One case was died.Ten cases were cured.CONCLUSIONS Tuberculosis patients with post-solid organ transplantation had atypical clinical symptom under immunosuppressive agents.Part of the patients are lacked of evidences from image,bacteriology or immunology.Diagnostic errors are made sometimes.Diagnostic therapy against tuberculosis should be put into practice for the patients with suspicious tuberculosis.
8.Preliminary comparison of whole-body diffusion-weighted MRI and PET on tumor imaging
Houyi KANG ; Weiguo ZHANG ; Rongbin JIN ; Yi WANG ; Jinhua CHEN ; Letian ZHANG ; Lili WANG ; Bo ZOU ; Changsuo MA
Chinese Journal of Medical Imaging Technology 2010;26(4):748-751
Objective To assess the value of clinical applications of whole-body diffusion-weighted imaging (WB-DWI) in diagnosing patients with malignant tumors compared with positron emission tomography (PET). Methods A total of 22 patients with highly suspected malignant tumors underwent WB-DWI after PET. The differences between the two imaging methods were compared in displaying lesions, and the correlation between ADC and SUV value was analyzed. Results More lesions were showed with WB-DWI than PET. There was no significant difference between the two methods in detecting the lesions of lung, mediastinal septum or abdomen (P>0.05), but more lesions in skeleton were showed with WB-DWI (P<0.05). No significant correlation between ADC and SUV value was found. Conclusion Compared with PET, WB-DWI can detect more tumor lesions. The sensitivity of WB-DWI in detecting metastatic tumors of bone is higher than that of PET.
9. Application of exosomal miRNA in early diagnosis and early screening of breast cancer
Letian CHEN ; Dongxian ZHOU ; Chen YAN
International Journal of Surgery 2020;47(1):48-54,f4
Breast cancer is the most common malignant tumor in women. The key to the prognosis of breast cancer lies in early diagnosis and early treatment.At present, the early diagnosis of breast cancer mainly relies on imaging methods, and there has been a lack of clinical methods for early diagnosis of it.Exosome are small molecules selectively released from breast cancer cells to the peripheral circulation for a certain period of time. miRNA contained in them are short, non-coding regulatory RNA, which can bind to the 3′UTR region of target genes and regulate the post-transcriptional expression of target genes. Exogenous miRNA can affect the development of breast cancer, It can provide a variety of information indicating the presence of breast cancer cells, clinical staging, molecular typing and other information, which may be put into clinical application in the future as an ideal marker for the early diagnosis of breast cancer.This article reviews the research and application of exogenous miRNA in early diagnosis of breast cancer.
10.Zoledronic acid affects osteogenic differentiation and bone formation by regulating the expression of SIRT3/P53
Jie HAN ; Letian QIAO ; Xiaoyi WANG ; Huihui CHEN ; Naying CHU ; Peili CHEN
Chinese Journal of Endocrine Surgery 2024;18(1):130-137
Objective:To explore the mechanism of zoledronic acid (ZOL) affects osteogenic differentiation and bone formation through the regulation of sirtuin 3 (SIRT3) / P53 expression.Methods:Bone marrow mesenchymal stem cells (BMSCs) were induced to differentiate into osteogenic cells, the expression of SIRT3 in the cells was detected, and the targeting regulation relationship between SIRT3 and P53 was analyzed. The intracellular expressions of SIRT3 and P53 were intervened and ZOL was used to treat the cells. MTT method, Western blot method and kit were used to detect cell viability, osteogenesis-related genes Osteoprotegerin (OPG), runt-related transcription factor 2 (Runx2) expression, alkaline phosphatase (ALP) activity and alizarin red S (ARS) staining, respectively. Ovariectomy (OVX) was used to construct a rat model and explore the effect of ZOL on the progression of osteoporosis (OP) in vivo.Results:ZOL promoted osteogenic differentiation of BMSCs. The expression of SIRT3 was down-regulated in the serum of OP patients (0.78±0.23) compared with that of healthy subjects (1.00±0.26 vs. 0.78±0.23. t=3.85, P<0.001). During the osteogenic differentiation of BMSCs, the expression level of SIRT3 gradually increased with the prolonged induction of osteogenesis. Compared with the p53 protein expression and BMSCs activity in the control group, SIRT3 knockout could increase the expression level of p53 protein (0.59±0.05 vs. 1.01±0.11. t=6.02, P=0.004) but inhibited the activity of BMSCs (100.00±8.41 vs. 51.26±5.59. t=8.36, P=0.001). After ZOL treatment, the inhibitory effect of SIRT3 on cell viability (49.61±5.11 vs. 87.61±7.31. t=7.38, P=0.002) and osteogenesis was relieved, and the level of P53 was inhibited (1.10±0.10 vs. 0.69±0.04. t=6.59, P=0.003). P53 overexpression partially offseted the effects of ZOL on cell viability (84.61±6.52 vs. 66.54±5.47. t=3.68, P=0.021) and osteogenesis. Compared with the sham surgery group, the OVX group showed inhibition of osteogenesis in rats, and ZOL treatment significantly improved osteogenic inhibition. ZOL treatment increased the expression level of SIRT3 protein in bone tissue of OVX rats, but inhibited the expression level of P53. Conclusion:ZOL promoted osteogenic differentiation and bone formation of BMSCs by promoting the ubiquitination and degradation of P53 by SIRT3.