Objective:To investigate the pharmacokinetics of mycophenolic acid( MPA)and its metabolites in different stages af-ter the administration of enteric-coated mycophenolate sodium( EC-MPS)tablets in Chinese liver transplant recipients. Methods:The blood samples of 24 patients were collected in 0-12h of the 1st and 3rd week after the administration of EC-MPS. The concentrations of MPA,AcMPAG and MPAG in plasma were measured by LC-MS/MS developed in our lab. The pharmacokinetic parameters of MPA and its metabolites were estimated by non-compartmental method. Results:After 1-and 3-week therapy with EC-MPS,Cmax ,AUC0-12 and t1/2 was(18. 1 ± 8. 75)and(20. 7 ± 16. 0)μg ml-1 ,(42. 7 ± 17. 5)and(47. 1 ± 23. 9)μg·h·ml-1 ,(3. 33 ± 2. 81)and (3.30 ±1.89)h for MPA;(2.50 ±1.86)and(1.78 ±1.72)μg·ml-1,(14.5 ±11.7)and(6.97 ±6.57)μg·h·ml-1, (4. 48 ± 2. 53)and(3. 76 ± 1. 8)h for AcMPAG;(171. 6 ± 135. 4)and(152. 2 ± 115. 9)μg·ml-1 ,(1299 ± 1 204)and(1 051 ± 561)μg·h·ml-1 ,(8. 73 ± 4. 25)and(7. 75 ± 2. 87)h for MPAG,respectively. There was no significant difference in the PK parameters of MPA after the 1-and 3-week therapy. The Cmax ,Tmax and t1/2 of MPA in the patients received EC-MPS were significantly higher than those in the patients received MMF(P<0. 05). Cmax and AUC0-12 of MPAG in the patients received EC-MPS were signifi-cantly higher than those in the patients received MMF after the 3-week therapy(P<0. 05). Conclusion:There is no significant accu-mulation of MPA after the therapy with EC-MPS at different stages. The absorption of MPA is delayed after the therapy with EC-MPS compared with that with MMF. There is no difference in MPA exposure between EC-MPS and MMF in Chinese liver transplant patients.

AIM: To examine the autoantibody against ? 1-adrenoceptor and its biologic activities during the development of renal hypertension. METHODS: Renal hypertension of rat was achieved by clipped renal artery, the titre of autoantibody to ? 1-adrenoceptor was detected using ELISA immunoassay. Furthermore, the biological offects of these autoantibodies on cultured cardiomyocytes were also examined. RESULTS: After two weeks of clipping renal arteries, both the frequency of occurrence and the titre of autoantibodies to cardiac ? 1-adrenergic receptor were significantly increased as compared with the control of pre-treatment. The increased autoantibodies lasted for several weeks and then automatically decreased gradually to the pre-clipping level at 12 weeks. The biological effects of these autoantibodies displayed an "agonistic-like" activities on the beating frequency of cultured neonatal cardiomyocytes. CONCLUSION: Autoantibodies against ? 1-adrenoceptor may play a role in the elevation of peripheral vascular resistance and in the development of cardiac hypertrophy in rats with renal hypertension.

Pathologic experiment teaching is special feature and stresses morphologic teaching,It is easy for stuents to learn passively.Problem-basedlearning ( PBL ) was introduced in pathologic experiment teaching in eight-year clinical medicine.program courses.In pathologic experiment class,questions was produced by analyzing various diseases,observing macroscopic and microscopic changes,discussed by clinical cases and solved by students themselves with bilingualistic teaching.In conclusion,PBL was significant in improving the quality of pathological experiment teaching,overcoming the shortage of morphologic learning,and making students more active in learning pathology.

Objective To find out a reference range of epidermal nerve fiber density in normal humans and compare the concordance between clinical features, electrophysiology and the results of skin biopsy. Methods Fifty-one patients with peripheral neuropathy and 10 normal controls were studied. Skin biopsies were obtained from distal leg and/or proximal leg and nerves identified using immunohistochemistry with antibody against protein gene product (PGP) 9. 5. Forty-one in 51 performed routine nerve conduction vdocity and electromyography, 21 in 51 performed sympathetic skin response(SSR). The concordance of the consequences was compared. Results Intraepidermal nerve fiber density (IENFD) was (21.4 + 2. 7) /mm in thigh and (15.4±2. 2) /mm in the distal part of the leg in normal controls. IENFD was (15.0± 6. 3)/mm and (8. 1±5.9) /mm in patients. The intraepidermal nerve fiber density was significantly lower in the patients than in the normal controls both in proximal (t = 2. 976, P = 0.004) and distal legs (t= 3.191, P=0.002). Forty-eight out of 51 patients showed abnormalities in skin biopsy, among which 33 patients had length-dependent neuropathy. In the group of abnormal skin biopsy, 41 received routine electrophysiology, among which 21 (51.2%) were abnormal and they were performed SSR, turning out that 17 (81.0%) were abnormal. In 29 patients who had only small fiber neuropathy, 27(93. 1%) showed abnormalities in skin biopsy, out of whom 20 were performed routine electromyography, and it identified that 6 (30. 0%) were abnormaL In 14 receiving SSR, 11 were abnormal. Conclusion Skin biopsy is safe and tolerable, which has a higher sensitivity especially in small fiber neuropathy.

Objective To investigate use of magnetic resonance diffusion tensor imaging (MR-DTI) for quantitatively evaluating the efficacy of Mailuoning Injection on non-compressive lumbar radiculitis.Methods Nine Bama mini pigs were selected and divided into group A,B and C,3 cases in each group.The non-compressive lumbar radiculitis model was established under CT-guiding.The corresponding therapeutic drugs (group A:10 mL Mailuoning;group B:10 mL normal saline;group C:10 mL diminishing inflammation fluid) were given by epidural injection on 14 d after constructing model.MR-DTI was performed before model construction,14 d after model construction and before treatment.One experimental pig in each group was taken on 3,7,14 d after treatment,performed MR-DTI and killed for taking the nerve root sample to conduct the immunohistochemical detection.The fractional anisotropy (FA) values of nerve root in MR-DTI imaging were measured.The FA values and immunohistochemical detection results were statistically analyzed.Results MR-DTI:the FA values after model construction in each group was decreased (P<0.05);the FA values on 14 d after treatment in the group A was increased,which showed statistically significant difference compared with before treatment (P<0.05);the FA values after 3,7 d treatment in the group A had no obvious increase,the difference between the group A and B was not statistically significant (P>0.05),but the FA values increase in the group C was earlier and more rapid than other two groups (P<0.05);the FA values after 14 d treatment in the group A was risen again,the FA values of bilateral nerve roots had no statistical difference between the group A with the group B and C (P>0.05),while the FA values had statistical difference between the group B and C (P<0.05).The immunohistochemical results:TNF-α integral absorbency value(IA value) on 7 d after treatment in the group A began to decline;the TNF-α IA value on 14 d after treatment in the group A and C was significantly decreased compared to group B,the difference was statistically significant (P<0.05).Conclusion Mailuoning Injection has a certain effect on non-compressive lumbar radiculitis,which can be evaluated by using DTI.

Purpose: The purpose of this study was to investigate the influences of sex comb on midleg like-2 (SCML2) on hepatocellular carcinoma (HCC) and potentially related mechanisms. Materials and Methods: SCML2 expression in tumor tissues and cells was analyzed using the TCGA database and/or qRT-PCR. The proliferation of HCC cells was detected by CCK-8, colony formation, and EdU assays. The migration and invasion of HCC cells were detected by transwell and wound healing assays. Apoptosis of HCC cells was determined by flow cytometry. Additionally, qRT-PCR and Western blot were used to detect the expression of SCML2 and Wnt/β-catenin/epithelial–mesenchymal transition (EMT) signaling. A xenograft model in mice was established to verify the in vitro findings. Results: We found that SCML2 was highly expressed in HCC tissues and cells and that high expression of SCML2 was correlated with poor prognosis in HCC patients. SCML2 overexpression promoted proliferation, invasion, and migration and repressed apoptosis of HCC cells. The reverse results were obtained in SCML2-silenced cells. Further, we found that SCML2 activated the Wnt/β-catenin/EMT pathway. SCML2 silencing reduced the protein levels of Wnt3a, β-catenin, N-cadherin, Vimentin, and Snail and enhanced E-cadherin protein expression both in vivo and in vitro. Conclusion SCML2 silencing inhibits the proliferation, migration, and invasion of HCC cells by regulating the Wnt/β-catenin/ EMT pathway.

OBJECTIVETo explore the relationship between DNA mismatch repair (MMR) and clinicopathologic features and prognosis in patients with stages II and III colon cancers.

METHODSThe clinical and pathological data of 440 patients with stage II/III colon cancer after radical resection were retrospectively reviewed and analyzed. Immunohistochemical staining was used to assess the expression of MMR proteins (MLH1, MSH2, MSH6 and PMS2), and the correlation between DNA MMR and clinicopathological features and prognosis of colon cancers was analyzed.

RESULTSOf the 440 tumor samples tested for DNA mismatch repair status, 90 (20.5%) demonstrated defective DNA mismatch repair and 350 (79.5%) had proficient DNA mismatch repair. Defective DNA mismatch repair (dMMR) was associated with young patients (≤ 60), proximal colon cancer, stage II, poorly differentiated adenocarcinoma and mucinous adenocarcinoma (P<0.05 for all). Among the 440 patients, 126 (28.6%) cases had recurrence or metastasis and 93 (21.1%) died during the median follow-up of 61.0 months. The five-year disease-free survival (DFS) rate was 82.2% among the patients with tumor exhibiting dMMR, significantly higher than that in patients with tumors exhibiting pMMR (68.9%, P=0.02). The univariate and mutlivariate analyses showed that the MMR status is an independent factor affecting 5-year disease-free survival and overall survival (OS) in colon cancer patients (P<0.05 for both).

CONCLUSIONSDefective DNA mismatch repair (dMMR) is associated with patients with proximal colon cancer, stage II and poorly defferentiated adenocarcinoma and mucinous adenocarcinoma. The prognosis for patients with dMMR is better than those with pMMR. dMMR may be a useful biomarker for the prognosis of colon cancer.

Adaptor Proteins, Signal Transducing ; metabolism ; Adenocarcinoma ; genetics ; metabolism ; mortality ; pathology ; Adenocarcinoma, Mucinous ; genetics ; metabolism ; mortality ; pathology ; Adenosine Triphosphatases ; metabolism ; Age Factors ; Analysis of Variance ; Colonic Neoplasms ; genetics ; metabolism ; mortality ; pathology ; DNA Mismatch Repair ; DNA Repair Enzymes ; metabolism ; DNA-Binding Proteins ; metabolism ; Disease-Free Survival ; Humans ; Mismatch Repair Endonuclease PMS2 ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; metabolism ; Neoplasm Recurrence, Local ; Nuclear Proteins ; metabolism ; Prognosis ; Retrospective Studies ; Survival Rate

Objective To investigate the effects of real-time feedback devices on chest compression quality test in non-medical staff during cardiopulmonary resuscitation (CPR) training.Methods A total of 120 volunteers were recruited and trained according to American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care set in 2015.CPR performance with compression for six minutes was tested on a manikin.Volunteers were randomized into 3 groups.Group A was tested without any feedback.Group B was self-corrected in compression quality(include compression depth、rate and rebound of chest wall) using a real-time feedback device (Link CPR).Group C was guided with a metronome.All compression data were collected via WiFi signal and stored.Results Significantly better mean chest compression depth was achieved in group B than that in group A and C(5.38 ± 0.483 cm vs.4.42 ± 0.572cm and 4.25 ± 0.843 cm,P ＜ 0.05).Significantly better compression rate were observed in both group B and C than that in group A (113.4 ± 5.9 and 109.0 ± 6.8 compressions/min vs.129.6 ± 8.3 compressions/min,P ＜ 0.05).Significantly less rebounding were observed in both group B and C compared with group A (56.10 ± 32.3 and 68.30 ± 28.8 compressions vs.174.30 ± 38.8compressions,P ＜ 0.05).Pearson correlation analysis confirmed the compression rate was positively correlated with the numbers of rebounding (r=0.776,P＜0.01).Significant statistical difference in accuracy was observed among the groups (9.8％ vs.72.9％ vs.58.5％,P ＜ 0.05).Conclusions In CPR training test real-time feedback device contributes to the improvement of chest compression quality through self-adjustment of compression depth,rate and rebound.

OBJECTIVETo investigate the role of DNA mismatch repair (MMR) as a prognostic indicator of radical resection and a predictor of fluorouracil-based adjuvant therapy benefit in patients with stage II/III colon cancer.

METHODSThe clinicopathological characteristics of 172 patients with stage II/III colon cancer who underwent radical resection were retrospectively analyzed. Immunohistochemical staining was used to detect the expression of DNA mismatch repair (MLH1/MSH2/MSH6/PMS2) in the tumor tissues.

RESULTSAmong a total of 172 patients, there were 38 (22.1%) cases with defective DNA mismatch repair (dMMR) and 134 (77.9%) cases with proficient DNA mismatch repair (pMMR). Among the 115 patients who did not receive adjuvant chemotherapy, those with tumor displaying dMMR had a better 5-year overall survival (OS) rate and disease-free survival (DFS) rate than the patients with proficient DNA mismatch repair (pMMR) (88.0% vs. 66.7%, P = 0.040; 84.0% vs. 60.0%, P = 0.034). The benefit of adjuvant chemotherapy differed significantly according to the MMR status. Adjuvant 5-Fu chemotherapy improved the 5-year overall survival rate among 134 patients with pMMR (86.4%) than that in patients treated by surgery alone (66.7%, P = 0.012). By contrast, there was no benefit of adjuvant 5-Fu chemotherapy in the patients with dMMR (61.5% vs. 86.4%, P = 0.062), which was even more clear the 5-year disease-free survival rate (53.8% vs. 84.0%, P = 0.038).

CONCLUSIONSMMR status is a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II/III colon cancer. Patients with stage II/III colon cancer displaying dMMR have a better prognosis than those with pMMR.

Antineoplastic Combined Chemotherapy Protocols ; Chemotherapy, Adjuvant ; Colonic Neoplasms ; diagnosis ; therapy ; Combined Modality Therapy ; DNA Mismatch Repair ; Disease-Free Survival ; Fluorouracil ; Humans ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Outcome

¹⁷⁷Lu- prostate specific membrane antigen (PSMA) radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China. Based on domestic clinical practice and experimental data and referred to international experience and viewpoints, the expert group forms a consensus on the clinical application of ¹⁷⁷Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.