Objective:To investigate the possible pathological mechanisms of tardive dyskinesia (TD) by analyzing brain cortex morphological changes and it's correlation to abnormal involuntary movement in schizophrenic patients with TD.Methods:Thirty-two schizophrenia patients with TD (TD group),31 schizophrenia patients without TD (non-TD group) and 21 healthy volunteers (control group) were recruited.Combined TD and non TD group into schizophrenia group.The psychopathological symptoms and abnormal involuntary movement were assessed with the Positive and Negative Syndrome Scale (PANSS) and Abnormal Involuntary Movement Scale (AIMS).The brain magnetic resonance imaging (MRI) data and Freesurfer software were used to measure the gray matter volume,cortical thickness,cortical surface area and volume of sub-conical regions among the three groups.Results:Schizophrenia group had significantly smaller gray matter volume in right nucleus accumbens,bilateral hippocampus,left superior frontal gyrus,left precentral sulcus superior part,and cortical surface area in left precentral sulcus superior part than the controls.The TD group had significantly smaller gray matter volume in right nucleus accumbens,larger gyrus gray matter volume and conical surface area in left precentral sulcus superior part than non-TD group (Ps ＜ 0.05).To test the difference between TD and non-TD group further,the chlorpromazine equivalent dose and PANSS negative scores Was controlled,the TD group still had significantly larger gray matter volume and surface area in left precentral sulcus superior part than the non-TD group [(2.03 ±0.07) × 103mm3 vs.(1.68-± 0.07) × 103 mm3,(1.01 ± 0.03) × 103 mm2 vs.(0.84 ± 0.03) × 103 mm2;Ps ＜ 0.05].Correlation analyses showed in schizophrenia group the cortical thickness in right inferior frontal gyrus correlated negatively with PANSS positive and general scores,positively with total scores;cortical volume in left occipital temporal sulcus correlated negatively with PANSS general and total scores,right inferior frontal gyrus correlated positively with PANSS positive scores,right intraparietal sulcus correlated positively with PANSS positive scores.In TD group,the cortical volume in left precentral sulcus superior part correlated positively with AIMS scores (r =0.46,P ＜0.01).Conclusions:The schizophrenia patients with TD had significantly increased gray matter volume and cortical surface area in left precentral sulcus superior part,which suggested there were motion compensation in the left precentral sulcus superior part in the pathogenesis of TD.

Objective: To investigate the protective effect of intraperitoneal transplantation of human liver-derived stem cells at different times against concanavalin A (ConA)-induced acute liver injury in mice. Methods: A total of 88 male C57BL/6 mice were randomly divided into normal control group (group C), ConA model group (group M), and human liver-derived stem cells (HYX1)+ConA group (group E); according to the interval between phosphate buffer/HYX1 injection and ConA injection, Groups M and E were further divided into 3-hour groups (M1 and E1 groups), 6-hour groups (M2 and E2 groups), 12-hour groups (M3 and E3 groups), 24-hour groups (M4 and E4 groups), and 48-hour groups (M5 and E5 groups). The levels of alanine aminotransferase (ALT), aspartate transaminase (AST), and total bilirubin (TBil) in peripheral blood were measured, liver tissue sections were used to observe pathological changes, and the Ishak score for liver inflammation was determined. The independent samples t-test was used for comparison between groups, and P < 0.05 was considered statistically significant. Results: The levels of ALT, AST, and TBil in group C were (36.25±1.16) U/L, (120.20±5.77) U/L, and (2.20±0.23) μmol/L, respectively; the levels of ALT, AST, and TBil and Ishak score were (8 721.23±837.39) U/L, (8 110.31±290.10) U/L, (8.41±0.10) μmol/L, and (13.32±1.30), respectively, in group M1, (8 334.31±666.50) U/L, (7 560.20±760.34) U/L, (10.40±0.80) μmol/L, and (12.67±0.81), respectively, in group M2, (8 960.75±551.93) U/L, (8 535.62±675.14) U/L, (10.95±1.43) μmol/L, and (14.57±0.65), respectively, in group M3, (8 618.57±886.40) U/L, (11 440.54 ± 1 327.86) U/L, (13.30±1.86) μmol/L, and (13.21±1.06), respectively, in group M4, and (10 170.13±1 112.37) U/L, (11 470.56±1 108.40) U/L, (12.75±1.55) μmol/L, and (15.07±1.58), respectively, in group M5. The levels of ALT, AST, and TBil and Ishak score were (1 016.35±163.47) U/L, (952.30±103.91) U/L, (7.77±0.62) μmol/L, and (3.50±0.21), respectively, in group E1, (42.10±6.20) U/L, (126.72±13.33) U/L, (3.41±0.53) μmol/L, and (2.01±0.40), respectively, in group E2, (44.21±4.30) U/L, (216.71±35.88) U/L, (3.47±0.44) μmol/L, and (2.13±0.25), respectively, in group E3, (2 909.69±212.14) U/L, (2 988.43±333.70) U/L, (7.03±0.93) μmol/L, and (4.70±0.50), respectively, in group E4, and (7 874.26±799.60) U/L, (10 940.54±947.35) U/L, (10.53±1.09) μmol/L, and (8.60±0.83), respectively, in group E5. Groups M1-M5 had significantly higher levels of ALT, AST, and TBil than group C (all P < 0.01), and groups M1-M4 had significantly higher levels of AST and ALT than groups E1-E4 (all P < 0.01), while there were no significant differences in the levels of AST and ALT between groups M5 and E5 (both P > 0.05). The pathological sections of liver tissue showed that compared with group M, group E had significant reductions in the degree of necrosis and Ishak score (both P < 0.05). Conclusion Intraperitoneal transplantation of human liver-derived stem cells has a protective effect against ConA-induced acute liver injury in mice, and the injection at 6 and 12 hours in advance has the best protective effect.

Objective To compare the safety and clinical efficacy between paclitaxel liposomes and paclitaxel in patients with advanced esophageal cancer .Methods A total of 90 patients with advanced esophageal cancer were enrolled into this study and were randomly divided into paclitaxel liposomes treatment group(treatment group) and paclitaxel treatment group(control group) . The patients of each group were treated with paclitaxel liposomes or paclitaxel 80 mg/m2 intravenously on day 1 and 8 ,and nedapla‐tin 75 mg/m2 intravenously on day 1 ,respectively .After two cycles of chemotherapy ,three weeks per period ,we evaluated the short term efficacy and adverse reactions according to the WHO standard .Results The short term efficacy between control group and treatment group showed no significance statistically (P>0 .05) .However ,the incidence of allergic reactions in the treatment group was significantly lower than control group (P<0 .05) .Conclusion Paclitaxel liposomal or paclitaxel combine with nedaplatin was effective equivalently in the treatment of patients with advanced esophageal cancer .But the allergic reactions of paclitaxel liposomal were lower than paclitaxel .It is worthy of clinical promotion .

Objective To assess the applicative value of near infrared fluorescence compound PZ -1009 in tumor imaging .Methods Near infrared fluorescence imaging properties of the compound was evaluated in a mouse model of ovarian cancer .The athymic nude mice were inoculated with SKOV -3 ovarian cancer cells and imaged in vivo and ex vivo after injecting PZ -1009 and were performed periodically .Results The tumor loca-tion was clearly imaged after 1 h of injection.The maximum fluorescence intensity was at 6 h time point and there was still a few fluorescent signal in tumors after 48hrs.A professional software was used to measure the intensity including all tumors and normal regions .The results showed that the intensity of tumors was higher than all normal regions in any time points .Conclusion The compound of PZ -1009 can efficiently target tumor sites and has great potential in noninvasive real time early tumor diagnosis .

Objective To investigate the clinical significance of ultrasound guided biopsy of peritoneum in diagnosis of unex-plained ascites .Methods A total of 95 patients with unexplained ascites after conventional examination were collected ,then under-went ultrasound inspection which showed thickened peritoneum and the relations to surrounding tissues around the planned perito-neum puncture point ,and conducted the peritoneal biopsy .Results A total of 95 were successfully biopsied with 2 -4 peritoneal tissues .Pathological examination showed that 37 cases (38 .9% ) were diagnosed as peritoneal metastatic carcinoma ,41 cases (43 . 1% ) with peritoneal tuberculosis ,5 cases (5 .2% ) with peritoneal mesothelioma ,1 case (1 .1% ) with eosinophilic granuloma ,4 ca-ses (4 .2% ) with fibrous hyperplasia ,and 7 cases (7 .4% ) with chronic inflammatory cell infiltration .The positive rate of ultra-sound guided peritoneal biopsy was 88 .4% .Conclusion The ultrasound guided biopsy of peritoneum is of clinically great signifi-cance in diagnosis of unexplained ascites .

Objective To investigate the tracing value of drug-loaded nano-active carbon for lymphatic visualization and its potential application in the lymphadenectomy of gastric cancer. Methods Sixty-three patients with advanced gastric carcinoma were randomized into 2 groups:control group and tracing group. For the tracing group, 5-Fu-loaded nano-active carbon (NP-5-FU) suspension was intratumorally administered by preoperative gastroscope-guided or intra-operative injection. No tracing reagents was given in the control group. The numbers of removed lymph nodes and metastasis-involved lymph nodes as well as the lymph node staining were recorded and compared between the two groups. The adverse effects was monitored. Results The resected lymph nodes in the tracing group were much more than that of control group (43.73 ± 9. 25 vs. 25. 36 ± 4. 73, t = 3.82,P ＜ 0. 05). For the N1, N2 and N3 lymph nodes, 27. 17 ± 5. 82,13.73 ± 4. 61 and 2. 83 ± 0. 15 per case of the tracing group were desected, while they were 14. 45 ± 2. 75,8. 27 ± 1.89, and 2. 64 ± 0. 11 per case in the control group,respectively (P ＜ 0. 05 ). 26. 2% (211/842) of the lymph nodes in the tracing group showed black intensity,higher than that of unstain lymph nodes (4. 5% ,21/470,χ2 =95. 108,P ＜0. 05) and that in control group (16.9%, 142/837)( χ2 =7.485 ,P ＜ 0.05, ). No local and systemic adverse reactions were observed for the local injection of nano-active carbon. No extension of operating time and increased complications occurred. Conclusion Local injection of nano-active carbon which was loaded with 5-FU around the tumor is a very useful measure to trace the lymph nodes and facilitate the lymphedetectomy and chemotherapy.

OBJECTIVETo explore the effects of rhEPO on the migration of bone marrow(BM) derived mesenchymal stem cells(MSCs) and its probable signal transduction mechanism.

METHODSMSC was cultured by classical whole BM adherence method; MSC characteristics was identified by multi-differentiation and surface marker (CD90, CD133, CD34, CD105). The effect of different concentrations EPO (1, 10, 100, 1000 IU/ml) on MSCs migration were observed. Then 30 minutes later, MSC were treated with signal transduction pathway inhibitors, 50 nmol/L wortmannin, 50 micromol/L PD98059, 10 micromol/L U73122, 4 microg/ml Anti EPO-R IgG, 30 micromol/L SB203580, 10 mmol/L Staurosporine, 6 nmol/L G06976 and 50 micromol/L Pseudo Z, respectively. The efficacy of MSC migration was analyzed by Transwell in vitro migration assay.

RESULTSCultured MSCs had the capacities for osteogenic and adipogenic differentiation and highly expressed CD105, CD90 and EPO-R. The efficiency of MSC in vitro migration increased gradually in a concentration-dependent manner with increasing concentration of rhEPO, and the ability peaked at a concentration of 100 IU/ml. Furthermore, the migration ability was decreased on treated with U73122, Anti EPO-R IgG, Staurosporine, Pseudo Z treatment.

CONCLUSIONEPO/EPO-R-mediated MSCs migration is related with MAPK, PI-PLC/PKC-zeta signal pathways, PKC-zeta signal pathway may be of central role for MSCs migration.

Animals ; Bone Marrow Cells ; cytology ; drug effects ; metabolism ; Cell Differentiation ; drug effects ; Cell Movement ; drug effects ; Cells, Cultured ; Erythropoietin ; pharmacology ; Humans ; Mesenchymal Stromal Cells ; cytology ; drug effects ; metabolism ; Protein Kinase C ; metabolism ; Rats ; Rats, Wistar ; Recombinant Proteins ; Signal Transduction ; drug effects

This study was aimed to investigate the effects of recombinant human erythropoietin (rhEPO) on proliferation of human bone marrow-derived mesenchymal stem cells (MSCs) in vitro. The aspirates of the bone marrow from healty volunteers were seeded in culture medium. Then MSCs were isolated according to characteristics adhering to the plastics. After three passages in culture, bone marrow-derived adherent cells were identified by growing morphological features, cell surface antigens and differentiation into multi-lineages. Then P3-MSCs which had been identified were incubated with different concentrations of rhEPO (0.5, 1, 5, 10 and 50 U/ml). Subsequently, proliferation of MSCs was measured by MTT assay, as well as cell counts. At the same time, cell cycle was detected by flow cytometry (FCM). The results indicated that the expressions of CD90 and CD105 in P3 bone marrow-derived adherent cells were positive, while the expressions of CD34 and CD45 were negative, and these cells could differentiate into adipocytes, osteocytes and chondrocytes in induction media. MTT assay showed that the optical density (OD) of group treated with EPO was significantly higher than that in the control group (p<0.05), and the group treated with 50 U/ml EPO achieved the most predominant effects. The results of cell count were coincident with that of MTT assay. Furthermore, the cell cycle analysis by FCM revealed that rhEPO could relatively decrease the cell ratio in G0/G1 phase, and increase the cell ratio in S and G2/M phases. As compared with the control group, all those differences were statistically significant (p<0.01). It is concluded that erythropoietin can promote proliferation of human bone marrow mesenchymal stem cells in vitro, which may be correlated with the increased entry into S and M phases of cell cycle of MSCs adjusted by EPO.
Bone Marrow Cells ; cytology ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Culture Media ; Erythropoietin ; pharmacology ; Humans ; Mesenchymal Stromal Cells ; cytology ; Recombinant Proteins

To explore the effect of different doses of thrombopoietin on proliferation of bone marrow mesenchymal stem cells (MSCs) in mice, 20 Kunming mice (35 +/- 5 g) were divided randomly into 4 groups: low-dose TPO group, moderate-dose TPO group, high-dose TPO group and normal control group (n = 5). The experimental groups were subjected to intraperitoneal injections of TPO at a dose of 25, 50, 100 microg/kg, respectively, and normal control group were treated with saline at a dose of 0.1 ml/g per day for 5 days. The bone marrow was harvested on 12 hours after the final administration. The bone marrow nucleated cells (BMNCs) were counted and seeded at a density of 10(6) cells/cm(2). The colony-forming unit-fibroblast (CFU-F) of MSCs was cultured and evaluated. The CFU-F of MSCs underwent osteo-genic induction and adipogenic induction, and cytochemical and immunocytochemical staining were performed to verify their multipotential. CFU-F and the cell percentage of CD90(+), CD105(+), CD34(+) in BMNCs were analyzed by flow cytometry. The results showed that the number of BMNCs and the cell percentage of CD90(+), CD105(+), CD34(+) and CFU-F increased obviously in TPO groups as compared with the normal control group (p < 0.05). The number of BMNCs increased most obviously in the 50 microg/kg TPO group. However, there was no significant difference in number of CFU-F between 50 microg/kg and 100 microg/kg TPO group (p > 0.05). The CFU-F of MSCs in bone marrow had their osteogenic and adipogenic differentiation potentials in vitro. It is concluded that the number of BMNCs and the cell percentage of CD90(+), CD105(+) and CFU-F increased after administration with TPO. It means that TPO can enhance MSCs to proliferate in bone marrow. However, the number of BMNCs and CFU-F can not increase with the increase of TPO dose.
Animals ; Bone Marrow Cells ; cytology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Mesenchymal Stromal Cells ; cytology ; Mice ; Thrombopoietin ; pharmacology

To evaluate the effects of rhG-CSF on mobilization of mesenchymal stem cells (MSCs) of mouse bone marrow at different time point, thirty mice were randomly divided into rhG-CSF treatment group and control group. The mice were subcutaneously injected with rhG-CSF in a dose of 80 microg/kg or saline for 5 days. The bone marrow and peripheral blood were obtained at time points of 6, 12, 168 hours after final injection of rhG-CSF or saline. Bone marrow mononuclear cells (BMMNCs) were seeded at density of 1 x 10(6) MNCs onto 12-well plate for culture expansion in DMEM supplemented with 10% FBS, and the number of colony forming unit - fibroblast (CFU-F) was counted after 14 days. The cells were collected by trypsinization and the surface antigens CD34, CD133, CD90 and CD105 were analyzed by flow cytometry. The multi-differentiation of MSCs were done in the culture condition of induced-adipocyte and osteocyte. Peripheral blood MNCs examination was same as the bone marrow. The results indicated that the number of CFU-F of bone marrow in rhG-CSF group was more than that in control group (p < 0.01), the number of CFU-F in rhG-CSF group at 6 hours was more than that at 12 hours and 168 hours, respectively (p < 0.01). There was no obvious difference between CFU-F at 12 hours and at 168 hours (p > 0.05). MSCs were positive for CD90, CD105 and negative for CD34 and CD133. MSCs were found to differentiate into adipocyte and osteocyte in vitro. The CFU-F of PBMNCs obtained and cultured in vitro in the same culture conditions could be observed after the rhG-CSF injection at 6 hours, but cloning efficiency was (0.50 +/- 0.11) x 10(-6) MNCs and showed statistical difference as compared with control. It is concluded that rhG-CSF to mobilize hemopoietic stem cells can be used to induce mouse MSCs in vivo expansion, which showed the peak value within 6 hours after final injection of rhG-CSF. rhG-CSF have the mini-mobilization effect on murine MSCs derived from bone marrow.
Animals ; Cells, Cultured ; Female ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoietic Stem Cell Mobilization ; Mesenchymal Stromal Cells ; cytology ; Mice ; Random Allocation ; Recombinant Proteins