OBJECTIVETo evaluate the effects of newborn rat hepatocyte intrasplenic transplantation combined with rat augmenter of liver regeneration (rALR) injection in treating rats with acute hepatic failure.

METHODSAcute hepatic failure (AHF) was induced in rats using D-gal (1.2 g/kg). The rats were then randomly divided into 6 groups. Group I received no further treatment and served as blank controls; group II received 1 ml buffered saline once through intrasplenic injection; group III received 1 ml rALR; group IV received 2 x 10(7)/ml hepatocytes; group V received 2 x 10(7) hepatocytes suspended in 1 ml rALR (50 microg/kg) and group VI received 2 x 10(7) hepatocytes in 1 ml cyclosporine A (10 mg/kg). The rats of the various treated groups were sacrificed at day 1, 5 and at week 2 and their livers and spleens were examined histopathologically. Blood samples of the rats were also obtained to determine the levels of TNF alpha and IL-1 beta.

RESULTSThere were no significant differences in survival between group I, II and III rats. 33.3% of the group IV rats survived for 2 weeks. At week 2, the survival rate of group V rats was significantly higher than that of group IV, but there was of no statistical significant increase when compared to that of group VI rats. Hepatocytes transplanted into spleens survived for 5-7 days in the spleens of group IV and VI rats, but they survived at least 2 weeks in group V. The average serum TNF alpha level in group IV was significantly higher than that in groups V and VI on the first postoperative day, but after four days, only the difference between group IV and group VI was significant (P < 0.05). The average serum level of TNF alpha in group II was higher than that in groups IV, V and VI on the first postoperative day (P < 0.05), but there were no significant differences between those in groups IV, V and VI on the 1st and the 5th postoperative days.

CONCLUSIONNewborn rat hepatocyte intrasplenic transplantation combined with rALR is effective in treating acute hepatic function failure induced by D-gal in rats. The transplanted hepatocytes can survive for at least 2 weeks in the spleens. The rALR mixed with the hepatocytes injected into the spleens may be able to facilitate the hepatocyte regeneration, to inhibit liver cell apoptosis and to suppress the cellular immunity.

Animals ; Cell Transplantation ; methods ; Female ; Hepatocytes ; transplantation ; Liver Failure, Acute ; immunology ; surgery ; Liver Regeneration ; Male ; Proteins ; therapeutic use ; Rats ; Rats, Wistar ; Spleen ; surgery

BACKGROUNDIn-stent restenosis (ISR) has become one of the most challenging problems in patients with coronary heart disease. At present, using non-invasive methods to assess ISR is a hot topic. In this investigation we attempted to explore the potential of magnetocardiography (MCG) in diagnosis of in-stent restenosis.

METHODSMCG was analyzed in 52 patients with coronary artery disease for three times: before stenting, one month and 7 months after successful intracoronary stenting.

RESULTSThe average classification of total maps (ACTM) and the ratio of abnormal maps (RAM) were lower in 1 month after intracoronary stenting compared with that obtained before stent planting (2.91 vs 2.52, 65.74% vs 42.80%, P < 0.01), while complex ventricular excitation index (CVEI) increased from -42.63 to -20.05 (P < 0.01). In ISR subgroup (n = 16), RAM decreased in 1 month after intracoronary stenting compared to it before stenting (68.99% vs 45.26%, P < 0.05). ACTM increased in 7 months compared to that obtained in 1 month after stenting (3.15 vs 2.51, P < 0.05). According to the ROC curve, ACTM showed its unique diagnostic value in restenosis patients. The sensitivity and specificity of ACTM were 80.0%, 69.40%, respectively. Its positive predictive value and negative predictive value were 54.6% and 88.5%, respectively.

CONCLUSIONSAfter successful intracoronary stenting, most parameters of MCG were improved. ACTM was of prognostic value in diagnosing ISR.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; Coronary Artery Disease ; diagnosis ; Coronary Restenosis ; diagnosis ; Female ; Humans ; Magnetocardiography ; methods ; Male ; Middle Aged ; Stents ; adverse effects

OBJECTIVETo investigate the magnetocardiography (MCG) changes in coronary artery disease (CAD) patients with normal or unspecific changes in resting electrocardiogram (ECG).

METHODSMCG mapping was performed by MCG-7 (MaGIC, Magiscan GmbH) installed in an unshielded room. All patients underwent ECG and coronary angiogram examinations and patients with normal or unspecified ECG changes and coronary artery narrowing > or = 70% in at least 1-vessel were defined as CAD group (n = 120). Patients with normal coronary angiogram served as control (n = 82). Four parameters: ACTM (average classification of total maps), RAM (ratio of abnormal maps), CVEI (complex ventricular excitation index) and R-max/T-max ratio, were analyzed in CAD and control groups.

RESULTSRAM (62% vs. 35%) and ACTM (2.62 +/- 0.98 vs. 2.29 +/- 0.90, P < 0.05) were significantly higher in CAD group than in control group. CVEI was found in abnormal zone (-100 - 0) in CAD group while in normal zone (0 - 100) in control group. The ratio of Rmax/Tmax in CAD group was also significantly higher in CAD group than in control group (6.41 +/- 3.29 vs. 4.10 +/- 2.00, P < 0.01). ROC curve analysis indicates that RAM, CVEI and Rmax/Tmax ratio were helpful parameters for CAD diagnosis and the diagnostic sensitivity was 67.1%, 65.9% and 64.3%; the specificity was 65.1%, 68.3% and 68.3% respectively.

CONCLUSIONMCG was a useful tool for diagnosing chronic myocardium ischemia in CAD patients with normal or unspecific changes resting ECG.

Adult ; Aged ; Aged, 80 and over ; Coronary Angiography ; Coronary Artery Disease ; diagnosis ; Electrocardiography ; Female ; Humans ; Magnetocardiography ; Male ; Middle Aged ; Sensitivity and Specificity

Objective: To assess the early experience and clinical value of left anteriolateral minor thoracotomy minimally invasive directly coronary artery bypass (MIDCAB) for treating multi-vessel lesion coronary artery disease (CAD) with bilateral internal mammary artery (BITA). Methods: Our research included in 2 groups: MIDCABG group, n=38 consecutive patients received left anteriolateral minor thoracotomy MIDCAB with BITA in our hospital from 2015-05 to 2017-01 and Control group, n=236 patients received conventional off-pump coronary artery bypass (OPCAB) by the same surgeon at same period. Peri-operative condition and relevant complications were compared between 2 groups. Results: In MIDCAB group, the success rate for harvesting BIMA was 94.7% (36/38), the mean time for harvesting right internal mammary artery (RIMA) and LIMA were (42.3±10.5) min and (35.2±8.3) min respectively; a total of 78 grafts were made in 38 patients with the mean of (2.05±0.31) graft/patient, no patient was switching to conventional CABG during the operation. Compared with Control group, MIDCAB group had reduced post-operative mechanical ventilation time (8.9±3.8) h vs (23.6±15.9) h, ICU stay time (29.3±20.8) h vs (56.5±38.3) h and hospital stay time (11.3±3.2) d vs (15.7±4.2) d, all P<0.05; while the incidence of peri-operative MACCE including death, myocardial infarction (MI), revascularization, cerebrovascular accident and poor incision healing were similar between 2 groups, P>0.05. No occlusion of anastomotic stoma was found by post-operative coronary angiography in neither group. The patients were followed-up for the average of 3 months, no death, angina or MI occurred. Conclusion: Through left anterolateral small incision, we can successfully get bilateral internal mammary artery and complete beating heart multi branch CABG.

Objective To explore the effects of Qa-1 and PD-L1 loaded artificial liposomal treatment in allograft rejection and its outcomes .Methods The extracellular domains of Qa-1 and PD-L1 were loaded on liposome surface by streptavidin-biotin system . Mixed lymphocyte reaction (MLR) was performed for measuring Qa-1/PD-L1 liposome biological function .Then liposome was co-transplanted with allo-islets via portal vein .The levels of blood glucose and C-peptide were detected daily after transplantation .Also hepatic lymphocytes after transplantation were isolated for determining the proportion of activated cells and signaling pathway changes .Results Artificial liposome could be easily loaded with biotinylated peptide and its diameter was between 50 to 500 nm . Qa-1/PD-L1 liposome could significantly suppress lymphocyte proliferation , activation and secretion of IFN-γ in MLR by an activation of SHP1/2 and an inhibition of Syk pathway .Qa-1/ PD-L1 liposomes could suppress the activation of hepatic lymphocytes in vivo by activating SHP1/2 ,protecting islet allografts and maintaining a normal level of blood glucose in recipients .Conclusions Qa-1/PD-L1 loaded liposome can effectively suppress allograft rejection and improve the outcomes of islet transplantation .

Objective To investigate the effects of adoptive reinfusion of regulatory T cell (Treg) on the recovery of islet function and graft survival time after islet allograft transplantation. Methods The diabetic model was established using C57BL/6 mice as recipients, and Balb/c mice were chosen as donors for islet allografts transplantation beneath the renal capsule. The recipient mice were divided into 3 groups and 3 mice in each group according to different processing Methods: Treg experiment group (Treg group, 1×10⁶ Treg cells were injected via tail vein at 1 d before operation), positive control group [sirolimus (SRL) group, SRL at a dose of 300 μg/(kg·d) was intragastrically given every day from 1 d before operation] and blank control group (control group, an equivalent volume of normal saline was intragastrically given every day from 1 d before operation). Enzyme-linked immune absorbent assay (ELISA) was used to detect the changes of blood glucose and C-peptide in mice within 14 days after transplantation. In vivo imaging technique was used to dynamically monitor the survival of mice within 14 days after transplantation. Results In each group, the blood glucose levels at postoperative 3 d were significantly decreased compared with those before transplantation (all P < 0.001). At postoperative 1 d, the C-peptide levels showed an explosive rise to varying degree in each group. At postoperative 3 d, the C-peptide levels in each group were significantly higher than that before operation (all P < 0.001). At the end of the observation period at 14 d after operation, the C-peptide levels in the SRL and Treg groups were (427±50) pmol/L and (833±57) pmol/L, relatively higher than that in the control group. But the blood glucose levels were (14.5±0.5) mmol/L and (12.1±0.6) mmol/L, significantly lower than that in the control group (all P < 0.001). Compared with the SRL group, the explosive release amount of C-peptide was significantly lower, the declining trend was more remarkably stable, and the C-peptide level was considerably higher in the Treg group at the end of the observation period (all P < 0.001). At postoperative 14 d, the grafts were almost completely apoptotic in the control group, over 50% of the grafts survived in the SRL group, and over 80% of the grafts survived in the Treg group. Conclusions Adoptive reinfusion of Treg cells can effectively protect islet grafts, prolong the survival time of grafts, and maintain the normal levels of blood glucose and C-peptide in the recipient mice.

Objective To observe the clinical efficacy and safety of atorvastatin calcium tablets in the treatment of nontraumatic subdural hematoma.Methods A total of 52 patients with nontraumatic subdural hematoma were randomly divided into control group and treatment group with 26 cases per group.Control group was given the treatment of drilling and drainage for 2-3 days.Treatment group received atorvastatin calcium 20 mg,qd,oral for 28 days,on the basis of control group.The clinical efficacy,serum superoxide dismutase (SOD),malondialdehyde (MDA),recurrence rate,and adverse drug reaction were compared between the two groups.Results After treatment,the total effective rates in treatment and control groups were 84.62％ (22/26 cases) and 57.69％ (15/26 cases) with significant difference (P ＜0.05).After treatment,the SOD in control and treatment groups were (115.29 ±13.34),(128.39±14.29) U·mL-1;MDA were (19.83 ±2.43),(15.40 ± 1.67) nmol · mL-1;recurrence rates were 26.92％ (7/26cases) and 0 (0/26 cases),the differences were statistically significant (all P ＜ 0.05).The adverse drug reactions in treatment group were based on increased hematoma volume and infection,which in control group were based on intracranial emphysema,increased hematoma volume,infection,abnormal liver function and brain damage.The incidences of adverse drug reactions in treatment and control groups were 7.69％ and 34.62％ with significant difference (P ＜ 0.05).Conclusion Atorvastatin calcium tablets have a definitive clinical efficacy and safety in the treatment of nontraumatic subdural hematoma.

OBJECTIVESOrthotopic liver transplantation (OLT) is an accepted therapy for selected patients with advanced liver diseases. However, the early mortality rate after OLT remains relatively high due to the poor selection of candidates with various serious conditions. The aim of this study is to assess the value of pretransplantation artificial liver support treatment in reducing the pre-operation risk factors relating to early mortality after OLT.

METHODS50 adult patients in various stages of different etiologies who underwent OLT procedures had been treated with molecular adsorbent recycling system (MARS) preoperatively. The study was designed in two parts: the first one was to evaluate the effectiveness of a single MARS therapy by using some clinical and laboratory parameters which were supposed to be therapeutical pretransplantation risk factors. The second part was to study the patients undergoing OLT by using the regression analysis on preoperation risk factors relating to early (within 30 d after OLT) mortality rate.

RESULTSAmong the 50 patients, a statistically significant improvement of the biochemical parameters was observed (pretreatment vs posttreatment). 8 patients cancelled their scheduled LTXs due to significant improvements in their clinical conditions or recovery of their failing liver functions. 8 patients died and 34 patients successfully underwent LTX. The immediate outcome (within 30 postoperative days) of these 34 patients was that 28 were kept alive and 6 died.

CONCLUSIONSPreoperation sequential organ failure assessment (SOFA), level of creatinine, INR, TNFalpha, and IL-10 are the main preoperative risk factors relating to early death after an operation. MARS treatment before a transplant operation can relieve these factors significantly, hence improve survival rate of liver transplantation or even make the transplantation unnecessary.

Aged ; Factor Analysis, Statistical ; Female ; Humans ; Interleukin-10 ; blood ; Liver Cirrhosis ; surgery ; Liver Neoplasms ; surgery ; Liver Transplantation ; methods ; Liver, Artificial ; Male ; Middle Aged ; Preoperative Care ; Risk Factors ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; blood

PURPOSE: The extranodal natural killer (NK)/T-cell lymphoma (NKTCL) of non-upper aerodigestive tract (NUAT) was found to have clinical heterogeneity compared with NKTCL of the upper aerodigestive tract (UAT) in small scale studies. We conducted this study in a much larger cohort to analyze the clinical characteristics, prognostic factors, treatment modality, and clinical outcomes of patients with NUAT-NKTCL. MATERIALS AND METHODS: From January 2001 to December 2017, a total of 757 NKTCL patients were identified and included in this study, including 92 NUAT-NKTCL patients (12.2%) and 665 UAT-NKTCLpatients (87.8%). RESULTS: NUAT-NKTCL patients had relatively poorer performance status, more unfavorable prognostic factors, and more advanced stage, compared with UAT-NKTCL patients. The 5-year overall survival (OS) was 34.7% for NUAT-NKTCL, which was significantly worse than UAT-NKTCL (64.2%, p<0.001). The median OS duration was 30.9 months for NUAT-NKTCL. Multivariate analysis showed that presence with B symptoms and elevated serum lactate dehydrogenase independently predicted worse OS. International prognostic index score and prognostic index of natural killer lymphoma score still had prognostic values in NUAT-NKTCL, while the Ann Arbor system could not accurately predict the OS. CONCLUSION: NUAT-NKTCL is a distinctive subtype of NKTCL in many aspects. Patients with NUAT-NKTCL have relatively poorer performance status, more unfavorable prognostic factors, more advanced stage, and poorer prognosis.
Cohort Studies ; Humans ; L-Lactate Dehydrogenase ; Lymphoma ; Lymphoma, Extranodal NK-T-Cell ; Multivariate Analysis ; Population Characteristics ; Prognosis

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.