Objective:To evaluate the effects of esketamine on myocardial injury and the relationship with nuclear factor-erythroid 2-related factor 2 (Nrf2) heme oxygenase-1 (HO-1) signaling pathway in septic rats.Methods:Thirty-two SPF healthy adult male Sprague-Dawley rats, weighing 200-230 g, were randomized into 4 groups ( n=8 each) using a random number table method: control group (group C), control plus esketamine group (group CE), sepsis group (group S) and sepsis plus esketamine group (group SE). Lipopolysaccharide (LPS) 10 mg/kg was intraperitoneally injected to establish the sepsis model.At 30 min after LPS or normal saline intraperitoneal injection, esketamine 10 mg/kg was intraperitoneally injected, and administration was repeated 12 h later in group SE and group CE.At 24 h after LPS injection, left ventricular ejection fraction (LVEF) was measured (using echocardiography), and serum cardiac troponin I (cTnI), brain natriuretic peptide (BNP), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), tumor necrosis factor alpha (TNF-α) and high mobility group box-1 (HMGB1) concentrations were determined (by enzyme linked immunosorbent assay). Myocardial tissues were obtained for examination of pathological changes (by hematoxylin-eosin staining) and for determination of expression of Nrf2, HO-1 and transcription factor Bach 1 (BTB-CNC allogeneic 1). Results:Compared with group C, LVEF was significantly decreased, concentrations of cTnI, BNP, LDH, CK-MB, TNF-α and HMGB1 in serum were increased, expression of Nrf2 and HO-1 was down-regulated, and expression of Bach 1 was up-regulated ( P<0.05), and the significant pathological changes of myocardial tissues were found in S and SE groups.No significant change was found in the parameters mentioned above in group CE ( P>0.05). Compared with group S, LVEF was significantly increased, concentrations of cTnI, BNP, LDH, CK-MB, TNF-α and HMGB1 in serum were decreased, expression of Nrf2 and HO-1 was up-regulated, and expression of Bach 1 was down-regulated ( P<0.05), and the pathological changes of myocardium were significantly attenuated in group SE. Conclusion:Esketamine can reduce myocardial injury, and the mechanism may be related to activating Nrf2/HO-1 signaling pathway in septic rats.

Renal cell carcinoma (RCC), one of the most common kidney cancers, has a poor prognosis. Epithelial to mesenchymal transition (EMT) is a hallmark of carcinoma invasion and metastasis. Several studies have examined the molecular regulation of EMT, but the relationship between histone demethylases and EMT is little understood. In this study, we investigated the role of retinoblastoma-binding protein-2 (RBP2), a histone demethylase that is highly expressed in RCC and is positively correlated with poor RCC prognosis in the regulation of EMT. We found that ectopic overexpression of RBP2 can induce cancer stem cell-like (CSC) phenotypes through EMT in RCC cells by converting them to a more mesenchymal phenotype. This results in increased resistance to apoptosis, which leads to enhanced tumor growth in xenograft models. Together, our data show that RBP2 is an epigenetic regulator that has an important role in the initiation of CSC phenotypes through EMT, leading to tumor progression. RBP2 is also a novel biomolecule for RCC diagnosis, and prognosis and may be a therapeutic target.
Apoptosis ; Carcinoma, Renal Cell* ; Diagnosis ; Epigenomics ; Heterografts ; Histone Demethylases ; Histones ; Kidney Neoplasms ; Neoplasm Metastasis ; Phenotype ; Prognosis

OBJECTIVETo investigate the dynamic changes of lymphocyte subsets before and after autologous hemopoietic stem cell transplantation (HSCT) in severe/refractory autoimmune disease (AID) and study the post-transplantation immunological reconstitution in AID.

METHODSThirteen patients with severe/refractory AID who registered for HSCT from April 2003 to April 2005 in Peking Union Medical College Hospital, including 8 patients with systemic lupus erythematosus, 4 patients with rheumatoid arthritis, and 1 patient with primary Sjögren's syndrome (pSS) were enrolled in this study. Blood samples were collected before/after mobilization, before conditioning, and 2 weeks, 1 month, 3 months, 6 months, 12 months, and 18 months post-transplantation. Lymphocyte subsets were tested by flow cytometry as follows: T cell (CD3 +), B cell (CD19 +), natural killer (CD3-CD16 + CD56 +), Th (CD3 + CD4 +), Tc (CD3 + CD8 +), naïve T (CD4 + CD45RA), memory T (CD4 + CD45RO), and CD4/CD8 ratio.

RESULTSLymphocyte subsets for SLE patients were severely abnormal compared to normal or RA patients (both P < 0.01). B cell reconstituted to normal level within 18 months, meanwhile NK and T cell remained low. The repopulations of Th and naive T cell were delayed, which caused the up-side-down of CD4/CD8 ratio and low level of naYve T cell percentage for a relatively long time.

CONCLUSIONSLymphocyte subsets abnormality in SLE patients are more severe than in RA patients. Although most autoimmune T/B cell in the grafts and patients can be effectively removed after transplantation, nonmyeloablative conditioning may be a risk for the relapse of AID. The long-term inhibition of CD4 + T cell may be related with the relief of AID after transplantation.

Arthritis, Rheumatoid ; blood ; immunology ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Lupus Erythematosus, Systemic ; blood ; immunology ; therapy ; Lymphocyte Subsets ; immunology ; pathology ; Sjogren's Syndrome ; immunology ; therapy

Objective To optimize plan for right lobe living donor hepatectomy based on the territorial volume drained by the middle hepatic vein (MHV) as shown by preoperative MR image in donors.Methods Utilizing preoperative MR dynamic enhancement scanning image,virtually plot three types of hepatic parenchyma transsection plane based on the variation of including MHV for right lobe graft procurement. Results From June 2006 to May 2010,65 adult-to-adult right lobe living donor liver transplantations was performed at General Hospital of Chinese PLA,in which there were 43 grafts including MHV (66.2％,43/65 ), eight grafts including partial MHV which was dissected before the V4b abouchement ( 12.3％,8/65) and 14 grafts not including MHV (21.5％,14/65). There was no postoperative death in donors and the postoperative complications developed in 10.76％ (7/65). The recipients' perioperative mortality was 7.69％ (5/65). Ttwenty-one complications developed in 18 recipients,and the morbidity was 32.31％. The cumulative survival rates were 86％,77％ and 68％respectively for 1,2 and 3 years. Conclusions The optimizing liver resection plane could be practically designed preoperatively for right lobe graft procurement based on the territorial volume drained by MHV.

We describe a case of systemic sclerosis (SSc) complicated with portal hypertensive ascites which did not improve with diuretics and ascitic drainage. When corticosteroid added, her ascites diminished dramatically. Though portal hypertension can be imputed to other causes, such as polycystic liver in this case, it can occur in limited SSc with positive anti-centromere antibody and respond to corticosteroid treatment.
Adrenal Cortex Hormones ; therapeutic use ; Aged ; Female ; Humans ; Hypertension, Portal ; diagnostic imaging ; drug therapy ; Radiography ; Scleroderma, Systemic ; diagnostic imaging ; drug therapy

Objective To evaluate the correlation of lens density (LD) measured by opacity lensmeter (OLM) and Pentacam with phacodynamics in patients with age-related nuclear cataract.Methods A prospective study was conducted in 78 patients (78 eyes) with age-related nuclear cataract.The lens density was measured with OLM and Pentacam respectively before operation,and the phacoemulsification kinetic parameters in phacoemulsification,including ultrasound time (UST),cumulated dissipated energy (CDE) and balanced salt solution (BSS) usage,were recorded for the analysis of the correlations of LD values with phacodynamics.Results LD measured by OLM and Pentacam was 32.83 ± 14.41 and 15.26 ±5.82,respectively.LD from OLM and Pentacam was positively correlated with both UST (r =0.645,0.807,respectively;both P ＜ 0.05)and CDE (r =0.669,0.828,respectively;both P ＜ 0.05).UST and CDE were more strongly correlated with LD from Pentacam than from OLM (Z =2.153,2.283;both P ＜0.05).Conclusion LD from both OLM and Pentacam are correlated with UST and CDE,and a stronger correlation is observed in Pentacam than OLM.

Epigenetics refers to the changes in gene expression level and function caused by non-genetic sequence changes.It can provide the time,location and mode of the genetic information for the execution of DNA sequences,including DNA methylation,histone modification,non-coding RNA and chromatin remodeling.Studies had shown that epigenetics plays an important role in the development of diabetic retinopathy (DR),and it had been found that epigenetic-related treatment regimens had a certain effect on the treatment of DR through animal experiments and in vitro experiments.It was benefit to regulate the development of diabetes and its complications by depth study of DNA methylation,histone modification,miRNA and metabolic memory.An understanding of changes in gene transcriptional mechanisms at the epigenetic level could help us to further study the prevention and control of diabetes and its complications,and to provide new ideas for treatment.

Objective To investigate the clinical features of IgG4-related autoimmune pancreatitis (IgG4-related AIP).Methods A prospective cohort study on IgG4 related disease (IgG4-RD) was carried out in Peking Union Medical College Hospital during December 2010 to June 2012,a total of 50 patients were recruited,including 14 IgG4-related AIP patients.The clinical manifestations,laboratory tests results,radiographic findings,histopatholo-gical lesions and response to treatment were analyzed.Results Fourteen AIP patients accounted for 28％ of IgG4-RD,of whom 9 cases were male,5 females,with the mean age of (55±10) (range 41-71) years.Painless obstructive jaundice was the major manifestation of AIP.All patients had extra-pancreatic organ involvement,including salivary glands enlargement (10 cases),lymph nodes swollen (7 cases),and bile duct tree (6 cases),lung (6 cases),kidney (2 cases),lacriminal gland (2 cases),retroperitoneal tissue (1 case),mesentery (1 case),and prostate (1 case) involvement.Serum levels of IgG4 subclass in all patients were significantly increased,with mean concentration of (11 ±10) (range 1.4-35.2) g/L.Radiographic findings showed diffuse (13 cases) or focal (1 case) pancreatic enlargement with irregular narrowing of the pancreatic duct (4 cases).Histopathological examinations were performed in 12 patients,which revealed massive infiltration with lymphocytes and IgG4 positive plasma cells with remarkable tissue fibrosis.Response to glucocorticosteroid or combined steroid and immunosuppressants were good.Conclusion IgG4-related AIP is a subtype of chronic pancreatitis,which is characterized by specific clinical spectrum,serological markers,radiographic and histopathological features.Glucocorticosteroid is the first choice,which can significantly improve the clinical and imaging abnormalities.

OBJECTIVETo evaluate the feasibility and safety of peripheral CD34+ cell mobilization in patients with severe autoimmune disease.

METHODSForty-two patients underwent a total of 46 mobilizations by the regimen of cyclophosphamide 2-3 g/m2+ recombinant human granulocyte colony stimulating factor (rhG-CSF) 5 microg x kg(-1) x d(-1). The positive selection of CD34+ cell was performed through the CliniMACS.

RESULTSIn 8.1 +/- 2. 3 days after administration of cyclophosphamide, the peripheral white blood cell and mononuclear cell (MNC) decreased to the lowest level. In 3.7 +/- 1.6 days after injection of rhG-CSF, the peripheral absolute MNC and CD34+ cell counts were 0.95 x 10(9)/L and 0.035 x 10(9)/L, respectively. After 2.4 +/- 0.6 times of leukapheresis, there gained 4.46 x 10(8)/kg of MNC and 5.26 x 10(6)/kg of CD34+, respectively. After mobilization, the underlying diseases were ameliorated more or less. In systemic lupus erythematosus (SLE) patients, SLE Disease Activity Index (SLEDAI) decreased from a median of 17 to 3 (P < 0.01). In rheumatic arthritis patients, an American College of Rheumatology criteria for 20% (ACR20) response was achieved in all five patients. Totally, 17.4% of patients whose absolute neutrophil count < 0.5 x 10(9)/L suffered infection, and 31.0% of patients had bone pain after the injection of rhG-CSF. Two patients suffered severe complications, one with acute renal failure and recovered by hemodialysis, the other died of thrombotic thrombocytopenic purpura. Failed mobilization occurred in three patients.

CONCLUSIONSSufficient CD34+ cells can be mobilized by low dose of cyclophosphamide and rhG-CSF. CD34+ cell mobilization for treatment of severe autoimmune disease not only is appropriate in both effectiveness and safety but ameliorates disease also.

Adolescent ; Adult ; Antigens, CD ; blood ; Antigens, CD34 ; blood ; Autoimmune Diseases ; therapy ; Cyclophosphamide ; pharmacology ; therapeutic use ; Female ; Hematopoietic Stem Cell Mobilization ; methods ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; immunology ; Humans ; Leukapheresis ; methods ; Leukocyte Count ; Leukocytes ; drug effects ; Leukocytes, Mononuclear ; drug effects ; Male ; Middle Aged ; Young Adult

Objective To study the correlation between pterygium area and the clinical manifestation and signs of primary pterygium obtained from OCULUS Keratograph.Methods A prospective case observation study was performed.Thirty-nine (55 eyes) primary pterygium patients were selected from June to September 2016 in Zhongshan People's Hospital.The area of the pterygium invaded cornea and duration of pterygium were recorded.The ocular surface condition was detected by corneal fluorescein staining.The break up time of tear film (BUT) and the gland function score were measured with OCULUS Keratograph.This study was approved by the Ethics Committee of Zhongshan People's Hospital (2015 [13]).All operations followed the Helsinki Declaration and all patients signed informed consent forms.Results The areas of pterygium invaded cornea was 2-20 mm2,the mean size was 5 (3,10) mm2;the duration of pterygium was 3-8 years,the mean duration was 5 (4,6)years;the BUT was 2.1-15.0 seconds,the mean BUT was (6.3±3.0) seconds.The mean gland function score was 2 (1,3).The area of pterygium was not significantly correlated with the duration of pteryguim (r =0.197,P =0.148),while it was negatively correlated with BUT (r=-0.711,P＜0.001) and positively correlated with the tarsal gland score (r =0.554,P＜0.001).What's more,82％ (45/55 eyes) of the patients' tear film rupture appeared firstly near pterygium's head.Conclusion OCULUS Keratograph can directly evaluate the ocular surface condition of pterygium patients in a non-contact and non-invasive method.Assessing the ocular surface damage by observing the area of pterygium invaded cornea may provide a prospective treatment for pterygium patients.