Objective To study the distribution of preterm infants' body temperature at admission and its effects on the clinical outcome.Method The distribution of preterm infants' body temperature at admission and its effects on their clinical outcome were searched in the Cochrane library,PubMed,Embase,Wanfang,CNKI,VIP from the initial establishment of these databases to June 2018.The quality of the included studies were assessed.STATA 12.0 software was used for statistical analysis.The odds ratio (OR) and 95％ confidence interval(CI) were used for continuous variables.Result A total of 16 studies (including 15 clinical trials) with 47 113 cases were included.The incidences of different admission temperatures were as follows:＜35℃:10.3％ (7.6％～13.1％),＜36℃:45.3％ (35.0％～55.5％),＜36.5℃:63.5％ (51.8％～75.2％),36.5～37.4℃:35.1％ (25.6％～44.7％),≥37.5℃:4.2％ (2.6％～5.7％).Compared with normothermia (36.5～37.4℃),hypothermia (＜35℃,35～35.9℃,36～36.4℃) increased the mortality,with the OR and 95％CI as follows:6.10(4.88～7.62),1.96(1.45～2.66),1.31(1.16～1.48);hyperthermia (≥37.5℃) was not associated with higher mortality (OR =0.98,95％CI 0.73～1.32,P=0.91).Compared with normothermia (36.5～37.4℃),hypothermia (＜36℃) increased the risks of severe retinopathy of prematurity (ROP),necrotizing enterocolitis (NEC),sepsis,periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH),with the OR and 95％CI as follows:ROP:1.70(1.45～2.00),NEC:1.27(1.08～1.49),sepsis:1.44(1.28～ 1.61),PVL/IVH:1.26(1.07～1.48),but not the risk of bronchopulmonary dysplasia (BPD,OR =1.03,95％CI 0.76～1.38,P=-0.87).Compared with normothermia (36.5～37.4℃),the temperature between 36～36.4℃ did not increase the risk of severe ROP,NEC,BPD,sepsis,PVL/IVH,with the OR and 95％CI as follows:1.19(0.92～ 1.54),1.01(0.86～1.18),0.91(0.68～1.22),1.02(0.91～1.14),0.98(0.85～1.14).Conclusion Admission temperature of ＜35℃,35～35.9℃,and 36～36.4℃ increased the mortality risk compared with 36.5～37.4℃,and the lower admission temperature,the higher mortality risk.Admission hypothermia (＜36℃) increased the risk of severe ROP,NEC,sepsis,PVL/IVH compared with normothermia (36.5～37.4℃).

AIM:To observe the changes of autophagy-related indexes during endoplasmic reticulum stress (ERS) induced by dithiothreitol (DTT) and its effect on apoptosis in human normal hepatocytes.METHODS:LO2 cells were treated with DTT at 2.0 mmol/L for 0, 6, 12 and 24 h to induce ERS.The expression of glucose-regulated protein 78 (GRP78) , protein kinase R-like endoplasmic reticulum kinase (PERK) , activating transcription factor 4 (ATF4) , C/EBP homologous protein (CHOP) , autophagy-related gene 12 (Atg12) , autophagy-related gene 5 (Atg5) and microtubule-associated protein 1 light chain 3 (LC3) at mRNA and protein levels was determined by real-time PCR and Western blot.The apoptosis was analyzed by flow cytometry.The formation of autophagosomes was observed under transmission electron microscope.After the LO2 cells were pretreated with rapamycin at 400 nmol/L for 1 h and treated with DTT at 2.0mmol/L for 24 h, the effect of rapamycin pretreatment on the apoptosis was analyzed by flow cytometry.RESULTS:After treatment with DTT at 2.0 mmol/L for 6, 12 and 24 h, the mRNA and protein levels of GRP78, PERK, ATF4, CHOP, Atg12, Atg5 and LC3 in the LO2 cells were significantly higher than those in 0 h group (P<0.05).At the same time, the ratio of LC3Ⅱ/LC3Ⅰwas also increased after DTT treatment (P<0.05).Observation under transmission electron microscope showed that autophagosomes were found in the LO2 cells treated with DTT for 6, 12 and 24 h.After DTT treatment for 6, 12 and 24 h, the apoptosis rate of LO2 cells was significantly higher than that in DTT 0 h group, while the apoptosis induced by DTT was significantly decreased after rapamycin pretreatment (P<0.05).CONCLUSION:ERS induces autophagy and rapamycin pretreatment alleviates the apoptosis of LO2 cells to some extent.

AIM:To investigate the effect of SET7/9 (SET domain containing 7/9) -mediated endoplasmic reticulum stress (ERS) on protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway, and to explore the mechanisms of arsenic-induced hepatocyte apoptosis.METHODS:Human liver LO2 cells were divided into control group, arsenic poisoning model group, negative transfection group and SET7/9 siRNA transfection group.The apoptosis of the LO2 cells in each group was analyzed by flow cytometry.The protein levels of SET7/9, glucose-regulated protein 78 (GRP78) , PERK and p-PERK in the LO2 cells of each group were observed by Western blot.RESULTS:Inhibition of SET7/9 expression reduced the apoptotic rate of arsenic-induced LO2 cells.Arsenic exposure increased the expression of SET7/9 in the LO2 cells.Arsenic exposure increased the protein levels of GRP78 and p-PERK in the LO2 cells, but decreased the protein levels of GRP78 and p-PERK after transfection with SET7/9 siRNA (P<0.05).CONCLUSION:Arsenic exposure induces hepatocyte apoptosis by increasing SET7/9 to activate ERS by PERK signaling pathway.

Objective To investigate early diagnosis and treatment of Paget disease of breast. Methods The clinicopathological data of 26 cases of breast Paget disease in the First Affiliated Hospital of Wenzhou Medical University from January 1995 to June 2018 was analyzed. Results The main clinical manifestation of 26 patients was eczema like papillae in 19 cases (73.1%), and associated with nipple discharge in 9 cases (34.6% ) and breast mass in 6 cases (23.1% ). The diagnosis of this disease was based on curettage cytology in 4 cases (15.4% ), biopsy in 8 cases (30.8% ), and needle aspiration cytology or post resection pathological examination in 14 cases (53.8% ). Paget disease consisted of simple papillary Paget disease in 3 cases (11.5%), ductal carcinoma in 18 cases (69.2%) and invasive ductal carcinoma in 5 cases (19.2%). Pathological TNM staging was 0 stage in 19 cases (73.1%), stageⅠin 3 cases (11.5%), stageⅡin 2 cases (7.7%), stageⅢin 2 cases (7.7%) and no stage inⅣcase. In this group, 2 cases underwent radical mastectomy, 18 cases underwent modified radical mastectomy, 4 cases underwent simple mastectomy, and 2 cases underwent mastectomy combined with low axillary lymph node dissection and intraoperative rapid frozen examination. Fourteen patients received adjuvant chemotherapy with CEF(cyclophosphamide + pharmorubicin + tegafur)/EC (pharmorubicin + cyclophosphamide) + T(docetaxel) or TP(docetaxel + cis- platinum)regiment after operation, 2 cases were treated with trastuzumab targeted therapy and 5 cases with adjuvant radiotherapy. Twenty-five of 26 patients were followed up for 8-108 months except one patient lost in follow-up. The 5-year survival rate was 96.0% (24/25), and the 10-year survival rate was 52.0% (13/25). Conclusions The diagnosis of Paget disease of the breast depends on cytology or pathology, and multidisciplinary treatment based on surgery is judged of by tumor stage and coincident other types of breast cancer and axillary lymph node involvement.

OBJECTIVE: To explore the protective effect of NANOG against hydrogen peroxide (H2O2) -induced cell damage in the human hair follicle mesenchymal stem cells (hHF-MSCs). METHODS: NANOG was expressed from a lentiviral vector, pLVX-IRES-ZsGreen. NANOG hHF-MSCs and vector hHF-MSCs were treated with 400 μmol/L hydrogen peroxide (H2O2) for 2 h, the cell survival rate, cell morphology, ROS production, apoptosis and expression of AKT, ERK, and p21 were determined and compared. RESULTS: Our results showed that NANOG could activate AKT and upregulate the expression of p-AKT, but not p-ERK. When treated with 400 μmol/L H2O2, NANOG hHF-MSCs showed higher cell survival rate, lower ROS production and apoptosis, higher expression of p-AKT, higher ratio of p-AKT/AKT. CONCLUSION Our results suggest that NANOG could protect hHF-MSCs against cell damage caused by H2O2 through activating AKT signaling pathway.
Cell Survival ; Drug Evaluation, Preclinical ; Hair Follicle ; cytology ; Humans ; Hydrogen Peroxide ; Lentivirus ; Mesenchymal Stem Cells ; drug effects ; metabolism ; Nanog Homeobox Protein ; metabolism ; pharmacology ; Oxidative Stress ; drug effects ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction

Breast cancer is one of the leading causes for cancer-related death among women worldwide. Coptidis Rhizoma has antibacterial,anti-inflammatory,anti-tumor and other pharmacological activities,but whether exercise could synergistically promote the role of RC in the treatment of breast cancer has not been reported. In this experiment,the effects and mechanism of total alkaloids of Coptidis Rhizoma combined with exercise on the tumor growth of orthotopically transplanted 4 T1 breast cancer were systemically studied in mice. Balb/C mice transplanted with 4 T1 cells in situ were used as models. The total alkaloids of RC(145 mg·kg-1·d-1) alone or in combination with exercise(10 m·min-1,30 min/time,5 times/week) were given for 28 days,and then the changes in body weight and tumor volume,tumor weight,interleukin-1β(IL-1β),serum estradiol(E2) content,and expression levels of estrogen receptor α(ERα),cell cycle related proteins CDK4,CDK6,cyclin D1,CDK2,and cyclin E in tumor tissues. The results showed that total alkaloids of Coptidis Rhizoma could significantly inhibit the growth of 4 T1 breast cancer in mice(P< 0. 01),and exercise significantly promoted the anti-tumor activity of total alkaloids of Coptidis Rhizoma(P<0. 01),and reduced E2 and IL-1β levels in mice. Western blot and flow cytometry showed that the total alkaloids of Coptidis Rhizoma combined with exercise could down-regulate the protein expression levels of ERα,CDK4,CDK6,cyclin D1,CDK2 and cyclin E in cancer cells,block the transformation of G1/S in 4 T1 cell cycle,and inhibit DNA synthesis in breast cancer cells. The total alkaloids of Coptidis Rhizoma combined with exercise showed synergistic effect in inhibition of tumor growth in mice with orthotopically transplanted 4 T1 breast cancer.
Alkaloids ; pharmacology ; Animals ; Breast Neoplasms ; therapy ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Female ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Physical Conditioning, Animal ; Rhizome

BACKGROUND: Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy. METHODS: A total of 966 centenarians were enrolled in this study from June 2014 to December 2016 in Hainan province, China. The GFR with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations were estimated. Agreement between these equations was investigated with the κ statistic and Bland-Altman plots. Sources of discrepancy were investigated by partial correlation analysis. RESULTS: The κ values of the MDRD and CKD-EPI equations, MDRD and BIS1 equations, and CKD-EPI and BIS1 equations were 0.610, 0.253, and 0.381, respectively. Serum creatinine (Scr) explained 10.96%, 41.60% and 17.06% of the variability in these three comparisons, respectively. Serum uric acid (SUA) explained 3.65% and 5.43% of the variability in the first 2 comparisons, respectively. Gender was associated with significant differences in these 3 comparisons (P < 0.001). CONCLUSIONS The strengths of agreement between the MDRD and CKD-EPI equations were substantial, but those between the MDRD and BIS1 equations and the CKD-EPI and BIS1 equations were fair. The difference in CKD staging of the first 2 comparisons strongly depended on Scr, SUA and gender, and that of CKD-EPI and BIS1 equations strongly depended on Scr and gender. The incidence at various stages of CKD staging was quite different. Thus, a new equation that is more suitable for the elderly needs to be built in the future.
Aged, 80 and over ; Asian Continental Ancestry Group ; Creatinine ; blood ; Cystatin C ; blood ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Male ; Renal Insufficiency, Chronic ; blood ; physiopathology ; Uric Acid ; blood

OBJECTIVE: To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT). METHODS: Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD. RESULTS: The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×10/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)＞0.5×10/L and platelet 20×10/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival. CONCLUSION UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.
Cord Blood Stem Cell Transplantation ; Core Binding Factor Alpha 2 Subunit ; Graft vs Host Disease ; Humans ; Leukemia, Myeloid, Acute ; Mycophenolic Acid ; Oncogene Proteins, Fusion ; Peripheral Blood Stem Cell Transplantation ; RUNX1 Translocation Partner 1 Protein ; Transplantation Conditioning

Objective To analyze the differences in biological functions between bone marrow(BM)-derived CD106 mesenchymal stem cells(MSCs)and the CD106 subgroup. Methods The MSCs from normal BM were isolated and expanded.The subgroups of CD106 and CD106 MSCs were sorted.The cell proliferation and adhesion functions,chemotactic activities,adipogenic and osteogenic potentials,senescence,and senescence protein 21(p21)were detected.The capacity of translocation into nucleus of nuclear factor-kappa B(NF-κB)when stimulated by tumor necrosis factor(TNF-α)was measured. Results The proliferative ability was higher in CD106 MSCs than that in CD106 MSCs.In 48 hours,the value of optical density(OD)was significantly higher in CD106 MSCs than that in CD106 subgroup(1.004±0.028 0.659±0.023,=3.946,=0.0225).In 72 hours,this phenomenon was even more pronounced(2.574±0.089 1.590±0.074,=11.240,=0.0000).The adhesive capacity of CD106 MSCs was significantly stronger than that of CD106 subgroup(0.648±0.018 0.418±0.023,=7.869,=0.0002).Besides,the metastasis ability of CD106 MSCs were significantly stronger than that of CD106 subgroup(114.500±4.481 71.000±4.435,=6.900,=0.0005).The CD106 MSCs had signifcnatly lower proportions of senescent cells.The expression of aging protein p21 in CD106 MSCs was significantly lower than that in CD106 MSCs [(17.560±1.421)% (45.800±2.569)%,=9.618,=0.0000].Furthermore,there were no visible pigmenting cells after β-galactosidase staining in CD106 MSCs subgroup.However,in CD106 MSCs,some colored green cells were detected.The rate of NF-κB translocation into nucleus after stimulated by TNF-α was significantly higher in CD106 MSCs than CD106 MSCs [(37.780±3.268)% (7.30±1.25)%,=8.713,=0.0001]. Conclusion Bone marrow-derived CD106 MSCs possess more powerful biological functions than CD106 MSCs.
Bone Marrow Cells ; cytology ; Cell Adhesion ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Humans ; Mesenchymal Stem Cells ; cytology ; NF-kappa B ; metabolism ; Protein Transport ; Tumor Necrosis Factor-alpha ; pharmacology ; Vascular Cell Adhesion Molecule-1 ; metabolism