To reveal the underlying mechanism of doxorubicin induced hepatotoxicity, an NMR-based metabolomic approach combined with multivariate statistical analysis was used to observe its metabolic alternations of rat liver. Sixteen differential metabolites between model rats and normal rats were characterized as potential pathological biomarkers related to doxorubicin induced hepatotoxicity. Six pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, and tyrosine metabolism were regarded as the targeted metabolic pathways according to Metabolic Pathway Analysis (MetPA). The results suggested that the metabolic perturbations in rats with doxorubicin induced hepatotoxicity were mainly involved in amino acid metabolism, lipid pathways, purine metabolism, energy metabolism, dysfunction of biotransformation and oxidative stress. The investigation revealed the effects of doxorubicin on liver in a holistic metabolic way, which laid a foundation for further studies on its toxicity mechanism.
Animals ; Biomarkers ; metabolism ; Doxorubicin ; toxicity ; Energy Metabolism ; Liver ; drug effects ; metabolism ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Metabolic Networks and Pathways ; Metabolomics ; Multivariate Analysis ; Oxidative Stress ; Rats

Objective To evaluate the role of early cleavage embryo in combination with embryo growth rate and morphology scoring in embryo selection in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods Six hundred and ten IVF/ICSI cycles were randomly assigned to group A(269 cycles) and group B(341 cycles). In group A, transferred embryos were chosen according to embryo growth rate and morphology scoring by 72 h(D3) after fertilization, while early cleavage embryo was added to the selecting system in group B. The pregnancy rate and implantation rate were compared between two groups, and the clinic outcomes were compared between transfers with early cleavage embryos and without early cleavage embryos in group B. Results The pregnancy rate and implantation rate in group B were significantly higher than those in group A (P < 0.05). Transfers with early cleavage embryos also achieved much higher pregnancy rate and implantation rate in group B (P < 0.01). Conclusion Compared with embryo growth rate and morphology scoring, early cleavage embryo in combination with embryo growth rate and morphology scoring can improve the clinical outcomes in IVF/ICSI cycles.

The study was aimed to observe the effect of recombinant human granulocyte-colony stimulating factors (rhG-CSF) in low dose on peripheral blood stem cell (PBSC) mobilization in unrelated healthy normal donors. G-CSF was administered at 5 microg/(kg x d) subcutaneously for successive 5 or 6 days to 56 unrelated donors. Stem cells were harvested on the fourth and fifth days or on the fifth and sixth days. The numbers of mononuclear cells (MNC), CD34(+) cells and Hb, Plt, and CD3(+), CD4(+), CD8(+) and CD20(+) cells were determined during the mobilization. The results showed that most common adverse events were bone pain (17.9%, 10/56), agrypnia (8.9%, 5/56) and lassitude (4.5%, 3/56) during rhG-CSF mobilization, but all donors were suffered less than grade II according to the WHO criteria, and did not need to stop the mobilization and not need to give special treatment. In harvest on day 4 - 5 and 5 - 6, MNC count was (5.95 +/- 1.52) x 10(8)/kg and (7.19 +/- 2.12) x 10(8)/kg; CD34(+) cells count was (3.03 +/- 1.09) x 10(6)/kg and (7.92 +/- 2.50) x 10(6)/kg. There were no significant differences in hemoglobin level and platelet count, the percentage of CD3(+) cells, CD4(+) cells, CD8(+) cells and CD20(+) cells between pre-mobilization and post-mobilization of rhG-CSF. It is concluded that the low dose of rhG-CSF 5 microg/(kg x d) for peripheral blood stem cell mobilization in unrelated healthy normal donors is safe and effective.
Adolescent ; Adult ; Blood Donors ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Hematopoietic Stem Cell Mobilization ; methods ; Humans ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Recombinant Proteins

Objective To evaluate the efficacy and safety of acute ureteroscopy for the treatment of ureterie stones during middle and late pregnancy.Methods From June 1998 to March 2005,17 pregnant women(mean age,27 years;age range,21-35 years)with ureteric stones were treated by ureteroscopy when the fetus was at 20-36 weeks of gestation(mean,29 weeks).All the cases presented with urgent symptoms such as recurrent renal colic(11 cases),fever(4)or acute obstructive anuria(2).Among 17 cases,the stones(between 6 mm?7 mm and 13 mm?21 mm)were located in the upper(8 cases),middle(5)or lower ureter(4);and on the left side(5 eases),on the right(10)and on both(2)of the lower ureter. Mild hydronephrosis were observed in 6 cases and moderate hydronephrosis in 11,Of the 17 cases,14 under- went ureteroscopic pneumatic lithotripsy;in 1 case the calculi were pushed to the renal pelvis;and 2 cases were treated by Double-J catheter drainage.Results All the urgent symptoms in 17 cases were relieved after treatment.The stone-free rate of initial treatment was 82.4%(14 of 17).Three cases with residual stones were treated by Douhle-J catheters,which were replaced every 3 months until the calculi were re- moved.No abortion,premature delivery or complications such as ureter perforation occurred.Mild renal colic occurred in 1 case after insertion of Douhle-J catheter,and it was relieved 3d later;gross hematuria occurred in l case and disappeared 6 d later without treatment.All 17 patients had normal delivery and gave birth to healthy children.Conclusions Ureteroscopy is a safe and reliable method for the treatment of ureteric calculi during middle and late pregnancy.

OBJECTIVETo explore the relationship between genetic polymorphisms of CACNA1C that encoded the a1c subunit of the L-type calcium channel and the efficacy of calcium channel blocker (CCB, Nifedipine extended release tablet/20 mg/d) in essential hypertension (EH) patients of Han Chinese in Wenzhou.

METHODSFor the enrolled 103 EH patients, Multiplex Polymerase Chain Reaction (Multi-PCR) and matrix assisted laser desorption ionization time of flight MS (MLDI-TOF MS) were performed to detect their genotypes (rs216008, rs1051375, rs2299661, rs10848683, rs215976), blood pressure (BP) after CCB monotherapy was compared among patients with different genotypes.

RESULTS(1) Blood pressure was significantly reduced in all patients post CCB (P < 0.05 vs. pre-CCB). (2) Diastolic blood pressure reduction was more significant in subjects with rs2299661 C/C genotype (wild genotype) than in subjects with rs2299661C/G and rs2299661G/G genotype (mutational genotype) [(12.46 ± 7.91) mm Hg (1 mm Hg = 0.133 kPa) vs. (7.22 ± 8.01) mm Hg and (5.93 ± 9.77) mm Hg, P < 0.05]. (3) Systolic blood pressure reduction was more significant in subjects with rs216008 C/C genotype (wild genotype) than in subjects with rs216008 C/T genotype (mutational genotype) [(20.60 ± 12.35) mm Hg vs. (13.62 ± 10.21) mm Hg, P < 0.05]. (4) Blood pressure reduction was similar between subjects with genotype of rs1051375, rs10848683 and rs215976.

CONCLUSIONEH patients with wild genotype of rs2299661 and rs216008 in CACNA1C are more likely to be responders of CCB monotherapy.

Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Calcium Channel Blockers ; therapeutic use ; Calcium Channels, L-Type ; genetics ; Female ; Humans ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

BACKGROUNDAlthough some certain infectious pathogens could be detected in the patients with coronary artery disease, the roles of these infectious factors in the development of coronary artery diseases remain largely unknown. Since the number of infectious pathogens has been argued to be relative to the coronary artery diseases, we therefore examined whether there is a link between the number of infections and the incidence of in-stent restenosis after stent implantation.

METHODSOne hundred and eighty-one patients were enrolled in this study. Infectious pathogens including serum anti-Chlymydia pneumoniae, cytomegalovirus, Helico pylori, human herpes simplex virus-1, human herpes simplex virus-2 antibodies and hepatitis B virus antigen were measured in all patients before coronary stent implantation. Coronary angiography was performed before, immediately after and 6 months after stent implantation.

RESULTSRestenosis rate 6 months post stent implantation was similar in patients with low pathogen burden (< 3 pathogens, 33.3%) to those with high pathogen burden (> or = 3 pathogens, 29.1%).

CONCLUSIONSPrevious infections with Chlymydia pneumoniae, cytomegalovirus, Helico pylori, human herpes simplex virus-1, human herpes simplex virus-2 and hepatitis B virus do not contribute to the incidence of restenosis after stent implantation.

Adult ; Aged ; Coronary Disease ; therapy ; Coronary Restenosis ; etiology ; Female ; Humans ; Infection ; complications ; Male ; Middle Aged ; Stents ; adverse effects

Objective At present no deep investigation has been done on the relationship between handgrip strength and appendicular lean mass (ALM) in patients with chronic obstructive pulmonary disease (COPD). The study aimed to explore the present situation of handgrip strength in patients with stable COPD and relationship between handgrip strength and ALM.Methods A total of 93 patients with stable COPD who hospitalized in our department from August 2016 to July 2017 were selected for the study. All the patients underwent handgrip strength test, body composition analysis, as well as the analysis of the relationship between handgrip strength and ALM.Results Multivariate linear regression analysis showed age(X1), education(X2), smoking(X3), course of disease(X4) and lower limb lean mass(X5) could be taken as predictive factors for the variation degree of handgrip strength (R2=50.5%), and multiple linear regression equation was Y=9.959-4.315X1+1.397X2+2.679X3-1.526X4+1.538X5. The variation degree decreased to 48.1% when the course of disease was removed from the model, 28.3% when the limb lean mass was removed, 26.5% when two variables were removed. The correlation coefficients of ALM, upper limb, lower limb and torso lean mass (\[22.32±3.25\]kg, \[6.48±1.05\]kg, \[15.83±2.26\]kg, \[22.27±3.22\]kg) with handgrip strength (\[32.27±7.27\]kgf) were respectively 0.484, 0.436, 0.496 and 0.496 (P＜0.01).Conclusion The handgrip strength in patients with stable COPD is closely associated with ALM, and the course of disease and the lower limb lean mass greatly affect the handgrip strength. Clinical workers should pay extra attention to the relationship in order to give timely clinical intervention.

This study was aimed to detect the expression level of cmtm 5 (CKLF-like MARVEL transmembrane domain containing member 5) gene in the bone marrow cells from patients with multiple myeloma (MM), and to investigate the correlation between the expression level of cmtm5 and various clinical characteristics. Real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) was used to measure the expression levels of cmtm5 gene in the bone marrow cells collected from MM patients, and the MM cell lines, namely, RPMI8226 and CZ1 cells. The normal donor marrow specimens were used as the reference. The ratio of cmtm5 copy number to abl (Abelson murine leukemia viral oncogene homolog) gene copy number was used for indicating the expression level. The results showed that the expression level of cmtm5 gene was significantly down-regulated in bone marrow cells of 51 untreated or relapsed/refractory MM patient as compared to those of normal donor marrow cells (0.047+/-0.062 for the untreated or relapsed/refractory MM patients versus 0.255+/-0.333 for the normal, p<0.01). According to the International Staging System (ISS), the cmtm5 expression level in marrow cells of patients in ISS III stage was significantly lower than that in patients in ISS I stage (0.034+/-0.034 for the ISS III stage versus 0.103+/-0.109 for ISSI stage, p<0.01). Similarly, lower expression levels of cmtm5 gene were also found in two human MM cell lines (0.014+/-0.009 for RPMI8226 cells and 0.004+/-0.006 for CZ1 cells). After the MM patients were effectively treated, their expression levels of cmtm5 gene significantly increased (0.020+/-0.005 for the untreated patients versus 0.227+/-0.038 for the effectively treated patients, p<0.01). A significant negative correlation was observed between the expression level of cmtm5 gene and the number of bone marrow plasma cells (r=-0.307, p<0.05). However, the correlation was not found between the expression level of cmtm5 gene and the clinical characteristics, such as gender, age, hemoglobin level, or M-protein level, etc. It is concluded that the expression level of cmtm5 gene is abnormally lower in the bone marrow cells from the MM patients, and are associated with ISS stages. Furthermore, the expression level of cmtm5 gene is negatively correlated with the number of bone marrow abnormal plasma cells in MM patients, which suggests that the abnormally lower expression of cmtm5 may be involved in the pathogenesis of the MM patients.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow Cells ; metabolism ; pathology ; Case-Control Studies ; Chemokines ; genetics ; metabolism ; Female ; Humans ; MARVEL Domain-Containing Proteins ; Male ; Middle Aged ; Multiple Myeloma ; metabolism ; pathology ; Neoplasm Staging ; Tumor Suppressor Proteins ; genetics ; metabolism ; Young Adult

OBJECTIVETo investigate the safety of autologous bone marrow mononuclear cell (BM-MNCs) transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI).

METHODSOne hundred and eighty-four patients with AMI treated with percutaneous coronary intervention (PCI) were randomized in a 1:1 way to either intracoronary transplantation of autologous BM-MNCs (n = 92) right after PCI or to sodium chloride concluding heparin (controlled, n = 92) via a micro infusion catheter. In the process of the intracoronary infusion of BM-MNCs, the complications should be recorded, which were aberration reflect (including of pale, syncope, nausea, hypotension and shock), deterioration of angina or heart failure, arrhythmias (including of bradycardia, sinus arrest or atrial ventricular block or ventricular fibrillation), embolism etc. Body temperature, blood pressure and heart rates should be monitored during the first week after transplantation. Holter, coronary angiography and ultrasonic cardiography were performed at the designed time points. Main heart accidents, restenosis and tumor were recorded during 2-years follow up.

RESULTSDuring the period of bone marrow puncture and intracoronary infusion of BM-MNCs, few patients occurred pale, dizziness, bradycardia and hypotension, which were transient and due to vagus reflect. No stem cell-related arrhythmias, deterioration of angina were noted. In BM-MNCs group one patient developed in-stent reocclusion in one week after transplantation, five developed in-stent restenosis during further follow-up 30 months, which were similar with control group. There were no deaths, major adverse cardiac events, tumor and other late adverse events during follow-up period in both groups.

CONCLUSIONIntracoronary transplantation of autologous BM-MNCs in the acute phase after AMI is feasible and seems safe in the 30 months of follow-up.

Adult ; Aged ; Bone Marrow Transplantation ; methods ; Coronary Vessels ; Female ; Follow-Up Studies ; Humans ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Middle Aged ; Myocardial Infarction ; surgery ; Transplantation, Autologous

OBJECTIVEThe aim of this study is to identify short-term result of cell transplantation in idiopathic dilated cardiomyopathy (IDC) patients who were treated by intracoronary transplantation of autologous mononuclear bone marrow cells (BMCs) in addition to standard therapy.

METHODSBased on given standard therapy, eighteen patients with idiopathic dilated cardiomyopathy were enrolled and divided into transplantation group and control group. The clinical characteristics of two groups were comparable. Among these patients, 10 patients were performed percutaneous coronary autologous BMCs transplantation. Blood routine test, hepatic function, renal function, glucose, triglyceride (TG), cholesterol, low density cholesterol (LDL), high density cholesterol (HDL), uric acid (UA) and high sensitive C-reactive protein (hsCRP) were measured at the time point of pre-operation and some time after transplantation. All patients were monitored under ultrasonic cardiography, Holter, six-minute-walk test and magnetic resonance imaging over a period of at least 6 months. Annual hospital days were recorded during two-year follow-up.

RESULTSBlood routine test, hepatic function, renal function, glucose, TG, cholesterol, LDL, HDL, UA and hsCRP had no significant differences among 48 hours, 3 months and 6 months after transplantation compared with control and pre-transplantation (P > 0.05). Six-minute-walk distance elevated significantly six months after BMCs transplantation compared with control and pre-transplantation [(494.3 +/- 62.8) m vs (307.2 +/- 75.0) m, (321.5 +/- 63.7) m, P < 0.05]. Left ventricular ejection fraction (LVEF) and the sizes of LVEDd had no significant changes compared with that of control and pre-transplantation (P > 0.05). Myocardium lesion area measured by (MRI) seemed decrease in transplantation group compared with that of control and pre-operation [(4.96 +/- 0.47) cm(2) vs (5.12 +/- 0.54) cm(2), (5.02 +/- 0.39) cm(2), P > 0.05], but there was no significance. None of proarrhythmias and side effects had been observed around transplantation and 2 years follow-up. There was no significant difference in survival between two groups in 2 years follow-up. Interestingly, annual hospital day in BMCs transplantation patients was significantly shorter than that in control group [(30.2 +/- 11.2) d vs (43.6 +/- 9.8) d, P < 0.05].

CONCLUSIONSAutologous bone marrow mononuclear cells transplantation can prolong six-minute-walk, decrease re-hospitalization rate, elevate exercise ability and help to improve cardiac function in patients with IDC. In addition, it was demonstrated that cell transplantation is safe.

Bone Marrow Transplantation ; Cardiomyopathy, Dilated ; surgery ; therapy ; Humans ; Transplantation, Autologous ; Treatment Outcome