ObjectiveThe purpose of this study was to assess the efficacy,safety and optimal dose of tacrolimus monotherapy in patients with refractory lupus nephritis(LN) who were resistant to cyclophosphamide(CYC).MethodsA total of 14 LN patients (2 men and 12 women) with persistent proteinuria who were resistant to CYC treatment more than 8 g for half a year were enrolled.Tacrolimus was initiated at 2 mg/d (patient weight＜60 kg) or 3 mg/d(patient weight≥60 kg) which was administered in two divided doses.Prospective data on daily proteinuria,serum album level and serologic lupus activity were collected and followed for 6 months.ANOVA and Pearson correlation analysis were used for statistical analysis.Results Mean age at baseline was(30±9) years.Mean urinary protein decreased significantly from(6.2±5.1) g at baseline to (1.1±0.9) g at 6 months (F=16.21,P＜0.01).Mean serum album level increased significantly from (27.9±9.7) g/L at baseline to(37.8±2.2) g/L at 6 months(F=16.71,P＜0.01 ).Complete or partial response was observed in 86％ of patients receiving tacrolimus therapy.The effective dosage in this study was 0.03-0.06mg·kg-1·d-1 of the patients who had complete response or partial response to tacrolimus.The tacrolimus level in partially and completely responding patients was less than 3 ng/ml.There was no significant difference among blood tacrolimus levels of complete,partial,and no response patients [(1.6-±0.4),(2.0±0.6) and (22±1.1) ng/nl],respectively).No definite correlation was found between efficacy and tacrolimus level.Tacrolimus was well tolerated at current dose,besides one with new onset hypertension and one with alopecia.ConclusionOur results suggest that tacrolimus at low dosage and serum level is potentially effective and safe for the treatment　of patients with LN and persistent proteinuria resistant to CYC.The optimal dosage of tacrolimus for LN may　be 0.03-0.06 mg·kg-1·d-1.

Objective: To observe the effects of electroacupuncture (EA) on the protein and gene expressions of Bax, Caspase-3 and Bcl-2 in cerebral cortex of type 2 diabetic rats with cognitive impairment (CI), and to explore the mechanism of EA in improving the learning and memory abilities. Methods: A total of 100 Sprague-Dawley (SD) rats were divided into a normal group (n=10) and a model group (n=90) by random number table method. Rats in the model group were intraperitoneally injected with a small dose of streptozotocin (STZ) to establish the type 2 diabetic models, after being fed with high-fat and high-sugar diet for 1 month. Twenty CI rats were selected from the 50 successful model rats by the Morris water maze (MWM) test and randomly divided into a model group and an EA group according to the blood glucose level and MWM data (n=10). Rats in the EA group received acupuncture at Zusanli (ST 36), Neiting (ST 44) and Yishu (Extra), of which Zusanli (ST 36) and Neiting (ST 44) were stimulated by EA apparatus, 20 min/time, once a day for 6 d a week and 4 consecutive weeks. The rats in the model and the normal groups were fixed without treatment. After 4-week treatment, the random blood glucose level of the rats was measured; the learning and memory abilities of rats were measured by MWM; terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was used to detect apoptotic cells; Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the protein and gene expressions of Bax, Caspase-3 and Bcl-2 in cerebral cortex. Results: After modeling, the random blood glucose level and the escape latency tested by MWM were significantly increased, and the number of crossing the platform tested by the MWM was decreased in the EA and model groups, and were significantly different from those in the normal group (P<0.05 or P<0.01), while the differences between the model group and the EA group were not statistically significant (all P>0.05). After 4-week treatment, the random glucose level and the escape latency tested by MWM were significantly increased (both P<0.05), and the number of crossing the original platform tested by the MWM was significantly reduced (P<0.01), the protein and gene expressions of Bax and Caspase-3 were significantly increased (all P<0.001), the protein and gene expressions of Bcl-2 were significantly reduced (both P<0.001), and the number of neuron apoptosis was significantly increased (P<0.001) in the model group than in the normal group; the random blood glucose level was significantly reduced (P<0.05), the escape latency tested by MWM was significantly shortened (P<0.05), and the number of crossing the original platform tested by MWM was significantly increased (P<0.05), the protein and gene expressions of Bax and Caspase-3 were significantly reduced (all P<0.001), the protein and gene expressions of Bcl-2 were significantly increased (both P<0.001), and the number of neuron apoptosis was significantly reduced (P<0.001) in the EA group than in the model group. Conclusion: EA can improve the learning and memory damages induced by type 2 diabetic model rats with CI; the action mechanism may be achieved via anti-apoptosis.

OBJECTIVETo investigate the expressions of leptin and its receptor in the epididymis of experimental varicocele (EV) rats.

METHODSForty male Sprague-Dawley rats were randomly divided into four groups: 4-week EV (n = 12), 8-week EV (n = 12), 4-week control (n = 8), and 8-week control (n = 8). EV models were established by partial ligation of the left renal vein. The expressions of leptin and its receptor in the rat epididymis were measured by immunohistochemistry, and their mRNA expressions determined by real-time quantitative PCR.

RESULTSThe expressions of leptin and its receptor in the epididymis were significantly higher in the 4- and 8-week EV groups than in the 4- and 8-week control groups (P < 0.01), with no significant difference between the two EV groups (P > 0.05). So were their mRNA expressions in the former two than in the latter two groups (P < 0.01), with no significant difference between the former two (P > 0.05).

CONCLUSIONThe expressions of leptin and its receptor are markedly increased in the epididymis of varicocele rats. Leptin may be involved in the mechanisms of varicocele inducing male infertility.

Animals ; Disease Models, Animal ; Epididymis ; metabolism ; Leptin ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Leptin ; metabolism ; Varicocele ; metabolism

BACKGROUND AND OBJECTIVECombined hypoxic cytotoxic drugs and chemoradiotherapy is an important mean of oncotherapy, and Tirapazamine (TPZ) is one of the most remarkable drugs. It has been shown that TPZ has a synergistic effect with radiotherapy on tumor cells, but whether TPZ would down-regulate the expression of the hypoxia-induced genes has not been reported. This study was to investigate the hypoxia-induced mRNA expressions of hypoxia inducible factor-1alpha (HIF-1alpha) and osteopontin (OPN) in human nasopharyngeal carcinoma HNE-1 and CNE-1 cells and the radiosensitization of TPZ, a hypoxia-specific drug, on HNE-1 and CNE-1 cells in vitro.

METHODSThe IC50 values of TPZ for HNE-1 and CNE-1 cells were measured using MTT assay, and the mRNA expressions of HIF-1alpha and OPN in HNE-1 and CNE-1 cells was determined using RT-PCR under aerobic and hypoxic conditions, respectively. The survival rates of HNE-1 and CNE-1 cells treated with or without TPZ at IC10 in the presence or absence of oxygen for 6 h were determined using colony formation assay following exposure to 1-6 Gy of 60Co radiation. The dose-survival curves were plotted and the values of D0, Dq and SER were calculated as a single-hit multitarget model.

RESULTSThe IC50 values of TPZ were 34.81 μmol/L and 35.02 μmol/L in HNE-1 and CNE-1 cells under aerobic condition, and 30.20 μmol/L and 28.48 μmol/L under hypoxic condition, respectively. The expressions of HIF-1alpha and OPN mRNA were reduced by TPZ in HNE-1 cells, but not in CNE-1 cells under hypoxic condition. For the HNE-1 cells, the respective values of D0 and Dq were 0.89 Gy and 0.28 Gy following normoxic irradiation versus 1.47 Gy and 0.44 Gy following hypoxic irradiation. For the CNE-1 cells, the respective values of D0 and Dq were 0.72 Gy and 0.68 Gy following normoxic irradiation versus 0.95 Gy and 0.56 Gy following hypoxic irradiation. The values of D0 and Dq for HNE-1 and CNE-1 cells treated with TPZ under hypoxic condition following irradiation were 0.66 Gy, 0.21 Gy and 0.85 Gy, 0.79 Gy, respectively.

CONCLUSIONTPZ can down-regulate hypoxia-induced expression of HIF-1alpha and OPN mRNA of HNE-1 cells and radiosensitize the HNE-1 cells but not CNE-1 cells, and act as a hypoxia modifier.

Antineoplastic Agents ; pharmacology ; Cell Hypoxia ; Cell Line, Tumor ; Cell Survival ; drug effects ; radiation effects ; Cobalt Radioisotopes ; Down-Regulation ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Inhibitory Concentration 50 ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Osteopontin ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Radiation Tolerance ; drug effects ; Radiation-Sensitizing Agents ; pharmacology ; Triazines ; pharmacology

OBJECTIVETo investigate function of the Lim-only protein(LMO2) in hemangioblast generated from murine embryonic stem cells differentiation to hematopoietic cells.

METHODSThe hemangioblast-specific expression vector with lmo2 or green fluorescence protein gene was constructed, respectively. The murine embryonic stem cells were transfected by the hemangioblast-specific expression vectors. The neomycin-resistance ES cell clones were obtained after having been screened by G418. The cell clones were spontaneously differentiated into embryo bodies(EB) containing hemangioblast.Expression of the hematopoietic genes was investigated by real-time reverse transcription-ploymerase chain reaction during EB differentiation.For the EB cells, blast-cloning forming cells analysis and blood-colony forming unit analysis were then performed, respectively. The numbers of the blasts were counted during hematopoietic differentiation.

RESULTSThe hemangioblast-specific expression vector with lmo2 or green fluorescence protein was transfected into ES cells.The neomycin-resistance ES cells generated EBs from 2.5 days to 10 days.Real time reverse transcription-ploymerase chain reaction analysis indicated that overexpression of lmo2 increased the expression of hematopoietic genes(gata1, tal1, Β-h1, and Β-major globin) during EB formation.Blast-cloning forming cells analysis showed that the numbers of the blasts generated by ES/lmo2 was 2-or 3-fold than those in the controls.The total numbers of the blood-colony forming unit or the numbers of the erythrocyte colony-forming unit generated by ES/lmo2 were 2.5 times or 3 times, respectively, when compared with the controls.

CONCLUSIONLMO2 enhances the proliferation and differentiation of hemangioblasts.

Adaptor Proteins, Signal Transducing ; physiology ; Animals ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Embryonic Stem Cells ; cytology ; Hematopoietic Stem Cells ; cytology ; metabolism ; LIM Domain Proteins ; physiology ; Mice

Objective To investigate the management and control of hypertension in patients with chronic kidney disease(CKD) and its associated factors.Methods Data of 726in-patients with CKD and hypertension who hospitalized in our hospital from March 2009 to April 2010 were studied.Results 91.74％ of patients was treated with antihypertensive medications,and 21.21％, 22.59％, 19.56％, 28.37％ of patients received 1, 2, 3, ≥4 antihypertensive drugs,respectively.42.4％ of patients with CKD and hypertension could be controlled up to the standard,and the mean blood pressure was(137.86±20.75)/(76.30±11.35) mm Hg.There was significant difference among stage 1 plus 2, 3, 4 plus 5 (non-dialysis), 5 (dialysis) kidney diseases, with the hypertension control rate being 50.8％, 46.7％, 42.0％, 33.5％, respectively.The hypertension control rate of non-dialysis patients was significantly higher than that of dialysis (44.9％ vs 33.5％,P＜0.05).There was no significant difference between blood dialysis group and peritoneal dialysis group(32.3％ vs 38.7％, P＞0.05).Multivariate Logistic regression analysis showed that female (OR=1.787, 95％CI 1.045-3.056)and ACEI application (OR=4.378, 95％CI1.830-10.472) were positively associated with hypertension control.Whereas, diabetes (OR=0.415, 95％CI 0.188-0.919)and pulse pressure (OR =0.847, 95％ CI 0.811-0.885) were associated with inadequate blood pressure control.ConclusionsDespite almost universal hypertension treatment is used in patients with CKD and high blood pressure, the hypertension control rate is still suboptimal.Female and ACEI are positively associated with adequate hypertension control, whereas diabetes and pulse pressure are negatively associated with the standard.

The plasma visfatin,endothelium-dependent artery dilation and intima-media thickness of common carotid arteries were measured in first-degree relatives of type 2 diabetes,obese patients and control subjects.Regional body fat were detected by MRI.The result suggested that plasma visfatin levels were significantly higher in obese subjects than those in non-obese subjects,and hypervisfatinemia is independently associated with fasting blood glucose.

Objective To find the changes of haemagglutination inhibition ( HI ) antibody level against A/California/07/2009 (H1N1) within one month after pandemic A/H1N1 influenza vaccine (A/H1N1InfV) vaccination, and to provide data for drawing up immunization protocols against novel influenza . Methods The HI antibodies against A/California/07/2009 (H1N1) in sera from the inoculated subjects were tested by HI test .The geometric mean titer ( GMT) , geometric mean increase ( GMI) , seroconversion (SC) rate, seroprotection (SP) rate of HI antibodies were compared among the sera collected on day 3, 7, 14, 30 post vaccination .Results 961 participants were injected with A/H1N1InfV.In subjects aged 3 to 11 years, the antibody level peaked on day 14 post vaccination, but neither on day 14 nor on day 30, the lower bound of the two -sided 95%CI for the SP rate could fulfill the criteria of the FDA for influenza vac-cine.In subjects aged 12 to 60 years, the antibody level peaked on day 14 post vaccination and the SC rate , SP rate and GMI fulfilled the criteria of the European Medicines Agency ( EMEA) and the FDA for influenza vaccine. In subjects aged more than 60 years, the antibody level peaked on day 30 post vaccination , and the SC rate, SP rate and GMI on day 30 fulfilled the criteria of the EMEA and the FDA .Conclusion One dose A/H1N1InfV vaccination was able to induce enough protection on day 14 for subjects aged 12 to 60 years, on day 30 for subjects aged more than 60 years;however , for subjects aged 3 to 11 years who were antibody-negative at baseline , the lower bound of the two-sided 95%CI for the SP rate on day 14 and day 30 couldn′t fulfill the criteria of the FDA for influenza vaccine .

Background and Objective: Combined hypoxic cytotoxic drugs and chemoradiotherapy is an important mean of oncotherapy, and tirapazamine (TPZ) is one of the most remarkable drugs. It has been shown that TPZ has a synergistic effect with radiotherapy on tumor cells, but whether TPZ would down-regulate the expression of the hypoxia-induced genes has not been reported. This study was to investigate the hypoxiainduced expression of hypoxia inducible factor-1α (HIF-1α) and osteopontin (OPN) mRNA in human nasopharyngeal carcinoma HNE-1 and CNE-1 cells and the radiosensitization of TPZ, a hypoxia-specific drug, on HNE-1 and CNE-1 cells in vitro. Methods: The IC_(50) values of TPZ for HNE-1 and CNE-1 cells were measured using MTT assay, and the expression of HIF-1α and OPN mRNA in HNE-1 and CNE-1 cells was determined using RT-PCR under aerobic and hypoxic conditions, respectively. The survival rates of HNE-1 and CNE-1 cells treated with or without TPZ at IC_(10) in the presence or absence of oxygen for 6 h were determined using colony forming assay following exposure to 1-6 Gy of ~(60)Co radiation, and the dose-survival curves were plotted and the values of D_0, D_q and SER were calculated as a singlehit multitarget model. Results: The IC_(50) values of TPZ were 34.81 μmol/L and 35.02 μmol/L in HNE-1 and CNE-1 cells under aerobic condition, and 30.20 μmol/L and 28.48 μmol/L under hypoxic condition. The expressions of HIF-1α and OPN mRNA were reduced by TPZ in HNE-1 cells, but not in CNE-1 cells under hypoxic condition. The values of D_0 and D_q in HNE-1 and CNE-1 cells following irradiation under aerobic and hypoxic conditions were 0.89 Gy, 0.28 Gy and 0.72 Gy, 0.68 Gy, and 1.47 Gy, 0.44 Gy and 0.95 Gy,0.56 Gy, respectively. The values of D_0 and D_q for HNE-1 and CNE-1 cells treated with TPZ under hypoxic condition following irradiation were 0.66 Gy,0.21 Gy and 0.85 Gy, 0.79 Gy, respectively. Conclusion: TPZ would downregulate hypoxia-induced expression of HIF-1α and OPN mRNA of HNE-1 cells and radiosensitize the HNE-1 cells but not CNE-1 cells, and act as a hpoxia modifier.

OBJECTIVETo observe early intervention effects of Modified Shuyu Pill (MSP) on vascular cognitive impairment no dementia (VCIND).

METHODSTotally 100 patients VCIND were randomly assigned to the treatment group (43 cases) and the control group (33 cases). On the basis of the treatment targeting risk factors of blood vessels, patients in the treatment group were treated by MSP, while those in the control group were treated by donepezil hydrochloride. The therapeutic course was 16 weeks. The neuropsychological scales [mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA) score] and Chinese medicine dementia syndromes scales were observed before and after treatment.

RESULTSThe MMSE and MOCA score of the two groups increased when compared with the same group before treatment (P < 0.01). But there was no statistical difference in MMSE or MOCA score after treatment between the two groups (P > 0.05). The Chinese medicine dementia syndromes scales significantly decreased in the treatment group when compared with before treatment (P < 0.01). But there was no statistical difference in Chinese medicine dementia syndromes scales in the control group between before and after treatment (P > 0.05). There was statistical difference in Chinese medicine dementia syndromes scales after treatment between the two groups (P < 0.01).

CONCLUSIONMSP could effectively intervene the progress of VCIND.

Aged ; Cognition Disorders ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Early Medical Intervention ; Female ; Humans ; Indans ; therapeutic use ; Male ; Middle Aged ; Piperidines ; therapeutic use