Objective To observe changes of dynamic functional connectivity(dFC)of brain networks in different stages of Parkinson disease(PD).Methods Totally 52 early-stage PD patients(early PD group),36 late-stage PD patients(late PD group)and 38 healthy controls(HC group)were prospectively enrolled,and resting-state functional MRI were performed.The sliding window,independent component analysis and k-means clustering were used to extract dFC intensity and temporal properties,including fractional windows,dwell time and transition frequency.Results Network connectivity patterns within and between visual network(VIS),sensorimotor network(SMN),default mode network(DMN),cerebellar network(CB)and cognitive executive network(CEN)were altered in PD patients.Four dFC states were identified,in which connections between components in states Ⅰ and Ⅱ were compact,while in states Ⅲ and Ⅳ were sparse.The fractional window and dwell time of late PD group,early PD group and HC group successively increased under state Ⅱ,but successively decreased under state Ⅲ(all P＜0.05).Under state Ⅰ and Ⅳ,no significant difference of fractional window nor dwell time was found between early PD group and late PD group(both P＞0.05),and the above indexes under state Ⅰ were both lower than those in HC group(all P＜0.05),the fraction window under state Ⅳ was higher than that in HC group(both P＜0.05).Conclusion The temporal properties of dFC in PD patients were altered,characterized by increased tendency toward segregated states.Furthermore,fractional windows and dwell time were associated with PD disease stages,suggesting that dFC parameters might serve as novel biomarkers for assessing clinical progression of PD.

Objective To observe changes of dynamic functional connectivity(dFC)of brain networks in different stages of Parkinson disease(PD).Methods Totally 52 early-stage PD patients(early PD group),36 late-stage PD patients(late PD group)and 38 healthy controls(HC group)were prospectively enrolled,and resting-state functional MRI were performed.The sliding window,independent component analysis and k-means clustering were used to extract dFC intensity and temporal properties,including fractional windows,dwell time and transition frequency.Results Network connectivity patterns within and between visual network(VIS),sensorimotor network(SMN),default mode network(DMN),cerebellar network(CB)and cognitive executive network(CEN)were altered in PD patients.Four dFC states were identified,in which connections between components in states Ⅰ and Ⅱ were compact,while in states Ⅲ and Ⅳ were sparse.The fractional window and dwell time of late PD group,early PD group and HC group successively increased under state Ⅱ,but successively decreased under state Ⅲ(all P＜0.05).Under state Ⅰ and Ⅳ,no significant difference of fractional window nor dwell time was found between early PD group and late PD group(both P＞0.05),and the above indexes under state Ⅰ were both lower than those in HC group(all P＜0.05),the fraction window under state Ⅳ was higher than that in HC group(both P＜0.05).Conclusion The temporal properties of dFC in PD patients were altered,characterized by increased tendency toward segregated states.Furthermore,fractional windows and dwell time were associated with PD disease stages,suggesting that dFC parameters might serve as novel biomarkers for assessing clinical progression of PD.

Objective To explore the image quality improvement of portal vein computed tomography venography(CTV)using CE-Boost technique with low dose and low contrast media usage.Methods A total of 50 patients with suspected portal vein disorders who underwent abdominal non-contrast and biphasic contrast-enhanced CT scans using the Canon 320-row CT machine were retrospectively selected.Images of portal venous phase(PVP)were postprocessed with CE-Boost technique.The CT values of each area,standard deviation(SD)values of the paraspinal muscles,volume CT dose index(CTDIvol),and dose length product(DLP)before and after CE-Boost were measured and recorded.The signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),effective dose(ED)of each blood vessel before and after CE-Boost were calculated.Subjective image quality was analyzed by two senior radiologists using a five-point scale in a double-blinded method.Statistical analysis was performed using paired t-test and Wilcoxon test.Results The CT values of each area with CE-Boost images were significantly higher than those without CE-Boost images(P＜0.001).SNR and CNR of each blood vessel with CE-Boost images were significantly higher than those without CE-Boost images(P＜0.001).The subjective scores of both images were above 3 points,which met the requirements of clinical diagnosis with good consistency(Kappa=0.772,0.697).The median subjective scores of images with CE-Boost were 5(5,5),which were significantly higher than those without CE-Boost images 5(5,4),(P=0.002).CTDIvol,DLP and ED were(1.85±1.12)mGy,(94.66±44.68)mGy·cm and(1.42±0.67)mSv,respectively.Conclusion CE-Boost technique can significantly improve the image quality of portal vein CTV with low dose and low contrast media usage.

Chronic kidney disease（CKD）has a significant impact on global public health and is one of the important factors leading to the rise of incidence rate and mortality of non communicable diseases.Intestinal microecology is involved in many pathophysiological activities，such as immunity and nutrient absorption.With proposal of the concept of intestine-kidney axis in 2002，researchers found that the decline of glomerular filtration rate led to accumulation of uremic toxins in intestine，destroyed the intestinal mucosal barrier，led to the translocation of toxins，activated the systemic oxidative stress response，further promoted the progress of CKD.This article reviewed the function of gut microbiota，intestine-gut kidney axis，and the application of microbial preparations in CKD.

The injury of vascular endothelial cells is not only the initial condition to promote the occurrence of early atherosclerosis （AS） plaques， but also an important link in the pathogenesis of AS. The microRNA （miRNA）， as an important medium of intercellular communication and gene regulatory factor， can affect vascular endothelial function and participate in the development of AS. The molecular mechanism of miRNA’s multi-target intervention in vascular endothelial cell injury has become a hot topic in the research of cardiovascular diseases. Monomers of traditional Chinese medicines such as ginsenoside Rb2 and paeonol， as well as traditional Chinese medicine for resolving phlegm and removing blood stasis could regulate miRNA to improve endothelial cell inflammation； astragaloside Ⅳ， dihydromyricetin and notoginsenoside could target miRNA and inhibit vascular endothelial oxidative stress； Danhong injection， Jianpi qutan and huayu prescription and paeonol could affect endothelial autophagy through miRNA； resveratrol， Bushen huoxue formula and Bushen tongmai formula could inhibit vascular endothelial aging by miRNA； dendrobine played an active role in regulating miRNA and improving endoplasmic reticulum stress. In the future， more in- depth research is needed on the effectiveness， mechanism of action， diagnosis and treatment plans， and safety of targeted regulation of miRNA for AS therapy by traditional Chinese medicine.

Objective:To investigate the role of IL-21/IL-21R-mediated CD4 + T cells in Chlamydia muridarum ( Cm) respiratory infection. Methods:C57BL/6 mice (WT mice) and IL-21R -/- mice were used to establish the models of Cm respiratory infection through intranasal inhalation of Cm. Flow cytometry was used to detect the proportion, number, activity and function of CD4 + T cells in lung and spleen tissues at 0, 3, 7 and 14 d after Cm respiratory tract infection. IFN-γ and IL-4 levels in spleen cell culture supernatants were detected by ELISA. Na?ve WT mice were transferred with CD4 + T cells in the spleen tissues of IL-21R -/- mice or WT mice on 7 d after infection and given Cm intranasally 2 h later. Then the mice were weighed daily and sacrificed on 14 d after infection. The bacterial load and pathological changes in lung were analyzed. Flow cytometry was performed to detect the proportions and numbers of neutrophils (CD45 + CD11b + Gr-1 high) and alveolar macrophages (CD45 + F4/80 + CD11c high)as well as the proportions of Th1 (IFN-γ + CD4 + ) and Th2 (IL-4 + CD4 + ) cells. ELISA was also performed to measure IFN-γ and IL-4 levels in spleen cell culture supernatants. Results:Compared with WT mice, IL-21R -/- mice showed elevated numbers and enhanced activation of CD4 + T cells, increased proportion of Th1 cells and decreased proportion of Th2 cells in spleen and lung tissues after Cm respiratory infection. Besides, IFN-γ levels increased, while IL-4 levels decreased in spleen cell culture supernatants of IL-21R -/- mice. After Cm infection, the na?ve WT transferred with CD4 + T cells from IL-21R -/- mice showed less body weight loss, reduced bacterial load and alleviated pathological changes in lung tissues, increased proportion of Th1 cells in lung tissue and higher IFN-γ level in spleen cell culture supernatants. Conclusions:IL-21/IL-21R-mediated CD4 + T cells could aggravate Cm respiratory infection by suppressing Th1 cell immune responses.

Background::Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia.Methods::Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients ( n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group ( n = 56) and a twice or three times per week intravenous epoetin alfa group ( n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion::Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Background::Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia.Methods::Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients ( n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group ( n = 56) and a twice or three times per week intravenous epoetin alfa group ( n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion::Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.