Kidney plays an important role in maintaining the homeostasis as an important excretory and endocrine organ.The occurrence and development of kidney disease is closely associated with glomerular filtration barrier dysfunction and renal interstitial remodeling.Matrix metalloproteinase-9 (MMP-9),a major enzyme in the extracellular matrix (ECM),plays an important role in the process of kidney disease by regulating the ECM components and its interaction with cytokines.The paper reviews the pathophysiology of MMP-9 in glomerular filtration barrier dysfunction and renal fibrosis to provide a theoretical basis for clinical treatment of kidney disease.

Objective To evaluate the role of silent information regulator fac tor 2-related enzyme 1 (SIRT1)/Forkhead Box O3 (FoxO3a) signaling pathway in berberine pretreatment-induced reduction of hypoxia/reoxygenation (H/R)-caused injury to hepatic parenchymnal cells.Methods Hepatic parenchymal cells obtained from AML12 mice were cultured and seeded in 6-well plates (2 ml/well) and in 96-well plates (200 μl/well) at the density of l×l06 cells/ml.The cells were divided into 4 groups (n=36 each)using a randomn number table:control group (group C),group H/R,berberine pretreatment group (group BP) and SIRT1-siRNA group (group SS).The cells were cultured in normal culture atmosphere (5％ CO2-21％ O2-74％ N2) in group C.In H/R,BP and SS groups,the cells were exposed to hypoxic air (5％ CO2-1％ O2-94％ N2) for 12 h,followed by 6 h reoxygenation in normal culture atmosphere (5％ CO2-21％ O2-74％ N2).In group SS,small interference RNA targeting SIRT1 (SIRT1-siRNA) was added to the culture medium at 24 h prior to hypoxia.Berberine (final concentration 5 μmol/L) was added at 2 h prior to hypoxia in BP and SS groups.At the end of reoxygenation,the cell viability was measured by methyl thiazolyl tetrazolium assay,the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were determined using enzyme-linked immunosorbent assay,cell apoptosis was detected by flow cytometry,the expression of SIRT1 and FoxO3α was detected by Western blot,and the acetylation of FoxO3α was measnred by using immunoprecipitation.Apoptotic rate was calculated.Results Compared with group C,the cell viability was significantly decreased,the MDA content was increased,the SOD activity was decreased,apoptotic rate was increased,the expression of SIRT1 and ratio of FoxO3α expression in nucleus/in cytoplasma were increased,and the acetylation of FoxO3α in the nucleus was increased in H/ R,BP and SS groups (P＜ 0.05).Compared with group H/R,the cell viability was significantly increased,the MDA content was decreased,the SOD activity was increased,apoptotic rate was decreased,the expression of SIRT1 and ratio of FoxO3α expression in nucleus/in cytoplasma were increased,and the acetylation of FoxO3α in the nucleus was increased in group BP (P＜0.05).Compared with group BP,the cell viability was significantly decreased,the MDA content was increased,the SOD activity was decreased,apoptotic rate was increased,the expression of SIRT1 and ratio of FoxO3α expression in nucleus/in cytoplasma were decreased,and the acetylation of FoxO3α in the nucleus was decreased in group SS (P＜O.05).Conclusion The mechanism by which berberine pretreatment attenuates H/R-caused injury to hepatic parenchymal cells is related to promotion of SIRT1 expression in cells and inhibition of FoxO3α acetylation in the nucleus.

Objective To investigate the effect of Janus kinase2/signal transducer and activator of transcription 1 (JAK2/STAT1) signaling pathway on acute kidney injury induced by liver cold ischemia reperfusion (IR) in rats.Methods Thirty healthy male Sprague-Dawley rats,weighing 220-250 g,were assigned randomly to 3 groups (n =10/group):sham operation group (Sham group);liver cold ischemia reperfusion model group (I/R group);JAK2 kinase inhibitor AG490 group (AG490 group) (AG490 at dose of 10 mg/kg was intraperitoneally injected 30 min before establishment of the model).Other groups were given the equal volume of normal saline at the same time points.Then the rats were sacrificed at 6 h after reperfusion (at 6 h after the end of operation in Sham group).The renal function and oxidative stress level were observed.The pathological changes of the renal tissues and nephritic cell apoptosis were analyzed,and the expression of p-JAK2,pSTAT1,Bcl-2 and Bax was detected by Western blotting.Results As compared with Sham operation group,renal histological lesion and renal dysfunction were aggravated,level of oxidative stress and apoptosis rate were increased in I/R group,the Bcl-2/Bax ratio was decreased and the expression of pJAK2 and p-STAT1 was up-regulated.As compared with I/R group,AG490 dramatically attenuated histological lesions and oxidative stress,restored the renal function,and reduced the number of apoptotic tubular epithelial cells.AG490 significantly increased the Bcl-2/Bax ratio,and inhibited the expression of p-JAK2 and p-STAT1.Conclusion Blockage of JAK2/STAT1 signaling pathway can alleviate acute kidney injury after liver cold ischemia reperfusion probable through inhibiting the oxidative stress and apoptosis.

Objective To evaluate the effect of dexmedetomidine pretreatment on activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway during intestinal injury in rats undergoing liver transplantation.Methods Thirty-two pathogen-free healthy adult male Sprague-Dawley rats,weighing 220-250 g,aged 8-10 weeks,were divided into 4 groups (n =8 each) using a random number table:sham operation group (S group),liver transplantation group (LT group),dexmedetomidine pretreatment group (D group) and dexmedetomidine plus atipamezole (specific α2-adrenergic receptor antagonist) group (D+A group).The model of liver transplantation was established in LT,D and D+A groups except group S.In group D,dexmedetomidine 50 μg/kg was injected intraperitoneally at 30 min before skin incision.In group D+A,atipamzole 250 μg/kg was injected intraperitoneally at 5 min before administration of dexmedetomidine.At 6 h of reperfusion,blood samples were collected from the inferior vena cava for determination of serum concentrations of intestinal fatty acid binding protein (iFABP),lipopolysaccharide (LPS),tumor necrosis factor-alpha (TNF-ct) and high-mobility group box 1 protein (HMGB1).Intestinal specimens were then obtained for examination of the pathological changes of intestinal tissues (under light microscope) and for determination of the expression of activated caspase-3,phosphorylated JAK2 (p-JAK2),phosphorylated STAT1 (p-STAT1) and phosphorylated STAT3 (p-STAT3).Intestinal damage was assessed and scored.Wet/dry weight ratio (W/D ratio) was calculated.Results Compared with group S,the concentrations of iFABP,LPS,TNF-α and HMGB1 in serum,intestinal damage scores and W/D ratio were significantly increased,and the expression of activated caspase-3,p-JAK2,pSTATI and p-STAT3 in intestinal tissues was up-regulated in LT and D groups (P＜0.05).Compared with group LT,the concentrations of iFABP,LPS,TNF-cα and HMGB1 in serum,intestinal damage scores and W/D ratio were significantly decreased,and the expression of activated caspase-3,p-JAK2,p-STAT1 and p-STAT3 in intestinal tissues was down-regulated in group D (P＜0.05).Compared with group D,the concentrations of iFABP,LPS,TNF-cα and HMGB1 in serum,intestinal damage scores and W/D ratio were significantly increased,and the expression of activated caspase-3,p-JAK2,p-STAT1 and p-STAT3 in intestinal tissues was up-regulated in group D+A (P＜0.05).The pathological changes of intestinal tissues were significantly attenuated in group D as compared with group LT.Conclusion The mechanism by which dexmedetomidine pretreatment reduces intestinal injury may be related to inhibition of JAK/STAT signaling pathway activation in rats undergoing liver transplantation.

OBJECTIVE:To observe the efficacy of small dose of uremic clearance granule combined with colon enema on aged patients with chronic renal failure(CRF) . METHODS:60 aged CRF patients were randomly divided into treatment group(n=30) and control group(n=30) . Two groups were given essential treatment. Control group were treated with medicinal carbon additionally. Treatment group were additionally treated with uremic clearance granule(p.o.) combined with colon enema. The course of treatment was 15 days and curative effects were compared between two groups after 30 days of treatment. RESULTS:30 days later clinical symptom of patients in treatment group was obviously improved and the levels of blood urea nitrogen,serum creatinine,blood uric acid and serum potassium were lower than before treatment with significant difference. CONCLUSION:Small dose of uremic clearance granule combined with colon enema show satisfactory effect on CRF in aged patients as well as simple,practical and good compliance. This therapy is worth of spreading and putting into application.

Objective:To study the influence of vitamin C ( VC) on dendritic cells ( DC) ,and detect DC maturation,to provide a feasible method and thought for quickly preparating DC vaccines.Methods:Collected the peripheral blood (about 50 ml) from healthy volunteers,and isolated peripheral blood mononuclear cells with lymphocyte separation medium and obtain DC.With stimulating with different concentrations of VC for (24 h),then washed with PBS,and set up blank control group (V0).The expression of DC surface co-stimulating molecules CD80/86 and HLA-DR, CD40 was detected by flow cytometry.By setting the concentration gradient and time gradient, exciting optimal concentration and stimulating time of VC on DC, and analyzed the reasons of VC promoting DC maturation.Results:VC could effectively stimulate DC,CD80/86 expression had significantly increased contrast to the blank control group (V0).And the experiments show that VC’s best stimulating concentration was 1 mmol/L,and on the third day,the CD80/86 expression rate of VC group was (78.6±4.6) %,and blank control group V0 was (34.1±5.7) %.DC surface HLA-DR expression:VC (56.8± 4.4) %,blank control group V0 (25.4 ±4.7) %,the difference between two groups was statistically significant,P<0.05.CD40 and CD40L expression and results show that VC 2.5 mmol/L group of CD40 expression rate up to (59.3±3.7) %,while V0 group was only (11.1 ±2.4) %,that illustrate VC could significantly regulate CD40 expression on DC surface,but CD40L not reflect.Fluorescence mi-croscope results showed that DC’ s antigen catching ability was also significantly promoted.Conclusion:VC can significantly regulate DC maturity,and may up regulate CD40,thus promoting the express of CD80/86 and HLA-DR.When the concentration is 1 mmol/L,VC expresses the strongest regulation function on DC.

Objective To investigate the prevalence of sleep-disordered breathing in elderly patients with permanent cardiac pacemaker implantation due to bradyarrhythmias, and the relationship between pacing mode and patients' sleep apnea-hypopnea index.Methods Forty-four elderly patients (＞60 years) with cardiac pacemaker and their 44 controls matched for gender, age, body mass index and cardiovascular morbidity were studied using polysomnography or portable sleep monitoring device. Results Prevalence of sleep-disordered breathing (apnea-hypopnea index ≥5/h) was 44.7% and the mean apnea-hypopnea index was 8.2 ±4.1/h in the cardiac pacemaker group, which were significantly higher than those in control subjects (25% and 4.6±2.4/h, respectively, P＜0.01 and P＜0.05). The mean apnea-hypopnea index of patients with DDD or AAI pacemaker was significantly lower than that of patients with VVI pacemaker. Conclusions Sleep-disordered breathing was more common in patients who had their cardiac pacemaker implanted due to bradyarrhythmias than in their matched controls. Compared with VVI pacing, DDD or AAI pacing may be more beneficial to patients with bradyarrhythmias and sleep-disordered breathing.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by thunderclap headache and reversible cerebral vasoconstriction, with other neurologic signs and symptoms. To the best of our knowledge, there were only a few cases of RCVS presenting both as both convexity subarachnoid hemorrhage (cSAH) and posterior reversible encephalopathy syndrome (PRES). Herein, we report a case of a 32-year-old woman with RCVS who presented with recurrent thunderclap headaches that occurred 50 days after delivery, with cSAH and PRES on magnetic resonance imaging (MRI). She had significant clinical and radiological recovery on 3 months’ follow-up. The clinical coexistence of cSAH and PRES in our case with RCVS is quite rare. This case illustrates the importance of awareness of the diagnosis of RCVS among clinicians even when initial brain and vascular imaging are normal. Early diagnosis and treatment are crucial for better prognosis.

Objective To use metabonomics method to study the change of the basic materials of month rhythm of wei qi deficiency syndrome; To find the potential markers so as to provides a new way for the essence of the wei qi deficiency syndrome research.Methods Based on the autumnal equinox in lunar calendar month, the beginning of a month (the first day of lunar August), the middle of a month (the 15th day of lunar August), and the end of a month (the 30th day of lunar August) were set as the three days to draw experimental materials. Two weeks before drawing materials, 20 rats were randomly divided into control group and model group, 10 rats in each group. The model rats were modeled by the stimulus of fatigue combined with coldness and hotness. Control group rats received conventional breeding. The rats in the both groups during the three experiments received decollation and the blood was taken at the 12 o’clock at noon. HPLC-MS was used to detect plasma metabolites, and partial least squares were used to make statistical analysis on the data for comparing plasma metabonomics original data of control group and model group. Possible metabolic markers of wei qi deficiency syndrome were explored, and the potential makers of month rhythm change of wei qi deficiency syndrome were deduced.Results Oleamide, phosphatidyl glycerol, cortisol, proline, dimethyl fumarate, and eicosapentaenoic acid may be potential markers of wei qi deficiency syndrome in the beginning of a month. Sphingosine-1-phosphate, malic acid, cortisol, oleamide, carnitine, eicosapentaenoic acid and dimethyl fumarate may be potential markers of wei qi deficiency syndrome in the middle of a month. Cholesteryl acetate, threonine, cortisol, dimethyl fumarate, oleamide, eicosapentaenoic acid and pyroglutamate may be potential markers of wei qi deficiency syndrome in the end of a month.Conclusion Month rhythm change of wei qi deficiency syndrome may be influenced by oleamide, cortisol, eicosapentaenoic acid, dimethyl fumarate, and aconitic acid, and may be closely related to energy metabolism, meanwhile accompanied by regulation of cell, hormone and nerves.

Objective To evaluate the effect of propofol on brain injury during hepatic ischemiareperfusion (I/R) in preadolescent mice.Methods Forty-eight healthy male C57BL/6 mice.aged 2 weeks,weighing 6-9 g,were allocated to one of 3 groups (n=16 each) using a random nunber table:sham operation group (group S),hepatic I/R group (group I/R) and propofol group (group P).Hepatic I/R was produced by occlusion of the blood supply to the median and left lobes of the liver for 60 min followed by reperfusion in anesthetized mice.In group P,1％ propofol 30 mg/kg was intraperitoneally injected at 30 min before skin incision,while the equal volume of normal saline was given instead in S and I/R groups.Blood samples were collected and brains were removed at 24 h of reperfusion,and hippocampi were then isolated.The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in hippocampi and levels of TNF-α,IL-1β,S-100β protein and neuron-specific enolase (NSE) in serum were determined by enzyme-linked immunosorbent assay.The pathological changes of hippocampi were examined with a light microscope,the apoptosis in hippocampal cells was measured using TUNEL,and the apoptotic index was calculated.Results Compared with group S,the TNF-α and IL-1β levels in serum and hippocampi,levels of S-100β protein and NSE in serum and apoptotic index were significantly increased (P＜0.01),and the pathological changes of hippocampi were aggravated in I/R and P groups.Compared with group I/R,the TNF-α and IL-1β levels in serum and hippocampi,levels of S-100β protein and NSE in serum and apoptotic index were significantly decreased (P＜0.05),and the pathological changes of hippocampi were attenuated in group P.Conclusion Propofol reduces brain injury induced by hepatic I/R,and the mechanism may be related to inhibition of systemic and central inflammatory responses of preadolescent mice.