Objective To explore the intervention effect of cathepsin B inhibitor (CBI) and its signaling pathways after flurothyl inducing brain injury in rats with recurrent seizures. Methods 6-day-old (P6) SD rats were randomly divided into: recurrent neonatal seizure group ( RS group, n = 30), CBI-treated seizure group ( CBI group, n=30) and the control group( CONT group). Rats in RS group were subjected to 5 seizures with flurothyl during the first 14 days of life. In CBI group,CBI was injected each day before seizures were induced. Then examined development indexes such as the physical growth, neural reflex, neural behavior and cognitive emotional competence. Western blot was employed to determine Cathepsin B expression at different time points ( 1.5h,3h,6h,24h and P35) after the last convulsion. Results The weights of rats in RS group( (27.28 ± 1.6) kg) were lighter than CONT group( ( 33.45 ± 1.57 ) kg). They had significant difference (P＜ 0.01 ) at the age of p14. The time of cliff avoidance in RS group( (2. 10 ± 1.45 ) s) was longer than CBI group( ( 1.05 ± 0. 32) s). It showed a statistically significant (P ＜ 0.05 ) in p12. In the open-field behavior test: the activities of RS group (20.00 ± 13.08 )were markedly reduced than CONT group ( 57.83 ± 33.22 ) in the horizontal movements, the RS group ( 2.50 ±2.43 ) were significantly decreased than the CONT group and CB1 group( ( 22.17 ± 10.74), (9.33 ± 5.39 ) ) in the vertical motions (P ＜ 0. 05 ). Cathepsin-B expression in RS group( 1.5h, 3h,6h and 24h )was significantly higher than that at the same time in CONT group(P＜ 0. 05 ). Cathepsin-B expression of CBI group was significantly decreased compared with that in RS group (P＜ 0. 05 ) at the time point (1.5h ,3h,6h and 24h). There were no significant differences among three groups at P35(P＞0.05 ). Conclusions CBI can improve brain injury and regulate the expression of abnormal molecules.

Objective To explore the dynamic expressions of autophagia and apoptosis associated protein Beclin-1, Cathepsin B and Bcl-2 in hippocampus and the intervention efficacy of cathepsin-B inhibitor (CBI) after recurrent neonatal seizure. Method Ninty 6-day-old SD rats were randomly (random number) divided into the recurrent neonatal seizure group (RS group, n = 30), CBI-treated seizure group (CBI group, n = 30) and the control group (n = 30). Rats in RS group were subjected to 55 attacks of seizure induced by using flurothyl during the consecutive 9 days beginning on the 6 th postnatal day (P6). In CBI group, CBI (2 μL, 0.5 μg/μL) was administered every day before seizures induced. Western blot was employed to determine the protein level at different intervals (1.5 h,3 h,6 h,24 h) after the last convulsion.Results There were higher expressions of Beclin-1 and Cathepsin B, and lower expressions of Bcl-2 expression in RS group(1. 5 h,3 h,6 h and 24 h) than those at the same time in control group (P ＜ 0.05). Beclin1 and Cathepsin B expressions were lower while Bcl-2 expressions were higher in CBI group at the intervals of 1.5 h,3 h,6 h and 24 h compared with those in RS group (P ＜ 0. 05). Conciusions Autophagic and apoptotic pathways were activated immediately after recurrent neonatal seizures as indicated by expression changes of Beclin-1, Cathepsin B and Bcl-2 in hippocampus, which suggests a synergistic effect of the two pathways in the pathophysiology of the long-term brain damage of neonateε resulted from the adverse effects of recurrent neonatal seizures.

Objective To observe and explore clinical efficacy ofTianma-Gouteng decoction combined valsartan in the treatment of patients with renal hypertension and its effects on renal function. Methods A total of 130 patients with renal hypertension were enrolled and randomly divided into a study group (68 patients) and a control group (62 patients). Both groups were given prescription of lower sodium diet, exercising and enalaprilscheme. On this basis, the control group plus valsartan, and the study group was further added withTianma-Gouteng decoction. After 2 courses treatment, renal function, and blood pressure of both groups were compared, and clinical efficacy on blood pressure were evaluated.Results After treatment, the SBP (126.8 ± 9.1 mmHg vs. 134.1 ± 8.8 mmHg,t=4.648), DBP (82.4± 5.0 mmHgvs. 85.3 ± 5.4 mmHg, t=3.167), Scr (148.5 ± 46.3μmol/Lvs. 172.1 ± 52.0μmol/L, t=2.723), BUN (8.3 ± 2.7 mmol/Lvs. 9.7 ± 3.1 mmol/L,t=2.734) and 24hAlb (1.7 ± 0.6 gvs. 1.9 ± 0.7 g,t=2.209) in the study group were significantly lower than control group (P<0.05 orP<0.01). The total effective rate in the study group was significantly increased than that in the control group (91.2%vs. 79.0%;χ2=0.383,P=0.050).Conclusion Valsartan combined with Tianma-Gouteng decocntion can reduce blood pressure, and alleviate the kidney damage effectively.

Objective To investigate the clinical effect ofYishen-Lishi formula combined with conventional treatment for gouty nephropathy.MethodsA total of 118 patients with gout nephropathy were included and divided randomly into a conventional treatment group (n=60) and a combined treatment group (n=58) according to the random number table method. The patients in the conventional treatment group were treated with allopurinol and those in the combined treatment group were treated with allopurinol and Yishen-Lishi formula, both for 3 months. Serum uric acid, blood urea nitrogen (BUN), serum creatinine (SCr), 24 h endogenous creatinine clearance (CCr), 24 h urine protein, urineb2 microglobulin, serum triacylglycerol (TG), serum total cholesterol (TC), serum apolipoprotein A1, 24 h urine volume and urine pH were determined. The therapeutic effect was evaluated.ResultsThe urine pH (6.43 ± 0.6vs.6.21 ± 0.4;t=2.351,P=0.020), 24 h urine volume (3.3 ± 0.4vs.2.8 ± 0.6 L;t=5.308,P<0.001), 24 h CCr (1.61 ± 0.11 ml/svs. 1.33 ± 0.10 ml/s;t=14.477,P<0.001) and serum apolipoprotein A1 (1.90 ± 0.40 g/Lvs. 1.01 ± 0.33 g/L;t=13.203,P<0.01) in the combined treatment groupwere significantly higher than those in the standard treatment group. The serum uric acid (312.01 ± 33.56mmol/Lvs.350.12 ± 35.21 mol/L;t=6.015,P<0.001), BUN (6.22 ± 0.91 mmol/Lvs.11.50 ± 4.01 mmol/L;t=9.586,P<0.001), SCr (87.32 ± 13.90mmol/Lvs.122.54 ± 18.37mmol/L;t=11.743,P<0.001), 24 h urine protein (0.7 ± 0.2 gvs.1.2 ± 0.5 g;t=7.087,P<0.001), urineb2 microglobulin (220.3 ± 90.3mg/Lvs.330.1 ± 90.1mg/L;t=6.611,P<0.01), serum TG (5.11 ± 0.50 mmol/Lvs.6.30 ± 0.50 mmol/L;t=12.923,P<0.001), serum TC (1.50 ± 0.50 mmol/Lvs.2.30 ± 0.52 mmol/L;t=8.689,P<0.001) in the combined treatment group were significantly higher than those in the standard treatment group. The total effective rate inthe standard treatment group was significantly higher than those in the standard treatment group (89.7%vs.70.0%;χ2=5.871,P=0.015). ConclusionYishen-Lishi formula combined with conventional treatmentmay protect renal function, and reduce the blood lipids, its therapeutic effect is superior to conventional treatment alone in patients with gouty nephropathy.

Strokes due to atrial fibrillation (AF) are common and frequently devastating.While oral anticoagulant agents are the mainstay in the prevention of embolic events,they have several limitations and not all patients can tolerate them long term.The left atrial appendage (LAA) has been identified as the source of thrombus formation in nonvalvular AF.Several LAA closure devices have been developed,they have been successful in stroke prevention in patients with nonvalvular AF and fewer periprocedural complications.This article reviews the application of percutaneous left atrial appendage closure for stroke prevention in patients with nonvalvular AF.

Objective To evaluate the improvement of lower urinary tract symptoms in benign prostatic hyperplasia (BPH) patients with bladder calculi by lithotripsy and adjuvant traditional Chinese decoction. Methods A total of 72 BPH patients with bladder calculi were recruited and randomly divided into the non-adjuvant treatment group (37 patients) and the adjuvant treatment group (35 patients). The adjuvant treatment group received adjuvant traditional Chinese decoction from 2 days before lithotripsy for 2 weeks. The maximum urinary flow rate (Qmax) , residual urine volume (RU), International Prostate Symptom Score (IPSS) and Quality of Life (QOL) were assessed before and after the treatment. The time of urine routine returned to normal and the indwelling time of catheter were compared between two groups. Urinary incontinence and recurrent bladder calculi were followed up for 6 months. Results After the treatment, the score of the IPSS (12.9 ± 4.5 vs. 15.7 ± 3.9;t=2.826, P=0.006) and the RU (47.3 ± 9.2 ml vs. 58.4 ± 11.3 ml;t=4.556, P<0.001) in the adjuvant treatment group were significantly lower than those in the non-adjuvant treatment group, and the Qmax (30.4 ± 4.7 ml/s vs. 21.4 ± 3.9 ml/s;t=8.862, P<0.001 ) was significantly higher. The indwelling time of catheter (5.7 ± 2.1 d vs. 8.1 ± 2.2d;t=4.730, P<0.001) and the time of urine routine returned to normal (6.9 ± 2.3 d vs. 10.2 ± 3.1 d;t=5.106, P<0.001) in the adjuvant treatment group were significantly shorter than those in the non-adjuvant treatment group. The 6-month follow-up showed that the incidence of urinary incontinence (2.9% vs. 18.9%;χ2=4.698, P=0.030) and recurrent bladder calculi (5.7% vs. 24.3%;χ2=4.813, P=0.028) in the adjuvant treatment group were significantly shorter than those in the non-adjuvant treatment group, and the total effective rate was significantly higher (62.9%vs. 29.7%; χ2=6.672, P=0.011). Conclusions Lithotripsy and adjuvant traditional Chinese decoction can reduce the IPSS score and RU, increase Qmax, decrease urinary incontinence and recurrent bladder calculi, and improve lower urinary tract symptoms in BPH patients with bladder calculi.

OBJECTIVETo study the promoter methylation status of SFRP genes and the effect of 5- aza- 2'- deoxycytidine (5- Aza- CdR)induced apoptosis via Wnt/β- catenin pathway by demethylation in Jurkat cells.

METHODSJurkat cells were treated with different concentrations of 5- Aza- CdR. The cell proliferation level of Jurkat cells was detected by MTT assay. Apoptosis was evaluated by flow cytometry. Methylation- spcific PCR (MSP) was used to determine the methylation status of SFRP genes. The expressions of SFRP genes were detected by real time fluorescence quantitative PCR. The mRNA expression levels of survivin, c- myc and cyclin- D1 were analyzed by RT- PCR. Western blot was used to detect the levels of β-catenin protein.

RESULTSCompared with control group, the different concentrations of 5-Aza-CdR could significantly inhibit the proliferation of Jurkat cells in a time-dose dependent manner (P<0.05). After being treated by 5- Aza- CdR for 48 hours, the cell early apoptosis rate in experiment group was significantly higher than that in control group (P<0.05). The promoters of SFRP1, SFRP2, SFRP4, SFRP5 genes were hypermethylation state in the control group, after being treated by 5-Aza-CdR for 72 hours, the brightness of SFRP1, SFRP2, SFRP4, SFRP5 genes' methylation strips weakened in a dose- dependent manner. SFRP mRNA expression increased (P<0.05) when 5- Aza- CdR concentration increased, and the level of β- catenin protein was dampened in a dose- dependent manner (P<0.05). As compared to the control group, the mRNA expressions of associated apoptosis genes survivin, c-myc and cyclin- D1, respectively were obviously down- regulated in a dose- dependent manner (P<0.05).

CONCLUSIONThe effect of demethylation could up- regulate SFRP genes expressions by reversing its hypermethylation and induced apoptosis by down-regulation of β-catenin and associated apoptosis genes.

Apoptosis ; Azacitidine ; analogs & derivatives ; pharmacology ; Cell Proliferation ; DNA Methylation ; Down-Regulation ; Gene Expression ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; Jurkat Cells ; Membrane Proteins ; genetics ; Promoter Regions, Genetic ; Wnt Signaling Pathway ; beta Catenin ; metabolism

BACKGROUND: Age, sex, body mass index, hepatitis C infection, immunosuppressive drugs and family history of diabetes mellitus are shown to be risk factors for new-onset diabetes mellitus after kidney transplantation, but their effects remain controversial. OBJECTIVE: To systematically assess the risk factors for new-onset diabetes mellitus after kidney transplantation, so as to provide evidences for preventing and controlling the disease. METHODS: PubMed, Embase, Cochrane Library and CBMdisc databases were searched for the articles concerning risk factors for new-onset diabetes mellitus after kidney transplantation published between January 2005 and May 2018. Two researchers extracted data from each study based on inclusion and exclusion criteria. Quality assessment was conducted in accordance with New castle-Ottawa Scale standard. Meta-analysis was performed on Revman 5.3 software to identify the risk factors for new-onset diabetes mellitus after kidney transplantation. RESULTS AND CONCLUSION: (1) Twenty-one studies involving 8 206 patients were included. There were 1 489 cases of new-onset diabetes mellitus after kidney transplantation, and the morbidity was 18.15％. (2) The meta-analysis identified the following seven significant risk factors, non-modifiable risk factors: age ≥ 50 years, and donor type; modifiable risk factors: body mass index ≥ 25 kg/m2, acute rejection, tacrolimus usage, hepatitis C infection and polycystic kidney. (3) Uncertain risk factor was family history of diabetes. (4) To conclude, age, donor type, body mass index ≥ 25 kg/m2, acute rejection, tacrolimus usage, hepatitis C infection and polycystic kidney are risk factors for new-onset diabetes mellitus after kidney transplantation. But whether the family history of diabetes mellitus is the risk factor remains uncertain.

Objective:To investigate the clinical manifestation, diagnosis and treatment of chronic lymphocytic leukemia patients with renal involvement.Methods:The clinical data of a chronic lymphocytic leukemia patient with nephrotic syndrome as the initial manifestation in Fujian Provincial People's Hospital in October 2020 were retrospectively analyzed, and the related literature was reviewed.Results:The patient was a 68-year-old male with recurrent edema and foam urine as the initial manifestations, and he was diagnosed as nephrotic syndrome in the nephrology department. After treatment, the symptoms showed no significant improvement, and the lymphocyte count gradually increased. The patient was diagnosed as chronic lymphocytic leukemia in the hematology department. After ibrutinib monotherapy, the lymphocyte count and urine protein gradually decreased to normal levels, and the clinical efficacy evaluation of the patient was complete remission at the end of follow-up.Conclusions:Chronic lymphocytic leukemia with nephrotic syndrome as the initial manifestation is rare, and the clinical presentations are variable. Early diagnosis is the guarantee of successful treatment. The efficacy and safety of first-line Bruton tyrosine kinase inhibitor monotherapy are good.

Objective To analyze the clinical efficacy of combined or single use of clofibrate and cytarabine in the treatment of adult patients with myelodysplastic syndromes (MDS) or acute leukemia (AL).Methods Clofarabine combined with cytarabine was used in the combined group and clofarabine or cyarabine alone was used in the control group.All the studies about cytarabine and clofarabine were searched in PubMed,Cochrance Library,Embase,CNKI,Wanfang and VIP database by computer,and then the data was extracted.Results The complete remission rate of the combined group was higher than that of the control group [33.1％ (93/281) vs.18.2％ (35/192),and the difference was statistically significant (RR =1.85,95％ CI 1.31-2.60,P ＜ 0.01).The overall response rate of the combined group was higher than that of the control group [44.0％ (124/282) vs.23.2％ (46/198)],and the difference was statistically significant (RR =1.92,95％ CI 1.44-2.56,P ＜ 0.01).However,the incidence of skin adverse reactions in the combined group was also higher than that in the control group [38.8％ (104/268) vs.3.1％ (6/192)],and the difference was statistically significant (RR =7.76,95％ CI 3.68-16.38,P ＜ 0.01).Conclusion The combination of clofarabine and cytarabine in the treatment of adult patients with MDS or AL has better clinical efficacy than single application,but it also has more serious skin adverse reactions.