Objective To investigate the effect of sodium butyrate on apoptosis of rat mesangial cells and the regulation of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signal pathway,and analyze the possible mechanism.Methods Primary cultured,isolated and purified rat mesangial cells.The cells were randomly divided into blank group,control group[10 μg·L-1 epidermal growth factor(EGF)],low dose experimental group(10μg·L-1 EGF+0.5 mmol·L-1 sodium butyrate),medium dose experimental group(10 μg·L-1 EGF+1.0 mmol·L-1 sodium butyrate)and high dose experimental group 10 μg·L-1 EGF+2.0 mmol·L-1sodium butyrate).Cell survival rate was detected by cell counting kit-8(CCK-8)method,cell cycle was detected by propyl iodide(PI)staining,cell apoptosis rate was detected by flow cytometry,and the expression of PI3K/AKT/mTOR channel-related proteins was detected by Western blot.Results After 24 h of treatment,the optical density of blank group,control group and low,medium,high dose experimental group were 0.36±0.03,0.66 ±0.03,0.57±0.05,0.47±0.02,0.41±0.01;which at 48 h of treatment were 0.55±0.03,0.83±0.04,0.68 ±0.03,0.65±0.02,0.60±0.02,respectively.The results showed that 10 μg·L-1 EGF significantly stimulated the proliferation and activation of mesangial cells(P＜0.05),and the proliferation of mesangial cells was significantly inhibited after treatment with different concentrations of sodium butyrate for 24 and 48 h(P＜0.05).PI staining showed that the G1 phase blocking rates of blank group,control group and low,medium,high dose experimental groups were(53.37±0.43)％,(46.84±0.67)％,(57.81±0.48)％,(62.77±0.77)％,(67.57±0.71)％,respectively.The results showed that sodium butyrate could induce cell cycle arrest in G1 phase in a concentration-dependent manner(P＜0.01).The apoptosis rates of blank group,control group and low,medium,high dose experimental groups were(4.43±0.48)％,(2.45±0.31)％,(6.16±0.33)％,(8.25±0.40)％and(12.12±0.41)％,the differences were statistically significant between control group and low,medium,high dose experimental groups(all P＜0.01).Conclusion Sodium butyrate can effectively inhibit the proliferation and induce apoptosis of rat mesangial cells,and its mechanism may be related to the inhibition of PI3K/AKT/mTOR signaling pathway.

OBJECTIVE: To investigate the effect of hydronidone on CCl₄-induced liver fibrosis in rats and explore the possible mechanism. METHODS: Sixty-six male SD rats were randomized into 5 groups, including a control group (n=10), a liver fibrosis model group (n=20), 2 hydronidone dose groups (100 and 250 mg/kg; n=12), and a pirfenidone (250 mg/kg) treatment group (n= 12). Rat models of liver fibrosis were established by subcutaneous injection of CCl₄ in all but the control group. Hydronidone and pirfenidone were given daily at the indicated doses by intragastric administration for 6 weeks. After the treatments, serum samples were collected from the rats for detecting liver function parameters, and hydroxyproline content in the liver tissue was determined. Inflammation and fibrosis in the liver tissue were observed using HE staining and Sirius Red staining. In the cell experiment, human hepatic stellate cell line LX-2 was stimulated with TGF-β1 and treated with hydronidone or pirfenidone, and the expression levels of α-SMA, collagen type I and phosphorylated Smad3, phosphorylated p38, phosphorylated ERK1/2 and phosphorylated Akt were detected with Western blotting. RESULTS: In the rat models of liver fibrosis, treatment with hydronidone obviously improved the liver functions, reduced the content of hydroxyproline in the liver tissue, and significantly alleviated liver fibrosis (P < 0.05). In LX-2 cells, hydronidone dose-dependently decreased the expression levels of α-SMA and collagen type I. In TGF- β1-stimulated cells, the phosphorylation levels of Smad3, P38, ERK, and Akt increased progressively with the extension of the treatment time, but this effect was significantly attenuated by treatment with hydronidone (P < 0.05). CONCLUSION Hydronidone can inhibit the phosphorylation of the proteins in the TGF-β signaling pathway, thereby preventing TGF-β1-mediated activation of hepatic stellate cells, which may be a possible mechanism by which hydronidone alleviates CCl₄-induced liver fibrosis in rats.
Animals ; Male ; Rats ; Carbon Tetrachloride/metabolism* ; Collagen Type I ; Hepatic Stellate Cells/pathology* ; Hydroxyproline/therapeutic use* ; Liver Cirrhosis ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Smad Proteins/metabolism* ; Transforming Growth Factor beta1/metabolism*

OBJECTIVETo investigate the factors upgrading the International Society of Urological Pathology (ISUP) Gleason score using the specimens from preoperative prostatic biopsy and radical prostatectomy.

METHODSA total of 164 patients diagnosed with prostate cancer by biopsy underwent radical prostatectomy. We retrospectively analyzed their age, prostate volume, preoperative PSA level, PSA density (PSAD) , the time interval between biopsy and surgery, the number of positive punctures, positive surgical margin, seminal vesicle invasion, lymphatic invasion, and Gleason scores from biopsy and prostatectomy. We also determined the predictors of Gleason score upgrading by logistic regression analysis.

RESULTSOf the 164 cases analyzed, 95 (57.93% ) showed a consistency between the Gleason score of preoperative prostatic biopsy and that after radical prostatectomy, 55 (33.54% ) increased and 14 (8.52%) decreased after prostatectomy as compared with preoperative biopsy. The prostate volume (P < 0.01) and biopsy score (P < 0.05) were independent predictors of Gleason score upgrading. The risk of Gleason score upgrading was 27 times higher in the patients with the prostate volume ≤ 25 ml and 9 times higher in the 25-40 ml group than in the > 60 ml group (P < 0.05).

CONCLUSIONLow Gleason score of biopsy (≤ 6) and small prostate volume (≤ 40 ml) may be the predictors of Gleason score upgrading after radical prostatectomy.

Biopsy ; Humans ; Male ; Neoplasm Grading ; Organ Size ; Prostate-Specific Antigen ; blood ; Prostatectomy ; Prostatic Neoplasms ; classification ; surgery ; Retrospective Studies ; Risk Factors

OBJECTIVETo investigate factors related to hemorrhagic transformation and favorable outcomes in wake-up ischemic stroke (WUIS) patients undergoing intravenous thrombolytic therapy.

METHODSClinical data of 600 patients undergoing multimodal image-guided intravenous recombinant tissue plasminogen activator (rt-PA) therapy in Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine center from May 2009 to May 2015 were retrospectively analyzed. Among 600 patients, 68 were diagnosed as WUIS including 17 cases aged 80 or older. Hemorrhagic transformation within the first 24 h after thrombolysis was assessed according to ECASS II criteria. Favorable outcome was defined as three-month modified Rankin Scale (mRS) 0-3. Univariate and binary logistic regression were used to analyze the risk factors of hemorrhagic transformation and poor clinical outcomes in WUIS patients.

RESULTSUnivariate analysis showed that WUIS patients aged ≥ 80 years had a lower rate in males (41.2% vs 76.5%, P=0.007), smokers (11.8% vs 43.1%, P=0.019) and favorable outcome (52.9% vs 78.4%, P=0.043); and a higher rate of cardiac embolism (64.7% vs 35.3%, P=0.034) compared with those aged <80 years. Binary logistic regression showed that age was not an independent risk factor for favorable outcome (OR=0.524, 95% CI:0.141-1.953, P=0.336) or hemorrhagic transformation (OR=1.039, 95% CI: 0.972-1.111, P=0.262).

CONCLUSIONOlder age is not related to the favorable outcome or hemorrhagic transformation in WUIS patients undergoing multimodal image-guided intravenous thrombolytic therapy.

Administration, Intravenous ; Age Factors ; Aged ; Aged, 80 and over ; Brain Ischemia ; diagnosis ; drug therapy ; Female ; Fibrinolytic Agents ; administration & dosage ; therapeutic use ; Humans ; Male ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Retrospective Studies ; Risk Factors ; Stroke ; diagnosis ; drug therapy ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; administration & dosage ; therapeutic use ; Treatment Outcome

OBJECTIVES: Infants with slight/mild or late-onset hearing impairment might be missed in universal newborn hearing screening (UNHS). We identified the mutation hot spot of common deaf gene in the newborns in Jinan area population by screening the mutation spot with neonate cord blood, in order to make clear whether the neonate cord blood for screening is feasible. METHODS: Six hundred and forty-six newborns were subjected to both UNHS and genetic screening for deafness by using neonate cord blood. The newborn genetic screening targeted four deafness-associated genes, which were commonly found in the Chinese population including gap junction beta-2 protein (GJB2), gap junction beta-3 protein (GJB3), solute carrier family 26 member 4 (SLC26A4), and mtDNA 12S rRNA. The most common 20 spot mutations in 4 deaf genes were detected by MassARRAY iPLEX platform and mitochondrial 12S rRNA A1555G and C1494T mutations were sequenced using Sanger sequencing. RESULTS: Among the 646 newborns, 635 cases passed the UNHS and the other 11 cases (1.7%) did not. Of the 11 failures, two cases were found to carry homozygous GJB2 p.R143W pathogenic mutation, one case was found to have heterozygous GJB2 235delC mutation, and another one case carried heterozygous GJB3 p.R180X pathogenic mutation. Six hundred and thirty-five babies passed the newborn hearing screening, in which 25 babies were identified to carry pathogenic mutations, including 12 heterozygotes (1.9%) for GJB2 235delC, eight heterozygotes (1.3%) for SLC26A4 IVS7-2A>G, one heterozygote (0.2%) for p.R409H, two homozygotes (0.3%) for m.1494C>T, and two homozygotes (0.3%) for m.1555A>G. CONCLUSION: Newborn genetic screening through the umbilical cord blood for common deafness-associated mutations may identify carriers sensitive to aminoglycoside antibiotic, and can effectively prevent or delay hearing loss occurs.
Asian Continental Ancestry Group ; China* ; Deafness* ; DNA, Mitochondrial ; Fetal Blood ; Gap Junctions ; Genetic Testing ; Hearing ; Hearing Loss ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Homozygote ; Humans ; Infant ; Infant, Newborn* ; Mass Screening*

Acetamides ; Aminopyrine ; Animals ; Breath Tests ; methods ; Carbon Isotopes ; Chemical and Drug Induced Liver Injury ; diagnosis ; pathology ; physiopathology ; Humans ; Liver ; injuries ; pathology ; physiopathology ; Liver Cirrhosis ; diagnosis ; pathology ; physiopathology ; Liver Diseases ; diagnosis ; pathology ; physiopathology ; Liver Function Tests ; Phenylalanine ; Prognosis

BACKGROUNDCongenital heart disease is a diverse group of diseases determined by genetic and environmental factors. Considerable research has been done on genes associated with development of the heart. A recent focus is the role of transcription factor TBX5 in the development of atria, left ventricle and conduction system. As part of a larger study, high density, single nucleotide polymorphism (SNP) scanning was used to explore the relationship between TBX5 gene polymorphism and susceptibility to ventricular septal defect not associated with forelimb malformation in the Chinese Han population.

METHODSOne hundred and ninety two paediatric patients with congenital ventricular septal defect and 192 matched healthy control subjects were studied. The haplotype reconstructions were calculated by PHASE2.0 software. Haploview software was used to perform linkage disequilibrium assessment and defining of haplotype blocks. The algorithm used for defining of blocks was the confidence interval method.

RESULTSThe TBX5 gene region can be divided into 3 haplotype blocks of 27, 15 and 2 SNPs. Strong linkage disequilibrium exists within each block. SNP rs11067075 within the TBX5 gene had significant correlation with ventricular septal defect (P = 0.0037) by single marker association analysis. In addition, a 20 kb haplotype composed of 27 SNPs correlated with ventricular septal defect (P = 0.05, multiple loci regression analyses based on reconstructed haplotype blocks).

CONCLUSIONSTBX5 is associated with the occurrence of ventricular septal defect and may be a predisposing gene to congenital heart disease in Han Chinese. This finding has set a direction for further genetic and functional studies.

Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; genetics ; Heart Septal Defects, Ventricular ; genetics ; Humans ; Linkage Disequilibrium ; genetics ; Polymorphism, Genetic ; genetics ; Polymorphism, Single Nucleotide ; T-Box Domain Proteins ; genetics

OBJECTIVETo evaluate the factors for the conversion of transurethral resection of the prostate (TURP) to open prostatectomy and to provide clinical evidence for surgical options.

METHODSFrom January 1997 to March 2005, we performed 1 086 TURP and made retrospective analyses of 11 risk factors concerning the demographics, clinical history, laboratory data, ultrasound results, and intraoperative complications of the patients. In addition, multivariate logistic regression was used to determine those variables predicting the conversion of TURP.

RESULTSThirty-nine (3.59%) of the TURP cases required conversion, mostly because of uncontrollable hemorrhage (71.79%). Multivariate analyses showed that a prostate volume > 85.2 ml (OR = 2.568, P < 0.01), intraoperative slit of capsula prostatic (OR = 1.916, P < 0.01) and a second midstream bladder specimen (VB2) white blood cell count of the urine > 13.5/HP (OR = 1.486, P < 0.01) predicted the conversion to open prostatectomy.

CONCLUSIONBenign prostatic hyperplasia (BPH) patients with a huge prostate and those with intraoperative slit of capsula prostatic undergoing TURP are more likely to be converted. And uncontrollable hemorrhage, huge prostate and poor endoscopic vision are the major reasons for the conversion.

Aged ; Aged, 80 and over ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Postoperative Hemorrhage ; etiology ; Prostatectomy ; methods ; Prostatic Hyperplasia ; surgery ; Retrospective Studies ; Risk Factors ; Transurethral Resection of Prostate ; adverse effects ; methods ; Treatment Outcome

OBJECTIVETo discuss the diagnosis and treatment of penile carcinoma in circumcised men.

METHODSWe reviewed 17 cases of penile carcinoma detected 1 month to 16 years after circumcision performed in our hospital from January, 1997 to December, 2004.

RESULTSOf the total number, 11 cases were diagnosed as penile carcinoma 1 - 12 months and the others 3 - 16 years after the circumcision. Sixteen of them were treated by partial penectomy, anti 1 first by extensive circumcision and later by partial and total penectomy successively after recurrence. Cloquet nodes biopsy showed 16 cases to be pathologically well-differentiated and I case moderately differentiated penile squamous carcinoma. One died of extensive metastasis, but the other 16 remained disease-free survivals.

CONCLUSIONCircumcised adult men, especially those over 40 years of age, are likely to develop penile carcinoma. Patients with inflammation, plaque or ulcer in the prepuce should be checked by pathological biopsy and followed up closely. For Stage-I penile squamous carcinoma, partial penectomy is shown to be an effective therapeutic option, and Cloquet's nodes biopsy is necessary for all patients.

Adult ; Carcinoma, Squamous Cell ; etiology ; Circumcision, Male ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Penile Neoplasms ; etiology ; Phimosis ; complications ; surgery ; Postoperative Period ; Retrospective Studies

OBJECTIVETo evaluate the effect of sexual-nerve-sparing radical cystectomy.

METHODSThirty-two male patients were treated with sexual-nerve-sparing radical cystectomy in our hospital in the past 5 years. The age of the patients ranged from 38 to 72 years, with the course of the disease ranging from 2 days to 20 years. All of them were potent preoperatively. Radical cystectomy was performed antegradely and retrogradely with the neurovascular bundle spared.

RESULTSThe patients were followed up for 6 to 54 months, 3 achieved sexual activity of Grade I, 6 Grade II and 23 Grade III after the operation. The recovery time of erectile function ranged from 2 to 14 months, averaging at 4. 5 months.

CONCLUSIONWhenever condition suits, sexual-nerve-sparing radical cystectomy is to be strongly recommended.

Adult ; Aged ; Coitus ; Cystectomy ; methods ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Penile Erection ; Penis ; innervation