Objective To investigate the protective effect and mechanism of taurine on the cytotoxicity of iohexol on HK-2 cells. Methods HK-2 cells were exposed to iohexol at different dosage (25, 50, 100, 125 gI/L) for 6 h and at the dose of 100 gl/L for different time(2 h, 4 h, 6 h). Then taurine (3,12,24 mmol/L) was coincubated with iohexol (100 gI/L) for 6 h.Cell viability was assessed by CCK-8 assay. Cell apoptosis was determined by Hoechest 33342 flurescence stains,flow cytometry with Annexin V-FITC/PI double stains and caspase-3 activity by colorimetric assay. Bcl-2 and Bax expression were examined by Western blot. Intracellular ROS was detected by flow cytometry with fluorescent probe DCFH-DA. Results Iohexol decreased HK-2 cell viability and induced apoptosis in concentration-dependant and time-dependant manner (all P＜0.05). ROS was increased following iohexol (100 gI/L for 6 h) treatment (P＜0.05). Taurine increased cell viability and attenuated apoptosis in dose-dependant manner. The cell viability levels in taurine intervention (3,12,24 mmol/L) group were significantly increased compared with that in iohexol treated group respectively [(88.00±1.00)%, (91.33±0.58)%, (95.67±1.52) % vs (76.67±1.53)%, all P＜0.05]. Apoptosis rate by flow cytometry were decreased respectively [(8.84±1.75)%,(7.86±1.82)%, (6.30±1.50)% vs (11.98±0.39)%, all P＜0.05]. Caspase-3 activities were decreased respectively [(1.33±0.10), (1.27±0.06), (1.10±0.04) vs (1.42±0.13), all P＜0.05].Taurine up-regulated the expression of Bcl-2, and decreased the intracellular ROS (all P＜0.05).Conclusions Iohexol induces cell apoptosis and oxidative stress. Taurine attenuates direct cytotoxic effect induced by iohexol. The anti-oxidative stress effect and up-regulated Bcl-2 expression may partly account for the protection of taurine.

The adiponeetin mRNA expression and secretion of human omental and subcutaneous preadipocytes were increaed by renin-angiotensin system (RAS) bloekers. Compared with thiazolidinedione, RAS blockers have stronger effects on human omental preadipoeytes in adiponeetin mRNA expression and secretion,suggesting a potential benefit of RAS blockers on metabolic syndrome with characteristic intra-abdominal obesity.

Objective To investigate the therapeutic effect of early stage minimally invasive laparoscopic retroperitoneal approach of catheter drainage on early inflammatory response of severe acute pancreatitis ( SAP ) . Methods 37 SAP patients with peritoneal effusion were divided into the observation group (19 cases with early laparoscopic retroperitoneal approach of catheter drainage )and normal treatment group(18 cases with conventional drainage)using a random number table.All patients were given conventional therapy , such as fasting, gastroin-testinal decompression , anti-infection, fluid resuitation and using gastric acid and trypsin inhibitors .In addition to conventional therapy , the observation group received the early laparoscopic retroperitoneal approach of catheter drainage.The inflammatory indexes responding to acute inflammation such as TNF-α,IL-6,IL-8, IL-10 and C-re-active protein(CRP)were detected before and after treatment .Meanwhile, the date of resume diet, APACHEⅡscores and duration of systemic inflammatory response ( SIRS) , incidence of multiple organ dysfunction syndrome ( MODS) and the mortality were observed .Results The acute inflammatory response occurred in both groups . The plasma levels of TNF-a,IL-6,IL-8,IL-10 and CRP in the two groups decreased obviously after 3-day treat-ment.However, the plasma levels of inflammatory mediators in the normal treatment group increased while those early laparoscopic retroperitoneal approach of catheter drainage group kept decreasing after 7-day treatment .There was a significant difference between the two groups (P<0.01).Time for resuming to diets and duration of SIRS in the observation group were less than those in the normal treatment group ( P<0.01 ) , APACHEⅡscore were significantly less than those in normal treatment group also (P<0.01).The rates of MODS, overall postoperative complication rate and mortality were significantly lower in the observation group (P<0.05).Conclusions Early laparoscopic retroperitoneal approach of catheter drainage can effectively improve the prognosis in patients with SAP and decrease the production of inflammatory mediators .Early laparoscopic retroperitoneal approach of cathe-ter drainage is simple , feasible and micro-invasive with encouraging outcomes , therefore it is an effective and safe treatment option for patients with SAP .

Objective To investigate the feasibility and clinical value of the road drainage after early mini-mally invasive treatment of severe acute pancreatitis (severe acute pancreatitis,SAP).Methods A retrospective analysis were used to investigate the clinical data of 37 patients with SAP in March 2011 to March 2011 after conven-tional treatment and early minimally invasive approach drainage treatment.Drainage of early after minimally invasive approach group were treated by laparoscopic retroperitoneal approach surgery in the early onset,and were removed of necrotic tissue and catheter drainage of the retroperitoneal clearance.Then postoperative double pipe for irrigation and the negative pressure drainage were applied.Two groups of postoperative complications,mortality,medical expenses, length of hospital stay,etc.were compared.Results Early minimally invasive drainage of into the road after acute physiology and chronic health evaluation (APACHE Ⅱ)was superior to the conventional treatment group (P =0.00).The overall incidence of complications and mortality of multiple organ dysfunction syndrome (multiple out-raged dysfunction syndrome,MODS),was superior to the conventional treatment group,and the differences were statis-tically significant (P =0.023,P =0.033,P =0.046).Early into the road drainage of hospitalization expenses after minimally invasive were reduced ((19.74 ±2.22)than (36.15 ±1.92)ten thousand yuan,t =23.989,P =0.000),hospitalization time were shorter (4.76 ±0.64)weeks than (6.03 ±0.73)weeks,t =5.635,P =0.000). Conclusion Early minimally invasive retroperitoneal approach of drainage treatment of SAP can reduce the incidence of complications and mortality,reduce hospitalization expenses,shorten hospitalization time,and has the clinical feasi-bility and application value.

Objective To analyze the clinical and imaging characteristics of congenital sensorineural hearing loss (CSNHL)children combined with white matter (WM)lesions in order to provide evidence for clinical practice. Methods With referral to the Department of Pediatrics,Peking University First Hospital from November 201 1 to De-cember 201 5,documents of 78 patients of CSNHL combined with WMlesions were collected and analyzed for the clini-cal and imaging characteristics.Results Bilateral severe -profound hearing loss existed in all 78 cases,48.1 %(25 /52 cases)of the patients exhibited gross motor development delay,98.1 %(51 /52 cases)of them had normal cognition development.One hundred percent (61 /61 cases)of patients had abnormal language development.Infection occurring during pregnancy existed in 21 .2%(1 1 /52 cases)of the patients,the premature and smaller for the gestational age in-fants accounted for 28.9% (1 5 /52 cases).The bilateral multiple WMlesions from the brain MRI were in dot to flake sizes with sharp boundary,the intensity of T1 -weighted imaging decreased,T2 -weighted imaging and fluid attenuated inversion recovery increased.Eighty -two point one percent (64 /78 cases)of the patients were found to have the periventricular and subcortical WM involvement.The most frequently affected periventricular region was the posterior horn (91 .9%,68 /74 cases),followed by the anterior horn and temporal horn,and the least with the body involvement. The former three had a combined lesion tendency (55.4% -68.9%).There was an extensive involvement in the sub-cortical WMof parietal,frontal,temporal and occipital lobes respectively(73.5% -88.2%).Subcortical WM involve-ment of multiple lobes was common (accounted for 67.6% -77.9%).The enlargement of bilateral ventricles existed in 37.2%(29 /78 cases)of the patients and cystic changes in the subcortical WM of anterior temporal lobe could be found in 9.0% (7 /78 cases)patients.Calcification in 2 CT cases was reported.Corpus callosum and basal ganglia of all cases were normal.For cases with MRI scans more than once,WMlesions of 96.0%(24 /25 cases)patients became silent or self -restored.Conclusions The clinical presentations of CSNHL combined with WM lesions are mild,not paralleled with their multiple foci.It is considered as demyelination or a delay of myelination.Due to its benign course, it is probably not the contraindication for the cochlear implantation.

Objective To analyze the clinical and MRI features of patients with type Ⅱ Alexander disease (AxD) in order to better understand and diagnose it earlier.Methods Four type Ⅱ AxD patients identified by glial fibrillary acidic protein gene mutations from Peking University First Hospital and 128 type Ⅱ AxD cases from published literatures were collected,and the clinical and MRI features were summarized.Results (1) In 4 type Ⅱ AxD patients,2 adult patients showed abnormal MRI features without clinical manifestation.The other 2 children patients both manifested motor dysfunction of lower limbs,pyramidal signs,paroxysmal deterioration,and seizures during the course of disease,while 1 of them had bulbar paralysis.The MRI of all the cases was abnormal,but only 1 case MRI corresponded with typical MRI features of type Ⅱ AxD.In the other 3 cases MRI showed thc atrophy in the medulla and upper spinal cord,or the brainstem lesions and abnormal signal in the periventricular white matter,and abnormal basal ganglia region.(2) In 128 reported type Ⅱ AxD cases,the age of onset was (32±19) years old.The initial syndromes mainly contained bulbar and/or pseudobulbar paralysis (32.48％,38/117 cases),motor dysfunction of the lower limbs (31.62％,37/117 cases) and autonomic nerve dysfunction (13.67％,16/117 cases).During the course of the disease,the clinical manifestation showed bulbar and/or pseudobulbar paralysis (73.50％,86/117 cases),pyramidal signs (60.68％,71/117 cases) and ataxia (51.28％,60/117 cases).The MRI of all cases was characterized by atrophy or abnormal signals in the brainstem,especially in medulla oblongata,and spinal cord.And abnormal signals in the cerebellar dentate nuclei,white matter,basal ganglia and thalamus were also commonly shown in the MRI.Conclusions The patients with type Ⅱ AxD are late-onsct.The clinical manifestation mainly contains bulbar and/or pseudobulbar paralysis,motor dysfunction of the lower limbs and pyramidal signs.The MRI is characterized by atrophy or abnormal signals in the brainstem (especially in medulla oblongata) and spinal cord.

Objective To explore the protective effect and mechanism of antioxidant N-acetyl-L-cysteine (NAC)on the cytotoxicity induced by iohexol in HK-2 cells. Methods The incubated HK-2 cells were divided into four groups:control group,iohexol group,NAC group,and NAC+iohexol group(pre-incubated with NAC and then co-incubated with iohexol).The cell viability was tested by CCK-8 assay;cell apoptosis was determined by Hoechst 33342 fluorescence staining and flow cytometry with Annexin V-FITC/PI double staining.Intracelluar ROS waft detected by flow cytometry with DCFH-DA fluorescence staining.The signaling transduction pathways were investigated by Western blotting and immunofluorescence staining. Results Iohexol decreased cell viability,and increased apoptosis in a dose-and time-dependent manner.In iohexol(100 gl/L,6 h)group,ROS was increased by 1.30-fold of control(P＜0.05).In NAC(5,10,15 mmol/L)+iohexol groups,the cell viability was increased by 104%,118%,130%respectively,and iohexol group was 63% (P＜0.05, respectively); apoptosis rate was decreased by 13.51%, 13.46%, 12.23% respectively, and iohexol group was 24.41% (P＜0.05, respectively); ROS was decreased by 1.05-fold, 0.93-fold, 0.86-fold respectively, and iohexol group was 1.3-fold (P＜0.05, respectively).Iohexol induced the increase of p53 phosphorylatian and activity, then up-regulation of Bax and down-regulation of Bcl-2 protein expression. Iohexol induced the release of cytochrome C from mitochondria to cytoplasm, all of which caused final activation of caspase-3. The expression levels of p53, Bax and caspase-3 were decreased, while Bcl-2 protein expression level was increased by NAC. Conclusions Iohexol induces the increase of apeptosis rate and ROS generation in HK-2 cells. NAC attenuates this iohexol-induced cytotoxicity by decreasing intracelluar ROS, which is mairdy through the intrinsic pathway.

Objective To analyze the clinical characteristics of 3 unrelated boys with paroxysmal nonkinesigenic dyskinesia and developmental delay caused by de novo mutation in KCNMA1,and to expand the knowledge of clinical phenotype of KCNMA1 mutation.Methods Clinical data of patients were collected,including gender,age,condition of the perinatal period,personal history,and family history.And the features of genotype data were collected including features of attack,developmental milestones,physical examinations,treatments,and responses to treatment.The data including blood biochemical results,results of metabolic screening and genetic testing and the pedigree validation were collected,while the relationship between phenotype and genotype was analyzed.Results (1)Phenotypic features:3 unrelated boys were diagnosed.The ages of disease onset were 20 days,7 months and 13 months,respectively.All the patients manifested paroxysmal nonkinesigenic dyskinesia and were characterized by the episodes that occurred during wakefulness,presented with sudden onset of asymmetric limb dystonic posture,sometimes with nystagmus and strabismus,or sudden decrease of voluntary movement of limbs with hypotonia and occasional esotropia and yawning.There was no loss of awareness during attack.No precipitating factors were observed before attacks.The developmental milestones were delayed.Three children had no response to anti-epilepsy drug before diagnosis.After diagnosis,2 cases used Clonazepam and 1 case showed less attack.There was not any epileptic seizure until the last follow-up at the ages of 3 years and 6 months old,7 years old,and 5 years and 8 months old,respectively.The frequency of attacks was decreased.The episodes were recorded during video-electroencephalogram(EEG) monitoring,which showed normal ictal and interictal EEG.(2)Genotypic features:all 3 children were detected to have KCNMA1 genetic heterozygous missense mutation,while c.2650G>A (p.Glu884Lys) mutation was identified in 1 patient,and c.3158A>G(p.Asn1053Ser)mutation in the other 2 patients,but no such mutation was found in their parents.Conclusion This finding expands the phenotype of KCNMA1mutation.KCNMA1 should be considered as one of the candidate genes for screening in patients with early onset of paroxysmal nonkinesigenic dyskinesia without triggers,or early-onset of developmental delay,with or without epilepsy.

Objective To summarize the phenotypic features of an unrecognized leukoencephalopathy in infants sharing same clinical features,and to better understand the disease and provide new evidence for identification of new leukoencephalopathy. Methods Clinical and follow-up data of 13 patients with unrecognized infantile leukoen-cephalopathy were collected from Peking University First Hospital from January, 2006 to December, 2014. Results (1) There were 7 male and 6 female. The average age of onset was 11 months (4-25 months). Thirty-eight percent (5/13 cases) of patients had incentives before the onset;all of the cases had acute onset and rapid motor function regression. Fifteen percent (2/13 cases) of the patients suffered from seizures in the course of the disease. Patients′condition became stable,and cognition and motor function improved gradually 1 month after onset. No patient died till the last follow-up. (2) Imaging features:magnetic resonance imaging (MRI) of the patients was characterized by im-plicating deep white matter,presenting T1 hypointense,T2 and fluid attenuated inversion recovery ( FLAIR) hyperin-tense in the periventricular area. All of MRI showed massive and symmetric lesions with heterogeneous signal and cystic degeneration. DWI showed patch or massive hyperintense in some of the lesions. The follow-up MRI showed the original lesions decreased in 88% ( 8/9 cases ) of patients, and white matters atrophied in 55% ( 5/9 cases ) of patients;the cystic degeneration still existed and even expanded;DWI showed regional linear or spot hyperintense in 88% (8/9 cases) of patients,which was smaller than before,and distributed around the original lesions. Conclusions The patients with leukoencephalopathy caused by unknown pathogenic gene were much likely to be mitochondrial leukoencephalopathy. This study provided evidence for further exploration of new pathogenic genes causing leu-koence-phalopathy.

Objective To investigate the changes of CD4+ CD25+ CD127low regulatory T cells (Treg) in peripheral blood samples collected from the patients with cervical cancer and its clinical signifi -cance , and to evaluate the correlations between Treg cells and the infection of high-risk human papillomavir-us ( HR-HPV) .Methods Flow cytometry analysis was performed to measure the percentages of CD4+ CD25+ CD127low Treg cells among CD4+T cells in peripheral blood samples collected from 249 patients with cervical cancer , 30 patients with cervix intraepithelial neoplasia ( CIN) and 60 healthy subjects .The corre-lations between the levels of Treg cells and the clinicopathological features of cervical cancer were analyzed . Flow-through hybridization and gene chip technology ( HybriMax) were used to analyze the genotypes of HPV strains isolated from the 339 subjects.The correlations between Treg cells and HR-HPV infection were ana-lyzed.Results Compared with the healthy subjects , the patients with cervical cancer or CIN showed higher percentages of CD4+ CD25+ CD127low Treg cells and rates of HR-HPV infection (P<0.01).The percentages of CD4+ CD25+ CD127low Treg cells in patients with cervical cancer were significantly correlated with the sta-ges of cervical cancer , which was staged by the Federation International of Gynecology and Obstetrics (FIGO) staging system,and the degrees of differentiation (P<0.05).The percentages of CD4+ CD25+ CD127low Treg cells in the peripheral blood of patients with positive HR-HPV were significantly higher than those in patients without HR-HPV infection (P<0.01).Conclusion The CD4+ CD25+ CD127low Treg cells in peripheral blood might play an important role in the oncogenesis and development of cervical carcinoma , thus it could be used as a potential marker for the evaluation of disease progression .Moreover , the CD4+ CD25+ CD127low Treg cells were closely related to the HR-HPV infection.