KCTD4 interacts with CLIC1 to disrupt calcium homeostasis and promote metastasis in esophageal cancer

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca2+-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner

As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.

Follow-up observation of carotid artery stent implantation by color Doppler ultrasound combined with TCD / 医疗卫生装备

Objective To apply color Doppler flow imaging (CDFI) and transcranial Doppler (TCD) to the follow-up observation of the changes of cervical vessel,intracranial hemodynamics and cerebrovascular reserve capacity (CVR) of the patients after carotid artery stent implantation.Methods Totally 96 patients with carotid artery stent implantation underwent CDFI and TCD examinations,and the changes of hemodynamics were compared before and 1 month,6 months,1 a and 2 a after implantation.Results The values of peak systolic velocity (PSV) and resistance index (RI) at the areas of carotid stenosis were lower significantly than those before implantation,while the values of PSV,pulsatility index (PI) and CVR of the middle cerebral artery were obviously higher than those before implantation (P＜0.05).There were no significant differences between the cervical and intracranial hemodynamics indexes 1 month,6 months,1 a and 2 a after treatment.Two-year follow-up found 4 cases of restenoses after implantation,and the rate for restenosis was 4.2％.Conclusion Carotid artery stent implantation improves significantly cervical and intracranial blood supply as well as CVR of the carotid stenosis patient,and CDFI combined with TCD can be used for the accurate evaluation of the efficacy and postoperative follow-up of carotid artery stent implantation.

Establishment of reference ranges for serum cystatin C in healthy middle-aged and elderly Chinese individuals / 中华老年医学杂志

Objective To establish normal reference ranges for serum cystatin C (Cys C)in relatively healthy middle-aged and elderly(＞50 years)Chinese individuals.Methods A total of 1087 candidates were consecutively selected and serum Cys-C levels were measured by transmission turbidimetry.Frequency analysis and histogram were used to establish the 95％ confidence reference range according to methods provided by CLSI (C28-A2).Results Based on the definition and verification procedures for clinical laboratory reference ranges(CLSI C28-A2,second edition),Cys-C levels of 1087 participants fell within the range of 0.30-1.55 mg/L;Male participants had higher serum Cys-C levels than female participants(Z=-10.19,P＜0.01).The serum Cys-C level increased with age,regardless of gender(R =0.600,P＜ 0.01).Differences in Cys-C levels between age groups were statistically significant (x2=411.17,P＜ 0.01).The reference ranges of normal serum Cys-C levels for different age groups (50-,55-,60-,65-,70-,75-,) were 0.42-0.98mg/L,0.45-1.04mg/L,0.47-1.34mg/L,0.46-1.38mg/L,0.61-1.33mg/L,0.61-1.28 mg/L,respectively,for males,and 0.39-0.94mg/L,0.42-1.01mg/L,0.40-0.91mg/L,0.46-1.03mg/L,0.57-1.04mg/L,0.55-1.27mg/L,respectively,for females.Conclusions This study established preliminary normal serum Cys-C reference ranges for healthy middle-aged and elderly(＞ 50 years)individuals in this region,which can serve as parameters for disease diagnosis and treatment evaluation.

Comparative study on ultrasonic assessments of left ventricular systolic synchronicity under different cardiac ;pacing modes / 中华超声影像学杂志

Objective To compare left ventricular (LV)synchronization of direct His-bundle pacing (DHBP)and right ventricular apical pacing (RVAP)with two-dimensional speckle tracking imaging (2D-STI)and tissue Doppler imaging (TDI),and discuss the diagnostic value of 2D-STI and TDI in evaluation of left ventricular systolic synchronicity.Methods Twenty-four patients implanted with DHBP and RVAP were observed.Conventional echocardiography examination were undergone both at the mode of DHBP or RVAP respectively.The time to peak radial strain of LV 1 8 segments were derived from the parasternal short-axis views by 2D-STI,then calculated the standard deviations (SD ) and the maximal temporal difference of LV 1 8 segments (Trs-SD and Trs-Dif),and the interval of time to peak radial strain between the anteroseptal wall and the posterior wall (Tas-post).The time to peak systolic velocity of LV 12 segments were derived from the apical axis views by TDI.The SD and the maximal temporal difference of 1 2 segments (Ts-SD and Ts-Dif)were calculated as the LV dyssynchrony index.Results All the systolic synchrony parameters derived from 2D-STI and TDI were more significantly shortened in DHBP than in RVAP (all P <0.01).For DHBP,the detection rate of LV synchronization was higher by 2D-STI than by TDI.For RVAP the detection rate of LV dyssynchronization was also higher by 2D-STI than by TDI with RVAP lead (all P <0.05).Conclusions DHBP is more beneficial than RVAP in LV syschronization and LV function,RVAP may induce left ventricular systolic asynchrony.Both 2D-STI and TDI can assess the LV synchronization quantitatively,but 2D-STI may be more superior on the detection rate than TDI.

Uterine artery chemotherapy and embolization in the treatment of special site pregnancy / 中国基层医药

Objective To investigate the clinical effect of uterine artery embolization chemotherapy in the treatment of special site pregnancy .Methods 36 patients with special site pregnacy were randomly divided into the observation group and control group .The control group received uterine curettage after uterine artery embolization treatment,the observation group received bilateral uterine artery perfusion of methotrexate combined with uterine cu -rettage after embolization therapy .Time of-HCG returned to normal ,intraoperative blood loss ,hospitalization time and incidence rate of complications were compared between the two groups .Results After treatment,the time of -HCG returned to normal,intraoperative blood loss and hospitalization time in the observation group were (27.3 ±3.2)h, (120.5 ±18.3) mL,(85.6 ±8.4) h,which were significantly less than (76.4 ±8.2) h,(375.1 ±68.4) ml and (147.1 ±10.5)h in the control group (t=6.75,4.54,4.43,all P<0.05).The incidence rate of complication in the observation group was 16.8%,which was significantly lower than 50.1% in the control group (χ2 =4.49,P <0.05).Conclusion The uterine artery chemotherapy and embolization in the treatment of special parts of pregnancy can significantly shorten the hospitalization time and time of -HCG returned to normal ,reduce the intraoperative blood loss,the clinical effect is good ,it can be used as an effective method for the treatment of special site pregnancy .

Study on the antibiotic resistance, homology of imipenem-resistant Pseudomonas aeruginosa strains isolated from older / 中华微生物学和免疫学杂志

Objective To identify the antibiotic resistance, homology of imipenem-resistant Pseudomonas aeruginosa strains isolated from older in Zhejiang Hospital and the carbapenemases determinants of imipenem-resistant strains. MethodsTwo hundred and sixty-two strains of Pseudomonas aeruginosa were isolated through May 2006 to May 2009 from older in Zhejiang Hospitals. K-B method was used to determine the 16 antimicrobial agents resistance of these 262 strains. The MICs of strains to 14 antimicrobial agents were determined by agar dilution and E test method. The coding sequence of Metallo-β-lactamases (MBL) were amplified, PCR products were purified, cloned and sequenced. The homology of these isolates was analyzed by pulse-field gel electrophoresis(PFGE). ResultsOne hundred and four strains of imipenem-resistant Pseudomonas aeruginosa were screened from 262 strains. The resistant rates of 104 isolates of Pseudomonas aeruginosa to ampicillin/sulbactam and cefoperazone/sulbactam were 78.9％ and 35.9％ ; polymyxin E had a minimal resistance of 6.0％ ; minocycline had a resistance rate of 58.3％. The resistant rates to other antimicrobial agents were more than 70.0％. Twelve imipenem-resistant Pseudomonas aeruginosa strains contained MBL gene and two kinds of integron were detected from 10 of these 12 strains. Twelve strains of Pseudomonas aeruginosa belonged to 5 epidemic PFGE-clone. ConclusionAll of the imipenem-resistant Pseudomonas aeruginosa which had cause outbreaks in Zhejiang Hospital. MBL were not the most popular gene type. All of the MBL gene types were VIM-2. The blaVIM-2 gene cassettes located in diflerent class 1 integrons. The integrons dissemination was the most important style of strains spread.

GC/MS Analysis of Volatile Constituents of Radix Isatidis / 中国药房

OBJECTIVE:To establish a GC-MS method to identify the volatile constituents in Radix Isatidis.METHODS:The method of wet distillation was applied to extracting volatile oil from Radix Isatidis,the chromatographic column was OV-1,and the flow rate was 1.0mL?min-1,EI ion source was used by MS.The volatile constituents in Radix Isatidis were identified and analyzed by NIS107 system.RESULTS:22 chromatographic peaks were separated,19 chemical compounds were identified,representing 90.51% of total amount,hexadecanoic acid had highest content,accounting for 38.52% of total amount.CONCLUSION:This experiment has provided initial usable data for comprehensive utilization of Radix Isatidis.

Effects of exercise on hemodynamic parameters and cardiovascular humoral factors in the elderly patients with hypertension / 中华物理医学与康复杂志

Objective To study the effects of exercise on hemodynamic parameters and cardiovascular humoral factors in the elderly patients with hypertension. Methods The modified Bruce assessment (MBA) was employed in an essential hypertension (EH) group (group 1, n =34) composed by elderly EH patients and a control group (group 2, n =31) composed of normal subjects. Heart rate (HR),systolic and diastolic blood pressure (SBP、DBP), and the quantum and duration of exercise (QE, DE) were explored, while the serum concentrations of nitric oxide (NO), endothelin 1(ET1), atrial natriuretic factor (ANF) and AngiotensinⅡ(AngⅡ) were measured at 3 min before and after treatment. Results There were no significant differences between groups 1 and 2 with regard to HR, SBP, DBP, total DE and peak QE before and after treatment, in addition, at the peak of exercise ( P 0.05). Pretreatment SBP and DBP were significantly and positively correlated with those at the peak of and after treatment ( r =0.648,0.630, P