Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P＜0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P＜0.01),and was positively associated with CRC clinical stage(P＜0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P＜0.001),induced cell apoptosis(P＜0.001),and led to cell cycle arrest in G1 phase(P＜0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P＜0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P＜0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P＜0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.

Antimicrobial resistance poses a serious threat to public health and is one of the major challenges worldwide. As global social, economic, and environmental changes lead to increased exposure of populations to antimicrobials, the antimicrobial resistance of pathogens has accelerated and resulted in weakened clinical infection treatment effects. This article reviews the main mechanisms and driving factors of the production and spread of antimicrobial resistance from the perspective of "One Health"and discusses methods and strategies for controlling antimicrobial resistance from multiple dimensions. It also looks forward to the prospects of research and prevention of drug resistance to explore antimicrobial resistance prevention and control strategies based on "One Health".

Antimicrobial resistance poses a serious threat to public health and is one of the major challenges worldwide. As global social, economic, and environmental changes lead to increased exposure of populations to antimicrobials, the antimicrobial resistance of pathogens has accelerated and resulted in weakened clinical infection treatment effects. This article reviews the main mechanisms and driving factors of the production and spread of antimicrobial resistance from the perspective of "One Health"and discusses methods and strategies for controlling antimicrobial resistance from multiple dimensions. It also looks forward to the prospects of research and prevention of drug resistance to explore antimicrobial resistance prevention and control strategies based on "One Health".

Liver transplantation has become the most effective treatment for end-stage liver diseases.Due to the shortage of organ,more and more extended criteria donors (ECD) grafts had been used,which expand the liver pool.However,a series of complications post transplantation were caused by ischemia,hypoxia,steatosis and so on.The non-anastomotic biliary strictures after liver transplantation is one of the major complications when the ECD donors was be used in clinic.The study on the protective effect of machine perfusion on liver donors is too numerous to list,and existing studies have found that MP can reduce the incidence of NAS after liver transplantation.This review provides an overview of the pathogenesis of NAS and the reduction incidence of NAS by MP.

Liver transplantation has become the most effective treatment option for end-stage liver diseases.The liver donation after cardiac death (DCD) had been increasingly used in clinical practice.Nevertheless,the DCD donated livers inevitably exposed to long-term ischemia and hypoxia makes the implanted organs with decreased function and more postoperative complications.Different from the conventional static cold storage,machine perfusion (MP) can be continuously used in vitro liver perfusion,which could simulate the in vivo liver status.Through the observation of ischemia injury status,we could evaluate the quality of donated liver,and thus reduce ischemia related complications.This review provides an overview and evaluation on the markers that have been investigated for the assessment of graft quality and viability testing during different types of MP.

Objective To systematically review the effect of donor ischaemic preconditioning in liver transplantation.Methods Databases including the Cochrane Library,PubMed,EMbase,CNKI,VIP and WanFang database were searched up to June 2016 for studies which involved donor ischaemic preconditioning (IPC) in liver transplantation.The data retrieved included 1-year mortality,incidence of Primary Graft Non-Functioning (PGNF),intensive therapy unit (ICU) hospitalization and liver function tests which were used to evaluate the treatment outcomes.The data were analyzed using both the fixed-effect and the random-effects models.For categorical outcomes,risk ratio (RR) with 95％ confidence intervals (CI) were calculated.For continuous outcomes,the mean difference (MD) with 95％ CI were calculated.The metaanalysis was performed using Review Manager 5.2 software.Results Six clinical studies with 322 patients were qualified for this meta-analysis.There were no significant differences in the 1-year mortality (OR =0.51,95％ CI 0.24 ～ 1.05,P ＞ 0.05),PGNF (OR =0.33,95％ CI 0.08 ～ 1.40,P ＞ 0.05) and ICU hospitalization (OR =-0.17,95 ％ CI-2.72 ～ 2.38,P ＞ 0.05) between the donor ischaemic preconditioning and the control groups.There were also no significant differences in the transaminase and bilirubin levels on postoperative day 1,3 and 7 between the two groups.Conclusion There is currently not enough evidence in evidenced based medicine to recommend the routine use of ischaemic preconditioning in donor liver retrieval.

OBJECTIVETo investigate the property of genipin-crosslinked silk fibroin(SF)/chitosan(CS) microspheres for slow releasing of bovine serum albumin (BSA).

METHODSBSA-loaded genipin-crosslinked SF/CS microspheres were prepared by emulsion cross-linking technique. The micropheres were observed for surface morphology and size distribution under scanning electron microscope (SEM), and X-ray diffractometry (XRD) and fourier transform infrared spectroscopy (FTIR) were used to analyze their structural characteristics. BCA method was used for determining the drug entrapment, loading rate and cumulative drug release in 21 days.

RESULTThe microspheres were spherical and showed a smooth surface with an average diameter of 7.84∓0.97 µm. The drug entrapment efficiency of the microspheres was (50.16∓4.32)% with a drug loading ratio of (1.25∓0.11)% and a cumulative release of the total drug of (75.2∓2.53)% in 21 days.

CONCLUSIONGenipin-crosslinked SF/CS microspheres have a high drug entrapment efficiency and possess good capacity of sustained drug release.

Chitosan ; chemistry ; Delayed-Action Preparations ; Emulsions ; Fibroins ; chemistry ; Iridoids ; chemistry ; Microscopy, Electron, Scanning ; Microspheres ; Particle Size ; Spectroscopy, Fourier Transform Infrared ; X-Ray Diffraction ; X-Rays

Objective To investigate the property of genipin-crosslinked silk fibroin(SF)/chitosan(CS) microspheres for slow releasing of bovine serum albumin (BSA). Methods BSA-loaded genipin-crosslinked SF/CS microspheres were prepared by emulsion cross-linking technique. The micropheres were observed for surface morphology and size distribution under scanning electron microscope (SEM), and X-ray diffractometry (XRD) and fourier transform infrared spectroscopy (FTIR) were used to analyze their structural characteristics. BCA method was used for determining the drug entrapment, loading rate and cumulative drug release in 21 days. Results The microspheres were spherical and showed a smooth surface with an average diameter of 7.84±0.97μm. The drug entrapment efficiency of the microspheres was (50.16±4.32)%with a drug loading ratio of (1.25 ± 0.11)% and a cumulative release of the total drug of (75.2 ± 2.53)% in 21 days. Conclusion Genipin-crosslinked SF/CS microspheres have a high drug entrapment efficiency and possess good capacity of sustained drug release.

Objective To investigate the property of genipin-crosslinked silk fibroin(SF)/chitosan(CS) microspheres for slow releasing of bovine serum albumin (BSA). Methods BSA-loaded genipin-crosslinked SF/CS microspheres were prepared by emulsion cross-linking technique. The micropheres were observed for surface morphology and size distribution under scanning electron microscope (SEM), and X-ray diffractometry (XRD) and fourier transform infrared spectroscopy (FTIR) were used to analyze their structural characteristics. BCA method was used for determining the drug entrapment, loading rate and cumulative drug release in 21 days. Results The microspheres were spherical and showed a smooth surface with an average diameter of 7.84±0.97μm. The drug entrapment efficiency of the microspheres was (50.16±4.32)%with a drug loading ratio of (1.25 ± 0.11)% and a cumulative release of the total drug of (75.2 ± 2.53)% in 21 days. Conclusion Genipin-crosslinked SF/CS microspheres have a high drug entrapment efficiency and possess good capacity of sustained drug release.

Objective To discuss the meaning of continuous intracranial pressure (ICP) monitoring in patients with severe traumatic craniocerebral injury. Methods One hundred and twenty four patients with severe craniocerebral injury treated from August 2004 to February 2011 in our hospital, were enrolled and divided randomly into ICP monitoring group (n = 62) and routine treatment group (n = 62). The patients of ICP monitoring group had adjusted treatment plan according to the changes of ICP at any time, whereas the patients in routine treatment group underwent routine neurosurgical treatment according to the doctors' experience. Results There were 7 cases of acute kidney function failure,and 11 cases of electrolyte disturbances in the ICP group.There were 15 cases of acute kidney function failure, and 25 cases of electrolyte disturbances in the routine group. The complication rate in the ICP group was lower than that in the routine group (x2 =3. 54 and 7.67 for acute kidney function failure and electrolyte disturbances respectively, Ps <0. 01). The days of mannite using were (6±2)dand (15 ±3)d, respectively; the dosage of mannite using were (749 ± 125) g and (1545 ±250) g,respectively. The good recovery and slight disability were 28 and 16 cases in the ICP group, and 13 and 9 cases in the routine group,respectively. The severe disability,vegetative state and death were 9,4 and 8 cases in the ICP group,and 17,7 and 13 cases in the routine group. The days and dosage of mannite using in the ICP group were much less than those in the routine group (t = 8. 32 and 7.41, Ps < 0. 01). The proportion of good recovery and slight disability in the ICP group were higher than those in the routine group(x2 =5. 07 and 3. 55,Ps <0.01). However, the proportion of severe disability, vegetative state and death in the ICP group were lower than those in the routine group (x2 =0.84,0.89 and 1.43, Ps < 0. 01) . Conclusion Continuous ICP monitoring in severe craniocerebral injury shows benefits in directing treatment plan adjustment, reducing complications and improving the prognosis.