Objective To compare the differences of lifestyle factors between patients with functional constipation (FC)and constipation-predominant irritable bowel syndrome (IBS-C).Methods From February 2011 to December 2014,255 patients with chronic constipation were enrolled.Among them,there were 170 FC patients and 85 IBS-C patients.At the same period,170 healthy volunteers without symptoms of digestive diseases within one year were recruited as control.The data of demographic information and lifestyle factors were collected.First,single variant analysis was performed for statistical analysis and then the statistically significant variants were analyzed by multivariate logistic regression. Then the factors of FC and IBS-C patients were analyzed by decision tree model and the effects of factors under different categories were analyzed.Results The results of single variant analysis indicated that there was no difference in lifestyle factors between FC group and IBS-C group (all P >0.05).The results of multivariate logistic regression analysis showed that no independent protective or risk factors were found in IBS-C group compared with FC group.According to decision tree model analysis,body mass index (BMI),water intake per day and constipation family history were finally enrolled.The incidence of FC was higher in patients with BMI < 23.56 kg/m2 (except 18.74 to < 19.83 kg/m2 )(79.75 %).The incidence of FC was higher in patients with BMI from 18.74 to <19.83 kg/m2 and water intake <1 L
(66.67%).The incidence of FC was highest in patients with BMI≥23.56 kg/m2 and family history of constipation (70.00%).The total prediction accuracy of this model was 64.6% (42/65 )and area under curve (AUC)value was 0.688.Conclusions FC and IBS-C are related with many lifestyle factors.Low BMI and less water intake per day are influence factors of FC,while higher BMI and family history of constipation are influence factors of IBS-C.

Objective To investigate the role and the mechanism of ppk1 gene (coding for polyphosphate kinase 1) in oxidative stress resistance in uropathogenic Escherichia coli (UPEC).MethodsMutant strains with ppk1-deletion (△pk1) and complemented strains (△pk1-C) were constructed based on the UPEC strain CFT073.A comparative analysis was conducted to analyze survival rates of CFT073, △pk1 and △pk1-C strains at different time points while they were under oxidative stress.Differences in protein expression between CFT073 and △pk1 strains were analyzed using mass spectrometric analysis.Differences between CFT073 and △pk1 strains in expression of katG and katE genes were analyzed using real-time quantitative RT-PCR.Results The survival rate of △pk1 strains was lower than that of CFT073 strains at every time point, while the survival rate of △pk1-C strains was basically the same as that of CFT073 strains.Gel image analysis and mass spectrometric analysis revealed that six proteins were down-regulated and one was up-regulated in △pk1 strains as compared with those in CFT073 strains.Expression of the catalase-coding genes katG and katE in △pk1 strains were respectively (20.5±8.2)% and (20.9±6.9)% of those in CFT073 strains (P<0.05).Conclusion The ppk1 gene plays an important role in oxidative stress resistance in UPEC by modulating the expression of catalase-coding genes katG and katE.

Objective To establish the golden hamster model of buccal squamous carcinoma and observe its biological character-istics .Methods 50 golden hamster were randomly divided into two group :experiment group (n=40) and control group(n=10) . Buccal mucosa of golden hamster were daubed by exposure 4-nitroquinoline-1-oxide (4NQO) in experiment group and tap water in control group .HE staining and immunohistochemistry were used to observe the tissue sample on the 8th and 12th week .The tissue samples of golden hamster buccal-mucosa cancer were used for the in-vitro subculture .Then flat cloning formation rate ,expression of CK and Vim ,and cell karyotype were detected .Results The observations of cell morphology and biology showed that the tissue of buccal squamous carcinoma were conformed to the basic characteristics of squamous carcinoma cell in 26 golden hamster(84 .6% ) after 12 weeks .The positive rate of CK and Vim were 96 .0% by immunohistochemical staining .The Chromosomes were tetraploid karyotype .Conclusion We successfully established the golden hamster model of buccal squamous carcinoma by the daub method of 4NQO .

Objective:To investigate the safety and effect of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) and sorafenib on large hepatocellular carcinoma (HCC) patients treatment.Methods:From Jan 2012 to Dec 2017, 36 patients (Male: 33, Female: 3, average age: 51.8) with large HCC lesions(5-7 cm) received TACE plus with RFA and sorafenib in the Third Affiliated Hospital of Sun Yat-sen University. Efficacy was evaluated after TACE. Each patient was received follow-up after RFA procedure. The occurrence rate of complications and overall survival (OS) were recorded. Log-rank univariate analysis was used to analyze the OS data.Results:The median TACE time was 4, and the RFA time was (1.7±0.7) . Mean duration time of sorafenib administration was (37.7±28.8) months. Adverse events of sorafenib: 26(72.2%) hand-foot skin reaction, 6(16.7%) hypertension, 22(61.1%) diarrhea, 17(47.2%) alopecia, 3(8.3%) oral ulcer and 1(2.8%) gastrointestinal hemorrhage. Median OS was 63.0 months, and 1-year, 3-year and 5-year survival rate was 100%, 72.7% and 52.6%. The cumulative survival rate of patients taking whole course of sorafenib ( n=21) was better than that of patients taking remedial ( n=15); the cumulative survival rate of patients with alpha fetal protein (AFP) <200 μg/L ( n=26) before treatment was better than ≥200 μg/L ( n=10); the cumulative survival rate of patients with good TACE response ( n=19) was better than that of patients with no response ( n=17), and the differences were statistically significant (all P<0.05). Conclusions:TACE plus with RFA and sorafenib are safe and effective for large HCC patients with 5-7 cm lesions and this treatment might improve OS. The whole-course sorafenib, lower base AFP value (<200 μg/L) and good TACE response were considered as the good factors for the combination therapy in large HCC patients.

Objective To evaluate the short-term outcome of local intraarterial thrombolysis in patients with acute ischemic stroke of the anterior circulation. Methods 24 patients with acute ischemic stroke of the anterior cir-culation within 8 hours were treated by local intraarterial thrombolysis. Arterial recanalization was divided into total, partial and occlusive respectively according to angiography. Evaluation of clinical outcome was performed on the 30th day after thrombolysis,and was classified as good for Modified Rankin Scale (MRS) scores of 0 to Ⅲ and poor for MRS scores of Ⅳ to Ⅵ. Results Total recanalization was obtained in 54.2 % of patients, partial recanalization in 25.0%. Clinical outcome was good in 15 patients (62.5%). Cerebral hemorrhage occurred in 4 patients (16.7%). Four patients died (16.7%). Conclusion Local intraarterial thrombolysis is an effective method for treatment of a-cute iachemic stroke of the anterior circulation. It needs further practice and long-term follow-up study on safety and long-term efficacy.

The Hippo pathway plays key roles in animal development. It suppresses tumorigenesis by controlling the transcription of the target genes that are critical for cell proliferation and apoptosis. The transcriptional coactivator YAP is the major downstream effector of the Hippo signaling. Upon extracellular stimulation, a kinase cascade in the Hippo pathway phosphorylates YAP and promotes its cytoplasmic sequestration by 14-3-3 and ubiquitin-dependent degradation. When the Hippo pathway is turned off, YAP (which lacks a DNA-binding domain) is dephosphorylated and translocates to the nucleus, where it associates with the transcription factor TEAD to form a functional heterodimeric transcription factor and to promote the expression of the Hippo-responsive genes. Recently, structures of the YAP-binding domain of TEAD alone or in complex with YAP have revealed the atomic details of the TEAD-YAP interaction. Here, I review these exciting advances, propose a strategy for targeting the TEAD-YAP interaction using small molecules, and suggest potential mechanisms by which phosphorylation and 14-3-3 binding regulate the cytoplasmic retention of YAP.
Animals ; DNA-Binding Proteins ; chemistry ; physiology ; Drosophila Proteins ; chemistry ; physiology ; Humans ; Intracellular Signaling Peptides and Proteins ; chemistry ; physiology ; Models, Molecular ; Nuclear Proteins ; chemistry ; physiology ; Phosphorylation ; Protein Interaction Domains and Motifs ; Protein-Serine-Threonine Kinases ; chemistry ; physiology ; Signal Transduction ; Trans-Activators ; chemistry ; physiology ; Transcription Factors ; chemistry ; physiology

Objective To generate mice with whole-body overexpression of human METRNL gene.Methods Based on Cre-loxP system,Dppa3-Cre mice were mated with Rosa26-LSL-METRNL knock-in mice(R26-LSL-METRNL+/-)to generate R26-L-METRNL+/-mice.The genotypes of the offsprings were identified,and tissues of the blood,heart,liver,spleen,lung,kidney,brain,white adipose and muscle were collected.The expression of human METRNL gene in mice was investigated by quantitative real-time PCR,western blot and enzyme linked immunosorbent assay.Results Compared with wild type control mice,human METRNL in R26-L-METRNL+/-mice significantly expressed at both mRNA and protein levels in tissues,with abundant METRNL protein in blood.Conclusion The mouse model overexpressing human METRNL gene(R26-L-METRNL+/-mouse)was successfully constructed.

Implantable drug delivery systems,as an emerging therapeutic approach,markedly amplify drug efficacy while mitigating drug toxicity and adverse effects,presenting an innovative avenue for postoperative tumor management.This review delineates pivotal triggers for postoperative tumor recurrence and their respective treatment modalities.Moreover,it comprehensively delves into recent strides in research and development of implantable drug delivery systems following anti-tumor surgery,encompassing implantable such drug delivery platforms as casting implants,electrospinning implants and hydrogel implants.The evolution of anti-tumor postoperative implantable drug delivery systems signifies a promising realm of research,poised to furnish more effective,tailored treatment modalities for cancer patients,heralding a beacon of fresh prospects in their rehabilitation.

Objective:To explore the expression of connexin 43 (Cx43) in hippocampus of post-stroke depression (PSD) model rats and its effect on cell apoptosis and depressive-like behavior.Methods:Sixty SPF-grade male SD rats aged 6-8 weeks were randomly divided into five groups (12 rats in each group): normal group, stroke group, depression group, PSD group and carbenoxolone(CBX) group. The stroke model was established by injection of endothelin-1.Chronic unpredictable mild stress (CUMS) combined with solitary rearing was used to establish a depression model. Rats in PSD group were given CUMS and raised alone on the seventh day of stroke modeling.Rats in CBX group were given intraperitoneal injection of CBX(20 mg/kg) on 14th day after PSD modeling. The depressive-like behavior of rats was evaluated by sugar water preference test and open field test. The expression of Cx43 mRNA in hippocampus of rats was detected by RT-PCR, the expression levels of Cx43, caspase-3, Bax and Bcl-2 were detected by Western blot, and the changes of apoptosis rate were detected by TUNEL staining. SPSS 23.0 software was used for statistical analysis, the behavioral data were analyzed by repeated measurement ANOVA, the remaining data were analyzed by one-way ANOVA, and the LSD- t test was used for further pairwise comparison. Results:(1)As for the preference rate of sugar water and the times of crossing the grid, the interaction effects between time and group were significant among the 5 groups( Finteraction=35.57, 111.43, both P<0.05). On the 28th day after operation, the preference rate of sugar water and the times of crossing grid in depression group and PSD group were lower than those in stroke group (all P<0.05), while the preference rate of sugar water and the times of crossing grid in CBX group were both lower than those in PSD group (both P<0.05). (2) The levels of Cx43 mRNA and Cx43 protein in the five groups were significantly different ( F=273.57, 64.56, both P<0.05). The levels of Cx43 mRNA and Cx43 protein in depression group ((0.59±0.05), (0.69±0.08)) and PSD group ((0.61±0.07), (0.63±0.12)) were lower than those in stroke group ((1.01±0.03), (1.05±0.08)) (all P<0.05). The levels of Cx43 mRNA and Cx43 protein in CBX group ((0.30±0.01), (0.37±0.09)) were lower than those in PSD group (both P<0.05). (3) The protein levels of caspase-3, Bax, Bcl-2 and Bcl-2/Bax and the apoptosis rate of the five groups were significantly different ( F=102.40, 90.27, 47.42, 159.99, 115.21, all P<0.05). The levels of caspase-3, Bax protein, apoptosis rate in stroke group ((0.44±0.06), (0.54±0.07), (29.16±5.03)) and depression group ((0.45±0.07), (0.59±0.09), (27.00±4.93)) were higher than those in normal group ((0.21±0.08), (0.33±0.07), (4.83±3.18)) (all P<0.05), the levels of Bcl-2 protein and Bcl-2/Bax in stroke group ((0.80±0.04), (1.51±0.20)) and depression group ((0.60±0.09), (1.03±0.09)) were lower than those in normal group ((1.04±0.13), (3.14±0.38)) (all P<0.05).The levels of caspase-3, Bax protein and apoptosis rate in PSD group ((0.76±0.05), (0.84±0.02), (44.50±3.83)) were all higher than those in stroke group and depression group (all P<0.05), and the levels of Bcl-2 protein and Bcl-2/Bax in PSD group ((0.50±0.14), (0.59±0.17)) were lower than those in stroke group and depression group (both P<0.05). The levels of caspase-3 and Bax protein and the apoptosis rate in CBX group ((1.03±0.10), (1.02±0.05), (56.00±4.81)) were higher than those in PSD group (all P<0.05).The levels of Bcl-2 protein and Bcl-2/Bax in CBX group((0.26±0.08), (0.25±0.08)) were lower than those in PSD group (both P<0.05). Conclusion:The expression level of Cx43 in the hippocampus of PSD model rats is downregulated, which can promote cell apoptosis and exacerbate depressive behavior.

OBJECTIVETo explore the clinical phenotype of a family affected with congenital dysfibrinogenemia and potential mutations underlying the disease.

METHODSCoagulation testing and hepatorenal function testing were conducted on 18 individuals from three generations. Plasma fibrinogen was extracted and analyzed with SDS-PAGE electrophoresis. All of the exons and flanking sequences of fibrinogen FGA, FGB, FGG genes were analyzed by PCR, and the products were subjected to Sanger sequencing.

RESULTSHepatorenal function, prothrombin time and activated partial thromboplastin time of the proband were all normal. However, his thrombin time was significantly prolonged. Fibrinogen activity was decreased, while the concentration of antigen was in the normal range. The results of his mother, brother, and nephew were similar. DNA sequencing has confirmed that the proband, his mother, brother, and nephew have all carried a g.5877G>A mutation in the exon 8 of the FGG gene, which resulted in replacement of arginine (Arg) by histidine (His) at position 275.

CONCLUSIONThe Arg275His mutation of the fibrinogen gamma chain probably underlies the pathogenesis of congenital dysfibrinogenemia in this family.

Adult ; Afibrinogenemia ; genetics ; metabolism ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Female ; Fibrinogen ; genetics ; metabolism ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Mutation, Missense ; Pedigree ; Point Mutation