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Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
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Humans , Epigenesis, Genetic , Gastric Mucosa/metabolism , Chromatin/metabolism , Stem Cells , Epithelium/metabolism , Fatty Acid-Binding Proteins/metabolismABSTRACT
Objective To investigate the prognosis relevant factors of laryngeal squamous cell carcinoma (LSCC).Methods From January 2013 to December 2013,the clinical data of 71 patients with LSCC who were initially treated in Zhejiang Cancer Hospital were retrospectively analyzed.Results Univariate analysis showed that there were statistically significant differences in survival rate between the group of supraglottic type and glottic type (60.0% vs.86.3% ,χ2 =6.284,P<0.05),the group of N0 and N+(41.7% vs.86.4% ,χ2 =16.803,P<0.01), the group of early and late stage(93.6% vs.50.0% ,χ2 =19.854,P<0.01).There were no statistically significant differences in survival rate between the group of age ≤50,>50-60,>60-70 and >70(88.9% vs.88.2% vs. 79.3% vs.62.5% ,χ2 =3.909,P>0.05),the group of T1+T2 and T3+T4(83.6% vs.62.5% ,χ2 =3.623,P>0.05),the group of high,medium,low differentiated and unsigned(75.0% vs.69.7% vs.83.3% vs.91.7% ,χ2 =3.780,P>0.05),the group of surgery,radiotherapy and surgery+radiotherapy (74.3% vs.90.9% vs.71.4% , χ2 =2.437,P>0.05).Multivariate analysis showed that age( P =0.003),treatment( P =0.048) had significant effect on the prognosis of patients,but tumor location(P=0.766),T stage(P=0.677),N stage(P=0.482),clinical stage(P=0.825),the degree of pathological differentiation(P=0.206) had no significant effect on the prognosis of patients.Conclusion More aggressive treatment should be supplied for patients with N+,advanced clinical stage and age whom the prognosis are usually poor. In addition, the proportion of tracheal tube extraction should be appreciated.
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Objective To investigate the predictive factors for central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma(PTMC).Methods A retrospective study including 2511 cases of PTMC admitted from Jan.2013 to Jan.2016 were enrolled in our study.Chi-square test was used in univariate analysis.Logistic regression analysis was applied for multivariate analysis.The relation between age,sex,tumor size,multifocality,thyroidal extension,nodular goiter and central lymph node metastasis is analyzed.Results Univariate analysis showed that age,sex,tumor size,multifocality,thyroidal extension and nodular goiter had statistical significance.Age less than 45(P＜0.001,x2=17.442);Male gender(P＜0.001,x2=17.029);Tumor size less than 5 mm (P＜0.001,x2=70.164.);Extrathyroid extension factor (P＜0.001,x2=63.197);Nodular hyperplasia factor (P=0.017,x2=5.611).Multivariate analysis showed there was a significant relationship between multifocality and the central lymph node positivity.The odds ratio (OR) was 1.587 in patients with tumor foci ≥2(P＜0.001).While OR increased sharply near to 3 in patients withtumor foci ≥3(OR=2.730).Tumor size(OR=1.926);Extrathyroid extension(OR=1.606).Conclusions Multifocalty,tumor size and thyroidal extension are the main predicative factors for central lymph node metastasis in PTMC.Among them,tumor foci ≥ 3 is an important predictor.Besides the conventional factors such as tumor size,thyroidal extension etc,multifocalty should also be taken into consideration.
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Objective To investigate the clinical features of papillary thyroid microcarcinoma(PTMC) and the risk factors of central lymph node metastasis (CLNM) in PTMC patients.Methods The clinical data of 855 patients with PTMC who underwent prophylactic central lymph node dissection were retrospectively reviewed.Results In the present study,the rate of CLNM was 21.9％ (187/855) in PTMC patients.In the univariate analysis,the incidence of CLNM was significantly higher in male patients,age ＜ 45 years,tumor size ＞ 5 mm,capsular invasion,multiple tumor and intracapsular spread (31.4 ％ vs.19.5 ％,x2 =11.429,P =0.001;29.3 ％ vs.15.9 ％,x2 =22.416,P =0.000;30.0％ vs.14.3％,x2 =30.669,P=0.000;29.4％ vs.16.8％,x2 =19.233,P =0.000;30.0％ vs.19.9％,x2 =8.205,P =0.004;42.9％ vs.21.3 ％,x2 =5.549,P =0.018,respectively).Multivariate analysis showed that male gender,age ＜ 45 years,tumor size ＞ 5mm,multiplicity and capsular invasion were independent risk factors for CLNM in PTMC patients (95％ CI:0.380-0.834,0.349-0.693,1.450-3.060,1.078-2.229,1.024-2.373,respectively).Conclusion A routine prophylactic central lymph node dissection should be considered particularly in male PTMC patients with age ＜45 years,tumor size ＞5 mm,capsular invasion and tumor multiplicity.
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AIM:To study the microRNA profiling in the serum of insulin-resistant mice and the mechanism of insulin resistance induced by related microRNAs.METHODS:A high-fat diet was used to induce insulin resistance model in KM mice.The microRNA profiling in serum of insulin-resistant and normal mice was analyzed by microarray chip and were validated by real-time PCR.miRanda data base was used to forecast target genes.miRBase was used to obtain the se-quences of related microRNAs, based on which protein interactions were predicted using the online analytical tool STRING. RESULTS:In serum of insulin-resistant mice, the expression of miR-125, miR-126, miR-143, miR-30a, miR-199a, miR-127, miR-184, miR-30e, miR-134, miR-195, miR-206, miR-429, miR-212, miR-362, miR-382, miR-154 and miR-466h was significantly up-regulated.miR-211, miR-504, miR-877 and miR-1930 were significantly down-regulated. miR-143 associated with insulin resistance was able to bind to 3'-UTR of fat mass and obesity-associated protein (FTO), and FTO was found to interact with Rpgrip1l, Tmem18, Mc4r, Npy, Hhex, Tcf712, Cdkal1, Slc30a8, Igf2bp2 and Tha-da.CONCLUSION:Twenty-one microRNAs in the serum of insulin-resistant mice induced by a high-fat diet are signifi-cantly different from those of normal mice, in which 17 kinds were significantly up-regulated.miR-143 closely related to in-sulin resistance is able to regulate FTO protein expression, which interacts with other 10 proteins associated with the occur-rence and development of diabetes.The results are also useful for further study of the molecular mechanisms in insulin re-sistance.
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The aim of this investigation was to assess the in-vitro interaction of two antifungal agents, econazole-nitrate and chelerythrine, against ten fluconazole-resistant clinical isolates and one ATCC type strain 10231 of Candida albicans. The checkerboard microdilution method was performed according to the recommendations of the National Committee for Clinical Laboratory Standards, and the results were determined by visual examination. The interaction intensity was tested in all isolates using the fractional inhibitory concentration index [FICI]. These experiments showed synergism between econazole-nitrate and chelerythrine in antifungal activity against C. albicans, and no antagonistic activity was observed in any of the strains tested. Moreover, time-kill curves were performed with selected strains to confirm the positive interactions. The similarity between the results of the FICI values and the time-kill curves revealed that chelerythrine greatly enhances the antifungal effects of econazole-nitrate against isolates of C. albicans. This synergistic effect may markedly reduce the dose of econazole-nitrate required to treat candidiasis, thereby decreasing the econazole-nitrate toxic side effects. This novel synergism might provide a potential combination treatment against fungal infections
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Objective To investigate the molecular mechanisms of protective effects of thioredoxin (Trx) on human vascular endothelial cells in atherosclerosis.Methods The cell models of Trx-overexpressing cells (Ad Trx) and the control cells (Ad-con) were established by adenovirus vector gene transfer technology in human umbilical vein endothelial cells (HUVECs).The oxidized low density lipoprotein,a risk factor of atherosclerosis,was used as a stimulator.Western blot and indirect immunofluorescence were used to detect the protein expression levels and the cellular localization of Trx,adhesion molecules (ICAM-1,VCAM-1) and the upstream signal pathways.Trx activity was detected by insulin disulfide reduction assay,and cellular reactive oxygen species (ROS)production was detected by fluorescent probe DCFH-DA.Results As compared with control group,Trx protein expression level was enhanced in Ad-trx group and the Trx activity in Ad-Trx group was upregulated by (26.2 ±3.3)％.The result of ROS detection showed that overexpression of Trx significantly inhibited the cellular ROS generation.As compared with control group,overexpression of Trx obviously inhibited the adhesion molecules expression but markedly promoted the phosphorylation of Smad3 in endothelial cells with or without oxLDL stimulation (P＜0.05).Pretreatment of cells with SIS3,a specific inhibitor of Smad3 phosphorylation,reversed Trx-induced inhibition of adhesion molecules expression.Further studies showed that pretreatment of cells with SIS3 enhanced oxLDL-induced AP-1 subunit c-fos nuclear expression.Conclusions The enhancement of Smad3 phosphorylation and c-Fos nuclear expression are mainly responsible for the Trx-induced downregulation of adhesion molecules.
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ObjectiveTo evaluate central compartment lymph node metastasis in cN0 papillary thyroid carcinoma(PTC) patients. MethodsThe clinical data of 166 cN0 PTC patients was retrospectively analyzed. ResultsThe central compartment lymph node metastasis rate of age ＜ 45 years group was higher than the group of age≥45 years(39％ vs.22％,P ＜0.05).Tumor size ＞0.5 cm tends to metastasize more often than tumor size ≤0.5 cm(P ＜0.05) ; there was significantly difference in central compartment lymph node metastasis rate between upper pole tumor ( 25％,12/48 ) and middle ( 45％,13/29 ) or lower pole (43％,31/72),P ＜ 0.01. ConclusionscN0 PTC patients with tumor located in middle pole or lower pole,tumor size ＞ 0.5 cm or age ＜ 45 years are at higher risks for central compartment lymph node metastasis.
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OBJECTIVE@#To discuss the effectiveness and advantage of application of pectoralis major flap in the reconstruction of massive defects after head and neck tumor excision.@*METHOD@#Thirteen patients with head and neck carcinoma underwent tumor excision, and the massive defects were fixed by pectoralis major myocutaneous flap. Ten patients with recurrent laryngeal carcinoma and 2 with hypopharyngeal carcinoma and 1 with thyroid carcinoma were included.@*RESULT@#Eleven cases healed well, 1 case appearance fistula of parotid gland, 1 case was lost to follow-up.@*CONCLUSION@#Pectoralis major myocutaneous flap with adequate vascularization, enough tissue and ideal healing ability cab be used to reconstruct massive defects. And so it can play an important role in providing a better life expectancy and can radically cure or relieve the complaint.
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Adult , Aged , Female , Humans , Male , Middle Aged , Head and Neck Neoplasms , General Surgery , Pectoralis Muscles , Transplantation , Postoperative Period , Plastic Surgery Procedures , Methods , Surgical FlapsABSTRACT
0.05). CONCLUSION The secar of oropharynx can be regarded as a predictive index for OSAHS severity and guideline for operation, but the change of secar after operation can not be used as a predicitive index for therapeutic effectiveness.
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OBJECTIVE@#To study the pathologic diagnosis and the injury time estimation in light closed encephalon injury.@*METHODS@#Mice were hurt by fluid percussion, and were killed at 15, 30 min, 1, 3 , 6, 12 h, 1, 4, 7, 14 d respectively after injury. The expression of Fas-L in the cerebral cortex, thalamus, and hippocampi was detected by immunohistochemistry and the results were assessed by image analysis system.@*RESULTS@#It is showed that the expression of Fas-L could be detected in 1 h after injury, and increased significantly in three hours, and it reached apex 12 h after injury, and decreased gradually four days after injury, and returned normal 14 days after injury.@*CONCLUSION@#This research demonstrated that Fas-L mediated apoptosis appeared not only around brain trauma but also in the brain tissue far away from the traumatic area. It indicted that the expression of Fas-L is a useful target for diagnosis of early brain injury; the regularity of Fas-L expression could be used as one of indication to date the time of brain injury.
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Animals , Male , Rats , Apoptosis , Brain/metabolism , Brain Injuries/pathology , Fas Ligand Protein , Image Processing, Computer-Assisted , Immunohistochemistry , Membrane Glycoproteins/biosynthesis , Rats, Wistar , Time Factors , Tumor Necrosis Factors/biosynthesisABSTRACT
Whether the ATP-sensitive potassium channel opener pinacidil can provide myocardial protective effects in prolonged isolated global ischemic rat heart was investigated. On modified isolated rat working heart model, 40 hearts were divided into four groups randomly: Hyperpolarized arrest H-K solution containing pinacidil (50 mumol/L) (P1 and P2) and depolarized arrest St. Thomas' solution (S1 and S2) subjected to 15 degrees C hypothermia, 60 min (P1 and S1) or 120 min (P1 and S2) of ischemia and 30 min reperfusion. The experimental indices included cardioplegic efficiency, cardiac function, coronary blood flow, myocardial enzyme release, myocardial water and ATP content. Hyperpolarized arrest provided significantly better recovery of cardiac function than depolarized arrest. Postischemic coronary flow and myocardial ATP content were higher. The arrest time of electro-mechanical activities were longer than depolarized arrest. There were no differences among the groups in myocardial water contents. The hyperpolarized arrest solution containing pinacidil can provide a marked myocardial protective effect during prolonged hypothermic myocardial ischemia.
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Animals , Male , Rats , Cardioplegic Solutions , Pharmacology , Cyclic Nucleotide-Gated Cation Channels , Heart Arrest, Induced , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels , In Vitro Techniques , Ion Channels , Metabolism , Myocardial Reperfusion Injury , Myocardium , Metabolism , Pinacidil , Pharmacology , Potassium Channels , Random Allocation , Rats, WistarABSTRACT
Objective To explore the effect of estradiol benzoate on the expressions of heat shock protein (HSP)70, 90 in endometrial glandular epithelial cell. Methods Normal endometrial glandular epithelial cells were isolated, and cultured by enzymolysis method and identified by electron microscopy and immunohistochemical analysis. The normal endometrial glandular epithelial cells were treated with culture medium only, estradiol benzoate (10 -9 , 10 -8 , 10 -7 or 10 -6 mol/L), estradiol benzoate(10 -9 , 10 -8 , 10 -7 or 10 -6 mol/L) and antiestrogen ICI 182780(fulvestrant,faslodex, 1?mol/L)and ICI 182780 only for 6, 12, 18, 24 hours respectively. The dose-and time-related effect of estradiol benzoate and ICI 182780 on the cell growth was measured by mononuclear cell direct cytotoxicity assay (methyl thiazolyl tetrazolium assay), and that on the expression of HSP70 and HSP90 in normal endometrial glandular epithelial cell in vitro was measured by immunohistochemical analysis and computerized image analysis system. Results Estradiol benzoate stimulated cell growth in a time-and dose-dependent manner and the effect was attenuated by the antiestrogen ICI 182780. The average cell growth rates of 10 -9 , 10 -8 , 10 -7 , 10 -6 mol/L estradiol benzoate for 24 hours were(170?9)%,(207?11)%,(231?12)%,(257?10)%, which were significantly higher than those of 6 hours (117?13)%, (129?10)%, (146?10)%, (176?6)%, P
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AIM: To explore whether AT2 receptor is expressed in skeletal muscular vasculature, and the expression of angiotensin Ⅱ receptors in pulmonary circulation of children with left-to-right shunt but without obstructive pulmonary hypertension. METHODS: Lung and skeletal muscular tissue were obtained from 20 children with left-to-right shunt by biopsy during operation. These skeletal muscular tissues were detected by reverse transcriptase/polymerase chain reaction (RT-PCR ) and immunohistochemistry techniques for AT2 receptors. mRNA of AT1 and AT2 receptors in lung tissues were detected by RT-PCR and analyzed semi-quantitatively. RESULTS: In all of the skeletal muscular tissues, mRNA of AT2 receptor was found by RT-PCR, and the results of immunohistochemistry staining for AT2 receptor of vessels were positive. In the lung tissues, the level of mRNA of AT2 receptor was different to AT1 receptor, and the former was higher than the latter (P