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BACKGROUND: Bowen's disease is a cutaneous squamous cell carcinoma (CSCC) in situ. If left untreated, BD may progress to invasive CSCC. CSCC is one of the most common cutaneous carcinoma in the elderly and the advanced, metastasis CSCC usually have a poor outcomes. However, the mechanisms of invasion and metastasis from Bowen's disease to CSCC is complicated and still unclear. OBJECTIVES: The aim of this study was to explore the biomarkers and molecular alterations in Bowen's disease development process via analyzing the proteomics changes in tissues of CSCC, Bowen disease and healthy skin. METHODS: A total of 7 individuals with CSCC (5 for proteomics study and 2 for validation), 7 individuals with Bowen disease (5 for proteomics study and 2 for validation) and 7 healthy controls (5 for proteomics study and 2 for validation) presented to the Department of Dermatology, Yijishan Hospital, the First Affiliated Hospital of Wannan Medical College between January 2021 and December 2021 were enrolled. The proteomics analysis was performed to screen differentially expressed proteins/gens (DEPs/DEGs) in the lesions of CSCC, Bowen disease and healthy skin tissues. The transcriptomic data (GSE32628) of CSCC was selected and downloaded from the GEO database. The common DEGs in our proteomics results and GSE32628 between CSCC and healthy skin tissues were selected. And then, the common DEGs which significantly up or down-regulated between CSCC and Bowen disease in our proteomics results were further screened to identify using Western blot methods in the validation group. CSCC A431 cells were transfected with SERPINB1 small interfering RNA (si-SERPINB1) or small interfering RNA negative control (si-NC). To explore the effect of SERPINB1 silencing on migration and invasion ability of A431 cells. RESULTS: A total of 501 proteins were differentially expressed between the CSCC and healthy skin tissues, with 332 up-regulated and 169 down-regulated at least 1.5-fold with a P value < 0.05. These DEPs involved multiple biological functions such as protein binding process, immune, inflammation, ribosome, protein digestion and absorption, ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway and others. A total of 20 common DEGs (COL3A1, LUM, TNC, COL1A1, ALDH3A2, FSCN1, SERPINB4, SERPINB1, CD36, COL4A1, CSTB, GPX3, S100A7, ACTN1, SERPINB3, S100A8, RAB31, STAT1, SPRR1B, S100A9) between CSCC and healthy skin tissues in GSE32628 and our proteomics results were found. Besides, the proteins of TNC, FSCN1, SERPINB1, ACTN1 and RAB31 in CSCC were significantly up-regulated, while COL3A1, COL1A1 and CD36 were significantly down-regulated relative to Bowen disease in proteomics results. These proteins were mainly involved in multiple pathways, including Focal adhesion, ECM-receptor interaction, Human papillomavirus infection, PI3K-Akt signaling pathway, PPAR signaling pathway, AMPK signaling pathway and others. These eight proteins were selected for further validation. According to the Western blotting analysis, when compared with the Bowen disease and healthy skin tissues, we found that the relative expression levels of TNC, FSCN1, SERPINB1, ACTN1 and RAB31 in the CSCC were significantly increased, while COL1A1 and CD36 were significantly decreased, and the differences were statistically significant (P < 0.05). Furthermore, the relative expression levels of TNC, FSCN1, SERPINB1 in the Bowen disease were also significantly increased, while the COL3A1 were also significantly decreased relative to the healthy control. SERPINB1 siRNA inhibited the expression of SERPINB1 at mRNA and protein levels in the A431 cells. After interfering with the expression of SERPINB1, the migration and invasion ability in the A431 cells were significantly decreased (P < 0.05). CONCLUSIONS: This study highlights that eight proteins, TNC, FSCN1, SERPINB1, ACTN1, RAB31, COL3A1, COL1A1, CD36, were significantly associated with the mechanisms of invasion and metastasis in Bowen's disease.
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Doença de Bowen , Carcinoma de Células Escamosas , Serpinas , Neoplasias Cutâneas , Idoso , Biomarcadores , Doença de Bowen/genética , Carcinoma de Células Escamosas/genética , Proteínas de Transporte , Humanos , Proteínas dos Microfilamentos , Fosfatidilinositol 3-Quinases , Proteômica , Proteínas Proto-Oncogênicas c-akt , RNA Interferente Pequeno , Neoplasias Cutâneas/genética , Transcriptoma/genéticaRESUMO
Objective To investigate the effect of anesthesia at different depths on postoperative cognitive disfunction (POCD) and inflammatory response in the elderly patients undergoing abdominal operation.Methods A total of 90 elderly patients who underwent abdominal operation in the Affiliated Hospital of Shaanxi University of Chinese Medicine from June 2014 to June 2016 were divided into observation group and control group according to the depth of anesthesia,45 cases in each group.The patients in the two groups were performed with combined intravenous and inhalation anesthesia,the bispeetral index (BIS) value was maintained at 30-39 during the operation in the observation group,and the BIS value was maintained at 50-59 during the operation in the control group.The mean arterial pressure (MAP) and heart rate(HR) of patients in the two groups were recorded at the time points of entering the operation room(T0),5 minutes after tracheal cannula(T1),opening abdominal cavity (T2),closing abdominal cavity (T3) and tracheal cannula extubation (T4).The mini-mental state examination (MMSE) score of the patients in the two groups was performed before operation and the first,third,seventh day after operation;and the incidence of POCD was recorded.The levels of serum interleukin-6(IL-6) and S-100β protein were detected at the time points of before operation,the end of the operation and the first,third day after operation in the two groups.Results Five cases in the control group and six cases in the observation group were eliminated,39 cases in the observation group and 40 cases in the control group were evaluated finally.The MAP at T1 and T2 was significantly lower than that at T0 in the two groups (P < 0.05).There was no significant difference in the MAP between T3,T4 and T0 in the two groups(P < 0.05).There was no significant difference in the HR each time point in each group(P < 0.05).There was no significant difference in the MAP and HR between the two groups at each time point(P < 0.05).There was no significant difference in the MMSE score between the two groups before operation(P < 0.05).The MMSE score of patients at the first and third day after operation was significantly lower than that before operation and the seventh day after operation in the two groups (P < 0.05).There was no significant difference in the MMSE score between before operation and the seventh day after operation in the two groups(P <0.05).The MMSE score in the observation group was significantly higher than that in the control group at the first and third day after operation (P < 0.05).There was no significant difference in the MMSE score between the two groups at the seventh day after opera tion(P < 0.05).The incidences of POCD at the first,third and seventh day after operation in the observation group were 28.21% (11/39),15.38% (6/39) and 7.69% (3/39) respectively;and they were 50.00% (20/40),37.50% (15/40) and 20.00% (8/40) respectively in the control group.The incidence of POCD in the observation group was significantly lower than that in the control group at the first and third day after operation (x =3.934,4.949;P < 0.05).There was no significant difference in the incidence of POCD between the two groups at the seventh day after operation(x2 =2.496,P < 0.05).There was no significant difference in the levels of serum IL-6 and S-100β protein between the two groups before operation (P <0.05).The levels of serum IL-6 and S-100β protein at the end of operation and the first,third day after operation were significantly higher than those before operation in the two groups(P < 0.05).The levels of serum IL-6 and S-100β protein in the observation group were significantly lower than those in the control group at the end of operation and the first,third day after operation (P < 0.05).Conclusion Deep anesthesia (BIS value is maintained at 30-39) can reduce the levels of inflammatory factors,the incidence of POCD after operation and the brain damage in the elderly patients with abdominal operation.
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Objective: To investigate the dynamic expression of the 20S proteasome in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic patients without vascular complications. Methods: PBMCs were prepared from 30 type 2 diabetic patients and 30 nondiabetic controls. The general indexes including weight, height and blood pressure were recorded. Fasting plasma glucose, fasting plasma insulin and glycosylated hemoglobin were measured. The protein level of the 20S proteasome was measured by Western blotting. The mRNA expression levels of the 20S proteasome β1, β2 and β5 submits were detected by real-time PCR. Results: Compared with that in the nondiabetic controls, the protein level of the 20S proteasome was significantly increased in the diabetic patients and was positively associated with glycosylated hemoglobin. Conclusion: Type 2 diabetic patients without vascular complications have an increased 20S proteasome expression, the significance of which needs to be explored by further study.
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This study was aimed to explore the correlation between effects of arsenic trioxide on NB4 cell differentiation and the change of beta(1)-subunit of 26S proteasome. NB4 cell in 0.5 micromol/L As(2)O(3) was incubated for 24 hours and 48 hours, then total protein was extracted, expressions of subunit beta(1) and PML-RARalpha fusion protein were determined by Western blot. The results indicated that the expression of 26S proteasome beta(1)-subunit increased after incubation with As(2)O(3) for 24 hours, but after culture with As(2)O(3) for 48 hours, the expression of beta-subunit decreased to the baseline. Meanwhile, the expression of PML-RARalpha fusion protein obviously decreased after 24 hours, and kept low level at 48 hours. It is concluded that the expression of 26S proteasome beta(1)-subunit increases after exposure to As(2)O(3). Increment of 26S proteasome beta(1)-subunit may be associated with the degradation of PML-RARalpha fusion protein and plays roles in the differentiation and apoptosis of NB4 cells.
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Humanos , Apoptose , Arsenicais , Farmacologia , Diferenciação Celular , Leucemia Promielocítica Aguda , Metabolismo , Proteínas de Fusão Oncogênica , Metabolismo , Óxidos , Farmacologia , Complexo de Endopeptidases do Proteassoma , Células Tumorais CultivadasRESUMO
<p><b>OBJECTIVE</b>To observe the expression of hepatocyte nuclear factor 4alpha (HNF4alpha) and the activity of key enzyme glucokinase (GK) in glucose metabolism, and further to investigate the possible mechanism of berberine in treating type 2 diabetes.</p><p><b>METHOD</b>Mouse primary hepatocytes were isolated by an improved single two-step perfusion method. The murine hepatocytes were cultured and incubated with berberine (0, 1, 3, 10, 30, 100 micromol x L(-1)) and 1 mmol x L(-1) metformin for 24 h respectively. The mRNA expression of HNF4alpha were quantified by RT-PCR and the protein expression of HNF4alpha were quantified by Western-blot. And the activity of GK were detected with enzyme kinetics method.</p><p><b>RESULT</b>As compared with the negative control group, at a certain concentration range, the expression of HNF4alpha mRNA and protein and the activity of GK were promoted by berberine. Both of them reached the top at the concentration of 30 micromol x L(-1) (P<0.01). But the metformin made no difference with the negative control group on the expression of HNF4alpha and the activity of GK.</p><p><b>CONCLUSION</b>It is suggested that the effects of berberine on improving glucose metabolism can be mechanically associated with its up-regulating the HNF4a expression and inducing the activity of hepatic glucokinase.</p>
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Animais , Masculino , Camundongos , Berberina , Farmacologia , Sobrevivência Celular , Células Cultivadas , Regulação da Expressão Gênica , Glucoquinase , Genética , Metabolismo , Fator 4 Nuclear de Hepatócito , Genética , Metabolismo , Hepatócitos , Biologia Celular , Metabolismo , Extratos Vegetais , FarmacologiaRESUMO
<p><b>OBJECTIVE</b>The aim of the study was to determine the prevalence and the distribution pattern of lesion site of intracranial vascular stenosis and to identify risk factors for the stenosis in patients with essential hypertension.</p><p><b>METHODS</b>A total of 231 consecutive inpatients with essential hypertension were included in this study. Patients with the history of cerebrovascular diseases and relevant neurological symptoms were excluded. Intracranial vascular stenosis (>50% diameter reduction) was detected using CT angiography (CTA).</p><p><b>RESULTS</b>Of 231 patients, 69 (29.87%) had intracranial artery stenosis. The most common stenosis site is middle cerebral artery (43.69%), followed by carotid siphon (20.39%). The stenosis in internal carotid arterial system (78.64%) was more common than in vertebrobasilar arterial system (21.56%, P < 0.05). The patients with intracranial vascular stenosis were older, had longer history of hypertension, higher levels of systolic blood pressure, higher plasma cholesterol, higher LDL-C. Lp (a), higher urinary microalbumin excretion, thicker ventricular septum, and lower levels of HDL-C than the patients without stenosis. Logistic analysis showed that systolic blood pressure (OR 1.650, 95% CI 1.134 - 2.400, P = 0.023), course of hypertension (OR 1.238, 95% CI 1.072 - 1.429, P = 0.006), LDL-C (OR 2.103, 95% CI 1.157 - 3.823, P = 0.014) and type 2 diabetes (OR 2.325, 95% CI 1.161 - 4.341, P = 0.011) were the independent risk factors of asymptomatic intracranial arterial stenosis.</p><p><b>CONCLUSIONS</b>Nearly 30% inpatients with essential hypertension had asymptomatic intracranial artery stenosis. The most common site of stenosis was middle cerebral artery. Hypertension, dyslipidemia and diabetes were risk factors for the development of intracranial arterial stenosis.</p>
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Angiografia Cerebral , Hipertensão , Epidemiologia , Patologia , Doenças Arteriais Intracranianas , Epidemiologia , Prevalência , Fatores de RiscoRESUMO
Objective To study the effects of self-management education on quality of life in children with asthma.Methods Seventy-five out-patients and in-patients with asthma were randomlydivided into 2 groups.The educational group(38 cases)received the basic knowledge education of asthma and self-management,while the control group received only the basic knowledge education of asthma.A inquiry was conducted in all patients using a Chinese PAQLQ(pediatric asthma quality of life questionnaire)before and 6 months after the treatment.The correlation and difference between 2 groups were analyzed.Results There were no significant difference before the therapy.After 6 months's treatment,there were uptrends on scorecard in some fields in such as symptom,activity,emotion and the total score in all patients(P
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<p><b>OBJECTIVE</b>To study the diagnosis and differential diagnosis of renal epithelial neoplasms.</p><p><b>METHODS</b>Ninety-one cases of renal epithelial neoplasms with detailed pathologic records were enrolled. In addition to microscopic examination, Mowy's colloidal iron staining and immunohistochemical studies (CD10, vimentin and CK7) were also performed.</p><p><b>RESULTS</b>Among the 91 cases, there were 78 (86%) clear cell renal carcinoma cases, 8 (9%) papillary renal carcinoma cases, 4 (4%) chromophobe renal carcinoma cases and 1 (1%) renal oncocytoma case. Sixty-three of the 78 clear cell renal carcinoma cases were positive for CD10 and 69 were positive for vimentin (81% and 88% respectively), with prominent cell membrane staining. The majority (74/78) of clear cell renal carcinoma were negative for CK7. All 17 clear cell renal carcinoma cases showed negative or focal coarse droplet-like staining pattern for Mowy's colloidal iron stain. All 4 chromophobe renal cell carcinoma cases showed prominent cell membrane staining for CK7 and blue reticular staining pattern for Mowy's colloidal iron stain. All of which were negative for CD10 and vimentin. The case of renal oncocytoma failed to react with antibodies to CD10, vimentin and CK7, or Mowy's colloidal iron stain.</p><p><b>CONCLUSIONS</b>CD10, vimentin, CK7 and Mowy's colloidal iron stains have proved to be useful in differential diagnosis of common renal tumors which may not be easily distinguished on the basis of histologic examination alone.</p>