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Cigarette smoke (CS)-induced activation of proteases such as matrix metalloproteinases (MMPs) contributes to lung alveolar destruction due to cell death. The aim of this study was to determine whether MMPs are produced in pulmonary artery endothelial cells (PAECs) and whether CS activation of MMPs is associated with apoptosis. Cultured PAECs were exposed to CS and subjected to assessments of apoptosis and MMPs. Western blotting and in situ zymography were performed to localize gelatinolytic activity and to identify enzymes. CS-induced apoptosis, i.e., enhanced annexin V binding and cleaved poly-ADP-ribose-polymerase (PARP), correlated with increased degradation of gelatin, a substrate of MMPs. The levels of pro-MMP-2 and active MMP-2 were increased in cytosolic and nuclear fractions isolated from CS-exposed cells. MMP-2 protein colocalized with gelatinolytic activity in the nucleus of CS-exposed cells undergoing apoptosis. These observations support the notion that MMP-2 contributes to CS-induced gelatinase activity, which localizes in the nuclear region primarily and correlates with annexin V binding and PARP cleavage. This suggests a novel function of MMP-2 in the degradation of the nuclear matrix in CS-induced endothelial apoptosis.
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Apoptose/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Animais , Anexina A5/metabolismo , Núcleo Celular/enzimologia , Núcleo Celular/patologia , Células Cultivadas , Endotélio Vascular/enzimologia , Endotélio Vascular/patologia , Poli(ADP-Ribose) Polimerases/metabolismo , Artéria Pulmonar/enzimologia , Artéria Pulmonar/patologia , Fumaça/efeitos adversos , Fumar/efeitos adversos , SuínosRESUMO
Objective To analyze the clinical features of patients with coronavirus disease 2019 (COVID-19) in Shanghai and to investigate the risk factors for disease progression to severe cases. Methods The clinical data of 292 adult patients with COVID-19 hospitalized in Shanghai Public Health Clinical Center from January 20, 2020 to February 10, 2020 were retrospectively analyzed, including 21 severe patients and 271 mild patients. The demographic characteristics, epidemiological history, history of underlying diseases and laboratory examinations were compared between the two groups. Measurement data were compared using t test or Mann-Whitney U test. The count data were compared using hi-square test. The binary logistic regression equation was used to analyze the risk factors for the progression of patients to severe cases. Results Among the 292 patients, 21 were severe cases with the rate of 7.2% (21/292). One patient died, and the mortality rate was 4.8% in severe patients. The severe patients aged (65.0±15.7) years old, 19 (90.5%) were male, 11 (52.4%) had underlying diseases, 7 (33.3%) had close relatives diagnosed with COVID-19. The mild patients aged (48.7±15.7) years old, 135 (49.8%) were male, 74 (27.3%) had underlying diseases, 36 (13.3%) had close relatives diagnosed with COVID-19. The differences between two groups were all significant statistically ( t =-4.730, χ 2 =12.930, 5.938 and 4.744, respectively, all P <0.05). Compared with the mild patients, the levels of absolute numbers of neutrophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatinine, serum cystatin C, C reactive protein (CRP), procalcitonin , D -dimer, pro-B-type natriuretic peptide (proBNP), serum myoglobin, creatine kinase (CK), creatine kinase isoenzyme (CK-MB), serum troponin I (cTnI) in severe patients were all significantly higher ( U =2 091.5, 1 928.0, 1 215.5, 729.0, 1 580.5, 1 375.5, 917.5, 789.5, 1 209.0, 1 434.0, 638.0, 964.5, 1 258.0 and 1 747.5, respectively, all P <0.05), while the levels of lymphocyte count, albumin, transferrin, CD3 + T lymphocyte count, CD8 + T lymphocyte count and CD4 + T lymphocyte count in severe patients were all significantly lower ( U =1 263.5, t =4.716, U =1 214.0, 962.0, 1 167.5 and 988.0, respectively, all P <0.05). Further logistic regression analysis showed that the albumin (odds ratio ( OR )=0.806, 95% CI 0.675-0.961), CRP ( OR =1.016, 95% CI 1.000-1.032), serum myoglobin ( OR =1.010, 95% CI 1.004-1.016), CD3 + T lymphocyte count ( OR =0.996, 95% CI 0.991-1.000) and CD8 + T lymphocyte count ( OR =1.006, 95% CI 1.001-1.010) at admission were independent risk factors for the progression of COVID-19 patients to severe illness (all P <0.05). Conclusions Severe cases of patients with COVID-19 in Shanghai are predominantly elderly men with underlying diseases. Albumin, CRP, serum myoglobin, CD3 + T lymphocyte count and CD8 + T lymphocyte count could be used as early warning indicators for severe cases, which deserve more clinical attention.
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Objective:To analyze the clinical features of patients with corona virus disease 2019 (COVID-19) in Shanghai and the risk factors for disease progression to severe cases.Methods:The clinical data of 292 adult patients with COVID-19 hospitalized in Shanghai Public Health Clinical Center from January 20 to February 10, 2020 were retrospectively analyzed, including 21 severe patients and 271 mild patients. The demographic characteristics, epidemiological history, history of underlying diseases and laboratory tests were compared between the two groups. Measurement data were compared using t test or Mann-Whitney U test. The count data were compared using chi-square test. The binary logistic regression equation was used to analyze the risk factors for the progression of patients to severe cases. Results:Among the 292 patients, there were 21 severe cases with the rate of 7.2%. One patient died, and the mortality rate was 4.8% in severe patients. The severe patients aged (65.5±15.7) years old, and 19 (90.5%) were male, 11 (52.4%) had underlying diseases, seven (33.3%) had close relatives diagnosed with COVID-19. The mild patients aged (48.7±15.7) years old, and 135 (49.8%) were male, 74 (27.3%) had underlying diseases, 36 (13.3%) had close relatives diagnosed with COVID-19. The differences between two groups were all significant statistically ( t=-4.730, χ2=12.930, 5.938 and 4.744, respectively, all P<0.05). Compared with the mild patients, the levels of absolute numbers of neutrophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatinine, serum cystatin C, C reactive protein (CRP), procalcitonin, D-dimer, pro-B-type natriuretic peptide (proBNP), serum myoglobin, creatine kinase (CK), creatine kinase isoenzyme (CK-MB), serum cardiactroponin I (cTn I) in severe patients were all significantly higher ( U=2 091.5, 1 928.0, 1 215.5, 729.0, 1 580.5, 1 375.5, 947.5, 789.5, 1 209.0, 1 434.0, 638.0, 964.5, 1 747.5 and 1 258.0, respectively, all P<0.05), while the levels of lymphocyte count, albumin, transferrin, CD3 + T lymphocyte count, CD8 + T lymphocyte count and CD4 + T lymphocyte count in severe patients were all significantly lower ( U=1 263.5, t=4.716, U=1 214.0, 962.0, 1 167.5 and 988.0, respectively, all P<0.05). Further logistic regression analysis showed that the albumin (odds ratio ( OR)=0.806, 95% confiderce interval ( CI)0.675-0.961), serum myoglobin ( OR=1.010, 95% CI 1.004-1.016), CRP ( OR=1.016, 95% CI 1.000-1.032), CD3 + T lymphocyte count ( OR=0.996, 95% CI 0.991-1.000) and CD8 + T lymphocyte count ( OR=1.006, 95% CI 1.001-1.010) at admission were independent risk factors for the progression of COVID-19 patients to severe illness (all P<0.05). Conclusions:Severe patients with COVID-19 in Shanghai are predominantly elderly men with underlying diseases. Albumin, CRP, serum myoglobin, CD3 + T lymphocyte count and CD8 + T lymphocyte count could be used as early warning indicators for severe cases, which deserve more clinical attention.
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Portal hypertensive gastropathy (PHG) has a high incidence rate in cirrhotic patients,leading to a high risk of upper gastrointestinal bleeding.Gastric mucosal injury is the major pathological change of PHG.There are few studies focusing on the clinical application of antacids in the treatment of PHG in cirrhotic patients and there are still controversies over this issue.This article reviews the influencing factors for PHG,the mechanism of gastric mucosal injury,and the application of antacids.It is pointed out that during the treatment of PHG,besides the reduction in portal venous pressure,the application of antacids such as proton pump inhibitors can improve the cure rate of PHG.Prospective randomized control trials with a large sample size are needed to further demonstrate the clinical effect and safety of antacids in the treatment of PHG in cirrhotic patients.
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In recent years, great progress has been made in the external treatment of traditional Chinese medicine (TCM) for cirrhotic ascites, including TCM umbilical compress therapy, TCM enema, acupuncture, moxibustion, and light therapy. The external treatment has similar effects as oral administration of TCM in relieving the clinical symptoms of cirrhotic ascites, and does not have gastrointestinal adverse reactions. This article reviews the research advances in external treatment of TCM for cirrhotic ascites, and the new research directions in the future are to establish an unified research protocol and expand the scope of application of external treatment of TCM.
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Objective To discuss clinic effect of pulmonary artery valvuloplasty for right ventricle outflow tract (RVOT) reconstruction in patients with repaired tetralogy of fallot (TOF). Methods A total of 93 cases TOF were randomly divided into Group A (n = 49) or Group B (n = 44) to perform the procedure with repaired tetralogy of fallot Group A received autogenous pericardium to enlarge RVOT and pulmonary valvuloplasty.Group B received autogenous pericardium to enlarge RVOT by routine therapy. Pulmonary regurgitation index (PRi) and the ratio between pulmonary regurgitant jet width and pulmonary annulus diameter were measured with echoeardiography. Results The mean follow-up was 3. 1 ± 0. 2 years. The PRi and the ratio between pulmonary regurgitant jet width and pulmonary annulus diameter in Group A were-significantly lower than Group B (0. 55 ± 0. 13 vs. 0. 61 ± 0. 10, t = 2. 685, P < 0.01) and ([52.0 ± 10.4] % vs. [57.1 ± 10. 5]% ,t = 2. 349, P < 0.05) . Three-dimensional ultrasound examination showed that 69% (34/69) of pulmonary valves in Group A was developed well. Conclusion Pulmonary valvuloplasty during transannular patch for repaired TOF may prevent fre'e pulmonary regurgitation and can obtain good clinical outcome.
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Objective:To observe the expression of chemokine receptor CCR7 and CXCR4 in human colorectal carcinoma and its significance,so as to assess their expression with the metastasis and prognosis of colorectal carcinoma. Methods:Immunohistochemistry was used to detect the expression of chemokine receptor CCR7 and CXCR4 in 110 patients with colon cancer.The relationship between the CCR7 and CXCR4 expression and the clinic pathological characters was statistically analyzed. Results:CCR7 and CXCR4 expression were positively expressed in 59.1% and 45.5%of the patients. The high expression rate of CCR7 and CXCR4 in lymph node metastasis positive cases was 81. 5% and 60.0% respectively,but the without lymph node metastasis positive cases were 26.7% and 24.4% respectively. The positive expression was significantely higher in the patients with lymph node metastasis than those non-lymph node metastasis(P
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Objective: To detect the expression of focal adhesion kinase (FAK) and vascular endothelial growth factor (VEGF) in human rectal carcinoma, to study their correlation in invasion and metastasis. Methods: The expression of FAK and VEGF in 86 specimens resected from patients with rectal carcinoma and 30 non-rectal carcinoma specimens, was investigated by immunohistochemical SABC method respectively. Results: the positive rate of FAK, VEGF was 80 % and 59% respectively in rectal carcinoma. However, non-rectal carcinoma was 10% and 13 % respectively. The diference was significant (P
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Objective:To investigate the expressions of Bag-1 and Bcl-2 in colorectal cancer and evaluate their clinical significance.Methods:Bag-1 and Bcl-2 expressions were studied by immunohistochemical Streptavidin-Biotin-Peroxidase Complex(SABC)method in 64 samples of colorectal cancer tissues,10 normal colorectal tissues.Results:Bag-1 was positively related to the tumor grade,distant metastasis,stages of Dukes and prognosis,but was not related to the pathological cell types,tumor diameter,depth of invasion and lymph node metastasis.Bcl-2 was not correlated to these clinicopathologic factors.There was a positive correlation between Bag-1 and Bcl-2(r=0.475).Conclusion:The over expression of Bag-1 and Bcl-2 protein in colorectal cancer can affect the generation of colorectal cancer by participating in the regulation of apoptosis.
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Classical description of central pathways has been that there are segregated routes for visceral and somatic inputs, for pain and tactile processing. Ample evidence in recent studies however calls for a revision of this traditional view. It has been demonstrated that visceral nociceptive inputs may travel in the dorsal column-medial lemnicus system along with skin tactile inputs, and convergence and interactions between the two distinct modalities have been demonstrated in route to the high brain centers. In the spinal cord and thalamus, skin inputs may inhibit noxious colorectal inputs; on the other hand pre-existing visceral nociception may cause abnormally high discharge of single neurons. These recent findings shine light on mechanisms of central processing of visceral nociception and its associated allodynia and referred pain, as well as for the effects of some traditional therapies such as acupuncture and massage.
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Objective To study the outcome of lost gallstones in peritoneal cavity. Methods Gallstones and bile collected from 51 patients undergoing laparoscopic cholecystectomy were analysed and cultured.One to three gallstones from each patient were placed into the peritoneal cavity of a corresponding Wistar rat on sterile condition. Results 8 rats died of peritoneal infection, intestinal fistula and ileus within one month. Abdominal wall abscess occured to one rat. All survival rats were sacrificed three months later. Pathologic results showed that the nidus of abscess appeared in tissue around the stone. Conclusions Lost gallstone is harmful to body. We should avoid gallstone lost in peritoneal cavity.
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Electrical vagus nerve stimulation (VNS) has been approved by FDA and is widely used in recent years for the treatment of epilepsy and possibly other medical conditions such as depression. The current success rate of VNS for epilepsy is about 50%, but there are complications, potential risks and cost concerns. One of the major limitations for this new therapy is that its antiseizure mechanisms are by no means clear. In particular, it is not known whether the therapeutic effect is vagal specific, what types of nerve fibers in the vagus nerve are contributing to the therapeutic effects, or what individual patients would benefit from the use of the expensive and invasive VNS implantation. There are controversies regarding how and where the VNS takes effect on epilepsy in the central nervous system. The poor understanding of VNS has inevitably limited the application and success of the therapy. The current review analyses the pros and cons of VNS for epilepsy in vis-?-vis other available therapies including Chinese medical methods, and explores the possible mechanisms in order to stimulate further improvement of this new technology.
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Objective:To study the expression and significance of HGF, MMP-2 and MMP-9 in pancreatic carcinoma. Methods:The expression of HGF, MMP-2 and MMP-9 were examined by immunohistochemical technique in 50 cases of pancreatic carcinomas and 10 cases of normal tissues. The relationship between the expression and tumor behaviors were also analyzed. Results:The expressions of HGF, MMP-2 and MMP-9 in pancreatic carcinoma and normal tissues had distinct differences (P
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To explore the relationship between serum resistin concentration, hypertension, degree of obesity and blood glucose, fasting serum resistin concentration was measured with EIA in 17 normotensives and 44 patients with essential hypertension. Serum resistin concentration was significantly correlated with age and body fat percectage (BF%). The concentration level was significantly higher in grade 2 hypertension group [(30.5?11.0)?g/L] than in grade 1 hypertension group [(24.3?10.5)?g/L] and in normotensives group [(21.5?6.1)?g/L]. The difference in serum resistin concentration between the three groups disappeared when age and BF% were corrected by analysis of covariance. Serum resistin concentration was significantly correlated with systolic blood pressure, age, BF%, fasting plasma glucose. A stepwise multiple linear regression analysis revealed that age, BF% and fasting plasma glucose were significantly independent predictors of serum resistin concentration. The results suggest that serum resistin concentration is not directly related to blood pressure, but the concentration level is actually correlated with age, BF% and glucose metabolism.
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Objective To investigate the effect of obesity on change of the levels of blood glucose and blood lipid after treatment with different combinations of antihypertensive drugs in patients with essential hypertension (EH). Methods One hundred and thirty-eight patients with mild to moderate EH were randomly divided into 3 groups with different combinations of drugs: reserpine with dihydralazine, hydrochlorothiazide, potassium chloride group (group 1), fosinopril with indapamide group (group 2), and nifedipine with atenolol group (group 3). Treatment period lasted for 14 months. Every group was divided into obesity subgroup and non-obesity subgroup according to Chinese obesity standard. Results After treatment, blood glucose levels were significantly decreased and blood lipid level was unchanged in both obesity subgroup and non-obesity subgroup of group 1. High density lipoprotein-cholesterol (HDL-C)/low density lipoprotein-cholesterol (LDL-C) ratio was significantly decreased and blood glucose was significantly increased in obesity subgroup, however, there was not significant change in the level of blood glucose and blood lipid in non-obesity subgroup of group 2. Blood glucose level was significantly increased and HDL-C/LDL-C ratio was significantly decreased in obesity subgroup, however, there was significant increase only in fasting blood glucose in non-obesity subgroup of group 3. Conclusions The results suggested that treatment with a combination of reserpine and dihydralazine, hydrochlorothiazide, potassium chloride showed beneficial effect on improving carbohydrate metabolism in both obese and non-obese patients with EH, while the treatment with the combination of fosinopril with indapamide deteriorated carbohydrate and lipid metabolism in obese patients with EH, and the treatment with combination of nifedipine with atenolol impaired carbohydrate and lipid metabolism in obese patients with EH.
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AIM: To investigate the effects of a 10-weeks treatment with angiotensin Ⅱ (Ang Ⅱ) subtype I receptor antagonist losartan on vascular remodeling of thoracic aorta in male spontaneously hypertensive rats (SHR). METHODS: SHR were treated from 16 to 26 weeks of age with losartan at 15 mg/kg?d -1 or 0.75 mg/kg?d -1. RESULTS: Losartan (15 mg/kg?d -1) treatment significantly decreased systolic blood pressure compared with the control group, while losartan (0.75 mg/kg?d -1) had no the effect, losartan(15 mg) prevents the development of aortic hypertrophy by preventing hypertrophy of vascular smooth muscle cells (VSMC). In the losartan 0.75 group, these parameters were not changed. But in the losartan 15 and losartan 0.75 groups, the collagen content of the aortic media decreased significantly. CONCLUSION: It is inferred that the effect of Ang Ⅱ on stimulating VSMC growth of the aorta in SHR is dependent on arterial pressure, while the effect on collagen fibers is through pressure independent mechanism.
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AIM: To study the interactions between skin tactile and visceral nociceptive inputs in the ventroposterior lateral (VPL) nucleus of the rat thalamus. METHODS: Visceral nociceptive inputs were generated by colorectal distension (CRD). Skin tactile inputs were generated by 10 Hz skin puff. They were delivered in sequence to investigate the changes in reaction to the test stimulus after the conditioning stimulation. RESULTS: Among the isolated 78 single VPL neurons that had response to both CRD and skin tactile stimuli, 44% (31/70) had their response to CRD reduced by the preceding conditioning tactile stimulation, and 54% (38/70) had their tactile response enhanced by the preceding CRD. The skin receptive fields of the majority of the cells were located along the caudal part of the Meridians of Stomach and Gallbladder of Chinese medicine. CONCLUSIONS: (1) Conditioning tactile inputs may inhibit noxious colorectal inputs, but this effect was short-lasting and limited at single neuron level. (2) On the other hand, pre-existing visceral nociception may cause abnormally high discharge of thalamic neurons, a phenomenon that may be related to the clinically seen allodynia on the body surface in visceral lesions.
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Objective: To explore the relationship between the expressions of chemokine receptor CXCR4 and vascular endothelial growth factor C (VEGF-C ) with lymph node metastasis in human rectal cancer. Methods: Immuohistochemical staining was used to detect the expressions of CXCR4 and VEGF-C in 73 samples of human rectal cancer. The relationship between CXCR4 and VEGF-C in 73 samples of human rectal cancer. The relationship between CXCR4 and VEGF-C expressions was analyzed. Results: The positive rate of CXCR4 expression with lymph node metastasis was higher than that without lymph node metastasis (60.1% vs 23.3%,P
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AIM: To investigate the effects of angiotensin II receptor antagonist on remodeling of renal arterioles in hypertension. METHODS: Eighteen 4 weeks old male rats were divided into three groups: Wistar-Kyoto rats (WKY) for normotensive group, and spontaneously hypertensive rats (SHR) for hypertensive group, and SHR treated with losartan orally (15 mg?kg -1 ?d -1 ). The rats were raised to 16 weeks old. The morphometric parameters of the renal arterioles, and the widths of vascular smooth muscle cells (VSMC) and intercellular space were studied on kidney slices by light microscope and electromicroscope respectively, combined with computer-assistant image analysis system. The minimal renal vascular resistance (RVR min ) was studied by isolated kidney perfusion system. RESULTS: The systolic blood pressure of the tail artery, wall thickness, wall area, ratio of wall thickness to inner diameter, width of VSMC of renal arterioles and RVR min were all smaller or lower in losartan group than those of SHR. CONCLUSION: Ang II receptor antagonist losartan can prevent the remodeling of renal arterioles in SHR.
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Objective: To explore the effect of CO 2 pneumoperitoneum in laparoscopic surgery on the cardiovascular function of the geriatric cholelithiasis.Methods:Sixty aged patients undergone laparoscopic surgery were selected.During various stage of CO 2 insufflation,the heart rate(HR),blood pressure,oxygen saturation ,electrocardiogram(ECG),and myocardial enzymes were dected,and the clinical values of these changes were analyzed.Results: when CO 2 pneumoperitoneum established ,the HR and blood pressure were increased obviously .The incidence of arrhythmia was 36% and the incidence of changes of ST segment was 30%,10 minutes after pneumoperitoneum eliminated,these changes were restored. The myocardial enzymes and the oxygon saturation of blood had no distinct changes. Conclusion: The procedure of CO 2 pneumoperitoneum caused temporany changes of the HR ,SBP/DSP and ECG.The laparoscopic surgery is effective and safe for geriatric cholelithiasis.It suggests that the dynamic monitoring of electrocardiogram is necessary,especially for those with abnormal heart function.