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Objective:To investigate the effects of 3-methyladenine(3-MA)on extracellular matrix deposition in early diabetic nephropathy(DN)and its mechanism.Methods:A streptozotocin(STZ)-induced type 1 diabetes mouse model was used, and the mice were divided into vehicle control group, diabetes group(STZ group), 3-MA group, and chloroquine(CQ)group, 8 mice in each group. After 6 weeks of intervention, both kidneys were harvested, and the kidney-to-body weight ratio was recorded. Western blotting was performed to detect protein expressions of renal cortex fibronectin, α-smooth muscle actin(α-SMA), LC3, Beclin 1, p62, and vascular endothelial growth factor(VEGF). Immunohistochemistry was used to observe kidney fibronectin staining. Bioinformatics analysis was conducted on shared genes between diabetic nephropathy(DN)gene targets and 3-MA predicted gene targets.Results:Both 3-MA and CQ exhibited certain hypoglycemic effects in diabetic mice. Compared to the STZ group, the kidney-to-body weight ratio decreased in the 3-MA group( P<0.05). Western blotting showed that 3-MA reduced the expression of renal cortex matrix-related proteins fibronectin and α-SMA in diabetic mice( P<0.05 or P<0.01). Immunohistochemistry also revealed that 3-MA reduced fibronectin staining in the kidneys of diabetic mice. Both 3-MA and CQ inhibited the protein expression of renal cortex Beclin 1 in diabetic mice(both P<0.05), while 3-MA increased the expression of renal cortex p62( P<0.05). Bioinformatics analysis indicated a connection between shared genes of DN gene targets and 3-MA predicted gene targets with the VEGF signaling pathway. Western blotting results further showed that 3-MA reduced renal cortex VEGF expression in diabetic mice( P<0.01). Conclusion:3-MA can alleviate extracellular matrix deposition in the kidneys of early DN mice by inhibiting the VEGF signaling pathway.
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The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a catastrophic impact on human life and economic life. Due to the combination of multiple underlying diseases and low vaccination rates, dialysis patients are susceptible to SARS-CoV-2 infection and are likely to have more severe illness and even death. Moreover, dialysis patients with SARS-CoV-2 infection may initially present as asymptomatic or with mild symptoms, which makes it very difficult to identify severe patients at an early stage. Here, the epidemiology, clinical characteristics, risk factors for prognosis, vaccination and therapeutic strategies of dialysis patients with SARS-CoV-2 infection were summarized and analyzed, and it is hoped to provide a reference for the diagnosis and treatment of SARS-CoV-2 infection in this special group of patients.
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Objective:To increase the understanding of neuroleptic malignant syndrome, rhabdomyolysis and acute renal injury in advanced-aged patients with Parkinson's disease after abdominal surgery.Methods:We report a case of malignant syndrome, rhabdomyolysis and acute renal injury in an 85-year-old patient with Parkinson's disease after abdominal surgery in our department.The diagnosis and successful treatment experience were summarized, and a literature review was conducted.Results:The body temperature was as high as 40.5℃ in this patient, accompanied by stiffness, sustained involuntary shaking, increased muscle tone, serum creatine kinase at 104 615 U/L, tachycardia, low blood pressure, accelerated breathing rate, disturbance of consciousness, excessive sweating and other clinical manifestations, which met the diagnostic criteria for neuroleptic malignant syndrome.The patient had complications including concurrent rhabdomyolysis, acute renal injury and shock.The emergency was resolved after an early diagnosis and proactive treatment.Conclusions:If patients with Parkinson's disease have a high fever with rigidity or sudden aggravation within a short period of time after medication, the possibility of neuroleptic malignant syndrome should be considered and the causes should be screened.
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Objectives To investigate the incidence rate of asthma and chronic obstructive pulmonary disease (COPD) overlap syndrome(ACOS)in elderly male patients with stable COPD by following-up,and to explore the characteristics and clinical significance of pulmonary function for ACOS.Methods According to GOLD and Spain's guidelines for the diagnosis and treatment of COPD,we screened ACOS patients in 299 elderly male patients with stable COPD by following up in Beijing Hospital between 2003 and 2014.All patients were divided into 2 groups of 51 ACOS patients and 248 non-ACOS patients with COPD.All patients underwent pulmonary function tests and bronchial dilation test in the stable condition.The differences in pulmonary functions were compared between stable ACOS patients and non-ACOS patients with COPD.Results Among 299 elderly male patients with stable COPD,ACOS patients accounted for 17.1 % (51/299).Compared with nonACOS patients with stable COPD,ACOS patients had significantly lower baseline values in forced expiratory volume in 1 seconds(FEV1) [(61.0 ± 14.5) % pred vs.(74.4 ± 20.0) % pred],in forced expiratory volume in 3 seconds(FEV3) [(71.6± 14.3)% pred vs.(82.7± 19.6)% pred]and in forced vital capacity(FVC) [(84.6 ± 16.4)% pred vs.(93.8 ± 20.6)% pred],and also had significantly higher values in residual volume(RV)[(139.4±55.8)% pred vs.(118.8±46.6)% pred]and in RV/total lung capacity(TLC) [(52.7±10.7)% pred vs.(48.1±10.9)% pred],all P<0.05.After bronchodilation test,there was no significant difference in FEV1,FEV3 and FVC between the two groups(all P>0.05).Patients with stable ACOS had lower value in forced expiratory flow rat (FEF25%±75%)than those with non-ACOS in baseline [FEF25%-75% % pred(26.8± 11.5) % vs.(36.1 ±17.5) % (P<0.05)],and the improvement of small airway function was significantly better in ACOS patients than in non-ACOS patients after bronchodilation test (P<0.05).Conclusions ACOS is very common in the elderly patients with COPD,stable ACOS patients have lower time vital capacity as compared with non-ACOS patients with stable COPD.But after bronchodilation test,the two groups have similar ventilation function,and the small airway function in ACOS patients improves more significantly.The ACOS patients have unique characteristics of pulmonary functions and suitable treatment may improve the prognosis.
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Objective To explore the effects of oxidative damage and selenium on the apoptosis of articular chondrocytes and the expression of selenoprotein genes.Methods C28/I2 chondrocytes were preincubated for 24 h,using sodium selenite (Na2SeO3) or t-butyl hydroperoxide (tBHP) for 24 h.The experiment was divided into six groups,including control group (C,0.00 mg/L Na2,SeO3 + 0.00 μmol/L tBHP),selenium beforehand protection group (S2,0.10 mg/L Na2SeO3),oxidative damage group (O,150.00 μmol/L tBHP),low dose selenium protection group (OS 1,0.05mg/L Na2SeO3 + 150.00 μmol/L tBHP),medium dose selenium protection group (OS2,0.10 mg/L Na2SeO3 + 150.00 μmol/L tBHP),and high dose selenium protection group (OS3,0.15 mg/L Na2SeO3 + 150.00 μmol/L tBHP).After 24 h,Hoechst 33342 staining method was used to observe apoptosis,mRNA expression of glutathione peroxidase 1 (GPX1),GPX4,deiodinase 2 (DIO2),DIO3,selenoprotein P (SEPP1),thioredoxin reductase 1 (TrxR-1) and selenoprotein W(Sel W) was detected by Real-time PCR,both experiments were done three times.Results Apoptotic rates of C,S2,O,OS1,OS2,OS3 groups [(0.78 ± 0.06)%,(13.61 ± 7.11)%,(92.27 ± 3.44)%,(71.38 ± 5.22)%,(44.31 ± 9.16)%,(72.46 ± 4.69)%] were compared between groups,the differences were statistically significant (F =120.10,P < 0.01).The apoptotic rates of O group was significantly higher than that of C group (P < 0.05);compared to O group,the apoptotic rates of OS1,OS2,OS3 groups decreased significantly (P< 0.05),OS2 group was the most obvious.DIO2,SEPP1,GPX1,GPX4,TrxR-1,Sel W mRNA levels were compared in the six groups,the differences were statistically significant (F =24.60,14.53,127.60,30.60,637.10,59.64,P < 0.01).Compared to C group (1.00 ± 0.00),the mRNA levels of GPX1 (0.10 ± 0.05),GPX4 (0.43 ± 0.09),TrxR-1 (0.11 ± 0.05) and Sel W (0.72 ± 0.15) in O groups were decreased significantly (P < 0.05);compared to 0 group,the mRNA levels of GPX1 in OS1 (0.20 ± 0.03),OS2 (0.74 ± 0.10),and OS3 (0.30 ± 0.07) were increased significantly (P < 0.05).Conclusion Down-regulated expression of selenoprotein genes are involved in the regulation process of articular cartilage apoptosis caused by oxidative stress,selenium also has a regulatory role in selenoprotein gene expression in articular chondrocytes.
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Objective To explore the effects of oxidative damage and selenium on the apoptosis of articular chondrocytes and the expression of selenoprotein genes.Methods C28/I2 chondrocytes were preincubated for 24 h,using sodium selenite (Na2SeO3) or t-butyl hydroperoxide (tBHP) for 24 h.The experiment was divided into six groups,including control group (C,0.00 mg/L Na2,SeO3 + 0.00 μmol/L tBHP),selenium beforehand protection group (S2,0.10 mg/L Na2SeO3),oxidative damage group (O,150.00 μmol/L tBHP),low dose selenium protection group (OS 1,0.05mg/L Na2SeO3 + 150.00 μmol/L tBHP),medium dose selenium protection group (OS2,0.10 mg/L Na2SeO3 + 150.00 μmol/L tBHP),and high dose selenium protection group (OS3,0.15 mg/L Na2SeO3 + 150.00 μmol/L tBHP).After 24 h,Hoechst 33342 staining method was used to observe apoptosis,mRNA expression of glutathione peroxidase 1 (GPX1),GPX4,deiodinase 2 (DIO2),DIO3,selenoprotein P (SEPP1),thioredoxin reductase 1 (TrxR-1) and selenoprotein W(Sel W) was detected by Real-time PCR,both experiments were done three times.Results Apoptotic rates of C,S2,O,OS1,OS2,OS3 groups [(0.78 ± 0.06)%,(13.61 ± 7.11)%,(92.27 ± 3.44)%,(71.38 ± 5.22)%,(44.31 ± 9.16)%,(72.46 ± 4.69)%] were compared between groups,the differences were statistically significant (F =120.10,P < 0.01).The apoptotic rates of O group was significantly higher than that of C group (P < 0.05);compared to O group,the apoptotic rates of OS1,OS2,OS3 groups decreased significantly (P< 0.05),OS2 group was the most obvious.DIO2,SEPP1,GPX1,GPX4,TrxR-1,Sel W mRNA levels were compared in the six groups,the differences were statistically significant (F =24.60,14.53,127.60,30.60,637.10,59.64,P < 0.01).Compared to C group (1.00 ± 0.00),the mRNA levels of GPX1 (0.10 ± 0.05),GPX4 (0.43 ± 0.09),TrxR-1 (0.11 ± 0.05) and Sel W (0.72 ± 0.15) in O groups were decreased significantly (P < 0.05);compared to 0 group,the mRNA levels of GPX1 in OS1 (0.20 ± 0.03),OS2 (0.74 ± 0.10),and OS3 (0.30 ± 0.07) were increased significantly (P < 0.05).Conclusion Down-regulated expression of selenoprotein genes are involved in the regulation process of articular cartilage apoptosis caused by oxidative stress,selenium also has a regulatory role in selenoprotein gene expression in articular chondrocytes.
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Objective To explore the characteristics of clinical features,diagnosis,treatment and prognosis in acute fibrinous and organizing pneumonia (AFOP) patients.Methods We described an 80-year-old woman who was diagnosed with AFOP and got better after treatment with glucocorticoids.Clinical data of 51 patients which have been published in literatures in China and abroad were retrospectively analyzed.The differences in characteristics of clinical features were compared between the elderly and non-elderly patients.Results The case reported herein,who was a 80-year-old female with latent autoimmune diabetes in adults (LADA),presented with fever,dry cough and progressive dyspnea.Chest CT scan showed bilateral multiple patchy consolidation.CT-guided needle aspiration was performed and the pathological examination finding was consistent with AFOP.The patient was treated with oral methylprednisolone and experienced a significant improvement in symptoms and imaging manifestations.But she presented with deterioration with relapsing clinical symptoms when she discontinued corticosteroid treatment by herself,and the clinical symptoms were improved by retreatment.Clinical data of 51 reported cases with AFOP including 27 males and 24 females aged 38 d to 80 years were enrolled and analyzed in the study.Patients aged 60 years and over accounted for 47.1% (24 cases).No risk or predisposing factor was found in most of cases.Autoimmune diseases were the most common combined diseases in AFOP patients.The top three symptoms were dyspnea (80.4%,41 cases),cough (64.7%,33 cases) and fever (52.9%,27 cases).The incidence of dyspnea was lower in elderly patients than in non-elderly patients [66.7% (16/24) vs.92.6% (25/27),P<0.05],and ground glass opacity in the chest image was also less in elderly patients than in non-elderly patients (P<0.05).15 patients (29.4%) got definitive diagnosis by minimally invasive procedures including percutaneous lung puncture biopsy or transbronchial lung biopsy.Corticosteroids were the main drug treatment,and 39 cases (76.5 %) received antibacterial drugs.The mortality rate of AFOP was 37.3% (15 cases).The average time from symptom onset to final diagnosis was shorter in dead cases than in recovered patients (19 days vs.40 days,P<0.05).The rate of using mechanical ventilation was higher in dead cases than in recovered patients [57.9 % (11/19) vs.9.4% (3/32),P<0.05].Conclusions There are no specific clinical and imaging features in AFOP,which is easily misdiagnosed as infectious diseases.AFOP is more common in elderly patients.Dyspnea and other symptoms can easily be ignored,and minimally invasive biopsy and pathological examination findings is helpful for diagnosis.The mortality rate of AFOP is high,and insufficient course of therapy is associated with the increased risk of AFOP relapse.Rapid progression of disease and the invasive mechanical ventilation predispose poor outcomes.
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Objective To investigate the effect of Cordyceps sinensis on renal fibrosis and its possible mechanism.Methods Thirty Sprague-Dawley rats were randomly divided into three groups:Sham operation group (Sham,n =10),5/6 subtotal uephrectomy group (SNx,n =10),and 5/6subtotal nephrectomy treated with Cordyceps sinensis group (CS,n =10).Body weights were assessed and 24-hour urine excretion was collected before and every four weeks after surgery.Rats were sacrificed at 12 weeks after surgery.Blood samples were taken for biochemical study,and kidney tissues were used for HE and Masson stains to assess histological changes.Immunohistochemical staining was used to detect the expression of transforming growth factor β1 (TGF-β1) and its receptors of type Ⅰ (TβR Ⅰ),type Ⅱ (TβR Ⅱ).Immunofluorescence was used to detect E-cadherin and α-SMA.The relative protein level of TGF-β1,TβR Ⅰ,TβR Ⅱ,p-Smad2/3,Smad7,E-cadherin,α-SMA were examined by Western blotting.Results CS group had higher body weights and lower urinary protein,BUN and Scr level compared with SNx group.Glomerulosclerosis index and tubulointerstitial injury score were significantly reduced in CS group compared with those in SNx group (all P < 0.05).The protein expressions of TGF-β1,TβR Ⅰ,TβR Ⅱ,p-Smad2/3 were decreased in CS group compared with those in SNx group (all P < 0.05).CS treatment up-regulated the expression of E-cadherin,Smad7 and down-regulated the expression of α-SMA compared with that in SNx group (all P < 0.05).Conclusion Cordyceps sinensis has inhibitory effect on renal fibrosis in 5/6 subtotal nephrectomy rat model,which might be related with the suppression of TGF-β 1 signal pathway.
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<p><b>OBJECTIVE</b>To identify risk factors for gestational diabetes mellitus (GDM) in women and to study the contribution of family history of type-2 diabetes to the risk for DDM.</p><p><b>METHODS</b>A case-control study was performed in 85 women with GDM and 177 cases controls. Univariate and multivariate logistic regression and log-linear model were used to identify risk factors of GDM.</p><p><b>RESULTS</b>Multivariate logistic regression showed that obesity before pregnancy, family history of type-2 diabetes, birth weight of pregnant women, age, fasting plasma level of triglyceride, physical inactivity, etc. all were risk factors for GDM. Analysis with log-linear model showed that parents' (father's or mother's) history of type-2 diabetes associated with GDM, with P-values of 0.012 and 0.017, respectively. Prevalence of diabetes in the mothers of proband with GDM was 9.41%, as compared with that in the fathers of proband with GDM 8.24%, with no statistical significance.</p><p><b>CONCLUSIONS</b>Obesity before gestation, family history of type-2 diabetes, low birth weight of mother, age, increased fasting plasma level of triglyceride, as well as parents' history of type-2 diabetes, all were risk factors for GDM. Physical exercise was found to be a protective factor for GDM. Mother's history of type-2 diabetes did not differ from father's in contributing to the onset of GDM in their offspring.</p>
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Adulto , Feminino , Humanos , Gravidez , Peso ao Nascer , Diabetes Mellitus , Genética , Diabetes Gestacional , Exercício Físico , Modelos Logísticos , Obesidade , Fatores de Risco , Triglicerídeos , SangueRESUMO
Objective To evaluate the feasibility of intra-utero fetal lamb surgical repair. Methods Six twin lambs underwent surgery intra-utero at 112 days of gestation (term 140~160 days). After maternal laparotomy and Hysterotomy, fetal lamb′s toe was excised or its cleft lip was repaired in one of twin. Results At 30 to 32 days post operation,five lambs were spontamcously delivered and the other was cesarean delivery to full term gestation. Fetal wounds healed without inflammation and scar formation. Conclusions The methods of fetal lamb intro utero surgical repair is feasible.
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Objective To analyze the effects of fetal anoxia, respiratory and metabolic acidosis on the activity of antioxidation in fetal distress Methods Blood samples were taken from umbilical artery in 386 neonates for blood gas analysis and detection of the concentration of superoxide dismutase (SOD) Normal situation, anoxia, acidosis, respiratory acidosis, metabolic acidosis and mixed acidosis were diagnosed in all neonates according to the results of blood gas values, and the neonate asphyxia was diagnosed according to the Apgar scores (one minute) The effect of anoxia and acidosis to SOD were analyzed with multiple factor analysis of variation Results (1) Among the all 386 cases, 317 were normal, 31 with anoxia, 17 with acidosis, and 21 with both anoxia and acidosis Among the total cases of acidosis, 8 respiratory, 21 metabolic, and 9 mixed acidosis (2) The plasma levels of SOD of umbilical artery blood in anoxia, acidosis, both anoxia and acidosis, and normal sitution were (118 5?7 1) mmol/L, (122 0?11 4) mmol/L,(140 0?7 0)mmol/L, and (98 5? 2 6) mmol/L,respectively The results of unvariate analysis of variance showed that anoxia: F =4 999 ( P 0 05) (3) The plasma levels of SOD with respiratory acidosis, metabolic acidosis and mixed acidosis were (127 3?18 4) mmol/L, (126 0?8 1) mmol/L, (150 0?10 4) mmol/L The results of univariate analysis of variance showed that respiratory acidosis: F =4 404 ( P 0 05) Conclusion The superoxidation and antioxidation can be effected by factors like anoxia and acidosis, respiratory acidosis and metabolic acidosis However, the mechanisms of these effects are different. There is additive, but not synergistic effects among them