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Objective:To evaluate the effect of metformin preconditioning on adenosine monophosphate-activated protein kinase(AMPK)/PTEN-induced putative protein kinase(PINK1) signaling pathway during ischemia-reperfusion (I/R) injury in diabetic rats.Methods:Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 6 weeks, weighing 120-160 g, were divided into 3 groups ( n=12 each) by the random number table method: diabetic sham operation group (DS group), diabetic myocardial I/R group (DI/R group) and diabetic myocardial I/R+ metformin preconditioning group(DI/R+ Met group). After 4 weeks of feeding a high-fat and high-glucose diet, the model of type 2 diabetes mellitus was induced by a single intraperitoneal injection of 1% streptozotocin 40 mg/kg. The myocardial I/R injury was induced by blocking the anterior descending branch of the left coronary artery for 30 min followed by 120-min reperfusion in anesthetized animals. In DI/R+ Met group, metformin 200 mg/kg was given by intragastric gavage once a day within 1 week before myocardial ischemia. Blood samples from the femoral vein were collected at 120 min of reperfusion for determination of the serum creatine kinase isoenzymes (CK-MB) and cardiac troponin I (cTnI) concentrations by enzyme-linked immunosorbent assay. Then the rats were sacrificed and myocardial tissues were obtained for examination of the pathological changes(by HE staining) and for determination of the percentage of myocardial infarct size (by the double staining of Ewan blue and TTC) and expression of myocardial autophagy-related protein Beclin-1, PTEN-induced putative kinase 1 (PINK1), phosphorylated 5′-adenosine monophosphate-activating protein kinase (p-AMPK), and ratio of microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ (LC3Ⅱ/Ⅰ) (by Western blot). Results:Compared with DS group, the percentage of myocardial infarct size and serum CK-MB and cTnI concentrations were significantly increased, the expression of Beclin-1, p-AMPK and PINK1 in myocardial tissues was up-regulated, the ratio of LC3II/I was increased( P<0.05), and the pathological changes were aggravated in DI/R group and DI/R+ Met group. Compared with DI/R group, the percentage of myocardial infarct size and serum CK-MB and cTnI concentrations were significantly decreased, the expression of Beclin-1, p-AMPK and PINK1 in myocardial tissues was up-regulated, the ratio of LC3Ⅱ/Ⅰ was increased ( P<0.05), and the pathological changes were significantly reduced in DI/R+ Met group. Conclusions:The mechanism by which metformin preconditioning reduces myocardial I/R injury is related to activation of AMPK/PINK1 signaling pathway and up-regulation of mitochondrial autophagy in diabetic rats.
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Objective:To study the effect of diabetes mellitus (DM) on sepsis in patients with pyogenic liver abscess (PLA).Methods:The clinical data of 116 patients with PLA treated in the Affiliated Hospital of Jiangnan University from January 2021 to May 2022 were retrospectively analyzed, including 64 males and 52 females, aged (62.3±12.6) years old. Patients were divided into DM group ( n=56) and non-DM group ( n=60), which were also divided into the sepsis group ( n=29) and the non-sepsis group ( n=87). The clinical features were compared among the groups, the risk factors of PLA complicated with sepsis were analyzed by multivariate logistic regression. Mediation model was used to analyze how DM affects the development of sepsis. Results:Compared with the non-DM group, patients in DM group had higher incidences of hypertension and acute physiology and chronic health evaluation II, a higher proportion of blood neutrophil count, a higher serum levels of triglyceride, urea nitrogen, fasting blood glucose and glycated hemoglobin at admission. The DM group also higher incidences of hypoproteinemia, pleural effusion, and sepsis, with longer hospital stay and higher hospitalization cost (all P<0.05). The levels of hemoglobin, albumin and hematocrit were lower in DM group (all P<0.05). Multivariate logistic regression analysis showed that comorbidity of DM ( OR=3.431, 95% CI: 1.245-9.455) and abscess with a larger diameter ( OR=1.664, 95% CI: 1.258-2.220) were associated with a higher risk of developing sepsis (all P<0.05). Mediation model showed that neutrophil count and triglyceride were the mediating variables of sepsis in patients with PLA. Conclusion:Comorbidity of diabetes is an independent risk factor of developing sepsis in patients with pyogenic liver abscess. Diabetes may induce sepsis by affecting the neutrophils and triglyceride.
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Cerebral small vessel disease (CSVD) is an important cause of ischemic stroke and vascular dementia, which brings heavy burden to families and society. The prevention and treatment of CSVD has always been a research hotspot, but its pathogenesis is still not completely clear. This article reviews the pathogenesis of CSVD, including chronic cerebral hypoperfusion, blood-brain barrier dysfunction, vascular endothelial dysfunction, interstitial fluid reflux disorder, inflammatory response, and genetic factors, in order to provide more sufficient theoretical basis for early intervention and treatment of CSVD.
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Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.
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Background@#Currently available guidelines contain conflicting recommendations on the management of blood pressure (BP) in patients with diabetes mellitus (DM). Therefore, it is necessary to appraise the guidelines and summarize the agreements and differences among recommendations. @*Methods@#Four databases and the websites of guideline organizations were searched for guidelines regarding BP targets and thresholds for pharmacologic therapy in DM patients, and the included guidelines were appraised with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. @*Results@#In 6,498 records identified, 20 guidelines met our inclusion criteria with 64.0% AGREE II scores (interquartile range, 48.5% to 72.0%). The scores of the European and American guidelines were superior to those of the Asian guidelines (both adjusted P140 mm Hg (10 guidelines, 50%) and diastolic BP thresholds >90 mm Hg (nine guidelines, 45%). The tiny minority of the guidelines provided the relevant recommendations regarding the lower limit of official BP targets and the ambulatory BP monitoring (ABPM)/home BP monitoring (HBPM) targets and thresholds in DM patients. @*Conclusion@#The lower official BP targets (<130/80 mm Hg) in patients with DM are advocated by most of the guidelines, but they contain conflicting recommendations on the official BP thresholds. Moreover, the gaps regarding the lower limit of official BP targets and the ABPM/HBPM targets and thresholds need to be considered by future study.
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Objective:To evaluate the effect of activating adenosine A2B receptors on autophagy during myocardial ischemia-reperfusion (I/R) and the role of phosphatidylinositol 3-kinase/serine/threonine protein kinase (PI3K/Akt) signaling pathway in rats.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, weighing 220-280 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (group Sham), myocardial I/R group (group I/R), adenosine A2B receptor agonist BAY 60-6583 group (group BAY) and BAY 60-6583+ PI3K inhibitor LY 294002 group (group BAY+ LY). Myocardial I/R was induced by occlusion of the anterior descending branch of the left coronary artery for 30 min followed by 120-min reperfusion.BAY 60-6583 1 mg/kg was intraperitoneally injected at 5 min before reperfusion in group BAY.BAY 60-6583 1 mg/kg was intraperitoneally injected at 5 min before reperfusion and LY 294002 10 mg/kg was intraperitoneally injected at 10 min before reperfusion in group BAY+ LY.Blood samples were obtained at the end of reperfusion for determination of concentrations of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in serum (by enzyme-linked immunosorbent assay). The animals were sacrificed, and myocardial tissues were obtained for measurement of the percentage of myocardial infarct size (by Evan Blue and TTC double-staining) and for determination of the expression of microtubule-associated protein 1 light chain 3 (LC3Ⅰ), LC3Ⅱ, Beclin-1 and phosphorylated Akt (p-Akt) (by Western blot). The ratio of LC3Ⅱ/LC3Ⅰ was calculated. Results:Compared with group Sham, the serum LDH and CK-MB concentrations and percentage of myocardial infarct size were significantly increased, the expression of p-Akt was down-regulated, the expression of Beclin-1 and LC3Ⅱ was up-regulated, and the ratio of LC3Ⅱ/LC3Ⅰ was increased in group I/R ( P<0.05). Compared with group I/R, the concentrations of serum LDH, CK-MB and percentage of myocardial infarct size were significantly decreased, the expression of p-Akt was up-regulated, the expression of Beclin-1 and LC3Ⅱ was down-regulated, and the ratio of LC3Ⅱ/LC3Ⅰ was decreased in the group BAY ( P<0.05), and no significant change was found in the parameters mentioned above in group BAY+ LY ( P>0.05). Compared with group BAY, the concentrations of serum LDH, CK-MB and percentage of myocardial infarct size were significantly increased, the expression of p-Akt was down-regulated, the expression of Beclin-1 and LC3Ⅱ was up-regulated and the ratio of LC3Ⅱ/LC3Ⅰ was increased in group BAY+ LY ( P<0.05). Conclusion:Activating adenosine A2B receptors can decrease autophagy of myocardial cells during myocardial I/R injury, and the mechanism may be related to activating PI3K/Akt signaling pathway in rats.
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Background@#Currently available guidelines contain conflicting recommendations on the management of blood pressure (BP) in patients with diabetes mellitus (DM). Therefore, it is necessary to appraise the guidelines and summarize the agreements and differences among recommendations. @*Methods@#Four databases and the websites of guideline organizations were searched for guidelines regarding BP targets and thresholds for pharmacologic therapy in DM patients, and the included guidelines were appraised with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. @*Results@#In 6,498 records identified, 20 guidelines met our inclusion criteria with 64.0% AGREE II scores (interquartile range, 48.5% to 72.0%). The scores of the European and American guidelines were superior to those of the Asian guidelines (both adjusted P140 mm Hg (10 guidelines, 50%) and diastolic BP thresholds >90 mm Hg (nine guidelines, 45%). The tiny minority of the guidelines provided the relevant recommendations regarding the lower limit of official BP targets and the ambulatory BP monitoring (ABPM)/home BP monitoring (HBPM) targets and thresholds in DM patients. @*Conclusion@#The lower official BP targets (<130/80 mm Hg) in patients with DM are advocated by most of the guidelines, but they contain conflicting recommendations on the official BP thresholds. Moreover, the gaps regarding the lower limit of official BP targets and the ABPM/HBPM targets and thresholds need to be considered by future study.
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Objective:To evaluate the role of endoplasmic reticulum stress in myocardial ischemia-reperfusion (I/R) injury and the relationship with autophagy in rats.Methods:Thirty-six healthy adult male Sprague-Dawley rats, weighing 250-300 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (Sham group), myocardial I/R group (IR group), and endoplasmic reticulum stress inhibitor 4-PBA group (PBA group). Myocardial I/R was produced by occlusion of left anterior descending branch of coronary artery for 30 min followed by reperfusion for 120 min.Sham group only underwent thoracotomy without block of left anterior descending branch of coronary artery.Endoplasmic reticulum stress inhibitor 4-PBA 500 mg·kg -1·d -1 was given intragastrically for 3 consecutive days before the I/R model was developed in PBA group, while the equal volume of normal saline was given instead in Sham and IR groups.The blood samples from the iliac vein were collected at 120 min of reperfusion for determination of the plasma creatine kinase isoenzymes (CK-MB) and cardiac troponin I (cTnI) concentrations (by enzyme-linked immunosorbent assay). The rats were then sacrificed, and myocardial tissues were removed for detection of myocardial glucose-regulated protein 78 (GRP78) and microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) and autophagy-related protein 5 (ATG5) expression (by Western blot). Result:Compared with Sham group, the concentrations of CK-MB and cTnI in plasma were significantly increased in IR and PBA groups, the expression of GRP78, ATG5 and LC3Ⅱ was up-regulated, and the pathological damage was aggravated in IR group ( P<0.05). Compared with IR group, the concentrations of CK-MB and cTnI in plasma were significantly decreased, the expression of GRP78, ATG5 and LC3Ⅱ was down-regulated ( P<0.05), and the pathological changes were significantly attenuated in PBA group. Conclusion:Endoplasmic reticulum stress is involved in the process of myocardial I/R injury, and the mechanism may be related to promotion of autophagy in rats.
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Objective:To construct and identify the lentiviral vector of adenosine RNAi-adenosine A2a receptor (A2aR) in rats.Methods:Three pairs of short hairpin RNA(shRNA)-A2aR sequences (shRNA-A2aR 1, shRNA-A2aR 2, shRNA-A2aR 3) were designed, and three pairs of double-stranded shRNA oligos were respectively inserted into the shRNA virus vector to gain three kinds of shRNA lentiviral recombinant plasmid.The recombinant plasmid, packaging vector, and shuttle vector were co-transfected into 293T cells to obtain virus liquid.The experiment was performed in two parts.Part Ⅰ The rat primary cardiomyocytes were divided into 3 groups ( n= 6 each) by a random number table method: vehicle group (V group), shRNA-A2aR 1 group and shRNA-A2aR 3 group.Each group was transfected with virus solution of MOI 10 for 48 h. The expression of A2aR was detected by Western blot to select the most efficient lentivirus vector.Part Ⅱ The cardiomyocytes were randomly divided into 6 groups ( n=36 each): vehicle group (V group), MOI5 group, MOI10 group, MOI15 group and MOI20 group.Each group was transfected with the corresponding MOI virus liquid (the most effective lentivirus vector). At 24, 48, and 72 h of transfection, the cell viability and cell death were observed with a fluorescent microscope, and the A2aR expression was detected by Western blot to determine the interference efficiency. Results:Part Ⅰ Two types of shRNA-A2aR lentiviral vectors (shRNA-A2aR 1, 3) were successfully constructed, among which shRNA-A2aR 3 virus solution with a titer of 3.5×10 8 TU/ml had the best effect.Compared with group V and group shRNA-A2aR 1, the expression of A2aR in cardiomyocytes was significantly down-regulated ( P<0.01), and the interference efficiency of shRNA-A2aR 3 was 73% in shRNA-A2aR 3 group.Part Ⅱ shRNA-A2aR 3 was selected to screen out the transfection plan.The cell survival rate in each group was more than 85% at 24 h of transfection, the cell survival rate was more than 80% at 48 h of transfection in MOI5 and MOI10 groups; the cell survival rate in each group was less than 70% at 72 h of transfection.Under an inverted fluorescent microscope, a slightly lower fluorescence density was found in MOI5 group, the fluorescent density was higher and the cell condition was better at 48 h of transfection in MOI10 group and at 24 h of transfection in MOI20 group, and the cardiomyocyte viability was significantly decreased, and dead cells were increased at 72 h of transfection in each group.The results of Western blot showed that the interference efficiency at 48 h of transfection in MOI10 group, 48 h in MOI15 group, 24 and 48 h in MOI20 group was all > 70%. Conclusion:MOI of 10, transfection for 48 h or MOI of 20, transfection for 24 h is the optimal transfection protocol.
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Pretargeting is an imaging strategy different from the imaging of traditional radiolabeled antibody,in which the antibody and radioisotope are administered in turn and then combined by coupling system within the body.Due to the high specificity and affinity between the coupling systems,the radioisotope is localized to the target in vivo,and then the radioactive labeling is achieved for imaging.Nuclear imaging using pretargeting methods can decrease the circulation duration of the radioisotope so as to reduce the uptake of the radioactivity in normal tissues,and facilitate the use of short-lived radioisotopes.This article provides a bird's-eye view of 4 main strategies:biotin-streptavidin (SA) system,bispecific antibodies (BsAb) system,complementary oligonucleotides sequence,and bioorthogonal click chemistry system.
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Objective:To compare the efficacy and safety between biphasic insulin aspart 30 injection and insulin glargine combined with repaglinide in the newly diagnosed type 2 diabetes in the elderly patients.Methods:A total of 60 elderly patients with type 2 diabetes who were newly diagnosed in the First Hospital Affiliated to Hebei Medical University were selected as study objects, and they were divided into group A and group B according to the random digital table method, with 30 cases in each group.Group A was treated with aspart 30 injection, and group B was treated with glargine combined with repaglinide tablets for 2 weeks.The BMI, FPG, 2hPG, HbA1c, 1, 5-AG were detected after treatment for 1 and 2 weeks, and the FCP, PCP were detected before and after treatment.Results:The FPG and 2hPG of the two groups decreased significantly after treatment for 1 week and 2 weeks, and the blood glucose of group A decreased significantly after 1 week of treatment compared with group B, and the difference was statistically significant(FPG t=2.58, 2hPG t=2.46, all P<0.05).1, 5-AG increased significantly at 1 week and 2 weeks after treatment.At 1 weekafter treatment, the increase was more significant in group A than group B, and the difference was statistically significant( t=8.93, P<0.05). After 2 weeks of treatment, the levels of FCP and 2hCP of both two groups were increased compared with before treatment, and the differences were statistically significant(FCP t=3.72, 3.45, 2hCP t=4.14, 3.54, all P<0.05). The time of blood glucose reaching the standard in group A was(10.35±4.10)d, which was shorter than that in group B [(12.38±4.22)d], and the difference was statistically significant( t=8.32, P<0.05). The dosage of insulin required by the patients in group A was(45.14±8.42) U·kg -1·d -1, which was higher than that in group B [(24.88±7.36)U·kg -1·d -1], and the difference was statistically significant( t=9.06, P<0.01). Conclusion:Both BIAsp30 and IG combined with repaglinide can effectively reduce FPG and 2hPG of patients with type 2 diabetes newly diagnosed in the elderly.Besides, the occurrence of hypoglycemia in the glargine group is lighter than that in the BIAsp30 group, and the time of blood glucose reaching the standard is longer than that in the aspart 30 injection group.Monitoring 1, 5-AG can be used as a reference for timely adjustment of hypoglycemia programs.
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Pretargeting is an imaging strategy different from the imaging of traditional radiolabeled antibody, in which the antibody and radioisotope are administered in turn and then combined by coupling system within the body. Due to the high specificity and affinity between the coupling systems, the radioisotope is localized to the target in vivo, and then the radioactive labeling is achieved for imaging. Nuclear imaging using pretargeting methods can decrease the circulation duration of the radioisotope so as to reduce the uptake of the radioactivity in normal tissues, and facilitate the use of short-lived radioisotopes. This article provides a bird′s-eye view of 4 main strategies: biotin-streptavidin (SA) system, bispecific antibodies (BsAb) system, complementary oligonucleotides sequence, and bioorthogonal click chemistry system.
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Objective@#To explore the effect of a home-based, nurse-led health program on quality of life and family function for postoperative patients with early-stage breast cancer.@*Methods@#A total of 140 early-stage breast cancer patients, from Union Hospital of Tongji Medical College Huazhong University of Science and Technology between August 2016 and August 2017, were divided into intervention group and control group by random digits table method. Patients in control group only received conventional nursing education. Patients in intervention group received an individual home-based, nurse-led health program, in addition to conventional nursing education. After six months of intervention, the family function was assessed by using Familiy Adaptability and Cohesion Scale, quality of life was assessed by using Functional Assessment of Cancer Therapy for Breast Cancer.@*Results@#In this study,13 patients were excluded in 140 patients, 65 cases in intervention group and 62 cases in control group. After six months of intervention, cohesion and adaptability scores in intervention group were (71.52±8.76), (52.09±5.97), respectively. Cohesion and adaptability scores in control group were (65.90±7.72), (46.59±6.98), the difference was statistically significant (t=3.838, 4.786, P<0.05). After three and six months of intervention, social/familial and total scores in intervention group were (16.75±3.28), (17.90±4.05) and (90.39±9.07), (96.38±8.86), respectively. While cohesion and adaptability scores in control group were (15.43±2.51), (15.02±4.02) and (85.93±8.57), (86.19±9.81), the scores mentioned above in intervention group were markedly higher than in control group, the difference was statistically significant (t=2.531-6.151, 4.786, P<0.05 or 0.01). In addition, after six months of intervention, emotional (17.60±3.32), functional (14.69±3.85), breast cancer (25.32±4.70) scores were also higher than in control group (15.37±3.28), (12.89±4.00), (22.48±3.94), the difference was statistically significant (t=3.805, 2.574,3.681, P<0.01 or 0.05).@*Conclusions@#A home-based, nurse-led health promotion program improves the quality of life and family function in postoperative patients with early-stage breast cancer.
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Objective To explore the effect of a home-based, nurse-led health program on quality of life and family function for postoperative patients with early-stage breast cancer. Methods A total of 140 early-stage breast cancer patients, from Union Hospital of Tongji Medical College Huazhong University of Science and Technology between August 2016 and August 2017, were divided into intervention group and control group by random digits table method. Patients in control group only received conventional nursing education. Patients in intervention group received an individual home-based, nurse-led health program, in addition to conventional nursing education. After six months of intervention, the family function was assessed by using Familiy Adaptability and Cohesion Scale, quality of life was assessed by using Functional Assessment of Cancer Therapy for Breast Cancer. Results In this study,13 patients were excluded in 140 patients, 65 cases in intervention group and 62 cases in control group. After six months of intervention, cohesion and adaptability scores in intervention group were (71.52±8.76), (52.09±5.97), respectively. Cohesion and adaptability scores in control group were (65.90± 7.72), (46.59±6.98), the difference was statistically significant (t=3.838, 4.786, P<0.05). After three and six months of intervention, social/familial and total scores in intervention group were (16.75±3.28), (17.90± 4.05) and (90.39 ± 9.07), (96.38 ± 8.86), respectively. While cohesion and adaptability scores in control group were (15.43±2.51), (15.02±4.02) and (85.93±8.57), (86.19±9.81), the scores mentioned above in intervention group were markedly higher than in control group, the difference was statistically significant (t=2.531-6.151, 4.786, P<0.05 or 0.01). In addition, after six months of intervention, emotional (17.60± 3.32), functional (14.69±3.85), breast cancer (25.32±4.70) scores were also higher than in control group (15.37 ± 3.28), (12.89 ± 4.00), (22.48 ± 3.94), the difference was statistically significant (t=3.805, 2.574, 3.681, P<0.01 or 0.05). Conclusions A home-based, nurse-led health promotion program improves the quality of life and family function in postoperative patients with early-stage breast cancer.
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Objective This study was to observe the meibomian gland scores,the miss rate of meibomian,break-up time of tear film (BUT) changes after long-term wearing orthokeratolog,and to evaluate orthokeratolog impact on meibomian gland function and the stability of the tear film.Methods A prospective case-controlled study was performed.Fifty patients 98 eyes with myopia were enrolled.According to the myopia correction mode,the patients were divided into control group (24 cases) and experimental group (overnight orthokeratolog treatment) group (26 cases).All subjects were underwent the examinations sequentially as follows:evaluation of ocular surface disease symptoms using the Ocular Surface Disease Index (OSDI),lid margin and ocular surface examination by slit lamp microscrope,infrared meibomian photography and BUT.All measurements were repeated at 3 months,6 months,24-months follow-up visit.All patients signed informed consent before examination.Results After wearing orthok-contact lens for 24 months,the meibomian gland score was 4.54±1.10 and 2.29±0.75 in the experimental group and control group,respectively,the difference was statistically significant (P＜0.05).The BUT was (6.35 ± 1.52) s 24 months after wearing orthokeratolog,which was less than (9.38 ± 1.88) s in the control group,the difference was statistically significant (P＜ 0.05).The miss rate of meibomian gland was 24.39 ± 5.54 and 22.81 ± 5.23 in the experimental group and control group,respectively.There was no statistically significant difference among the the miss rate of meibomian gland between groups and within groups (all at P＞0.05).Conclusions Long-term wearing orthokeratolog has negetive effects on meibomian gland function and the stability of the tear film.
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Objective To explore the changes of urine albumin-creatinine ratio ( ACR) and urina-ry podocalyxin (PCX) and the relationship of score of Montreal cognitive assessment (MoCA) with urine ACR and PCX in patients with type 2 diabetic mild cognitive impairment. Methods Sixty patients with type 2 diabetes mellitus were used as the control group, and 60 patients with type 2 diabetic mild cognitive impairment as the mild cognitive impairment ( MCI) group. The sex, age, and course of disease and years of education of patients were recorded, the fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), sys-tolic blood pressure ( SBP) , diastolic blood pressure ( DBP) , triglyceride ( TG) , total cholesterol ( TC) , low density lipoprotein ( LDL) , high-density lipoprotein ( HDL) , and urine ACR and PCX were measured, and the score of MoCA was assessed. Results The patients with type 2 diabetic nephropathy in the MCI group were significantly more than the control group (χ2 =73. 818,P<0. 01). The score of MoCA of the MCI group was significantly lower than the control group (P<0. 01), while urine ACR and PCX were high-er than the control group (P<0. 01). The score of MoCA was inversely associated with the urine ACR (r=-0. 868,P<0. 01) and PCX (r= -0. 785,P<0. 01), and those were the independent risk factors for the score of MoCA ( P<0. 01 ) . Conclusions The urine ACR and PCX were closely related to the cognitive function of type 2 diabetes mellitus, which can be used as the screening indexes of type 2 diabetic mild cog-nitive impairment.
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Objective To investigate the change of urinary podocalyxin(PCX) and vascular endothelial growth factor (VEGF) levels and its association with the oxidative stress in the patients with type 2 diabetes mellitus(T2DM ) complicating dif‐ferent degrees of diabetic nephropathy .Methods Totally 186 patients with T2DM were divided into the pure T2DM (SDM ,62 ca‐ses) ,trace amount group(NA group ,60 cases) and massive amount group(MA group ,64 cases) according to the 24 h urinary albu‐min excretion rate(UAER) .60 cases of normal 24 h UAER were taken as the control group(NC group) .The levels of PCX ,VEGF , superoxide dismutase (SOD) ,malondialdehyde(MDA) and glutathione peroxidase (GSH‐px)were determined .Results Compared with other three groups ,the level of VEGF ,PCX and MDA in the MA group were highest(P<0 .01) ,while the levels of SOD and GSH‐px were lowest(P<0 .01 ,P<0 .05) .VEGF ,UAER ,HbA1c were the independent risk factors for urinary PCX .Conclusion In patients with diabetic nephropathy ,urinary PCX and VEGF are correlated with the oxidative stress ,while the oxidative stress is closely correlated with glomerular podocyte injury .
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Objective To explore the clinical significance of expression of soluble mesothelin relatedprotein(SMRP)and carbo-hydrate antigen (CA125)in the serum and tumor tissues of the patients with ovarian cancer.Methods The preoperative and post-operative levels of SMRP and CA125 in serum and ovarian cancer tissues were detected in 82 patients with ovarian cancer (group A),76 cases of benign ovarian tumor (group B)and 53 healthy women (group C)by using ELISA and the immunohistochemical method respectively.Serum levels of SMRP and CA125 in the ovarian cancer patients were measured after one year by ELISA.The correlation among the various statistical indexes was analyzed.Results The positive expression rates of SMRP and CA125 in the group A were significantly higher than those in the group B(P <0.05);compared with the group B and C,the preoperative serum level of CA125 and SMRP in the group A was significantly increased (P <0.001);the preoperative serum CA 125 level in the group B was higher than that in the group C;compared with the stage Ⅰ and Ⅱ,the serum CA125 and SMRP in the stage Ⅲ and Ⅳ of o-varian cancer were significantly increased(P <0.05 );compared with before operation,the postoperative SMRP and CA125 levels were significantly decreased(P <0.05).After 1 year of discharge from hospital,compared with the basically stable patients,serum CA125 and SMRP levels in the patients with ovarian cancer recurrence were significantly increased(P <0.05).The sensitivity and specificity for diagnosing ovarian cancer,any single detection was inferior to the combination detection of CA125 and SMRP.Conclu-sion The combination detection of CA125 and SMRP has an important value for increasing the sensitivity and specificity of ovarian cancer diagnosis,early diagnosis,illness condition monitoring and effect evaluation.
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Objective To construct a eukaryotic expression system of IFN-λ,examine the expression of IFN-λand evaluate its bio-functions including anti-proliferation and anti-viral activity.Methods The genes of human IFN-λ1 /2 (hIFN-λ1 /2)were cloned from the mRNA of poly I∶C treated HuH-7 cells.The PCR product was examined with DNA sequencing.The genes of IFN-λ1 /2 were sub-cloned into pcDNA3 vector.The correct insertion of the gene IFN-λ1 /2 was identified with enzyme digestion.The constructed pcDNA3-IFN-λ1 /2 plasmids were transfected into COS-7 cells and IFN-λ1 /2 protein was checked in the supernatant and lysis of transfected cells using Western blotting analysis.The human esophageal carcinoma YES5 and T.Tn cells were treated with the IFN-λ1 /2 from the transfected cells and the proliferation of carcinoma cells were measured with CCK-8 kit.In the treated carcinoma cells,the apoptosis and antivirus related molecules such as caspase-3,ISG15 and MxA was analyzed with Western blotting or Quantitative real time PCR.Results The sequence of hIFN-λ1 /2 fragment matched that of the gene bank and the gene of the cytokines was inserted into pcDNA3 vector correctly.With Western blotting analysis,IFN-λ1 /2 protein was detected in the pcDNA3-IFN-λ1 /2 transfected COS-7 cells.The IFN-λ1 /2 from the transfected COS-7 cells inhibited the growth of YES5 and T.Tn cells, activated apoptosis related caspase-3,and up-regulated the anti-virus gene expression of ISG15 and MxA.Conclusion COS-7 cells can express IFN-λ1 /2 after transfection with pcDNA3-IFN-λ1 /2,suggesting that eukaryotic expression system of IFN-λis established.IFN-λ1 /2 from the system can perform bio-functions,such as proliferation inhibition,apoptosis induction and anti-viral gene up-regulation,which indicates that the system can contribute to further investigations of IFN-λbio-activity and its clinical application.
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Objective To investigate the efficacy and safety of the combined therapy of cyclophosphamide and thalidomide in the treatment of refractory Crohn's disease (CD).Methods This study was a prospective and open study.A total of 15 patients with refractory CD were enrolled.All patients received intravenous cyclophosphamide 200 mg every other day for two weeks,then followed by intravenous 400 mg once a week until the cumulative dose reached 6 to 8 g.when the cyclophosphamide treatment started,at the same time thalidomide was taken 25 to 75 mg every night according to the tolerance of patients.Before the treatment,two weeks' after the treatment and at the time when the cumulative dose of cyclophosphamide reached 6 to 8 g,Crohn's disease activity index (CDAI),hemoglobin (Hb),white blood cell (WBC) count,erythrocyte sedimentation rate (ESR) and high-sensitivity C-reactive protein (hs-CRP) were recorded.Endoscopy examination was conducted before the treatment and at the time when the cumulative dose of cyclophosphamide reached 6 to 8 g.The condition of mucosa healing was observed and scored by simple endoscopic score for crohn's disease (SES-CD).Adverse effects of all patients were monitored.Paired t test was performed for statistical analysis.Results Before the treatment,the CDAI of 15 patients with refractory CD was 235.87±59.87,two weeks after the treatment the CDAI declined to 135.33 ± 29.23,and the difference was statistically significant (t=7.50,P＜0.01).Before the treatment,ESR and hs-CRP was (42.13±22.80) mm/1 h and (13.73± 2.18) mg/L.Two weeks after treatment they declined to (23.80±16.63) mm/1 h and (5.77±4.77) mg/L,and the differences were statistically significant (t=2.43 and 6.17,both P＜0.05).After two-week treatment,10 patients achieved clinical remission.After the cumulative dose of cyclophosphamide reached 6 to 8 g combined therapy,CDAI of patients was 108.14 ± 47.10,which decreased significantly compared with that before treatment (t=6.30,P＜0.01).ESR,hs-CRP and WBC count was (19.35± 19.18) mm/1 h,(6.16± 5.02) mg/L and (6.28 ± 3.42) × 109/L,respectively,which decreased compared with those before treatment,and the differences were statistically significant (t=5.90,5.40 and 3.71,all P＜0.01).Twelve patients achieved clinical remission.And the lesions of 12 patients improved under endoscope,furthermore,the mucosa of four patients healed.Before the treatment,SES-CD was 9.14 ± 5.39,which declined to 5.07 ± 4.58 after the treatment,and the difference was statistically significant (t =3.14,P ＜ 0.01).During the treatment,five patients had adverse effects.Alanine aminotransferases (ALT) increased in three patients,WBC count decreased in one patient and one patient got a severe urinary infection.Conclusions Patients with refractory CD could achieve clinical remission,mucosa healing under endoscopy and better efficacy with the combined therapy of cyclophosphamide and thalidomide.However,adverse effects should be monitored during the treatment.