10.3969/j.issn.2095-4344.2013.25.015

Objective To prepare and evaluate the biocompatibility of polycarbonate coated with low molecular weight heparin (LMWH) and partial oxidation sodium alginate(OSA).Methods Coating material was prepared by means of chemical graft-modification and the feature of the material was determined with infrared spectrum and the stablity of the coating in fluid was examined.Biocompatibility was evaluated by contact angle and in-vitro tests including protein adhesion,platelet adhesion and caugulation.Results LMWH or OSA was tightly combined with polycarbonate.After being coated,the contact angle,albumin and fibrinogen adhering to materials were decrease (P＜0.05).The anticoagulant activity was notably promoted by coating.Compared with LMWH coated material,the contact angle,albumin and fibrinogen adhering were decreased significantly,but the improvement of anticaugulation was limited(P＜0.05).Conclusion Chemical graft-modification LMWH or OSA can be applied to polycarbonate.The biocompatibility of the coated materials was significantly promoted.

Objective:To explore the influence of hypercholesterolemia on the risk of chronic kidney disease (CKD) in the middle-aged and elderly population and the gender differences.Methods:The data came from the "Epidemiological Survey of Chronic Kidney Disease among Adults in Urban Communities in Henan Province". The subjects came from 20 communities in Henan Province, aged ≥45 years old. Groups were based on the quartile of total blood cholesterol level and gender. Multivariate logistic regression and Cochran-Armitage trend test were used to analyze the effect of hypercholesterolemia on the risk of CKD and its gender differences.Results:A total of 4 779 subjects were enrolled into the study, with 1 934 males (40.5%) and 2 845 females (59.5%). The age was (61.3±7.7) years old and the blood cholesterol was (5.0±1.0) mmol/L. The prevalence rates of hypercholesterolemia, albuminuria, and reduced estimated glomerular filtration rate (eGFR) were 10.7%(305/2 845), 6.4%(182/2 845) and 2.8%(79/2 845) in females and 12.7%(245/1 934), 6.9%(133/1 934) and 2.3%(45/1 934) in males respectively. Compared with Q1 group, the prevalence of reduced eGFR in females were higher in Q2 and Q4 groups (both P<0.05). Among males, the prevalence of albuminuria and reduced eGFR increased with increasing blood cholesterol quartile (Cochran-Armitage trend test Z=12.231, 8.862, both P<0.001). Multivariate logistic regression analysis showed that hypercholesterolemia was an independent influencing factor for albuminuria and reduced eGFR ( OR=1.49, 95% CI 1.08-2.07, P=0.016 and OR=1.65, 95% CI 1.03-2.65, P=0.037, respectively). In subgroup analysis of different genders, female hypercholesterolemia was an independent influencing factor for albuminuria and reduced eGFR, while male hypercholesterolemia was not an independent influencing factor ( OR=1.54, 95% CI 0.96~2.46, P=0.075; OR=1.89, 95% CI 0.93-3.89, P=0.082, respectively). Further subgroup analysis based on the interquartile range of serum cholesterol levels found that female hypercholesterolemia was an independent influencing factor for reduced eGFR in the Q2 and Q4 groups ( OR=2.35, 95% CI 1.29-7.61, P=0.003; OR=2.51, 95% CI 1.38-8.39, P=0.001). In males, hypercholesterolemia was an independent influencing factor for albuminuria in the Q2, Q3 and Q4 groups ( OR=1.80, 95% CI 1.01-3.41, P=0.047; OR=1.85, 95% CI 1.02-3.35, P=0.044; OR=2.33, 95% CI 1.33-4.33, P=0.002). Conclusions:Hypercholesterolemia is an independent risk factor for CKD in middle-aged and elderly population, and there are gender differences, which provides a new idea for clinical prevention and control of CKD.

Objective To observe the clinical effect of a modified version of constraint-induced movement therapy(MCIMT)on motor recovery in the upper extremities of stroke patients. Methods Twenty-seven stroke patients were randomly divided into a treatment group(n=14)and a routine group(n=13).The Bobath approach and functional arm exercise were administered to the patients in the routine group(2 h/d,5 times a week)for ten weeks.The MCIMT administered to the treatment group involved restriction of the functional arm by a sling during 90%of waking time and during training(by shaping)of the affected extremity(1 hour per day,three times a week)in addition to activities of daily living exercise for at least 2 hours every day.The main outcome measures were the ten items of the simplified test for evaluating hand function(STEF)and Wolf's Motor Function Test(WMFT). Results No significant difference was observed between the 2 groups with regard to WMFT and STEF scores before treatment.After treatment,both groups had improved their WMFT and STEF scores significantly,but there was a significant difference between the treatment and the control groups with regard to WMFT scores and 7 items of the STEF test. Conclusion Modified constraint-induced movement therapy is effective not only for promoting motor recovery of the upper extremity,but also for improving the flexibility and velocity of movement instroke patients.

Objective To observe the prevalence of hyperuricemia(HUA)among obese children,and to ex-plore the association between uric acid(UA)levels and cardiometabolic risk factors,acanthosis nigricans and non - al-cohol fatty liver disease(NAFLD). Methods By using representative sampling method,1 753 obese children aged 6 -17 years old from 18 schools in 3 districts of Beijing(Xicheng,Haidian,Miyun)were selected to participate in the clini-cal examinations,including anthropometric measurements(height,weight)and blood pressure. Serum biochemical pa-rameters were assessed,including fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG),high - densi-ty lipoprotein cholesterol(HDL - C),low - density lipoprotein cholesterol(LDL - C)and UA. Acanthosis nigricans and B - model ultrasonography of the liver were conducted. Results The prevalence of hypertension,impaired fasting glu-cose,dyslipidemia,acanthosis nigricans,and NAFLD among these 1 753 obese children was 33. 6%(589 cases), 66. 5%(1 156 cases),54. 3%(943 cases),23. 3%(408 cases),and 17. 0%(298 cases),respectively. The preva-lence of HUA was 40. 70%(714 / 1 753 cases),with 50. 17%(581 / 1 158 cases)in boys and 22. 34%(133 / 595 ca-ses)in girls. There was a significant increase in body mass index,systolic blood pressure,diastolic blood pressure, FPG,TG and LDL - C with the increase of UA,but there was a decrease in HLD - C with the increase of UA(all P ﹤0. 05). In boys,the adjusted odds ratios( OR)and 95% CI of the highest quartile of UA for hypertension,impaired fasting glucose,dyslipidemia,acanthosis nigricans,and NAFLD were 1. 16(0. 77 - 1. 74),1. 34(0. 90 - 1. 99),1. 29 (0. 89 - 1. 87),1. 89(1. 17 - 3. 04),and 1. 71(1. 03 - 2. 84),respectively;in girls,the adjusted OR and 95% CI of the highest quartile of UA for hypertension,impaired fas-ting glucose,dyslipidemia,acanthosis nigricans,and NAFLD was 0. 70(0. 40 - 1. 24),0. 60(0. 40 - 1. 00),1. 69(1. 04 - 2. 70),1. 67(0. 80 - 3. 49),and 1. 33(0. 48 - 3. 66),re-spectively. Conclusions The prevalence of HUA is relatively high in obese children and there is a strong association between UA and some car-diovascular metabolic disorders,acanthosis nigricans and NAFLD.

Acute myocardial infarction (AMI) and acute massive pulmonary embolism can be characterized by no pulse electrical activity. Patients of cardiac arrest (CA) with no pulse electrical activity have a high mortality rate before the cause was corrected. Extracorporeal membrane oxygenation (ECMO), as a kind of artificial heart-lung support organ, provides treatment for CA patients. A case of massive pulmonary embolism similar to AMI was treated in the Third Central Hospital of Tianjin, who received interventional thrombolysis assisted by ECMO. Through the review of the overall development of the case, we aim to broaden the diagnosis and treatment of CA patients with no pulse electrical activity, and to improve the understanding of the complications secondary to ECMO.

Since the approval of gemtuzumab ozogamicin, an antibody–drug conjugate (ADC) targeting CD33 in 2000, 13 ADC drugs have been approved by the FDA. Although these drugs have clearly improved the survival of patients with various types of advanced cancers, their significant toxicity has compromised their therapeutic benefits. The adverse reactions of ADC drugs are complex and include on-target and off-target toxicities, where the payload drug is a determining factor. Antibody and linker may also affect the degree of toxicity. Combination therapy becomes an important strategy in anticancer treatment because of its increased efficiency, but treatment-related adverse reactions also increase accordingly. This review comprehensively analyzes the toxicity mechanisms of current ADC drugs and proposes various optimization strategies, including but not limited to optimizing linker molecules, upgrading antibody design, and changing drug administration strategies, to improve the overall safety profile of ADC drugs.

The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients' outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol-miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo, thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*