Protective Effects of Magnesium Glycyrrhizinate on Methotrexate-Induced Hepatotoxicity and Intestinal Toxicity May Be by Reducing COX-2

Magnesium isoglycyrrhizinate (MgIG), which has been widely employed to treat chronic hepatitis, is synthesized from 18-β glycyrrhizic acid, a main component of traditional Chinese medicine Glycyrrhiza uralensis Fisch. Although the protective effects of MgIG on methotrexate (MTX)-induced liver toxicity have been well-documented, the underlying mechanism remains elusive. MTX was initially used to treat pediatric acute leukemia, and has been widely applied to psoriasis therapy. However, its clinical applications are limited due to hepatotoxicity and intestinal toxicity. Herein, prophylactic administration of MgIG (9 and 18 mg/kg/day) significantly reduced the levels of aspartate aminotransferase and alanine aminotransferase in the serum of rats receiving intravenous injection of MTX (20 mg/kg body weight). MgIG also attenuated MTX-induced hepatic fibrosis. Moreover, it better protected against MTX-induced hepatocyte apoptosis and decreased the serum level of malondialdehyde than reduced glutathione (80 mg/kg/day) did. Interestingly, MTX-induced cyclooxygenase-2 (COX-2) expression, intestinal permeability and inflammation were attenuated after MgIG administration. In addition, MgIG (9 and 18 mg/kg) reduced MTX-induced colocalization of zonula occludens-1 (ZO-1) and connexin 43 (Cx43) in intestinal villi. In conclusion, MgIG exerted beneficial effects on MTX-induced hepatotoxicity and intestinal damage, as a potentially eligible drug for alleviating the hepatic and intestinal side effects of MTX during chemotherapy

Breaking Glucose Transporter 1/Pyruvate Kinase M2 Glycolytic Loop Is Required for Cantharidin Inhibition of Metastasis in Highly Metastatic Breast Cancer

Aerobic glycolysis plays a decisive role in cancer growth. However, its role in cancer metastasis was rarely understood. Cantharidin a natural compound from an arthropod insect cantharis exerts potent anticancer activity. Here we found cantharidin possesses significant anti-metastatic activity on breast cancer dependent on inhibition of aerobic glycolysis. Cantharidin indicates significant inhibition on migration and invasion of breast cancer cells, angiogenesis in vitro, and inhibits breast cancer cells metastasizing to liver and lung in vivo. Subsequent results revealed that cantharidin decreases the extracellular acidification rates (ECAR) but increases the oxygen consumption rates (OCR) in high metastatic cells, leading to suppression of aerobic glycolysis. This was considered to be due to inhibiting the activity of pyruvate kinase (PK) and further blocking pyruvate kinase M2 (PKM2) translocation in nucleus. Fructose-1,6-bisphosphate (FBP) and L-cysteine can significantly reverse cantharidin inhibition on breast cancer cell migration, invasion, and PKM2 translocation. Furthermore, glucose transporter 1 (GLUT1) forming a metabolic loop with PKM2 is downregulated, as well as epidermal growth factor receptor (EGFR), the regulator of the glycolytic loop. Totally, cantharidin inhibits the PKM2 nuclear translocation and breaks GLUT1/PKM2 glycolytic loop, resulting in aerobic glycolysis transformation to oxidation and subsequent reversing the metastases in breast cancer. Based on inhibiting multi signals mediated aerobic glycolysis, cantharidin could be prospectively used for prevention of metastasis in breast cancer patients

Targeting Thioredoxin System with an Organosulfur Compound, Diallyl Trisulfide (DATS), Attenuates Progression and Metastasis of Triple-Negative Breast Cancer (TNBC)

Background/Aims: Metastasis is the leading cause resulting in high mortality in triple negative breast cancer (TNBC) patients. Cancer cells are skilled at utilizing thioredoxin (Trx) system as an efficient antioxidant system to counteract oxidative damage, facilitating the occurrence of metastasis. Here, we identified an organosulfur compound named DATS isolated from garlic, that inhibits the expression of Trx-1 and the enzyme activity of Trx reductase in breast cancer cells. Methods: Tissue microarray of breast cancer patients and immunohistochemical method were used to analyze the role of Trx-1 in breast cancer metastasis. Spotaneous metastasis model and experimental metastasis model combined with HE staining, immunohistochemistry were used to verify in vivo anti-metastatic effect of DATS as well as its regulation on thioredoxin. Western blot, immunofluorescence, redox state assessment and detection of enzyme activity were employed to determine the effect of DATS on thioredoxin system. Trx-1 siRNA interference was used to investigate the conclusive evidence that Trx-1 was the target of DATS. Results: In agreement with reduced Trx-1 nuclear translocation from cytoplasm by DATS, the production of reduced form of Trx-1 was dramatically decreased. Furthermore, in vivo, DATS administration was observed to significantly suppress spontaneous and experimental metastasis in nude mice. Delivery of DATS also resulted in decreased expression of Trx-1 as the direct target, as well as expression of NF-κB and MMP2/9 in primary tumor and lung tissue. Notably, the effects of DATS on the expression of downstream metastasis-associated genes were mediated by Trx-1, as demonstrated by the combination use of DATS and Trx-1 siRNA. Conclusion: Collectively, this present study indicates that targeting Trx system with DATS may provide a promising strategy for treating metastasis of TNBC

Serum Fetuin-A Associates with Type 2 Diabetes and Insulin Resistance in Chinese Adults

Previous studies have demonstrated that fetuin-A is related to insulin resistance among subjects with normal glucose tolerance but not patients with type 2 diabetes. There are limited data available concerning fetuin-A and insulin resistance in Chinese. We aimed to study the association of fetuin-A with insulin resistance among participants with or without type 2 diabetes in a large sample size of adults aged 40 and older.A community-based cross-sectional study was performed among 5,227 Chinese adults. The average age of our study was 61.5±9.9 years. Serum fetuin-A concentrations were not significantly different between male and female (296.9 vs. 292.9 mg/l, p = 0.11). Compared with the lowest quartile, the highest quartile of serum fetuin-A revealed a significant higher proportion of type 2 diabetic patients (34.8% vs. 27.3%, p<0.0001). In the multinomial logit models, the risk of type 2 diabetes was associated with each one quartile increase of serum fetuin-A concentrations when referenced not only to normal glucose tolerance (OR 1.24, 95% CI 1.07-1.43, p = 0.004) but also to impaired glucose regulation (OR 1.25, 95% CI 1.08-1.44, p = 0.003, respectively), after adjustment for age, sex, community, current smoking, and current drinking. The logistic regression analysis showed that fetuin-A were associated with elevated HOMA-IR and fasting serum insulin both among the participants with or without type 2 diabetes in the full adjusted analysis. There was no significant association between elevated serum fetuin-A concentrations and impaired glucose regulation (all p≥0.12).Higher fetuin-A concentrations were associated with type 2 diabetes and insulin resistance in middle aged and elderly Chinese

A Real Time QRS Detection Algorithm Based on ET and PD Controlled Threshold Strategy

As one of the important components of electrocardiogram (ECG) signals, QRS signal represents the basic characteristics of ECG signals. The detection of QRS waves is also an essential step for ECG signal analysis. In order to further meet the clinical needs for the accuracy and real-time detection of QRS waves, a simple, fast, reliable, and hardware-friendly algorithm for real-time QRS detection is proposed. The exponential transform (ET) and proportional-derivative (PD) control-based adaptive threshold are designed to detect QRS-complex. The proposed ET can effectively narrow the magnitude difference of QRS peaks, and the PD control-based method can adaptively adjust the current threshold for QRS detection according to thresholds of previous two windows and predefined minimal threshold. The ECG signals from MIT-BIH databases are used to evaluate the performance of the proposed algorithm. The overall sensitivity, positive predictivity, and accuracy for QRS detection are 99.90%, 99.92%, and 99.82%, respectively. It is also implemented on Altera Cyclone V 5CSEMA5F31C6 Field Programmable Gate Array (FPGA). The time consumed for a 30-min ECG record is approximately 1.3 s. It indicates that the proposed algorithm can be used for wearable heart rate monitoring and automatic ECG analysis

Satisfaction with service coverage and drug list may influence patients’ acceptance of general practitioner contract service: a cross-sectional study in Guangdong, China

Abstract Background General practitioner (GP) system is proved to be effective in over 50 countries worldwide. Guangdong province, as a reform pilot in China, initiated its patient-GP contract service reform in 2014. This study is designed to assess the patients’ acceptance of General Practitioners Contract (GPC) reform and explore its influencing factors. Methods This survey interviewed 1010 participants from 16 primary health centers (PHCs) chosen from 4 pilot cities in Guangdong during July and December in 2015. Data were collected through face-to-face interviews. The questionnaire was developed to discover the acceptance of GPC and covered three parts: respondents’ socio-demographic characteristics, health service utilization, and the patients’ assessment of primary health care centers. A binary logistic regression model was used to measure the influencing factors of respondents’ acceptance of GPC policy. Results A total of 611(60.5%) participants accepted GPC policy. Compared to patients visited PHCs over 7 times in the previous year, those visited PHCs fewer times reported lower acceptance of GPC policy (OR:0.68, 95% CI:0.49–0.96 for visits ≤3 times and OR:0.57, 95% CI:0.38–0.84 for visits = 4–6 times). Patients’ satisfaction with medical service coverage was positively associated with patients’ acceptance of GPC (OR: 1.72, 95% CI:1.01–3.98 for the satisfied versus the dissatisfied; OR: 1.38, 95% CI:0.92–3.30 for neutral versus the dissatisfied), and the satisfaction with drug list also positively influenced patients’ acceptance of GPC policy (OR: 1.44, 95% CI:1.26–2.73 for the satisfied versus the dissatisfied; OR:1.61, 95% CI:1.36–2.99 for neutral versus the dissatisfied). Meanwhile, age and education had positive impacts on the acceptance of the GPC policy. Conclusion This study finds out that patients’ satisfaction with medical service coverage and drug list are the influencing factors for the acceptance of GPC policy. Therefore, improvement of medical service accessibility such as better follow-up of patients with chronic diseases and enhanced referral service, as well as the expansion of drug list, will improve patients’ acceptance of GPC policy. It also finds that patients using more primary health service are inclined to accept GPC policy, so more attractive and high-quality service should be provided in PHCs

Strength characteristics of the sliding zone soil of bedding deep cutting slopes and early warning analysis of the reserved thickness of the base

Objective Bedding deep cutting slopes containing weak interlayers are commonly found in slope engineering, whose stability is influenced by two key factors: The strength of the sliding zone soil and the reserved thickness of the base (the distance from the base of an excavated slope to the weak interlayer). Methods In this research, taking the K42 cutting slope of the Yang-Xuan Expressway as an example, the evolution process of slope deformation was analyzed, especially the characteristics of basal heave deformation. The properties of the deep sliding zone soil in the slope were revealed by ring shear tests, which are suitable for studying the shear strength of soil that has experienced large shear displacements. Moreover, the residual strength parameters of the saturated sliding zone soil were applied to analyze the reserved thickness of the base. Results The results show that sliding zone soils exhibit obvious strain softening characteristics, which become more evident as the normal stress decreases. As the soil shear strength transitions from peak strength to residual strength, both the cohesion force and internal friction angle decrease, with the cohesion force decreasing to a greater extent than the internal friction angle. The residual cohesion force of sliding zone soil varies slightly with the shear rate, while the relationship between the residual internal friction angle and shear rate varies as a logarithmic function. When the shear rate is less than 2 mm/min, the residual shear strength parameter of sliding zone soil is more sensitive to the shear rate and vice versa. Conclusion Furthermore, according to the regression equations of the critical states of slope stability, the reserved thickness of the base under different slope rates was divided into four zones: A (extremely unstable zone), B (unstable zone), C (basically stable zone) and D (stable zone), and based on this, the criterion and early warning model of the reserved thickness of the base for slope excavation were established

Quality of Primary Care Services: a Perspective from Chronic Disease Patients

Background Since the number of chronic disease patients is increasing, relevant prevention and treatment services have become important long-term tasks for primary care institutions. However, problems in the provision of primary care services seriously affect the perception of such services in residents, especially chronic disease patients. Objective To understand chronic disease patients&apos; assessment of the quality of primary care services, providing evidence for improving the quality of chronic disease management services in primary care. Methods A survey was conducted between July and August, 2020 with chronic disease patients (n=630) selected from primary care settings in Guangdong&apos;s Chaozhou by use of multistage stratified random sampling. The Primary Care Assessment Tool-Adult Simplified Version (PCAT-AS) (consists of 10 domains, including first contact accessibility, coordination, ongoing, comprehensiveness, community orientation and other 5 domains) was used in the survey for understanding chronic disease patients&apos; assessment of the quality of primary care services. Multiple linear regression was adopted to identify factors potentially associated with the PCAT-AS score. Results Altogether, 553 cases (87.8%) who returned responsive questionnaires were enrolled for analysis. The average total PCAT-AS score for all respondents was (95.88±13.44) . The top three domains ranked in terms of average standardized score were comprehensiveness (services needed) (7.89) , first contact accessibility (7.72) , and first contact utilization (7.58) , and the bottom three-ranked domains were coordination (referrals) (5.61) , community orientation (6.11) and patient and family centeredness (6.40) . Multiple linear regression analysis indicated that higher total PCAT-AS score was associated with living in urban areas in contrast to rural areas〔b (95%CI) =-6.983 (-10.598, -3.368) 〕, senior high school and higher education level instead of junior high school and lower education level〔b (95%CI) =4.046 (0.966, 7.125) 〕, permanent residents without the local hukou in contrast to those with local hukou〔b (95%CI) =-5.360 (-9.517, -1.202) 〕, good self-rated health instead of relatively poor self-rated health〔b (95%CI) =-4.962 (-8.438, -1.486) 〕 or poor self-rated health〔b (95%CI) =-7.787 (-12.789, -2.786) 〕, having a contracted family doctor instead of having no contracted family doctor〔b (95%CI) =4.686 (2.508, 6.865) 〕, first choosing a community health center for treating common diseases instead of a village clinic〔b (95%CI) =-5.865 (-9.951, -1.779) 〕 or a district/county-level hospital or tertiary hospital〔b (95%CI) =-6.061 (-11.330, -0.792) 〕, 4-6 primary care visits instead of 1-3 primary care visits〔b (95%CI) =5.876 (3.367, 8.384) or 7 or more primary care visits instead of 1-3 primary care visits〔b (95%CI) =9.045 (6.512, 11.579) 〕, and high satisfaction with primary care services instead of fair satisfaction〔b (95%CI) =-2.844 (-4.817, -0.870) 〕 or dissatisfaction〔b (95%CI) =-10.418 (-17.050, -3.786) 〕. Conclusion Overall, Chaozhou chronic disease patients reported a sound level of treatment experience in primary care. Specifically, they reported good primary care experience in three domains, including comprehensiveness, first contact accessibility and first contact utilization, but poor experience in community orientation, and coordination (including information systems and referrals) . However, urban patients reported better primary care experience than rural patients. So continued efforts are needed to strengthen primary care performance in rural areas

Dual Cluster Head Optimization of Wireless Sensor Networks Based on Multi-Objective Particle Swarm Optimization

Energy conservation is one of the main problems in a wireless sensor network (WSN). Compared with a single cluster head (CH), a dual CH optimization was proposed for less energy consumption by the WSN and an acquisition delay by the mobile sink (MS). Firstly, a fuzzy c-means clustering algorithm and a multi-objective particle swarm optimization were utilized for the determinations of the first and second CHs. Following that, the ideal trajectory of MS was assessed using the improved ant colony algorithm. Finally, the lifetimes, the death rounds of the first node and the 50% node, and the number of packets received at the base station were compared among the proposed approach. Moreover, five algorithms were compared to validate the optimization, and the improved trajectory was compared with the original one as well. It was found that, for 100 nodes, the number of dead rounds from the proposal increased by 7.9%, 22.9%, 25.1%, 61%, and 74.4% for the first node, and that of the 50% nodes increased by 27.8%, 34.2%, 98.3%, 213.1%, and 211.2%, respectively. The base station packet reception increased by about 19.3%, 53.5%, 27%, 86.8%, and 181.2%, respectively. The trajectory of MS could also decrease by about 10%