Publications by authors named "Yingchun Chen"

55 Publications

Sodium houttuyfonate attenuates neurological defects after traumatic brain injury in mice via inhibiting NLRP3 inflammasomes.

J Biochem Mol Toxicol 2021 Sep 17;35(9):e22850. Epub 2021 Aug 17.

Department of Neurosurgery, The Third People's Hospital of Hubei Province, Wuhan, Hubei, China.

Sodium houttuyfonate (SH) is a chemical compound synthesized by houttuynin and sodium bisulfite. As it has antinflammatory effects, SH has been widely used to treat autoimmune diseases, including post events following traumatic brain injury (TBI). Meanwhile, NOD-like receptor with pyrin domain containing-3 (NLRP3) inflammasomes in microglia may play a central role in TBI. But to date, the intracellular mechanisms involved in the anti-inflammatory effects of SH in TBI remain unknown, especially whether regulating NLRP3. To gain an insight into this possibility, we conducted cell culture and biochemical studies on the effect of SH on NLRP3 inflammasome in microglia. The results showed that SH inhibited TLR4 and NLRP3 inflammasome activation in the microglia cell. In parallel, phosphorylation of ERK and NF-κB p65, which play a key role in NLRP3 inflammasome formation, was decreased. Intraperitoneal injection of SH into TBI mice significantly reduced the modified neurological severity score (mNSS), as well as the degree of microglia apoptosis post-controlled cortical impact (CCI). Immunohistochemistry, Western blot analysis, and reverse-transcription polymerase chain reaction (RT-PCR) revealed that SH markedly reduced NLRP3 inflammasome activation, TLR4 activity, phosphorylation of ERK and NF-κB. Moreover, SH significantly inhibited microglia activation post-CCI, but effectively promoted the astrocyte activation and angiopoiesis. Taken together, our research provides evidence that SH attenuated neurological deficits post TBI through inhibiting NLRP3 inflammasome activation, via influencing the TLR4/NF-κB signaling pathway. These findings explain the intracellular mechanism of the anti-inflammatory activity caused by SH treatment following TBI.
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http://dx.doi.org/10.1002/jbt.22850DOI Listing
September 2021

What intensity of exercise is most suitable for the elderly in China? A propensity score matching analysis.

BMC Public Health 2021 07 15;21(1):1396. Epub 2021 Jul 15.

School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Background: The strategy of successful ageing is an important means to deal with the challenges of the current ageing society. This paper aims to explore the effects of different intensities of physical activity on the successful ageing of the elderly.

Methods: Our data were from wave 4 of the China Health and Retirement Longitudinal Survey (CHARLS), involving 9026 residents aged 60 years and older. The intensity of physical activity was divided into three levels: vigorous, moderate and mild. The concept of successful ageing adopted a four-dimensional model of life satisfaction added to the theoretical model of Rowe and Kahn's. Propensity score matching (PSM) with controlling nine confounding factors were used to analyse the effects of different intensities of physical activity.

Results: The percentage of successful ageing was 1.88% among all subjects. Among them, 30.26, 29.57 and 29.40% of the elderly often participated in vigorous, moderate and mild physical activity, respectively. The results of PSM showed that participation in moderate activity increased the probability of successful ageing of the elderly by 0.76-0.78% (P < 0.001), while participation in vigorous and mild physical activity had no significant effect on successful ageing (P > 0.05). Moderate physical activity had statistically significant effects on four components of successful aging, including major disease, physical function, life satisfaction, and social participation (P < 0.05).

Conclusion: Moderate-intensity physical activity was most beneficial to the successful ageing of the elderly and should be promoted in the elderly population.
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http://dx.doi.org/10.1186/s12889-021-11407-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281566PMC
July 2021

Vagus nerve stimulation affects inflammatory response and anti-apoptosis reactions via regulating miR-210 in epilepsy rat model.

Neuroreport 2021 Jun;32(9):783-791

Department of Neurosurgery, The Third People's Hospital of Hubei Province, Wuhan, Hubei, China.

Background: Studies have shown that vagus nerve stimulation (VNS) significantly reduces the frequency of seizures. MicroRNAs (miRNAs) in cerebrospinal fluid are expected to become a new biomarker of epilepsy. Therefore, studying the interaction mechanism between the VNS and miRNAs is hopeful of bringing a new therapeutic direction for the treatment of epilepsy.

Methods: Kainic acid was used to induce the Sprague-Dawley rat epilepsy model, and the rats were treated with VNS. The miR-210 expression was determined by quantitative reverse transcription PCR (qRT-PCR). Racine score was adopted to evaluate the performance of behavioral seizures, whereas qRT-PCR and ELISA were employed to test inflammatory factors. Western blotting was implemented to testify the inflammatory and apoptotic proteins.

Results: Kainic acid-induced the Sprague-Dawley rat epilepsy model and upregulated the expression of miR-210, inflammatory response, inflammation and apoptosis-related proteins in brain tissues. In addition, compared with the epilepsy model group, miR-210 in the hippocampus of the epilepsy model rats treated with VNS was downregulated, and the expression of apoptosis-related proteins and inflammatory factors was reduced. Moreover, after further inhibiting the expression of miR-210, the inhibition of VNS on epilepsy, inflammation and apoptosis were significantly enhanced.

Summary: VNS relieves the inflammatory response and apoptosis of epileptic rats via inhibiting miR-210.
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http://dx.doi.org/10.1097/WNR.0000000000001655DOI Listing
June 2021

Cooperation of ATF4 and CTCF promotes adipogenesis through transcriptional regulation.

Cell Biol Toxicol 2021 May 5. Epub 2021 May 5.

Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People's Republic of China.

Adipogenesis is a multi-step process orchestrated by activation of numerous TFs, whose cooperation and regulatory network remain elusive. Activating transcription factor 4 (ATF4) is critical for adipogenesis, yet its regulatory network is unclarified. Here, we mapped genome-wide ATF4 binding landscape and its regulatory network by Chip-seq and RNA-seq and found ATF4 directly modulated transcription of genes enriching in fat cell differentiation. Motifs of TFs especially CTCF were found from ATF4 binding sites, suggesting a direct role of ATF4 in regulating adipogenesis associated with CTCF and other TFs. Deletion of CTCF attenuated adipogenesis while overexpression enhanced adipocyte differentiation, indicating CTCF is indispensable for adipogenesis. Intriguingly, combined analysis of Chip-seq data of these two TFs showed that ATF4 co-localized with CTCF in the promoters of key adipogenic genes including Cebpd and PPARg and co-regulated their transactivation. Moreover, ATF4 directly regulated CTCF expression and interacted with CTCF in differentiated 3T3-L1 cells. In vivo, downregulation of ATF4 suppressed the expression of CTCF, Cebpd, and PPARg, leading to reduced adipose tissue expansion in refeeding mice. Consistently, mRNA expression of ATF4 and CTCF was positively correlated with each other in human subcutaneous adipose tissue and inversely associated with BMI, indicating a possible involvement of these two TFs in adipose development. Taken together, our data propose for the first time that ATF4 and CTCF work cooperatively to control adipogenesis and adipose development via orchestrating transcription of adipogenic genes. Our findings reveal novel therapeutic targets in obesity treatment.
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http://dx.doi.org/10.1007/s10565-021-09608-xDOI Listing
May 2021

Use of machine learning approach to predict depression in the elderly in China: A longitudinal study.

J Affect Disord 2021 03 30;282:289-298. Epub 2020 Dec 30.

Department of Health Management, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Research Center for Rural Health Services, Hubei Province Key Research Institute of Humanities and Social Sciences, Wuhan, China. Electronic address:

Background: Early detection of potential depression among elderly people is conducive for timely preventive intervention and clinical care to improve quality of life. Therefore, depression prediction considering sequential progression patterns in elderly needs to be further explored.

Methods: We selected 1,538 elderly people from Chinese Longitudinal Healthy Longevity Study (CLHLS) wave 3-7 survey. Long short-term memory (LSTM) and six machine learning (ML) models were used to predict different depression risk factors and the depression risks in the elderly population in the next two years. Receiver operating curve (ROC) and decision curve analysis (DCA) were used to evaluate the prediction accuracy of the reference model and ML models.

Results: The area under the ROC curve (AUC) values of logistic regression with lasso regularisation (AUC=0.629, p-value=0.020) was the highest among ML models. DCA results showed that the net benefit of six ML models was similar (threshold: 0.00-0.10), the net benefit of lasso regression was the largest (threshold: 0.10-0.17 and 0.22-0.25), and the net benefit of DNN was the largest (threshold: 0.17-0.22 and 0.25-0.40). In two ML models, activities of daily living (ADL)/ instrumental ADL (IADL), self-rated health, marital status, arthritis, and number of cohabiting were the most important predictors for elderly with depression.

Limitations: The retrospective waves used in the LSTM model need to be further increased.

Conclusion: The decision support system based on the proposed LSTM+ML model may be very valuable for doctors, nurses and community medical providers for early diagnosis and intervention.
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http://dx.doi.org/10.1016/j.jad.2020.12.160DOI Listing
March 2021

Effect of Social Participation on the Physical Functioning and Depression of Empty-Nest Elderly in China: Evidence from the China Health and Retirement Longitudinal Survey (CHARLS).

Int J Environ Res Public Health 2020 12 16;17(24). Epub 2020 Dec 16.

Department of Health Management, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

This study aimed to explore the impact of social participation (SP) on physical functioning and depression among empty-nest elderly taking part in the fourth wave of the China Health and Retirement Longitudinal Survey (CHARLS, 2018). The instrumental variable (IV) method and propensity score matching (PSM) method were used to analyse the impact of SP. The two-stage regression results of the IV method showed that SP has a significant negative impact on the physical functioning scores of empty-nest elderly (β = -3.539, < 0.001) and non-empty-nest elderly (β = -4.703, < 0.001), and SP has a significant negative impact on the depression scores of empty-nest elderly (β = -2.404, < 0.001) and non-empty-nest elderly (β = -1.957, < 0.001). The results of the PSM method were basically consistent with the IV method. Compared with non-empty-nest elderly, SP had more positive effects on the depression of empty-nest elderly (Wald χ = 6.62, = 0.010). Providing a friendly and supportive environment for the SP of empty-nest elderly was an important measure to promote healthy ageing. Targeted SP may be one of the greatest opportunities to improve the mental health of empty-nest elderly.
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http://dx.doi.org/10.3390/ijerph17249438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766298PMC
December 2020

Assessment of left ventricular systolic function by non-invasive pressure-strain loop area in young male strength athletes.

Cardiovasc Ultrasound 2020 Nov 13;18(1):45. Epub 2020 Nov 13.

Department of Ultrasound, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China.

Background: The health of athletes has been recognized as a worldwide public concern with more reported sudden cardiac deaths (SCD). Therefore, early detection of abnormal heart function in athletes can help reduce the risk of exercise. A novel valid non-invasive method to evaluate left ventricular (LV) myocardial work (MW) using LV pressure-strain loop (PSL), was used in this paper to explore LV systolic function in young male strength athletes.

Methods: Thirty-six professional young male strength athletes (the athlete group) and 32 healthy, age-matched young men (the control group) were involved in the study. The LVMW parameters were calculated as the area of PSL by two-dimensional speckle tracking echocardiography (2D-STE) and peak systolic LV pressure. The differences between two groups of data and the predictive efficacy of MW parameters for LV systolic function were analyzed.

Results: The athlete group had significantly higher values of global wasted myocardial work (GWW) and peak strain dispersion (PSD) than did the control group (P<0.05). Global myocardial work index (GWI), global constructive myocardial work (GCW) and global longitudinal strain (GLS) were lower in the athlete group than that in the control group, although statistical significance was not reached (P>0.05). Due to the proportion of GWW and GCW, statistically significant reduction was found in global myocardial work efficiency (GWE) in the athlete group. Conventional echocardiography parameters were well correlated with GWW and GWE (P<0.05). The best predictor of LV myocardial contractile performance in the athletes using receiver operating characteristic curve (ROC) was GWE, with the area under ROC (AUC) of 0.733, sensitivity of 83.3% and specificity of 59.4%.

Conclusions: Subclinical changes have appeared in the hearts of young male strength athletes after long-term intensive exercise and LVMW parameters by PSL play an important role in the evaluation of athlete's LV contractile performance.
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http://dx.doi.org/10.1186/s12947-020-00227-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666446PMC
November 2020

Downregulation of glucose-6-phosphatase expression contributes to fluoxetine-induced hepatic steatosis.

J Appl Toxicol 2021 08 12;41(8):1232-1240. Epub 2020 Nov 12.

Institute of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Fluoxetine is a first-line selective serotonin reuptake inhibitor widely applied for the treatment of depression; however, it induces abnormal hepatic lipid metabolism. Considering decreased expression or function of glucose-6-phosphatase (G6Pase), a key enzyme in gluconeogenesis, or the upregulation of fatty acid uptake, causes hepatic lipid accumulation. The aim of this study was to elucidate whether G6Pase regulation and fatty acid uptake alteration contribute to fluoxetine-induced abnormal hepatic lipid metabolism. Our study revealed that 8-week oral administration of fluoxetine dose-dependently increased hepatic triglyceride, causing hepatic steatosis. Concomitantly, the expression of G6Pase in mouse livers and primary mouse hepatocytes (PMHs) was downregulated in a concentration-dependent manner. Furthermore, fluoxetine increased the concentrations of glucose-6-phosphate (G6Pase substrate) and acetyl CoA (the substrate for de novo lipogenesis) in mouse livers. Additionally, fluoxetine also induced lipid accumulation and downregulated G6Pase expression in HepG2 cells. However, the uptake of green fluorescent fatty acid (BODIPY™ FL C16) in PMHs was not changed after fluoxetine treatment, indicating that fluoxetine-induced hepatic steatosis was not associated with fatty acid uptake alteration. In conclusion, fluoxetine downregulated hepatic G6Pase expression, subsequently enhanced the transformation of glucose to lipid, and ultimately resulted in hepatic steatosis, but with no impact on fatty acid uptake.
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http://dx.doi.org/10.1002/jat.4109DOI Listing
August 2021

Experience in Neurosurgery During the Prevalence of COVID-19.

J Craniofac Surg 2020 Sep;31(6):e622-e624

Third People's Hospital of Hubei Province, Wuhan, China.

In order to summarize the experience of neurosurgery in The Third People's Hospital of Hubei Province after the outbreak of COVID-19 in 2019, 28 patients were admitted from January 5, 2020 to February 17, 2020. A series of department formulates and constant improvements were made, including elective operation cancellation, altered conventional outpatient service into online outpatient service, strict control of inter department consultation prevention and entering the department, improvements in operation and treatment processes, and strict ward management. As a result, 1 patient with hypertensive cerebral hemorrhage and deep vein thrombosis of the right lower extremity died suddenly due to pulmonary embolism during anticoagulation treatment. Two patients with deep coma gave up treatment and died. No patient was confirmed to be infected with COVID-19 in hospital. One doctor had a low fever and cough in January, and CT showed a small nodule in the lower left lung. After 2 weeks isolation and oral anti-infective drugs, the chest nodule disappeared. One nurse was isolated as a close contact with infected parents. One nurse was confirmed to be infected with COVID-19 in a mild symptom. She was discharged after being cured in the infected department. In conclusion, measures like sufficient theoretical training and protection upgrading for medical staff, continuous improvement on the understanding of COVID-19 characteristics and transmission routes, formulation of strict department management system, monitoring of patients and their families, could effectively deal with the epidemic situation in the neurosurgery department.
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http://dx.doi.org/10.1097/SCS.0000000000006619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480795PMC
September 2020

Performance and Sociodemographic Determinants of Excess Outpatient Demand of Rural Residents in China: A Cross-Sectional Study.

Int J Environ Res Public Health 2020 08 17;17(16). Epub 2020 Aug 17.

School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Excess healthcare utilization is rapidly rising in rural China. This study focused on excess outpatient demand (EOD) and aimed to measure its performance and sociodemographic determinants among China's rural residents. A total of 1290 residents from four counties in central China were enrolled via multistage cluster random sampling. EOD is the condition in which the level of hospital a patient chooses is higher than the indicated level in the governmental guide. A multilevel logistic regression was used to examine the sociodemographic determinants of EOD. Residents with EOD accounted for 85.83%. The risk of EOD was 51.17% and value was 5.69. The value of EOD in diseases was higher than that in symptoms (t = -21.498, < 0.001). Age (OR = 0.489), educational level (OR = 1.986) and hospital distance difference (OR = 0.259) were the main sociodemographic determinants of EOD. Excess outpatient demand was evident in rural China, but extreme conditions were rare. Results revealed that age, educational level and hospital distance were the main sociodemographic determinants of EOD. The capacity of primary healthcare institutions, universality of common disease judgement and understanding of institution's scope of disease curing capabilities of residents should be improved to reduce EOD.
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http://dx.doi.org/10.3390/ijerph17165963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460206PMC
August 2020

Comparison of inpatient distribution amongst different medical alliances in a county: a longitudinal study on a healthcare reform in rural China.

Int J Equity Health 2020 08 20;19(1):142. Epub 2020 Aug 20.

School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

Background: China has launched the medical alliances (MAs) reform to drive the development of primary medical institutions and decrease health inequality in rural areas. Three different types of MAs were built to promote township hospitals in Y County. This study aims to evaluate the actual effect of China's MAs reform in rural areas on inpatient distribution especially amongst different types of MAs.

Methods: We obtain 2008-2015 claims data from the New Cooperative Medical Scheme (NCMS) in Y County, Hubei Province of China. We consider January 2008-December 2010 as the pre-reform period and January 2011-December 2015 as the post-reform period. We use independent sample t-test and single-group interrupted time series analysis (ITSA) to compare the number of inpatients per month in the three MAs, including three county and 10 township hospitals before and after the reform. We use paired t-test and multiple-group ITSA between seven township hospitals within MAs and seven township hospitals outside MAs.

Results: The MAs reform in Y County increased the number of inpatients in county and township hospitals within MAs. After the reform, the number of inpatients per month in county hospitals had an upward trend, with a slope of 31.01 person/month (P < 0.000). Approximately 19.99 new inpatients were admitted to township hospitals monthly after the reform (P < 0.000). Furthermore, township hospitals within MAs had a substantial increase in the number of inpatients (10.45 new inpatients monthly) compared with those outside MAs.

Conclusion: The MAs reform in Y County significantly improved the capability of medical institutions within MAs. After the reform, township hospitals within MAs had greater development advantages than those outside MAs. However, it also caused further imbalance in the county region, which contained the new health inequality risk.
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http://dx.doi.org/10.1186/s12939-020-01260-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441726PMC
August 2020

Comprehensive identification and analysis of DELLA genes throughout the plant kingdom.

BMC Plant Biol 2020 Aug 6;20(1):372. Epub 2020 Aug 6.

Shandong Academy of Grape, Shandong engineering research center for Grape cultivation and deep-processing, Jinan, 250100, China.

Background: DELLAs play key roles in plant gibberellin signaling pathways and are generally important in plant development and growth. However, DELLAs in many plant taxa have not yet been systematically analyzed.

Results: In our study, we searched for DELLA genes across 58 green plant genomes and found 181 DELLAs. Structure analysis showed some DELLA domains do not contain "D-E-L-L-A" sequences and instead contain similar domains, including DGLLA and DSLLH domains. "VHYNP" motifs in plant DELLAs comprise 23 types of sequences, while some DELLAs did not contain GRAS domains. In grape, we found that the DELLA protein GSVIVT01015465001 contains an F-box domain, while apple DELLA proteins MDP0000220512 and MDP0000403162 contain a WW domain and a BCIP domain, respectively. These DELLAs can be divided into 22 homologous groups and 17 orthologous groups, and 35 paralogous genes were identified. In total, 35 positively selected genes (PSGs) and 121 negatively selected genes (NSGs) were found among DELLAs based on selective pressure analysis, with an average K of NSGs that was significantly higher than that of PSGs (P < 0.05). Among the paralogous groups, CBI and Fop were significantly positively correlated with GC, GC1, GC2, GC12, and GC3, while CAI was significantly positively correlated with GC, GC1, GC12, and GC. The paralogous groups with ω values exceeding 1 had significantly higher K values. We also found some paralogous groups with ω values exceeding 1 that differed in their motifs.

Conclusions: This study provides helpful insights into the evolution of DELLA genes and offers exciting opportunities for the investigation of DELLA functions in different plants.
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http://dx.doi.org/10.1186/s12870-020-02574-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409643PMC
August 2020

Organic Cation Transporter 1 and 3 Contribute to the High Accumulation of Dehydrocorydaline in the Heart.

Drug Metab Dispos 2020 10 28;48(10):1074-1083. Epub 2020 Jul 28.

Laboratory of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China

Dehydrocorydaline (DHC), one of the main active components of , is an important remedy for the treatment of coronary heart disease. Our previous study revealed a higher unbound concentration of DHC in the heart than plasma of mice after oral administration of extract or DHC, but the underlying uptake mechanism remains unelucidated. In our investigations, we studied the transport mechanism of DHC in transgenic cells, primary neonatal rat cardiomyocytes, and animal experiments. Using quantitative real-time polymerase chain reaction and Western blotting, we found that uptake transporters expressed in the mouse heart include organic cation transporter 1/3 (OCT1/3) and carnitine/organic cation transporter 1/2 (OCTN1/2). The accumulation experiments in transfected cells showed that DHC was a substrate of OCT1 and OCT3, with of 11.29 ± 3.3 and 8.96 ± 3.7 μM, respectively, but not a substrate of OCTN1/2. Additionally, a higher efflux level (1.71-fold of MDCK-mock) of DHC was observed in MDCK-MDR1 cells than in MDCK-mock cells. Therefore, DHC is a weak substrate for MDR1. Studies using primary neonatal rat cardiomyocytes showed that OCT1/3 inhibitors (quinidine, decynium-22, and levo-tetrahydropalmatine) prevented the accumulation of DHC, whereas OCTN2 inhibitors (mildronate and l-carnitine) did not affect its accumulation. Moreover, the coadministration of OCT1/3 inhibitors (levo-tetrahydropalmatine, THP) decreased the concentration of DHC in the mouse heart. Based on these findings, DHC may be accumulated partly by OCT1/3 transporters and excreted by MDR1 in the heart. THP could alter the distribution of DHC in the mouse heart. SIGNIFICANCE STATEMENT: We reported the cardiac transport mechanism of dehydrocorydaline, highly distributed to the heart after oral administration of o extract or dehydrocorydaline only. Dehydrocorydaline (an OCT1/3 and MDR1 substrate) accumulation in primary cardiomyocytes may be related to the transport activity of OCT1/3. This ability, hampered by selective inhibitors (levo-tetrahydropalmatine, an inhibitor of OCT1/3), causes a nearly 40% reduction in exposure of the heart to dehydrocorydaline. These results suggest that OCT1/3 may contribute to the uptake of dehydrocorydaline in the heart.
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http://dx.doi.org/10.1124/dmd.120.000025DOI Listing
October 2020

What causes high costs for rural tuberculosis inpatients? Evidence from five counties in China.

BMC Infect Dis 2020 Jul 11;20(1):501. Epub 2020 Jul 11.

Research center for Rural Health Services, Hubei Province Key Research Institute of Humanities and Social Sciences, Wuhan, 430030, Hubei, China.

Background: Tuberculosis (TB) still causes high economic burden on patients in China, especially for rural patients. Our study aims to explore the risk factors associated with the high costs for TB inpatients in rural China from the aspects of inpatients' socio-demographic and institutional attributes.

Methods: Generalized linear models were utilized to investigate the factors associated with TB inpatients' total costs and out-of-pocket (OOP) expenditures. Quantile regression (QR) models were applied to explore the effect of each factor across the different costs range and identify the risk factors of high costs.

Results: TB inpatients with long length of stay and who receive hospitalization services cross provincially, in tertiary and specialized hospitals were likely to face high total costs and OOP expenditures. QR models showed that high total costs occurred in Dingyuan and Funan Counties, but they were not accompanied by high OOP expenditures.

Conclusions: Early diagnosis, standard treatment and control of drug-resistant TB are still awaiting for more efforts from the government. TB inpatients should obtain medical services from appropriate hospitals. The diagnosis and treatment process of TB should be standardized across all designated medical institutions. Furthermore, the reimbursement policy for migrant workers who suffered from TB should be ameliorated.
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http://dx.doi.org/10.1186/s12879-020-05235-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353759PMC
July 2020

Diversity and spoilage potential of microbial communities associated with grape sour rot in eastern coastal areas of China.

PeerJ 2020 16;8:e9376. Epub 2020 Jun 16.

Shandong Academy of Grape, Jinan, China.

As a polymicrobial disease, sour rot decreases grape berry yield and wine quality. The diversity of microbial communities in sour rot-affected grapes depends on the cultivation site, but the microbes responsible for this disease in eastern coastal China, has not been reported. To identify the microbes that cause sour grape rot in this important grape-producing region, the diversity and abundance of bacteria and fungi were assessed by metagenomic analysis and cultivation-dependent techniques. A total of 15 bacteria and 10 fungi were isolated from sour rot-affected grapes. High-throughput sequencing of PCR-amplicons generated from diseased grapes revealed 1343 OTUs of bacteria and 1038 OTUs of fungi. and were dominant phyla among the 19 bacterial phyla identified. was the dominant fungal phylum and the fungi , , , , and represented the vast majority ofmicrobial species associated with sour rot-affected grapes. An in vitro spoilage assay confirmed that four of the isolated bacteria strains (two species, and ) and five of the isolated fungi strains (three species, , and ) spoiled grapes. These microorganisms, which appear responsible for spoiling grapes in eastern China, appear closely related to microbes that cause this plant disease around the world.
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http://dx.doi.org/10.7717/peerj.9376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315622PMC
June 2020

Influence of socio-ecological factors on COVID-19 risk: a cross-sectional study based on 178 countries/regions worldwide.

medRxiv 2020 Apr 29. Epub 2020 Apr 29.

The initial outbreak of COVID-19 caused by SARS-CoV-2 in China in 2019 has been severely tested in other countries worldwide. We established the Potential Risk Assessment Framework for COVID-19. We used spatial econometrics method to assess the global and local correlation of COVID-19 risk indicators. To estimate the adjusted IRR, we modelled negative binomial regression analysis with spatial information and socio-ecological factors. We found that 37, 29 and 39 countries/regions were strongly opposite from the IR, CMR and DCI index "spatial autocorrelation hypothesis", respectively. The IR, CMR and DCI were significantly associated with some socio-economic factors. We also found that climatic factors (temperature, relative humidity, precipitation and wind speed) did not significantly reduce COVID-19 risk. To fight against COVID-19 more effectively, countries/regions should pay more attention to controlling population flow, improving diagnosis and treatment capacity, and improving public welfare policies.
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http://dx.doi.org/10.1101/2020.04.23.20077545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276015PMC
April 2020

Long-chain non-coding RNA HOTAIR promotes the progression of osteoarthritis via sponging miR-20b/PTEN axis.

Life Sci 2020 Jul 18;253:117685. Epub 2020 Apr 18.

Department of Spinal Surgery, Beijing Shijitan Hospital, Beijing 100038, China. Electronic address:

Aims: Cumulative evidence suggests that long-chain non-coding RNA (lncRNA) is involved in the pathogenesis of osteoarthritis (OA). The present study aimed to explore the regulatory role and related mechanisms of HOX transcript antisense intergenic RNA (HOTAIR) in OA.

Material And Methods: The OA mouse model was constructed by the medial meniscus (DMM) method, and Interleukin (IL)-1β-induced chondrocytes were used to simulate OA in vitro.

Key Findings: Results found that HOTAIR was significantly up-regulated in articular cartilage tissues of OA mice and IL-1β-induced chondrocytes, accompanied by down-regulation of miR-20b and increased expression of the phosphatase and tensin homolog (PTEN). HOTAIR silencing improved cartilage tissue damage in OA mice, and promoted the expression of collagen II and aggrecan in cartilage tissue, while inhibited the expression of matrix metalloproteinases (MMP)-13 and ADAMTS-5. Overexpression of HOTAIR inhibited the proliferation of IL-1β-induced chondrocytes and promoted apoptosis and extracellular matrix (ECM) degradation, whereas the effect of HOTAIR knockdown was reversed. Bioinformatics software and luciferase reporter experiments confirmed that HOTAIR could negatively regulate miR-20b, and PTEN was a target gene of miR-20b. An increase in PTEN expression induced by HOTAIR overexpression could be reversed by the introduction of miR-20b mimic. HOTAIR overexpression significantly reversed miR-20 mimic-mediated inhibition of apoptosis and ECM degradation in IL-1β-induced chondrocytes, whereas the introduction of si-HOTAIR eliminated anti-miR-20b-mediated apoptosis and ECM degradation.

Significance: HOTAIR can participate in OA by promoting chondrocyte apoptosis and ECM degradation, which may be related to its targeted regulation of miR-20b/PTEN axis.
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http://dx.doi.org/10.1016/j.lfs.2020.117685DOI Listing
July 2020

Discovery of Novel Autophagy Inhibitors and Their Sensitization Abilities for Vincristine-Resistant Esophageal Cancer Cell Line Eca109/VCR.

ChemMedChem 2020 06 22;15(11):970-981. Epub 2020 Apr 22.

Department of Pharmaceutical Chemistry, Third Military Medical University, Chongqing, 400038, China.

Resistance phenomena, especially acquired drug resistance, have been severely hampering the application of chemotherapeutics during cancer chemotherapy. Autophagy plays a role in maintaining the survival of cancer cells and might mediate resistance to chemotherapy drugs. Herein, a new series of 5-amino-2-ether-benzamide derivatives were synthesized and evaluated as autophagy inhibitors. Selected from 14 synthesized compounds as lead autophagy inhibitor, N-(cyclohexylmethyl)-5-(((cyclohexylmethyl)amino)methyl)-2-((4-(trifluoromethyl)benzyl)oxy)benzamide (4 d) showed the most obvious effect of LC3B protein conversion. Further, its autophagy inhibition, evaluated by using transmission electron microscopy and confocal microscopy, showed that the fusion of autophagosomes and lysosomes in the final stage of autophagic flux was suppressed. We also found that 4 d could enhance the chemosensitivity of vincristine in vincristine-resistant esophageal cancer cell line Eca109/VCR in a synergistic, associative manner. Moreover, a computational study showed that 4 d might bind with p62-zz to inhibit autophagy. We also found 4 d to be relatively less cytotoxic to normal cells versus cancer cells than the reported p62-zz inhibitor.
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http://dx.doi.org/10.1002/cmdc.202000004DOI Listing
June 2020

Characterizing the Binding Sites for GK Domain of DLG1 and DLG4 via Molecular Dynamics Simulation.

Front Mol Biosci 2020 23;7. Epub 2020 Jan 23.

Department of Pharmaceutical Chemistry, Third Military Medical University, Chongqing, China.

Discs-large (DLG) is a member that belongs to the membrane-associated guanylate kinase (MAGUK) family. The GK domain of DLGs has evolved into a protein-protein interaction module that could bind with kinds of proteins to regulate diverse cellular functions. Previous reports have demonstrated the GK domain of DLGs functioned as a phosphor-peptide-binding module by resolving the crystal structures. Here we investigated into the interactions of DLG1 and DLG4 with their reported phosphor-peptides by molecular dynamics simulations. Post-dynamics analysis showed that DLG1/4 formed extensive interactions with phosphorylated ligands, including hydrophobic and hydrogen bonding interactions. Among them, the highly conserved residues among the DLGs in phosphor-site and β5 sheet were crucial for the binding according to the energy decomposition calculations. Additionally, the binding interactions between DLG4 and reported unphosphorylated peptides including MAP1A and designed GK inhibitory (GKI-QSF) peptides were analyzed. We found the key residues that played important roles in DLG4/unphosphorylated peptide systems were very similar as in DLG4/phosphor-peptide systems. Moreover, the molecular dynamic simulation for the complex of DLG1 and GKI-QSF was carried out and predicted that the GKI-QSF could bind with DLG1 with similar d value compared to DLG4/GKI-QSF, which was verified by using ITC assay (d = 1.20 ± 0.29 μM). Our study might be helpful for the better understanding of the structural and biological function of DLGs GK domain and encourage the discovery of new binders.
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http://dx.doi.org/10.3389/fmolb.2020.00001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989407PMC
January 2020

Gut microbiome associated with APC gene mutation in patients with intestinal adenomatous polyps.

Int J Biol Sci 2020 1;16(1):135-146. Epub 2020 Jan 1.

Guangxi Medical University Affiliated Tumor Hospital, Nanning, Guangxi, 530021, China.

The 'adenoma-carcinoma sequence' is a well-recognized model of colorectal cancer (CRC) development. However, the interaction between gut microbiota and genetic variation in the initiation of CRC is not clear. Our study attempts to demonstrate the relationship between gut microbiota and host genetics in patients with intestinal adenomatous polyps. The entire exon region of the APC gene was sequenced in 35 patients with pathologically diagnosed adenomatous polyps. Patients with highly pathogenic APC mutation were classified as the case group, while the others were classified as the control group. The patients'stool and serum samples were respectively collected for metagenomics and metabolomics measurements. In the analysis of gut microbiome, there were three most important species, in which Fusobacterium_mortiferum was significantly increased while Faecalibacterium_prausnitzii and Bifidobacterium_pseudocatenulatum were significantly decreased in the case group. The significantly low abundance of the Photosynthesis pathway in patients with APC mutation was due to the low abundance of species Faecalibacterium_prausnitzii and Bifidobacterium_pseudocatenulatum. Moreover, there were two clusters of KEGG pathways correlated with two clusters of species characterized by Faecalibacterium_prausnitzii and Fusobacterium_mortiferum. As to serum metabolomics, the abundance of (R)-3-Hydroxybutyric acid and 2-Hydroxyphenethylamine were significantly higher in patients with APC mutation, while the abundance of 1-Aminocyclopropanecarboxylic acid,7-Ketocholesterol, DL-lactate, and L-Pyroglutamic acid were significantly higher in controlgroup. After analyzing the metabolome and microbiome data by sparCCmethod, we found that there was a significantly negative correlation between the abundance of Faecalibacterium_prausnitzii and Fusobacterium_mortiferum, and a significantly positive correlation between Faecalibacterium_prausnitzii abundance and the steroid hormone Hydrocortisone (Cortisol) in serum. Host's APC mutation was closely related to the changes of gut microbiota and serum metabolites, and some species of gut microbiome like Faecalibacterium_prausnitzii and Fusobacterium_mortiferum might have the potential to predict the development of CRC from intestinal adenomatous polyps.
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http://dx.doi.org/10.7150/ijbs.37399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930378PMC
November 2020

Has the Efficiency of China's Healthcare System Improved after Healthcare Reform? A Network Data Envelopment Analysis and Tobit Regression Approach.

Int J Environ Res Public Health 2019 12 2;16(23). Epub 2019 Dec 2.

School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Background: A healthcare system refers to a typical network production system. Network data envelopment analysis (DEA) show an advantage than traditional DEA in measure the efficiency of healthcare systems. This paper utilized network data envelopment analysis to evaluate the overall and two substage efficiencies of China's healthcare system in each of its province after the implementation of the healthcare reform. Tobit regression was performed to analyze the factors that affect the overall efficiency of healthcare systems in the provinces of China.

Methods: Network DEA were obtained on MaxDEA 7.0 software, and the results of Tobit regression analysis were obtained on StataSE 15 software. The data for this study were acquired from the China health statistics yearbook (2009-2018) and official websites of databases of Chinese national bureau.

Results: Tobit regression reveals that regions and government health expenditure effect the efficiency of the healthcare system in a positive way: the number of high education enrollment per 100,000 inhabitants, the number of public hospital, and social health expenditure effect the efficiency of healthcare system were negative.

Conclusion: Some provincial overall efficiency has fluctuating increased, while other provincial has fluctuating decreased, and the average overall efficiency scores were fluctuations increase.
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http://dx.doi.org/10.3390/ijerph16234847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926868PMC
December 2019

Numerical Investigation on the Effects of Dielectric Barrier on a Nanosecond Pulsed Surface Dielectric Barrier Discharge.

Molecules 2019 Oct 31;24(21). Epub 2019 Oct 31.

Commercial Aircraft Corporation of China, Ltd., Shanghai 200120, China.

In order to understand the impacts of dielectric barrier on the discharge characteristics of a nanosecond pulsed surface dielectric barrier discharge (NS-DBD), the effects of dielectric constant and dielectric barrier thickness are numerically investigated by using a three-equation drift-diffusion model with a 4-species 4-reaction air chemistry. When the dielectric constant increases, while the dielectric barrier thickness is fixed, the streamer propagation speed (), the maximum streamer length (), the discharge energy ( Q D _ e i ), and the gas heating ( Q G H ) of a pulse increase, but the plasma sheath thickness (), the fast gas heating efficiency η , and the charge densities on the wall surface decrease. When the dielectric barrier thickness increases, while the dielectric constant is fixed, , , Q D _ e i , and Q G H of a pulse decrease, but , η , and the charge densities on the wall surface increase. It can be concluded that the increase of the dielectric constant or the decrease of the dielectric barrier thickness results in the increase of the capacitance of the dielectric barrier, which enhances the discharge intensity. Increasing the dielectric constant and thinning the dielectric barrier layer improve the performance of the NS-DBD actuators.
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http://dx.doi.org/10.3390/molecules24213933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864468PMC
October 2019

Binding interactions of epididymal protease inhibitor and semenogelin-1: a homology modeling, docking and molecular dynamics simulation study.

PeerJ 2019 5;7:e7329. Epub 2019 Aug 5.

Department of Obstetrics and Gynecology, Southwest Hospital, The Third Military Medical University, Chongqing, China.

Epididymal protease inhibitor (EPPIN) that is located on the sperm surface and specific to the male reproductive system is a non-hormonal contraceptive target, since the binding of EPPIN with the seminal plasma protein semenogelin-1 (SEMG1) causes a loss of sperm function. Here, we investigated the binding interactions between EPPIN and SEMG1 by homology modeling, docking and molecular dynamics simulation. Since no crystal structure was reported for EPPIN, its 3D structure was constructed by homology modeling and refined by dynamics simulation, illustrating the C-terminus domain of EPPIN could bind with its N-terminus domain through the residues 30-32 and 113-116. The binding interaction of SEMG1 peptide and EPPIN was investigated by Z-DOCK and dynamics simulation. After evaluating the models according to the calculated binding free energies, we demonstrated that C-terminus domain of EPPIN was important for the binding of SEMG1 via residues Tyr107, Gly112, Asn116, Gln118 and Asn122, while residue Arg32 in N-terminus domain also had contribution for their binding interaction. Additionally, the binding pocket of EPPIN was defined according to these key residues and verified by molecular docking with reported inhibitor , suggesting that the pocket formed by Arg32, Asn114, Asn116, Phe117 and Asn122 could be important for the design of new ligands. This study might be helpful for the understanding of biological function of EPPIN and would encourage the discovery of non-hormonal contraceptive leads/drugs in the future.
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http://dx.doi.org/10.7717/peerj.7329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686837PMC
August 2019

Does capitation prepayment based Integrated County Healthcare Consortium affect inpatient distribution and benefits in Anhui Province, China? An interrupted time series analysis.

Int J Integr Care 2019 Jul 8;19(3). Epub 2019 Jul 8.

Tongji Medical College, Huazhong University of Science and Technology, CN.

Objective: This study aims to compare the level and trend changes of inpatient and funds distribution, as well as inpatient benefits before and after the official operation of the ICHC in Anhui.

Methods: A total of 1,013,815 inpatient cases were collected from the hospitalisation database in two counties in Anhui Province, China, during the course of the study from January 2014 to June 2017. The effect of the reform was assessed beginning with its formal operation in February 2016. Longitudinal time series data were analysed using segmented linear regression of an interrupted time series analysis.

Results: The average hospitalisation expenses showed a decreasing trend and the actual compensation ratio increased significantly (p-value < 0.01). Most of the indicators in the two counties performed well, and the effect of ICHC policy was better in Funan County than in Dingyuan County. The distribution of inpatients and NRCMS funds outside the county after the reform in Dingyuan showed an increasing trend (0.27, 95%CI: 0.12 to 0.42, p-value < 0.01; 0.70, 95%CI: 0.32 to 1.09, p-value < 0.01) and the distribution of inpatients and NRCMS funds in THs showed a more obvious upward trend after the reform in Funan (0.44, 95%CI: 0.22 to 0.67, p-value < 0.001; 0.34, 95%CI: 0.23 to 0.45, p-value < 0.001).

Conclusions: This study suggests that the ICHC policy provides effective strategies in promoting the integration of the healthcare delivery system in China. These strategies include strengthening family doctor signing service system and health management, developing telemedicine technology, reducing the weak points of the healthcare services, and introducing private hospitals to form new ICHCs.
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http://dx.doi.org/10.5334/ijic.4193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625539PMC
July 2019

Effect of an Integrated Payment System on the Direct Economic Burden and Readmission of Rural Cerebral Infarction Inpatients: Evidence from Anhui, China.

Int J Environ Res Public Health 2019 05 3;16(9). Epub 2019 May 3.

School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Rural China is piloting an integrated payment system, which prepays a budget to a medical alliance rather than a single hospital. This study aims to evaluate the effect of this reform on the direct economic burden and readmission rates of cerebral infarction inpatients. The settlement records of 78,494 cerebral infarction inpatients were obtained from the New Rural Cooperative Medical Scheme (NRCMS) database in Dingyuan and Funan Counties in the Anhui Province. The direct economic burden was estimated by total costs, out-of-pocket expenditures, the out-of-pocket ratio, and the compensation ratio of the NRCMS. Generalized additive models and multivariable linear/logistic regression were applied to measure the changes of the dependent variables along with the year. Within the county, the total costs positively correlated to the year ( = 313.10 in 2015; 163.06 in 2016). The out-of-pocket expenditures, out-of-pocket ratios, and the length-of-stay positively correlated to the year in 2015 ( = 105.10, 0.01, and 0.18 respectively), and negatively correlated to the year in 2016 ( = -58.40, -0.03, and -0.30, respectively). The odds ratios of the readmission rates were less than one within the county (0.70 in 2015; 0.53 in 2016). The integrated payment system in the Anhui Province has considerably reduced the direct economic burden for the rural cerebral infarction inpatients, and the readmission rate has decreased within the county. Inpatients' health outcomes should be given further attention, and the long-term effect of this reform model awaits further evaluation.
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http://dx.doi.org/10.3390/ijerph16091554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539045PMC
May 2019

Determinants of inappropriate admission of elderly people in county-level hospitals: a cross-sectional study in rural China.

BMJ Open 2019 05 1;9(4):e026443. Epub 2019 May 1.

School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Objective: The purpose of this paper is to investigate the characteristics and determinants of inappropriate admission to hospital of elderly people in rural China.

Design: A cross-sectional study of a comparison between the elderly and non-elderly groups of people.

Setting: The survey was conducted on the largest county-level general hospitals in four counties in central and western China.

Participants: A total of 652 rural patients admitted in hospitals were surveyed, who were divided into two groups according to age: elderly group (n=230, age ≥60 years) and non-elderly group (n=422, age <60 years).

Primary Measures: The Chinese version of the appropriateness evaluation protocol was used to evaluate the inappropriate admission rates. The interactive regression models based on the relationship of age (elderly and non-elderly) with other factors and binary logistic regression models were used in the analysis of the specific factors and determinants of the inappropriate admission of elderly people.

Result: The inappropriate admission rate for the rural elderly was 30%, which was lower than that of the non-elderly people (40.8%). Compared with the non-elderly group, women in the elderly group (OR=0.33, 95% CI 0.15 to 0.73) had a lower incidence of inappropriate admission, and elderly people with chronic diseases (OR=3.33, 95% CI 1.23 to 9.04) were more prone to being inappropriately admitted than non-elderly people with chronic diseases. The binary logistic regression analysis shows that county, age (OR=0.94. 95% CI 0.90 to 0.99), gender (OR=0.49, 95% CI 0.25 to 2.98), department and response to doctor's admission request were the determinants of the inappropriate admission of elderly patients.

Conclusion: The inappropriate admission rate of elderly people in rural China was high. We found that gender and chronic disease are the specific factors that were specific to non-elderly people. County, age, gender, department and response to a doctor's admission request had substantial influence on the inappropriate admission of the elderly in rural China.
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http://dx.doi.org/10.1136/bmjopen-2018-026443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502026PMC
May 2019

Is There a Difference in the Utilisation of Inpatient Services Between Two Typical Payment Methods of Health Insurance? Evidence from the New Rural Cooperative Medical Scheme in China.

Int J Environ Res Public Health 2019 04 19;16(8). Epub 2019 Apr 19.

School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

This study aimed to evaluate the effects of the differences between two typical payment methods for the new rural cooperative medical scheme (NRCMS) in China on the utilisation of inpatient services. Interrupted time-series analysis (ITSA) and propensity score matching (PSM) were used to measure the difference between two typical payment methods for the NRCMS with regard to the utilisation of inpatient services. After the reform was formally implemented, the level and slope difference after reform compared with pre-intervention (distribution of inpatients in county hospitals (DIC), distribution of inpatients in township hospitals (DIT) and the actual compensation ratio of inpatients (ARCI)) were not statistically significant. Kernel matching obtained better results in reducing the mean and median of the absolute standardised bias of covariates of appropriateness of admission (AA), appropriateness of disease (AD). The difference in AA and AD of the matched inpatients between two groups was -0.03 (-value = 0.042, 95% CI: -0.08 to 0.02) and 0.21 (-value < 0.001, 95% CI: -0.17 to 0.25), respectively. The differences in the utilisation of inpatient services may arise owing to the system designs of different payment methods for NRCMS in China. The causes of these differences can be used to guide inpatients to better use medical services, through the transformation and integration of payment systems.
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http://dx.doi.org/10.3390/ijerph16081410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518194PMC
April 2019

Metal-Free Aerobic Oxidative Selective C-C Bond Cleavage in Heteroaryl-Containing Primary and Secondary Alcohols.

Org Lett 2019 05 17;21(9):3028-3033. Epub 2019 Apr 17.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital , Sichuan University , Chengdu , Sichuan 610041 , China.

A transition-metal-free aerobic oxidative selective C-C bond-cleavage reaction in primary and secondary heteroaryl alcohols is reported. This reaction was highly efficient and tolerated various heteroaryl alcohols, generating a carboxylic acid derivative and a neutral heteroaromatic compound. Experimental studies combined with density functional theory calculations revealed the mechanism underlying the selective C-C bond cleavage. This strategy also provides an alternative simple approach to carboxylation reaction.
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http://dx.doi.org/10.1021/acs.orglett.9b00563DOI Listing
May 2019

Iodine Clathrated: A Solid-State Analogue of the Iodine-Starch Complex.

Chemistry 2019 Jun 7;25(31):7485-7488. Epub 2019 May 7.

Department of Chemistry, University of Jyvaskyla, P. O. Box 35, 40014, Jyväskylä, Finland.

Co-crystallizing iodine with a simple dicationic salt (1,8-diammoniumoctane chloride) results in the clathration of the iodine (I ) molecules inside trigonal and hexagonal helical channels of the crystal lattice with 72 wt % overall I loading. The I inside the bigger trigonal channel forms a I-I⋅⋅⋅I-I⋅⋅⋅I-I halogen-bonded infinite helical chain, while the I in the smaller hexagonal channel is disordered. In both channels the I interaction with the channel wall happens through I-I⋅⋅⋅Cl halogen bonds. The helical channels in the crystal lattice are constructed via the strong charge-assisted H N H⋅⋅⋅Cl hydrogen bonds between the dications and the chloride anions. The structure shows a marked similarity with the well-known starch-I system, and thus may provide insight for the yet unresolved structure of the I in the helical starch channel.
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http://dx.doi.org/10.1002/chem.201901734DOI Listing
June 2019

Maternal Plasma l-Carnitine Reduction During Pregnancy Is Mainly Attributed to OCTN2-Mediated Placental Uptake and Does Not Result in Maternal Hepatic Fatty Acid -Oxidation Decline.

Drug Metab Dispos 2019 06 27;47(6):582-591. Epub 2019 Mar 27.

Laboratory of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences (M.B., Y.C., M.C., P.L., Z.M., H.Z., S.Z., H.J.) and Women's Hospital, School of Medicine (Q.Z., D.S., C.Z.), Zhejiang University, Hangzhou, People's Republic of China

l-Carnitine (l-Car) plays a crucial role in fatty acid -oxidation. However, the plasma l-Car concentration in women markedly declines during pregnancy, but the underlying mechanism and its consequences on maternal hepatic -oxidation have not yet been clarified. Our results showed that the plasma l-Car level in mice at gestation day (GD) 18 was significantly lower than that in nonpregnant mice, and the mean fetal-to-maternal plasma l-Car ratio in GD 18 mice was 3.0. Carnitine/organic cation transporter 2 (OCTN2) was highly expressed in mouse and human placenta and upregulated as gestation proceeds in human placenta, whereas expressions of carnitine transporter (CT) 1, CT2, and amino acid transporter B were extremely low. Further study revealed that renal peroxisome proliferator-activated receptor (PPAR) and OCTN2 were downregulated and the renal l-Car level was reduced, whereas the urinary excretion of l-Car was lower in late pregnant mice than in nonpregnant mice. Meanwhile, progesterone (pregnancy-related hormone) downregulated the expression of renal OCTN2 via PPAR-mediated pathway, and inhibited the activity of OCTN2, but estradiol, corticosterone, and cortisol did not. Unexpectedly, the maternal hepatic level of l-Car and -hydroxybutyrate (an indicator of mitochondrial -oxidation), and mRNA levels of several enzymes involved in fatty acid -oxidation in GD 18 mice were higher than that in nonpregnant mice. In conclusion, OCTN2 mediated l-Car transfer across the placenta played a major role in maternal plasma l-Car reduction during pregnancy, which did not subsequently result in maternal hepatic fatty acid -oxidation decrease.
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http://dx.doi.org/10.1124/dmd.119.086439DOI Listing
June 2019
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