Leonurine inhibits ferroptosis in renal tubular epithelial cells by activating p62/Nrf2/HO-1 signaling pathway / 中国中药杂志

To investigate the protective effect and the potential mechanism of leonurine(Leo) against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells), an in vitro erastin-induced ferroptosis model was constructed to detect the cell viability as well as the expressions of ferroptosis-related indexes and signaling pathway-related proteins. HK-2 cells were cultured in vitro, and the effects of Leo on the viability of HK-2 cells at 10, 20, 40, 60, 80 and 100 μmol·L~(-1) were examined by CCK-8 assay to determine the safe dose range of Leo administration. A ferroptosis cell model was induced by erastin, a common ferroptosis inducer, and the appropriate concentrations were screened. CCK-8 assay was used to detect the effects of Leo(20, 40, 80 μmol·L~(-1)) and positive drug ferrostatin-1(Fer-1, 1, 2 μmol·L~(-1)) on the viability of ferroptosis model cells, and the changes of cell morphology were observed by phase contrast microscopy. Then, the optimal concentration of Leo was obtained by Western blot for nuclear factor erythroid 2-related factor 2(Nrf2) activation, and transmission electron microscope was further used to detect the characteristic microscopic morphological changes during ferroptosis. Flow cytometry was performed to detect reactive oxygen species(ROS), and the level of glutathione(GSH) was measured using a GSH assay kit. The expressions of glutathione peroxidase 4(GPX4), p62, and heme oxygenase 1(HO-1) in each group were quantified by Western blot. RESULTS:: showed that Leo had no side effects on the viability of normal HK-2 cells in the concentration range of 10-100 μmol·L~(-1). The viability of HK-2 cells decreased as the concentration of erastin increased, and 5 μmol·L~(-1) erastin significantly induced ferroptosis in the cells. Compared with the model group, Leo dose-dependently increased cell via-bility and improved cell morphology, and 80 μmol·L~(-1) Leo promoted the translocation of Nrf2 from the cytoplasm to the nucleus. Further studies revealed that Leo remarkably alleviated the characteristic microstructural damage of ferroptosis cells caused by erastin, inhibited the release of intracellular ROS, elevated GSH and GPX4, promoted the nuclear translocation of Nrf2, and significantly upregulated the expression of p62 and HO-1 proteins. In conclusion, Leo exerted a protective effect on erastin-induced ferroptosis in HK-2 cells, which might be associated with its anti-oxidative stress by activating p62/Nrf2/HO-1 signaling pathway.

Lysosome TMEM175 Potassium Channel Protein and Parkinson’s Disease / 中国生物化学与分子生物学报

Parkinson’s disease (PD)is a complex neurodegenerative disorder by motor impairments and non-motor symptoms. While dopamine-based therapies are effective in fighting the symptoms in the early stages of the disease‚ a lack of neuroprotective drugs means that the disease continues to progress. New disease modifying therapies and novel therapeutic strategies are in high demand for PD patients. Genetic studies indicated that both rare and common genetic variants could induce the development PD. As a risk candidate gene for Parkinson’s disease‚ TMEM175 encodes a lysosomal potassium channel protein with new structures‚ and the protein plays an important role in maintaining lysosomal membrane potential and pH stability. With the in-depth understanding for its structure and function‚ TMEM175 deficiency results in decreased lysosomal catalytic activity and the pathological aggregation of α-synuclein. In view of the importance of lysosome potassium channel TMEM175‚ it could be an interesting target for the development of drugs to treat Parkinson’s disease and other neurodegenerative diseases. Herein we review the structure and function TMEM175‚ and focuses on its involvement in the occurrence and development of PD by affecting the function of lysosome as a homeostatic regulator. Future drug screenings based on lysosome TMEM175 may be carried out to maintain the active state or enhance the expression of TMEM175 to improve the condition of PD patients. Further investigations are needed to study how to maintain the balance between the open and closed state of TMEM175 channels to regulate the ion homeostasis of lysosomes. Studies of this ion channel protein will bring new strategies and ideas for the treatment of PD‚ and provide support for establishing the molecular status of TMEM175 in the diagnosis and treatment of PD.

Correlation of Betel Quid with Oral Cancer from 1998 to 2017: A Study Based on Bibliometric Analysis / 中华医学杂志(英文版)

Background@#Betel quid chewing has been a major risk factor for oral cancer (OC) in southern China. This study aimed to analyze the scientific publications on the relationship between betel quid chewing and OC and construct a model to quantitatively and qualitatively evaluate pertinent publications from 1998 to 2017.@*Methods@#The publications from 1998 to 2017 were retrieved from the Web of Science Core Collection database. Microsoft Excel, Thomson Data Analyzer, VOSviewer, and CiteSpace software were used to analyze the publication outcomes, journals, countries/regions, institutions, authors, research areas, and research frontiers.@*Results@#A total of 788 publications on the relationship between betel quid chewing and OC published until October 25, 2017, were identified. The top 4 related journals were Journal of Oral Pathology Medicine, Oral Oncology, Plos One, and International Journal of Cancer. The top five countries engaged in related research included China, India, the United States, the United Kingdom, and Malaysia. The corresponding disciplines, such as oncology, oral surgery, pathology, environmental and occupational health, and toxicology, were mainly concentrated in three disciplines. The subject terms squamous cell carcinoma, OC, betel quid, expression, oral submucous fibrosis, India, and p53 ranked first among research hotspots. The burst terms squamous cell carcinoma, OC, betel quid, and expression ranked first in research frontiers.@*Conclusions@#Research in this area emphasized hotspots such as squamous cell carcinoma, OC, oral submucosal fibrosis, betel quid, and tobacco. The annual number of publications steadily decreased from 1998 to 2017, with a lack of a systematic study from interdisciplinary perspectives, inadequate pertinent journals, limited regions with the practice of betel quid chewing, and insufficient participation of researchers, which indicate that as the prevalence of OC increases, particularly in China, research in this area warrants further expansion.

Characteristics and Institutional Arrangements for Outpatient Service Price Setting across OECD countries / 中国卫生经济

The particularity of healthcare markets made the pricing of medical services a contentious issue.It reviewed the characteristics,technical and institutional arrangements for the outpatient service price setting across Organization for Economic Co-operation and Development(OECD) countries,aiming at providing international experiences for medical service pricing reform in China.

Comparison of benazepril monotherapy to amlodipine plus benazepril in the treatment of patients with mild and moderate hypertension: a multicentre, randomized, double-blind, parallel-controlled study / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and tolerability of the fixed combination of amlodipine 5 mg/benazepril 10 mg once-daily therapy, compared with benazepril, 10 mg, monotherapy in patients with mild and moderate hypertension, and to evaluate the 24 h antihypertensive efficacy and the duration of action by ambulatory blood pressure monitoring.</p><p><b>METHODS</b>In a multicenter, randomized, double-blind, parallel controlled trial, 356 cases of hypertensive patients after 2 weeks wash-out, and then given 4 weeks of benazepril 10 mg monotherapy, 220 patients with mean seated diastolic blood pressure (SeDBP) remained ≥ 90 mm Hg (1 mm Hg = 0.133 kPa) were randomly divided into benazepril 10 mg/amlodipine 5 mg (BZ10/AML5) fixed-dose combination therapy group (once a day, n = 113), and benazepril monotherapy group (daily 20 mg, n = 107). In the two groups the patients with SeDBP ≥ 90 mm Hg were doubled the dosage of the initial regimen at the end of 4-week treatment for additional 4 weeks, and the patients with SeDBP < 90 mm Hg remained the initial regimen for additional 4 weeks. The primary endpoint was to evaluate the improvement of SeDBP at the end of 8-week treatment. There were 74 patients (the combination therapy group n = 38, monotherapy therapy group n = 36) completed the 24 h ambulatory blood pressure monitoring which was included in the final efficacy analysis.</p><p><b>RESULTS</b>The randomized, double-blind treatment for 8 weeks, the mean value of SeDBP reduction, the reaching target blood pressure rate and total successful response rate to the treatment (a SeDBP < 90 mm Hg or a decrease of 10 mm Hg or more from baseline) were (11.7 ± 6.8) mm Hg, 65.7% and 88.5% in the combination therapy group, respectively, and were (7.7 ± 6.9) mm Hg, 35.5% and 65.5% in the monotherapy group, respectively. There were statistically significant difference between the combination therapy and the monotherapy groups in all the 3 indexs (P < 0.001). The fixed combination significantly reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) values throughout the 24 h. The trough to peak ratios of DBP/SBP in the fixed compound of benazepril/amlodipine (10 mg/5 mg) and benazepril (20 mg) alone were 83.1%/76.0% and 85.8%/79.5%, respectively. Adverse events rates were 16.8% in the combination therapy group and 35.5% in the monotherapy group (P < 0.001).</p><p><b>CONCLUSIONS</b>The combination therapy with benazepril/amlodipine was superior to benazepril monotherapy and was well tolerated in patients with essential hypertension and allowing a satisfactory BP control for 24 hours.</p>

Effect of lamivudine treatment on the quality of life of chronic hepatitis B / 中南大学学报(医学版)

OBJECTIVE@#To assess the quality of life of 3 types of chronic hepatitis B before and after the treatment of lamivudine, and to find an ideal way of medical treatment for chronic hepatitis B.@*METHODS@#One hundred and fifty patients with chronic hepatitis B were investigated in this study, among whom 5 1 were in mild state illness, 53 were middle-range and the other 46 were severe. The quality of life of the patients was assessed by the quality of life questionnaire (SF-36). The marks of questionnaire were compared before and after the use of lamivudine to assess its comprehensive curative effect on chronic hepatitis B.@*RESULTS@#The total score of SF-36, score of physical function, role-physical, mental health, social function, bodily pain and vitality were significant different before and after the treatment. Statistically significant differences were found among the 3 types of chronic hepatitis B before and after the treatment.@*CONCLUSION@#The quality of life of patients with chronic hepatitis B can be improved by using lamivudine. Assessment of quality of life may be taken as an important index in treating chronic hepatitis B.

Trend of death cause of residents in Changde from 1973 to 2002 / 中南大学学报(医学版)

OBJECTIVE@#To discuss the cause of death for residents in Changde and guarantee the evidence for the health decision-making and control of diseases by the use of YPLL analysis and comprehensive evaluation on the dynamic cause of death of residents in Changde from 1973 to 2002.@*METHODS@#The data is processed by the use of SPSS software package (version 11.0) and EXCEL software (version 2000) with the statistic methods of Cause Eliminated Life Table, Life Table, YPLL and etc.@*RESULTS@#The average population reached 5384519 and the average gender proportion of male and female is 1.12 to 1 in Changed during 1973-2002. Since 1973, total population has risen from 483 to 596 at average annual rate of 7.89% while the birthrate has decreased from 53.78% in 1973 to 8.39% in 2002. The composition of population in Changde experienced great shift in the past 30 years. The proportion of children (0 - 14) in 2002 declined by 16.15% compared with that in 1973 and the proportion of elder people has increased by 2.88% compared with that in 1973. The proportion of gender has ranged little by 1973-2002 although that of neonatal has ranged greatly.@*CONCLUSION@#The total death number of Changde in 2002 reached 1103233 and the mortality rate has sustained decline since 1973. The top 5 causes of death were diseases of respiratory system, circular system, damnification & poisoning, contagion & schistosomiasis, tumor and etc in 2002 and shifted a lot compared with that in 1973. The average life expectancy of residents in Changde was 67.6 from 1973 to 2002. The average life expectancy of males and females increased 12.63 and 11.93 years in 2002 compared with those in 1972. In the past 30 years, the diseases of respiratory system has greatly influenced the life span of residents in Changde.