Inflammation Triggers Chondrocyte Ferroptosis in TMJOA via HIF-1α/TFRC.

Inflammation and loss of articular cartilage are considered the major cause of temporomandibular joint osteoarthritis (TMJOA), a painful condition of the temporomandibular joint (TMJ). To determine the cause of TMJ osteoarthritis in these patients, synovial fluid of TMJOA patients was compared prior to and after hyaluronic lavage, revealing substantially elevated levels of interleukin (IL) 1ß, reactive oxidative stress (ROS), and an overload of Fe3+ and Fe2+ prior to lavage, indicative of ferroptosis as a mode of chondrocyte cell death. To ask whether prolonged inflammatory conditions resulted in ferroptosis-like transformation in vitro, we subjected TMJ chondrocytes to IL-1ß treatment, resulting in a shift in messenger RNA sequencing gene ontologies related to iron homeostasis and oxidative stress-related cell death. Exposure to rat unilateral anterior crossbite conditions resulted in reduced COL2A1 expression, fewer chondrocytes, glutathione peroxidase 4 (GPX4) downregulation, and 4-hydroxynonenal (4-HNE) upregulation, an effect that was reversed after intra-articular injections of the ferroptosis inhibitor ferrostatin 1 (Fer-1). Our study demonstrated that ferroptosis conditions affected mitochondrial structure and function, while the inhibitor Fer-1 restored mitochondrial structure and the inhibition of hypoxia-inducible factor 1α (HIF-1α) or the transferrin receptor 1 (TFRC) rescued IL-1ß-induced loss of mitochondrial membrane potential. Inhibition of HIF-1α downregulated IL-1ß-induced TFRC expression, while inhibition of TFRC did not downregulate IL-1ß-induced HIF-1α expression in chondrocytes. Moreover, inhibition of HIF-1α or TFRC downregulated the IL-1ß-induced MMP13 expression in chondrocytes, while inhibition of HIF-1α or TFRC rescued IL-1ß-inhibited COL2A1 expression in chondrocytes. Furthermore, upregulation of TFRC promoted Fe2+ entry into chondrocytes, inducing the Fenton reaction and lipid peroxidation, which in turn caused ferroptosis, a disruption in chondrocyte functions, and an exacerbation of condylar cartilage degeneration. Together, these findings illustrate the far-reaching effects of chondrocyte ferroptosis in TMJOA as a mechanism causing chondrocyte death through iron overload, oxidative stress, and articular cartilage degeneration and a potential major cause of TMJOA.

[The enlightenment of foreign MD-MPH double degree program to the cultivation of high-level applied public health talents in China].

Objective: To understand the current status of foreign dual-degree programs of Medical Doctor (MD) and Master of Public Health (MPH) and provide evidence-based decision-making reference for promoting the education of high-level applied public health talents in China. Methods: The list of involved institutions and information of foreign MD-MPH dual-degree programs was collected through literature retrieval, online information searching, and additional survey of key figures. We extracted the details of each project regarding professional fields, core competence, length of schooling, teaching and learning arrangement, internship eligibility, and graduation assessment. Python 3.8.0 was used for data cleaning, and the occurrence frequency of related items in each dimension was calculated. Results: A total of 99 MD-MPH programs from 104 foreign institutions were included, among which 97.1% of them were implemented in universities from the United States. The School of Public Health provided 42.4% (42/99) of the programs. Epidemiology was the major discipline set up among most programs, accounting for 12.0% (29/241) of all the specialties involved. Epidemiological research methods, health policy management and practice, and public health practice were the top 3 core competencies to be mastered. Of the 99 programs, 87 gave information on the length of the program, of which 74.7% (65/87) were five years, 6.9% (6/87) were four years, and 18.4% (16/87) included both 4-year and 5-year programs. Conclusions: The international MD-MPH programs were sophisticated and mainly organized by the School of Public Health alone or in conjunction with the School of Medicine. Epidemiology is the core course and competence objective, with a length of 4-5 years. Through learning experience from international MD-MPH programs and the Chinese unique medical development background, China should optimize its medical education system to develop a suitable talent training strategy for MD-MPH dual-degree programs in the new era.

Pioglitazone up-regulates long non-coding RNA MEG3 to protect endothelial progenitor cells via increasing HDAC7 expression in metabolic syndrome.

Long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) is expressed in endothelial cells and involved in angiogenesis and vascular function. It was proposed that MEG3 participates in the process of endothelial progenitor cells (EPCs) functions in metabolic syndrome (MetS). In this study, the circulating EPCs number and function were decreased in MetS subjects. The MEG3 expression was expressed at a lower level and microRNA-140-5p (miR-140-5p) was expressed at a higher level in circulating EPCs of subjects with MetS. Pioglitazone reversed the alterations of EPCs function and the expression levels of MEG3 and miR-140-5p in EPCs. In bone marrow-derived EPCs exposed to palmitate, down-regulation of miR-140-5p canceled the increase of MEG3 expression level induced by Pioglitazone. Overexpression of MEG3 resulted in the down-regulation of miR-140-5p. The luciferase reporter assay and RIP assay showed that MEG3 targeted miR-140-5p. In addition, the HDAC7 expression levels were regulated by miR-140-5p and MEG3. These findings demonstrated that Pioglitazone up-regulated MEG3 expression to protect EPCs via decreasing miR-140-5p expression and increasing HDAC7 expression in MetS, which may be a novel therapeutic target for preventing and treating MetS.

Environmental risk factors for women with polycystic ovary syndrome in china: a population-based case-control study.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrinology disease with heterogeneous phenotype. Environmental factors are thought to be involved in the development of PCOS. The present study aimed to explore the potential environmental risk factors of PCOS. A cross-sectional study and stratified population-based case-control study were carried out. Pre-designed questionnaires were prepared, including questions about medication history, contact history of endocrine disruptors (EDs), environment and habituation. Fasting blood was collected for measurement of sex hormone, glucose and insulin. Matched logistic regression analysis was used to find the potential independent risk factor of PCOS. One thousand eight hundred fifty-four participants (aged 12-44 years) were analyzed in the cross-sectional investigation. One hundred sixty-nine PCOS patients and 338 matched controls were compared. PCOS patients were more frequent than controls in eating plastic-packaged food (p=0.001), contacting pesticide (p=0.021), eating fruit with pericarp (p=0.001), living beside a garbage heap (p=0.001), working at an acid plant (p=0.028), taking Chinese patent drugs (p=0.001), smoking (p=0.028) and drinking alcohol (p=0.001). However, PCOS patients were less likely to use kitchen ventilators (p=0.002), eat canned food (p=0.049), contact decorated materials, use skin care products (p=0.01) and cosmetics (p=0.027). No difference was found in taking antiepileptic drugs (p=0.93). Eating plastic-packaged food (p=0.001, OR=44.449), eating fruit with pericarp (p=0.03, OR=5.7) and drinking alcohol (p=0.001, OR=29.632) were found to be the independent risk factors for PCOS. The existence of an association between EDs and PCOS was proved. Plastic-packaged food, fruit with pericarp and drinking alcohol should be avoided as possible as we can. However, the causal relationships among these factors and PCOS should be proved by further research.

[Effects of Astragalus membranaceus on left ventricular function and oxygen free radical in acute myocardial infarction patients and mechanism of its cardiotonic action].

Dynamic observations for 4 weeks were made on left ventricular function and oxygen free radical (OFR) in 43 patients first suffering from acute myocardial infarction and hospitalized in Coronary Care Unit with an attack less than 36 hours. The results showed that the Astragalus membranaceus (AM) could strengthen the left ventricular function and had an effect of anti-OFR. After administration of AM, the ratio of pre-ejection period/left ventricular ejection time (PEP/LVET) was decreased, the superoxide dismutase (SOD) activity of red blood cell was increased, and the lipid peroxidation (LPO) content of plasma was reduced. There was a significant difference between the AM group and the control group in the parameters above-mentioned. The study demonstrated that the PEP/LVET ratio was closely correlated with the SOD and LPO. It suggested that the anti-OFR effect of AM was one of the mechanisms of its cardiotonic action.

Prefabricated dentitions for complete-denture prosthodontics.

A technique employed in China to simplify the fabrication of complete dentures is described. Prefabricated dentitions (an alignment of teeth en bloc with little denture base) are used instead of arranging individual teeth into an arch. This procedure can be performed intraorally without articulator mounting. It is economical and saves time. The results of clinical application of this technique are presented.

Clinical and experimental studies of coronary heart disease treated with yi-qi huo-xue injection.

The purpose of the present work was to evaluate the clinical efficacy and the mechanism of Yi-qi Huo-xue Injection (YHI) in treatment of coronary heart disease. YHI consists of Ginseng, Astragalus and Angelicae Sinensis. The 10% dextrose serves as a placebo. The results were as follows: 1. the frequency and severity of angina episodes were reduced by 90.63%; 2. the ischemic ST-T in ECG was improved in 56.25% of cases; 3. the tolerance to treadmill exercise was increased from 348.50 to 503.50 M.; 4. the left ventricular function was strengthened, PEP/LVET ratio reduced from 0.45 to 0.36, the activity of (Na(+)-K+) ATPase in myocardial cell membrane of rats inhibited by 19.2%; 5. the blood viscosity and erythrocyte electrophoretic time lowered; 6. the adhesion and aggregation of platelet in patients with CHD were inhibited by 27% and 59.4% respectively; 7. the plasma TXB2 level in CHD was reduced from 260.28 +/- 164.4 to 139.29 +/- 57.01 pg/ml; 8. the plasma 6-keto-PGF1 alpha level in CHD was increased from 33.45 +/- 22.5 to 57.48 +/- 13.1 pg/ml, and in rats from 185.77 to 366.33 pg/ml. The differences were all statistically significant (P less than 0.05-0.01) in comparison with the placebo group.