Hypermethylation of the Bmp4 promoter dampens binding of HIF-1α and impairs its cardiac protective effects from oxidative stress in prenatally GC-exposed offspring.

The exposure to an unhealthy environment in utero can lead to the occurrence of cardiovascular diseases in the offspring. Glucocorticoids (GC) are essential for normal development and maturation of fetal organs and is a first-line treatment for pregnant women affected by autoimmune diseases. However, excess prenatal GC exposure might program the development of fetal organs and cause a number of chronic diseases in later life. Our previous studies indicated that cardiac functions were significantly compromised in rat offspring prenatally exposed to the synthetic glucocorticoid dexamethasone (DEX), only after ischemia-reperfusion. In the present study, we further observed that DNA hypermethylation of bone morphogenetic protein 4 (Bmp4) promoter in cardiomyocytes caused by prenatal DEX exposure substantially dampened the binding activity of transcription factor HIF-1α induced by cardiac ischemia. Therefore, prenatal DEX exposure inhibits the induction of BMP4 upon I/R and attenuates the protective effects of BMP4 in cardiomyocytes, which eventually manifests as malfunction of the adult heart. Moreover, we employed two cardiac-specific Bmp4 knock-in mouse models and found that in vivo BMP4 overexpression could rescue the cardiac dysfunction caused by prenatal GC exposure. In depth mechanistic research revealed that BMP4 protects the cardiomyocytes from mitophagy and apoptosis by attenuating mitochondrial PGC-1α expression in a p-Smad and Parkin-dependent manner. These findings suggest that prenatal GC exposure increases the susceptibility of the offspring's heart to a "second strike" after birth, due to the failure of hypoxia-induced HIF-1α transactivation of the hypermethylated Bmp4 promoter in cardiomyocytes. Pretreatment with the DNA methylation inhibitor, 5-Aza-2'-deoxycytidine, could be a potential therapeutic method for this programming effect of GC exposure during pregnancy on neonatal cardiac dysfunction.

[Placental mechanisms underlying the effects of maternal stress on the fetal development].

Placenta is the only link between the pregnant woman and fetus, and the basis for maintaining the normal pregnancy process and fetal development. Maternal stress is the maternal physiological and psychological changes caused by various factors, characterized by the increased level of glucocorticoid, which affects the hypothalamic-pituitary-target gland axis and regulates the expression of target genes. Maternal stress also changes the weight, metabolism and nutrient transportation of the placenta, which will substantially influence the development of fetus. This paper will firstly summarize the characteristics of maternal stress and its influence on offspring. Then, the changes in the body under maternal stress will be described. Finally, we will clarify the proven mechanisms underlying maternal stress and raise some important problems that have not been clarified in this area. The study of maternal stress on fetus and its underlying mechanisms will serve as theoretical basis for the diagnosis and treatment of the stress-related pregnant diseases and disorders.

Comparison of Fusion Rate and Clinical Outcomes in Minimally Invasive and Conventional Posterior Fusion for Lumbar Degenerative Disease: A Network Meta-Analysis.

BACKGROUND: The fusion rate, clinical efficacy, and complications of minimally invasive fusion surgery and open fusion surgery in the treatment of lumbar degenerative disease are still unclear. METHODS: We conducted a literature search using PubMed, Embase, Cochrane Library, CNKI, and WANFANG databases. RESULTS: This study included 38 retrospective studies involving 3097 patients. Five intervention modalities were considered: unilateral biportal endoscopic-lumbar interbody fusion (UBE-LIF), percutaneous endoscopic-lumbar interbody fusion (PE-LIF), minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF), transforaminal lumbar interbody fusion (TLIF), and posterior lumbar interbody fusion (PLIF). Quality assessment indicated that each study met acceptable quality standards. PE-LIF demonstrated reduced low back pain (Odds Ratio = 0.50, Confidence Interval: 0.38-0.65) and lower complication rate (Odds Ratio = 0.46, Confidence Interval: 0.25-0.87) compared to PLIF. However, in indirect comparisons, PE-LIF showed the lowest fusion rates, with the ranking as follows: UBE-LIF (83.2%) > MIS-TLIF (59.6%) > TLIF (44.3%) > PLIF (39.8%) > PE-LIF (23.1%). With respect to low back pain relief, PE-LIF yielded the best results, with the order of relief as follows: PE-LIF (96.4%) > MIS-TLIF (64.8%) > UBE-LIF (62.6%) > TLIF (23.0%) > PLIF (3.2%). Global and local consistency tests showed satisfactory results, and heterogeneity tests indicated good stability. CONCLUSIONS: Compared to conventional open surgery, minimally invasive fusion surgery offered better scores for low back pain and Oswestry Disability Index, lower complication rates, reduced bleeding, and shorter hospital stays. However, minimally invasive fusion surgery did not show a significant advantage in terms of fusion rate and had a longer operative time.

[Medication compliance and diet compliance in 309 oral lichen planus patients].

PURPOSE: To evaluate the feasibility and clinical outcomes of an atraumatic extraction technique using Benex Extraction System in flapless immediate implant placement in anterior teeth. METHODS: Twenty-five patients with single hopeless anterior maxillary teeth were enrolled in the study. The involved teeth were extracted using Benex Extraction System and implants were immediately placed in a flapless way. Healing abutments were connected immediately. After 4-6 months of healing, screw-retained implant temporary crowns were used to reshape the peri-implant gingiva. Permanent restorations were delivered 3 months later. Extraction time was recorded and the technique feasibility was evaluated using visual analogue scale (VAS). Peri-implant marginal bone resorption was measured in X- ray films after loading for 1 year later. Pink esthetic score (PES) was checked to evaluate the gingival esthetics. Questionnaire was delivered and collected to assess patients' satisfaction on surgical experience and esthetic outcomes. SPSS 13.0 software package was used for statistical analysis. RESULTS: Twenty-five implants osseointegrated successfully. The marginal bone resorption was (0.21±0.23) mm and PES was 8.8±1.19 after loading for 1 year. The mean extraction time was 6.87 minutes and the VAS was 3.32. All patients were satisfied with the final esthetic outcomes and felt comfort during surgery. CONCLUSIONS: According to the limited data in the study, Benex extraction System is a convenient, atraumatic and predictable technique during flapless immediate implant placement in anterior teeth.

[Construction and application of the tissue bank and database of oral mucosa precancerous lesions in the Yangtze delta].

PURPOSE: To construct a database and a tissue bank of oral mucosa precancerous lesions and to estimate the application values. METHODS: Patients in the Yangtze delta suffering oral mucosa precancerous lesions were enrolled into this study. The patients' clinical data and samples of oral precancerous mucosa, salivary and blood were collected to create a tissue bank, based on which a database was constructed using Microsoft Access software, Brower/Server structure and ASP language. RESULTS: The tissue bank and database of oral mucosa precancerous lesions were successfully built. The procedure to harvest, store and transport the samples had been standardized. The database showed good interactive interface, convenient for data collection, query and share in the internet. CONCLUSIONS: We constructed the tissue bank and database of oral mucosa precancerous lesions for the first time, which not only help preserve the biological resource of oral mucosa precancerous lesions, but also provide enormous convenience in clinical work, researching and teaching. Supported by Research Fund of Science and Technology Committee of Shanghai Municipality (08ZR1416700).