Pre-eclampsia (PE), which results from abnormal placentation, is a primary cause of maternal and neonatal morbidity and mortality. However, the causes of abnormal development of the placenta remain poorly understood. BHLHE40 is a transcriptional repressor in response to hypoxia. Bioinformatics analysis demonstrated that BHLHE40 negatively regulates miR-196a-5p expression, which may decrease miR-196a-5p to target SNX16. Since SNX16 exerts an inhibitory effect on cell migration, it may disrupt trophoblast cell migration in placentation. Therefore, the objective of this study was to explore a possible role of the BHLHE40/miR-196a-5p/SNX16 axis in PE pathogenesis. BHLHE40, miR-196a-5p and SNX16 mRNA and/or protein levels were detected in PE and normal placenta tissues. PE models in vitro and in vivo were constructed by culturing trophoblasts under hypoxia and reducing the uterine perfusion pressure in pregnant C57/BL6N mice, respectively. BHLHE40 and SNX16 were upregulated in PE placenta, while miR-196a-5p was downregulated. Knockdown of BHLHE40 reversed miR-196a-5p expression in trophoblasts under hypoxia, and upregulation of miR-196a-5p inhibited SNX16 expression. As indicated by ChIP assay, BHLHE40 bound to the promoter of the miR-196a-5p gene; luciferase reporter analysis showed that miR-196a-5p could bind to the 3ʹ-untranslated region of SNX16 mRNA. Knockdown of either BHLHE40 or SNX16, or an increase in miR-196a-5p, restored cell viability, migration, invasion and matrix metalloprotein (MMP)-2 and MMP-9 expression under hypoxia. BHLHE40 knockdown also alleviated PE symptoms in pregnant C57/BL6N mice. This study supports involvement of the BHLHE40/miR-196a-5p/SNX16 axis in PE pathogenesis; Proper adjustment of the BHLHE40/miR-196a-5p/SNX16 axis is able to attenuate PE symptoms.

MicroRNAs (miRNAs) are emerging as important regulators of various physiological and pathological processes and may serve key roles in the maintenance of bone homeostasis via effects on osteoblast differentiation. The aim of the present study was to define the role of miR‑877‑3p in osteoblast differentiation using MC3T3‑E1 cells, an osteoblast precursor cell line. It was demonstrated using RT‑qPCR analysis that miR‑877‑3p was gradually increased in MC3T3‑E1 cells during the osteoblastic differentiation induced by transforming growth factor (TGF)‑β1. Gain‑of‑function and loss‑of‑function experiments revealed that the overexpression of miR‑877‑3p promoted the osteoblastic differentiation of MC3T3‑E1 cells, whereas depletion of miR‑877‑3p inhibited this process in vitro and in vivo. Bioinformatics analysis and validation experiments demonstrated that Smad7, which acts as a negative regulator of osteogenesis, was a target of miR‑877‑3p. Furthermore, the overexpression of Smad7 partially reversed the osteoblastic differentiation of MC3T3‑E1 cells induced by miR‑877‑3p. In conclusion, the results of the present study suggest that the miR‑877‑3p/Smad7 axis is associated with the osteoblastic differentiation of MC3T3‑E1 cells and may indicate a potential therapeutic approach for osteogenesis disorders.

INPLASY202110065 The Effect of Lidocaine on the prevention of post-mastectomy pain syndrome: A Meta-Analysis and Systematic Review Keywords: Breast cancer; lidocaine; Mastectomy; post-mastectomy pain syndrome. Download PDF – 202110065

Intractable hiccups serve no physiological purpose, but significantly reduce the quality of life. There are a variety of medications suggested for the treatment of persistent or intractable hiccups. However, it remains a great challenge for the management of intractable hiccups. In this case report, we describe the technique of percutaneous laser cervical discectomy under the sonographic guidance in treatment of intractable hiccups. A 41-year-old male, who suffered intractable hiccups over 11 years, came to our pain department in December 2020. Neither oral medication nor phrenic nerve block achieved satisfactory relief of hiccups. Magnetic resonance imaging and computed tomography scan revealed cervical disc herniation of C4/5 and C5/6. Following selective cervical nerve root block, complete but short-term control of symptoms lasted less than 48 hours. Percutaneous laser cervical discectomy was then performed under ultrasound guidance and achieved complete and enduring symptomatic relief up to 14-month follow-up. Cervical degenerative changes may be considered as potential cause for intractable hiccups, and ultrasound-guided percutaneous laser cervical discectomy may be used to treat hiccups caused by cervical discogenic etiology.