Placental mechanisms underlying the effects of maternal stress on the fetal development / 生理学报

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.

Granulomatosis with polyangiitis with nasal symptoms as the first clinical manifestation: clinical analysis of 18 cases / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze and summarize the diagnosis, treatment and prognosis of granulomatosis with polyangiitis (GPA) with nasal symptoms as the first clinical manifestation. Methods: The data of 18 patients of GPA with nasal mucosal symptoms as the first clinical manifestation from the Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University between 2005 and 2019 was collected, including 8 males and 10 females, aged from 5 to 68 years. Nasal endoscopy, imaging examination, laboratory examination, immunological and histopathological examination of nasal mucosa were completed. All patients were treated with glucocorticoid combined with cyclophosphamide and were followed up for 2 to 15 years. Descriptive statistical method was used for analysis. Results: All the 18 patients had the nasal mucosal symptoms as the first clinical manifestation, including nasal obstruction, running nose and epistaxis. Nasal endoscopy showed swelling, erosion, scab and bleeding of nasal mucosa, and 6 cases had nasal septal perforation. Nasal sinus CT scan showed high density shadow of sinus, as well as hyperostosis and osteosclerosis. CT imaging features of pulmonary showed nodular lesion or patchy infiltration in 12 patients and cavitation was found in 6 cases. Laboratory results showed that 13 cases were positive for anti-neutrophil cytoplasmic antibodies (ANCA), and 5 cases were negative. During follow-up period, thirteen patients were symptomatic controlled and survived; two patients died of disease progression; one patient gave up treatment and died; two patients were lost to follow-up. Conclusions: Nasal symptoms are the first clinical manifestation of GPA. Early diagnosis and early treatment with glucocorticoid combined with cyclophosphamide can effectively improve the survival rate.

Recent Advances of Epigenetics in Heart Failure / 中国医学科学院学报

Heart failure(HF)is the terminal stage of cardiovascular diseases and has long been one of the most deadly condition due to its high morbidity and mortality.Since the currently available treatment options cannot meet the clinical needs,new therapeutic strategies for HF should be actively explored.Epigenetics does not involve the changes of genetic sequences but focuses on the stable inheritance of genes in different individuals.It is affected by the interaction between genes and environments,which may result in DNA methylation,histone modification,and other changes.This article summarizes the recent research advances in epigenetics in HF.

Study on quality control of Miao medicine Inula cappa based on anti-inflammatory active ingredients / 中草药

Objective: To study the quality control method of Miao medicine Inula cappa based on anti-inflammatory active ingredients. Methods: Firstly, a representative and characteristic chemical composition of effective components in I. cappa was established as an indicator component for multi-index quantitative fingerprinting. Then, the quality of I. cappa in different areas of Guizhou Province was evaluated by quantitative analysis of multiple indicators and fingerprint analysis. Results: The HPLC fingerprints and multi-index content determination methods of 35 batches of I. cappa were established. Eight of 17 common peaks of the liquid chromatographic fingerprints of I. cappa were identified. The results showed that the similarity was 0.898-0.997, eight components of which were used as indicators to determine the content of chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, cynarin and luteolin, which were 0.353-3.765, 0.056-0.495, 0.086-0.526, 0.306-2.526, 0.861-7.353, 0.729-4.268, 0.052-0.424, 0.148-1.102 mg/g, respectively. Conclusion: The fingerprinting and multi-index content determination methods based on anti-inflammatory active ingredients established have high sensitivity, good accuracy, stability and reliability, which can be used for quantitative control of Miao medicine I. cappa.

Inhibitors of aquaporin 1 and its role in tumor development and progression / 药学学报

Aquaporin 1 (AQP1), the first water channel protein discovered among the aquaporin family, is a hydrophobic transmembrane protein involved in transcellular water movement. Recent evidence shows that AQP1 plays a role in tumor cell proliferation and migration, angiogenesis and tumor development and progression, representing a potential therapeutic target. In this review, we discuss the structures, functions and inhibitors of AQP1, as well as the involvement of AQP1 in tumor development and progression.

Programming effect of glucocorticoid exposure during rat pregnancy on cardiac functions and expression of serum- and glucocorticoid-regulated protein kinase 1 in offspring / 第二军医大学学报

Objective To investigate the programming effects of glucocorticoids (GCs) exposure during rat pregnancy on the cardiac functions of adult offspring, so as to explore the cardiac protective effect of GCs and the underlying mechanisms. Methods Advanced pregnancy GCs exposure model was established with rats. The infarction degrees of myocardium of offspring rats were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining after ischemia-reperfusion (I/R) injury. The mRNA levels of cardio-protective factors serum- and glucocorticoid-regulated protein kinase 1(Sgk1), corticotropin-releasing hormone receptor 2 (Crhr2), urocortin (Ucn), and Ucn2 were determined by real-time PCR. The protein level of SGK1 was detected using Western blotting analysis. Bisulfite sequencing PCR (BSP) was employed to determine the methylation level of Sgk1 promoter. Results The body mass of the offsprings of GCs-exposed pregnant rats were significantly lower than that of the normal saline-injected pregnant rats (P<0.01). The ratio between infarction area and risk area of hearts after ischemia-reperfusion in the male adult offspring from GCs-exposed group was significantly larger than that from the vehicle group(P<0.01). The mRNA and protein levels of SGK1 were significantly decreased in male adult offspring hearts exposed to GCs prenatally (P<0.01, P<0.05), whereas Ucn and Ucn2 mRNA expressions were significantly decreased in the hearts of female adult offspring exposed to GCs prenatally (P<0.05). There were multiple CpG islands in Sgk1 promoter, with the proximal CpG island in the Sgk1 promoter being significantly hypermethylated in the heart of adult male offspring exposed to GCs during late pregnancy (P<0.01). Conclusion GCs exposure during pregnancy can cause programming effects on cardiac functions of male adult offspring in rats, probably via the down-regulation of SGK1 expression in the heart, which is largely due to the hypermethylation on Sgk1 promoter.

Antinociceptive Effect of Najanalgesin from Naja Naja Atra in a Neuropathic Pain Model via Inhibition of c-Jun NH2-terminal Kinase / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Najanalgesin, a toxin isolated from the venom of Naja naja atra, has been shown to exert significant analgesic effects in a neuropathic pain model in rats. However, the molecular mechanism underlying this protective effect of najanalgesin is poorly understood. The present study sought to evaluate the intracellular signaling pathways that are involved in the antinociceptive effect of najanalgesin on neuropathic pain.</p><p><b>METHODS</b>The antinociceptive properties of najanalgesin were tested in hind paw withdrawal thresholds in response to mechanical stimulation. We analyzed the participation of the mitogen-activated protein kinase p38, extracellular-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) by western blot analysis. This inhibition of JNK was confirmed by immunohistochemistry.</p><p><b>RESULTS</b>The phosphorylation levels of JNK (as well as its downstream molecule c-Jun), p38, and ERK were significantly increased after injury. Najanalgesin only inhibited JNK and c-Jun phosphorylation but had no effect on either ERK or p38. This inhibition of JNK was confirmed by immunohistochemistry, which suggested that the antinociceptive effect of najanalgesin on spinal nerve ligation-induced neuropathic pain in rats is associated with JNK activation in the spinal cord.</p><p><b>CONCLUSION</b>The antinociceptive effect of najanalgesin functions by inhibiting the JNK in a neuropathic pain model.</p>

Inhibitory effect of medicinal plant-derived carboxylic acids on the human transporters hOAT1, hOAT3, hOATP1B1, and hOATP2B1 / 中国天然药物

A significant number of organic carboxylic acids have been shown to influence the absorption and distribution of drugs mediated by organic anion transporters (OATs). In this study, uptake experiments were performed to assess the inhibitory effects of cinnamic acid, ferulic acid, oleanolic acid, deoxycholic acid, and cynarin on hOAT1, hOAT3, hOATP1B1, and hOATP2B1. After a drug-drug interaction (DDI) investigation, cinnamic acid, ferulic acid, deoxycholic acid, and cynarin were found and validated to inhibit hOAT1 in a competitive manner, and deoxycholic acid was found to be an inhibitor of all four transporters. The apparent 50% inhibitory concentrations of cinnamic acid, ferulic acid, deoxycholic acid, and cynarin were estimated to be 133.87, 3.69, 90.03 and 6.03 μmol·L(-1) for hOAT1, respectively. The apparent 50% inhibitory concentrations of deoxycholic acid were estimated to be 9.57 μmol·L(-1) for hOAT3, 70.54 μmol·L(-1) for hOATP1B1, and 168.27 μmol·L(-1) for hOATP2B1. Because cinnamic acid, ferulic acid, and cynarin are ingredients of food or food additives, the present study suggests there are new food-drug interactions to be disclosed. In addition, deoxycholic acid may be used as a probe for studying the correlation of OATs and OATPs.

Clinical efficacies of resurfacing and non-resurfacing patella in total knee arthroplasty for osteoarthritis: A meta-analysis / 第二军医大学学报

Objective: The compare the clinical efficacies of resurfacing and non-resurfacing the patella in primary total knee arthroplasty (TKA) in osteoarthritis patients, so as to provide evidence for clinical practice. Methods: A comprehensive search for relevant studies was performed in PubMed (January 1966 to December 2010), EMBASE(1969 January to December 2010) and the Cochrane Libray databases. Only randomized control trials comparing the outcomes (incidence of anterior knee pain, revision rate, and reoperation rate, etc.) of resurfacing and nonresurfacing patella in patients undertaking primary TKA were included in the present analysis. Results: Nine independent randomized clinical trials were finally identified. Analysis of these trials showed that patellar resurfacing failed to make difference in incidence of anterior knee pain, revision rate, or reoperation rate compared with the non-surfacing group. Conclusion: Patellar resurfacing can not reduce the incidence of anterior knee pain, revision rate, or reoperation rate in patients undergoing primary TKA, and therefore can not contribute to a better outcome in these patients.

Reduced expression of miR-218 and its significance in gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression and function of miR-218 in gastric cancer.</p><p><b>METHODS</b>miR-218 levels were evaluated in 20 non-cardia gastric cancer tissues using TaqMan stem-loop real-time PCR analysis. Pre-miR-218 and anti-miR-218 inhibitor were used to change the miR-218 expression level and examine its effects on cell proliferation, apoptosis, cell cycle and cell invasion.</p><p><b>RESULTS</b>Comparing with the corresponding normal tissues, miR-218 expression was significantly reduced in the gastric cancer tissue (P < 0.01). Forced expression of miR-218 increased apoptosis in AGS cells. The proportion of apoptosis cells induced by transfection of pre-miR-218 was greater than that induced by control (21.6% vs. 10.4%, P = 0.032). Pre-miR-218 resulted in a significantly decreased cell growth activity (P < 0.01) and cell invasion (P < 0.05) of AGS cells compared with that of the control.</p><p><b>CONCLUSION</b>miR-218 expression is reduced in gastric cancer. miR-218 may function as a tumor suppressor in gastric carcinoma.</p>

The relation and evaluation of the vertebral artery and the nerve root to posterior lateral mass screw fixation / 中华外科杂志

<p><b>OBJECTIVE</b>To determine the location of the vertebral artery foramens from C(3) to C(6) and their relationship to the point 1 mm medial to the center of the lateral mass and to identify the value of oblique radiograph for cervical lateral mass screw trajectory by a cadaveric study.</p><p><b>METHODS</b>(1) Twenty-eight cervical specimens (C(3)-C(7)) of human cadavers aged from 28 to 79 years were analysed. The transverse radiographs of C(3)-C(6) vertebrae were taken and the angle between the parasagittal plane and the line connecting the point of the lateral mass with the lateral limit of the transverse process foramen of C(3)-C(6) were measured. (2) The K-wires were drilled into lateral mass of C(3)-C(6) starting 1 mm medial to the center of the lateral mass and exiting by the juncture between the transverse process and the facet in ten specimens. Four wire placements under direct visualization, including placement of the wire tip staying the ventral cortex and 2, 4, 6 mm over-penetration of the ventral cortex of lateral mass, were performed separately on each specimen. After each placement, radiographs were taken on 45 degrees oblique left and 45 degrees oblique right views. Each intervertebral foramen on the oblique radiographs was divided into two parts: superior and inferior parts. The former is the true intervertebral foramen, while the latter is the intertransverse foramen on the gross specimen. The number of wire tips in each part was quantified for each placement. All results on the radiographs were compared with those on the gross anatomy.</p><p><b>RESULTS</b>(1) The angles between the parasagittal plane and the line connecting the posterior starting point of the lateral mass with the lateral limit of the transverse foramen (C(3)-C(6)) were lateral to the sagittal plane, ranging from 5 degrees to 12 degrees. Among the vertebrae, there were no statistically significant difference (P > 0.05). (2) 15% of the wires without over-penetration and 41.3% with 2 mm over-penetration were found in the inferior parts of the intervertebral foramen in oblique views, while the wires were not noted in the intervertebral foramen by gross anatomy. with 4 mm over-penetration of the ventral cortex, 35% and 65% of wires were noted in the superior and inferior parts of the intervertebral foramen respectively, while only 28.8% of wires were found in the inferior part approximating the nerve roots in gross specimens. With 6 mm over-penetration, the number in the intervertebral foramen were 63.8% superiorly and 36.2% inferiorly on the oblique radiographs while all the tips were at the inferior part (intertransverse foramens) in gross specimens. The tip of wire crossed the line connecting the posterior borders of the intervertebral foramens in oblique radiographs when it penetrated the ventral cortex of lateral mass 4 mm or more.</p><p><b>CONCLUSIONS</b>(1) There is no risk of damaging the vertebral artery if a screw is directed more than 15 degrees lateral to the sagittal plane at C(3 approximately 6) starting 1 mm medial to the center of the lateral mass. (2) Ideal screw tip position on oblique radiograph may not cross the line connecting the posterior borders of the intervertebral foramen on radiograph. If the screw tip is noted in the superior part of intervertebral foramen on the oblique radiograph, the screw may be identified as dangerous.</p>