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Aim: To study analgesic effects of dexmedetomidine or sufentanil, both combined with ropivacaine, in epidural analgesia during labor. Methods: We recruited 160 primigravidae with full-term pregnancy who received epidural anesthesia during labor and randomized them into four groups to receive epidural administration of ropivacaine combined with sufentanil (RS 1 and RS 2 groups) or with dexmedetomidine (RD 1 and RD 2 groups). Systolic blood pressure, diastolic blood pressure and heart rate before anesthesia (T 1 ), 15 min after anesthesia induction (T 2 ), on delivery (T 3 ) and 2 h postpartum (T 4 ), together with visual analogue scale scores, Bromage scores, Ramsay scores, adverse reactions during analgesia and urinary retention at 6 and 24 h postpartum were recorded; the pH, PCO 2 and PO 2 of umbilical cord arterial blood and Apgar scores at 1, 5 and 10 min after childbirth were assessed. Results: RS 1 group had significantly lower systolic blood pressure, diastolic blood pressure and heart rate than RD 1 group at T 2 and T 3 (all P < 0.05), but not at T1. At T 2 and T 3 , the other three groups were lower than RS 2 group in visual analogue scale and Ramsay scores (all P < 0.05). After childbirth, RD 2 group had significantly higher PO 2 result than other three groups (P < 0.05). At 6 h postpartum, RD 2 group had significantly fewer cases of urinary retention than RD 1 and RS 1 groups (both P < 0.05). Conclusion: A relatively low concentration of ropivacaine, combined with dexmedetomidine, is better in analgesia during labor.

Mammalian STE20-like kinase 1 (Mst1) is well recognized as a major tumor suppressor in cancer development, growth, metabolic reprogramming, metastasis, cell death and recurrence. However, the roles of Mst1 in non-small cell lung cancer (NSCLC) A549 cell phenotypic alterations remain to be elucidated. The present study aimed to explore the functional role and underlying mechanisms of Mst1 with regards to A549 cell proliferation, migration and apoptosis; this study focused on mitochondrial homeostasis and Rho-associated coiled-coil containing protein kinase 1 (ROCK1)/F-actin pathways. The results demonstrated that Mst1 was downregulated in A549 cells compared with in a normal pulmonary epithelial cell line. Subsequently, overexpression of Mst1 in A549 cells reduced cell viability and promoted cell apoptosis. Furthermore, overexpression of Mst1 suppressed A549 cell proliferation and migration. At the molecular level, the reintroduction of Mst1 in A549 cells led to activation of mitochondrial apoptosis, as evidenced by a reduction in mitochondrial potential, overproduction of ROS, cytochrome c release from the mitochondria into the nucleus, and upregulation of pro-apoptotic protein expression. In addition, Mst1 overexpression was closely associated with impaired mitochondrial respiratory function and suppressed cellular energy metabolism. Functional studies illustrated that Mst1 overexpression activated ROCK1/F-actin pathways, which highly regulate mitochondrial function. Inhibition of ROCK1/F-actin pathways in A549 cells sustained mitochondrial homeostasis, alleviated caspase-9-dependent mitochondrial apoptosis, enhanced cancer cell migration and increased cell proliferation. In conclusion, these data firmly established the regulatory role of Mst1 in NSCLC A549 cell survival via the modulation of ROCK1/F-actin pathways, which may provide opportunities for novel treatment modalities in clinical practice.

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Purpose The purpose of this study was to evaluate the features of sclerosing angiomatoid nodular transformation (SANT) in spleen on the imaging of computed tomography (CT) and magnetic resonance (MR). Materials and Methods From July 2006 to April 2017, 12 patients with SANT confirmed by pathology were evaluated in a retrospective study. Eight patients were with CT imaging only, 2 patients were with MR imaging only, and 2 patients were with both CT and MR. Three professional senior radiologists analyzed the imaging features on CT and MR. The main characteristic analysis included size, margin, density, signal intensity, and enhancement pattern. The significant enhancement was defined as the degree of enhancement of lesion that is higher than the surrounding spleen parenchyma, and the mild enhancement was defined as the degree of enhancement of lesion that is lower than the surrounding spleen parenchyma. Results All the 12 patients (5 men, 7 women; mean age, 45.8 years; age range, 21–62 years) presented as single lesion without special clinical symptoms. The range of lesions on diameter was from 25 to 80 mm. On CT images, 9 (90%) of 10 presented as hypodense in comparison with the parenchyma of spleen, 1 (10%) of 10 presented as isodense, and calcification was observed in 4 (40%) of 10 cases. On MR images, 4 (100%) of 4 manifested heterogeneous hypointensity on in-phase sequence and 3 (75%) of 4 performed as isointensity on out-of-phase sequence of T1-weighted. On the sequences of T2-weighted and diffusion-weighted image, 4 (100%) of 4 showed hypointensity. On CT and MR enhancement images, the number of significant enhancement and mild enhancement was 2 and 10, respectively. Seven (58%) of 12 showed progressive enhancement with the pattern of “spoke-wheel.” Conclusions Imaging features on CT and MR have a high diagnostic value for SANT, especially when CT combined with MR examination.

Cystic fibrosis (CF) is a life-shortening disease caused by the mutations that generate nonfunctional CF transmembrane conductance regulator (CFTR) protein. A rare serine-to-tyrosine (S1045Y) CFTR mutation was earlier reported to result in CF-associated fatality. We identified an African-American patient with the S1045Y mutation in CFTR, as well as a stop-codon mutation, who has a mild CF phenotype. The underlying mechanism of CF caused by S1045Y-CFTR has not been elucidated. In this study, we determined that S1045Y-CFTR exhibits twofold attenuated function compared with wild-type (WT)-CFTR. We report that serine-to-tyrosine mutation leads to increased tyrosine phosphorylation of S1045Y-CFTR, followed by recruitment and binding of E3-ubiquitin ligase c-cbl, resulting in enhanced ubiquitination and passage of S1045Y-CFTR in the endosome/lysosome degradative compartments. We demonstrate that inhibition of tyrosine phosphorylation partially rescues S1045Y-CFTR surface expression and function. Based on our findings, it could be suggested that consuming genistein (a tyrosine phosphorylation inhibitor) would likely ameliorate CF symptoms in individuals with S1045Y-CFTR, providing a unique personalized therapy for this rare CF mutation.

Watery diarrhoea, hypokalaemia and achlorhydria (WDHA) syndrome was caused by vasoactive intestinal polypeptide (VIP)-producing tumour. A 3-year-old Chinese girl with watery diarrhoea, abdominal distension and hypokalaemia due to a thoracic paraspinal VIP-secreting ganglioneuroma is reported. The girl coughed, fevering up to 39 degrees C after a flu-like episode. She had eight to ten abundant stools daily which is not improved by dietary treatment, resulting in an important weight loss. She weighed 6.8 kg (nl P50 at 6 months of age) and is 76 cm (nl P50 at 9 months of age) in height. Blood electrolytes showed 129 mmol/L sodium, 2.42 mmol/L potassium, 94 mmol/L chloride and 18.6 mmol/L bicarbonate; urinary catecholamines were normal. Computed tomography scan evidenced a left side paravertebral mass of 4 x 6 cm in the lower thoracic region leading to the blood determination of vasoactive intestinal polypeptide which amounted 830 pmol/L(normal < 25 pmol/L). Surgical removal showed a ganglioneuroma of 160 g and was associated with disappearance of the diarrhoea and normalization of VIP level below 20 pmol/L. Review of the 63 reported cases in children with WDHA showed that many of the cases presented with non-treatable watery diarrhoea, hypokalaemia. Achlorhydria is not necessarily part of the WDHA syndrome. The male to female ratio is 1:1.5. Ganglioneuroblastoma and ganglioneuroma are the commonest tumours. Location of the tumour is variable: abdomen, chest or neck. Abdominal distension, flushing, episodic hypertension and colonic dilatation, constipation and ataxia were the other associated features. Surgical resection is the treatment of choice of VIP-producing tumours.