Cesarean Scar Pregnancies Treated by Uterine Artery Chemotherapy Embolization Combined With Ultrasound-Guided Dilation and Curettage: A Retrospective Study.

OBJECTIVES: To explore the effect of cesarean scar pregnancy (CSP) treatment by comparing uterine artery chemotherapy embolization (UACE) combined with dilation and curettage (D&C) with or without ultrasound guidance. METHODS: CSP patients treated with UACE combined with D&C from January 2013 to December 2020 at Shuguang Hospital, affiliated to Shanghai University of Traditional Chinese Medicine were included in this retrospective study. The patients were divided into groups A and B according to whether D&C was guided by ultrasound. RESULTS: Forty-eight patients with CSP diagnosed by transvaginal ultrasound were included in this study, whose gestational age was <8 weeks. There were no significant differences in the basic clinical characteristics of the two groups. The success rates of the 2 groups were no significant difference, 100% (27/27) in group A and 85.7% (18/21) in group B. The maximal intraoperative blood loss of group A was 100 mL and that of group B was 150 mL. There was no uterine perforation during the operation. Ultrasound guidance can shorten the D&C operation time, reduce intraoperative bleeding during D&C, and decrease the residual rate of trophoblastic tissue after D&C. CONCLUSIONS: Ultrasound guidance can improve the safety and efficiency of UACE combined with D&C in the treatment of CSP and reduce its complications. We believe it is an optimal treatment for CSP patients who do not plan to have children in the future.

Paeoniflorin Ameliorates Colonic Fibrosis in Rats with Postinfectious Irritable Bowel Syndrome by Inhibiting the Leptin/LepRb Pathway.

Postinfectious irritable bowel syndrome (PI-IBS) is a highly prevalent gastrointestinal disorder associated with immune dysregulation and depression- and anxiety-like behaviors. Through traditional medicine, the active ingredient of Paeoniae Radix called paeoniflorin (PF) was previously found to prevent the symptoms of PI-IBS. However, there is limited information on the effects of PF on intestinal function and depression- and anxiety-like symptoms in PI-IBS animal models. Here, we aimed to determine the effects of PF treatment on the symptoms of PI-IBS in a rat model. The PI-IBS rat model was established via early postnatal sibling deprivation (EPSD), trinitrobenzenesulfonic acid (TNBS), and chronic unpredictable mild stress (CUMS) stimulation and then treated with different dosages of PF (10, 20, and 40 mg/kg) and leptin (1 and 10 mg/kg). The fecal water content and body weight were measured to evaluate the intestinal function, while the two-bottle test for sucrose intake, open field test (OFT), and elevated plus maze test (EMT) were performed to assess behavioral changes. The serum leptin levels were also measured using an enzyme-linked immunosorbent assay. Furthermore, the expressions of leptin and its receptor, LepRb, were detected in colonic mucosal tissues through an immunohistochemical assay. The activation of the PI3K/AKT signaling pathway and the expression of brain-derived neurotrophic factor (BDNF) were also detected via western blotting. After the experimental period, the PI-IBS rats presented decreased body weight and increased fecal water content, which coincided with elevated leptin levels and heightened depression- and anxiety-like behaviors (e.g., low sucrose intake, less frequency in the center areas during OFT, and fewer activities in the open arms during EMT). However, the PF treatment ameliorated these observed symptoms. Furthermore, PF not only inhibited leptin/LepRb expression but also reduced the PI3K/AKT phosphorylation and BDNF expression in PI-IBS rats. Notably, cotreatment with leptin (10 mg/kg) reduced the effects of PF (20 mg/kg) on colonic fibrosis, leptin/LepRb expression, and PI3K/AKT activation. Therefore, our findings suggest that leptin is targeted by PF via the leptin/LepRb pathway, consequently ameliorating the symptoms of PI-IBS. Our study also contributes novel insights for elucidating the pharmacological action of PF on gastrointestinal disorders and may be used for the clinical treatment of PI-IBS in the future.

Prone positioning improves ventilation-perfusion matching assessed by electrical impedance tomography in patients with ARDS: a prospective physiological study.

BACKGROUND: The physiological effects of prone ventilation in ARDS patients have been discussed for a long time but have not been fully elucidated. Electrical impedance tomography (EIT) has emerged as a tool for bedside monitoring of pulmonary ventilation and perfusion, allowing the opportunity to obtain data. This study aimed to investigate the effect of prone positioning (PP) on ventilation-perfusion matching by contrast-enhanced EIT in patients with ARDS. DESIGN: Monocenter prospective physiologic study. SETTING: University medical ICU. PATIENTS: Ten mechanically ventilated ARDS patients who underwent PP. INTERVENTIONS: We performed EIT evaluation at the initiation of PP, 3 h after PP initiation and the end of PP during the first PP session. MEASUREMENTS AND MAIN RESULTS: The regional distribution of ventilation and perfusion was analyzed based on EIT images and compared to the clinical variables regarding respiratory and hemodynamic status. Prolonged prone ventilation improved oxygenation in the ARDS patients. Based on EIT measurements, the distribution of ventilation was homogenized and dorsal lung ventilation was significantly improved by PP administration, while the effect of PP on lung perfusion was relatively mild, with increased dorsal lung perfusion observed. The ventilation-perfusion matched region was found to increase and correlate with the increased PaO2/FiO2 by PP, which was attributed mainly to reduced shunt in the lung. CONCLUSIONS: Prolonged prone ventilation increased dorsal ventilation and perfusion, which resulted in improved ventilation-perfusion matching and oxygenation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04725227. Registered on 25 January 2021.

CXCL16/CXCR6 is involved in LPS-induced acute lung injury via P38 signalling.

Although several chemokines play key roles in the pathogenesis of acute lung injury (ALI), the roles of chemokine (C-X-C motif) ligand 16 (CXCL16) and its receptor C-X-C chemokine receptor type 6 (CXCR6) in ALI pathogenesis remain to be elucidated. The mRNA and protein expression of CXCL16 and CXCR6 was detected after lipopolysaccharide (LPS) stimulation with or without treatment with the nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC). Lung injury induced by LPS was evaluated in CXCR6 knockout mice. CXCL16 level was elevated in the serum of ALI patients (n = 20) compared with healthy controls (n = 30). CXCL16 treatment (50, 100, and 200 ng/mL) in 16HBE cells significantly decreased the epithelial barrier integrity and E-cadherin expression, and increased CXCR6 expression, reactive oxygen species (ROS) production, and p38 phosphorylation. Knockdown of CXCR6 or treatment with the p38 inhibitor SB203580 abolished the effects of CXCL16. Moreover, treatment of 16HBE cells with LPS (5, 10, 20 and 50 µg/mL) significantly increased CXCL16 release as well as the mRNA and protein levels of CXCL16 and CXCR6. The effects of LPS treatment (20 µg/mL) were abolished by treatment with PDTC. The results of the luciferase assay further demonstrated that PDTC treatment markedly inhibited the activity of the CXCL16 promoter. In conclusion, CXCL16, whose transcription was enhanced by LPS, may be involved in ROS production, epithelial barrier dysfunction and E-cadherin down-regulation via p38 signalling, thus contributing to the pathogenesis of ALI. Importantly, CXCR6 knockout or inhibition of p38 signalling may protect mice from LPS-induced lung injury by decreasing E-cadherin expression.

Effects of interleukin-6 and IL-6/AMPK signaling pathway on mitochondrial biogenesis and astrocytes viability under experimental septic condition.

OBJECTIVE: Interleukin-6 (IL-6) is a neuromodulation factor with extensive and complex biological activities. IL-6 has been reported to activate AMPK, while AMPK regulates mitochondrial biogenesis and autophagy. The aim of this study was to investigate the role of IL-6 in mitochondrial biogenesis using astrocytes under experimental septic condition and examined how IL-6/AMPK signaling pathway affected this process. METHODS: The primary cultures of cerebral cortical astrocytes were randomly allocated into six groups: control group, LPS+IFN-γ group, IL-6 group (LPS+IFN-γ+IL-6), C group (LPS+IFN-γ+IL-6+Compound C), siRNA group (LPS+IFN-γ+IL-6+IL-6R siRNA) and siRNA+C group (LPS+IFN-γ+IL-6+IL-6R siRNA+ Compound C). All groups were stimulated for 6 h. Cytokines and reactive oxygen species (ROS) analyses, detection of adenosine triphosphate (ATP), mtDNA content and cell viability, evaluation of the mitochondrial ultrastructure and volume density, western blots of proteins associated with mitochondrial biogenesis and phospho-adenosine monophosphate activated protein kinase (p-AMPK) were performed respectively. RESULTS: Compared with LPS+IFN-γ group, IL-6 group had milder ultrastructural damage of mitochondria, higher mtDNA content and mitochondrial volume density, higher expression of proteins associated with mitochondrial biogenesis (PGC-1α, NRF-1 and TFAM) and p-AMPK, and thus higher cell viability, whereas blocking IL-6/AMPK signaling pathway, the protective effect of IL-6 has been diminished, compared with IL-6 group. CONCLUSION: IL-6 enhances mitochondrial biogenesis in astrocytes under experimental septic condition through IL-6/AMPK signaling pathway.

The efficacy of parenteral fish oil in critical illness patients with sepsis: a prospective, non-randomized, observational study.

BACKGROUND AND OBJECTIVES: To investigate the clinical outcomes in septic patients receiving parenteral fish oil. METHODS AND STUDY DESIGN: A prospective, non-randomized, observational clinical study was carried out in 112 patients with sepsis from March, 2013 to May, 2015 in the surgical intensive care unit (SICU) of a tertiaryreferral hospital. The patients were put into one of two groups; either the control or the study group. Patients received the standard treatment of sepsis based on guidelines in the control group. In the study group, patients received parenteral nutrition (PN) containing fish oil. The Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, the length of ICU and hospital stay, duration of mechanical ventilation, mortality, and readmission into the ICU were recorded. Tumor necrosis factor (TNF)-α and procalcitonin (PCT) levels were also evaluated. RESULTS: The study group showed a significant reduction for all-cause mortality (20.0% vs 10.0% in study and control groups, p=0.034) and APACHE II score on day 5 (p=0.015), day 7 (p=0.036) and day out of SICU (p=0.045) compared with the control group. The study group tended to show a shortened length of stay in the ICU compared to the control group. However, TNF-α and PCT level, 28 d mortality, the length of hospital stay and the duration of mechanical ventilation did not show statistical differences between the two groups. There were no drug-related adverse effects shown during the study. CONCLUSIONS: PN with fish oil is probably safe and may improve clinical outcome in critical ill patients with sepsis.

Naringenin Regulates CFTR Activation and Expression in Airway Epithelial Cells.

BACKGROUND/AIMS: Sputum symptoms are commonly seen in the elderly. This study aimed to identify an efficacious expectorant treatment stratagem through evaluating the secretion-promoting activation and cystic fibrosis transmembrane conductance regulator (CFTR) expression of the bioactive herbal monomer naringenin. METHODS: Vectorial Cl- transport was determined by measuring short-circuit current (ISC) in rat airway epithelium. cAMP content was measured by ELISA in primary cultured epithelial cells and Calu-3 cells. CFTR expression in Calu-3 cells was determined by qPCR. RESULTS: Addition of naringenin to the basolateral side of the rat airway led to a concentration-dependent sustained increase in ISC. The current was suppressed when exposed to Cl--free solution or by bumetanide, BaCl2, and DPC but not by DIDS and IBMX. Forskolin-induced ISC increase and CFTRinh-172/MDL-12330A-induced ISC inhibition were not altered by naringenin. Intracellular cAMP content was significantly increased by naringenin. With lipopolysaccharide stimulation, CFTR expression was significantly reduced, and naringenin dose-dependently enhanced CFTR mRNA expression. CONCLUSION: These results demonstrate that naringenin has the ability to stimulate Cl- secretion, which is mediated by CFTR through a signaling pathway by increasing cAMP content. Moreover, naringenin can increase CFTR expression when organism CFTR expression is seriously hampered. Our data suggest a potentially effective treatment strategy for sputum.

Glucocorticoid attenuates acute lung injury through induction of type 2 macrophage.

BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe inflammatory lung diseases. Methylprednisolone (MP) is a common drug against inflammation in clinic. In this study, we aim to investigate the protective effect of MP on ALI and potential mechanisms. METHODS: Male BABL/c mice were injected through tail vein using lipopolysaccharide (LPS, 5 mg/kg) with or without 5 mg/kg MP. Lung mechanics, tissue injury and inflammation were examined. Macrophage subsets in the lung were identified by flow cytometry. Macrophages were cultured from bone marrow of mice with or without MP. Then, we analyzed and isolated the subsets of macrophages. These isolated macrophages were then co-cultured with CD4+ T cells, and the percentage of regulatory T cells (Tregs) was examined. The expression of IL-10 and TGF-ß in the supernatant was measured. The Tregs immunosuppression function was examined by T cell proliferation assay. To disclose the mechanism of the induction of Tregs by M2c, we blocked IL-10 or/and TGF-ß using neutralizing antibody. RESULTS: Respiratory physiologic function was significantly improved by MP treatment. Tissue injury and inflammation were ameliorated in the MP-treated group. After MP treatment, the number of M1 decreased and M2 increased in the lung. In in vitro experiment, MP promoted M2 polarization rather than M1. We then induced M1, M2a and M2c from bone marrow cells. M1 induced more Th17 while M2 induced more CD4+CD25+Fxop3+ Tregs. Compared with M2a, M2c induced more Tregs, and this effect could be blocked by anti-IL-10 and anti-TGF-ß antibodies. However, M2a and M2c have no impact on Tregs immunosuppression function. CONCLUSION: In conclusion, MP ameliorated ALI by promoting M2 polarization. M2, especially M2c, induced Tregs without any influence on Tregs immunosuppression function.

[The relationship of vitamin D endocrine system and estrogen receptor expression with bone mineral density in initial systemic lupus erythematosus].

OBJECTIVE: To study the incidence of osteopenia in patients with initial systemic lupus erythematosus (SLE). Investigate the levels of the vitamin D (VitD) endocrine system in peripheral blood of SLE patients and its relation to bone mineral density (BMD). Analyse the relationship between the estrogen receptor (ER) and BMD and evaluate the role of ER in the pathogenesis osteopenia. METHODS: Serum levels of 25-OH VitD(3) and 1,25-(OH)(2) VitD(3) were detected by enzyme linked immunosorbent assay. The gene expression levels of VitD receptor (VDR) and ER were determined by real-time PCR. BMD measurements in the lumbar spine (L1-L4) and left proximal femur (femoral neck) were performed using dual X-ray absorptiometry before treatment. RESULTS: The initial SLE patients had significantly lower BMD values, and higher frequency of bone loss at both sites of measurement compared with normal controls (P < 0.05). The levels of 25-OH VitD(3) and 1,25-(OH)(2) VitD(3) were lower in the initial SLE patients than normal controls (P < 0.01 both). There is no difference in the levels of 25-OH VitD(3) and 1,25-(OH)(2) VitD(3) between the osteopenia SLE group and the normal BMD SLE group (P > 0.05, P > 0.05). There are no correlations between the VitD and BMD in initial SLE patients (P > 0.05 both). The expressions of VDR gene were significantly increased in the initial SLE patients compared with the normal controls (P < 0.01). There was no difference in VDR gene expression between osteopenia SLE group and normal BMD SLE group (P > 0.05). The VDR gene expression does not correlate with the bone mass (P > 0.05). The levels of ER-beta gene expression are higher in the initial SLE group than the normal controls (P < 0.01). CONCLUSIONS: The incipient SLE patients may have lower BMD than expected. SLE patients present abnormal VitD endocrine system and higher ER-beta mRNA expression than those in normal controls, but these weren't concerned with osteopenia.

The effects of dietary fatty acids on liver fatty acid composition and Delta(6)-desaturase expression differ with ambient salinities in Siganus canaliculatus.

Delta(6)-Desaturase (linoleoyl-CoA desaturase, EC 1.14.19.3) is the rate-limiting enzyme in the biosynthetic pathway of highly unsaturated fatty acid (HUFA). In this report, a Delta6 desaturase-like cDNA was cloned, and the relation of HUFA biosynthetic activity in liver with ambient salinity as well as dietary fatty acids was investigated in the euryhaline teleost Siganus canaliculatus. After the juveniles were fed four formulated diets (D1-D4) with different essential fatty acid composition (D1 with 23.49% HUFA, D2-D4 were HUFA-free, linoleic and alpha-linolenic acids account for 21.1% and 0.38%, 13.99% and 11.64%, 18.31% and 5.82% of the total fatty acids, respectively) for nine weeks, the growth performance showed no difference among groups in brackish water (10 ppt) or seawater (32 ppt) (P>0.05). Comparing liver fatty acids with fish fed D1, the content of arachidonic acid in fish fed D2 or D4 was significantly higher in 10 ppt (P<0.05), but showed no difference in 32 ppt; the contents of eicosapentaenoic (EPA), docosapentaenoic (DPA) and docosahexaenoic (DHA) acids in 10 ppt, as well as EPA in 32 ppt in fish fed D3 showed no difference, whereas those of DPA and DHA were significantly lower in 32 ppt (P<0.05). These data suggest that S. canaliculatus may convert linoleic and alpha-linolenic acids into HUFA and such a capacity was stronger in low salinity than that in high salinity. Consistent with this, the liver levels of Delta6 desaturase mRNA in fish fed D2-D4 were generally higher than in fish fed D1 in both salinities, and the total expression level in 10 ppt was about 1.56 times of that in 32 ppt, suggesting that transcriptional control of Delta6 desaturase is involved in such a HUFA biosynthesis. To our knowledge, this is the first report showing the relation of HUFA biosynthetic activity with ambient salinity in a euryhaline fish.

[Relationship between early enhanced helical CT and tumor angiogenesis in bladder cancer].

OBJECTIVE: To study the relationship between enhanced degree in the cancer lesion and angiogenesis in the tumor through early manifestations in enhanced helical CT in patients with bladder cancer. METHODS: Fifty-three patients with bladder carcinoma were examined by pelvic plain CT and helical CT scan at peak enhancement of cancer lesion. Histologic grade, vascular endothelial growth factor (VEGF) and micro-vascular density (MVD) were analyzed for each resected cancer lesion. Pearson and Spearman correlation tests were used to assess the relationship between CT enhancement and histologic grade, VEGF or MVD. RESULTS: In early enhancing phase of helical CT, different degrees of enhancement were observed in 73 bladder cancer lesions. The difference between average CT attenuation and MVD in different histologic grade cancer lesions was statistically significant (P < 0.001). A positive correlation was found between the CT enhancement and MVD (gamma = 0.936, P < 0.001), histologic grade (gamma = 0.75, P < 0.001), but VEGF of bladder cancer did not correlate with the CT enhancement or MVD. CONCLUSION: The early enhancement of helical CT enhancement of bladder cancer, showing a positive relation to MVD and histologic grade, can reflect the tumor angiogenesis and blood supply.