Krüppel-like factor 12 regulates aging ovarian granulosa cell apoptosis by repressing SPHK1 transcription and sphingosine-1-phosphate (S1P) production.

Oxidative stress triggered by aging, radiation, or inflammation impairs ovarian function by inducing granulosa cell (GC) apoptosis. However, the mechanism inducing GC apoptosis has not been characterized. Here, we found that ovarian GCs from aging patients showed increased oxidative stress, enhanced reactive oxygen species activity, and significantly decreased expression of the known antiapoptotic factor sphingosine-1-phosphate/sphingosine kinase 1 (SPHK1) in GCs. Interestingly, the expression of Krüppel-like factor 12 (KLF12) was significantly increased in the ovarian GCs of aging patients. Furthermore, we determined that KLF12 was significantly upregulated in hydrogen peroxide-treated GCs and a 3-nitropropionic acid-induced in vivo model of ovarian oxidative stress. This phenotype was further confirmed to result from inhibition of SPHK1 by KLF12. Interestingly, when endogenous KLF12 was knocked down, it rescued oxidative stress-induced apoptosis. Meanwhile, supplementation with SPHK1 partially reversed oxidative stress-induced apoptosis. However, this function was lost in SPHK1 with deletion of the binding region to the KLF12 promoter. SPHK1 reversed apoptosis caused by hydrogen peroxide-KLF12 overexpression, a result further confirmed in an in vitro ovarian culture model and an in vivo 3-nitropropionic acid-induced ovarian oxidative stress model. Overall, our study reveals that KLF12 is involved in regulating apoptosis induced by oxidative stress in aging ovarian GCs and that sphingosine-1-phosphate/SPHK1 can rescue GC apoptosis by interacting with KLF12 in negative feedback.

Bioinspired PROTAC-induced macrophage fate determination alleviates atherosclerosis.

Atherosclerosis is a major cause of death and disability in cardiovascular disease. Atherosclerosis associated with lipid accumulation and chronic inflammation leads to plaques formation in arterial walls and luminal stenosis in carotid arteries. Current approaches such as surgery or treatment with statins encounter big challenges in curing atherosclerosis plaque. The infiltration of proinflammatory M1 macrophages plays an essential role in the occurrence and development of atherosclerosis plaque. A recent study shows that TRIM24, an E3 ubiquitin ligase of a Trim family protein, acts as a valve to inhibit the polarization of anti-inflammatory M2 macrophages, and elimination of TRIM24 opens an avenue to achieve the M2 polarization. Proteolysis-targeting chimera (PROTAC) technology has emerged as a novel tool for the selective degradation of targeting proteins. But the low bioavailability and cell specificity of PROTAC reagents hinder their applications in treating atherosclerosis plaque. In this study we constructed a type of bioinspired PROTAC by coating the PROTAC degrader (dTRIM24)-loaded PLGA nanoparticles with M2 macrophage membrane (MELT) for atherosclerosis treatment. MELT was characterized by morphology, size, and stability. MELT displayed enhanced specificity to M1 macrophages as well as acidic-responsive release of dTRIM24. After intravenous administration, MELT showed significantly improved accumulation in atherosclerotic plaque of high fat and high cholesterol diet-fed atherosclerotic (ApoE-/-) mice through binding to M1 macrophages and inducing effective and precise TRIM24 degradation, thus resulting in the polarization of M2 macrophages, which led to great reduction of plaque formation. These results suggest that MELT can be considered a potential therapeutic agent for targeting atherosclerotic plaque and alleviating atherosclerosis progression, providing an effective strategy for targeted atherosclerosis therapy.

Perioperative anesthesia management in pediatric liver transplant recipient with atrial septal defect: A case report.

BACKGROUND: Preoperative conditions in pediatric liver transplant recipients are understandably complex. Compared with adults, children have lesser compensatory abilities and demand greater precision during procedural executions. In the setting of end-stage liver disease, the heightened perioperative risk of coexistent cardiovascular pathology may impact graft survival as well. Requirements for anesthesia and perioperative management are thus more rigorous, calling for individualized treatments that reflect specific cardiovascular constraints and proposed surgical plans. CASE SUMMARY: Reports of perioperative anesthesia management and liver transplant prognostication in pediatric patients with concurrent atrial septal defects are scarce. Herein, we detail the course of liver transplantation in a child with dual afflictions, focusing on perioperative anesthesia management and the important contributions of the anesthesiologist (pre- and perioperatively) to a positive therapeutic outcome, despite the clinical hurdles imposed. CONCLUSION: Children with atrial septal defects bear substantially more than customary perioperative risk during orthotopic liver transplants, given their compromised cardiopulmonary reserves and functional states. Comprehensive preoperative cardiovascular assessments, including use of agitated-saline contrast echocardiography (to characterize intracardiac shunting) and multidisciplinary deliberation, may offer insights into structural cardiac pathophysiologic effects and transplant-related hemodynamic changes that impact new grafts. At the same time, active and effective monitoring and other measures should be taken to maintain hemodynamic stability in the perioperative period, avoid entry of bubbles into the circulation, and ease congestion in newly grafted livers. Such efforts are crucial for transplantation success and graft survival.

Association of sexually transmitted infection with semen quality in men from couples with primary and secondary infertility.

This study aims to compare the prevalence of sexually transmitted infections (STIs) with semen quality in men from couples with primary and secondary infertility. Semen samples were collected from 133 men who requested fertility evaluation. Seminal tract infection with Ureaplasma spp. (UU), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and herpes simplex virus-2 (HSV-2) was assessed by PCR-based diagnostic assays. Among all patients, the prevalence of STIs was higher in men from couples with primary infertility than that in men from couples with secondary infertility (39.7% vs 21.7%, P = 0.03). The prevalence of UU was 28.8% and 13.3% in men from couples with primary and secondary infertility, respectively. Men from couples with primary infertility were more likely to be positive for UU than men from couples with secondary infertility (P = 0.04). Regarding the UU subtype, the prevalence of Ureaplasma urealyticum (Uuu) and Ureaplasma parvum (Uup; including Uup1, Uup3, Uup6, and Uup14) did not differ between the two groups. No associations between the prevalence rates of MH, MG, and CT were found in men from either infertility group. A lower sperm concentration was associated with STI pathogen positivity in men with primary infertility according to the crude model (P = 0.04). The crude and adjusted models showed that semen volume (both P = 0.03) and semen leukocyte count (both P = 0.02) were independently associated with secondary infertility. These findings suggest the importance of classifying the type of infertility during routine diagnosis of seminal tract infections.

Comparison of the in-vivo effect of two tranexamic acid doses on fibrinolysis parameters in adults undergoing valvular cardiac surgery with cardiopulmonary bypass - a pilot investigation.

BACKGROUND: The blood saving efficacy of TXA in cardiac surgery has been proved in several studies, but TXA dosing regimens were varied in those studies. Therefore, we performed this study to investigate if there is a dose dependent in-vivo effect of TXA on fibrinolysis parameters by measurement of fibrinolysis markers in adults undergoing cardiac surgery with CPB. METHODS: A double-blind, randomized, controlled prospective trial was conducted from February 11, 2017 to May 05, 2017. Thirty patients undergoing cardiac valve surgery were identified and randomly divided into a placebo group, low-dose group and high-dose group by 1: 1: 1. Fibrinolysis parameters were measured by plasma levels of D-Dimers, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), plasmin-antiplasmin complex (PAP), tissue plasminogen activator (tPA) and thrombomodulin (TM). Those proteins were measured at five different sample times: preoperatively before the TXA injection (T1), 5 min after the TXA bolus (T2), 5 min after the initiation of CPB (T3), 5 min before the end of CPB (T4) and 5 min after the protamine administration (T5). A Thrombelastography (TEG) and standard coagulation test were also performed. RESULTS: Compared with the control group, the level of the D-Dimers decreased in the low-dose and high-dose groups when the patients arrived at the ICU and on the first postoperative morning. Over time, the concentrations of PAI-1, TAFI, and TM, but not PAP and tPA, showed significant differences between the three groups (P <  0.05). Compared with the placebo group, the plasma concentrations of PAI-1 and TAFI decreased significantly at the T3 and T4 (P <  0.05); TAFI concentrations also decreased at the T5 in low-dose group (P < 0.05). Compared with the low-dose group, the concentration of TM increased significantly at the T4 in high-dose group. CONCLUSIONS: The in-vivo effect of low dose TXA is equivalent to high dose TXA on fibrinolysis parameters in adults with a low bleeding risk undergoing valvular cardiac surgery with cardiopulmonary bypass, and a low dose TXA regimen might be equivalent to high dose TXA for those patients. TRIAL REGISTRATION: ChiCTR-IPR-17010303 , Principal investigator: Zhen-feng ZHOU, Date of registration: January 1, 2017.

Effects of etibatide combined with emergency percutaneous coronary intervention on blood perfusion and cardiac function in patients with acute myocardial infarction.

OBJECTIVES: To investigate the effects of etibatide combined with emergency percutaneous coronary intervention (PCI) on blood perfusion and cardiac function in acute myocardial infarction (AMI) patients. METHODS: This was a prospective, randomized, controlled study. From November 2015 to June 2019, 196 patients with ST-segment elevation myocardial infarction (STEMI) undergoing emergency PCI admitted to Baoding First Central Hospital were enrolled. The 196 STEMI patients were randomly divided into experimental group and control group. In the experimental group, STEMI patients were treated with emergency PCI + etibatide; while in the control group, only PCI was performed. Observation indexes included: general data, myocardial perfusion and cardiac function indexes and major adverse cardiac events (MACE). RESULTS: There was no significant difference in general data between the two groups (P > 0.05). The rate of ST-segment resolution (STR) in the experimental group was better than that in the control group (P < 0.05). In myocardial contrast echocardiography (MCE), higher peak intensity (PI) and shorter time-to-peak (TP) were observed in the experimental group compared with the control group (P < 0.05). The platelet aggregation rate was compared between the two group at the time points of before PCI, after PCI and two hour after drug withdrawal, and there was no significant change in the platelet aggregation rate of the control group between different time points (before PCI, after PCI and two hour after drug withdrawal); while the platelet aggregation rate of the experimental group was significantly lower after PCI and two hour after drug withdrawal than that before PCI (P < 0.05), and an obviously decreased platelet aggregation rate was found in the experimental group(P < 0.05). After three months of follow-up, there was one case of MACE in the experimental group and 1 case of MACE in the control group, without any difference in the incidence of MACE between the two groups (P > 0.05). CONCLUSION: Etibatide combined with emergency PCI could improve myocardial reperfusion and cardiac function in patients with acute STEMI without increasing the incidence of MACE.

Pseudomonas laoshanensis sp. nov., isolated from peanut field soil.

A novel Gram-stain-negative, aerobic strain, designated Y22T, was isolated from peanut field soil in Laoshan Mountain in China. Cells of strain Y22T were rod-shaped and motile by a single flagellum. The strain was found to be oxidase- and catalase-positive. 16S rRNA gene sequence based on phylogenetic analysis indicated that strain Y22T belonged to the genus Pseudomonas, and showed the highest 16S rRNA gene sequence similarity of 99.0% to Pseudomonas pelagia JCM 15562T, followed by Pseudomonas salina JCM 19469T (98.4%), Pseudomonas sabulinigri JCM 14963T (97.9%), Pseudomonas bauzanensis CGMCC 1.9095T (97.6%) and Pseudomonas litoralis KCTC23093T (97.5%). The phylogenetic analysis based on multilocus sequence analyses with concatenated 16S rRNA, gyrB, rpoD and rpoB genes indicated that strain Y22T belonged to Pseudomonas pertucinogena lineage. The average nucleotide identity scores between strain Y22T and closely related species were 74.6-82.8%, and the Genome-to-Genome Distance Calculator scores were 16.4-44.9%. The predominant cellular fatty acids of strain Y22T were C18:1ω7c (29.6%), C17:0 cyclo (17.5%) and summed feature 3 (C16:1ω7c and/or C16:1ω6c) (17.4%). The genomic DNA G+C content was 57.9 mol%. On the basis of phenotypic characteristics, phylogenetic analyses and in silico DNA-DNA relatedness, a novel species, Pseudomonas laoshanensis sp. nov. is proposed. The type strain is Y22T (= JCM 32580T = KCTC 62385T = CGMCC 1.16552T).

Mesenchymal stem cells regulate the Th17/Treg cell balance partly through hepatocyte growth factor in vitro.

INTRODUCTION: Mesenchymal stem cells (MSCs) exert immunomodulatory functions by inducing the development and differentiation of naive T cells into T cells with an anti-inflammatory regulatory T cell (Treg) phenotype. Our previous study showed that hepatocyte growth factor (HGF) secreted by MSCs had immunomodulatory effects in the context of lipopolysaccharide (LPS) stimulation. We hypothesized that HGF is a key factor in the MSC-mediated regulation of the T helper 17 (Th17) cell/regulatory T (Treg) cell balance. METHODS: We investigated the effects of MSCs on the differentiation of CD4+ T cells and the functions of Th17/Treg cells in response to LPS stimulation by performing in vitro coculture experiments. MSCs were added to the upper chambers of cell culture inserts, and CD4+ T cells were plated in the lower chambers, followed by treatment with LPS or an anti-HGF antibody. Th17 (CD4+CD3+RORrt+) and Treg (CD4+CD25+Foxp3+) cell frequencies were analysed by flow cytometry, and the expression of Th17 cell- and Treg cell-related cytokines in the CD4+ T cells or culture medium was measured by quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Neutrophil functions were determined by flow cytometry after a coculture with Th17/Treg cells. RESULTS: The percentage of CD4+CD25+Foxp3+ cells was significantly increased in the CD4+ T cell population, while the percentage of CD4+CD3+RORrt+ cells was significantly decreased after MSC coculture. However, the MSC-induced effect was significantly inhibited by the anti-HGF antibody (p < 0.05). Furthermore, MSCs significantly inhibited the CD4+ T cell expression of IL-17 and IL-6 but increased the expression of IL-10 (p < 0.05 or p < 0.01); these effects were inhibited by the anti-HGF antibody (p < 0.05). In addition, CD4+ T cells cocultured with MSCs significantly inhibited neutrophil phagocytic and oxidative burst activities (p < 0.05 or p < 0.01); however, these MSC-induced effects were inhibited by the anti-HGF antibody (p < 0.05). CONCLUSION: These data suggested that MSCs induced the conversion of fully differentiated Th17 cells into functional Treg cells and thereby modulated the Th17/Treg cell balance in the CD4+ T cell population, which was partly attributed to HGF secreted by the MSCs.

Admission delay is associated with worse surgical outcomes for elderly hip fracture patients: A retrospective observational study.

BACKGROUND: The influence of surgical delay on mortality and morbidity has been studied extensively among elderly hip fracture patients. However, most studies only focus on the timing of surgery when patients have already been hospitalized, without considering pre-admission waiting time. Therefore, the present study aims to explore the influence of admission delay on surgical outcomes. METHODS: In this retrospective study, we recorded admission timing and interval from admission to surgery for included patient. Other covariates were also collected to control confounding. The primary outcome was 1-year mortality. The secondary outcomes were 1-month mortality, 3-month mortality, ICU admission and postoperative pneumonia. We mainly used multivariate logistic regression to determine the effect of admission timing on postoperative outcomes. An additional survival analysis was also performed to assess the impact of admission delay on survival status in the first year after operation. RESULTS: The proportion of patients hospitalized on day 0, day 1, day 2 after injury was 25.4%, 54.7% and 66.3%, respectively. And 12.6% patients visited hospital one week later after injury. Mean time from admission to surgery was 5.2 days (standard deviation 2.8 days). Hospitalization at one week after injury was a risk factor for 1-year mortality (OR 1.762, 95% CI 1.026-3.379, P=0.041). CONCLUSION: Admission delay of more than one week is significantly associated with higher 1-year mortality. As a supplement to the current guidelines which emphasizes early surgery after admission, we also advocate early admission once patients get injured.

Role of spinal adenosine A1 receptors in the analgesic effect of electroacupuncture in a rat model of neuropathic pain.

OBJECTIVE: The aim of this study was to determine the role of spinal adenosine A1 receptors (A1Rs) in the analgesic effects of electroacupuncture (EA) for neuropathic pain. METHODS: We performed EA for 30 minutes at the zusanli acupoint in the legs of rats with previously induced chronic constriction injuries and observed the mechanical and thermal pain thresholds 1 hour later. We also examined adenosine levels by high-performance liquid chromatography and A1R expression in the L4-6 spinal cord by western blot analysis. We then injected A1R short interfering RNA (AV-shA1RNA) into the L4-6 spinal cord to downregulate A1R expression and re-examined the mechanical and thermal pain thresholds. RESULTS: Adenosine levels and A1R expression in the L4-6 spinal cord were increased at 1 hour after EA. In addition, EA exhibited an analgesic effect that was reversed by AV-shA1RNA. CONCLUSIONS: Our results suggest that EA at the zusanli acupoint elicits an analgesic effect against neuropathic pain, mediated by A1Rs in the spinal cord.

RETRACTED: LSAMP-AS1 binds to microRNA-183-5p to suppress the progression of prostate cancer by up-regulating the tumor suppressor DCN.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the editor after publication concerns were raised with respect to data presented in Figure 2. The journal contacted Southern Medical University, Guangzhou, Guangdong Province, China, who formed an Academic Committee to investigate. According to the "Academic Ethics and Implementation Rules" of Southern Medical University, the Committee reported evidence of improper preservation of original data and incorrect use of pictures, and recommended immediate withdrawal of the paper. Specifically, in the PC-3 group of Fig. 2H, the 'Control' cell migration image had been partially duplicated in the 'Empty vector' image. As per journal policy, original files used to create the entire figure were requested. Raw western blot images were not available for Figure 2 C+F, and experimental repeats yielded protein level discrepancies with the original published data. The editors therefore no longer have confidence in the integrity of these data.

Additional femoral nerve block analgesia does not reduce the chronic pain after total knee arthroplasty: A retrospective study in patients with knee osteoarthritis.

Femoral nerve block analgesia was deemed to the gold standard for acute pain management after total knee arthroplasty (TKA). But effect on chronic pain management is not investigated fully. We conducted a retrospective study to explore the effect of single-injection femoral nerve block on postsurgical chronic pain.All medical records of patients undertaking TKA between January, 2013 and June, 2014 were reviewed via the Docare anesthesia database. Patients who administrated with the self-controlled intravenous analgesia were assigned to group P. Patients who received a single-injection femoral never block combined with patient self-controlled intravenous analgesia were assigned to group N + P. The visual analog scale (VAS) score before surgery, the first postoperative day (POD 1), POD 2, 3 months, 6 months, and 12 months after surgery were extracted from medical records. Pain score was compared over these 2 groups to investigate treatment outcomes.In all, 470 patients met the selection criteria for group P and 266 patients met the selection criteria for group N + P. Compared with group P, the VAS score decreased significantly in group N + P at POD 1 (P < .001), and the same was observed at POD 2 (P < .001); the moderate to severe pain incidence rate decreased significantly in group N + P at POD 1 (P < .01) and POD 2 (motion, P < .001). The rescued anesthesia rate reduced significantly in group N + P in POD 1 (P = .001), whereas no difference was found in POD 2 (P = .864). No difference was found at 3, 6, and 12 months after surgery (all P > .05).The single-injection femoral nerve block could relieve the acute postsurgical pain in a short period of time. But no evidence was found that it could reduce the chronic pain between 3 and 12 months after TKA.

Pseudomonas qingdaonensis sp. nov., an aflatoxin-degrading bacterium, isolated from peanut rhizospheric soil.

A Gram-stain-negative, aerobic, mobile, and rod-shaped bacterium, designated JJ3T, was isolated from peanut rhizospheric soil in Qingdao, Shandong Province, China, and was characterized using a polyphasic approach. Strain JJ3T grew at 4-40 °C, at pH 5.0-9.0 and 0-4% NaCl. The strain was positive for both catalase and oxidase tests, and was able to degrade aflatoxin B1. According to the 16S rRNA gene sequence comparisons, the strain JJ3T was identified as a member of the genus Pseudomonas and was most closely related to Pseudomonas japonica JCM 21532T and Pseudomonas alkylphenolica JCM 16553T with sequence similarity of 99.0% and 98.9%, respectively. A multilocus sequence analysis (MLSA) of concatenating 16S rRNA, gyrB and rpoD gene sequences showed that strain JJ3T belonged to the Pseudomonas putida subcluster. Genomic comparison of strain JJ3T with its closest phylogenetic type strain using average nucleotide index (ANI) and digital DNA-DNA relatedness revealed 76.7-82.9% and 20.2-37.1%, respectively. All values were distinctly lower than the thresholds established for species differentiation. The predominant cellular fatty acids of strain JJ3T were C17:0 cyclo (24.0%), C16:0 (21.4%), summed features 3 (C16:1ω7c and/or C16:1ω6c) (11.5%) and summed features 8 (C18:1ω7c and/or C18:1ω6c) (10.5%). The major polar lipids of strain JJ3T were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The physiological, biochemical, and genetic characteristics support the assignment of JJ3T to the genus Pseudomonas, but are different to those of phylogenetically neighboring species to represent a novel species. The name Pseudomonas qingdaonensis sp. nov. is proposed, with JJ3T (= JCM 32579T = KCTC 62384T = CGMCC 1.16493T) as the type strain.

[Effects of perioperative transcutaneous electrical acupoint stimulation on postoperative analgesia in patients undergoing shoulder arthroscopic surgery].

OBJECTIVE: To observe and evaluate the effects of transcutaneous electrical acupoint stimulation (TEAS) at different time points on postoperative analgesia in perioperative period in patients undergoing shoulder arthroscopic surgery, and to explore the optimal time to use TEAS for shoulder arthroscopic surgery. METHODS: A total of 120 patients undergoing unilateral shoulder arthroscopy under general anesthesia, graded withⅠtoⅡaccording to ASA criteria were randomly divided into 3 groups, 40 patients in each one. The patients in the group A were treated with preoperative TEAS at sham acupoints combined with postoperative TEAS at Hegu (LI 4) and Neiguan (PC 6); the patients in the group B were treated with preoperative TEAS at Hegu (LI 4) and Neiguan (PC 6) combined with postoperative TEAS at sham acupoints; the patients in the group C were treated with TEAS at sham acupoints before and after operation. The parameters of TEAS were dilatational wave, 2 Hz/100 Hz in frequency, 30 min. When the resting-state visual analogue scale (VAS) of incision was more than 3 points, the patient-controlled intravenous analgesia (PCIA) pump of sufentanil was administered to maintain the VAS no more than 3 points. The time point when PCIA pump was firstly used, the used dose of sufentanil and effective pressing number of PCIA pump within 24 hours after surgery were recorded. Intraoperative anesthetic doses were recorded in the three groups. The resting-state and task-state VAS were evaluated at 0, 6, 12, 24 hours after surgery; the patient's satisfaction rate and adverse effects were recorded. RESULTS: The time when PCIA pump was firstly used in the group A and the group B was significantly longer than that in the group C, and the used dose of sufentanil and effective pressing number of PCIA pump within 24 hours after surgery in the group A and group B were significantly less than those in the group C (all P<0.05); the incidence of postoperative nausea-vomiting and sore throat was reduced (all P<0.05). The time when PCIA pump was firstly used in the group A was significantly longer than that in the group B, and the used dose of sufentanil and effective pressing number of PCIA pump within 24 hours after surgery in the group A were significantly less than those in the group B (all P<0.05); no significant difference of the incidence of postoperative nausea-vomiting and sore throat was observed between the group A and group B (both P>0.05). There were no statistically significant difference in VAS score at different postoperative time points and postoperative analgesia satisfaction rate between the two groups (all P>0.05). CONCLUSION: Perioperative TEAS could improve the postoperative analgesia in patients undergoing arthroscopic shoulder surgery, delay the time when PCIA pump is firstly used, reduce the dosage of postoperative analgesics and adverse events. Compared before surgery, postoperative TEAS has better analgesia.

FAP-a and GOLPH3 Are Hallmarks of DCIS Progression to Invasive Breast Cancer.

Biological markers that could predict the progression of ductal carcinoma in-situ (DCIS) to invasive breast cancer (IDC) are required urgently for personalized therapy for patients diagnosed with DCIS. As stroma was invaded by malignant cells, perturbed stromal-epithelial interactions would bring about tissue remodeling. With the specific expression of the fibroblast activation protein-alpha (FAP-a), Carcinoma-associated fibroblasts (CAFs) are the main cell populations in the remodeled tumor stroma. Golgi phosphoprotein 3 (GOLPH3), a documented oncogene possessing potent transforming capacity, is not only up-regulated in many tumors but also an efficient indicator of poor prognosis and more malignant tumors. The present study aimed to retrospectively evaluate the pathological value of FAP-a and GOLPH3 in predicting the recurrence or progression of DCIS to invasive breast cancer. Immunohistochemical techniques were applied to investigate the expression of FAP-a GOLPH3 in 449 cases of DCIS patients received extensive resection and with close follow-up, but not being treated with any form of chemo- or radio-therapy. The combination of FAP-a and GOLPH3 in predicating the recurrence or progression of DCIS into invasive breast cancer was specifically examined. The study demonstrated that the overexpression of FAP-a in stromal fibroblasts and GOLPH3 in carcinoma cells are highly predictive of DCIS recurrence and progression into invasive breast cancer. Both FAP-a and GOLPH3 have high specificity and sensitivity to predict the recurrence of DCIS. Moreover, the combination of FAP-a and GOLPH3 tends to further improve the specificity and sensitivity of DCIS recurrence by 9.72-10.31 and 2.72-3.63%, respectively. FAP-a and GOLPH3 serve as novel markers in predicting the recurrence or progression of DCIS into invasive breast cancer.

Continuous intravenous infusion of remifentanil improves the experience of parturient undergoing repeated cesarean section under epidural anesthesia, a prospective, randomized study.

BACKGROUND: Unsatisfactory analgesia would occur frequently during repeated cesarean section under epidural anesthesia. The aim of this study is to observe the effects of intravenous remifentanil on maternal comfort, maternal and neonatal safety during repeated cesarean section under epidural anesthesia. METHODS: A total of 80 parturients undergoing repeated cesarean section were involved in the study. The patients were randomly divided into the intravenous remifentanil- assisted epidural group (group R) and epidural group (group E), respectively (n = 40). In group R, the remifentanil was continuously intravenously infused as an adjuvant to epidural anesthesia. In group E, 0.75% ropivacaine epidural or intravenous ketamine was administered as needed. Parturient baseline characteristics, vital signs, VAS scores, and comfort scores during surgery were recorded. Adverse effects were also recorded. RESULTS: A total of 80 patients were enrolled in the current study and the final analyses included 39 patients in group R and 38 patients in group E. No differences in patients' baseline characteristics were found between the two groups (p > 0.05). Compared with group E, the comfort score was significantly higher in group R (9.1 ± 1.0 vs. 7.5 ± 1.3, p <  0.001), whereas the maximum VAS score was significantly lower in group R (1.8 ± 1.2 vs. 4.1 ± 1.0, p <  0.001). Maternal and neonatal adverse effects did not differ between the two groups during surgery (p > 0.05). CONCLUSIONS: Continuous intravenous infusion of low-dose remifentanil can significantly improve the experience of parturients undergoing repeated cesarean section under epidural anesthesia, without noticeable maternal or neonatal adverse effects. TRIAL REGISTRATION: This study was pre-registered at http://www.chictr.org.cn/index.aspx (ChiCTR1800018423) on 17/09/2018.

[Application of sevoflurane and laryngeal mask in cesarean section in women with heart disease].

OBJECTIVE: To compare the safety of sevoflurane anesthesia with laryngeal mask and tracheal intubation in cesarean section in women with heart disease. METHODS: Fifty-two pregnant women with heart diseases undergoing cesarean section were randomized into laryngeal mask (LAM) group and tracheal intubation group. In LAM group, 6% sevoflurane was given at the rate of 6 L/min for induction with a maintenance sevoflurane concentration of 3%. In the intubation group, 1.5 mg/kg propofol and 1 µg/kg remifentanil were injected intravenously, and after achieving D0 with Narcotrend monitoring, 0.9 mg/kg rocuronium was injected and intubation was performed 1 min later. The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded in the two groups before anesthesia induction (T0), at intubation or laryngeal mask placement (T1), skin incision (T2), and extubation or laryngeal mask removal (T3). The surgery to fetal birth time, uterine incision to fetal childbirth time, drug discontinuation to awake time, and newborn Apgar scores were also recorded. Sevoflurane consumption and maternal comfort during hospitalization were compared between the two groups. RESULTS: In LAM group, HR and MBP at T1 and T3 were significantly lower than those in the intubation group (P<0.05). The drug discontinuation to extubation time and to awaken time were significantly shorter in LAM group than in the intubation group (P<0.05), but the operation time and fetal child birth time were comparable between the two groups (P>0.05). The women in LAM group reported better physical and psychological comforts than those in the intubation group (P<0.05). The neonatal Apgar scores and the scores of health education, satisfaction with hospital environment and service were all similar between the two groups (P>0.05). CONCLUSION: Sevoflurane anesthesia with laryngeal mask can achieve satisfactory anesthetic effects in cesarean section in women with heart disease.

Intraoperative tranexamic acid is associated with postoperative stroke in patients undergoing cardiac surgery.

BACKGROUND: Stroke is a devastating and potentially preventable complication of cardiac surgery. Tranexamic acid (TXA) is a commonly antifibrinolytic agent in cardiac surgeries with cardiopulmonary bypass (CPB), however, there is concern that it might increase incidence of stroke after cardiac surgery. In this retrospective study, we investigated whether TXA usage could increase postoperative stroke in cardiac surgery. METHODS: A retrospective study was conducted from January 1, 2010, to December 31, 2015, in 2,016 patients undergoing cardiac surgery, 664 patients received intravenous TXA infusion and 1,352 patients did not receive any antifibrinolytic agent. Univariate and propensity-weighted multivariate regression analysis were applied for data analysis. RESULTS: Intraoperative TXA administration was associated with postoperative stroke (1.7% vs. 0.5%; adjusted OR, 4.11; 95% CI, 1.33 to 12.71; p = 0.014) and coma (adjusted OR, 2.77; 95% CI, 1.06 to 7.26; p = 0.038) in cardiac surgery. As subtype analysis was performed, TXA administration was still associated with postoperative stroke (1.7% vs. 0.3%; adjusted OR, 5.78; 95% CI, 1.34 to 27.89; p = 0.018) in patients undergoing valve surgery or multi-valve surgery only, but was not associated with postoperative stroke (1.7% vs. 1.3%; adjusted OR, 5.21; 95% CI, 0.27 to 101.17; p = 0.276) in patients undergoing CABG surgery only. However, TXA administration was not associated with postoperative mortality (adjusted OR, 1.31; 95% CI, 0.56 to 3.71; p = 0.451), seizure (adjusted OR, 1.13; 95% CI, 0.42 to 3.04; p = 0.816), continuous renal replacement therapy (adjusted OR, 1.36; 95% CI, 0.56 to 3.28; p = 0.495) and resternotomy for postoperative bleeding (adjusted OR, 1.55; 95% CI, 0.55 to 4.30; p = 0.405). No difference was found in postoperative ventilation time (adjusted B, -1.45; SE, 2.33; p = 0.535), length of intensive care unit stay (adjusted B, -0.12; SE, 0.25; p = 0.633) and length of hospital stay (adjusted B, 0.48; SE, 0.58; p = 0.408). CONCLUSIONS: Based on the 5-year experience of TXA administration in cardiac surgery with CPB, we found that postoperative stroke was associated with intraoperative TXA administration in patients undergoing cardiac surgery, especially in those undergoing valve surgeries only. This study may suggest that TXA should be administrated according to clear indications after evaluating the bleeding risk in patients undergoing cardiac surgery, especially in those with high stroke risk.