Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion

The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Puerperium experience and lifestyle in women with gestational diabetes mellitus and overweight/obesity in China: A qualitative study

IntroductionWomen with overweight or obesity and gestational diabetes mellitus (GDM) are at a high risk of developing type 2 diabetes mellitus (T2DM) and other metabolic diseases. Healthy postpartum lifestyles in women with GDM are important for effectively preventing early T2DM occurrence; however, few studies and guidelines focus in China on this issue.AimsThis qualitative study aimed to understand the puerperium experience and lifestyle of women with overweight/obesity and GDM.MethodsA face-to-face, in-depth, and semi-structured interview was conducted using a hermeneutical phenomenology method to collect data that were analyzed through thematic analysis.ResultsOut of 61 recruited women with overweight/obesity and history of GDM, 14 women underwent an interview and provided detailed descriptions of their lifestyle experiences during puerperium. The interview data were used to generate four themes—puerperium dietary behavior, weight perception and “confinement” behavior, family support, disease knowledge, and perceived risk—and nine sub-themes.ConclusionUnhealthy lifestyles, misconceptions about food, the conflict between physical activity and confinement behavior, a lack of social and family support, and low awareness of disease risk are all common among overweight/obese women with a history of GDM. Thus, we emphasized that healthcare providers should provide continuous preventive care from pregnancy to postpartum and promote long-term health in high-risk populations with a history of GDM associated with overweight/obesity

Effects of different exercise durations on Keap1-Nrf2-ARE pathway activation in mouse skeletal muscle

The purpose of this study was to investigate the effects of acute exercise stress on the nuclear factor-erythroid2 p45-related factor 2 (Nrf2)/antioxidant response element (ARE) transactivation, Kelch-like ECH-associated protein 1(Keap1) cytosolic protein and Nrf2 nucleoprotein expressions, Nrf2 target genes mRNA expressions, and GSH/GSSG ratio level; with a particular focus on the changes of Keap1-Nrf2-ARE pathway activation following different durations of exercise. Wild-type mice (C57BL/6J, two months old) were separated into one-hour and six-hour treadmill running groups, as well as a non-exercise control group (n=10 in each group). Measurements of Nrf2/ARE transactivation, Nrf2 nucleoprotein expressions, Keap1 cytosolic protein expression, Nrf2 target genes' mRNA expressions (superoxide dismutase-1 (SOD1), superoxide dismutase-2 (SOD2), γ-glutamyl cysteine ligase-modulatory (GCLm), γ-glutamylcysteine ligase-catalytic (GCLc), glutathione reductase (GR), glutathione peroxydase-1 (Gpx1), catalase (CAT) and hemoxygenase-1 (Ho-1)), and glutathione redox (GSH/GSSG) ratio were carried out immediately after exercise. The results showed significant increases in Keap1-Nrf2-ARE pathway activation and the mRNA expressions of six measured enzymes in skeletal muscle after six hours of exercise; while in the one-hour exercise group, there was no change in Keap1-Nrf2-ARE pathway activation and only two enzymes' mRNA expressions were increased. It is suggested that the changes in Keap1-Nrf2-ARE pathway activation and its target genes' mRNA expressions were dependent on the exercise duration, with longer duration associated with higher responses

Effects of acute hypoxia exposure with different durations on activation of Nrf2-ARE pathway in mouse skeletal muscle.

BackgroundHypoxia training enhances the endurance capacity of athletes. This response may in part be attributed to the hypoxia-induced increase in antioxidant capacity in skeletal muscles. Nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor which regulates the expression of genes via binding to the antioxidant-response element (ARE) of these genes, plays a crucial role in stimulating the body's defense system and potentially responds to hypoxia. Meanwhile, hypoxia-inducible factor-1α (HIF-1α) is an important player in protecting cells from hypoxic stress. The purpose of this study was to investigate the effects of acute hypoxia exposure with different durations on the activation of Nrf2-ARE pathway and a possible regulatory role of HIF-1α in these responses.MethodsC57BL/6J mice were allocated into the non-hypoxia 0-hour, 6-hour, 24-hour, and 48-hour hypoxic exposure (11.2% oxygen) groups. The quadriceps femoris was collected immediately after hypoxia. Further, to investigate the possible role of HIF-1α, C2C12 myoblasts with HIF-1α knockdown by small interfering RNA (siRNA) and the inducible HIF-1α transgenic mice were employed.ResultsThe results showed that 48-hour hypoxia exposure up-regulated protein expression of Nrf2, Nrf2/ARE binding activity and the transcription of antioxidative genes containing ARE (Sod1 and others) in mouse skeletal muscle. Moreover, HIF-1α siRNA group of C2C12 myoblasts showed a remarkable inhibition of Nrf2 protein expression and nuclear accumulation in hypoxia exposure for 72 hours compared with that in siRNA-Control group of the cells. In addition, HIF-1α transgenic mice gave higher Nrf2 protein expression, Nrf2/ARE binding activity and expressions of Nrf2-mediated antioxidative genes in their skeletal muscle, compared with those in the wild-type mice.ConclusionsThe findings suggested that the acute hypoxia exposure could trigger the activation of Nrf2-ARE pathway, with longer duration associated with higher responses, and HIF-1α expression might be involved in promoting the Nrf2-mediated antioxidant responses in skeletal muscle

Genome-Wide Analysis of the PIN Auxin Efflux Carrier Gene Family in Coffee

Coffee is one of the most popular beverages around the world, which is mainly produced from the allopolyploid Coffea arabica. The genomes of C. arabica and its two ancestors C. canephora and C. eugenioides have been released due to the development of next generation sequencing. However, few studies on C. arabica are related to the PIN-FORMED (PIN) auxin efflux transporter despite its importance in auxin-mediated plant growth and development. In the present study, we conducted a genome-wide analysis of the PIN gene family in the three coffee species. Totals of 17, 9 and 10 of the PIN members were characterized in C. Arabica, C. canephora and C. eugenioides, respectively. Phylogenetic analysis revealed gene loss of PIN1 and PIN2 homologs in C. arabica, as well as gene duplication of PIN5 homologs during the fractionation process after tetraploidy. Furthermore, we conducted expression analysis of PIN genes in C. arabica by in silico and qRT-PCR. The results revealed the existence of gene expression dominance in allopolyploid coffee and illustrated several PIN candidates in regulating auxin transport and homeostasis under leaf rust fungus inoculation and the tissue-specific expression pattern of C. arabica. Together, this study provides the basis and guideline for future functional characterization of the PIN gene family

Pancreaticoduodenectomy Combined with Vascular Resection and Reconstruction for Patients with Locally Advanced Pancreatic Cancer: A Multicenter, Retrospective Analysis

<div><p>Objective</p><p>The aim of this study was to present the therapeutic outcome of patients with locally advanced pancreatic cancer treated with pancreatoduodenectomy combined with vascular resection and reconstruction in addition to highlighting the mortality/morbidity and main prognostic factors associated with this treatment.</p><p>Materials and Methods</p><p>We retrospectively analyzed the clinical and pathological data of a total of 566 pancreatic cancer patients who were treated with PD from five teaching hospitals during the period of December 2006–December 2011. This study included 119 (21.0%) patients treated with PD combined with vascular resection and reconstruction. We performed a detailed statistical analysis of various factors, including postoperative complications, operative mortality, survival rate, operative time, pathological type, and lymph node metastasis.</p><p>Results</p><p>The median survival time of the 119 cases that received PD combined with vascular resection was 13.3 months, and the 1-, 2-, and 3-year survival rates were 30.3%, 14.1%, and 8.1%, respectively. The postoperative complication incidence was 23.5%, and the mortality rate was 6.7%. For the combined vascular resection group, complications occurred in 28 cases (23.5%). For the group without vascular resection, complications occurred in 37 cases (8.2%). There was significant difference between the two groups (p = 0.001). The degree of tumor differentiation and the occurrence of complications after surgery were independent prognostic factors that determined the patients’ long-term survival.</p><p>Conclusions</p><p>Compared with PD without vascular resection, PD combined with vascular resection and reconstruction increased the incidence of postoperative complications. However, PD combined with vascular resection and reconstruction could achieve the complete removal of tumors without significantly increasing the mortality rate, and the median survival time was higher than that of patients who underwent palliative treatment. In addition, the two independent factors affecting the postoperative survival time were the degree of tumor differentiation and the presence or absence of postoperative complications.</p></div

Comparison of the survival curves of the 119 cases treated with PD combined with vascular resection and reconstruction and those of the 447 cases treated with PD without vascular resection and reconstruction.

<p>Comparison of the survival curves of the 119 cases treated with PD combined with vascular resection and reconstruction and those of the 447 cases treated with PD without vascular resection and reconstruction.</p

The relationship between the parameters of patients treated with combined vascular resection and reconstruction and postoperative survival time.

<p>A. The patients were divided into three groups based on the degree of differentiation. The median survival times and 95% confidence intervals for each group were 5.9 (4.3, 7.4), 14.9 (10.7, 19.2), and 20.6 (0, 45.1), respectively, with p = 0.002. B. The patients were divided into two groups with or without postoperative complications. The median survival times and 95% confidence intervals were 7 (4.0, 10.0) and 15.9 (11.6, 20.1), respectively, with p = 0.002. C. The patients were divided into four groups according to the different methods of vascular reconstruction. The median survival time and 95% confidence intervals for each group were 14.1 (7.1, 21.1), 13.1 (8.5, 17.8), 12.9 (8.0, 17.8), and 9.2 (4.0, 14.3), respectively, with p = 0.857. D. The patients were divided into three groups according to the volume of intraoperative blood loss: less than 800 ml, 800 to 1500 ml, and more than 1500 ml. The median survival times and 95% confidence intervals for each group were 13.2 (9.7, 16.8), 12.7 (7.1, 18.3), and 9.1 (5.4, 12.7), respectively, with p = 0.659.</p