Search

This paper aims to solve the scheduling optimization problem in the emergency management of long-distance natural gas pipelines, with the goal of minimizing the total scheduling time. To this end, the objective function of the minimum total scheduling time is established, and the relevant constraints are set. A scheduling optimization model based on the particle swarm optimization (PSO) algorithm is proposed. In view of the high-dimensional complexity and local optimal problems, the neighborhood adaptive constrained fractional particle swarm optimization (NACFPSO) algorithm is used to solve it. The experimental results show that compared with the traditional particle swarm optimization algorithm, NACFPSO performs well in both convergence speed and scheduling time, with an average convergence speed of 81.17 iterations and an average scheduling time of 200.00 minutes; while the average convergence speed of the particle swarm optimization algorithm is 82.17 iterations and an average scheduling time of 207.49 minutes. In addition, with the increase of pipeline complexity, NACFPSO can still maintain its advantages in convergence speed and scheduling time, especially in scheduling time, which further verifies the optimization effect of the algorithm in emergency management. [ABSTRACT FROM AUTHOR]

Drug package inserts are a crucial foundation for clinical medication practices and serve as the legal basis for guiding rational drug use and ensuring patient safety and efficacy. As rare disease treatments evolve, current package inserts often need to meet the clinical requirements for treating such conditions, frequently resulting in off-label drug use. This consensus is derived from discussions between Guangdong Pharmaceutical Association Hematologic Rare Diseases Group experts. The consensus aims to provide a framework and reference for the clinical application of off-label drug use in treating rare hematologic diseases. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the application of different uterine artery embolization procedures under balloon occlusion of the abdominal aorta in patients with Placenta Accreta Spectrum (PAS) undergoing cesarean section. Materials and Methods: A retrospective analysis was performed on clinical data from 72 patients who underwent uterine artery embolization for hemostasis during cesarean section with PAS. The patients were divided into two groups according to the embolization method used during surgery: group A (n = 43) underwent uterine artery embolization by withdrawing the balloon and inserting a Cobra catheter into the uterine artery for embolization, while group B (n = 29) underwent uterine artery embolization with a Cobra catheter inserted via contralateral puncture of the femoral artery and balloon occlusion. General information, surgical data, and postoperative recovery were compared between the 2 groups. Results: The bleeding and transfusion volumes were lower in group B than in group A and the differences between the 2 groups were statistically significant. There were no significant differences in surgical duration, number of embolized vessels, length of hospital stay, postoperative complications, or menstrual recovery between the 2 groups. Conclusion: For patients with PAS undergoing cesarean section, uterine artery embolization for hemostasis is preferably performed by inserting a Cobra catheter via contralateral puncture of the femoral artery under abdominal aortic balloon occlusion. [ABSTRACT FROM AUTHOR]

Background: The unicellular protozoan parasite Giardia intestinalis, which primarily infects humans and animals such as cattle and sheep, is having a major negative impact on public health. Giardia is able to evade the recognition and elimination of the host immune system because of the trophozoite surface and extracellular vesicles (EVs) covered by variant-specific surface proteins (VSPs). As key proteins for immune evasion, whether VSPs can regulate Giardia-induced pyroptosis and promote Giardia evasion of host immune responses has not been reported. Methods: To examine the role of Giardia VSPAS7 on Giardia-induced activation of the signaling pathway, secretion of pro-inflammatory cytokines, pyroptosis and the mechanism involved, we constructed the pcDNA3.1-vspas7 expression plasmid and transfected this plasmid into mouse macrophages. Key proteins for pyroptosis, IL-1β secretion and LDH release were detected in pcDNA3.1-vspas7-transfected wild-type (WT) cells and NLRP3-deficient cells by western blot, ELISA and LDH assays, respectively. The interactions of Giardia VSPAS7 and mouse NLRP3 were examined using immunofluorescence assays (IFA), co-immunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays. Results: VSPAS7 could decrease the levels of phosphorylated-p65 (P-p65), P-IκBα and P-ERK caused by Giardia and reduce the production levels of Giardia-induced pro-inflammatory cytokine IL-6, IL-12 p40 and TNF-α. The results showed that VSPAS7 inhibited Giardia-mediated activation of NF-κB, ERK/MAPK signaling and secretion of pro-inflammatory cytokines. Furthermore, VSPAS7 suppressed Giardia-induced macrophage pyroptosis by reducing GSDMD cleavage, caspase-1 activation, IL-1β secretion and LDH release. We further found that VSPAS7 could interact with mouse NLRP3 directly, and in NLRP3-deficient cells the suppression of Giardia-induced macrophage pyroptosis by VSPAS7 was significantly attenuated. Conclusions: Overall, VSPAS7 could inhibit Giardia-induced activation of signaling pathways and pyroptosis in host macrophages, allowing Giardia evasion of host immune responses. Studies on Giardia VSP-mediated immune evasion provide an important theoretical basis for in-depth studies on Giardia pathogenicity. [ABSTRACT FROM AUTHOR]

The experience of a physician at a clinical center is among the critical factors in managing chronic myeloid leukemia (CML) during its treatment with tyrosine kinase inhibitors (TKIs). The authors conducted a cross-sectional questionnaire to investigate barriers to physician use of published evidence-based guidelines in CML management in a real-world setting. Among the participating physicians (N = 407), 99.8% of physicians reported that CML guidelines were useful; however, only 62.9% of physicians reported that they follow guidelines in real-time. Although 90.7% of physicians prefer second-generation TKIs as the first-line treatment, imatinib (88.2%) remains the most widely administered TKI in the first-line setting. Only 50.6% of physicians switched the treatment when patients failed to achieve early molecular response (at 3 months), whereas 70.3% of physicians switched the treatment when patients' response to TKI was inadequate at 6 months and/or 12 months. Moreover, only 43.5% of physicians considered treatment-free remission (TFR) as one of the top 3 goals for their patients. The major concern to obtain TFR was patients' adherence. This study demonstrated that CML management was generally in line with the current guidelines, but some of the details at the point of care are needed to be improved in CML. [ABSTRACT FROM AUTHOR]

Background: Giardia duodenalis (referred to as Giardia) is a flagellated binucleate protozoan parasite, which causes one of the most common diarrheal diseases, giardiasis, worldwide. Giardia can be infected by Giardiavirus (GLV), a small endosymbiotic dsRNA virus belongs to the Totiviridae family. However, the regulation of GLV and a positive correlation between GLV and Giardia virulence is yet to be elucidated. Methods: To identify potential regulators of GLV, we performed a yeast two-hybrid (Y2H) screen to search for interacting proteins of RdRp. GST pull-down, co-immunoprecipitation and bimolecular fluorescence complementation (BiFC) assay were used to verify the direct physical interaction between GLV RdRp and its new binding partner. In addition, their in vivo interaction and colocalization in Giardia trophozoites were examined by using Duolink proximal ligation assay (Duolink PLA). Results: From Y2H screen, the Giardia chaperone protein, Giardia DnaJ (GdDnaJ), was identified as a new binding partner for GLV RdRp. The direct interaction between GdDnaJ and GLV RdRp was verified via GST pull-down, co-immunoprecipitation and BiFC. In addition, colocalization and in vivo interaction between GdDnaJ and RdRp in Giardia trophozoites were confirmed by Duolink PLA. Further analysis revealed that KNK437, the inhibitor of GdDnaJ, can significantly reduce the replication of GLVs and the proliferation of Giardia. Conclusion: Taken together, our results suggested a potential role of GdDnaJ in regulating Giardia proliferation and GLV replication through interaction with GLV RdRp. [ABSTRACT FROM AUTHOR]

Recombinant human TPO (rhTPO) is effective for refractory/relapsed primary immune thrombocytopenia (ITP), but optimal dosing regimen remains elusive. In this multicenter, randomized, controlled trial, a total of 282 adult ITP patients (mean age 47.3 years; 82 men) with a platelet count ≤30 × 109/L or >30 × 109/L with active bleeding randomly received a once daily (QD) subcutaneous injection of 7500 U (n = 64) or 15000 U rhTPO for 14 injections, or 15000 U or 30000 U rhTPO once every other day (QOD) for 7 injections. The primary outcomes included change from baseline in platelet count and total response rate (TRR) on day 14. On day 14, the median increase of platelet count from baseline was the highest in the 15000-U QD group (167.5 × 109/L, interquartile range [IQR] 23.0–295.0 × 109/L), followed by the 30000-U QOD group (57.5 × 109/L, IQR 9.0–190.0 × 109/L) (ANCOVA P <.001; P =.266 with baseline count as a covariate). The TRR on day 14 was also the highest in the 15000-U QD group (63.2%), followed by the 30000-U QOD group (59.7%). The rate of grade 3 and above adverse events did not differ among the four groups. There were no new safety concerns. All 4 regimens are safe and well-tolerated. The 30000-U QOD regimen is practically indistinguishable in efficacy to the 15000-U QD regimen. What is the context? Relative thrombopoietin deficiency is implicated in primary immune thrombocytopenia (ITP), which is characterized by increased platelet destruction and impaired megakaryopoiesis. Patients who are innately unresponsive to or have relapsed after glucocorticoid treatment have limited treatment options. Recombinant human thrombopoietin (rhTPO) improves treatment response of primary ITP patients when added to high-dose dexamethasone. What is new? This trial sought to identify an optimal dosing regimen of rhTPO for patients who had failed or relapsed after glucocorticoid therapy. Of the 4 regimens, once daily 15000 U rhTPO for 14 injections yielded the greatest median increase in platelet count (167.5 × 109/L) from baseline and attained the highest total response rate on day 14 (63.2%). 30000 U rhTPO once every other day for 7 injections was effective in rapidly increasing platelet counts in the first 7 days. All 4 regimens were safe and well-tolerated. What is the impact? The 30000 U rhTPO once every other day regimen may offer an effective and safe regimen with less frequent injections, but future trials with longer follow-up are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Neospora caninum is an apicomplexan parasite with worldwide distribution, infecting cattle, goats and other kinds of warm-blooded animals. However, specific medicines for the prevention or treatment of Neospora caninum are still limited. This study is aimed at selecting a potential immunoprotective antigen of N. caninum and evaluating the adjuvant function of interleukin (IL)-18 in mice or goats; NcSRS2, NcSRS17 and NcSRS52 from the SRS superfamily were considered to be targets. The results reveal that the recombinant proteins NcSRS2, NcSRS17 and NcSRS52 can all induce humoral and cellular immune responses, and NcSRS17 showed itself to be a promising new antigen candidate. IL-18 had a certain immunoenhancing effect in both experimental animal mice and intermediate host goats and could be used as an adjuvant. Neosporosis is caused by Neospora caninum (N. caninum), which mainly infects cattle and goats and severely threatens the animal industry. In this study, the inhibitory effects of polyclonal antiserum anti-NcSRS17, NcSRS2 and NcSRS52 were explored. Cytokines in mice or goat serum were detected after immunization. After infection, the survival of mice was recorded. The pathological changes and parasite loads were observed and detected in tissues. The results showed that anti-NcSRS2, NcSRS17 and NcSRS52 antibodies all inhibit the invasion and proliferation of N. caninum. The IFN-γ level in the NcSRS17 group was higher than that in the NcSRS2 and NcSRS52 groups, and higher in the NcSRS2-mIL-18 group than in the NcSRS2 group. The survival rates of mice were 16% in the positive control group, 67% in the SRS52 group, 83% in the SRS2 and mIL-18 groups and 100% in the SRS17 and SRS2-mIL-18 groups. Goats immunized with NcSRS17-gIL-18 developed high levels of IL-4, IL-12 and IFN-γ compared with those immunized with NcSRS-17. Parasite loads in the brains of animals in the NcSRS17 and NcSRS17-gIL-18 groups were significantly reduced, and were significantly lower in the NcSRS17-gIL-18 group (p ≤ 0.01). This study indicates that SRS17 may be an antigen candidate for vaccine development against neosporosis, and IL-18 can enhance the immune protective efficiency of antigen candidates. [ABSTRACT FROM AUTHOR]

In this study, we found that I P. hominis i infection in Siberian tigers occurs in northeast China, providing additional data on the parasitic infection of Siberian tigers. Therefore, Siberian tigers can act as a natural host for I P. hominis i and also as a transmission source for I P. hominis i infections in humans (Maritz I et al i . 2014). To determine I P. hominis i infection in the captive animal, stool samples of the Siberian tiger were examined by nested polymerase chain reaction (PCR) using partial 18S rRNA and ITS sequences of I P. hominis i as target genes. Genetic analysis of the 18S rRNA sequences revealed that all I P. hominis i obtained in this study belonged to the genotype CC1, suggesting potential zoonotic transmission of I P. hominis i between Siberian tigers and other hosts. [Extracted from the article]