A Case History of Super-Large Scale Bridge Pile Foundation in Soft Soil

The Sutong Yangtze River Bridge is the longest cable-stayed bridge in the world with main span of 1088 m. The pile cap is 113.8 m by 48.1 m by 13.3 m under each pylon and the foundation is super-long large-diameter drilled pile groups consisting of 131 piles with the length of 114/117 m and the diameter of 2.8/2.5m. This paper presents the static loading tests on single piles, centrifugal model tests on pile groups, finite element analysis, cap model tests and field monitoring for the super-large scale pile foundation. The results show that: the super-long large-diameter bored pile of Sutong Bridge is floating piles, and it is difficult for the resistance at pile bottom to play. based on the comprehensive consideration of theoretical calculation, centrifugal model tests and finite element analysis, the pile group effect coefficient of the Sutong Yangtze Bridge is 0.82. The pile-head load distribution of pile foundation under main bridge pylon presents a “W” shape, which is larger at both the edges and intermediate connection and smaller at other position of pylon. According to the results of cap model tests, the soften-coordinated spatial truss model was suitable for the stress analysis of cap. The calculated results agree well with the field monitoring results

Laparoscopic Surgery Can Reduce Postoperative Edema Compared with Open Surgery

Aim. The study aimed to investigate the impact of laparoscopic surgery and open surgery on postoperative edema in Crohn’s disease. Methods. Patients who required enterectomy were divided into open group (Group O) and laparoscopic group (Group L). Edema was measured using bioelectrical impedance analysis preoperatively (PRE) and on postoperative day 3 (POD3) and postoperative day 5 (POD5). The postoperative edema was divided into slight edema and edema by an edema index, defined as the ratio of total extracellular water to total body water. Results. Patients who underwent laparoscopic surgery had better clinical outcomes and lower levels of inflammatory and stress markers. A total of 31 patients (26.05%) developed slight edema and 53 patients (44.54%) developed edema on POD3. More patients developed postoperative edema in Group O than in Group L on POD3 (p=0.006). The value of the edema index of Group O was higher than that of Group L on POD3 and POD5 (0.402±0.010 versus 0.397±0.008, p=0.001; 0.401±0.009 versus 0.395±0.007, p=0.039, resp.). Conclusions. Compared with open surgery, laparoscopic surgery can reduce postoperative edema, which may contribute to the better outcomes of laparoscopic surgery over open surgery

Clinical and Experimental Studies of a Novel P525R FUS Mutation in Amyotrophic Lateral Sclerosis

Objective: To describe the clinical features of a novel fused in sarcoma (FUS) mutation in a young adult female amyotrophic lateral sclerosis (ALS) patient with rapid progression of weakness and to experimentally validate the consequences of the P525R mutation in cellular neuronal models. Methods: We conducted sequencing of genomic DNA from the index patient and her family members. Immunocytochemistry was performed in various cellular models to determine whether the newly identified P525R mutant FUS protein accumulated in cytoplasmic inclusions. Clinical features of the index patient were compared with 19 other patients with ALS carrying the P525L mutation in the same amino acid position. Results: A novel mutation c.1574C\u3eG (p.525P\u3eR) in the in the FUS gene was identified in the index patient. The clinical symptoms are similar to those in familial ALS patients with the P525L mutation at the same position. The P525R mutant FUS protein showed cytoplasmic localization and formed large stress granule–like cytoplasmic inclusions in multiple cellular models. Conclusions: The clinical features of the patient and the cytoplasmic inclusions of the P525R mutant FUS protein strengthen the notion that mutations at position 525 of the FUS protein result in a coherent phenotype characterized by juvenile or young adult onset, rapid progression, variable positive family history, and female preponderance

microRNA-144/451 decreases dendritic cell bioactivity via targeting interferon-regulatory factor 5 to limit DSS-induced colitis

The microRNAs miR-144/451 are highly conserved miRNA that is strongly induced during erythropoiesis. Despite the biological functions of miR-144/451 have been extensively studied in erythropoiesis and tumorigenesis, few studies have been conducted in immune responses. In this study, we showed that miR-144/451-/- DCs exhibit increased activation. Mechanistically, the miR-144 directly targets the 3`-UTR of IRF5 and represses the expression of IRF5 in DCs. Ectopic expression of miR-144/451 by lentiviruses downregulates the levels of IRF5 and suppresses DCs function. In addition, knockdown of IRF5 by shRNA significantly inhibits activities of the miR-144/451-/- DCs. Expression of miR144/451 was decreased in DCs from both patients with IBD and mice with DSS-colitis compared with controls. Human PBMC derived DCs were downregulated expression of miR144/451 after LPS stimulation. In the DSS-induced colitis mice model, we showed that ablation of the miR-144/451 gene causes severe colitis, and their DCs from both periphery and MLN expressed higher co-stimulatory molecules and pro-inflammatory cytokines than wild-type mice. In addition, DCs isolated from miR-144/451-/- mice transfusion exacerbates mice colitis. In the bone marrow transplanted chimeric mice model, we show that miR-144/451-/- bone marrow transplantation deteriorated DSS-induced colitis. At last, we treat the mice with miR-144/451 delivered by chitosan nanoparticles revealing protective effects in DSS-induced colitis mice. Thus, our results reveal a novel miR144/451-IRF5 pathway in DCs that protects experimental colitis. The manipulation of miR-144/451 expression and DCs activation in IBD patients may be a novel therapeutic approach for the treatment of inflammatory diseases

Local Gene Transfer of OPG Prevents Joint Damage and Disease Progression in Collagen-Induced Arthritis

This study examined the influence of osteoprotegerin (OPG) gene transfer on a murine collagen-induced arthritis model. A single periarticular injection of AAV-OPG or AAV-LacZ on the arthritic paw successfully incorporated the exogenous gene to the local tissue and resulted in marked transgene expression in the joint homogenate for at least three weeks. Clinical disease scores were significantly improved in OPG treated mice starting at 28-day post-treatment (P<0.05). Histological assessment demonstrated that OPG gene transfer dramatically protected mice from erosive joint changes compared with LacZ controls (P<0.05), although treatment appeared less effective on the local inflammatory progress. MicroCT data suggested significant protection against subchondral bone mineral density changes in OPG treated CIA mice. Interestingly, mRNA expressions of IFN-g and MMP3 were noticeably diminished following OPG gene transfer. Overall, gene transfer of OPG effectively inhibited the arthritis-associated periarticular bone erosion and preserved the architecture of arthritic joints, and the study provides evidence that the cartilage protection of the OPG gene therapy may be associated with the down-regulation of MMP3 expression

How kindness can be contagious in healthcare.

Pay-it-forward programs, whereby someone receives a gift or free service and then gives a gift to another person in return, have expanded during the COVID-19 pandemic and provide an opportunity for healthcare providers to reduce costs, increase uptake of interventions such as testing and vaccines, and promote sustainability

FH535, a β-catenin Pathway Inhibitor, Represses Pancreatic Cancer Xenograft Growth and Angiogenesis

The WNT/β-catenin pathway plays an important role in pancreatic cancer carcinogenesis. We evaluated the correlation between aberrant β-catenin pathway activation and the prognosis pancreatic cancer, and the potential of applying the β-catenin pathway inhibitor FH535 to pancreatic cancer treatment. Meta-analysis and immunohistochemistry showed that abnormal β-catenin pathway activation was associated with unfavorable outcome. FH535 repressed pancreatic cancer xenograft growth in vivo. Gene Ontology (GO) analysis of microarray data indicated that target genes responding to FH535 participated in stemness maintenance. Real-time PCR and flow cytometry confirmed that FH535 downregulated CD24 and CD44, pancreatic cancer stem cell (CSC) markers, suggesting FH535 impairs pancreatic CSC stemness. GO analysis of β-catenin chromatin immunoprecipitation sequencing data identified angiogenesis-related gene regulation. Immunohistochemistry showed that higher microvessel density correlated with elevated nuclear β-catenin expression and unfavorable outcome. FH535 repressed the secretion of the proangiogenic cytokines vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, and tumor necrosis factor-α, and also inhibited angiogenesis in vitro and in vivo. Protein and mRNA microarrays revealed that FH535 downregulated the proangiogenic genes ANGPT2, VEGFR3, IFN-γ, PLAUR, THPO, TIMP1, and VEGF. FH535 not only represses pancreatic CSC stemness in vitro, but also remodels the tumor microenvironment by repressing angiogenesis, warranting further clinical investigation

Azithromycin Treatment Failure Among Primary and Secondary Syphilis Patients in Shanghai

Azithromycin has been used to treat primary and secondary syphilis and as prophylaxis for sexual partners. We evaluated syphilis treatment failure in patients who received azithromycin therapy

Mesenteric excision surgery or conservative limited resection in Crohn’s disease: study protocol for an international, multicenter, randomized controlled trial

Background The structures of the mesentery including adipose tissue, nerves, and lymphatics play an important role in the pathogenesis and disease progression of Crohn’s disease (CD). Conventional surgical resection for CD usually does not involve resecting the mesentery en bloc with the specimen. This contrasts with complete mesocolic excision (CME) in colorectal cancer, which involves radical resection of the mesentery. Preliminary evidence from smaller studies suggests that applying the principle of mesocolic excision to CD surgery may reduce the risk of postoperative recurrence. This randomized controlled trial is designed to test whether applying the principles of mesocolic excision to CD results in reduced postoperative recurrence. It also aims to evaluate intra- and postoperative morbidity between the two approaches. Methods This international, multicenter, randomized controlled trial will randomize patients (n = 116) scheduled to undergo primary ileocolic resection to either receive extensive mesenteric excision (EME) or conventional ileocolic resection with limited mesenteric excision (LME). Five sites will recruit patients in three countries. In the EME group, the mesentery is resected following CME, while avoiding the root region, i.e., 1 cm from the root of the ileocolic artery and vein. In the LME group, the mesentery is retained, i.e., “close shave” or < 3 cm from the border of bowel. The primary end point will be surgical recurrence after surgery. The secondary end points will be the postoperative endoscopic and clinical recurrence, and intra- and postoperative morbidity. Demographics, risk factors, laboratory investigations, endoscopy, postoperative prophylaxis and imaging examination will be assessed. Analysis of the primary outcome will be on an intention-to-treat basis. Discussion If mesocolic excision in CD reduces postoperative disease recurrence and does not increase morbidity, this trial has the potential to change practice and reduce recurrence of CD after surgical resection. Trial registration Clinical Trials.gov, ID: NCT03769922. Registered on February 27, 2019