[Impact of different admission ways on treatment efficiency in patients with acute ST-segment elevation myocardial infarction].

Objective: To analyze the impact of different admission ways on the timeliness of percutaneous coronary intervention and in-hospital mortality in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: A total of 1 044 patients with STEMI, who received primary percutaneous coronary intervention (PPCI) in 9 hospitals in Chengdu from January 2017 to June 2019, were retrospectively enrolled. According to the admission ways, patients were divided into ambulance group (n=100), self-transport group (n=584) and transferred group (n=360). Timeliness and in-hospital mortality were compared among the groups. Indicators of timeliness included the time from symptoms onset to arrive at the hospital, the time from arrive at the hospital to balloon and the total myocardial ischemia time (the time from symptoms to balloon). Multivariate logistic regression analysis was used to verify whether the admission ways was the determinant for in-hospital death in STEMI patients receiving PPCI. Results: The median total myocardial ischemic time in the ambulance group was significantly shorter than that in the self-transport group (180.0 (135.0, 282.0) minutes vs. 278.0 (177.8, 478.5) minutes, P<0.05) and the transferred group (180.0 (135.0, 282.0) minutes vs. 301.0 (204.3, 520.8) minutes, P<0.05). The median time from symptoms to door was as follows: ambulance group0.05). Multivariate logistic regression analysis showed that admission way was not significantly associated with in-hospital death (P>0.05). Conclusions: STEMI patients, who are admitted through the medical emergency system, are more likely to receive timely interventional therapy.Different admission ways have no impact on in-hospital mortality.

Establishing a low-expression renalase gene model in cardiac tissue of Sprague-Dawley rats.

BACKGROUND: Renalase is a novel secretory amino oxidase expressed in the kidney and heart. To study the protective mechanism of renalase in local heart tissue, we established a low-expression renalase model with lentivirus (LV)-mediated RNA interference technology. MATERIALS AND METHODS: Three renalase-targeting oligonucleotides were designed after analyzing the mRNA of renalase. LV particles were prepared with LV expression systems (using the Trono 3 plasmid component system), after which LV-RNLS-shRNAs and LV-NC-shRNA were transfected into H9C2 cells in different cell culture plates. The optimal oligonucleotide was screened by real-time PCR and Western blot. These techniques were also used to detect renalase gene expression in the heart tissue. RESULTS: In the cell screening experiment, the efficacy of the inhibition of renalase mRNA expression was 93.7 % and that of renalase protein expression was 83.1 % in H9C2 cells. When the oligonucleotide was injected into the pericardial cavities of the SD rats on the 10th day, it inhibited 63.9 % of the expression of renalase protein in the heart tissue. CONCLUSION: LV-RNLS-RNAi (19813-1) can be used to establish an optimal renalase low-expression model for further research on the renalase system.

Clinical significance of multi-slice spiral CT, MRI combined with gastric contrast-enhanced ultrasonography in the diagnosis of T staging of gastric cancer.

PURPOSE: To explore the application value of multi-slice spiral CT (MSCT), magnetic resonance imaging (MRI) combined with gastric contrast-enhanced ultrasonography in the diagnosis of T staging of gastric cancer. METHODS: The subjects of study were 109 gastric cancer patients with T stages admitted to our hospital for diagnosis and treatment from December 2016 to December 2018. All the patients were examined with MSCT, MRI and gastric contrast-enhanced ultrasonography before operation to observe corresponding imaging results. T staging of gastric cancer patients was conducted according to the examination results, which was then compared with postoperative pathological staging. It was performed to analyze the accuracy of the three diagnostic methods and combined diagnosis of gastric cancer T staging. RESULTS: The sensitivity of MSCT in the diagnosis of T staging of gastric cancer was 60.00%, 67.74%, 72.22%, 76.47%, the specificity was 95.24%, 88.46%, 86.30%, 94.56% and the diagnostic coincidence rate was 87.16%, 82.57%, 81.65%, 91.74%; the sensitivity of MRI in the diagnosis of T staging of gastric cancer was 68.00%, 70.97%, 77.78%, 76.47%, the specificity was 92.86%, 88.46%, 91.78%, 95.65%, and the diagnostic coincidence rate was 87.16%, 83.49%, 87.16%, 92.66%; the sensitivity of gastric contrast-enhanced ultrasonography in the diagnosis of T staging of gastric cancer was 80.00%, 83.87%, 86.11%, 82.35%, the specificity was 97.62%, 92.31%, 91.78%, 97.83%, and the diagnostic coincidence rate was 93.58%, 89.91%, 89.91%, 95.41%; the sensitivity of combined MSCT, MRI and gastric contrast-enhanced ultrasonography in the diagnosis of T staging of gastric cancer was 88.00%, 93.55%, 97.22%, 94.12%; the specificity was 100%, 97.44%, 95.89%, 98.91%; and the diagnostic coincidence rate was 97.25%, 96.33%, 96.33%, 98.17%, respectively. Statistical analysis revealed that the sensitivity, specificity and diagnostic coincidence rate of combined detection of the three methods were significantly higher than those of single detection (P < 0.05). CONCLUSION: Combined use of MSCT, MRI and gastric contrast-enhanced ultrasonography can significantly improve the diagnostic sensitivity, specificity and diagnostic coincidence rate of T staging of gastric cancer. It may provide a certain reference value for guiding the selection of clinical therapeutic approaches and evaluation of curative effect.

Transfemoral amputation following total knee arthroplasty: mortality and functional outcomes.

AIMS: The aim of this study was to characterize the factors leading to transfemoral amputation after total knee arthroplasty (TKA), as well as the rates of mortality and functional independence after this procedure in these patients. PATIENTS AND METHODS: This was a multicentre retrospective review with a prospective telephone survey for the assessment of function. All patients with a TKA who subsequently required transfemoral amputation between January 2001 and December 2015 were included. Demographic information, medical comorbidities, and postoperative mortality data were collected. A 19-item survey was used for the assessment of function in surviving patients. RESULTS: A total of 111 patients were included. Their mean age was 61.0 years (42.0 to 88.0) at the time of TKA, with a subsequent mean of 3.7 operations (0 to 15) over a mean period of 6.1 years (0.05 to 30.1) before amputation. The indication for amputation was chronic infection in 97 patients (87.4%). The rate of five-year survival was 51.7%, and advanced age (p = 0.001) and renal failure (p = 0.045) were associated with an increased risk of mortality. Of the 62 surviving patients, 34 completed the survey; 32 (94.1%) owned a prosthesis but only 19 (55.9%) used it; 19 (55.9%) primarily used a wheelchair for mobility; 27 (79.5%) had phantom pain; and 16 (47.1%) required chronic pain medication. Only 18 patients (52.9%) were satisfied with the quality of life. CONCLUSION: Patients with complications after TKA, in whom transfemoral amputation is considered, should be made aware of the high rate of mortality and the poor functional outcome in the survivors. Alternative forms of treatment including arthrodesis of the knee should be investigated.

The Impact of Incorporating Antimicrobials into Implant Surfaces.

With the increase in numbers of joint replacements, spinal surgeries, and dental implantations, there is an urgent need to combat implant-associated infection. In addition to stringent sterile techniques, an efficacious way to prevent this destructive complication is to create new implants with antimicrobial properties. Specifically, these implants must be active in the dental implant environment where the implant is bathed in the glycoprotein-rich salivary fluids that enhance bacterial adhesion, and propagation, and biofilm formation. However, in designing an antimicrobial surface, a balance must be struck between antimicrobial activity and the need for the implant to interact with the bone environment. Three types of surfaces have been designed to combat biofilm formation, while attempting to maintain osseous interactions: 1) structured surfaces where topography, usually at the nanoscale, decreases bacterial adhesion sufficiently to retard establishment of infection; 2) surfaces that actively elute antimicrobials to avert bacterial adhesion and promote killing; and 3) surfaces containing permanently bonded agents that generate antimicrobial surfaces that prevent long-term bacterial adhesion. Both topographical and elution surfaces exhibit varying, albeit limited, antimicrobial activity in vitro. With respect to covalent coupling, we present studies on the ability of the permanent antimicrobial surfaces to kill organisms while fostering osseointegration. All approaches have significant drawbacks with respect to stability and efficacy, but the permanent surfaces may have an edge in creating a long-term antibacterial environment.

Correction: eEF-2 kinase is a critical regulator of Warbrug effect through controlling PP2A-A synthesis.

In this article, the authors recently noticed that the tubulin blots in Figs. 2a and 6a were inadvertently misplaced during the preparation of these figures due to their similarity. The amended versions of the figures are now shown below. The conclusions of this paper are not affected. The authors sincerely apologize for these errors.

Quadriceps sparing total knee replacement. The initial experience with results at two to four years.

The aim of this study was to compare the results in patients having a quadriceps sparing total knee replacement (TKR) with those undergoing a standard TKR at a minimum follow-up of two years. All patients who had a TKR with a high-flex posterior-stabilised prosthesis prior to December 2002 were reviewed retrospectively. There were 57 patients available for follow-up. Those with a quadriceps sparing TKR had less pain peri-operatively with a greater degree of flexion at all the post-operative visits and at the final follow-up, but their operations took longer, with less accurate radiological alignment. There was no difference in the complications and in the Knee Society scores between the two groups at the final follow-up. Total knee replacement through a quadriceps sparing approach has some peri-operative advantages over the standard incision. At a minimum follow-up of two years the clinical results were similar to those with a standard incision, but the radiological outcomes of the quadriceps sparing group were inferior.

eEF-2 kinase is a critical regulator of Warburg effect through controlling PP2A-A synthesis.

Cancer cells predominantly metabolize glucose by glycolysis to produce energy in order to meet their metabolic requirement, a phenomenon known as Warburg effect. Although Warburg effect is considered a peculiarity critical for survival and proliferation of cancer cells, the regulatory mechanisms behind this phenomenon remain incompletely understood. We report here that eukaryotic elongation factor-2 kinase (eEF-2K), a negative regulator of protein synthesis, has a critical role in promoting glycolysis in cancer cells. We showed that deficiency in eEF-2K significantly reduced the uptake of glucose and decreased the productions of lactate and adenosine triphosphate in tumor cells and in the Ras-transformed mouse embryonic fibroblasts. We further demonstrated that the promotive effect of eEF-2K on glycolysis resulted from the kinase-mediated restriction of synthesis of the protein phosphatase 2A-A (PP2A-A), a key factor that facilitates the ubiquitin-proteasomal degradation of c-Myc protein, as knockdown of eEF-2K expression led to a significant increase in PP2A-A protein synthesis and remarkable downregulation of c-Myc and pyruvate kinase M2 isoform, the key glycolytic enzyme transcriptionally activated by c-Myc. In addition, depletion of eEF-2K reduced the ability of the transformed cells to proliferate and enhanced the sensitivity of tumor cells to chemotherapy both in vitro and in vivo. These results, which uncover a role of the eEF-2K-mediated control of PP2A-A in tumor cell glycolysis, provide new insights into the regulation of the Warburg effect.

Transfer and expression of recombinant nitric oxide synthase genes in the cardiovascular system.

Gene therapy involves the transfer of a functional gene into host cells to correct the malfunction of a specific gene or to alleviate the symptoms of a disease. For gene transfer to the cardiovascular system, adenoviral vectors are the most efficient means of transfer. Recently, transfer and functional expression of recombinant nitrio oxide synthase (NOS) genes to cerebral and cardiovascular beds have been demonstrated both ex vivo and in vivo. Here, Alex Chen and colleagues review current progress in the field of vascular NOS gene transfer and the potential use of NOS gene therapy for a number of cardiovascular diseases. Although the feasibility of the NOS gene transfer approach has been demonstrated in animal models, currently available vectors have a number of technical and safety limitations that have to be solved before human NOS gene therapy for cardiovascular disease can be attempted.

Integrating Multiple Evidence Sources to Predict Adverse Drug Reactions Based on a Systems Pharmacology Model.

Identifying potential adverse drug reactions (ADRs) is critically important for drug discovery and public health. Here we developed a multiple evidence fusion (MEF) method for the large-scale prediction of drug ADRs that can handle both approved drugs and novel molecules. MEF is based on the similarity reference by collaborative filtering, and integrates multiple similarity measures from various data types, taking advantage of the complementarity in the data. We used MEF to integrate drug-related and ADR-related data from multiple levels, including the network structural data formed by known drug-ADR relationships for predicting likely unknown ADRs. On cross-validation, it obtains high sensitivity and specificity, substantially outperforming existing methods that utilize single or a few data types. We validated our prediction by their overlap with drug-ADR associations that are known in databases. The proposed computational method could be used for complementary hypothesis generation and rapid analysis of potential drug-ADR interactions.

Relationships of adenine nucleotide metabolism to platelet-collagen adhesion.

Adhesion of platelets to collagen fibrils in a stirred system was inhibited by preincubation of platelets with combinations of 2-deoxy-D-glucose and oligomycin or antimycin. The inhibition of adhesion was associated with a decrease in metabolic ATP to 6% of control levels. Without metabolic inhibitors, platelets adherent to collagen fibrils were found to have catabolized approximately 57% of their metabolic ATP, and converted a major part of this to IMP. Storage pool ATP and ADP contents were also diminished in the adherent platelets. Pretreatment with imipramine resulted in 76% inhibition of the release reaction, but only 5% inhibition of adhesion. Imipramine-treated platelets that were adherent to collagen showed significant depletion of metabolic ATP, but markedly diminished conversion of ATP to IMP as compared to control adherent platelets. Inhibition of deamination of platelet AMP by coformycin or erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) did not inhibit adhesion, although platelets adherent to collagen after treatment with these agents showed depletion of metabolic ATP. These studies suggest that adhesion is an energy dependent process, occurring independently of release, and not associated with conversion of ATP to IMP. The energy dependent portions of the adhesion process are probably disc to sphere transformation and pseudopod formation, the ATP threhold requirement is relatively low, and the ATP utilized can probably be regenerated during the adhesion process via glycolysis and oxidative phosphorylation.

Cerebellopontine angle tumor composed of Schwann and meningeal proliferations.

Tumors found in the cerebellopontine angle are predominantly vestibular schwannomas. Mixed tumors found within the cerebellopontine angle are thought to be exceedingly rare and exclusively associated with neurofibromatosis 2. We report a case of a mixed tumor composed of Schwann and meningeal cell proliferations in a patient who was not diagnosed as having neurofibromatosis 2. Mixed tumors composed of neoplastic Schwann and meningeal cells have rarely been reported. However, new evidence indicates that these mixed tumors may be more common than was previously thought and may have an interrelated mechanism of pathogenesis. Although the case we describe does not fulfill the current diagnostic criteria for neurofibromatosis 2, a presumptive diagnosis was given, suggesting that the current diagnostic criteria for neurofibromatosis 2 may be too narrow.

MYO1F as a candidate gene for nonsyndromic deafness, DFNB15.

BACKGROUND: Earlier studies have mapped the autosomal recessive nonsyndromic deafness locus, DFNB15, to chromosomes 3q21.3-q25.2 and 19p13.3-13.1, identifying one of these chromosomal regions (or possibly both) as the site of a deafness-causing gene. Mutations in unconventional myosins cause deafness in mice and humans. One unconventional myosin, myosin 1F (MYO1F), is expressed in the cochlea and maps to chromosome 19p13.3-13.2. OBJECTIVE: To evaluate MYO1F as a candidate gene for deafness at the DFNB15 locus by determining its genomic structure and screening each exon for deafness-causing mutations to identify possible allele variants of MYO1F segregating in the DFNB15 family. METHODS: We used radiation hybrid mapping to localize MYO1F on chromosome arm 19p. We next determined its genomic structure using multiple long-range polymerase chain reaction experiments. Using these data, we completed mutation screening using single-stranded conformational polymorphism analysis and direct sequencing of affected and nonaffected persons in the original DFNB15 family. RESULTS: Radiation hybrid mapping placed MYO1F in the DFNB15 interval, establishing it as a positional candidate gene. Its genomic structure consists of 24 coding exons. No mutations or genomic rearrangements were found in the original DFNB15 family, making it unlikely that MYO1F is the disease-causing gene in this kindred. CONCLUSIONS: Although we did not find MYO1F allele variants in one family with autosomal recessive nonsyndromic hearing loss, the gene remains an excellent candidate for hereditary hearing impairment. Given its wide tissue expression, MYO1F might cause syndromic deafness.

Prenatal diagnosis of intracardiac rhabdomyoma: a case report.

We report on a case of intracardiac rhabdomyoma diagnosed prenatally from two-dimensional echocardiograms. The tumor was diagnosed by intrauterine echocardiography at the 38th week of gestation. Autopsy proved that the intracardiac tumor was a rhabdomyoma. Tuberous sclerosis spots in the brain tissue were also found.

[Synthesis of N,N-alkylene-bis-(substituted-phenol)glycine for removal of radio-actinides in rats].

The synthesis of 16 compounds of N, N-alkylene-bis (substituted phenol) glycine is reported. They showed good effects on the removal of redinuclide thorium-234 from rats, except compound 3 and compound 4. Two of them can remove more than 70% of injected thorium. The relationship between structure and effects of these compounds was discussed.

Proceedings of the International Consensus on Periprosthetic Joint Infection.

Louis Pasteur once said that: "Fortune favours the prepared mind." As one of the great scientists who contributed to the fight against infection, he emphasised the importance of being prepared at all times to recognise infection and deal with it. Despite the many scientific discoveries and technological advances, such as the advent of antibiotics and the use of sterile techniques, infection continues to be a problem that haunts orthopaedic surgeons and inflicts suffering on patients. The medical community has implemented many practices with the intention of preventing infection and treating it effectively when it occurs. Although high-level evidence may support some of these practices, many are based on little to no scientific foundation. Thus, around the world, there is great variation in practices for the prevention and management of periprosthetic joint infection. This paper summaries the instigation, conduct and findings of a recent International Consensus Meeting on Surgical Site and Periprosthetic Joint Infection.

The economics and timing of preoperative antibiotics for orthopaedic procedures.

BACKGROUND: The efficacy of antibiotics in preventing surgical site infections (SSIs) depends on the timing of administration relative to the start of surgery. However, currently, both the timing of and recommendations for administration vary substantially. AIM: To determine how the economic value from the hospital perspective of preoperative antibiotics varies with the timing of administration for orthopaedic procedures. METHODS: Computational decision and operational models were developed from the hospital perspective. Baseline analyses looked at current timing of administration, while additional analyses varied the timing of administration, compliance with recommended guidelines, and the goal time-interval. FINDINGS: Beginning antibiotic administration within 0-30 min prior to surgery resulted in the lowest costs and SSIs. Operationally, linking to a pre-surgical activity, administering antibiotics prior to incision but after anaesthesia-ready time was optimal, as 92.1% of the time, antibiotics were administered in the optimal time-interval (0-30 min prior to incision). Improving administration compliance from 80% to 90% for this pre-surgical activity results in cost savings of $447 per year for a hospital performing 100 orthopaedic operations a year. CONCLUSION: This study quantifies the potential cost-savings when antibiotic administration timing is improved, which in turn can guide the amount hospitals should invest to address this issue.

Clinical significance of multi-slice spiral CT, MRI combined with gastric contrast-enhanced ultrasonography in the diagnosis of T staging of gastric cancer

Purpose To explore the application value of multi-slice spiral CT (MSCT), magnetic resonance imaging (MRI) combined with gastric contrast-enhanced ultrasonography in the diagnosis of T staging of gastric cancer. Methods The subjects of study were 109 gastric cancer patients with T stages admitted to our hospital for diagnosis and treatment from December 2016 to December 2018. All the patients were examined with MSCT, MRI and gastric contrast-enhanced ultrasonography before operation to observe corresponding imaging results. T staging of gastric cancer patients was conducted according to the examination results, which was then compared with postoperative pathological staging. It was performed to analyze the accuracy of the three diagnostic methods and combined diagnosis of gastric cancer T staging. Results The sensitivity of MSCT in the diagnosis of T staging of gastric cancer was 60.00%, 67.74%, 72.22%, 76.47%, the specificity was 95.24%, 88.46%, 86.30%, 94.56% and the diagnostic coincidence rate was 87.16%, 82.57%, 81.65%, 91.74%; the sensitivity of MRI in the diagnosis of T staging of gastric cancer was 68.00%, 70.97%, 77.78%, 76.47%, the specificity was 92.86%, 88.46%, 91.78%, 95.65%, and the diagnostic coincidence rate was 87.16%, 83.49%, 87.16%, 92.66%; the sensitivity of gastric contrast-enhanced ultrasonography in the diagnosis of T staging of gastric cancer was 80.00%, 83.87%, 86.11%, 82.35%, the specificity was 97.62%, 92.31%, 91.78%, 97.83%, and the diagnostic coincidence rate was 93.58%, 89.91%, 89.91%, 95.41%; the sensitivity of combined MSCT, MRI and gastric contrast-enhanced ultrasonography in the diagnosis of T staging of gastric cancer was 88.00%, 93.55%, 97.22%, 94.12%; the specificity was 100%, 97.44%, 95.89%, 98.91%; and the diagnostic coincidence rate was 97.25%, 96.33%, 96.33%, 98.17%, respectively (AU)