健脾消癌方通过PI3K/Akt信号通路抑制结肠癌血管生成的研究＊

目的 观察结肠癌HCT116细胞健脾消癌方的条件培养液对HUVEC细胞管腔形成的影响，从PI3K/Akt生物轴调控角度探讨其作用机制。方法 培养HCT116细胞，细胞设3组：对照组，健脾消癌方组（加入15%健脾消癌方含药血清）及人参皂苷Rg3组；制备HCT116细胞健脾消癌方条件培养液（分组及制备方法见实验方法），用条件培养液干预HUVEC（脐静脉内皮细胞，Human Umbilical Vein Endothelial Cells），Matrigel基质胶法检测HCT116细胞健脾消癌方条件培养液对HUVEC小管形成的影响。随后采用蛋白免疫印迹法（Western blot）检测各组HCT116细胞磷脂酰肌醇3-激酶（PI3K）、蛋白激酶B（Akt）、p-Akt、VEGF（血管内皮生长因子，Vascular endothelial growth factor）蛋白表达。最后在结肠癌HCT116荷瘤小鼠中验证健脾消癌方对肿瘤生长速度的影响，并经瘤组织VEGF蛋白表达、CD31免疫组化染色检测肿瘤内血管生成情况。结果 模型组HUVEC细胞管腔形成较空白血清组显著增加（P<0.05）；健脾消癌方组及人参皂苷Rg3组较模型组HUVEC细胞管腔形成显著减少（P<0.01）。p-Akt和VEGF蛋白表达水平模型组高于空白血清组（P<0.05），健脾消癌方组及人参皂苷Rg3组显著低于模型组（P<0.01）；PI3K、Akt蛋白表达量组间差异无统计学意义。与对照组比较，模型组荷瘤小鼠肿瘤体积显著性增大，瘤组织内VEGF表达、CD31阳性面积显著性增加，差异有统计学意义（P<0.05）；与模型组比较，健脾消癌方组及人参皂苷Rg3组荷瘤小鼠肿瘤体积显著减小，瘤组织内VEGF表达、CD31阳性面积降低，差异有统计学意义（P<0.05）。结论 健脾消癌方可抑制肿瘤的血管生成和生长，其作用机制可能与PI3K/Akt生物轴调控VEGF表达有关。     

Phase 1/2 clinical trial of COVID-19 vaccine in Japanese participants: A report of interim findings

We initiated a randomized, placebo-controlled, phase 1/2 trial to evaluate the safety and immunogenicity of the S-268019-b recombinant protein vaccine, scheduled as 2 intramuscular injections given 21 days apart, in 60 randomized healthy Japanese adults. We evaluated 2 regimens of the S-910823 antigen (5 μg [n = 24] and 10 μg [n = 24]) with an oil-in-water emulsion formulation and compared against placebo (n = 12). Reactogenicity was mild in most participants. No serious adverse events were noted. For both regimens, vaccination resulted in robust IgG and neutralizing antibody production at days 36 and 50 and predominant T-helper 1-mediated immune reaction, as evident through antigen-specific polyfunctional CD4+ T-cell responses with IFN-γ, IL-2, and IL-4 production on spike protein peptides stimulation. Based on the interim analysis, the S-268019-b vaccine is safe, produces neutralizing antibodies titer comparable with that in convalescent serum from COVID-19-recovered patients. However, further evaluation of the vaccine in a large clinical trial is warranted.     

Prolyl and lysyl hydroxylases in collagen synthesis

Collagens are the most abundant proteins in the extracellular matrix. They provide a framework to build organs and tissues and give structural support to make them resistant to mechanical load and forces. Several intra‐ and extracellular modifications are needed to make functional collagen molecules, intracellular post‐translational modifications of proline and lysine residues having key roles in this. In this article, we provide a review on the enzymes responsible for the proline and lysine modifications, that is collagen prolyl 4‐hydroxylases, 3‐hydroxylases and lysyl hydroxylases, and discuss their biological functions and involvement in diseases.     

Immediate effects of rhythmic joint mobilization of the temporomandibular joint on pain,mouth opening and electromyographic activity in patients with temporomandibular disorders

BackgroundRhythmic joint mobilizations (RJM) of the temporomandibular joint (TMJ) are employed to relieve pain and improve function in patients with temporomandibular disorders (TMD). However, the evidence on the immediate effects of RJM in patients with TMD is scarce. The aim of this study was to assess the immediate clinical and functional effects of RJM in patients with TMD.Materials and methodsThis was a one-group quasi-experimental before and after study. Thirty-eight patients with TMD were assessed by means of pain intensity (visual analogue score, VAS), pressure pain threshold (PPT, measured through pressure algometry on the masseter and temporal muscles), mouth opening (MO, measured with a ruler), and surface electromyographic activity of the masseter and temporal muscles (asymmetry index, AI). Measurements were performed before and after a single, 1-min session of RJM of each TMJ. All statistical analyses were performed using the SPSS version 20.0 statistical package.ResultsA statistical significant difference was found in pain intensity, PPT and MO after the intervention (p < 0.05). No difference was found in the AI. A large effect size was observed for pain intensity, PPT of the left and right masseter muscles and MO (d = 0.85–1.13), whereas for the left and right temporal muscles the effect size was moderate (d = 0.62) and small, respectively (d = 0.49).ConclusionIn this sample of patients with TMD, a single session of RJM of the TMJ seemed to be effective in reducing pain intensity, increasing PPT and improving MO immediately after the intervention, without differences in the AI.     

COVID-19 Gender Disparities and Mitigation Recommendations: A Narrative Review

The coronavirus disease 2019 (COVID-19) pandemic has rapidly created widespread impacts on global health and the economy. Data suggest that women are less susceptible to severe illness. However, sex-disaggregated data are incomplete, leaving room for misinterpretation, and focusing only on biologic sex underestimates the gendered impact of the pandemic on women. This narrative review summarizes what is known about gender disparities during the COVID-19 pandemic and the economic, domestic, and health burdens along with overlapping vulnerabilities related to the pandemic. In addition, this review outlines recommended strategies that advocacy groups, community leaders, and policymakers should implement to mitigate the widening gender disparities related to COVID-19.     

Interrelationships between Cellular Density,Mosaic Patterning,and Dendritic Coverage of VGluT3 Amacrine Cells

Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina.     

Moral Distress and Burnout in NICU Nurses

The objectives of this study were to factor analyze the Moral Distress Scale–Revised (MDS-R) in NICU nurses and to evaluate the relationships among dimensions of the MDS-R and the demoralization, exhaustion, and loss of motive dimensions of the Burnout Measure (BM). A total of 142 NICU nurses completed modified pen-and-paper versions of the MDS-R and BM. Exploratory and confirmatory factor analyses showed that the MDS-R-14 was a relatively good fit for the data. The compromised care dimension predicted BM demoralization (β = 0.24) and exhaustion (β = 0.22), the futile care dimension predicted BM exhaustion (β = 0.18), and the untruthful care dimension predicted BM demoralization (β = .25). Strategies to mitigate moral distress and resulting burnout in NICU nurses should address futile care, compromised care, and untruthful care.     

Intraoperative complications in temporomandibular joint arthroscopy: A retrospective observational analysis of 899 arthroscopies

This study aims to describe intraoperative complications in temporomandibular joint arthroscopy in patients with Wilkes stage II, III y IV. An analytic observational retrospective study. Inclusion criteria were patients who had no improvement with conservative treatment diagnosed as Wilkes II stage to Wilkes stage IV, and no previous TMJ surgery. Exclusion criteria were disc perforation observed by arthroscopy. Data collected from 458 patients (899 arthroscopies). Of this population, 772 (85.8%) arthroscopies correspond to women, and 127 men (14.1%). Of the sample evaluated, 368 (40.9%) were arthroscopic without discopexy, and 531 (59%) were arthroscopic with discopexy using resorbable pins. In total, 330 complications (36.7%) were found, of which 293 (32.5%) were implicated with iatrogenic damage to the anatomy, and 36 (4%) were associated with some instrument failure. Of this total number of complications, 191 (51.9%) of 386 corresponded to the arthroscopy without discopexy group and 138 (25.9%) of 531 corresponded to the arthroscopy with discopexy group. These study data suggest that the main complications were irrigation fluid extravasation (p = 0.000), and intra-articular bleeding (p = 0.001) followed by pin problems (p = 0.001) in cases of arthroscopies with discopexy. Within the limitations of the study it seems that the learning curve has an important influence on the occurrence of complications. At the beginning of the learning curve, complications are more related to anatomy. Afterwards, the rate of complications decreases but they are more related to the instruments used in advanced techniques. Therefore, proper training and a wide learning curve can reduce the risk of complications and if any occur, more timely management could be given.     

Prior surgical fixation of proximal humerus fractures is associated with increased complications following subsequent reverse shoulder arthroplasty

BackgroundThe objective of this study was to compare complication rates between patients undergoing reverse shoulder arthroplasty (RSA) after a prior open reduction and internal fixation (ORIF) for proximal humerus fracture (PHF) to those undergoing RSA as a primary treatment for PHFs, glenohumeral osteoarthritis, or rotator cuff tear arthropathy (CTA).MethodsPatients who underwent RSA between 2015 and 2020 were identified in the Mariner database. Patients were separated into 3 mutually exclusive groups: (1) RSA for osteoarthritis, rotator cuff tear, or CTA (Control-RSA); (2) RSA as a primary treatment for PHF (PHF-RSA); and (3) RSA for patients with prior ORIF of PHFs (ORIF-RSA). Ninety-day medical and 2-year postoperative surgical complications were identified. In addition, patients in the PHF-RSA group were subdivided into those undergoing RSA for PHF within 3 months of the fracture (acute) vs. those treated greater than 3 months from diagnosis (delayed). Multivariate regression was performed to control for differences in comorbidities and demographics.ResultsA total of 30,824 patients underwent primary RSA for arthritis or CTA, 5389 patients underwent RSA as a primary treatment for a PHF, and 361 patients underwent RSA after ORIF of a PHF. ORIF before RSA was associated with an increased risk of overall revision (odds ratio [OR] 2.45, P = .002), infection (OR 2.40, P < .001), instability (OR 2.43, P < .001), fracture (OR 3.24, P = .001), minor medical complications (OR 1.59, P = .008), and readmission (OR 2.55, P = .001) compared with the Control-RSA cohort. RSA as a primary treatment for PHF was associated with an increased risk of 2-year revision (OR 1.60, P < .001), infection (OR 1.51, P < .001), instability (OR 2.84, P < .001), and fracture (OR 2.54, P < .001) in addition to major medical complications (OR 2.02, P < .001), minor medical complications (OR 1.92, P < .001), 90-day emergency department visits (OR 1.26, P < .001) and 90-day readmission (OR 2.03, P < .001) compared with the Control-RSA cohort. The ORIF-RSA group had an increased risk of periprosthetic infection (OR 1.94, P = .002) when compared with the PHF-RSA cohort. There were no differences in medical or surgical complications in the RSA-PHF cohort between patients treated in an acute or delayed fashion.ConclusionRSA following ORIF of a PHF is associated with increased complications compared with patients undergoing RSA for nonfracture indications. Prior ORIF of a PHF is also an independent risk factor for postoperative infection after RSA compared with patients who undergo RSA as a primary operation for fracture. The timing of RSA as a primary operation for PHF does not appear to impact the rates of postoperative medical and surgical complications.