Quantitative Proteomic and Phosphoproteomic Profiling of Lung Tissues from Pulmonary Arterial Hypertension Rat Model.

Pulmonary arterial hypertension (PAH) is a rare but fatal disease characterized by elevated pulmonary vascular resistance and increased pressure in the distal pulmonary arteries. Systematic analysis of the proteins and pathways involved in the progression of PAH is crucial for understanding the underlying molecular mechanism. In this study, we performed tandem mass tags (TMT)-based relative quantitative proteomic profiling of lung tissues from rats treated with monocrotaline (MCT) for 1, 2, 3 and 4 weeks. A total of 6759 proteins were quantified, among which 2660 proteins exhibited significant changes (p-value < 0.05, fold change < 0.83 or >1.2). Notably, these changes included several known PAH-related proteins, such as Retnla (resistin-like alpha) and arginase-1. Furthermore, the expression of potential PAH-related proteins, including Aurora kinase B and Cyclin-A2, was verified via Western blot analysis. In addition, we performed quantitative phosphoproteomic analysis on the lungs from MCT-induced PAH rats and identified 1412 upregulated phosphopeptides and 390 downregulated phosphopeptides. Pathway enrichment analysis revealed significant involvement of pathways such as complement and coagulation cascades and the signaling pathway of vascular smooth muscle contraction. Overall, this comprehensive analysis of proteins and phosphoproteins involved in the development and progression of PAH in lung tissues provides valuable insights for the development of potential diagnostic and treatment targets for PAH.

Efficacy and safety of combined targeted therapy and immunotherapy versus targeted monotherapy in unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Cancer therapy has evolved from non-specific cytotoxic agents to a selective, mechanism-based approach that includes targeted agents and immunotherapy. Although the response to targeted therapies for unresectable hepatocellular carcinoma (HCC) is acceptable with the improved survival, the high tumor recurrence rate and drug-related side effects continue to be problematic. Given that immune checkpoint inhibitor alone are not robust enough to improve survival in unresectable HCC, growing evidence supports the combination of targeted therapy and immunotherapy with synergistic effect. METHODS: Online databases including PubMed, EMBASE, Cochrane Library, and Web of Science were searched for the studies that compared targeted monotherapy with the combination therapy of targeted drug and checkpoint inhibitors in unresectable HCC patients. Eligibility criteria were the presence of at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (version 1.1) for unresectable HCC patients, an Eastern Cooperative Oncology Group performance status of 0-2, and a Child-Pugh score ≤ 7. Outcome measurements include overall survival (OS), progression-free survival (PFS), and treatment-related adverse event (TRAE). RESULTS: Three phase II/III randomized controlled trials were included in this study. The pooled results showed that combination therapy significantly improved survival than targeted monotherapy, in terms of OS (hazard ratio (HR) = 0.67; 95% confidence interval [CI]: 0.50-0.91) and PFS (HR = 0.58; 95% CI: 0.51-0.67), respectively. In the incidence of grade 3-5 TRAEs, the combination therapy was significantly higher than targeted monotherapy (odds ratio = 1.98; 95% CI: 1.13-3.48). CONCLUSION: For unresectable HCC, combined targeted drug and immunotherapy significantly improved survival compared with targeted monotherapy. However, the incidences of AEs of combinational therapy were higher than targeted monotherapy.

Finite element analysis of dynamic changes in spinal mechanics of osteoporotic lumbar fracture.

AIM: This study aims to explore the effects of finite element biomechanical properties of different methods in the treatment of osteoporotic thoracolumbar fractures. METHODS: Based on the ultra-thin computed tomography scan data of a volunteer's thoracolumbar spine, the finite element method was used to simulate the treatment of osteoporotic thoracolumbar fracture. Spiral computed tomography scanning was used to obtain images of the thoracolumbar region, which was then imported into Mimics software to obtain the three-dimensional geometric model. The finite element model of normal T11 - L2 segment was established by finite element software Abaqus and the validity of the model loading was verified. The finite element model of T11 vertebral compression fracture was established based on normal raw data. The clinical overextension reduction manipulation was simulated by different treatment methods and the changes in stress and displacement in different parts of injured vertebrae were analyzed. RESULTS: An effective finite element model of T11-L2 segment was established. The maximum stress, axial compression strength, axial compression stiffness, and transverse shear stiffness were significantly better in the percutaneous kyphoplasty and percutaneous vertebroplasty treatment group than in the conservative treatment group and open treatment group (P < 0.05). Additionally, there was no significant difference between the open treatment group and conservative treatment group, or between the PKP and PVP treatment group. CONCLUSION: Percutaneous vertebroplasty and percutaneous kyphoplasty not only met the requirements of normal functional kinematics of thoracolumbar spine, but also restored the stability of thoracolumbar spine. They had good biomechanical properties and remarkable application effects. The application of finite element analysis can help select a scientific, reasonable, and effective treatment scheme for the clinical diagnosis and treatment of osteoporotic thoracolumbar fractures.

Role of stimulus types and valence on the affective memory performance of adults with anxiety.

Previous studies have found that the emotion of anxiety in adults is easily influence by negative stimuli However, few studies have explored the effect of stimulus types on working memory performance and cognitive processing of adults with anxiety. This study aimed to explore the effects of anxiety on affective working memory and the role of stimulus types and valences on affective working memory performance. Forty adults were recruited for the experiment and were divided into two groups according to their anxiety levels. The valence and type of stimulus were manipulated in a memory recognition experiment. The results indicated that individuals with anxiety performed poorer when subjected to positive stimuli than for neutral and negative stimuli, whereas healthy adults exhibited the opposite. Furthermore, participants outperformed on affective pictures than affective words, but the effect size of the words was larger than that of the pictures for the difference between the valence and anxiety groups. This study highlights the differences in affective working performance across stimulus types and valences between healthy adults and adults with anxiety. The findings clarified the effect of positive valence and affective words on the affective working memory processing mechanism in adults with anxiety.

[Intensive Care Unit-Acquired Weakness].

Intensive care unit (ICU)-acquired weakness is a common neuromuscular complication of critical illness that is considered to be associated with prolonged duration on mechanical ventilation and systemic inflammatory response syndrome. In addition, nutrition and metabolic alternations, which are commonly seen in patients in the ICU, may further accelerate muscle wasting and increase the incidence of ICU-acquired weakness. The clinical features of ICU-acquired weakness include acute generalized muscle weakness that develops after the onset of critical illness. Diaphragmatic dysfunction, post-extubation dysphagia, and functional decline also are common in patients with ICU-acquired weakness. As the recovery of these physical functions is lengthy and difficult, a multidisciplinary team management is recommended. This mini-review was conducted to provide a scientific overview for ICU-acquired weakness, including its definition, etiology, diagnosis/screening, impacts, and potential intervention strategies. We hope that increasing the understanding of frontline staff will promote the timely planning and implementation of related screenings and interventions to enhance the functional recovery of patients receiving care in the ICU.

Environmental monitoring and benchmarking of VCM airborne emissions for a major PVC plant in Taiwan with 15 PVC plants in the USA.

Vinyl chloride monomer (VCM) is classified as group 1 carcinogenic to humans by the International Agency for Research for Cancer (IARC). In 2012, USEPA promulgated a new VCM emission standard as part of National Emission Standards for Hazardous Air Pollutants (NESHAP) for polyvinyl chloride (PVC) and copolymer plants. The standard was set by benchmarking of peer plants with maximum achievable control technology (MACT). This study performs an emission assessment of a world-class PVC plant in Taiwan according to the MACT analysis. The emission data obtained were then benchmarked with baseline emission estimates of 15 PVC plants in the USA. Results of this study show seven types of VCM emissions: stripped resin of suspension/dispersion, wastewater, process vent, heat-exchange system, storage tank, equipment leaks, and other sources (gasholder). All the emission factors are complied with their MACT emission limitations (MEL) and ranked either #1 or #2 among the 15 plants. They are also summed and benchmarked against the production capacity of each plant, showing a negative power function with a fair correlation (R2 = 0.73). Among seven types of emissions, stripped resin contributes the highest (51.7%) by average emission factor of the 15 plants plus this study plant.

Effect of selected strains on physical and organoleptic properties of breads.

The use of selected Saccharomyces cerevisiae PS7314, Lactobacillus rossiae NOS7307, Lactobacillus brevis NOS7311, and Lactobacillus plantarum NOS7315 as mono-culture or co-culture for production of sourdoughs, their breads showed different physical and organoleptic properties. The pH of breads fermented with sourdoughs incubated with mono-culture or co-culture all decreased. An opposite trend was found for TTA. The use of single lactobacillus for the dough fermentation decreased the specific volume of bread, which was 4.15-19.10% lower than that of control bread (CB). However, the synergetic fermentation helped the improvement of bread quality. Compared to CB, the mixed culture 4 sourdough remarkably decreased the hardness by 52.08%, increased the specific volume by 5.29%, improved porosity of final product by 24.90%, and gave a preferable sensory characteristic to bread. Thus, the MC4 could be recommended for replacing spontaneous sourdough for improving the quality of bread.

[A new furanolabdane diterpene glycoside from Phlomis younghusbandii Mukerjee].

In order to find the compound basis of Phlomis younghusbandii Mukerjee that related to pharmacodynamic action, various chromatographic techniques were used to separate and purify the constituents of this plant, and physicochemical and spectral data were used to identify the structures of obtained compounds. A new furanolabdane diterpene glycoside, named as phlomisoside F, was isolated and identified, which was 15,16-epoxy-8(9),13(16), 14-labdatrien-7-ketone-19-oic acid-beta-D-glucopyranosyl ester.

[Studies on anti-inflammation chemical constitutes of Patrinia villosa].

Patrinia villosa (Thunb. ) Juss. is a Chinese folk medicine, in order to find the material basis that were related to anti-inflammation pharmacodynamic action, we investigated for chemical constituents by chemical and spectroscopic analysis. By phytochemical research, 9 compounds were isolated from the acetic acid ethyl ester & N-Butanol of P. villosa and identified 7 compounds (beta-sitosterol, Villosol, Quercetin, Ferulic acid, Ursolic acid, beta-daucosterol, Rutin), and three compounds (Ferulic acid, Ursolic acid and Rutin) are firstly obtained from P. villosa.