Therapeutic Effect of Tympanoplasty on Patients with Chronic Otitis Media with Tinnitus and Influencing Factors.

Objective: This research was conducted to investigate the therapeutic effects of tympanoplasty on patients with chronic otitis media with tinnitus and analyze the possible influencing factors for patient prognosis. Methods: This is a pre-post control group study, 86 patients with chronic otitis media were included as the subjects and enrolled into tinnitus group (n = 46) and the non-tinnitus group (n = 40). All patients underwent tympanoplasty under microscope or ear endoscopy. A tinnitus severity and efficacy assessment scale was employed for the evaluation of the severity of tinnitus among the subjects. In addition, tinnitus handicap inventory (THI) was utilized to evaluate disease alleviation. Results: Before treatment, the proportions of the patients with tinnitus at grades I, II, III, IV, and V amounted to 15.22%, 32.61%, 21.74%, 17.39%, and 13.04%, respectively, while they were 30.43%, 45.65%, 13.04%, 8.71%, and 2.17%, respectively 3 months after treatment (P < .05). THI scores for the patients in the tinnitus group before and 3 months after treatment amounted to 17.96 ± 3.66 and 16.21 ± 3.29, respectively (P < .05). After treatment, the air conduction (AC) and bone conduction (BC) thresholds and air-bone gap (ABG) of the two groups apparently declined (P < .05). No statistical significance was detected in the differences in disease classification, disease courses, and whether an electric drill was used among the patients between effective and invalid groups (P > .05). Conclusion: To some extent, tympanoplasty alleviated tinnitus among patients with chronic otitis media and promoted the restoration of hearing. Hence, it is worthy of application in clinical treatment.

Role of epigenetic modifications mediated by vitamins and trace elements in inflammatory bowel disease.

Graphical abstract [Formula: see text] Numerous environmental factors frequently emerge as primary determinants of inflammatory bowel disease (IBD). Diet is a major component of environmental factors, and the consumption of vitamins (A, B, C and D) and trace elements (calcium, iron, zinc and selenium) exerts an impact on the progression of IBD through epigenetic modifications. Intake of vitamins A, B, C and D, as well as excessive amounts of iron and calcium, can modulate the condition of IBD by regulating the levels of DNA methylation, histone acetylation and miRNA. Zinc and selenium alleviate the progression of IBD by regulating the levels of promoter methylation or histone ubiquitination, respectively. Graphical Abstract was adapted from 'Epigenetic levels (layout)', by BioRender.com. Retrieved from https://app.biorender.com/biorender-templates.

Oral Nanotherapeutics of Andrographolide/Carbon Monoxide Donor for Synergistically Anti-inflammatory and Pro-resolving Treatment of Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology affecting the colon and rectum. Current therapeutics are focused on suppressing inflammation but are ineffective. Combining anti-inflammatory therapeutic approaches with pro-resolution might be a superior strategy for UC treatment. Andrographolide (AG), an active compound from the plant Andrographis paniculata, presented anti-inflammatory effects in various inflammatory diseases. Gaseous mediators, such as carbon monoxide (CO), have a role in inflammatory resolution. Herein, we developed a dextran-functionalized PLGA nanocarrier for efficient delivery of AG and a carbon monoxide donor (CORM-2) for synergistically anti-inflammatory/pro-resolving treatment of UC (AG/CORM-2@NP-Dex) based on PLGA with good biocompatibility, slow drug release, efficient targeting, and biodegradability. The resulting nanocarrier had a nano-scaled diameter of ∼200 nm and a spherical shape. After being coated with dextran (Dex), the resulting AG/CORM-2@NP-Dex could be efficiently internalized by Colon-26 and Raw 264.7 cells in vitro and preferentially localized to the inflamed colon with chitosan/alginate hydrogel protection by gavage. AG/CORM-2@NP-Dex performed anti-inflammatory effects by eliminating the over-production of pro-inflammatory mediator, nitric oxide (NO), and down-regulating the expression of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), while it showed pro-resolving function by accelerating M1 to M2 macrophage conversion and up-regulating resolution-related genes (IL-10, TGF-ß, and HO-1). In the colitis model, oral administration of AG/CORM-2@NP-Dex in a chitosan/alginate hydrogel also showed synergistically anti-inflammatory/pro-resolving effects, therefore relieving UC effectively. Without appreciable systemic toxicity, this bifunctional nanocarrier represents a novel therapeutic approach for UC and is expected to achieve long-term inflammatory remission.

Effects of school indoor visual environment on children's health outcomes: A systematic review.

Children's visual perceptions are critical for their comfort and health. This review explores the impacts of school indoor visual environment on children's health outcomes. A systematic search yielded 5704 articles, of which 32 studies were reviewed. Five environmental themes were identified: lighting, access to nature, window characteristics, art/environmental aesthetics, and ergonomics/spatial arrangement. Results affirm that visual environment affects children's health. There are disparities across environmental themes, with more extensive evidence for lighting and access to nature, but relatively limited in other areas. This study suggests a need for multi-disciplinary collaboration to develop a holistic perspective.

Composition, functional properties, health benefits and applications of oilseed proteins: A systematic review.

Common oilseeds, such as soybean, peanut, rapeseed, sunflower seed, sesame seed and chia seed, are key sources of edible vegetable oils. Their defatted meals are excellent natural sources of plant proteins that can meet consumers' demand for health and sustainable substitutes for animal proteins. Oilseed proteins and their derived peptides are also associated with many health benefits, including weight loss and reduced risks of diabetes, hypertension, metabolic syndrome and cardiovascular events. This review summarizes the current status of knowledge on the protein and amino acid composition of common oilseeds as well as the functional properties, nutrition, health benefits and food applications of oilseed protein. Currently, oilseeds are widely applied in the food industry regarding for their health benefits and good functional properties. However, most oilseed proteins are incomplete proteins and their functional properties are not promising compared to animal proteins. They are also limited in the food industry due to their off-flavor, allergenic and antinutritional factors. These properties can be improved by protein modification. Therefore, in order to make better use of oilseed proteins, methods for improving their nutrition value, bioactive activity, functional and sensory characteristics, as well as the strategies for reducing their allergenicity were also discussed in this paper. Finally, examples for the application of oilseed proteins in the food industry are presented. Limitations and future perspectives for developing oilseed proteins as food ingredients are also pointed out. This review aims to foster thinking and generate novel ideas for future research. It will also provide novel ideas and broad prospects for the application of oilseeds in the food industry.

An Evaluation of Fluorouracil plus Paclitaxel and Oxiliplatin as a First-Line Treatment for Advanced Gastric Squamous Cell Carcinoma.

Objective: To investigate the efficacy of fluorouracil (FU) combined with paclitaxel (PTX) and oxaliplatin (OXA) as the first-line treatment for advanced gastric signet ring cell carcinoma (SRCC) and its influence on human epidermal growth factor receptor 2 (HER-2) expression. Methods: We collected one hundred and sixty-eight patients with advanced gastric SRCC, including 87 patients treated with FU combined with PTX and OXA as the study group (SG) and 81 patients treated with FU combined with OXA as the control group (CG). We compared indicators such as efficacy and adverse reactions after treatment between the two groups and also detected serum HER-2 expression pre- and post-treatment. Results: The incidence of adverse reactions differed insignificantly between SG and CG (P > 0.05). SG presented a notably higher objective response rate (ORR) and disease control rate (DCR) than that of CG (P < 0.05). After treatment, the serum HER-2 expression level of patients in both groups decreased significantly (P < 0.05), and that in SG was significantly declined compared to CG (P < 0.05). HER-2 was negatively correlated with the efficacy of both SG and CG. The 1-year survival rate in SG (29.89%) was significantly higher than that in CG (16.05%) (P < 0.05). The median OS and PFS were higher in DG than that in CG (P < 0.05). Conclusion: FU combined with PTX and OXA can effectively improve the efficacy of first-line treatment for advanced gastric SRCC while reducing HER-2 expression, without increasing the adverse reaction rate. This treatment is worthy of clinical promotion.

Platycodin D Suppresses Type 2 Porcine Reproductive and Respiratory Syndrome Virus In Primary and Established Cell Lines.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a continuous threat to the pork industry as it continues to cause significant economic loss worldwide. Currently, vaccination strategies provide very limited protection against PRRSV transmission. Consequently, there is an urgent need to develop new antiviral strategies. Platycodin D (PD) is one of the major bioactive triterpenoid saponins derived from Platycodon grandiflorum, a traditional Chinese medicine used as an expectorant for pulmonary diseases and a remedy for respiratory disorders. Here, we demonstrate that PD exhibits potent activity against PRRSV infection in Marc-145 cells and primary porcine alveolar macrophages. PD exhibited broad-spectrum inhibitory activities in vitro against high pathogenic type 2 PRRSV GD-HD strain and GD-XH strain as well as classical CH-1a and VR2332 strains. PD at concentrations ranging 1⁻4 µM significantly inhibited PRRSV RNA synthesis, viral protein expression and progeny virus production in a dose-dependent manner. EC50 values of PD against four tested PRRSV strains infection in Marc-145 cells ranged from 0.74 to 1.76 µM. Mechanistically, PD inhibited PRRSV replication by directly interacting with virions therefore affecting multiple stages of the virus life cycle, including viral entry and progeny virus release. In addition, PD decreased PRRSV- and LPS-induced cytokine (IFN-α, IFN-ß, IL-1α, IL-6, IL-8 and TNF-α) production in PAMs. Altogether, our findings suggested that PD is a potent inhibitor of PPRSV infection in vitro. However, further in vivo studies are necessary to confirm PD as a potential novel and effective PPRSV inhibitor in swine.

Effect of electroacupuncture stimulation at Zusanli acupoint (ST36) on gastric motility: possible through PKC and MAPK signal transduction pathways.

BACKGROUND: Electroacupuncture (EA) stimulation has been shown to have a great therapeutic potential for treating gastrointestinal motility disorders. However, no evidence has clarified the mechanisms contributing to the effects of EA stimulation at the Zusanli acupoint (ST.36). This study was designed to investigate the regulative effect of EA stimulation at the ST.36 on gastric motility and to explore its possible mechanisms. METHODS: Thirty Sprague-Dawley rats were randomly divided into three groups: the ST.36 group, the non-acupoint group, and the control group. EA stimulation was set at 2 Hz, continuous mode, and 1 V for 30 min. The frequency and average peak amplitude of gastric motility were measured by electrogastrography. The protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) signaling pathways were assessed using real-time polymerase chain reactions. Caldesmon (CaD) and calponin (CaP) protein expression in the gastric antrum were detected on Western blots. A Computed Video Processing System was used to evaluate morphological changes in smooth muscle cells (SMCs) from the gastric antrum. RESULTS: EA stimulation at ST.36 had a dual effect on the frequency and average peak amplitude. Additionally, EA stimulation at ST.36 regulated the expression of some genes in the PKC and MAPK signaling pathways, and it regulated the expression of the CaD and CaP proteins. EA serum induced SMC contractility. Promotion of gastric motility may correlate with up-regulation of MAPK6 (ERK3), MAPK13, and Prostaglandin-endoperoxide synthase 2 (PTGS2) gene expression, and the down-regulation of the collagen, type I, alpha 1 (COL1A1) gene and CaD and CaP protein expression. Inhibition of gastric motility may correlate with down-regulation of the Interleukin-1 receptor type 2 (IL1R2) and Matrix metalloproteinase-9 (MMP9) genes, and up-regulation of CaD and CaP protein expression. CONCLUSIONS: EA stimulation at ST.36 regulated gastric motility, and the effects were both promoting and inhibiting in rats. The possible mechanisms may correlate with the PKC and MAPK signal transduction pathways.

The noncytotoxic dose of sorafenib sensitizes Bel-7402/5-FU cells to 5-FU by down-regulating 5-FU-induced Nrf2 expression.

BACKGROUND: Acquired resistance to 5-fluorouracil (5-FU) is a serious therapeutic obstacle in advanced hepatocellular carcinoma (HCC) patients. AIM: To investigate whether nuclear factor erythroid 2-related factor 2 (Nrf2) was associated with drug resistance in 5-FU resistant Bel-7402 (Bel-7402/5-FU) cells, and if sorafenib, an oral multikinase inhibitor targeting the tumor and vasculature, could reverse drug resistance in Bel-7402/5-FU cells at the noncytotoxic dosage. METHODS: We used MTT to detect the resistance reversal activity of sorafenib, compared Nrf2 expression in various conditions by western blot and qRT-PCR, and analyzed subcellular localization of Nrf2 by immunofluorescence. RESULTS: The endogenous expression of Nrf2 in Bel-7402/5-FU cells was similar to that observed in Bel-7402 cells. However, Nrf2 expression levels were increased by 5-FU treatment in Bel-7402/5-FU cells higher than that in Bel-7402 cells, which is to highlight the Nrf2 contribution to the enhanced resistance of Bel-7402/5-FU cells to 5-FU. Moreover, intracellular Nrf2 protein level was significantly down-regulated by Nrf2-shRNA in Bel-7402/5-FU cells, resulting in partial reversal of 5-FU resistance. Sorafenib down-regulated the increased expression of Nrf2 induced by 5-FU treatment and partly reversed 5-FU resistance in Bel-7402/5-FU cells. CONCLUSIONS: These results suggested that more sensitive cell defense mediated by Nrf2 was associated with drug resistance of Bel-7402/5-FU cells. Sorafenib reversed drug resistance, and its reversal mechanism might be due to the suppression of Nrf2 expression induced by 5-FU, indicating the feasibility of using Nrf2 inhibitors to increase efficacy of chemotherapeutic drugs in HCC patients.