Sarcopenia is a geriatric syndrome characterized by the decline in muscle mass and function associated with aging.Many studies have revealed that secondary sarcopenia associated with chronic obstructive pulmonary disease(COPD)can further reduce lung function and the ability of conducting daily living activities for the patients.Moreover, inflammation, increased energy expenditure, decreased physical endurance induced by COPD may accelerate the deterioration of sarcopenia.The aim of this review is to tentatively explore possible mechanisms linking the two diseases and promote early intervention for sarcopenia.

Objective To investigate the characteristics of peroperative blood pressure and heart rate in patients with normotensive incidental pheochromocytomas in order to provide the basis for peroperative treatment. Methods This retrospective study collected the data of 104 patients with a pathological diagnosis of unilateral pheochromocytoma at PLA General Hospital during January 2011 to December 2016. They were divided into normotensive incidental pheochromocytomas(NIP) group (n＝50) if the patients were normotensive and HIP group ( n＝54) if the patients were with hypertension. The clinical features, imaging features and peroperative hemodynamics were analyzed. Results ( 1) The age, urinary norepinephrine, daily dosage and duration of phenoxybenzamine in NIP group were less than those of HIP group (all P<0.05). (2) Preinduction blood pressure, maximum blood pressure, and total fluid intake in NIP group were lower than those in HIP group(all P<0.05). The blood pressure range, heart rate range, increased blood pressure, minimum mean arterial pressure, vasoactive medication were without statistical significance between these two groups. ( 3) The times and rate of intraoperative systolic blood pressure more than 30% baseline, 200 mmHg (1 mmHg＝0.133 kPa), 180 mmHg, 160 mmHg, intraoperative tachycardia, bradycardia, intraoperative hypotension and postoperative hypotension were without statistical significance between these two groups. (4) Stratified analysis of age (50 years), phenoxybenzamine (40 mg/d), tumor diameter (50 mm) and preinduction blood pressure (130/80 mmHg) showed that intraoperative blood pressure and heart rate were without statistical significance between these two groups. ( 5) There was no correlation between phenoxybenzamine ( daily dosage or duration ) and peroperative hypotension. Applying phenoxybenzamine or vasoactive medication was not correlated with peroperative hypotension in NIP group. Conclusion The peroperative blood pressure and heart rate of patients with NIP are similar to those of patients with HIP. Adequate peroperative treatment should be applied to NIP to avoid hemodynamic instability.

PURPOSE: Th17-associated inflammation is increased in chronic rhinosinusitis with nasal polyp (CRSwNP), and is associated with disease severity and steroid resistance. Overexpressed interleukin (IL)-17A affects CRSwNP by tissue remodeling, eosinophilic accumulation, and neutrophilic infiltration. We aimed to identify the role of IL-17A in CRSwNP and to evaluate the effects of anti-IL-17A blocking antibody on nasal polyp (NP) formation using a murine NP model. Moreover, we sought to investigate whether the inhibition of mechanistic target of the rapamycin (mTOR) signal pathway could suppress IL-17A expression and NP formation.METHODS: Human sinonasal tissues from control subjects and patients with chronic rhinosinusitis (CRS) were analyzed using immunohistochemistry (IHC) and immunofluorescence staining. The effects of IL-17A neutralizing antibody and rapamycin were evaluated in a murine NP model. Mouse samples were analyzed using IHC, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay.RESULTS: IL-17A+ inflammatory cells were significantly increased in number in NP from patients with CRSwNP compared to that in uncinate process tissues from control subjects and patients with CRS without NP or CRSwNP. CD68+ M1 macrophages dominantly expressed IL-17A, followed by neutrophils and T helper cells, in NP tissues. Neutralization of IL-17A effectively reduced the number of NPs, inflammatory cytokines, and IL-17A-producing cells, including M1 macrophages. Inhibition of IL-17A via the mTOR pathway using rapamycin also attenuated NP formation and inflammation in the murine NP model.CONCLUSIONS: IL-17A possibly plays a role in the pathogenesis of CRSwNP, the major cellular source being M1 macrophage in NP tissues. Targeting IL-17A directly or indirectly may be an effective therapeutic strategy for CRSwNP.
Animals ; Antibodies, Neutralizing ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Inflammation ; Interleukin-17 ; Interleukins ; Macrophages ; Mice ; Nasal Polyps ; Neutrophils ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Sinusitis ; Sirolimus ; T-Lymphocytes, Helper-Inducer

Objectives: . Limited information is available regarding strain-related differences in mouse models of allergic rhinitis induced by Dermatophagoides farinae (Der f1). In this study, we compared differences between two mouse strains and determined the optimal dose of Der f1 for allergic rhinitis mouse models. Methods: . Forty-eight mice were assigned to the following six groups (n=8 per group): group A (control, BALB/c), group B (Der f1-sensitized BALB/c, 25 µg), group C (Der f1-sensitized BALB/c, 100 µg), group D (control, C57BL/6), group E (Der f1-sensitized C57BL/6, 25 µg), and group F (Der f1-sensitized C57BL/6, 100 µg). Allergic inflammation was induced with Der f1 and alum sensitization, followed by an intranasal challenge with Der f1. Rubbing and sneezing scores, eosinophil and neutrophil infiltration, and immunoglobulin, cytokine, and chemokine levels in the nasal mucosa and from splenocyte cultures were assessed. Results: . Rubbing and sneezing scores were higher in groups B, C, E, and F than in groups A and D, with a similar pattern in both strains (i.e., group B vs. E and group C vs. F). Serum immunoglobulin levels were significantly elevated compared to the control in groups B and C, but not in groups E and F. Eosinophil and neutrophil infiltration increased (all P<0.05) after the Der f1 challenge (groups B, C, E, and F) compared to the control (groups A and D) in both the BALB/c and C57BL/6 strains, without any significant difference between the two strains (group A vs. D, group B vs. E, and group C vs. F) (P>0.05). BALB/c mice (group B) showed a greater elevation of splenic interleukin (IL)-4 (P<0.01), IL-5 (P<0.01), and IL-6 levels (P<0.05) and nasal IL-4 mRNA levels (P<0.001) than the C57BL/6 mice (group E). Interestingly, mice treated with 100 µg Der f1 showed a weaker allergic response than those treated with 25 µg. Conclusion . We found 25 µg to be a more appropriate dose for Der f1 sensitization. BALB/c mice are more biased toward a Th2 response and are a more suitable model for allergic rhinitis than C57BL/6 mice. This study provides information on the appropriate choice of a mouse model for allergic rhinitis.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC_50s for BD and BC were 11.63 and 11.71 μmol·L^-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
Humans ; Lung Neoplasms/metabolism* ; STAT3 Transcription Factor/metabolism* ; Antineoplastic Agents/chemistry* ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation