What are the clinical symptoms and physical signs for non-small cell lung cancer before diagnosis is made? A nation-wide multicenter 10-year retrospective study in China.

BACKGROUND: Most lung cancer patients are diagnosed after the onset of symptoms. However, whether the symptoms of lung cancer were independently associated with the diagnosis of lung cancer is unknown, especially in the Chinese population. METHODS: We conducted a 10 years (2005-2014) nationwide multicenter retrospective clinical epidemiology study of lung cancer patients diagnosed in China. As such, this study focused on nonsmall cell lung cancer (NSCLC). We calculated the odds ratios (ORs) for variables associated with the symptoms and physical signs using multivariate unconditional logistic regressions. RESULTS: A total of 7184 lung cancer patients were surveyed; finally, 6398 NSCLC patients with available information about their symptoms and physical signs were included in this analysis. The most common initial symptom and physical sign was chronic cough (4156, 65.0%), followed by sputum with blood (2110, 33.0%), chest pain (1146, 17.9%), shortness of breath (1090, 17.0%), neck and supraclavicular lymphadenectasis (629, 9.8%), weight loss (529, 8.3%), metastases pain (378, 5.9%), fatigue (307, 4.8%), fever (272, 4.3%), and dyspnea (270, 4.2%). Patients with squamous carcinoma and stage III disease were more likely to present with chronic cough (P < 0.0001) and sputum with blood (P < 0.0001) than patients with other pathological types and clinical stages, respectively. Metastases pain (P < 0.0001) and neck and supraclavicular lymphadenectasis (P = 0.0006) were more likely to occur in patients with nonsquamous carcinoma than in patients with other carcinomas. Additionally, patients with stage IV disease had a higher percentage of chest pain, shortness of breath, dyspnea, weight loss, and fatigue than patients with other stages of disease. In multivariable logistic analyses, compared with patients with adenocarcinoma, patients with squamous carcinoma were more likely to experience symptoms (OR = 2.885, 95% confidence interval [CI] 2.477-3.359) but were less likely to present physical signs (OR = 0.844, 95% CI 0.721-0.989). The odds of having both symptoms and physical signs were higher in patients with late-stage disease than in those with early-stage disease (P < 0.0001). CONCLUSIONS: The symptoms and physical signs of lung cancer were associated with the stage and pathological diagnosis of NSCLC. Patients with squamous carcinoma were more likely to develop symptoms, but not signs, than patients with adenocarcinoma. The more advanced the stage at diagnosis, the more likely that symptoms or physical signs are to develop. Further prospective cohort studies are needed to explore these results.

Dimethyl Cardamonin Exhibits Anti-inflammatory Effects via Interfering with the PI3K-PDK1-PKCα Signaling Pathway.

Consumption of herbal tea [flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae)] is associated with health beneficial effects against multiple diseases including diabetes, asthma, and inflammatory bowel disease. Emerging evidences have reported that High mobility group box 1 (HMGB1) is considered as a key "late" proinflammatory factor by its unique secretion pattern in aforementioned diseases. Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone, DMC) is a major ingredient of C. operculatus flower buds. In this study, the anti-inflammatory effects of DMC and its underlying molecular mechanisms were investigated on lipopolysaccharide (LPS)-induced macrophages. DMC notably suppressed the mRNA expressions of TNF-α, IL-1ß, IL-6, and HMGB1, and also markedly decreased their productions in a time- and dose-dependent manner. Intriguingly, DMC could notably reduce LPS-stimulated HMGB1 secretion and its nucleo-cytoplasmic translocation. Furthermore, DMC dose-dependently inhibited the activation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), and protein kinase C alpha (PKCα). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-α, IL-1ß, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKCα signaling pathway.

Preparative separation and purification of fumigaclavine C from fermented mycelia of Aspergillus fumigatus CY018 by macroporous adsorption resin.

In this work, the separation and purification of fumigaclavine C (FC), an ergot alkaloid with strong anti-inflammatory activity from fermented mycelia of Aspergillus fumigatus was systematically evaluated. Among the eight tested resins, the non-polar resin D101 displayed the best adsorption and desorption based on of static adsorption and desorption tests. Adsorption isotherms were constructed on D101 resin and fitted well to the Freundlich model. Dynamic adsorption and desorption tests on a column packed with D101 resin have been investigated for optimization of chromatographic parameters. Under optimized conditions, the contents of FC increased from 7.32% (w/w) in the crude extract to 67.54% in the final product with a recovery yield of 90.35% (w/w) via one run. Furthermore, a lab scale-up separation was carried out, in which the FC content and recovery yield were 65.83% and 90.13%, respectively. These results demonstrated that this adsorption-desorption strategy by using D101 resin was simple and efficient, thus showing potential for large scale purification and preparation of FC in the future.

Enhanced production of fumigaclavine C by ultrasound stimulation in a two-stage culture of Aspergillus fumigatus CY018.

Stimulation by physical means including ultrasound is important to cell morphology and the product yield. In this work, the effect of ultrasound on the production of fumigaclavine C (FC), a conidiation-associated alkaloid with strong anti-inflammatory activity, was investigated in a newly developed two-stage culture of Aspergillus fumigatus CY018. The optimum ultrasonication conditions consisted of exposing cultures (at 12h of growth phase) to 10-min repeated irradiation (4 times) with a 24-h interval at the fixed power (500 W). Under this condition, FC production reached 118.09 mg/L, which was 89% higher than the control and much higher than previous reported values. Morphological analysis demonstrated that mycelia morphology from ultrasonication was in the form smaller and looser pellets as compared to that of the control. In addition, conidia that is closely related to FC biosynthesis were significantly increased after ultrasound stimulation, with 3 folds of that from the control.

Enhanced production of Fumigaclavine C in liquid culture of Aspergillus fumigatus under a two-stage process.

Fumigaclavine C (FC) produced by Aspergillus fumigatus is a conidiation associated ergot alkaloid with strong anti-inflammatory activity. However, its wide application has been severely limited by low FC production from submerged culture. In this work, a novel two-stage culture process by combining shake culture with static culture was proposed to enhance the production of FC. After the process optimization, the FC production reached 62.7 mg/L, which was significantly higher than ever report. For scaling up this new culture process, the gas-liquid interfacial area per unit volume (Agas-liq) was identified as the key factor. The results showed that in a combined stirred-static bioreactor system, a maximum FC production (58.97 mg/L) was obtained at an Agas-liq value of 1.30 cm(2)/mL. These results demonstrated that two-stage culture is an efficient strategy to enhance FC production and the information obtained will be useful to production of this powerful bioactive compound on a large scale.