Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland.

The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the highest calcification rate among all organs and tissues of the human body. Pineal calcification jeopardizes melatonin's synthetic capacity and is associated with a variety of neuronal diseases. In the current review, we summarized the potential mechanisms of how this process may occur under pathological conditions or during aging. We hypothesized that pineal calcification is an active process and resembles in some respects of bone formation. The mesenchymal stem cells and melatonin participate in this process. Finally, we suggest that preservation of pineal health can be achieved by retarding its premature calcification or even rejuvenating the calcified gland.

FBW7 increases drug sensitivity to cisplatin in human nasopharyngeal carcinoma by downregulating the expression of multidrug resistance-associated protein.

F-box/WD repeat-containing protein 7 (FBW7) is a member of the F-box protein family that regulates cell cycle progression and cell growth and differentiation. FBW7 also functions as a tumor suppressor. A cisplatin (CDDP)-based multidrug chemotherapy regimen is standard for nasopharyngeal carcinoma (NPC), but drug resistance is an increasing problem. Here, we evaluated the relationship between FBW7 and multidrug resistance-associated protein (MRP), and its correlation with drug resistance in NPC, and explored the mechanism underlying drug resistance to CDDP in this disease. We used cell viability assays, Western blotting, and small interfering RNA (siRNA) interference to investigate the underlying mechanism underlying CDDP resistance in a NPC cell line. The expression of FBW7 and MRP was detected by Western blotting after siRNA interference in the CDDP-resistant NPC cell line, CNE2-CDDP. The 3-(4 5-dimethyl-2-thiazolyl)-2 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to evaluate drug sensitivity of various types of antitumor drugs, including paclitaxel (PCX), CDDP, fluorouracil (5-FU), and vincristine (VCR). We found that siRNA-mediated upregulation of FBW7 significantly increased CDDP chemosensitivity. The IC50 values of CDDP in siRNA-FBW7-CNE2-CDDP and FBW7-CNE2-CDDP-NC cells were 2.485 ± 0.155 and 4.867 ± 0.442 µmol/mL, respectively. The IC50 values of PCX, CDDP, 5-FU, and VCR were significantly decreased in siRNA-FBW7-CNE2 than in FBW7-CNE2-NC (3.46 ± 0.14 vs. 46.21 ± 6.03 µmol/mL; 3.76 ± 0.54 vs. 39.45 ± 0.96 µmol/mL; 2.14 ± 1.67 vs. 28.76 ± 1.89 µmol/mL; 4.43 ± 0.89 vs. 87.90 ± 3.45 µmol/mL, respectively). The IC50 of CDDP was significantly less in siRNA-FBW7-CNE2-CDDP than in FBW7-CNE2-CDDP-NC. The level of FBW7 expression in CNE2 cells was correlated with CDDP chemosensitivity. siRNA-mediated upregulation of FBW7 expression downregulated the expression of MRP, significantly increasing drug sensitivity in CNE2 cells.

Value of chest CT in the diagnosis and management of tracheobronchial foreign bodies.

BACKGROUND: The aim of the present study was to investigate the value of chest multidetector computed tomography (CT) in the evaluation of children with suspected foreign body aspiration. METHODS: Chest CT was performed in 45 consecutive children with suspected foreign body aspiration, and plain chest X-ray was conducted at the same time. Multiplanar reformatted imaging was carried out after multidetector CT. Rigid bronchoscopy and removal of the foreign body was performed under general anesthesia. RESULTS: All 42 patients (100%) with tracheobronchial foreign bodies were identified on chest CT. Three patients avoided unnecessary operations due to negative CT scans. For the patients with tracheobronchial foreign bodies, the occurrence of unilateral hyperlucent lung and post-obstructive lobar or segmental infiltrates on plain chest X-ray was 42.9% (18/42) and 4.8% (2/42), respectively. Twenty-two of the 42 patients (52.4%) had no abnormalities on plain X-ray. The difference between multidetector CT and plain X-ray results was statistically significant (P < 0.001). Surgical plans were designed and appropriate foreign body forceps were selected based on the CT scans. All foreign bodies were removed successfully, and no severe complications were observed. The location, shape, and volume of the foreign bodies found at surgery were consistent with the CT images. CONCLUSIONS: The diagnosis of foreign body aspiration of the airway in children can be accomplished by using chest multidetector CT. It is often useful in delineating the exact shape, location, volume and form of a bronchial foreign body and can help the surgeon plan for operative bronchoscopy and safe removal of the foreign body.

Melatonin protects cochlear hair cells from nicotine-induced injury through inhibiting apoptosis, inflammation, oxidative stress and endoplasmic reticulum stress.

Hearing loss positively links with cigarette smoking. However, the involved mechanism and treatment strategies are largely unrevealed. This study aimed to investigate the damaging effect of nicotine on cochlear hair cells, reveal the underlying mechanism and evaluate the therapeutic effect of melatonin on nicotine-induced injury. The results showed that nicotine induced cytotoxicity of House Ear Institute-Organ of Corti 1 (HEI-OC1) cochlear hair cells in a dose-dependent manner (0, 2.5, 5, 10, 20, 40 and 80 µM). Functional investigations showed that nicotine (10 µM) stimulation dramatically promoted apoptosis, inflammatory response, oxidative stress and endoplasmic reticulum stress in HEI-OC1 cells. Moreover, melatonin treatment dose-dependently alleviated the nicotine-induced cytotoxicity in HEI-OC1 cells (0, 10 25, 50 and 100 µM). Further investigation showed that melatonin (100 µM) effectively attenuated the nicotine-induced apoptosis, inflammation, oxidative stress and endoplasmic reticulum stress in HEI-OC1 cells. Collectively, we demonstrated that nicotine induced apoptosis, inflammation, oxidative stress and endoplasmic reticulum stress of cochlear hair cells in an in vitro cell model. Melatonin showed protective effect on these aspects, suggesting that melatonin may be a potential agent for treating smoking-induced hearing loss.

Chrysene accelerates the proceeding of chronic obstructive pulmonary disease with the aggravation of inflammation and apoptosis in cigarette smoke exposed mice.

Chrysene, one of the basic polycyclic aromatic hydrocarbons (PAHs), has been reported to make damages to human health and living environment. Chronic obstructive pulmonary disease (COPD) is a progressive disorder with high morbidity and mortality. To investigate the role of chrysene in the development of COPD, male C57BL/6 mice were exposed to the cigarette smoke (CS) followed with the administration of chrysene. Morphological analyses indicated that chrysene caused earlier and severer pathological changes in CS-exposed mice. Besides, CS-exposed mice with chrysene treatment showed obvious collagen deposition, elevated α-smooth muscle actin (α-SMA) expression and reduced E-cadherin abundance at earlier stage, which suggested the acceleration and aggravation of pulmonary fibrosis. Moreover, quantification of leukocytes and pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung tissues implied that chrysene significantly exacerbated the proceeding of inflammation in CS-exposed mice. Furthermore, significantly increased apoptotic rates, augmented expressions of apoptotic related proteins and highly expressed TRPV1 were determined in CS-exposed mice with chrysene treatment, which indicated the association between COPD pathogenesis and TRPV1 channel. In summary, our findings elucidate that chrysene accelerates the development of COPD in a murine model with new molecular mechanisms.

Analysis of clinical features and prognostic factors of lung cancer patients: A population-based cohort study.

OBJECTIVES: This paper analyses clinical features of lung cancer patients and discusses factors influencing the lung cancer occurrence and prognosis. METHODS: Patients diagnosed with lung cancer from 1975 to 2016 are analysed based on SEER database. The samples are divided into groups according to the number of positive lymph nodes of LN > 3 and LN ≤ 3. Univariate and multivariate Cox risk models are performed. After balancing the clinicopathological features of the two groups with the propensity score matching (PSM) method, the survival rates of the two groups are compared. RESULTS: A total of 30 864 patients are included in this study. Kaplan-Meier curves show that the survival rate of patients with LN ≤ 3 is higher than that of patients with LN > 3 (P < 0.0001). Univariate and multivariate Cox proportional risk model analysis suggests that the number of lymph nodes is an independent prognostic risk factor for lung cancer. LN ≤ 3 group shows better OS (HR2.066; 95% CI 1.941-2.199, P < 0.01) and better CSS (HR 2.461; 95% CI 2.304-2.629, P < 0.01). In addition, age at diagnosis, gender, Laterality, Derived AJCC T, 7th ed (2010-2015), Derived AJCC N, 7th ed (2010-2015) and Derived AJCC M, 7th ed, (2010-2015) have also been proved to be potential prognostic factors. A total of 1,851 pairs of patients are screened after 1:1 PSM matching. Patients with LN ≤ 3 have significant improvements in OS and CSS (HR 1.09; 95% CI 1.001-1.187, P < 0.05 and HR 1.127; 95% CI 1.03-1.232, P < 0.001). CONCLUSION: The number of lymph nodes is an independent prognostic risk factor for lung cancer. Patients with fewer lymph node positives have a better survival prognosis than patients with more lymph nodes.

[Multi-center comparative study of methylprednisolone and dexamethasone in treatment of all-frequency sudden hearing loss].

OBJECTIVE: Through a prospective cohort study, to assess the clinical efficacy of methylprednisolone (MP) and dexamethasone (DXM) in treatment of all-frequency sudden hearing loss. METHODS: A total of 76 cases of all-frequency sudden hearing loss were included in this study and divided into two groups. The MP group (n = 40) was treated with MP 40 mg qd, for 5 days, combined with conventional treatment. The DXM group (n = 36) was treated with DXM 10 mg qd, for 5 days, combined with conventional treatment. The total period of treatment was 14 days. RESULTS: After the treatment for 14 days, in the MP group,17 cases were cured (42.5%), 7 cases were markedly improved (17.5%), 9 cases were effective (22.5%), and 7 cases were invalid (17.5%), the total effective rate was 82.5%. As for the patients in the DXM group, 13 cases were cured (36.1%), 6 cases were markedly improved (16.7%), 8 cases were effective (24.2%), and 9 cases were invalid (25%), the total effective rate was 75.0%. The pure tone audiometry in all-frequency was improved (31.5 ± 17.8) dB in the MP group, and (33.1 ± 24.2) dB in the DXM group. The speech recognition rate was improved (41.7 ± 29.8) %, and (42.0 ± 39.1) % in the DXM group. There were no significant differences between two groups. CONCLUSION: There is no significant difference of therapeutic efficacy between the low-dose MP group and High-dose DXM group.