[Study on risk factors of abnormal pulmonary function among dust-exposed workers and prediction model].

Objective: To explore the influencing factors of abnormal pulmonary function in dust-exposed workers and establish the risk prediction model of abnormal pulmonary function. Methods: In April 2021, a total of 4255 dust exposed workers from 47 enterprises in 2020 were included in the study. logistic regression was used to analyze the influencing factors of abnormal pulmonary function in dust-exposed workers, and the corresponding nomogram prediction model was established. The model was evaluated by ROC curve, Calibrationpolt and decision analysis curve. Results: logistic regression analysis showed that age (OR=1.03, 95%CI=1.02~1.05, P<0.001) , physical examination type (OR=4.52, 95%CI=1.69~12.10, P=0.003) , dust type (Comparison with coal dust, Cement dust, OR=3.45, 95%CI=1.45~8.18, P=0.005, Silica dust (OR=2.25, 95%CI=1.01~5.03, P=0.049) , blood pressure (OR=1.63, 95%CI=1.22~2.18, P=0.001) , creatinine (OR=0.08, 95%CI=0.05~0.12, P<0.001) , daily exposure time (OR=1.06, 95%CI=1.10~1.12, P=0.034) and total dust concentration (OR=1.29, 95%CI=1.08~1.54, P=0.005) were the influencing factors of abnormal pulmonary function. The area under the ROC curve of risk prediction nomogram model was 0.764. The results of decision analysis curve showed that the nomogram model had reference value in the prevention and intervention of abnormal pulmonary function when the threshold probability exceeded 0.05. Conclusion: The accuracy ofthe nomogram model constructed by logistic regression werewell in predicting the risk of abnormal lung function of dust-exposed workers.

ASIC1a involves the acid-mediated activation of pancreatic stellate cells associated with autophagy induction.

The acidic tumor microenvironment (TME) of pancreatic cancer affects the physiological function of pancreatic stellate cells (PSCs), which in turn promotes cancer progression. Acid-sensing ion channel 1a (ASIC1a) is responsible for acidosis-related physiopathological processes. In this study, we investigated the effect of acid exposure on the activation and autophagy of PSCs, and the role of ASIC1a in these events. The results showed that acidic medium upregulated the expression of ASIC1a, induced PSCs activation and autophagy, which can be suppressed by inhibiting ASIC1a using PcTx1 or ASIC1a knockdown, suggesting that ASIC1a involves these two processes. In addition, the acid-induced activation of PSCs was impaired after the application of autophagy inhibitor alone or in combination with ASIC1a siRNA, meaning a connection between autophagy and activation. Collectively, our study provides evidence for the involvement of ASIC1a in the acid-caused PSCs activation, which may be associated with autophagy induction.

Global disease burden of COPD from 1990 to 2019 and prediction of future disease burden trend in China.

OBJECTIVES: This study aimed to assess and predict the disease burden attributable to chronic obstructive pulmonary disease (COPD) in a timely, comprehensive, and reliable manner, thereby mitigating the health hazards of COPD. STUDY DESIGN AND METHODS: Data on the disease burden owing to COPD from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) Study 2019. Linear regression analysis was used to calculate the estimated annual percentage change (EAPC) in the age-standardized rates. Non-parametric tests were used for subgroup analysis. The Bayesian age-period-cohot (BAPC) model integrated nested Laplace approximations to predict the disease burden over the next 25 years. Sensitivity analysis was performed using the Norpred APC model. RESULTS: Globally, the COPD-related age-standardized incidence rate decreased from 216.48/100,000 in 1990 to 200.49/100,000 in 2019, with an EAPC of -0.33. But the number of new cases increased from 8,722,966 in 1990 to 16, 214, 828 in 2019. Trends in prevalence, deaths, and disability-adjusted life years (DALYs) were the same as incidence. There were significant differences in disease burden between the genders and all age groups (P < 0.05) in China. The projections suggested that the COPD-related number of new cases and deaths in China would increase by approximately 1.5 times over the next 25 years. CONCLUSIONS: The number of incidence, prevalence, deaths, and DALYs had all increased in China in the past and would continue to grow over the next 25 years. Therefore, measures should be taken to target risk factors and high-risk groups.

[Effect and prognosis of new type of re-dilated stent in the treatment of pulmonary artery bifurcation stenosis].

the early and med-term follow-up results and technical points of new re-dilated stent in the treatment of pulmonary artery bifurcation opening stenosis, and explore its feasibility and advantages. From March 2019 to October 2020, 10 children [5 males, mean age (7±3) years], mean weight 18.75(13.35,23.05) kg with pulmonary artery bifurcation opening stenosis were treated with new re-dilated stents in the Central China Fuwai Hospital. Including 5 cases of tetralogy of Fallot, 4 cases of pulmonary atresia, 1 case of anomalous origin of coronary artery, all children were given new re-dilated stent implantation. Echocardiography, chest X-ray and electrocardiogram were performed 1 day, 3, 6, 12 months after intervention. Pulmonary artery CTA was performed after 6 or 12 months to evaluate the results, including restenosis, malposition and rupture. A total of 16 stents were implanted in 10 children, 5 cases had simultaneous stenosis of bifurcation openings of pulmonary arteries, and 1 stent was implanted in each of the left and right pulmonary artery openings. The pressure of right ventricular and gradient was significantly decreased immediately after intervention, from preoperative (38-80) mmHg(1 mmHg=0.133 kPa) to postoperative (0-22) mmHg, only one patient's pressure gradient is over 20 mmHg (22 mmHg), and all cases discharged successfully. Stent restenosis, malposition, fracture and other abnormalities were not observed in follow-up. Stents implantation for patients with pulmonary artery bifurcation opening stenosis is very more difficult. A good strategy can ensure that the intervention is safe and effective. It not only avoids the risk of repeated surgery, but also achieves good med-term follow-up results.

A non-coding cancer mutation disrupting an HNF4α binding motif affects an enhancer regulating genes associated to the progression of liver cancer.

BACKGROUND: Somatic mutations in coding regions of the genome may result in non-functional proteins that can lead to cancer or other diseases, however cancer mutations in the non-coding regions have rarely been studied and the interpretation of their effects is difficult. Non-coding mutations might act by breaking or creating transcription factor binding motifs in promoters, enhancers or silencers resulting in altered expression of target gene(s). A high number of mutations have been reported in coding and non-coding regions in cells of liver cancer. Hepatocyte nuclear factor 4α is a transcription factor that regulates the expression of several genes in liver cells, while the motifs it binds are frequently mutated in promoters and enhancers in liver cancer. AIM: The aim of the study is to evaluate the genetic effects of a non-coding somatic mutation frequently observed in liver cancer. MATERIALS AND METHODS: We evaluated experimentally the effects of a somatic mutation frequently reported in liver cancer as a motif-breaker for the binding of hepatocyte nuclear factor 4α. The effects of the mutation on protein binding and enhancer activity were studied in HepG2 cells via electrophoresis mobility shift assay and dual luciferase reporter assays. We also studied genome-wide promoter-enhancer interactions performing targeted chromosome conformation capture in liver tissue to identify putative target genes whose expression could be altered by the mutation. RESULTS: We found that the mutation leads to reduced protein binding and a decrease in enhancer activity. The enhancer harboring the mutation interacts with the promoters of ANAPC13, MAP6D1 and MUC13, which have been implicated in liver cancer. CONCLUSIONS: The study highlights the importance of non-coding somatic mutations, vastly understudied, but likely to contribute to cancer development and progression.

[Clinical effect analysis of 146 cases of ipsilateral simultaneous pancreas and kidney transplantation].

Objective: To investigate the clinical effect of ipsilateral simultaneous pancreas and kidney transplantation (SPK). Methods: A total of 146 cases of SPK surgeries completed in the Second Affiliated Hospital of Guangzhou Medical University from September 2016 to June 2020 were selected to summarize the outcome, curative effect and complications of the operation. Results: The patients were followed up for 1 to 45 months. Good clinical results were obtained in 146 patients. Renal function indicators suggest that on the 7th day after operation, the serum creatinine returned to normal level [142.4 (108.6, 213.4)µmol/L]. The index of pancreatic function decreased to the normal level as expected. The level of blood amylase was 160.5(109.3, 249.8) U/L within 7 days after operation, and then decreased. The trend of urinary amylase was similar to that of blood amylase, which was 240(121.0, 370.0) U/L 7 days after operation, and glycosylated hemoglobin decreased to the normal level (5.8%±1.4%) 1 month after operation. The main medical complications were infection including pulmonary infection (26.03%, 38/146), urinary tract infection (26.03%,38/146), and abdominal infection (4.79%,7/146), acute rejection including renal graft rejection (5.8%,8/146), pancreas/duodenum rejection (18.49%,27/146), and renal graft combined pancreatic graft rejeciton (6.85%,10/146), as well as gastrointestinal bleeding (30.82%,45/146), of which 5 cases were severe bleeding (3.42%, 5/146). The main surgical complications were poor incision healing (10.27%, 15/146), serious surgical complications including arteriovenous thrombosis of the transplanted pancreas (2.05%, 3/146) and intestinal leakage (0.68%,1/146). The 1-year and 3-year patient, renal and pancreatic survival rates were both 92.5%, 91.5% and 89.5%, respectively, and despite the death, the 1-year, 3-year transplanted kidney survival rate was both 99.3%, and 95% for the the 1-year, 3-year pancreas survival rate. Conclusion: Strict preoperative evaluation of the function of large organs, reasonable surgical methods, perioperative anticoagulation, and prompt diagnosis of complications can achieve good clinical results for patients with SPK.

Towards a global-scale soil climate mitigation strategy.

Sustainable soil carbon sequestration practices need to be rapidly scaled up and implemented to contribute to climate change mitigation. We highlight that the major potential for carbon sequestration is in cropland soils, especially those with large yield gaps and/or large historic soil organic carbon losses. The implementation of soil carbon sequestration measures requires a diverse set of options, each adapted to local soil conditions and management opportunities, and accounting for site-specific trade-offs. We propose the establishment of a soil information system containing localised information on soil group, degradation status, crop yield gap, and the associated carbon-sequestration potentials, as well as the provision of incentives and policies to translate management options into region- and soil-specific practices.

[Difficulties and countermeasures for the perioperative management of megasplenectomy in patients with advanced schistosomiasis].

The etiology, pathology, clinical features and prognosis of megalosplenic advanced schistosomiasis have their specific features, and therefore, the perioperative management of this disorder has special countermeasures. The review analyzes the difficult problems in the perioperative management of megalosplenic advanced schistosomiasis, including ultra - low platelet counts, extensive and severe adhesive splenomegaly, massive hemorrhage during surgery and portal vein thrombosis, and proposes countermeasures to tackle these problems, with aims to guide the clinical treatment and cure of schistosomiasis, thereby improving the prognosis, reducing complications and improving the quality of life.

[A pathological report of three COVID-19 cases by minimal invasive autopsies].

Objective: To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19). Methods: Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV. Results: Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs. Conclusions: The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.

[Clinical efficacy and safety of combined induction therapy with rituximab and ATG in highly sensitized kidney transplant recipients].

Objective: To summarize the efficacy and safety of the combination of rituximab and ATG as induction therapy in highly sensitized kidney transplant recipients. Methods: Clinical data of patients who received kidney transplantation from donation after cardiac death(DCD) in Organ Transplant Center of Second Affiliated Hospital of Guangzhou Medical University from January 1st 2015 to December 31th 2016 was retrospectively analyzed. Highly sensitized patients with over 30% active panel reactive antibody (PRA>30%) received rituximab, while non-sensitized recipients as controlled group. All selected patients were observed in the renal function, urine protein, hemogram and the variation of PRA at each time point. Acute rejection, infection required hospitalization, delayed graft function(DGF), primary nonfunction (PNF), graft dysfunction, the mortality rate of patients with good allograft function and the graft survival rate were also observed. Results: 46 groups of patients were selected into highly-sensitized group and non-sensitized group. In both groups, there was no statistical difference in the renal function, urine protein and WBC (all P>0.05). Highly sensitized recipients at day 7 and day 14 following the surgery, had a significantly lower percentage of lymphocyte counts and lymphocyte proportion compared to other groups, with statistical differences(all P<0.05). Both groups had a similar incidence of DGF(2.2%) and no occurrence of PNF. 19.5% of highly sensitized recipients experienced acute rejection and 13% in control group. More specifically, no statistical difference was noted in the rate of infection required hospitalization(30.4% vs 22.2%), graft loss(2.2% vs 0) and the mortality rate of patients with good allograft function(4.3% vs 2.2%)(all P>0.05). The graft survival rate was 97.8% in the highly-sensitized group, while 100% in the control group. And the rate of patient survival in these two groups was 95.7% and 97.8%, with no statistical differences(all P>0.05). Conclusions: Immune-induction therapy that combines Rituximab with ATG can significantly inhibit lymphocyte proliferation. It is effective and safe in treating hypersensitive patients. The survival rate of human/kidney of hypersensitive patients in the short and medium term is comparable to those with low immune risk.

[Clinical application of renal autotransplantation in complex urological diseases].

Objective: To summarize the experience of renal autotransplantation for severe iatrogenic proximal ureteral damage and renal artery aneurysms in eight patients and to explore the clinical application value of renal autotransplantation. Methods: Two patients of renal artery aneurysms and six patients of severe iatrogenic proximal ureteral damage between January 2010 and March 2018 in our center were retrospectively reviewed. Results: The procedures of eight cases were successful, with immediate return of renal function in the patients. The warm ischemia time was (3±1) minutes, the total operation time was (340±164) min, and the estimated blood loss was (180±60) ml, respectively. For renal artery anastomosis, six patients of severe iatrogenic proximal ureteral damage received end-to-end anastomosis between the internal iliac artery and renal artery, and two patients of renal artery aneurysms were treated with renal artery and internal iliac artery for reconstruction, then end-to-side anastomosis to recipien external iliac artery. A direct ureterovesical anastomosis was performed in seven patients, one patient was received pyeloureteroplasty. No serious complications of blood vessel and ureter were found during perioperative and long-term follow-up. All cases follow-up hitherto have normal renal function and blood pressure. Conclusions: Renal autotransplantation can be appropriate for patients with proximal ureteral loss and complex hilar renal artery aneurysms. In addition, it is able to protect renal functions to the most extent and provides a surgical alterative for complex renal diseases.

Clinicopathologic analysis of 2736 salivary gland cases over a 11-year period in Southwest China.

OBJECTIVE: To investigate the epidemiological and clinicopathological characteristics of salivary gland tumors in southwest China in order to provide data for clinical diagnosis and other similar research. METHODS: Between March 2007 and December 2017, 2736 patients with salivary gland tumors were recruited, the clinical and pathological data were retrospectively analyzed. RESULTS: A total of 2736 patients had a ratio of males to females of about 1.02:1. The ratio of benign to malignant tumors was 3.46:1. Pleomorphic adenoma and adenoid cystic carcinoma had 50.8% and 7.2%, respectively. About 65.4% tumors occurred in the parotid gland. There was no significant difference between the tumor in the left or right parotid and the use of cell phones. There were significant differences between gender and both the characteristics and locations of salivary gland tumors (p < .05). There were also significant differences between the pathological characteristics and location of the salivary gland (p < .05). CONCLUSIONS: The salivary gland benign and malignant tumors were more common in pleomorphic adenoma and adenoid cystic carcinoma, most occurred in the parotid gland. The minor gland tumors are lower than other parts of China. The incidence of parotid gland tumors is not related to the use of cell phones.

Transgenic characterization of two silkworm tissue-specific promoters in the haemocyte plasmatocyte cells.

Haemocytes play crucial roles in insect metabolism, metamorphosis, and innate immunity. As a model of lepidopteran insects, the silkworm is a useful model to study the functions of both haematopoiesis and haemocytes. Tissue-specific promoters are excellent tools for genetic manipulation and are widely used in fundamental biological research. Herein, two haemocyte-specific genes, Integrin ß2 and Integrin ß3, were confirmed. Promoter activities of Integrin ß2 and Integrin ß3 were evaluated by genetic manipulation. Quantitative real-time PCR and western blotting suggested that both promoters can drive enhanced green fluorescent protein (EGFP) specifically expressed in haemocytes. Further evidence clearly demonstrated that the transgenic silkworm exhibited a high level of EGFP signal in plasmatocytes, but not in other detected haemocyte types. Moreover, EGFP fluorescence signals were observed in the haematopoietic organ of both transgenic strains. Thus, two promoters that enable plasmatocytes to express genes of interest were confirmed in our study. It is expected that the results of this study will facilitate advances in our understanding of insect haematopoiesis and immunity in the silkworm, Bombyx mori.

SOX8 regulates cancer stem-like properties and cisplatin-induced EMT in tongue squamous cell carcinoma by acting on the Wnt/ß-catenin pathway.

A sub-population of chemoresistant cells exhibits biological properties similar to cancer stem cells (CSCs), and these cells are believed to be a main cause for tumor relapse and metastasis. In our study, we explored the role of SOX8 and its molecular mechanism in the regulation of the stemness properties and the epithelial mesenchymal transition (EMT) of cisplatin-resistant tongue squamous cell carcinoma (TSCC) cells. We found that SOX8 was upregulated in cisplatin-resistant TSCC cells, which displayed CSC-like properties and exhibited EMT. SOX8 was also overexpressed in chemoresistant patients with TSCC and was associated with higher lymph node metastasis, advanced tumor stage and shorter overall survival. Stable knockdown of SOX8 in cisplatin-resistant TSCC cells inhibited chemoresistance, tumorsphere formation, and EMT. The Wnt/ß-catenin pathway mediated the cancer stem-like properties in cisplatin-resistant TSCC cells. Further studies showed that the transfection of active ß-catenin in SOX8 stable-knockdown cells partly rescued the SOX8 silencing-induced repression of stem-like features and chemoresistance. Through chromatin immunoprecipitation and luciferase assays, we observed that SOX8 bound to the promoter region of Frizzled-7 (FZD7) and induced the FZD7-mediated activation of the Wnt/ß-catenin pathway. In summary, SOX8 confers chemoresistance and stemness properties and mediates EMT processes in chemoresistant TSCC via the FZD7-mediated Wnt/ß-catenin pathway.

[Analysis of gene mutation of early onset epileptic spasm with unknown reason].

Objective: To summarize the gene mutation of early onset epileptic spasm with unknown reason. Method: In this prospective study, data of patients with early onset epileptic spasm with unknown reason were collected from neurological department of Children's Hospital of Fudan University between March 2016 and December 2016. Patients with known disorders such as infection, metabolic, structural, immunological problems and known genetic mutations were excluded. Patients with genetic disease that can be diagnosed by clinical manifestations and phenotypic characteristics were also excluded. Genetic research methods included nervous system panel containing 1 427 epilepsy genes, whole exome sequencing (WES), analysis of copy number variation (CNV) and karyotype analysis of chromosome. The basic information, phenotypes, genetic results and the antiepileptic treatment of patients were analyzed. Result: Nine of the 17 cases with early onset epileptic spasm were boys and eight were girls. Patients' age at first seizure onset ranged from 1 day after birth to 8 months (median age of 3 months). The first hospital visit age ranged from 1 month to 2 years (median age of 4.5 months). The time of following-up ranged from 8 months to 3 years and 10 months. All the 17 patients had early onset epileptic spasm. Video electroencephalogram was used to monitor the spasm seizure. Five patients had Ohtahara syndrome, 10 had West syndrome, two had unclear classification. In 17 cases, 10 of them had detected pathogenic genes. Nine cases had point mutations, involving SCN2A, ARX, UNC80, KCNQ2, and GABRB3. Except one case of mutations in GABRB3 gene have been reported, all the other cases had new mutations. One patient had deletion mutation in CDKL5 gene. One CNV case had 6q 22.31 5.5MB repeats. Ten cases out of 17 were using 2-3 antiepileptic drugs (AEDs) and the drugs had no effect. Seven cases used adrenocorticotropic hormone (ACTH) and prednisone besides AEDs (a total course for 8 weeks). Among them, five cases had no effect and two cases were seizure free recently. A case with GABRB3 (C.905A>G) had seizure controlled for 3 mouths. A case with ARX (C.700G>A) had seizure controlled for 6 mouths. Conclusion: The early onset epileptic spasm with unknown reason is highly related to genetic disorders. A variety of genetic mutations, especially new mutations were found. Genetic heterogeneity of epileptic spasm is obvious.

Melatonin at pharmacological concentrations suppresses osteoclastogenesis via the attenuation of intracellular ROS.

Osteoporosis is linked to age-related decline of melatonin production; however, the direct effects of melatonin on osteoclastogenesis remain unknown. Our study demonstrates that melatonin at pharmacological concentrations, rather than at physiological concentrations, significantly inhibits osteoclastogenesis. Melatonin-mediated anti-osteoclastogenesis involves a reactive oxygen species (ROS)-mediated but not a silent information regulator type 1 (SIRT1)-independent pathway. INTRODUCTION: Osteoporosis is a bone disorder linked to impaired bone formation and excessive bone resorption. Melatonin has been suggested to treat osteoporosis due to its beneficial actions on osteoblast differentiation. However, the direct effects of melatonin on osteoclastogenesis in bone marrow monocytes (BMMs) remain unknown. This study was to investigate whether melatonin at either physiological or pharmacological concentrations could affect osteoclast differentiation. METHODS: Primary BMMs were isolated from the femurs and tibias of C57BL/6 mice and were induced toward multinucleated osteoclasts, in the presence of melatonin at either physiological (0.01 to 10 nM) or pharmacological (1 to 100 µM) concentrations. Tartrate-resistant acid phosphatase (TRAP) staining was used to label multinucleated osteoclasts and the levels of osteoclast-specific genes were evaluated. To further explore the underlying mechanisms, the roles of silent information regulator type 1 (SIRT1) and reactive oxygen species (ROS) were evaluated. RESULTS: We found that melatonin at pharmacological concentrations, rather than at physiological concentrations, significantly inhibited osteoclast formation in a dose-dependent manner. The number of TRAP-positive cells and the gene expression of osteoclast-specific markers were significantly downregulated in melatonin-treated BMMs. The melatonin-mediated repression of osteoclast differentiation involved the inhibition of the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. The treatment with SIRT1 inhibitors did not affect osteoclast differentiation but, when supplemented with exogenous hydrogen peroxide, a partial rescue of melatonin-suppressed osteoclastogenesis was observed. CONCLUSION: Melatonin at pharmacological doses directly inhibited osteoclastogenesis of BMMs by a ROS-mediated but not a SIRT1-independent pathway.

Tanshinone IIA ameliorates lead (Pb)-induced cognitive deficits and oxidative stress in a rat pup model.

OBJECTIVE: Chronic lead (Pb) exposure affects the developing central nervous system, whereas Tanshinone IIA (TSA) improves cognitive deficits. METHODS: In this study, we investigated the effects of TSA against lead-induced neurotoxicity in a rat pup model. A total of thirty two healthy male Wistar rats were randomly divided into four groups: lead-treated group, lead plus TSA-treated 1 group, lead plus TSA-treated 2 group, and controls. After a 4-week lead exposure, memory function was determined using Morris water maze and the concentration of lead was measured in blood. Total superoxide dismutase (T-SOD), glutathione (GSH), malonaldehyde (MDA) and brain-derived neurotrophic factor (BDNF) activities were determined in hippocampus samples. RESULTS: Lead exposure causes decrease of body weight; increase of the blood lead concentration; decrease of antioxidant activities and BDNF content. However, co-administration of TSA with lead ameliorated the weight loss. Furthermore, TSA inhibited neurotoxicity as evidenced by decreased latency period and increase in percentage of time spent in the target quadrant. Administration of TSA also improved antioxidant activities by increased T-SOD, GSH, and decreased MDA activities compared to lead-treated group. CONCLUSION: This study provides evidence of that TSA has a neuroprotective effect against lead-induced cognitive deficit by enhancing antioxidant activities in the brain (Tab. 2, Fig. 3, Ref. 27).

[Correlation between expression of long non-coding RNA ZXF1 and prognosis of lung adenocarcinoma and its potential molecular mechanism].

Objective: To investigate the correlation between expression of long non-coding RNA (lncRNA) ZXF1 and clinicopathological characteristics, as well as prognosis of lung adenocarcinoma; and to explore its potential molecular mechanism. Methods: A total of 83 lung adenocarcinoma tissue samples and 83 paracancerous lung tissue samples from lung adenocarcinoma patients were collected. The mRNA expression of ZXF1 in the tumors and the corresponding adjacent non-tumor tissues were determined by real-time fluorescence quantitative PCR. The correlation between ZXF1 level and clinicopathological characteristics such as age, gender, smoking history, tumor size, tumor differentiation and lymph node metastasis was evaluated. Survival analysis was performed using Kaplan-Meier and Cox multivariate regression, based on the data of a 12-56 months follow-up after surgery. In vitro ZXF1 was over-expressed in lung adenocarcinoma A549 cells, and then the proteins functionally related to ZXF1 were identified by protein array analysis. Results: Of the 83 cases of lung adenocarcinoma, the ZXF1 mRNA levels in the tumor and adjacent non-tumor tissues were 8.32±3.05 and 1.05±0.47, respectively (P<0.05), and a high-level the high expression of ZXF1 in the tumor tissues was detected in 56 cases. The expression status of ZXF1 was closely correlated with the tumor differentiation and lymph node metastasis (P<0.05), but was not significantly related to age, gender and tumor size. Based on a 12-56 months follow-up, the patients with high level ZXF1 expression had a shorter disease free survival (DFS) and overall survival (OS) than that of the group with low level ZXF1 (all P<0.05). Multivariate analysis showed that ZXF1 expression, tumor size and lymph node metastasis were independent risk factors to DFS; and ZXF1 expression, tumor size, lymph node metastasis and tumor differentiation were independent risk factors to OS. The protein array data revealed that expressions of bone morphogenetic protein 5 (BMP-5)and stem cell factor receptor (SCFR)were upregulated upon overexpression of the ZXF1 in A549 cells. Conclusions: lncRNA ZXF1 is overexpressed in lung adenocarcinoma, and is closely correlated with tumor differentiation and lymph node metastasis. As an independent risk factor, a high expression of ZXF1 indicates a poor prognosis for the patients. ZXF1 may influence the biological behavior of lung adenocarcinoma by enhancing the protein expression of BMP-5 and SCFR.