Interleukin-17A plays a key role in pulmonary fibrosis following Propionibacterium acnes-induced sarcoidosis-like inflammation.

Sarcoidosis is a granulomatous disease of unknown etiology, with limited therapeutic options. Chronic sarcoidosis can result in pulmonary fibrosis and can be lethal. Enhanced expression of pro-inflammatory cytokines, such as interleukin-17A (IL-17A), has been observed in sarcoid granulomas in humans. However, the role of IL-17A in the pathogenesis of chronic sarcoidosis or sarcoidosis-related pulmonary fibrosis and its potential therapeutic effects remain unclear. This study investigated whether IL-17A is critical in granulomatosis and its role in chronic inflammation in a profibrotic manner. Wild-type and IL-17A-knockout C57BL/6 mice were repeatedly challenged with heat-killed Propionibacterium acnes (PA) to induce sarcoidosis-like granulomata and sarcoidosis-related pulmonary fibrosis. Wild-type mice with granulomatosis were treated with anti-IL-17A antibody. Administration of PA enhanced the expression of IL-17A, granulomatosis, and fibrosis in mouse lungs after boost stimulation. Neither granulomata nor fibrosis were observed in IL-17A-knockout mice, even in the presence of interferon-γ enhancement. Neutralizing IL-17A antibody reduced inflammatory cells in bronchoalveolar lavage fluid and ameliorated both granulomatosis and fibrosis in sarcoidosis mice. In conclusion, our data demonstrate that IL-17A plays a critical role in PA-induced sarcoidosis-like inflammation in both granulomatosis inflammation and disease progression to pulmonary fibrosis, thus providing novel insights into the treatment of chronic sarcoidosis or sarcoidosis-related pulmonary fibrosis.

USP13 Deficiency Impairs Autophagy and Facilitates Age-related Lung Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an age-related disease. Failure of the proteostasis network with age, including insufficient autophagy, contributes to the pathology of IPF. Mechanisms underlying autophagy disruption in IPF are unclear and may involve regulation of USP (ubiquitin-specific protease) by post-translational modifications. To expand our previous observation of low USP13 expression in IPF, this study evaluated the role of USP13 in age-related lung fibrosis. Here, we demonstrated that Usp13-deficient aged mice exhibited impaired autophagic activity and increased vulnerability to bleomycin-induced fibrosis. Mechanistically, USP13 interacted with and deubiquitinated Beclin 1, and Beclin 1 overexpression abolished the effects of USP13 disruption. In addition, Beclin 1 inhibition resulted in insufficient autophagy and more severe lung fibrosis after bleomycin injury, consistent with the phenotype of aged Usp13-deficient mice. Collectively, we show a protective role of USP13 in age-related pulmonary fibrosis. Aging-mediated USP13 loss impairs autophagic activity and facilitates lung fibrosis through Beclin 1 deubiquitination. Our findings support the notion that age-dependent dysregulation of autophagic regulators enhances vulnerability to lung fibrosis.

A male germ-cell-specific ribosome controls male fertility.

Ribosomes are highly sophisticated translation machines that have been demonstrated to be heterogeneous in the regulation of protein synthesis1,2. Male germ cell development involves complex translational regulation during sperm formation3. However, it remains unclear whether translation during sperm formation is performed by a specific ribosome. Here we report a ribosome with a specialized nascent polypeptide exit tunnel, RibosomeST, that is assembled with the male germ-cell-specific protein RPL39L, the paralogue of core ribosome (RibosomeCore) protein RPL39. Deletion of RibosomeST in mice causes defective sperm formation, resulting in substantially reduced fertility. Our comparison of single-particle cryo-electron microscopy structures of ribosomes from mouse kidneys and testes indicates that RibosomeST features a ribosomal polypeptide exit tunnel of distinct size and charge states compared with RibosomeCore. RibosomeST predominantly cotranslationally regulates the folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm. Moreover, we found that specialized functions of RibosomeST were not replaceable by RibosomeCore. Taken together, identification of this sperm-specific ribosome should greatly expand our understanding of ribosome function and tissue-specific regulation of protein expression pattern in mammals.

IL-17A promotes lung fibrosis through impairing mitochondrial homeostasis in type II alveolar epithelial cells.

The dysfunction of type II alveolar epithelial cells (AECIIs), mainly manifested by apoptosis, has emerged as a major component of idiopathic pulmonary fibrosis (IPF) pathophysiology. A pivotal mechanism leading to AECIIs apoptosis is mitochondrial dysfunction. Recently, interleukin (IL)-17A has been demonstrated to have a pro-fibrotic role in IPF, though the mechanism is unclear. In this study, we report enhanced expression of IL-17 receptor A (IL-17RA) in AECIIs in lung samples of IPF patients, which may be related to the accumulation of mitochondria in AECIIs of IPF. Next, we investigated this relationship in bleomycin (BLM)-induced PF murine model. We found that IL-17A knockout (IL-17A-/- ) mice exhibited decreased apoptosis levels of AECIIs. This was possibly a result of the recovery of mitochondrial morphology from the improved mitochondrial dynamics of AECIIs, which eventually contributed to alleviating lung fibrosis. Analysis of in vitro data indicates that IL-17A impairs mitochondrial function and mitochondrial dynamics of mouse primary AECIIs, further promoting apoptosis. PTEN-induced putative kinase 1 (PINK1)/Parkin signal-mediated mitophagy is an important aspect of mitochondria homeostasis maintenance. Our data demonstrate that IL-17A inhibits mitophagy and promotes apoptosis of AECIIs by decreasing the expression levels of PINK1. We conclude that IL-17A exerts its pro-fibrotic effects by inducing mitochondrial dysfunction in AECIIs by disturbing mitochondrial dynamics and inhibiting PINK1-mediated mitophagy, thereby leading to apoptosis of AECIIs.

Krebs von den Lungen-6 levels in untreated idiopathic pulmonary fibrosis.

BACKGROUND: Serum Krebs von den Lungen-6 (KL-6) has been reported to be elevated in patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVE: The aim of this study was to evaluate the diagnostic value of KL-6 and whether the expression value of KL-6 could indicate the severity of the disease in IPF patients. To address this question, it is necessary to see whether the patients' physical characteristics and other clinical conditions could affect the baseline KL-6 level. DESIGN: We conducted a study of 100 patients who were diagnosed with IPF. Lung function, computed tomography (CT), and serological lab tests data were analyzed. RESULTS: The tests showed that there is a significant elevation of KL-6 in IPF patients compared with other interstitial lung disease (ILD) and healthy controls. It was noted that serum KL-6 is a stable biomarker not affected by lung infection and smoking, though IPF patients with antinuclear antibody (ANA) showed higher KL-6 levels. KL-6, in conjunction with poor pulmonary function and higher radiological fibrosis scores, indicates the severity of the disease but not poor survival. CONCLUSIONS: It is identified that serum KL-6 is a useful noninvasive biomarker to help improve the certainty of IPF diagnosis from other interstitial lung disease and assist evaluation of disease severity and prognosis.

Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. METHODS: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. RESULTS: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. CONCLUSIONS: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. LAY SUMMARY: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

Water-Soluble C60 Protects Against Bleomycin-Induced Pulmonary Fibrosis in Mice.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia. And, oxidation/antioxidant imbalance plays an important role in the progress of IPF. Fullerene is considered to be a novel "structural" antioxidant. This study aimed to explore if water-soluble C60 (C60(OH)22) can exhibit antifibrotic activity in its antioxidant role. METHODS: Healthy C57BL/6J mice were randomly grouped and induced pulmonary fibrosis by intratracheal injection of bleomycin. RESULTS: The survival rate of mice was observed and found that 10mg/kg was the optimal dose of water-soluble C60 for pulmonary fibrosis. We observed that water-soluble C60 can alleviate the severity of pulmonary fibrosis by observing the chest computed tomography, pulmonary pathology, and content of collagen, alpha smooth muscle actin and fibronectin in lung. Compared with bleomycin group, ROS, the content of TNF-α in BALF, and the number of fibroblasts was significantly decreased and the number of type Ⅱ alveolar epithelial cells was increased after treatment with C60. CONCLUSION: Therefore, thanks to its powerful antioxidant action, water-soluble C60 can reduce the severity of pulmonary fibrosis induced by bleomycin in mice.

TP53TG1 enhances cisplatin sensitivity of non-small cell lung cancer cells through regulating miR-18a/PTEN axis.

BACKGROUND: The acquisition of drug resistance has been considered as a main obstacle for cancer chemotherapy. Tumor protein 53 target gene 1 (TP53TG1), a p53-induced lncRNA, plays a vital role in the progression of human cancers. However, little is known about the detailed function and molecular mechanism of TP53TG1 in cisplatin resistance of NSCLC. METHODS: qRT-PCR analysis was used to detect the expression of TP53TG1, miR-18a and PTEN mRNA in NSCLC tissues and cells. Western blot analysis was performed to determine the protein level of PTEN and cleaved caspase-3. Cell viability and IC50 value were measured by MTT assay. Cell apoptosis was confirmed by flow cytometry assay. Subcellular fractionation assay was used to identify the subcellular location of TP53TG1. Dual-luciferase reporter assay, RNA pull down assay and RNA immunoprecipitation assay were carried out to verify the interaction between TP53TG1 and miR-18a. Xenografts in nude mice were established to verify the effect of TP53TG1 on cisplatin sensitivity of NSCLC cells in vivo. RESULTS: TP53TG1 level was downregulated in NSCLC tissues and cell lines. Upregulated TP53TG1 enhanced cisplatin sensitivity and apoptosis of A549/DDP cells, while TP53TG1 depletion inhibited cisplatin sensitivity and apoptosis of A549 cells. TP53TG1 suppressed miR-18a expression in A549 cells. Moreover, TP53TG1-mediated enhancement effect on cisplatin sensitivity was abated following the restoration of miR-18a expression in A549/DDP cells, while si-TP53TG1-induced decrease of cisplatin sensitivity and apoptosis was counteracted by miR-18a inhibitor in A549 cells. Furthermore, TP53TG1 promoted PTEN expression via inhibiting miR-18a. Finally, TP53TG1 sensitized NSCLC cells to cisplatin in vivo. CONCLUSION: TP53TG1 increased the sensitivity of NSCLC cells to cisplatin by modulating miR-18a/PTEN axis, elucidating a novel approach to boost the effectiveness of chemotherapy for NSCLC.

Opinions Regarding Reuse or Replacement of Implant Prosthesis Retaining Screws: A Systematic Review.

PURPOSE: To identify whether reuse or replacement is better for managing loose screws. MATERIALS AND METHODS: An electronic search was performed utilizing PubMed, and a further manual search of the reference lists of relevant reviews and articles was conducted. Selected inclusion and exclusion criteria were used to limit the search. RESULTS: The electronic and manual search provided 243 titles and abstracts. Full-text analysis was performed for 98 articles, resulting in a total of 15 articles that qualified for inclusion in this study. All the included articles reported that loose screws were reused and retightened or were replaced by new screws. The time of screw loosening ranged from 1 month to 3 years after delivery. Available details of numbers and frequency of screw loosening permitted only limited analysis from very few articles. A total of 44 loose screws reported in two articles did not loosen again after retightening once. CONCLUSION: From the very limited available literature, it appears that retightening an occlusal screw or abutment screw is an acceptable procedure, as the evidence shows that retightened screws seem to remain tight. Replacement of screws as a routine procedure cannot be recommended. Routine assessment of screw tightness is recommended to minimize additional and more severe complications.

Radiologic and Clinicopathologic Findings of Inflammatory Myofibroblastic Tumor.

PURPOSE: The aim of the study was to describe the clinical, radiographic, and pathologic features of inflammatory myofibroblastic tumor (IMT) to enhance the recognition of this rare disease. MATERIALS AND METHODS: The clinical, imaging, and pathologic findings were retrospectively reviewed in 54 patients with IMT lesions, which were conformed by biopsy or surgical pathology. Of 54 patients, 51 had preoperative computed tomography (CT) examination and 13 had preoperative magnetic resonance imaging records. RESULTS: The clinical appearances of these 54 patients had some relationship with the locations of lesions. Of 54 IMT patients, 87.0% cases (47/54) had solitary lesion. The mean long diameter of the lesions located at the sites of chest, abdomen, and pelvic regions was bigger than that of other locations (F = 3.025, P = 0.038). On plain CT images, soft tissue mass was found in all IMT lesions, except for 3 lesions that arose in the intestine tract, appearing as focal or diffuse thickening in the bowel wall. After contrast administration, all lesions were persistently enhanced; 72.7% cases (24/33) demonstrated heterogeneous enhancement with various cystic regions. Comparing the CT features with different anatomic lesions, ill-defined margin on the plain CT images and calcification were seen more frequently in the lesions of the head and neck (P = 0.010 and 0.035); however, the other radiological findings had no significant differences (all P > 0.05). Twelve of 51 IMT patients showed invasion into adjacent structures. On magnetic resonance imaging, 92.3% lesions (12/13) showed soft tissue masses demonstrating isointense to hypointense contrast compared with skeletal muscle on T1-weighted images and heterogeneously high signals on T2-weighted images; 85.7%(6/7) of lesions were heterogeneously enhanced with cystic changes. Immunohistochemistry showed that the percentage of positive staining for SMA, vimentin, anaplastic lymphoma kinase, CD68, CD34, CD99, B-cell lymphoma/leukemia-2, cytokeratin, Desmin, and S-100 protein were 88.9%, 87.0%, 44.4%, 59.3%, 53.7%, 29.6%, 42.6%, 28.5%, 13.0%, and 24.1%, respectively. CONCLUSIONS: Inflammatory myofibroblastic tumor can involve any part of the body, and the clinical and radiological appearances are various owing to different anatomic sites. An ill-defined soft tissue mass heterogeneous enhancement with or without invasion into adjacent structures on computed tomographic or magnetic resonance images and positive staining for SMA and vimentin on immunohistochemical examination could suggest the diagnosis.

CT and clinical findings of peripheral primitive neuroectodermal tumour in children.

OBJECTIVE: To describe the clinical, CT and pathological findings of paediatric peripheral primitive neuroectodermal tumours (pPNETs) to enhance the recognition of these rare tumours. METHODS: The clinical, CT and pathological findings of 18 paediatric patients with pPNETs confirmed by biopsy or surgical pathology were retrospectively reviewed. RESULTS: The age of these 18 paediatric patients with pPNETs ranged from 4 months to 15 years, with a mean age of 7.7 years. The lesions of these 18 paediatric patients with pPNETs were located in the head and neck (n = 4), chest (n = 2), abdomen and pelvic cavity (n = 6), spine (n = 3), ilium (n = 2) and femur (n = 1). Immunohistochemical examination revealed Homer-Wright rosettes in seven lesions, and 94.4% of lesions showed consistent positive staining for CD99. On plain CT images, the majority of pPNETs showed lesions that were ill-defined (72.2%), irregularly shaped (83.3%), heterogeneous (66.7%) or hypodense masses (94.4%), and together with osteolytic bone destruction when the lesion originated in the bone. Calcifications were found in three lesions. After contrast administration, all soft-tissue masses were persistently enhanced heterogeneously with various cystic or necrotic regions, and 71.4% of them had linear enhancement. 94.4% of soft-tissue masses showed a moderate degree of enhancement. Seven cases had lymph node metastasis at diagnosis. CONCLUSION: Paediatric pPNET can involve any part of the body, and a large, ill-defined, aggressive soft-tissue mass and moderate heterogeneous enhancement with varying cystic regions and linear enhancement, with or without osteolytic bone destruction, on CT images could suggest the diagnosis. ADVANCES IN KNOWLEDGE: Primitive neuroectodermal tumours constitute a rare type of malignant neuroectodermal tumours that have chromosomal translocations identical to Ewing's sarcoma, and reports about radiological characteristics of this disease in children are insufficient. This study has described the clinical features and CT and pathological findings in 18 paediatric patients diagnosed with pPNETs in different locations, as a way to enhance the recognition of these tumours and help to differentiate from other types of paediatric malignant bone and soft-tissue tumours.

A pilot study using low-dose Spectral CT and ASIR (Adaptive Statistical Iterative Reconstruction) algorithm to diagnose solitary pulmonary nodules.

BACKGROUND: Lung cancer is the most common cancer which has the highest mortality rate. With the development of computed tomography (CT) techniques, the case detection rates of solitary pulmonary nodules (SPN) has constantly increased and the diagnosis accuracy of SPN has remained a hot topic in clinical and imaging diagnosis. The aim of this study was to evaluate the combination of low-dose spectral CT and ASIR (Adaptive Statistical Iterative Reconstruction) algorithm in the diagnosis of solitary pulmonary nodules (SPN). METHODS: 62 patients with SPN (42 cases of benign SPN and 20 cases of malignant SPN, pathology confirmed) were scanned by spectral CT with a dual-phase contrast-enhanced method. The iodine and water concentration (IC and WC) of the lesion and the artery in the image that had the same density were measured by the GSI (Gemstone Spectral Imaging) software. The normalized iodine and water concentration (NIC and NWC) of the lesion and the normalized iodine and water concentration difference (ICD and WCD) between the arterial and venous phases (AP and VP) were also calculated. The spectral HU (Hounsfield Unit ) curve was divided into 3 sections based on the energy (40-70, 70-100 and 100-140 keV) and the slopes (λHU) in both phases were calculated. The ICAP, ICVP, WCAP and WCVP, NIC and NWC, and the λHU in benign and malignant SPN were compared by independent sample t-test. RESULTS: The iodine related parameters (ICAP, ICVP, NICAP, NICVP, and the ICD) of malignant SPN were significantly higher than that of benign SPN (t = 3.310, 1.330, 2.388, 1.669 and 3.251, respectively, P <0.05). The 3 λHU values of venous phase in malignant SPN were higher than that of benign SPN (t = 3.803, 2.846 and 3.205, P <0.05). The difference of water related parameters (WCAP, WCVP, NWCAP, NWCVP and WCD) between malignant and benign SPN were not significant (t = 0.666, 0.257, 0.104, 0.550 and 0.585, P > 0.05). CONCLUSIONS: The iodine related parameters and the slope of spectral curve are useful markers to distinguish the benign from the malignant lung diseases, and its application is extremely feasible in clinical applications.

Radiologic and clinicopathologic findings of peripheral primitive neuroectodermal tumors.

BACKGROUND: Primitive neuroectodermal tumors (PNETs) constitute a rare type of malignant neuroectodermal tumors that have chromosomal translocations identical to Ewing's sarcoma (ES), and the characteristics of this disease remain unclear. PURPOSE: To describe the clinical, radiological, and pathological features of peripheral PNETs (pPNETs) to enhance their recognition. MATERIAL AND METHODS: The clinical, imaging, and pathologic findings of 35 patients with pPNETs were retrospectively reviewed, all being confirmed by biopsy or surgical pathology. All 35 patients had preoperative computed tomography (CT) examinations; 10 patients had preoperative magnetic resonance imaging (MRI) studies. RESULTS: Of 35 pPNET patients, 54.3% had a primary tumor in soft tissue, the others in bone. On plain CT images, 33 lesions demonstrated heterogeneous hypodense masses with multiple lamellar lower density, and with osteolytic destruction if the tumor originated in bone. Calcification was only found in five lesions arising in soft tissue. All lesions enhanced heterogeneously with varying areas of cystic changes, and all lesions in bone and 52.6% of lesions in soft tissue showed ill-defined margins after contrast administration. On MRI, these tumors appeared in conjunction with osteolytic bone destruction and irregular soft tissue masses iso- to hypointense to skeletal muscle on T1-weighted images and showed heterogeneously high intensity on T2-weighted images. All lesions enhanced heterogeneously with cystic changes. Homer-Wright rosettes were observed in 15 lesions, and 97.1% lesions were positive for CD99 in histopathological results. CONCLUSION: pPNETs can involve any part of the body, and a large, ill-defined, aggressive soft tissue mass and heterogeneous enhancement with or without osteolytic bone destruction on CT or MR images could suggest the diagnosis.

Attributable causes of esophageal cancer incidence and mortality in China.

BACKGROUND: To estimate the contribution of tobacco smoking, alcohol drinking, low vegetable intake and low fruit intake to esophageal cancer mortality and incidence in China. METHODOLOGY/PRINCIPAL FINDINGS: We calculated the proportion of esophageal cancer attributable to four known modifiable risk factors [population attributable fraction (PAF)]. Exposure data was taken from meta-analyses and large-scale national surveys of representative samples of the Chinese population. Data on relative risks were also from meta-analyses and large-scale prospective studies. Esophageal cancer mortality and incidence came from the 3(rd) national death cause survey and population-based cancer registries in China. We estimated that 87,065 esophageal cancer deaths (men 67,686; women: 19,379) and 108,206 cases (men: 83,968, women: 24,238) were attributable to tobacco smoking, alcohol drinking, low vegetable intake and low fruit intake in China in 2005. About 17.9% of esophageal cancer deaths among men and 1.9% among women were attributable to tobacco smoking. About 15.2% of esophageal cancer deaths in men and 1.3% in women were caused by alcohol drinking. Low vegetable intake was responsible for 4.3% esophageal cancer deaths in men and 4.1% in women. The fraction of esophageal cancer deaths attributable to low fruit intake was 27.1% in men and 28.0% in women. Overall, 46% of esophageal cancers (51% in men and 33% in women) were attributable to these four modifiable risk factors. CONCLUSIONS/SIGNIFICANCE: Tobacco smoking, alcohol drinking, low vegetable intake and low fruit intake were responsible for 46% of esophageal cancer mortality and incidence in China in 2005. These findings provide useful data for developing guidelines for esophageal cancer prevention and control in China.

[Effects of selenium and zinc on the proliferation of human esophageal cancer cell line studied by serophysiology].

OBJECTIVE: The effect of serum from rats supplemented with selenium and zinc on the proliferation of human esophageal cancer cell line Eca109 was observed by serophysiology. METHODS: Rats were randomly divided into seven groups. Eight rats in each group were fed with basic feeds (deprived of both selenium and zinc). The experimental rat groups were supplemented with selenium or zinc at low or high dosage intragastrically for 30 days Serum selenium and zinc content of rats was measured by Graphite Furnace Atomic Absorption Spectrometry (GFAAS) and Flame Atomic Absorption Spectrophotometry (FAAS). MTT assay,3H-TDR incorporation and flow cytometry were used to explore the effect of serum from different rat groups on the growth and proliferation of cancer cell line Ecal09 cells. RESULTS: (1) The content of serum zinc in the high zinc group was the highest and the content of serum zinc was the lowest in basic diet group. The content of serum selenium in high selenium and high zinc group was the highest and the content of serum selenium was the lowest in the basic diet group. (2) In comparing the growth of control cancer cell group cultured with calf serum, the growth of cancer cells cultured with the serum from high selenium and high zinc rats was inhibited in culturing for 72 h, but the growth of normal liver cells were also inhibited. The growth of cancer cells were promoted by serum from other groups. (3) Both MTT assay and 3H-TDR incorporation test showed that the DNA synthesis in cancer cells was inhibited by the serum from high selenium and high zinc group, but the DNA synthesis of normal liver cells was also inhibited by this type of serum. The result of DNA synthesis in other cell groups was closed to the control group. CONCLUSIONS: Low serum selenium and zinc might promote the growth of EC cell. Elevating the content of serum selenium and zinc by increasing selenium and zinc intake might inhibit EC cell proliferation.

Attributable causes of lung cancer incidence and mortality in China.

The aims of our study were to estimate the contribution of known lung cancer risk factors, and provide evidence to support the National Cancer Prevention and Control Program in China. We calculated the proportion of lung cancer attributable to specific risk factors. Data on exposure prevalence were from meta-analyses and large-scale national surveys of representative samples of the Chinese population. Data on relative risks were from meta-analyses and large-scale prospective studies. Lung cancer mortality and incidence were taken from the Third National Death Survey and from cancer registries in China. We estimated that in China 285 304 lung cancer deaths and 327 465 cases were attributable to smoking, involuntary smoking (women only), occupational exposure, indoor radon, and low fruit intake in 2005. The proportion of lung cancer deaths attributable to smoking, involuntary smoking among non-smoking women, occupational exposure, indoor radon and low fruit intake was 56.9%, 11.1%, 9.5%, 0.2% and 12.4%, respectively. About 41% of lung cancer mortality and incidence in women was caused by risk factors in our study. However, over half of lung cancer deaths and cases among women were not attributable to known risk factors. It is necessary to conduct large-scale studies to identify additional risk factors of lung cancer in non-smoking women.

Attributable causes of cancer in china: fruit and vegetable.

OBJECTIVE: To provide an evidence-based and consistent assessment of the burden of cancer attributable to inadequate fruit and vegetable intake in China in 2005. METHODS: The proportions of cancers attributable to low consumption of vegetable and fruit were calculated separately to estimate the burden of related cancers for the year 2005 in China. Data on the prevalence of exposure were derived from a Chinese nutrition and health survey. Data on relative risks were mainly derived from meta-analysis. Attributable fractions were calculated based on the counterfactual scenario which was a shift in the exposure distribution. RESULTS: The total cancer burden attributable to inadequate consumption of fruit was up to 233,000 deaths (13.0% of all cancers) and 300,000 cases (11.6% of all cancers) in 2005. Increasing consumption of vegetable to the highest quintile could avoid total cancer deaths and cases by 3.6% (64,000 persons) and 3.4% (88,000 persons). The contributions to cancer burden were higher in rural areas than in urban areas. They have greater influence on men than on women. The largest proportions of cancer burden attributable to low fruit and vegetable intake were for oral and pharyngeal cancers. CONCLUSION: This study showed that inadequate intake of fruit and vegetable makes a significant contribution to the cancer burden. Increasing consumption of fruit and vegetable could prevent many cancer deaths and save many lives. Promoting the consumption of fruit and vegetable is an important component in diet-based strategies for preventing cancer.

Estimation of cancer incidence and mortality attributable to alcohol drinking in China.

BACKGROUND: Cancer constitutes a serious burden of disease worldwide and has become the second leading cause of death in China. Alcohol consumption is causally associated with the increased risk of certain cancers. Due to the current lack of data and the imperative need to guide policymakers on issues of cancer prevention and control, we aim to estimate the role of alcohol on the cancer burden in China in 2005. METHODS: We calculated the proportion of cancers attributable to alcohol use to estimate the burden of alcohol-related cancer. The population attributable fraction was calculated based on the assumption of no alcohol drinking. Data on alcohol drinking prevalence were from two large-scale national surveys of representative samples of the Chinese population. Data on relative risk were obtained from meta-analyses and large-scale studies. RESULTS: We found that a total of 78,881 cancer deaths were attributable to alcohol drinking in China in 2005, representing 4.40% of all cancers (6.69% in men, 0.42% in women). The corresponding figure for cancer incidence was 93,596 cases (3.63% of all cancer cases). Liver cancer was the main alcohol-related cancer, contributing more than 60% of alcohol-related cancers. CONCLUSIONS: Particular attention needs to be paid to the harm of alcohol as well as its potential benefits when making public health recommendations on alcohol drinking.

Effects of a regional Chinese diet on proliferation of human esophageal cancer cell line Eca-109 by a sero-physiology method.

Esophageal squamous cell carcinoma (ESCC) is prevalent in Yanting (YT) country located in southwestern China. Residents in the YT region have an unusual diet pattern and the role of the YT diet on the risk of ESCC is still uncertain. The present study was to examine the possible effects of sera from rats fed with the YT diet on proliferation of human esophageal cancer cell line Eca-109 by means of a sero-physiology approach. Firstly, two feasibilities were assessed to set up the sero-physiology method. We found that rats fed with a human adult diet in Chengdu region (ESCC-low-risk-area) for 30d had very close body weight gains in comparison with the control rats fed with the conventional diet, confirming the feasibility of feeding rats with a human diet without affecting their normal growth. Cell growth results showed that 5% non-deactivated rat serum had exactly the same effect on the proliferation of Eca-109 cells compared with the fetal bovine sera (FBS) control, confirming the feasibility of cultivating Eca-109 cells with the rat serum instead of FBS. Subsequently, cell proliferation results indicated that rats' sera fed with the YT diet significantly promoted Eca-109 cells proliferation but inhibited human normal liver epithelial cell line control HL7702 proliferation, whereas rats' sera fed with the Chengdu diet didn't have these effects on the two cell lines. The different effects of the two human diets on proliferation of Eca-109 cells demonstrated that the sero-physiology method is effective in studying the relationship between diet and cancer, and there maybe exist cancer-promoting factors in the YT diet.

[Effect of selenium and zinc on the proliferation of human esophageal cancer Eca109 cell line in vitro].

OBJECTIVE: To observe the effect of selenium and zinc alone or in combination on the growth and proliferation of human esophageal cancer Eca109 cell line in vitro. METHODS: Different doses of sodium selenite and zinc sulfate were added into the culture medium of Eca109 cells and normal liver epithelial HL7702 cells (control), and the changes in the cell growth were assessed by means of cell growth curve, (3)H-thymidine incorporation assay and flow cytometry. RESULTS: High-concentration selenium (0.3 micro g/ml) and zinc (3.5 microg/ml) alone both obviously inhibited Eca109 cell proliferation, and the inhibitory effect was enhanced by a combined treatment. At high concentrations, both selenium and zinc promoted HL7702 cell proliferation, but when combined, they produced inhibitory effect on the cell growth. Selenium and zinc at the physiological concentrations ( 0.1 microg/ml and 1.0 microg/ml, respectively) produced similar effects on Eca109 cells and the control cells. Selenium at 0.3 microg/ml caused Eca109 cell growth arrest in S phase, but this effect was not statistically significant; 3.5 microg/ml zinc significantly increased the number of Eca109 cells in G(1) phase. When combined, 0.3 microg/ml selenium and 3.5 microg/ml zinc caused significant G(1) arrest and promoted apoptosis of the cancer cells, an effect stronger than that of either of the agents used alone. CONCLUSION: High-concentration selenium and zinc show a synergetic effect in inducing growth inhibition of human esophageal cancer Eca109 cell line possibly by causing cell cycle arrest and promoting cell apoptosis, and their combined use can be toxic to normal human liver epithelial cells.