Boosting ferroptosis and microtubule inhibition for antitumor therapy via a carrier-free supermolecule nanoreactor / 药物分析学报

Traditional microtubule inhibitors fail to significantly enhance the effect of colorectal cancer;hence,new and efficient strategies are necessary.In this study,a supramolecular nanoreactor(DOC@TA-Fe3+)based on tannic acid(TA),iron ion(Fe3+),and docetaxel(DOC)with microtubule inhibition,reactive oxygen species(ROS)generation,and glutathione peroxidase 4(GPX4)inhibition,is prepared for ferroptosis/apoptosis treatment.After internalization by CT26 cells,the DOC@TA-Fe3+nanoreactor escapes from the lysosomes to release payloads.The subsequent Fe3+/Fe2+conversion mediated by TA reducibility can trigger the Fenton reaction to enhance the ROS concentration.Additionally,Fe3+can consume gluta-thione to repress the activity of GPX4 to induce ferroptosis.Meanwhile,the released DOC controls microtubule dynamics to activate the apoptosis pathway.The superior in vivo antitumor efficacy of DOC@TA-Fe3+nanoreactor in terms of tumor growth inhibition and improved survival is verified in CT26 tumor-bearing mouse model.Therefore,the nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer therapy.

Review on role of NLRP3 inflammasome in pathogenesis of silicosis / 环境与职业医学

Silicosis is one of the most common forms of pneumoconiosis globally. Workers who engage in mining, construction, ceramics, and many other industries have a high risk of developing silicosis. Chronic and repeated inhalation of free silica (SiO2) dust (<5 μm) during working can lead to inflammatory reactions, resulting in interstitial lung disease characterized by extensive nodular fibrosis in both lungs. Once silicosis occurs, it will develop progressively even when the workers are removed from the silica dust environment. The pathogenesis of silicosis is complex, especially the role of nod-like receptor family protein 3 (NLRP3) inflammasome in the pathogenesis and progression of silicosis remains to be further studied. NLRP3 inflammasome, a multi-protein complex composed of NLRP3, apoptosis-associated speck-like protein, and cysteinyl aspartate specific proteinase 1 is involved in oxidative stress, inflammatory response, apoptosis, and pyroptosis, and has become one of the hot spots in silicosis research. This review summarized the structure, function, and activation mechanism of NLRP3 inflammasome. Furthermore, the cellular and molecular mechanisms of NLRP3 in mediating oxidative stress, inflammatory response, apoptosis, and pyroptosis in the progression of silicosis were reviewed. Finally, the potential therapeutic drugs for silicosis based on NLRP3-associated mechanisms were outlined. More attention should be paid to the role of NLRP3 inflammasome in the pathogenesis and progression of silicosis in the future, which will provide new ideas for the prevention and treatment of silicosis.

Research progress of C-X-C motif chemokine ligand 12 and its receptor signaling axis in the regulation of pulmonary fibrosis / 中华劳动卫生职业病杂志

Pulmonary fibrosis is an irreversible interstitial lung disease characterized by lung parenchyma remodeling and collagen deposition. In recent years, the incidence and mortality of pulmonary fibrosis caused by unknown causes have risen. However, its pathogenesis is still unclear. C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C chemokine receptor 4 (CXCR4)/CXCR7 signal axis plays a critical regulatory role in pulmonary fibrosis disease. In addition, the signal axis has been shown to regulate recruitment and migration of circulating fibrocytes, mesenchymal stem cells to the damage lung tissue, the migration of endothelial cells, the proliferation and differentiation of fibroblasts and endothelial cells, which further affects the occurrence and progression of pulmonary fibrosis. In this review, we summarized the pathogenesis and treatment research progress of CXCL12 and its receptor CXCR4/CXCR7 in the occurrence and progression of pulmonary fibrosis.

Construction and Verification of a Radiation Pneumonia Prediction Model Based on Multiple Parameters.

OBJECTIVE: Patients with lung cancer are at risk of radiation pneumonia (RP) after receiving radiotherapy. We established a prediction model according to the critical indicators extracted from radiation pneumonia patients. MATERIALS AND METHODS: 74 radiation pneumonia patients were involved in the training set. Firstly, the clinical data, hematological and radiation dose parameters of the 74 patients were screened by Logistics regression univariate analysis according to the level of radiation pneumonia. Next, Stepwise regression analysis was utilized to construct the regression model. Then, the influence of continuous variables on RP was tested by smoothing function. Finally, the model was externally verified by 30 patients in validation set and visualized by R code. RESULTS: In the training set, there was 40 patients suffered≥ level 2 acute radiation pneumonia. Clinical data (diabetes), blood indexes (lymphocyte percentage, basophil percentage, platelet count) and radiation dose (V15 > 40%, V20 > 30%, V35 >18%, V40 > 15%) were related to radiation pneumonia (P < 0.05). Particularly, stepwise regression analysis indicated that the history of diabetes, the basophils percentage, platelet count and V20 could be the best combination used for predicting radiation pneumonia. The column chart was obtained by fitting the regression model with the combined indicator. The receiver operating characteristic (ROC) curve showed that the AUC in the development term was 0.853, the AUC was 0.656 in the validation term. And calibration curves of both groups showed the high stability in efficiently diagnostic. Furthermore, the DCA curve showed that the model had a satisfactory positive net benefit. CONCLUSION: The combination of the basophils percentage, platelet count and V20 is available to build a predictive model of radiation pneumonia for patients with advanced lung cancer.

Identification of Key Genes in Lung Adenocarcinoma and Establishment of Prognostic Mode.

BACKGROUND: The development of human tumors is associated with the abnormal expression of various functional genes, and a massive tumor-based database needs to be deeply mined. Based on a multigene prediction model, access to urgent prognosis of patients has become possible. MATERIALS AND METHODS: We selected three RNA expression profiles (GSE32863, GSE10072, and GSE43458) from the lung adenocarcinoma (LUAD) database of the Gene Expression Omnibus (GEO) and analyzed the differentially expressed genes (DEGs) between tumor and normal tissue using GEO2R program. After that, we analyzed the transcriptome data of 479 LUAD samples (54 normal tissue samples and 425 cancer tissue samples) and their clinical follow-up data from the (TCGA) database. Kaplan-Meier (KM) curve and receiver operating characteristic (ROC) were used to assess the prediction model. Multivariate Cox analysis was used to identify independent predictors. TCGA pancreatic adenocarcinoma datasets were used to establish a nomogram model. RESULTS: We found 98 significantly prognosis-related genes using KM and COX analysis, among which six genes were found to be the DEGs in GEO. Using multivariate analysis, it was found that a single gene could not be used as an independent predictor of prognosis. However, the risk score calculated by weighting these six genes could serve as an independent prognosis predictor. COX analysis performed with multiple covariates such as age, gender, tumor stage, and TNM typing showed that risk score could still be utilized as an independent risk factor for patient survival rate (p = 0.013) and had an applicable reliability (area under the curve, AUC = 0.665). By combining risk score and various clinical features, the nomogram model was constructed, which had been proven to have high consistency for the prediction of 3- and 5-year survival rate (concordance = 0.751) and high accuracy as tested by ROC (AUC = 0.71;AUC = 0.708). CONCLUSION: We proposed a method to predict the prognosis of LUAD by weighting multiple genes and constructed a nomogram model suitable for the prognostic evaluation of LUAD, which could provide a new tool for the identification of therapeutic targets and the efficacy evaluation of LUAD.

Artesunate promotes sensitivity to sorafenib in hepatocellular carcinoma.

Enhancing sensitivity of carcinoma to sorafenib (Sor) is critical to overcome the limits of high frequency resistance and moderate efficiency during chemotherapy for advanced hepatocellular carcinoma (HCC). Here, we promote sensitivity of HCC to Sor by combination with Artesunate (Art), a derivative of artemisinin extracted from Chinese medical herb. The positive synergy of Art on inhibiting HCC growth contributes 48% dosage of Sor to reduce tumor cell viability in vitro and tumor size in vivo. Mechanically, in spite of effective suppression of RAF/MEK/ERK pathway, Sor is not able to eliminate chemoresistance of HCC driven by PI3K/AKT/mTOR pathway, while Art inhibits phosphorylation of AKT and mTOR significantly. Furthermore, combination with Art and Sor further improves apoptosis of HCC by dual inhibition of both pathways. Our study reveals a function of Art that induces HCC apoptosis via PI3K/AKT/mTOR pathway inhibition and suggests a potential therapeutic regimen of combination with Art and SOR against advanced HCC.

Dependence of artesunate on long noncoding RNA-RP11 to inhibit epithelial-mesenchymal transition of hepatocellular carcinoma.

As a first line medicine for malaria treatment, artesunate (ART) also shows antitumor potential. However, little is known about the effect of ART on the cancer cell epithelial-mesenchymal transition (EMT). In this study, we found that ART inhibited cell growth in SK-HEP1 and SM7721 hepatocellular carcinoma cell lines. A microarray was used to identify differentially expressed protein-coding RNAs (pcRNA) and long noncoding RNAs (lncRNA) between SK-HEP1 cells with and without ART treatment. A differentially expressed lncRNA-RP11, the most related to the EMT of liver cancer cells-RP11 was identified by abioinformatics method Overexpressing and silencing assays were used to verify the role of RP11 in cancer cell EMT. The levels of RP11- and EMT-related genes in liver cancer samples from 75 patients were detected by using qualitative polymerase chain reaction or immunohistochemistry. We identified 1334 pcRNAs and 1670 lncRNA with differential expression induced by ART. ART inhibits EMT, proliferation, migration, invasion, and adhesion of liver cancer cells. RP11 depresses the inhibitory effect of ART on cancer cell EMT. The level of RP11 is associated with cancer cell EMT and metastasis and survival rate of the patient. These data suggest that RP11-linking ART and cancer cell EMT are important for ART-inhibited metastasis of liver cancer.

Survey of epidemic status of paragonimiasis in western mountainous areas in Hubei Province / 中国血吸虫病防治杂志

Objective To understand the current status of paragonimiasis epidemic in western mountain areas in Hubei Prov-ince. Methods Four counties(cities)of Western Hubei Province(Xingshan,Enshi,Yunxi,Baokang)were selected as the investigation sites for active surveillance. Crabs were captured and the metacercariae of Paragonimus were detected. Meanwhile, the blood samples were collected from the residents in the surveillance sites and the unique IgG and IgM antibodies against Para-gonimus in the sera were detected by ELISA. In addition,a questionnaire survey about knowledge and behavior of prevention and control of paragonimiasis was taken among the residents. Results A total of 1143 residents were investigated in the active surveillance,the total positive rate of the serology test was 1.84%(21/1143),while the rates of the male and the female were 1.78%(10/562)and 1.89%(11/581),respectively,with no statistical significance between them(χ2=0.002,P>0.05). The average weight of 161 fresh-water crabs captured was 11.72 g,with the positive rate of 9.32%(15/161)and the infective density of 7.07 metacercariae per positive crab. The positive rates of the male and female crabs were 11.54%(9/78)and 7.23%(6/83), respectively(χ2=0.884,P>0.05),and the infective densities were 6.67 and 7.67 metacercariae per positive crab,respective-ly. Totally 1143 residents were investigated by questionnaires,and 0.44%of them had the behavior of eating raw or half-done fresh-water crab,and 0.87% of them had the behavior of drinking un-boiled stream water. Conclusions The transmission chain of paragonimiasis still exists in the nature environment of mountain area in Western Hubei Province. The positive rate of the second intermediate host rebounds in some investigation sites. Therefore,the measures of continuous surveillance and health education should be taken to avoid the appearance of the prevalence or outbreak.

Effect of miR-200a on the proliferation, migration and apoptosis of lung cancer cell line A549 / 临床与实验病理学杂志

Purpose To investigate the expression of miR200a in different lung cancer cell lines and its effect on proliferation,migration,and apoptosis in A549 cells.Methods The expressions of miR-200a in different lung cancer cell lines were detected by RT-PCR.miR-200a mimics was transfected into A549 cells by Lipofectamine RNAiMax.The change of proliferation ablility of A549 cells was detected by CCK-8 method and plate clone formation assay.Cell migration was examined by Transwell chamber assay.The flow cytometry was used to examine the changes of apoptosis.The possible target genes of miR-200a were forecasted by bioinformatics tools.Results The results of RT-PCR showed that the expression of miR-200a was significantly down-regulated in A549,H23 and H460 cell lines than 16HBE cell line.CCK-8 assay showed that the OD values of the mimics group at 4,and 5 days were significantly lower than those in the negative control (NC) group (P ＜ 0.05).Plate clone formation assay showed rate of colony formation in the mimics group was significantly lower than that in the NC group [(33.13±0.74)％ vs (45.57 ±1.27)％,P＜0.05].Transwell migration assay showed that the cell number of mimics group that passed the Transwell membrane was significantly lower than that of the NC group [(71.60 ± 17.90) vs (140.20 ± 17.88),P ＜0.05].Flow cytometry showed that the apoptosis rate of the mimics group was significantly higher than that of the NC group [(17.80± 1.90)％ vs (11.33 ± 1.96)％,P ＜ 0.05].Tiam1 may be one of the target gene of miR-200a.Conclusion miR-200a can inhibit the proliferation and migration,and promote apoptosis of lung cancer A549 cells,suggesting a potential new therapeutic agent for lung cancer cell.MiR-200a may play a function of regulation of tumor development through target gene Tiam1.

A study on the relationship between the lifestyle and chronic non-communicable diseases of the landless peasants / 中华疾病控制杂志

Objective To investigate the prevalence of chronic non-communicable diseases among farmers,land less peasants and urban population in a certain area of Anhui Province,to explore the relationship between the lifestyles of landless peasants and their chronic non-communicable diseases.Methods A total of 761 valid questionnaires were collected by cross-sectional epidemiological study,including 119 farmers,259 landless peasants and 383 urban groups.The enumeration data was analyzed by x2 test and the measurement data analyzed by variance.The risk of chronic non-communicable diseases in each group was analyzed by Logistic regressions.Results General demographic characteristics showed that there were differences in three groups of people in the respects of drinking,eating habits and physical activity and other lifestyles (all P ＜ 0.05).Logistic regression analysis showed that the onset risk of hypertension and overweight obesity in the famer group and the landless peasant group was lower than that in the urban group,but higher than that in the peasant group.After adjusting for confounding factors,the prevalence of hypertension in the farmer group (OR =0.20,95％ CI:0.12-0.33) and the lost land group (OR =0.65,95％ CI:0.44-0.95) was lower than that in the urban group,the overweight obesity in the farmer group (OR =0.44,95％ CI:0.27-0.74) and the lost land group(OR =0.67,95％ CI:0.47-0.96) was lower than that in the urban group.The incidence of atherosclerosis in the farmer group (OR =2.48,95 ％ CI:1.45-4.23) and the lost land group(OR =2.00,95％ CI:1.33-3.02) was higher than that in the urban group.Conclusions The living style of landless peasants is different from those of rural group and urban group,and the incidence of hypertension and overweight obesity is higher than that of farmers.We should take interventions against chronic non-communicable diseases in landless peasants.

ESAT6 inhibits autophagy flux and promotes BCG proliferation through MTOR.

In recent years, increasing studies have found that pathogenic Mycobacterium tuberculosis (Mtb) inhibits autophagy, which mediates the anti-mycobacterial response, but the mechanism is not clear. We previously reported that secretory acid phosphatase (SapM) of Mtb can negatively regulate autophagy flux. Recently, another virulence factor of Mtb, early secretory antigenic target 6 (ESAT6), has been found to be involved in inhibiting autophagy, but the mechanism remains unclear. In this study, we show that ESAT6 hampers autophagy flux to boost bacillus Calmette-Guerin (BCG) proliferation and reveals a mechanism by which ESAT6 blocks autophagosome-lysosome fusion in a mammalian target of rapamycin (MTOR)-dependent manner. In both Raw264.7 cells and primary macrophages derived from the murine abdominal cavity (ACM), ESAT6 repressed autophagy flux by interfering with the autophagosome-lysosome fusion, which resulted in an increased load of BCG. Impaired degradation of LC3Ⅱ and SQSTM1 by ESAT6 was related to the upregulated activity of MTOR. Contrarily, inhibiting MTOR with Torin1 removed the ESAT6-induced autophagy block and lysosome dysfunction. Furthermore, in both Raw264.7 and ACM cells, MTOR inhibition significantly suppressed the survival of BCG. In conclusion, our study highlights how ESAT6 blocks autophagy and promotes BCG survival in a way that activates MTOR.

Establishment of rat model of silicotuberculosis and its pathological characteristic.

OBJECTIVE: To establish different stages of silicosis rat model complicated with tuberculosis infection, and compare the pathological characteristics and analyze the impact of silicosis on tuberculosis infection. METHODS: SD rats were subjected to intratracheal administration of silica with non-exposure method at the 1st, 30th, or 60th day. At the 50th day, the rats were injected with the suspension of H37Rv (a virulent standard strain of Mycobacterium tuberculosis) via tail-vein. After 40 days post-infection, rats were sacrificed, the lung tissues were isolated, and paraffin was embedded and sectioned. The sections were treated using HE staining for structure observation, acid fast stain of Ziehl-Neelsen for bacterial detection, and Warthin-Starry silver staining for displaying the distribution of dust particles. The bacterial load was quantified by colony counting. RESULTS: Primary to tertiary silicosis could be discovered at the 30th, 60th, and 90th day of post-infection. The rats could be infected by injection of M. tuberculosis via tail vein, with tuberculosis load and the degree of lung tissue lesions positively correlated with silicosis. CONCLUSION: The rat model of silicotuberculosis was established successfully, which facilitated understanding the 'cross-talk' of silicosis and tuberculosis during the process they drive each other.

Control study on life style on college students from urban and rural / 中华行为医学与脑科学杂志

Objective To explore the differences of the life styles and their influencing factors among students who came from city,countryside or migrant families.Methods The stratified cluster random sampling method was conducted to recruit 1980 college students from 4 colleges of Huainan,Anhui.Results The study showed that under the ternary social structure college students from city preferred to the higher degree of T1,T2 or T3 dietary patterns,of which the OR (95％ CI) were 0.432 (0.255-0.730),0.140 (0.073-0.267) and 0.402 (0.236-0.683),respectively.They chose to exercise in middle-intensity physical activity for 30 minutes,of which OR (95％CI) was 0.524(0.352-0.779).Also there were much more drinkers in this group,of which the OR (95％ CI) was 0.564(0.325-0.981).Secondly,college students from migrant families in city preferred to T2 and T4 dietary pattern in low degree,of which OR (95％ CI) were 1.714(1.165-2.519) and 1.592(1.100-2.305),respectively.And they exercise 5 times or less per week in middle-intensity physical activity and the OR (95％ CI) was 0.699(0.535-0.912).Thirdly,college students from countryside preferred to T1,T2 and T3 dietary pattern in low degree and the OR (95％ CI) were 1.548 (1.083-2.213),1.498 (1.048-2.141) and 1.740(1.216-2.491),respectively.However,they preferred T4 dietary pattern in high degree rather than in low degree,in which the OR (95％ CI) was 0.624(0.436-0.893).They exercise more than 5 times and more than 30 minutes per time in middle-intensity physical activity,of which OR (95 ％ CI) were 1.314 (1.022-1.688) and 1.472 (1.071-2.022).Conclusion College students from three groups lived in different life styles and much more attention should be paid to them.

Influence of different dietary patterns on bone mineral density and body mass index of college freshmen in nrban and rural areas of China / 中华流行病学杂志

Objective To find out the differences of dietary patterns among freshmen coming from urban and rural areas that might have influenced their bone mineral density and body mass index (BMI).Methods With stratified random sampling method,dietary patterns and their bone mineral density,BMI of 1319 freshmen were studied.Results (1) The ratios of urban freshunen who chose "western food" pattern ( x2=31.548,P=0.000; x2=13.068,P=0.001 ),"animal food" pattern ( x2=8.279,P=0.016; x2=41.137,P=0.000) or "calcium food" pattern (x2=37.254,P=0.000; x2=15.651,P=0.000) were higher than that of rural freshmen,and the ratios of rural freshmen who chose "Chinese traditional" pattern (x2=36.194,P=0.000; x2=25.936,P=0.000) were higher than that of urban freshmen.(2) The average height,weight,BMI,speed of sound (SOS) of male freshmen from rural areas were lower than that from the city and the differences were statistically significant (P＜0.05).Among those female freshmen,only height and weight were significantly different (P＜0.05).(3) In both rural and urban frestunen,the factor scores of "westem food" pattern had a positive correlation with BMI,with the correlation coefficients as 0.187,0.192,0.551,0.465 (P＜0.001).The factor scores of "calcium food" pattern were positively related to bone mineral density (SOS values)with correlation coefficients as 0.680,0.342,0.841,0.786,P＜ 0.001 respectively.The factor scores on "Chinese traditional" pattern were negatively correlated with BMI,with correlation coefficients as -0.223,-0.093 (P＜0.05) which were positively related to bone mineral density (SOS values) in both rural and urban male freshmen,with correlation coefficients as 0.905,0.711 (P＜0.001).Conclusion Different dietary patterns chosen by urban and rural freshmen had a significant impact on both bone mineral density and BMI.

Dietary patterns and its influencing factors among freshmen students in college / 中华流行病学杂志

Objective To investigate the dietary pattern in college freshmen students and to analyze the influencing factors on their dietary patterns. Methods A questionnaire survey on situation of dietary pattern and influencing factors was conducted among 1319 freshmen students.Results Four major dietary patterns were noticed and they were: Ⅰ , high consumption in hamburger,fried food, nuts, biscuit, chocolate, cola, coffee, sugars, Ⅱ, high consumption in pork, mutton, beef,poultry meat, animal liver, Ⅲ, high consumption in fresh fruits, eggs, fish and shrimps, kelp laver and sea fish, milk and dairy products, beans and bean products, Ⅳ, high consumption in rice and grain,fresh fruits, fresh vegetables, pork. Risk factors on dietary pattern were presented as follows: ( 1 )boys: having the food pattern Ⅰ and Ⅱ showed a strong positive association with the place where they live (OR= 1.67, 95％CI: 0.87-3.19; OR= 1.51,95％CI: 0.79-2.88), eating place (OR=1.63,95％CI: 1.O3-2.59; OR= 1.83, 95％CI: 1.04-3.23), level of mother' s education (OR=2.52,95％CI: 1.07-5.95; OR=3.38, 95％CI: 1.50-7.63), family income (OR=2.24, 95％CI: 1.30-3.88;OR=3.06, 95％ CI: 1.77-5.29) and the status of passive smoking (OR= 1.80, 95％CI: 0.70-4.59;OR=1.83, 95％CI: 0.75-4.45). Inverse correlations was found on the level of mother's education (OR=0.56,95％CI: 0.17-1.79). The food pattern Ⅳ showed a strong positive association with place of eating(OR= 1.83,95％CI: 1.04-3.23) but having an inverse correlation with the level of mother's education (OR=0.56, 95％CI: 0.17-1.79). (2)girls when compared with boys, the food pattern Ⅰ showed minor association with the places of living and eating; while the food pattern Ⅱ and Ⅲ had minor association with the status of passive smoking. Conclusion Socio-demographic factors and lifestyle had influenced on the dietary patterns among college freshmen students who should be guided to have a reasonable, balanced diet in the college.

Evaluation of the value of ultrasound-guided core needle biopsy in the diagnosis of breast lesions / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the accuracy, consistency and related affecting factors in pathological results of breast lesions diagnosed by ultrasound-guided core needle biopsy (CNB) and conventional excision histopathology.</p><p><b>METHODS</b>The clinical data of 177 consecutive cases of breast lesions examined by ultrasound-guided CNB and subsequently excised were reviewed from Jan. 2003 to Nov. 2009. The agreement of pathological diagnosis between the CNB and subsequent excision pathology was analyzed.</p><p><b>RESULTS</b>There were 136 cancers in the final diagnosis after surgical excision among 386 breast lesions and 129 of them were diagnosed by CNB. The sensitivity (true positive) of CNB was 94.9%, false negative rate was 5.1%, specificity (true negative) was 100%, false positive rate 0, Youden's index was 0.949, and positive predictive value and negative predictive value were 100% and 85.4%, respectively. Condensation rate was 96.0% and Kappa value was 0.895.</p><p><b>CONCLUSION</b>Ultrasound-guided CNB with histopathological assessment is accurate in diagnosis of breast lesions and has a great consistency with conventional excision pathology. It is a reliable method for the diagnosis of breast lesions to avoid an over-reliance on excision pathological examination.</p>