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BACKGROUND@#The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex.@*METHODS@#The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases.@*RESULTS@#WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group.@*CONCLUSIONS@#This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
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Animals , Mice , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Mutation , Liver Neoplasms/geneticsABSTRACT
Tear film hyperosmolarity plays a core role in the development of dry eye disease (DED) by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface epithelium. In this study, the mechanisms involving the hyperosmolar microenvironment, glycolysis mediating metabolic reprogramming, and pyroptosis were explored clinically, in vitro, and in vivo. Data from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes, including PKM2 and GSDMD, was significantly upregulated and that the secretion of IL-1β significantly increased. In vitro, the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells (HCECs) was used to discuss the interaction among cells. The hyperosmolar environment was found to greatly induce HCECs' metabolic reprogramming, which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression. 2-Deoxy-d-glucose (2-DG) could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of macrophages. In vivo, 2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis. In summary, our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis.
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Objectives To analyze and understand the risk factors related to HIV new infections among men who have sex with men (MSM).Methods A longitudinal observational study among MSM was conducted to collect information on HIV related behaviors and sero-conversion.Univariate and multivariate generalized estimating equations (GEE) were used to discuss the risk factors for HIV new infection.Results A total number of 4 305 MSM were followed during 2013-2015.Among those self-reported MSM who are seeking partners on the Interner tended to have higher proportion on receptive anal intercourse and consistent condom use during anal intercourse than the subgroups seeking their partners in gay bars or bathrooms.HIV incidence among followed MSM during the study period appeared as 4.3/100 person years,with adjusted RR (aRR) of HIV infection for receptive anal intercourse as group 2.20 (95％ CI:1.49-3.24) times than that of insertion anal intercourse group.Those who used rush-poppers (aRR=1.55,95％CI:1.10-2.17),unprotected anal intercourse (aRR=2.24,95％ CI:1.62-3.08),and those with syphilis infection (aRR=2.95,95％ CI:2.00-4.35) were also risk factors for HIV new infections.After controlling other factors,the relationship between the ways of seeking partners and HIV new infection was not statistical significant.Conclusion Risk factors for HIV new infection among MSM appeared complex and interactive,suggesting that further studies are needed to generate tailored strategies for the prevention of HIV epidemic among MSM population.
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Objectives To analyze and understand the risk factors related to HIV new infections among men who have sex with men (MSM).Methods A longitudinal observational study among MSM was conducted to collect information on HIV related behaviors and sero-conversion.Univariate and multivariate generalized estimating equations (GEE) were used to discuss the risk factors for HIV new infection.Results A total number of 4 305 MSM were followed during 2013-2015.Among those self-reported MSM who are seeking partners on the Interner tended to have higher proportion on receptive anal intercourse and consistent condom use during anal intercourse than the subgroups seeking their partners in gay bars or bathrooms.HIV incidence among followed MSM during the study period appeared as 4.3/100 person years,with adjusted RR (aRR) of HIV infection for receptive anal intercourse as group 2.20 (95％ CI:1.49-3.24) times than that of insertion anal intercourse group.Those who used rush-poppers (aRR=1.55,95％CI:1.10-2.17),unprotected anal intercourse (aRR=2.24,95％ CI:1.62-3.08),and those with syphilis infection (aRR=2.95,95％ CI:2.00-4.35) were also risk factors for HIV new infections.After controlling other factors,the relationship between the ways of seeking partners and HIV new infection was not statistical significant.Conclusion Risk factors for HIV new infection among MSM appeared complex and interactive,suggesting that further studies are needed to generate tailored strategies for the prevention of HIV epidemic among MSM population.
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Objective To investigate the density seasonal fluctuation and insecticide resistance of Anopheles sinensis in the Taibai Lake area and to provide a scientific basis for formulation of Anopheles sinensis control strategy.Methods The surveillance was carried out from June to October in 2013-2016.The adult mosquito density was monitored using human bait trapping method.WHO bioassay method was used to measure the sensibility of mosquitoes to insecticides.Results In 2013-2016,totally 2 318 Anopheles sinensis were captured,the Anopheles sinensis peaked in late July till early August,which were 67-127,317-386,77-89,107-139,respectively.Anopheles sinensis showed high resistance to dichlorodiphenyltrichloroethane,malathion,and initial resistance to propoxur and deltamethrin (mortality ratio:38.10％,41.82％,86.11％,83.02％).Conclusions The Taibai Lake area has a diverse Anopheles sinensis population,its seasonal fluctuations and insecticide resistance monitoring can provide effective guidance for malaria control.In order to prevent the development of resistance to the insecticides,integrated management measures should be adopted in the future.
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BACKGROUND:Delayed graft function (DGF) occurs frequently in kidney transplants from donation after cardiac death if creatinine level is high in kidney recipients. OBJECTIVE:To analyze the clinical effects of renal transplantation with kidneys from donors dying of cardiac death in organophosphate poisoning. METHODS:Data were col ected from kidney transplants from two donors dying of cardiac death in organophosphate poisoning. After some donor maintenance, donor organ were obtained and perfused with impulse type machine. Recipients were treated with intervention of immunity induction, anti-rejection drugs and infection prevention drugs during and after renal transplantation. Pathological data of donor kidney zero needle biopsy, DGF after kidney transplantation, complication rate (such as acute rejection), renal al ograft recovery situation, the survival rate of recipients and kidney transplants were col ected and analyzed. RESULTS AND CONCLUSION:Needle biopsy results from four donor kidneys showed that glomerular morphology was normal, but there were edema and degeneration in kidney tubules in some degree. Donor DGF rate was 75%(3/4), acute rejection rate was 0%(0/4), perioperative period donor kidney and recipient survival rate were 100%(4/4). Al recipients showed a good result of transplanted kidney, their creatinine and urea nitrogen were at low level, and had no proteinuria. One recipient died of severe pulmonary infection 4 months after surgery. For some organophosphate poisoning donors dying of cardiac death, donor kidney quality can be improved by suitable donor maintenance and high-quality donor kidney preservation using machine perfusion. Kidney transplants from donors dying of cardiac death in organophosphate poisoning who receive the maintenance of organ function may be a promising candidate for renal transplantation due to a severe lack of kidney donor sources.
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<p><b>OBJECTIVE</b>To evaluate the efficacy of endoscopic purse-string suture (EPSS) with metallic clips and endoloop for the gastric wall defect after postoperative perforation.</p><p><b>METHODS</b>Clinical data of 25 patients with gastric tumors(1 of gastric adenocarcinoma, 24 of gastric gastrointestinal stromal tumor, GIST) undergoing EPSS in Jiangsu Province People's Hospital and The Second Affiliated Hospital of Nanjing Medical University from January 2013 to May 2014 were retrospectively analyzed. During the procedure, EPSS was performed in 8 cases with perforation after endoscopic submucosal dissection(ESD), and in 17 cases with active perforation after endoscopic full-thickness resection.</p><p><b>RESULTS</b>Twenty-five patients underwent EPSS successfully. The procedure time was 35.0-75.0(49.8±10.1) min. No severe operational and postoperative complications occurred. Tumor resection margin were all negative. Time to withdraw gastrointestinal decompression drainage tube was 1-3(1.3±0.8) d. Postoperative hospital stay was 2-10(4.8±2.1) d and total cost was 10-31(19±0.5) thousand Yuan. One month after the procedure, all the patients received follow-up with no complaint of discomfort, and endoscopy confirmed that all the lesions healed.</p><p><b>CONCLUSION</b>EPSS with metallic clips and endoloop is effective and safe to close the gastric wall defect after full-thickness resection.</p>
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Humans , Adenocarcinoma , Digestive System Surgical Procedures , Gastrointestinal Stromal Tumors , Gastroscopy , Postoperative Complications , Postoperative Period , Retrospective Studies , Stomach Neoplasms , SuturesABSTRACT
Body mass index [BMI] has been demonstrated to be associated with serum uric acid [SUA] level in many developed countries, however, there is still a lack of large sample study in Jiangsu Province, one of the most economically developed regions in China, where fat-rich diet is common. Through retrospective analysis in healthy subjects, we determined the association of BMI with hyperuricemia risk. Data of 39,736 participants from January 2011 to June 2013 in China were analyzed for parameters including physical examinations and biochemical blood analysis. On univariate analysis, SUA was positively correlated with age, SBP, DBP, BMI, FPG, red blood cell count, hemoglobin, white blood cell count, platelet, cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, ALT, AST, bilirubin, albumin, BUN and creatinine. SUA was significantly elevated in a linear fashion as BMI increased, and SUA in obesity was significantly higher than underweight. The prevalence of hyperuricemia remained approximately 2.98 times greater among individuals with overweight, and 5.96 times greater among obesity, compared to individuals with underweight. There is a positive relationship between BMI and SUA among healthy subjects in Jiangsu province, China
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Humans , Male , Female , Body Mass Index , Cross-Sectional Studies , Retrospective StudiesABSTRACT
Objective To study the biological characteristics of cypermethrin?resistance strain and?susceptible strain of Ae?des albopictus under different controlled temperatures in the laboratory. Methods The two strains were raised at three different temperatures 20 25℃and 28℃respectively and the biological characteristics of the two mosquito strains such as reproduc?tion development and life expectancy were observed and recorded in the laboratory. Results The life expectancy of both strains became shorter as the temperature raised and the resistant strain 69.37%± 0.01% 77.04%± 0.07% lived shorter than the susceptible strain 85.24%±0.03% 88.23%±0.05% in average. Under 25℃ the hatching rate of resistant strain decreased by 25.88% and the pupation rate decreased by 11.18%. In the three temperatures all the life expectancy expanded as the tem?perature went up the periods for the susceptible strain were 19.75±0.10 23.65±0.07 d and 25.08±0.08 d under 28 25℃and 20℃. While life expectancy for the resistant strain decreased to 17.21±0.09 20.95±0.09 22.58±0.10 d. Under the same tem?perature the development timing of the resistance strain was longer than that of the susceptible strain and the period was the longest under 28 ℃ 156.2 h 137.1 h . In the three temperatures all the development periods expanded as the temperature went up the susceptible and resistant larvae developed 137.1 d and 163.3 d 247.7 d and 156.2 d 182.3 d and 263.2 d under 28 25℃and 20℃. The differences show statistic significance P<0.05 . Conclusion The resistance of A. albopictus to cy?permethrin results in the decrease of adaptability to the environment change and the disadvantage of reproduction at different temperatures.
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<p><b>OBJECTIVE</b>To explore whether strontium ranelate (Sr) promotes osteoblast lineage differentiation of rat bone mesenchymal stem cells (BMSCs) through the bone morphogenetic protein-2 (BMP-2)/Smad signaling pathway.</p><p><b>METHODS</b>Cultured rat BMSCs were exposed to different concentrations of Sr, noggin (an inhibitor of BMP-2) or Smad1 siRNA. The activity of alkaline phosphatase (ALP) in the exposed cells was detected by colorimetry, and the formation of mineralized nodules was observed with alizarin red staining. The expressions of phosphorylated (p) Smad1/5/8 and Runt-related transcription factor 2 (Runx2) in the cells were detected by Western blotting.</p><p><b>RESULTS</b>Exposure to Sr at 0.1 to 10 mmol/L for 1 h markedly increased the expression of p-Smad1/5/8 in the BMSCs, and the increment was the most obvious following 1 mmol/L Sr exposure. Preconditioning with 100 ng/ml noggin for 2 h inhibited Sr-induced up-regulation of p-Smad1/5/8 expressions. Exposure of the cells to 0.1 to 5 mmol/L Sr for 6 h significantly enhanced Runx2 expression, and the peak enhancement occurred following 1 mmol/L Sr exposure. Transfection of the BMSCs with Smad1 siRNA decreased the basal level of Smad1/5/8 protein expression, and also inhibited Sr-induced up-regulation of p-Smad1/5/8 and Runx2 expressions as well as Sr-induced enhancement of ALP activity and formation of mineralized nodules.</p><p><b>CONCLUSION</b>The BMP-2/Smad pathway is involved in Sr-induced osteoblast differentiation of rat BMSCs.</p>
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Animals , Rats , Alkaline Phosphatase , Metabolism , Bone Marrow Cells , Cell Biology , Bone Morphogenetic Protein 2 , Metabolism , Cell Differentiation , Cells, Cultured , Mesenchymal Stem Cells , Cell Biology , Osteogenesis , Rats, Sprague-Dawley , Signal Transduction , Smad1 Protein , Metabolism , Strontium , Pharmacology , Thiophenes , PharmacologyABSTRACT
Bile leak is a commonly complication after biliary tract surgery.In the past,operation was considered priorly to deal with bile leak besides putting a drainage tube in advance.Minimally invasive surgery has gradually become a primary management of bile leak,with the development of minimally invasive surgery such as abdominoscope in the 20th century.
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Objective To establish a HPLC method for determination of geniposide content in Qingkailing Capsule. Methods HPLC with Gracesmart C18 was used and detection wavelength was 238 nm with acetonitrile-water (15∶85) as mobile phase. The flow rate was 1.0 mL/min. Results The standard curve was linear over the range of 0.060 4～0.302 0 ?g (r=0.999 8). The average recovery was 98.73%, and RSD was 1.61%. Conclusion This method is reliable, accurate and suitable for the determination of geniposide in Qingkailing Capsule.
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On the basis of thermal stability of andrographolide and dehydroandrographolide,the influences of medicinal material factors(habitats,collecting time,storage time),thermal stability,production technology(solvent,temperature,heating time and storage condition)on the content of andrographolide and dehydroandrographolide in Andrographis Tablet(AT)were explored so as to increase the quality of AT.The results showed that the excellent medicinal material of Herba Andrographis,optimized production technology,shorter heating time and lower temperature are the effective measures for increasing the quality of AT.