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The increasing incidence of obesity and diabetes has made diabetic kidney disease （DKD） the main cause of chronic kidney disease and end-stage renal disease. Despite current pharmacological interventions for blood glucose control and renin-angiotensin system inhibition， the risk of kidney disease progression and complications remains high. At present， the pathogenesis of DKD has been clarified to be related to chronic inflammatory response， oxidative stress， glucose and lipid metabolism disorders， and hemodynamic abnormalities. According to recent studies， the programmed cell deaths （PCD） of renal intrinsic cells such as pyroptosis and necroptosis play a key role in the occurrence and development of DKD. Pyroptosis and necroptosis， the two newly discovered routes of PCD， can protect the hosts from being invaded by microbial pathogens， but their dysregulation is associated with multiple autoimmunity and autoinflammatory responses. Pyroptosis and necroptosis are closely interlinked and cross-regulated. Different from apoptosis， these two cellular suicide mechanisms cause membrane rupture and release of cell contents through their respective gasdermin D （GSDMD） and mixed lineage kinase domain-like protein （MLKL）， with damage-associated molecular patterns （DAMPs） and inflammatory cytokines like interleukin-1β （IL-1β） involved to trigger inflammation， and chronic inflammatory responses are key factors leading to the progression of DKD. Traditional Chinese medicine （TCM） has long been employed for the prevention and treatment of DKD and the resulting clinical outcomes are remarkable. TCM has been proved to exert a protective effect against DKD by affecting the expression of nucleotide oligomerization domain-like receptor protein 3 （NLRP3） inflammasome， receptor-interacting protein kinase 3 （RIPK3）， and MLKL. This paper reviewed the relationship of pyroptosis and necroptosis with DKD and its intervention with TCM.
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ObjectiveTo observe the effect of Danggui Buxuetang on podocyte pyroptosis in diabetic kidney disease （DKD） rats and to explore the possible mechanism of its prevention and treatment of DKD and podocyte pyroptosis. MethodEight of the 50 male SD rats were randomly classified into a normal group， and the remaining 42 were fed a high-glucose and high-fat diet for six weeks and then intraperitoneally injected with 35 mg·kg-1 streptozotocin （STZ） for inducing type 2 diabetes. After successful modeling， they were randomized into the model group， low- （0.72 g·kg-1） and high-dose （1.44 g·kg-1） Danggui Buxuetang group， and irbesartan （0.017 g·kg-1） group and gavaged with the corresponding drugs， while those in the normal group and model group with an equal volume of normal saline， once per day， for 20 weeks. During the medication， the fasting blood glucose （FBG） and 24 h urine protein （24 h-UTP） were measured regularly. After administration， the pathological changes in renal tissues were observed by periodic acid-silver metheramine （PASM） staining， followed by the observation of ultrastructural changes in podocytes under the transmission electron microscope （TEM）. Serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were determined by enzyme-linked immunosorbent assay （ELISA）. The DNA damage in renal tissue cells of rats was detected by in situ nick end-labeling （TUNEL） assay. The protein expression levels of thioredoxin interacting protein （TXNIP）， cysteine-dependent aspartate-directed protease-1 （Caspase-1）， and gasdermin D （GSDMD） in renal tissues of rats were detected by immunohistochemistry （IHC）， the expression levels of nucleotide binding domain like receptor protein 3 （NLRP3） and Wilms tumor protein-1 （WT-1） in podocytes by immunofluorescent （IF） staining， and the expression levels of TXNIP/NLRP3/Caspase-1/GSDMD pathway proteins and Synaptopodin in renal podocytes by Western blot. ResultCompared with the normal group， the model group exhibited increased FBG and 24 h UTP， glomerular hypertrophy， mesangial hyperplasia， increased extracellular matrix， thickened basement membrane， K-W nodules， vacuolar degeneration in renal tubular epithelial cells， foot process fusion or loss， elevated serum IL-1β and IL-18 levels and TUNEL-positive cells in renal tissue， enhanced NLRP3 but diminished WT-1 expression in podocytes， down-regulated Synaptopodin protein expression， and up-regulated TXNIP/NLRP3/Caspase-1/GSDMD protein expression （P<0.01）. Compared with the model group， Danggui Buxuetang high-dose group remarkably lowered FBG， 24-h UTP， and TUNEL-positive cells in renal tissue， improved renal histopathology and podocyte injury and loss， down-regulated NLRP3 expression in podocytes and TXNIP/NLRP3/Caspase-1/GSDMD protein expression levels， and up-regulated WT-1 expression in podocytes and Synaptopodin protein expression （P<0.05， P<0.01）. ConclusionDanggui Buxuetang inhibits podocyte pyroptosis to reduce proteinuria and delays the development of DKD possibly by regulating the TXNIP/NLRP3/GSDMD signaling pathway.
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ObjectiveTo observe the effect of Danggui Buxuetang on the podocyte injury and receptor-interacting protein kinase 1/receptor-interacting protein kinase3/mixed lineage kinase domain-like protein （RIPK1/RIPK3/MLKL） signaling pathway in diabetic kidney disease （DKD） ratsand to explore its possible mechanism against DKD. MethodEight of the 50 SD rats were randomly classified intoa normal group， and the remaining were fed a high-glucose and high-fat diet for six weeks and then intraperitoneally injected with 0.035 g·kg-1streptozotocin （STZ） for inducing type 2 diabetes. After successful modeling，they were randomized into the model group，high- and low-dose （1.44，0.72 g·kg-1） Danggui Buxuetang groups， and irbesartan （0.017 g·kg-1）group. After 20 weeks of drug intervention， the fasting blood glucose （FBG）， kidney index （KI），and urinary microalbumin-to-urine creatinine ratio （UACR）were detected in each group. The pathological changes in renal tissue were observed by hematoxylin-eosin （HE） staining， followed by the observation of ultrastructural changes in podocytes under the transmission electron microscope. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in renal tissue of rats were determined by enzyme-linked immunosorbent assay （ELISA）， and the protein expression levels of RIPK1， RIPK3， and MLKL in rat kidney tissue by immunohistochemistry. The apoptosis rate of podocytes was detected by in situ nick end-labeling （TUNEL） assay. The mRNA expression levels of RIPK1， RIPK3， and MLKL in kidney tissue of rats were measured by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expression levels of RIPK， RIPK3， and MLKL and podocyte marker Wilms tumor protein-1 （WT-1） in rat kidney tissue were assayed by Western blot. ResultCompared with the normal group， the model group exhibited elevated FBG， UACR， and KI （P<0.01）， glomerular hypertrophy， thickened basement membrane， increased extracellular matrix， mesangial hyperplasia， foot process fusion or loss， enhanced apoptosis in renal tissue， up-regulated TNF-α and IL-6 levels （P<0.01） and RIPK1/RIPK3/MLKL mRNA and protein expression （P<0.01）， and down-regulated WT-1 protein expression. Compared with the model group， Danggui Buxuetang high-dose group significantly reduced the levels of FBG， UACR， and KI， improved renal histopathology， podocyte loss， and apoptosis in renal tissue， down-regulated TNF-α and IL-6 levels and RIPK1/RIPK3/MLKL mRNA and protein expression （P<0.05， P<0.01）， and up-regulated WT-1 protein expression. ConclusionDanggui Buxuetang alleviates podocyte injury and delays the development of DKD possibly by regulating the RIPK1/RIPK3/MLKL signaling pathway.
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ObjectiveTo investigate the intervention effect of Danggui Buxuetang on oxidative stress and inflammatory response in diabetic kidney disease （DKD） rats from its improvement of podocyte mitochondrial dysfunction. MethodSD rats were randomly divided into the control group and modeling group， and the ones in the latter group rats were fed a high-glucose and high-fat diet and then intraperitoneally injected with a small dose of streptozotocin （STZ） for inducing type 2 diabetes. The successfully modeled rats were randomized into the model group， high- and low-dose （1.44 and 0.72 g·kg-1） Danggui Buxuetang groups， and irbesartan （0.017 g·kg-1）group and gavaged with the corresponding drugs， while those in the normal and model groups with an equal volume of normal saline. After 20 weeks of drug intervention， the urinary microalbumin-to-urine creatinine ratio （UACR） and serum malondialdehyde （MDA） content and manganese superoxide dismutase （MnSOD） activity in each group were measured. The pathological changes in renal tissue were observed by Masson trichrome staining， and periodic acid-silver metheramine （PASM） staining， followed by the observation of ultrastructural changes in podocytes under the transmission electron microscope （TEM）. The expression level of reactive oxygen species （ROS） in rat kidney tissue was detected using a fluorescent probe dihydroethidium （DHE）. The protein expression levels of peroxisome proliferator-activated receptor γ -coactivator -1α （PGC-1α）， nucleotide-binding domain like receptor protein 3 （NLRP3）， and Wilms tumor protein-1 （WT-1） were measured by immunohistochemistry （IHC）， and the expression levels of NLRP3， interleukin-1β （IL-1β），and WT-1 in podocytes by immunofluorescence （IF） assay. The mRNA expression levels of PGC-1α and NLRP3 in the renal tissues were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expression levels of PGC-1α， MnSOD， NLRP3， and IL-1β were assayed by Western blot. ResultCompared with the normal group， the model group exhibited elevated UACR and MDA content， weakened MnSOD activity （P<0.01）， glomerular hypertrophy， thickened basement membrane， mesangial hyperplasia， increased extracellular matrix， K-W nodules， podocyte mitochondrial swelling， disordered mitochondrial cristae， foot process fusion or loss， vacuolization， increased ROS （P<0.01）， enhanced NLRP3 and IL-1β but diminished WT-1 expression in podocytes， down-regulated PGC-1α mRNA expression （P<0.01） and PGC-1α and MnSOD protein expression （P<0.01）， and up-regulated NLRP3 mRNA expression and NLRP3 and IL-1β protein expression （P<0.01）. Compared with the model group， Danggui Buxuetang high-dose group significantly decreased UACR and MDA， enhanced MnSOD activity （P<0.05， P<0.01）， improved renal histopathology and podocyte mitochondrial ultrastructure， decreased ROS （P<0.05， P<0.01） and NLRP3 and IL-1β expression in podocytes， enhanced WT-1 expression in podocytes， up-regulated the mRNA and protein levels of PGC-1α and MnSOD， and down-regulated the mRNA and protein levels of NLRP3 and IL-1β （P<0.05， P<0.01）. ConclusionDanggui Buxuetang alleviates oxidative stress， reduces inflammatory response， protects kidney， and delays the progression of DKD possibly by improving the mitochondrial dysfunction in podocytes of DKD rats.
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Aim: This study aimed to compare clinical and oncological outcomes of robot-assisted and laparoscopic surgery for rectal cancer. Materials and Methods: We searched PubMed/Medline, Embase, the Cochrane Library, Yahoo, and Google Scholar databases for relevant articles published up to 2017. Studies based on comparability between robot-assisted and laparoscopic surgery for rectal cancer were designated. Clinical outcomes included operative time, conversion to open surgery, estimated blood loss (EBL), bowel function recovery time, length of hospital stay (LOS), anastomosis leak, and postoperative complications. Oncological outcomes comprised the number of lymph nodes extracted, the positive circumferential margin (PCRM), and the distal resection margin (DRM) Results: Twenty studies were designated totaling 5496 patients, comprising a robot-assisted surgery patient group (n = 2168, 39.4%) and a laparoscopic surgery patient group (n = 3328, 60.6%). The robot-assisted surgery group was associated with longer operative time (odds ratio [OR] 0.48, 95% confidence interval [CI]; 0.14, 0.82), lower conversion to open surgery rate (OR 0.55, 95% CI; 0.44, 0.69), shorter LOS (OR − 0.15, 95% CI; −0.30, 0.00), faster bowel function recovery (OR − 0.38, 95% CI; −0.74, −0.02), and lower postoperative complications (OR 0.79, 95% CI; 0.65, 0.97). EBL, anastomosis leak rate, and oncological outcomes including the number of lymph nodes extracted, the DRM, and the PCRM showed no significant differences between groups. Conclusion: Robot-assisted surgery for rectal cancer showed longer operative time, lower conversion, faster bowel function recovery rates, and shorter hospital stay, and similar oncological outcomes compared to laparoscopic surgery
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Abstract Achillinoside was isolated from methanol extract of Achillea alpina L., Asteraceae. The structure of the compound was characterized based on various spectrum data, including IR, HR-ESI-MS, 1D and 2D NMR. The cardiovascular protective effect of achillinoside was tested on H2O2-induced H9c2 cells. In our research, achillinoside could increase the cell viability dose-dependently in H2O2-induced H9c2 cells. In addition, the levels of caspase-3/9 cells were significantly decreased in H2O2 and achillinoside incubated H9c2 cells.
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Objective@#To understand the epidemic trend of tobacco use among junior middle school students in Shunyi District of Beijing in recent 5 years, and to provide scientific basis for formulating adolescent tobacco control strategies and intervention measures.@*Methods@#The two stage sampling method was used to survey 3 junior middle school schools randomly selected from Shunyi District, Beijing, in November 2013, December 2015 and November 2017. The number of students surveyed each year was 1 520, 1 404 and 1 467 respectively.@*Results@#A total of 4 500 questionnaires were distributed and 4 391 questionnaires were valid, with an effective rate of 97.6%. The current smoking rate and the attempting smoking rate in Shunyi District junior high school students increased substantially, the difference was statistically significant(χ2=9.15, 11.54, P<0.01). The exposure rate of second-hand smoke among junior high school students in Shunyi District is increasing year by year. The current smoking rate and the attempting smoking rate of second-hand smoke at home and in public places were higher than those of non-exposed ones. The differences in the current smoking rates of junior high school students (χ2=25.86, 37.61, P<0.01) and the attempting smoking rate (χ2=49.51, 63-86, P<0.01) were statistically significant. The influence of Shunyi District junior high school students through different tobacco information access channels on the current smoking rate of junior high school students increased year by year. Different tobacco information access channels have significant difference in the influence of the junior middle school students’ attempting smoking rate(P<0.05).@*Conclusion@#The overall tobacco use of junior high school students in Shunyi District of Beijing is increasing by year. The exposure of second-hand smoke is not optimistic, and the supervision of tobacco information acquisition channels is urgent to be strengthened.
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Objective:To observe the effect of Bushen Tongluo prescription on the pathogenesis of lung fibrosis induced by bleomycin and the transforming growth factor β1(TGF-β1)/Smads pathway protein in rats,and reveal the mechanism of this formula in inhibiting pulmonary fibrosis. Method:Totally 48 male SD rats were randomly divided into five groups:normal group(8 rats),model group(10 rats),high and low-dose Bushen Tongluo group(10 rats)and hydrocortisone sodium succinate group(10 rats). The model of pulmonary fibrosis was made with bleomycin except for normal group.Since day 3 after surgery,14.2,7.1 g·kg-1 Bushen Tongluo prescription were given by ig in high and low-dose Bushen Tongluo groups,and 4.58 g·kg-1 hydrocortisone sodium succinate was given by gavage(ig) in normal group and model group.All of the rats were put to death after 28 days.The contents of hydroxyproline (HYP),hyaluronic acid (HA) and laminin (LN) were measured after the death of the rats.Hematoxylin-eosin staining (HE) and Masson tricolor staining were used to observe the pathological changes of lung tissue. Real-time PCR and Western blot were used to observe the changes of mRNA and protein expressions of lung tissues TGF-β1, Smad2, Smad3, Smad7 in each group. Result:Compared with normal group, the level of pulmonary fibrosis was more significant in model group, and the serum HYP,HA and LN were increased obviously(PPβ1, Smad2,Smad3 proteins and mRNA in lung tissues were increased obviously(PPPPPβ1, Smad2, Smad3 protein and mRNA were decreased obviously(PPConclusion:Bushen Tongluo prescription can effectively improve the pathological process of pulmonary fibrosis, and the mechanism may be related to the regulation of TGF-β1/Smads pathway.
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ObjectiveTo observe the thyroid status of pregnant women during the 1st and 2nd trimester of gestation,and its role in brain and neural development of their offspring's.MethodsFrom 2008 to 2009,pregnant women from nine townships of two counties in Wushi and Baicheng in Aksu prefecture of Xinjiang were selected as research subjects according to the survey standard.After informed consent signed,their urinary iodine,serum thyroid stimulating hormone(TSH) and free thyroxin(FT4) were analyzed.The value of thyroid hormone of normal pregnant women was used in diagnosis of subclinical hypothyroidism and hypothyroxinemia in pregnant women.From 2010 to 2011, The brain and neural development status among offspring born by those pregnant women were evaluated with DDST.In accordance with the results of Denver Development Screen Test (DDST) screening,pregnant women were classified into survey and control groups,and the survey group was the suspicious and abnormal of the result of DDST screening(delay),the control group was normal of the result.According to gestational age,pregnant women were divided into 4 gestation groups:G1(6 to 13 weeks),G2(14 to 18 weeks),G3 ( 19 to 23 weeks) and G4(24 to 28 weeks).ResultsA total of 396 cases of pregnant women during the 1st and 2nd trimester of gestation were investigated(survey group 102 cases,control group 294 cases).The median value of urinary iodine concentration among pregnant women in survey group was 152.4 μg/L The prevalence of subclinical hypothyroidism and hypothyroxinemia among pregnant women was 10.78％(11/102) and 3.93％(4/102),respectively.In control group,the median value of urinary iodine concentration was 180.0 μg/L The prevalence of subclinical hypothyroidism and hypothyroxinemia among pregnant women was 7.48％ (22/294) and 4.42％ (13/294),respectively.During the pregnant period from G1 to G3,the median serum TSH of pregnant women in DDST survey group (2.24,3.49,2.85 mU/L) was higher than that of DDST control group( 1.59,2.70,2.28 mU/L).Especially,the difference of TSH between the two groups during the period of G3 was statistically significant (t =4.906,P ＜ 0.05 ).ConclusionsHypothyroidism tendency of pregnant women during the period from gestation week 19th to 23rd may be an important factor in the development of brain abnormalities of their offsprings.