الملخص
Objective To observe the effects of Gegen Qinlian Decoction on pancreatic endoplasmic reticulum stress in mice with type 2 diabetes mellitus(T2DM);To explore its mechanism of action in the treatment of T2DM.Methods Totally 75 SPF male db/db mice were randomly divided into model group,metformin group,and Gegen Qinlian Decoction high-,medium-,low-dosage groups,with 15 mice in each group.15 db/m mice were set as the blank group.The administration groups received corresponding medicine for gavage for 12 weeks.Body mass,fasting blood glucose(FBG)and glycated hemoglobin(HbA1c)in mice were detected,HE staining was used to observe the pathological changes of pancreatic tissue,the apoptosis of islet cells was determined by TUNEL staining,Western blot was used to detect pancreatic tissue glucose regulatory protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK),p-PERK,activated transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)protein expression,RT-PCR was used to detect pancreatic tissue PERK,ATF4,CHOP mRNA expressions.Results Compared with the blank group,the body mass,FBG and HbA1c contents in the model group significantly increased(P<0.01);the pancreatic tissue structure was incomplete,with blurry boundaries and vacuoles inside,leading to a significant increase in pancreatic islet cells apoptosis(P<0.01);the expressions of GRP78,p-PERK,ATF4,and CHOP proteins in pancreatic tissue significantly increased(P<0.01),and the mRNA expressions of PERK,ATF4 and CHOP significantly increased(P<0.01).Compared with the model group,the body mass,FBG and HbA1c contents of mice in each administration group significantly decreased(P<0.05,P<0.01);pathological changes in pancreatic tissue was reduced,and islet cells apoptosis decreased to varying degrees(P<0.05,P<0.01);the expressions of GRP78,p-PERK,ATF4 and CHOP proteins in pancreatic tissue significantly decreased(P<0.01)in Gegen Qinlian Decoction high-and medium-dosage groups and the metformin group,and the expressions of PERK,ATF4 and CHOP mRNA significantly decreased(P<0.05,P<0.01).Conclusion Gegen Qinlian Decoction may decreased pancreatic islet cells apoptosis,protect pancreatic cell function,and delay the progression of T2DM by inhibiting the endoplasmic reticulum stress PERK/ATF4/CHOP signaling pathway,and down-regulating the expressions of related genes and proteins.
الملخص
ObjectiveTo validate the alleviating effect of Gegen Qinliantang （GGQLT） on insulin resistance in db/db diabetic mice by regulating the silent information regulator 1 （SIRT1）/forkhead transcription factor O1 （FoxO1） autophagy pathway. MethodSeventy-five SPF-grade spontaneous type 2 diabetic db/db mice and 15 control db/m mice were selected and maintained on regular feed for one week before measuring blood glucose. They were randomly divided into six groups， with 15 mice in each group. The groups included a normal group （physiological saline， 0.2 g·kg-1）， a metformin group （0.2 g·kg-1）， high-， medium-， and low-dose GGQLT groups （31.9， 19.1， 6.9 g·kg-1）， and a model group （physiological saline， 0.2 g·kg-1）. They were orally treated with corresponding drugs for eight weeks， once daily. Fasting blood glucose （FBG） was measured using a Roche glucometer. Serum levels of high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG）， and total cholesterol （TC） were measured using an automated biochemical analyzer. Fasting serum insulin （INS） levels were determined using enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment of insulin resistance （HOMA-IR） was calculated. Western blot was used to detect the expression of Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， and SIRT1/FoxO1 autophagy pathway-related proteins in liver tissues. Immunohistochemistry was performed to assess the expression of SIRT1， FoxO1， Beclin-1， and LC3B proteins in liver tissues. Transmission electron microscopy was used to observe the formation of autophagosomes in the liver. ResultCompared with the normal group， the model group showed significant increases in FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.01）， and significant increases in the expression of SIRT1， Beclin-1， LC3， and FoxO1 proteins in liver tissues （P<0.01）. Transmission electron microscopy revealed the highest number of autophagosomes in the model group. Compared with the model group， the metformin group and the low-， medium-， and high-dose GGQLT groups showed significant decreases in serum FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.05， P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， LC3 （P<0.05， P<0.01）， and up-regulated FoxO1 protein （P<0.01）. Transmission electron microscopy showed a reduction in the degree of autophagy in the treatment groups. Compared with the metformin group， the medium- and high-dose GGQLT groups showed significant decreases in FBG， FINS， and TG levels （P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， and LC3 in liver tissues （P<0.05， P<0.01）， and reduced FoxO1 protein （P<0.01）. The high-dose GGQLT group showed reduced HOMA-IR， TC， LDL-C， and HDL-C levels （P<0.05， P<0.01）. Transmission electron microscopy revealed a significant reduction in autophagosomes in the medium- and high-dose GGQLT groups. ConclusionGGQLT can significantly improve glucose and lipid metabolism disorders， alleviate insulin resistance in db/db mice， and prevent and treat type 2 diabetes by activating the SIRT1/FoxO1 autophagy pathway.
الملخص
Objective:To observe the effects of different doses of Gegen Qinlian Decoction on nucleotide oligomeric domain-like receptor protein 3 (NLRP3)/Caspase-1/IL1β inflammatory signaling pathway in liver of db/db mice with type 2 diabetes mellitus (T2DM).Methods:Totally 75 SPF male db/db mice were randomly divided into model group, metformin group (0.2 g/kg), Gegen Qinlian Decoction high-, medium-, and low-dosage groups (61.80, 30.90, 15.45 g/kg), with 15 mice in each group. Another 15 db/m male mice were selected as blank control group. Each administration group was given relevant medicine for gavage, while the blank group and model group were given 0.9% sodium chloride solution for gavage, once a day, for 12 weeks. The body weight, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) contents of each group were measured after treatment. The mRNA expression levels of NLRP3, Caspase-1 and interleukin-1β (IL-1β) in liver were detected by real-time quantitative PCR. The expression levels of NLRP3, Caspase-1, IL-1β and IL-18 in liver tissues were detected by Western Blot. HE staining was used to observe the morphology of liver tissues.Results:Compared with model group, body weight, fasting blood glucose and HbA1c contents of mice in Gegen Qinlian Decoction high- and medium-dosage groups and metformin groups decreased ( P<0.05), the body weight and fasting blood glucose levels of mice in Gegen Qinlian Decoction low-dosage group decreased ( P<0.05); the mRNA levels of NLRP3 and IL-1β in liver tissues of all treatment groups decreased ( P<0.05), the mRNA level of Caspase-1 in liver tissue decreased in Gegen Qinlian Decoction high- and medium-dosage groups ( P<0.05); the expression of NLRP3, Caspase-1, and IL-18 in liver tissue of each treatment group decreased ( P<0.05), while the expression of IL-1β in Gegen Qinlian Decoction high- and medium-dosage groups and the metformin group decreased ( P<0.05); compared with the metformin group, the body weight and fasting blood glucose of mice in the Gegen Qinlian Decoction high-dosage decreased ( P<0.05), while the HbA1c levels in the Qinlian Decoction high- and medium-dosage decreased ( P<0.05); the expressions of NLRP3, Caspase-1 and IL-18 in liver tissues of Gegen Qinlian Decoction high-dosage group decreased ( P<0.05), the expression of IL-1β, NLRP3, Caspase-1, IL-1β, and IL-18 decreased ( P<0.05); HE staining showed that the pathological changes of liver tissue were reduced in all treatment groups. Conclusion:Gegen Qinlian Decoction may reduce blood sugar by inhibiting the activation of NLRP3/Caspase-1/IL-1β inflammatory signaling pathway in liver of db/db mice, thereby improving the inflammatory damage of T2DM.
الملخص
Objective To investigate the impact of prescribed adaptive statistical iterative reconstruction V (Pre-ASiR-V) on imaging quality and radiation dosage of pure ground glass nodules (pGGN) in chest phantom,in order to obtain the optimal level of Pre-ASiR-V.Methods CT scanning for a chest phantom containing 4 artificial pGGNs was performed with Revolution CT,and the Pre-ASiR-V level was set as 0,20％,40％,60％,80％ and 100％ group,respectively.The mean noise,effective dose (ED) and the subjective scores of pGGN imaging were recorded and compared.Results The mean noise of groups (Pre-ASiR-V 0,20％,40％,60％,80％ and 100％) was (17.93±2.20)HU,(17.30±3.68)HU,(18.20± 3.44)HU,(18.80±0.20)HU,(19.87±2.56)HU and (15.90±4.56)HU,respectively (F=0.568,P=0.723).ED of these groups was 7.40 mSv,5.16 mSv,3.36 mSv,1.97 mSv,0.97 mSv and 0.33 mSv,respectively.Compared with imaging of PreASiR-V 0,the reduction percentage of ED was 30.27％,54.59％,73.38％,86.89％ and 95.54％,respectively.The subjective score of the image quality evaluated by the 2 observers had high agreement (Kappa=0.778,P=0.003),and all the scores were greater than 3.The subjective score of Pre-ASiR-V 80％ and 100％ group was slightly lower than those in other groups.Conclusion Different Pre-ASiR-V level slightly impacts the noise of high-resolution CT images of chest phantom,while reduces radiation dosage significantly.Pre-ASiR-V level of 60％ is the optimal protocol.
الملخص
Data were collected from 236 patients with advanced ClllllCerB through questionnaire survey,home visit,oncology clinics and counseling service.The data were evaluated and classified according to VAS and NCCN aduh cancer pain practice guidelines.Two hundred and eleven in 236 advancad cancer patients(89.4%)Suffered from Cancer pain,with mild pain in 31,moderate in 83 and severe in 97.One hundred and seventeen patients(49.6%)received therapy for pain relief,among whom 78(66.7%)had complete remission(CR),26(22.2%)partial remission(PR)and 13 cages(11.1%)noremission.The main reason for declining pain relief wag being scared of morphine addiction.