Mechanism of Astragaloside Ⅳ on db/db Mice with Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease Based on AMPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the mechanism of astragaloside Ⅳ （AS Ⅳ） on db/db mice with type 2 diabetes mellitus （T2DM） and non-alcoholic fatty liver disease （NAFLD） based on network pharmacology and experimental validation. MethodA total of 24 db/db mice were randomly divided into four groups： model group， metformin group， and low-dose and high-dose AS Ⅳ groups. Six C57 mice were used as the blank group. The low-dose and high-dose AS Ⅳ groups were given AS Ⅳ of 0.015 and 0.030 g·kg-1 by gavage， and the metformin group was given 0.067 g·kg-1 by gavage. The blank and model groups were given equal volumes of distilled water by gavage. After intragastric administration， fasting blood glucose （FBG） was detected， and an oral glucose tolerance test was performed. Serum lipid level and liver histopathology were detected. The target and enrichment pathway of AS Ⅳ for treating T2DM and NAFLD were predicted by network pharmacology， and the main enrichment pathway was verified by molecular biology techniques. The protein expressions of AMPK， p-AMPK， sterol regulatory element-binding protein-1 （SREBP-1）， and fatty acid synthetase （FAS） in liver tissue were detected by Western blot. ResultCompared with the blank group， the levels of body mass， liver weight coefficient， fasting blood glucose， serum total cholesterol， triglyceride， and low-density lipoprotein cholesterol in mice treated with AS Ⅳ were decreased （P<0.05， P<0.01）. The pathology of liver tissue showed significant improvement in lipid accumulation， and imaging results showed that the degree of fatty liver was reduced after AS Ⅳ therapy. Network pharmacological prediction results showed that vascular endothelial growth factor α （VEGFA）， galactoagglutinin 3 （LGALS3）， serine/threonine kinase B2 （Akt2）， RHO-associated coiled-coil protein kinase 1 （ROCK1）， serine/threonine kinase B1 （Akt1）， signaling and transcriptional activator protein （STAT3）， and messtimal epidermal transformation factor （MET） were key targets in "drug-disease" network. The results from the Kyoto encyclopedia of genes and genomes （KEGG） enrichment showed that the AMP-dependent protein kinase （AMPK） signaling pathway was strongly associated with T2DM and NAFLD. Western blot results showed that compared with the blank group， the expression levels of p-AMPK/AMPK in the model group were significantly down-regulated， while those of SREBP-1 and FAS proteins were significantly up-regulated （P<0.01）. Compared with the model group， the expression levels of p-AMPK/AMPK in the metformin group and high-dose AS Ⅳ group were significantly up-regulated， while those of SREBP-1 and FAS proteins were significantly down-regulated （P<0.05， P<0.01）. ConclusionAS Ⅳ regulates the expression of lipid proteins by activating the AMPK signaling pathway， thereby improving lipid metabolism.

Effect of Jingui Shenqiwan on Diabetic Osteoporosis in Mice via AGEs/RANKL/NF-κB Pathway Based on Theory of "Kidneys Governing Bones" / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Jingui Shenqiwan on diabetic osteoporosis （DOP） in mice by regulating the advanced glycation end products （AGEs）/receptor activator of nuclear factor-κB ligand （RANKL）/nuclear factor-κB （NF-κB） signaling pathway based on the theory of "kidneys governing bones". MethodForty 6-week-old male and female skeletal-muscle-specific， dominant negative insulin-like growth factor-1 receptor （MKR） mice were selected and fed on a high-fat diet for eight weeks to establish the DOP model. The model mice were randomly divided into a model group， low- and high-dose Jingui Shenqiwan group （1.3， 2.6 g·kg-1）， and an alendronate sodium group （0.01 g·kg-1）， with 10 mice in each group. Additionally， 10 FVB/N mice of the same age were assigned to the normal group. The corresponding drugs were administered orally to each group once a day for four weeks. After the administration period， fasting blood glucose （FBG） measurement and oral glucose tolerance test （OGTT） were conducted. Kidney function and kidney index were measured. Renal tissue pathological changes were observed through hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry was performed to assess the protein expression levels of AGEs， phosphorylated NF-κB （p-NF-κB）， and RANKL in renal tissues. Western blot analysis was conducted to measure the expression of proteins related to the AGEs/RANKL/NF-κB signaling pathway， osteoprotegerin （OPG）， and Runt-related transcription factor 2 （RUNX2） proteins in femoral bone tissues. ResultCompared with the normal group， mice in the model group exhibited significantly increased FBG （P<0.01）， trabecular bone degeneration， abnormal bone morphological parameters， significantly increased area under the curve （AUC） of OGTT （P<0.01）， enlarged kidney volume， significantly increased kidney function indicators and kidney index （P<0.01）， disrupted renal glomeruli and renal tubule structures， significantly increased expression of AGEs， RANKL， and p-NF-κB/NF-κB in renal tissues （P<0.05）， and significantly decreased expression of OPG and RUNX2 in femoral bone tissues （P<0.01）. Compared with the model group， mice in the Jingui Shenqiwan groups showed a significant decrease in OGTT AUC （P<0.01）. Histopathological analysis revealed alleviated structural lesions in renal glomeruli and renal tubules. Furthermore， the expression of AGEs， RANKL， and p-NF-κB/NF-κB in renal tissues was significantly reduced （P<0.05， P<0.01）， and the expression of RUNX2 and OPG in femoral bone tissues was significantly increased （P<0.05， P<0.01）. ConclusionJingui Shenqiwan can improve kidney function and downregulate the AGEs/RANKL/NF-κB signaling pathway to inhibit inflammatory reactions， thereby alleviating the symptoms of DOP in mice， demonstrating a therapeutic effect on DOP from the perspective of the kidney.

Prognostic value of diffusion kurtosis imaging histogram based nomogram model for cervical cancer / 中华放射肿瘤学杂志

Objective:To analyze the prognostic value of nomogram model for cervical cancer based on the imaging features of diffusion kurtosis imaging (DKI) histogram.Methods:The DKI and clinical data of 272 patients with cervical cancer who were admitted to Affiliated Hospital of Guangdong Medical University from March 2015 to February 2022 were collected and retrospectively analyzed. All patients were randomly divided into the training group ( n=190) and validation group ( n=82) at a ratio of 7 vs. 3. The parameters of DKI histogram were obtained by GE AW 4.2 MRI software. The best prognostic imaging features were screened by LASSO regression. The DKI radiomics score was calculated by linear combination. The independent risk factors of prognosis were identified by univariate and multivariate regression analyses, and a nomogram model was constructed. The model discrimination was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). The internal consistency of the model was evaluated by the calibration map. Results:Adenocarcinoma ( HR=2.496, 95% CI=1.312-4.749, P=0.005), DKI score ( HR=24.087, 95% CI=6.062-95.711, P<0.001), depth of invasion ≥ 1/2 muscular layer ( HR=2.277, 95% CI=1.156-4.487, P=0.017) and neutrophil to lymphocyte ratio (NLR) ( HR=1.800, 95% CI=1.313-2.468, P<0.001) were the independent risk factors for prognosis of cervical cancer. The AUC of the nomogram model in the training and validation groups were 0.860 and 0.757, respectively. The calibration curve was well fitted with the 45° diagonal. The prediction results of long-term prognosis of this model were in good agreement with the actual situation. Conclusions:Adenocarcinoma, NLR, DKI score and depth of invasion ≥ 1/2 muscular layer are the independent risk factors for the prognosis of patients with cervical cancer. The constructed nomogram model could reliably predict the 3-year survival rate of patients with cervical cancer.

Relationship between 13q14 deletion and prognosis in initial-treatment patients with multiple myeloma / 中国医师杂志

Objective:To analyze relationship between 13q14 deletion and prognosis in initial-treatment patients with multiple myeloma (MM).Methods:The follow-up data of 121 patients with newly diagnosed MM admitted to the First People's Hospital of Xiangtan City from January 2012 to December 2016 were collected and divided into deletion group ( n=39) and non deletion group ( n=82) according to the deletion of 13q14.The prognosis situations were compared among patients with different 13q14 deletion. Univariate analysis was performed for 3-year overall survival (OS) and progression free survival (PFS) in patients with MM. Results:As of the follow-up time, the 3-year OS rate, 3-year OS, 3-year PFS rate, 3-year PFS and median PFS were 71.90%(87/121), 5.8-36 months, 47.93%(58/121), 2.3-36 months and 34.8 months, respectively. The age, hypoproteinemia, high lactic dehydrogenase (LDH) and 13q14 deletion were independent influencing factors of OS ( P<0.05). The age, high LDH and 13q14 deletion were independent influencing factors of PFS ( P<0.05). The 3-year OS rate and 3-year PFS rate in 13q14 deletion group were 61.54%(24/39) and 25.64%(10/39), lower than those in non-deletion group ( P<0.05). Conclusions:The short-term prognosis is poor in initial-treatment MM patients with 13q14 deletion. Conducting risk stratified treatment for patients based on common influencing factors of OS and PFS is conducive to improving their prognosis.

Application of Data Mining Technology in Risk Prediction Model for Lung Cancer / 肿瘤防治研究

Objective To establish a lung cancer risk prediction model using data mining technology and compare the performance of decision tree C5.0 and artificial neural networks in the application of risk prediction model, and to explore the value of data mining techniques in lung cancer risk prediction. Methods We collected the data of 180 patients with lung cancer and 240 patients with benign lung lesion which contained 17 variables of risk factors and clinical symptoms. Decision tree C5.0 and artificial neural networks models were established to compare the prediction performance. Results There were 420 valid samples collected in total and proportioned with the ratio of 7:3 for the training set and testing set. The accuracy, sensitivity, specificity, Youden index, positive predictive value, negative predictive value and AUC of artificial neural networks model were 65.3%, 61.7%, 73.3%, 0.350, 54.9%, 73.1% and 0.675 (95%CI: 0.628-0.720) in testing set; those of decision tree C5.0 model were 61.0%, 47.8%, 80.4%, 0.282, 35.3%, 80.6% and 0.641 (95%CI: 0.593-0.687) in testing set. Conclusion The artificial neural networks model is superior to the decision tree C5.0 model at overall performance and it has potential application value in the risk prediction of lung cancer.

Application Thoughts of Shuyu Pill in Treatment of Diabetes / 中国中医药信息杂志

Shuyu Pill is the representative prescription for treating deficiency-essence. This article discussed the consistency of diabetes and deficiency-essence from TCM syndromes and etiology and pathogenesis, and probed into the correlation between Shuyu Pill and diabetic Western medicine of pathomechanism diabetes from the modern pharmacological research on Shuyu Pill. Therefore, it proposed that diabetes has the essence of deficiency-essence;the pathogenesis of diabetes should meet the efficacy of Shuyu Pill; pharmacological effects of Shuyu Pill can affect various pathological mechanism of diabetes, with a purpose to provide new ideas for the clinical treatment of diabetes.

DNA methylation and telomere damage in occupational people exposed to coal tar pitch / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the promoter methylation of p16, FHIT and RASSF1A gene and telomere damage in the workers exposed to coal tar pitch, and to explore the effective biomarker of occupational exposure to coal tar pitch.</p><p><b>METHODS</b>180 cases of workers exposed to coal tar pitch in a certain carbon plant named as exposure group, and 145 healthy cases with a medical examination in the first affiliated hospital of Zhengzhou University were selected as control group. Relative telomere length in peripheral blood DNA was detected using real-time quantitative PCR, and the promoter methylation rate of p16, RASSF1A and FHIT gene in peripheral blood DNA were determined by real-time quantitative methylation specific PCR. The relative telomere length and gene promoter methylation in two groups were compared, and influencing factors were analyzed.</p><p><b>RESULTS</b>Relative telomere length in exposed group was lower than that in the control group, and the difference was statistically significant (Z = -5.395, P < 0.001). There was no significant difference in the promoter methylation rate of p16, FHIT and RASSF1A gene between the two groups (P > 0.05). Stratification analysis by gender, age, and smoking, we found that when the age was less than or equal to 40, the promoter methylation rate of p16 in exposed group was more than that in control group, and the difference was statistically significant (Z = -1.914, P = 0.011).</p><p><b>CONCLUSION</b>Occupational exposure to coal tar pitch may induce leukocyte DNA telomere length of human peripheral blood shortened, and may not change the promoter methylation rates of p16, FHIT and RASSF1A gene.</p>

Effects of Zuogui Jiangtang Yishen Decoction on Expressions of Glucose Regulated Protein78 and C/EBP Homology Protein in Podocyte of MKR Mice with Diabetic Nephropathy / 中国中医药信息杂志

Objective To investigate the specific expression of endoplasmic reticulum stress-related GRP78 and CHOP in podocyte of MKR mice with diabetic nephropathy (DN);To discuss the intervention effect of Zuogui Jiangtang Yishen Decoction (ZGJTYS). Methods 8-week old MKR mice were randomly divided into five groups:blank group, model group, ZGJTYS group, 4-Phenylbutyric acid group, gliquidone+benazepril group, and normal control group consisting of wild type C57BC/6 mice, 10 mice per group. All mice from model group and each treatment group received high-fat diet feed and unilateral nephrectomy to make the DN model. Mice from treatment groups received medicine intervention for four weeks. The levels of FBG were detected by electrochemical detection method, and the UmAlb was detected by ELISA. The expressions of GRP78, CHOP mRNA, and protein were detected by RT-PCR and Western blot. The morphological structure changes of the podocytes were observed by transmission electron microscopes. Results Compared with blank group, FBG and UmAlb in the model group increased significantly (P<0.01);the expressions of GRP78 mRNA and protein markedly decreased (P<0.01);the expressions of CHOP mRNA and protein increased (P<0.01). Compared with the model group, FBG and UmAlb in each treatment group significantly decreased (P<0.01);the expressions of GRP78 mRNA and protein in the ZGJTYS group and 4-Phenylbutyric acid group increased (P<0.01), the expressions of CHOP mRNA and protein decreased (P<0.01). The renal pathological lesions of each treatment group were significantly improved compared with model group. Conclusion ZGJTYS Decoction can effectively improve the damaged podocyte induced by endoplasmic reticulum stress, delay DN progress.

Effects of Zuogui Jiangtang Yishen Decoction on Expression of Nephrin and Podocin in Podocyte of MKR Mice with Diabetic Nephropathy / 中国中医药信息杂志

Objective To investigate the effects of Zuogui Jiangtang Yishen decoction (ZGJTYS) on the expression of nephrin and podocin in podocyte of MKR mice with diabetic nephropathy (DN), and explore its mechanism. Methods Forty MKR mice (8 weeks old) were randomly divided into four groups as follows:negative control group (group A), DN model group (group B), ZGJTYS group (group C) and positive control group (group D, Gliquidone and benazepri). All mice from group B, C and D were received high-fat diet feed and unilateral nephrectomy. Four weeks after operation, all mice were received drug intervention, and four weeks later, all mice were put to death. The levels of UmAlb were observed by ELISA, the serum BUN and Cr by biochemical, and the FBG by electrochemical detection method. The nephrin and podocin mRNA expression were measured by RT-PCR and the protein expression by western blotting. The morphological structure changes of the podocytes were observed by transmission electron microscopes. Results As compared with group A, FBG, BUN, SCr and urine UmAlb in the mice of group B increased significantly (P<0.01), the expression level of nephrin and podocin mRNA and protein were markedly decreased (P<0.01). After intervention of drugs, all biochemical indicators above in the mice of group C and D significantly decreased (P<0.01), the expression level of nephrin and podocin mRNA and protein were markedly increased (P<0.01, P<0.05), compared with group B. The renal pathological lesions of group C and D were significantly improved compared with group B. Conclusion ZGJTYS decoction exerts reno-protective effect via reinstating nephrin and podocin expression to repair the damaged podocyte.

Tumor necrosis factor-α and NF-κB play a role in macrophage-like THP-1 cells promoting coal tar pitch extract-induced tumorigenic transformation of human bronchial epithelial cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To characterize the role of tumor necrosis factor-α (TNF-α) and NF-κB play a role in macrophage-like THP-1 cells promoting coal tar pitch extract (CTPE)-induced tumorigenic transformation of human bronchial epithelial cells (BEAS-2B).</p><p><b>METHODS</b>From passage 10, CTPE-induced BEAS-2B cells cocultured with THP-1 cells were treated with NF-κB inhibitor-Pyrrolidine dithiocarbamate (PDTC) every 3 passages and TNF-α antibody every passage. Alterations of cell cycle, karyotype and colony formation in soft agar of BEAS-2B cells at passages 20, indicative of tumorigenicity, were determined, respectively. In addition, mRNA and protein levels of TNF receptor associated factor2 (TRAF2) and Cyclin D1 in BEAS-2B cells were measured with Real Time-PCR and Western blot, respectively.</p><p><b>RESULTS</b>The percentages of S-phase BEAS-2B cells at passage 20 in PDTC group and TNF-α antibody group were (33.97±2.16)% and (34.29±2.04)% respectively, which were less than that in Co-culture+CTPE group of 20th passage [(44.46±0.83)%], P < 0.05; The number of cells with aneuploidy in 100 cells in 20th passage PDTC group and TNF-α antibody group were 40 and 37, and there were significantly different when comparing to that of 20th passage Co-culture+CTPE group (75); The number of colony formation and the rate of colony formation of BEAS-2B cells in soft agar at passage 20 in PDTC group were (15.17±2.48) and (1.51‰±0.25‰), (13.33±2.58)and (1.33‰±0.26‰) in TNF-α antibody group, which were less that those in 20th passage Co-culture+CTPE group [(172.33±12.09) and (17.23‰±1.20‰)], P < 0.05; at the same time, the mRNA and protein levels of TRAF2 and Cyclin D1 in BEAS-2B cells were decreased after PDTC and TNF-α antibody treatment.</p><p><b>CONCLUSION</b>TNF-α and NF-κB could play an important role in THP-1 cells promoting coal tar pitch extract-induced tumorigenic transformation of BEAS-2B cells by influencing the expression of TRAF2 and Cyclin D1.</p>

Imaging features of peripheral primitive neuroectodermal tumors / 中国基层医药

Objective To investigate the X-ray,CT and MRI features of peripheral primitive neuroectodermal tumors (pPNETs).Methods 14 patients were pathologically diagnosed with pPNETs.The imaging of X-ray (twelve image),Computed Tomography(eleven image) and Magnetic Resonance Imaging(five image) were retrospectively analyzed.Results Of 14 patients,there were two sites of tumour:soft tissue( eight patients) and bones( six patients).For tumoura of the soft tissue region,the appearance of X-ray and CT imaging showed equal or lower density soft mass without dear boundary.In some cases,tumours invaded adjacent bones.The appearance of MRI imaging showed large heterogeneous masses inside soft tissue without clear boundary.Tumours displaced adjacent cortical bone and cavitas medullaris.All masses were heterogeneous enhancement on contrast images.For tumours of bone region,X-ray and CT scan showed large scale osteolysis osteoclasia in bone surrounding with soft tissue masses of various size.The lesions were equal or lower signal on T1 WI.All masses were intermediate or hyperintense signal with heterogeneous midrange or obvious enhancement on T2WI.Conclusion Imaging characteristics of pPNETs were described.X-ray,CT and MRI were useful in understanding the property,extent and staging of tumor and very useful in the diagnosis.

Diffusion weighted imaging diagnosis of cancerization nodules of liver cirrhosis / 中国医学影像技术

Objective To investigate the clinical value of diffusion weighted imaging (DWI) in diagnosis of atypical cancerization nodules (CNs) of liver cirrhosis. Methods Totally 34 patients with atypical CNs of liver cirrhosis confirmed pathologically underwent routine MR, dynamic enhancement, and DWI (b=0, 500, 1000 s/mm~2). The detection rate of CNs of liver cirrhosis between routine MR and DWI was compared. Results Totally 21 patients with 28 cancerization nodules were diagnosed with routine and dynamic enhancement MR, while 27 patients with 37 cancerization nodules were detected with DWI. Significant difference was found in the detection rate between routine scan and DWI (P=0.025). Conclusion DWI shows more advantage than routine and dynamic enhancement MR for detection of liver cirrhosis with atypical CNs.

Expression of HGF in gastric carcinoma and the correlation with lymphangiogenesis and lymph node metastasis / 肿瘤研究与临床

Objective To detect the expressive levels of hepatocyte growth factor and D2-40 and its correlation with clinicopathological factors and microlymphatic density in gastric carcinoma. Methods Immunohistochemistry method was used to detect the expression of HGF and D2-40 in gastric cancer tissue, with microlymphatic density(MLD) counted. Results The expression of HGF had the positive correlation with histologic types, infiltration depth, clinical stage and lymph node metastasis (P <0.05). No correlation was found in age, tumor diameter(P >0.05). In gastric cancer, the MLD in the HGF-positive group (22.8±10.9) was higher than that in the HGF-negative group(14.0±4.2, P <0.05). Conclusion The expressive levels of HGF have the positive correlation with histologic types, infiltration depth, clinical stage, lymph node metastasis and MLD in gastric carcinoma. HGF can be used to predict prognosis of gastric carcinoma.

Application of breath hold two dimensional fast imaging employing steady state acquisition sequence for aortic dissection magnetic resonance many time phases imaging / 中国基层医药

Objective To evaluate the imaging characteristic and the value of application of breath hold two dimensional fast imaging employing steady state acquisition(FIFSTA) sequence, for aortic dissection(AD) magnetic resonance many time phases imaging. Methods To analyze retrospectively the manifestation of 5 cases with aortie dissection diagnosed, Bakey type Ⅰ,Ⅱ, Ⅲ, in 1, 1 and 3, all were examined using ECG triggered, two dimensional FIESTA sequence during end-expiratory breath hold. Scan with the long axes of aortic position(oblique position parallel with aortic arch) and transitional position. The results were analyzed by the soft of workstation AW4.2. Results The display rate of the true lumen and the false lumen of AD were 100% ,the display rate of membrane in aorta was 100% ,4 cases showed the hole of intimal tear,2 cases with thrombus,2 cases with aortic regurgitation,2 cases with ejecting in the hole of intimal tear. Conclusion Need not any contrast media, quickly acquired imaging, high contrast to noise ratio, least artifact,and especially show membrane in aorta and for the hole of intimal tear of aortic dissection(AD) magnetic resonance many time phases imaging with two dimensional FIESTA sequence.

CYP2D6 gene G4268C single nucleotide polymorphism and genetic susceptibility to lung cancer / 第二军医大学学报

Objective:To evaluate the relation between the single nucleotide polymorphism of CYP2D6 gene G4268C and the genetic susceptibility to lung cancer. Methods: A case-control study was conducted among 118 lung cancer patients and 118 control subjects (matched for sex, age) to investigate the role of CYP2D6 gene G4268C polymorphism in lung cancer; PCR-RFLP was used to identify the genotypes of polymorphism. Logistic regression was used to analyze the relationship between polymorphism and genetic susceptibility to lung cancer. Results: The frequency of G4268→C mutation in case and control group were 69.49% and 75.00%, respectively. Non-C4268/C genotype (including G4268/G and G4268/C genotype) was correlated to the high risk of lung cancer, with OR adjusted by gender, age and smoking being 1.80 (95% CI=1.06-3.06), especially to lung adenocarcinoma (OR being 2.95 95% CI=1.39-6.23). After stratified analysis of smoking history and adjusting by gender and age, it was revealed that non-C4268/C genotype was associated with significantly increased risk of lung cancer in non-smokers and light-smokers group, with OR=2.12 (95% CI=1.03-4.36) and OR=3.75 (95% CI=1.15-12.22), respectively. Conclusion: C4268/C genotype may be a protective factor in lung adenocarcinoma patients and may decrease the risk of lung cancer in non-smokers and light-smorkers.