miR-195 regulates FOXK1 gene and inhibits PI3K/Akt pathway’s biological behavior in stomach adenocarcinoma / 中华内分泌外科杂志

Objective:To investigate the effect and mechanism of miR-195 regulating FOXK1 gene and PI3K/Akt pathway on stomach adenocarcinoma proliferation, invasion and migration ability.Methods:Public database samples were employed to analyze the expression differences and prognostic significance of miR-195 in stomach adenocarcinoma. After overexpression of mir-195-5p in two cell lines, MGC803 and AGS, altered cell proliferation, invasion, and migration abilities were detected by Alamar Blue, Wound healing, and Transwell assays. The potential target genes and binding sites of miR-195 were predicted by the starBase. Western blot was used to detect the expression levels of foxk1 and phosphorylation sites in the PI3K/Akt pathway of target genes after overexpression of mir-195-5p. A Dual-luciferase reporter assay was used to verify the relationship between mir-195-5p and foxk1. Statistical analyses were performed with IBM SPSS 22 software and R 4.0.3.Results:Our results showed a significant over-expression of miR-195 in the tumor tissues, compared with the paired normal tissues ( P<0.001) , which could inhibit the proliferation and invasion of stomach carcinoma cells and significantly correlated with survival ( P=0.011) . Moreover, our study indicated that miR-195 depressed the expression of FOXK1 and significantly reduced the activation of the PI3K/Akt pathway, which had a negative effect on the proliferation and invasion of stomach carcinoma cells. The phosphorylated Akt (s473 site) expression in the PI3K/Akt pathway was significantly decreased after overexpression of miR-195. Conclusion:Overall, our studies clarify the important function of the miR-195 in the diagnosis and therapy of patients with stomach carcinoma and reveal the FOXK1 and PI3K/Akt pathway regulation by the miR-195, which are of important clinical significance in the differential diagnosis.

Intensive phototherapy vs. exchange transfusion for the treatment of neonatal hyperbilirubinemia: a multicenter retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia.@*METHODS@#This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years.@*RESULTS@#A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group.@*CONCLUSIONS@#In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.

Prediction of the bioequivalence of different crystal forms of rifampicin based on physiologically based pharmacokinetic model / 中国药科大学学报

@#The physiologically based pharmacokinetic (PBPK) modeling strategy was adopted to predict the pharmacokinetic behavior of crystal forms I and II of rifampicin in humans, which was used to determine whether the two were bioequivalent.After conducting studies in vitro of the two crystal forms, a rat PBPK model was established based on the pharmacokinetic data of intravenous administration in rats.The model was optimized by the pharmacokinetic data of oral administration in rats.Species were extrapolated to healthy humans, and the extrapolation model was used to predict such pharmacokinetic behaviors as the drug-time curve, absorption site, and absorption amount of the two crystal forms of rifampicin in healthy humans.The prediction results of the healthy human model showed that the cmax of form I and form II rifampicin were 8.42 and 10.35 μg/mL, tmax were 0.40 and 0.32 h,and AUC0-t were both 62.90 μg·h/mL.According to the prediction results of absorption, neither crystal form I nor crystal form II rifampicin was absorbed in the stomach, yet both were completely absorbed in the intestinal tract, with both the absorption site and the absorption amount were basically the same.The pharmacokinetic parameters of both crystal forms I and II of rifampicin were very close, which could indicate bioequivalence.

Effects of Propofol on Hepatoma Carcinoma HepG2 Cell Invasion / 中国药房

OBJECTIVE:To study the effects of propofol on invasion of hepatoma carcinoma HepG2 cell. METHODS:MTT method was used to detect the viability of HepG2 cells which were cultured with 0(negative control),1,3 and 10 μg/ml propofol for 48 h. The ability of cell invasion was detect by Tranaswell method. The phosphorylation level of nuclear factor-κB p65(NF-κB p65) and the expression of matrix metalloproteinase 2 (MMP-2),MMP-9,E-cadhherin and Snail were detected by Western blot method. RESULTS:Compared with negative control,1,3,10 μg/ml propofol inhibited the cell viability and invasion,down-regu-lated the expression of Snail and the phosphorylation level of NF-κB p65,and up-regulated the expression of E-cadherin (P<0.01). 3,10μg/ml propofol down-regulated the expression of MMP-2 and MMP-9(P<0.01). Above effects depended on drug con-centration(P<0.01). CONCLUSIONS:Propofol can suppress HepG2 invasion,which might be related to the inhibition of NF-κB/Snail signal pathway.

Comparative study on Wnt, Notch signaling pathway molecules in primary breast cancer and matched lymph nodes metastasis stem cells / 临床与实验病理学杂志

Purpose To investigate the gene expression and significance ofβ-catenin, Cyclin D1 and Notch1 in primary breast cancer stem cells ( BCSC) and matched lymph node metastasis stem cells. Methods 30 cases of breast invasive ductal carcinoma and matched metastasis lymph nodes were made into single cell suspensions, then BCSC were separated from them by immunomagnetic sor-ting. β-catenin, Cyclin D1 and Notch1 gene expressions of Wnt, Notch signaling pathway were detected by real time PCR. ResultsThe expression of β-catenin in primary BCSC and matched lymph nodes metastasis stem cells had statistically no differences ( P >0.05), while the expression of Cyclin D1 and Notch1 in matched lymph nodes metastasis stem cells were significantly higher than the expression in primary BCSC (P<0.01, respectively). Conclusion Compared with the primary cancer stem cells, Cyclin D1 and Notch1 activation in metastasis cancer stem cells are in higher level, which leades to a higher capability of invasion and metastasis, which may be a new therapeutic target.

The role of CD4+CD25+ regulatory T cells in peripheral blood and intestinal endotoxin in liver injury of rat severe acute pancreatitis / 中华肝胆外科杂志

ObjectiveTo investigate the role of CD4+ CD25+ regulatory T cells(Treg) in peripheral blood and intestinal endotoxin (ET) in liver injury of rat severe acute pancreatitis (SAP).MethodsSixty male Wistar rats were randomly allocated into sham operation group(SO group) and severe acute pancreatitis group(SAP group).The rats in SAP group recevied the injection of Sodium Taurocholate(NaTc) into their far-end of bile-pancreatic duct and were sacrificed in 3-,6-and 12-hour,serum amylase(AMY) and alanine aminotransferase(ALT) determined by full-automatic biochemistry instrument,limulus reagent method is used to determine ET content in plasma,the proportion of Treg among peripheral lymphocytes was determined by Flow Cytometry(FCM),HE stain is used to observe pathological changes in liver and pancreas,the protein of Foxp3 activity was evaluated by immunohistochemistry staining,and the relationships between these indicators were analyzed using Pearson correlation analysis test.ResultsHistopathologic examination and the level of ALT revealed the occurrence of pancreatic inflammation and pathological changes of liver in SAP group.The percentage of Treg in SAP groups significantly increased at 3 h(2.26％ ±0.32％),6 h(2.36 ％ ±0.48％)and 12 h(2.80％ ±0.35％) comparing to the SO groups(P＜0.01) ; plasma ET levels compared with the SO group was statistically significant (P＜ 0,01 ),and 12 h (0.85 ± 0.11) compared to,3 h (0.74±0.11) and 6 h (0.78-±-0.07) was no significant difference (P＞0.05).The expression of Foxp3 protein on the livers were upregulated markedly.Pearson correlation analysis teat showed that quantities of Treg were positively proportional to the levels of ET(r=0.89,P＜0.01) after liver injury of SAP.ConclusionsSAP may lead to liver injury and the high plasma levels of ET and Treg in peripheral blood may play an important role in liver injury of SAP.

Effects of Shuangligan and Glycine on Th1/Th2 balancing in rats with severe acute pancreatitis / 中国综合临床

Objective To investigate the effects of Shuangligan and Glycine on Thl/Th2 balancing on severe acute pancreatitis ( SAP) in rats. Methods Thirty-two Wistar rats weighing (260 ± 20) g were randomly divided into sham operation (SO) group, SAP group, SAP + Slg (with the treatment by Shuangligan) group and SAP + Gly (with the treatment by Glycine ) group. Each group included 8 rats, which accepted different treatment according to the experimental design. Changes of plasma level of endotoxin ( ET) and serum amylase (AMY) and the effects of Shuangligan and Glycine on Thl/Th2 ratio at the 24th hour after operation were observed respectively. Results The plasma endotoxin (ET) level ( (0. 67 ±0. 11) EU/ml),proinflammatory cytokine (INF-γ:(8.43 ± 0.86) ng/L, IL-12: (8.26 ± 1.97) ng/L) and Thl/Th2 ratio (0.36 ± 0.07) in SAP group were significantly higher than those in SO group( ET: (0. 44 ±0.07) EU/ml, INF-γ: (3. 80 ±0. 55) ng/L, IL-12: (3. 34 ± 1. 34)ng/L,Thl/Th2 ratio (0. 24 ±0. 05) ) (P <0. 05). Compared with SAP group, SAP + Slg and SAP + Gly group had remarkably decreased plasma ET level ( (0. 57 ± 0. 08,0. 52 ± 0. 04) EU/ml) (P < 0. 05) and the Thl/Th2 ratio reached equilibrium ( SAP + Slg group; (0. 29 ± 0. 04 ), SAP + Gly group: (0. 25 ± 0. 06 )) . Conclusions In the earlier stage of SAP, the rising plasma ET level may cause the overreaction of the cell mediated immune response, which leads to the aggravated damages in tissue cells. Our data indicates that Shuangligan and Glycine can restrain the formation of intestinal endotoxemia and alleviate or prevent the tissue injuries.

Effects of rhein on renal tubular epithelial cells transdifferentiation in diabetic rats / 中国医师杂志

Objective To study the effect of rhein on the process of tubular epithelial-mesenchymat transformation in kidney of diabetic rats. Methods Wistar male rats were randomly assigned to 3 groups: Control group (N group, n=12),diabetic group(D group, n=12), rhein treatment group(R group, n=12).The rats of rhein treatment group were treated with daily intragastric administration of periment. The excretion of urinary protein and serum creatine were measured. Histological changes of renal tissue were observed by HE and MASSON stain. Immunohistochemistry was performed to investigate the expression of E-cadherin, α-SMA,FN and TGF-β1 in kidney. Results Compared with the control group, the tubulointerstitial injury and the accumulation of extraeellular matrix protein in diabetic models were obvious(P＜0.01).Compared with the control group, the expression of E-cadherin was decreased significantly and the expression of α-SMA,FN and TGF-β1 was increased significantly in diabetic group. E-cadherin was negatively correlated with TGF-β1(rs=-0.60,P＜0.05),α-SMA and FN was positively correlated with TGF-β1(rs=0.88,P＜0.05;rs:0.91,P＜0.01).In comparison with diabetic group,rhein could up-regulate the expression of E-cad and down-regulate the expression of α-SMA and FN in renal tubular epithelial cells(P＜0.01).Conclusion Rhein could protect kidney by ameliorating interstitial fibrosis in diabetic rats. The mechanism may be depend on down-regulating the expression of TGF-β1 and suppressing tubular epithelial-mesenchymal transformation.

EFFECT OF WHEY PROTEIN PEPTIDES ON ANTIOXIDANT ABILITIES IN AGED MICE / 营养学报

Objective To observe the antioxidant activities of whey protein peptides (WPP) in aged mice.Method The subacute aged model mice were made by neck back subcutaneous injection of D-galactose every day.Compared with VE as positive control,the mice were given three different doses of WPP,100,200,400 mg/(kg bw?d) respectively,the effect of WPP on the content of catalase (CAT),malondialdehyde (MDA),superoxide dismutase (SOD),glutathione peroxidase (GSH-PX)in serum,liver and brain were observed after 45 d.Results The CAT,SOD and GSH-PX activities in aged model group were significantly decreased,but MDA was significantly increased as compared to normal mice.While in the aged mice treated with WPP 200 and 400 mg/(kg bw?d),the activity of CAT,SOD and GSH-PX were significantly increased and the content of MDA significantly decreased as compared to aged mice.Conclusion WPP shows dose-dependant antioxidant effect in aged mice.