OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.
Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-met/metabolism* ; Liver Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Animals ; Humans ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Amphibian Venoms/therapeutic use* ; Cell Line, Tumor ; Neoplasm Metastasis ; Cell Survival/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Neoplasm Invasiveness ; Mice, Inbred BALB C ; Mice, Nude ; Mice ; Male ; Bufanolides/therapeutic use* ; Protein Precursors ; Prothrombin ; Biomarkers

Objective:To establish a Fourier transform infrared spectroscopy (FT-IR) method for rapid identification of Cremastrae Pseudobulbus Pleiones Pseudobulbus and its adulterants.Methods:The Fourier transform infrared spectra of Cremastrae Pseudobulbus Pleiones Pseudobulbus and its adulterants were established, and the second derivative spectral analysis, clustering analysis, principal component analysis, opls-da and cluster independent soft mode classification model were analyzed to explore the difference characteristic peaks of Cremastrae Pseudobulbus Pleiones Pseudobulbus and its adulterants.Results:The first order infrared spectrum showed that the peak shape and peak intensity of Cremastrae Pseudobulbus Pleiones Pseudobulbus and its adulterants were different. Clustering analysis, principal component analysis and OPLS-DA results showed that Cremastrae Pseudobulbus Pleiones Pseudobulbus and its adulterants showed good clustering characteristics. SIMCA method was used to construct the model, and the accuracy of the training set and the verification set were 100%, which further verified the feasibility of this method in identifying the authenticity of Cremastrae Pseudobulbus Pleiones Pseudobulbus.Conclusions:The second-order infrared spectroscopy can accurately distinguish the differences between Cremastrae Pseudobulbus Pleiones Pseudobulbus and its adulterants. The method is fast and accurate, and can be used for the authenticity identification of Cremastrae Pseudobulbus Pleiones Pseudobulbus.

Objective To investigate the expression of kinesin family member 23(KIF23)in rectal cancer and its association with prognosis.Methods This study included 90 patients with rectal cancer who underwent surgical treatment at the First Central Hospital of Baoding from May 2017 to October 2019.Immunohistochemical staining was used to detect KIF23 expression,and the results were analyzed in combination with clinical and pathological data.Survival analysis was conducted using Kaplan-Meier methods and Cox proportional hazards models to assess the association between KIF23 expression and patient prognosis.Results Compared with adjacent non-tumor tis-sues,the expression level of KIF23 protein was significantly higher in rectal cancer tissues.Positive expression of KIF23 was significantly correlated with TNM stage,lymph node metastasis and distant metastasis in rectal cancer patients(P＜0.05).Kaplan-Meier analysis revealed that individuals expressing high levels of KIF23 experienced notably diminished disease-free survival(DFS)and overall survival(OS)relative to those with low KIF23 expression(P＜0.05).Cox regression analysis revealed that advanced TNM stage,lymph node metastasis,distant metastasis,and elevated KIF23 expression served as an independent predictor of adverse outcomes in pa-tients with rectal cancer(P＜0.05).Conclusions The expression level of KIF23 is closely related to the prognosis of rectal cancer.

Objective To predict the potential suitable habitats of Scutellaria barbata D.Don across China;To provide a theoretical basis for its artificial cultivation and standardized planting practices.Methods Distribution data were collected from 186 sample sites,combined with data from 90 environmental factors,and the MaxEnt model and ArcGIS 10.8.1 software were used to screen the main environmental factors affecting the distribution of Scutellaria barbata D.Don and to analyse and predict the distribution of Scutellaria barbata D.Don suitability zones in China.Results The dominant environmental factors affecting the distribution of Scutellaria barbata D.Don were the driest month precipitation,vegetation subclasses,minimum temperature in September,precipitation in October,and soil base saturation.The high-suitability zones for Scutellaria barbata D.Don are primarily concentrated in the northern Guangxi Zhuang Autonomous Region and its bordering areas with Hunan Province,the central of Guangdong Province,and the border regions between Jiangxi Province and Fujian Province.Conclusion The predicted results of this study can provide a reference for the selection of sites for artificial cultivation and standardized planting of Scutellaria barbata D.Don in southeast China and eastern southwest China(e.g.Zhejiang Province,Jiangxi Province,Sichuan Province,etc.),and provide a reference for the sustainable utilization of Scutellaria barbata D.Don medicinal resources.

Objective:To establish risk warning model for intraoperative hypothermia in patients undergoing laparoscopic myomectomy based on the nomogram model.Methods:127 patients undergoing laparoscopic myomectomy were divided into non-hypothermia group(86 cases)and hypothermia group(41 cases)according to whether intraoperative hypothermia occurred.Multivariate Logistic regression was used to analyze the influencing factors of intraoperative hypothermia in patients,and Nomogram prediction model was constructed and verified according to the influencing factors.Results:The intraoperative irrigation volume and intravenous input volume in the hypothermia group were higher than those in the non-hypothermia group,the basal body temperature at admission,intraoperative infusion temperature,and the proportion of intraoperative warmth were lower than those in the non-hypothermia group,the operation time and anesthesia time were longer than that in the non-hypothermia group(all P＜0.05).Multivariate logistic regression analysis showed that,excessive intraoperative irrigation volume,low basal body temperature and excessive intravenous input volume were risk factors for intraoperative hypothermia in patients undergoing laparoscopic myomectomy(P＜0.05),while intraoperative warmth was protective factor(P＜0.05).A nomogram prediction model was constructed based on influencing factors,and it was verified that the model had good discrimination(area under the curve was 0.881,P＜0.05),calibration degree(C-index=0.852,mean absolute error=0.002)and clinical applicability.Conclusion:Intraoperative irrigation volume,basal body temperature,intravenous input volume,and intraoperative warmth are the influence factors that intraoperative hypothermia in patients undergoing laparoscopic myomectomy,this Nomogram model based on these factors has a good predictive efficacy and clinical value for the prediction of intraoperative hypothermia in patients undergoing laparoscopic myomectomy.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

Objective To evaluate the effects of fasting and high-fat diet on the pharmacokinetics of rabeprazole sodium enteric-coated tablets in healthy Chinese subjects.Methods A single-center,randomized,open,two-agent,two-sequence,four-cycle,fully repeated crossover,single-dose trial design was used in this study,healthy subjects were assigned to receive single dose of rabeprazole sodium enteric-coated tablets 0.1 g in either fasting or high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of rabeprazole sodium enteric-coated in plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS),the model method of the non-compartmental was used to calculate the pharmacokinetic parameters by Phoenix WinNonlin 8.2.Results The main pharmacokinetic parameters of rabeprazole sodium enteric-coated tablets in fasting state and high-fat diet state were as follows:Cmax were(339.63±156.47)and(318.86±132.13)ng·mL-1;t1/2 were(2.34±0.68)and(3.60±2.40)h;AUC0_t were(556.62±251.65)and(528.50±201.78)ng·mL-1·h;AUC0-∞ were(563.39±255.69)and(535.15±203.24)ng·mL-1·h;tmax were 3.65 and 6.99 h.After high-fat diet,the Cmax and AUC of rapeprazole sodium after high-fat and high-calorie diet decreased,Cmax decreased by 6.12％,AUC0-t decreased by 5.05％,AUC0-∞ decreased by 5.01％,andtmaxwas delayed by about 3.34 h.Cmax,AUC0-t and AUC0-∞ 90％confidence interval were 73.13％-115.10％,83.22％-112.28％and 83.40％-112.13％,respectively.Neither was between 85.00％-125.00％.Conclusion High-fat diet affects the absorption rate and degree of rabeprazole sodium enteric-coated,so it is suitable to be administered on an empty stomach.