OBJECTIVE To investigate the regulatory effects of couplet medicinals of Atractylodes macrocephala-Aucklandia lappa on gut microbiota and short-chain fatty acids （SCFAs） in the diarrhea-type irritable bowel syndrome （IBS-D） rats with spleen deficiency. METHODS The IBS-D rat model with spleen deficiency was induced by intragastric administration of Senna alexandrina combined with restraint stimulation. The model rats were divided into model group， positive control group （pinaverium bromide 1.5 mg/kg）， A. macrocephala-A. lappa low-dose， medium-dose and high-dose groups （0.7， 1.4， 2.8 g/kg）， with 6 rats in each group. Another 6 healthy rats were taken as the blank control group. The blank control group and the model group were given normal saline intragastrically， and other groups were given relevant drug liquid intragastrically， once a day， for consecutive 14 days. The general characteristics of rats and fecal water content were observed， and intestinal sensitivity [evaluating by abdominal wall withdrawal reflex （AWR） threshold] and the intestinal propulsion rate were determined. The serum levels of 5- hydroxytryptamine（5-HT）and SP were detected， and the pathological changes of colon tissue were observed； the protein expressions of 5-HT-3 receptor（5-HT3R）， 5-HT4R and 5-HT transporter（SERT） in colon tissue of rats were detected. 16S rRNA sequencing was performed for the feces of rats in blank control group， model group and A. macrocephala-A. lappa high-dose group； the contents of acetic acid， propionic acid and butyric acid in the feces of the rats were determined. RESULTS Compared with the model group， the body weight after 7 and 14 days of medication， fecal water content， AWR threshold， and the protein expressions of 5-HT4R and SERT in colon tissue were increased significantly in the A. macrocephala-A. lappa medium-dose and high-dose groups （P＜0.05 or P＜0.01）； serum contents of 5-HT and SP， intestinal propulsion rate （except for A. macrocephala-A. lappa medium-dose group）， the protein expression of 5-HT3R in colon tissue were decreased significantly （P＜0.01）； diarrhea relief， mental state recovery， and partially recovery of the structure of colon tissue were all found； moreover， the diversity and species number of gut microbiota were reduced in A. macrocephala-A. lappa high-dose group and the content of butyric acid in fecal samples was significantly reduced （P＜0.05）. CONCLUSIONS The compatibility of A. macrocephala and A. lappa can improve intestinal motility and sensitivity of IBS-D model rats with spleen deficiency， and alleviate diarrhea. This may be related to improving changes in intestinal microbiota structure， reducing 5-HT expression and butyric acid content， and increasing 5-HT4R and SERT expression.

Objective:To establish a model C-GALAD for detecting hepatocellular carcinoma (HCC) from the chronic liver disease and healthy people based on the serum markers.Methods:A clinical cohort including 229 hepatocellular carcinoma patients, 2 317 patients with chronic liver disease and 982 healthy people, was retrospectively collected from eight hospitals or physical examination institutions from April 2018 to October 2020. The data were divided into a training set and a testing set by stratified sampling with a 6∶4 ratio. A predictive model was established on the training set using a logistic backward regression method and validated on the testing set. In addition, clinical data from March to July 2021 in Beijing You′ an Hospital affiliated to Capital Medical University, including 84 patients with liver cancer and 204 patients with chronic liver disease collected were used for external independent validation of the model. The receiver operating characteristic curve (ROC) area under curve (AUC), the sensitivity and the specificity were used to evaluate the effectiveness of the model.Results:Through the logistic backward regression method, the seven signatures including age, gender, alpha-fetoprotein (AFP), alpha-fetoprotein alloplasm-3 ratio (AFP-L3%), des-gamma-carboxyprothrombin(DCP), platelet (PLT) and total bilirubin (TBIL) were selected as risk factors in the detection model. The area under the ROC curve (AUC) of the model on the testing set was 0.954, with an 88.04% sensitivity and a 94.85% specificity, and the AUC of model on the external independent validation set was 0.943, with an 89.29% sensitivity and a 90.2% specificity, which were better than other published models.Conclusion:The C-GALAD Ⅱ model can accurately predict the risk of hepatocellular carcinoma occurrence, and thus provide a trustworthy diagnosis method of hepatocellular carcinoma.

Primary liver cancer (PLC) is an aggressive tumor and prone to metastasize and recur. According to pathological features, PLC are mainly categorized into hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed hepatocellular cholangiocarcinoma, and fibrolamelic hepatocellular carcinoma, etc. At present, surgical resection, radiotherapy and chemotherapy are still the main treatments for PLC, but the specificities are poor and the clinical effects are limited with a 5-year overall survival rate of 18%. Liver cancer stem cells (LCSCs) are a specific cell subset existing in liver cancer tissues. They harbor the capabilities of self-renewal and strong tumorigenicity, driving tumor initiation, metastasis, drug resistance and recurrence of PLC. Therefore, the identification of molecular markers and the illustration of mechanisms for stemness maintenance of LCSCs can not only reveal the molecular mechanisms of PLC tumorigenesis, but also lay a theoretical foundation for the molecular classification, prognosis evaluation and targeted therapy of PLC. The latest research showed that the combination of 5-fluorouracil and CD13 inhibitors could inhibit the proliferation of CD13+ LCSCs, thereby reducing overall tumor burden. Taken together, LCSCs could be the promising therapeutic targets of PLC in the future. This review summarizes the latest progress in molecular markers, mechanisms for stemness maintenance and targeted therapies of LCSCs.
Carcinoma, Hepatocellular/genetics* ; Humans ; Liver Neoplasms/genetics* ; Neoplastic Stem Cells ; Prognosis

The biocompatibility of nanomaterials has attracted much attention. Graphene oxide (GO) is a nanomaterial widely used in biomedicine, but its toxicity can not be ignored. In this study, the effect of GO on the blood system (the hemolysis rate, the fragility of erythrocyte, and acetylcholinesterase activity) was systematically investigated. The results showed that the hemolysis rate of erythrocytes was lower than 8% when the GO concentration was below 100 μg/mL (P<0.01). GO at low concentration levels (<5 μg/mL) had no significant effect on the fragility of erythrocytes, but GO at high concentration (10 μg/mL) increased the fragility of erythrocytes (P=0.01). Moreover, GO increased the activity of acetylcholinesterase on erythrocytes. The concentration of 20 μg/mL graphene oxide with the size >5 μm (LGO) increased the activity of acetylcholinesterase by 42.67% (P<0.05). Then molecular dynamics simulation was used to study how GO interacted with acetylcholinesterase and increased its activity. The results showed that GO was attached to the cell membrane, thus may provide an electronegative environment that helps the hydrolysate to detach from the active sites more quickly so as to enhance the activity of acetylcholinesterase.
Acetylcholinesterase ; Erythrocytes ; Graphite ; Nanostructures

Objective To discuss the application of self-developed novel 16-slice mobile CT head scan.Methods A total of 391 patients were performed 16-slice mobile CT scan:145 were scanned in the emergency department,156 in the neurosurgical ICU,55 in the operated room,and 35 in the ambulance vehicle.Sixty-eight patients were with brain injury,122 were with cerebral hemorrhage,120 were with cerebral infarction,59 were with brain tumors,and 22 were with hemifacial spasm.Thirty-five patients were randomly selected from 391 patients and 8-slice mobile CT head scan was performed on them,which included 12 with brain injury,6 with cerebral hemorrhage,12 with cerebral infarction,3 with brain tumors and 2 with hemifacial spasm.The resolution,imaging quality,radiation doses,power consumption and performance stability of novel 16-slice mobile CT and 8-slice mobile CT head scan were compared.Results The resolution line pairs of brain tissues were 91 p/cm by 16-slice mobile CT and 71 p/cm by 8-slice mobile CT,respectively.The imaging quality of the two kinds of mobile CT head scans was high level to the clinic diagnostic criteria.The radiation dose of 16-slice mobile CT were 40.43 mGy,which decreased by 51.01％ as compared with that of 8-slice mobile CT (82.52 mGy).The personal power consumption of 16-silce mobile CT (0.29 kW· h) decreased by 38.30％ as compared with those of 8-layer mobile CT (0.47 kW· h).The 16-slice mobile CT kept regularly,while 8-slicer mobile CT stopped to work twice during clinical trial.Conclusion The 16-slice mobile CT scan has high resolution,fine imaging quality,low radiation dose,small power consumption and stable working performance.

Objective To evaluate the impact of the re-modified Sugiura procedure on portal hemodynamics and liver function in cirrhotic patients with portal hypertension.Methods Forty patients with cirrhosis and portal hypertension who underwent the re-modified Sugiura procedure in the Yichang Second People's Hospital from June 2006 to October 2014 were studied.Changes in the free portal pressure (FPP),portal venous flow (PVF) and liver functions before and after operation were analyzed.Results (1) The FPP at different phases of the operation (after opening the abdomen,after splenectomy,and after devascularization) were (43.2 ± 1.8) cmH2O,(34.8 ± 1.6) cmH2O and (35.2 ± 1.7) cmH2O,respectively.There were significant differences in FPP between the phases of after splenectomy and after opening the abdomen,as well as after devascularization and after opening the abdomen (P ＜ 0.05).There was no significant difference in FPP between after devascularization and after splenectomy (P ＞ O.05).(2) The PVF,which were measured with Doppler sonography at 4 time points (preoperative 1 day,postoperative 10 days,postoperative 6 months,postoperative 18 months),were (1 420.4 ± 137.7) ml/min,(1 205.2 ± 126.7) ml/min,(875.8 ± 118.0) ml/min and (893.8 ± 114.7) n1/min,respectively.There were significant differences in PVF between postoperative 10 days and preoperative 1 day,between postoperative 6 months and postoperative 10 days,as well as between postoperative 18 months and preoperative 1 day (P ＜0.05).There was no significant difference in PVF between postoperative 18 months and postoperative 6 months (P ＞0.05).(3)The liver functions were evaluated using the Child-Pugh score at 4 time points (preoperative 1 day,postoperative 10 days,postoperative 6 months,postoperative 18 months).There were no significant differences among the time points,(P ＞ 0.05).Conclusion The re-modified Sugiura's procedure durably,appropriately and effectively reduced the PVF and FPP,but it did not have any negative effects on the liver functions of patients with cirrhosis.

Objective To study the application of 99Tcm in rabbit cerebral thromboembolic stroke and thrombolysis effect of recombinant tissue plasminogen activator (rt-PA).Methods The 0.5 mL radioactive pertechnetate sodium (specification:5 mCi/2mL and radiation intensity 92.5 MBq/mL) was combined with 30 μL stannous chloride (5 mg/mL),and the 20 μL mixture was joined to whole blood,red blood cells,and plasma for labelling.Then 50 μL CaCl2 (0.5 mol/L) and bovine thrombin (50 IU/mL) were doped in mixture,and rapidly sucked into a polyethylene plastic pipe (PE80).Thrombus was formed for 2 h at 37 ℃ and cut into small pieces of 10 mm.Autologous blood clots combined with 99Tcm from external carotid artery were injected to internal carotid artery of rabbit,the radioactivity (counts per minute,CPM) was measured by gamma counting instrument,and the improvement of rt-PA 4.5 mg/kg (clinical equivalent dose) on this model was observed.Results After thromboembolism,CPM increased approximately by (5.1 ± 1.3) times,which suggested that the model was reliable.The rt-PA 4.5 mg/kg had significant progressive thrombolysis effect.Conclusion 99Tcm tracer technology could be applied to rabbit cerebral stroke model,which is stable and reliable

Aim To investigate TY501′s role in bleo-mycin ( BLM )-induced pulmonary fibrosis in rats. Methods Forty rats were randomly divided into 5 groups, including the sham operation, BLM, PFD, TY501(high and low dose) groups. After administra-tion of BLM intratracheally, PFD and TY501 were giv-en in each group daily, according to the dosage de-signed during 21 days. Lung coefficient, PaO2 were tested before killing the rats. The contents of ALB, ALP, LDH, GSH, HYP were detected by regent kit respectively. PCⅢ and COL4 were determined by ELISA. Results ( 1 ) Some indicators of alveolitis in early stage of IPF: the contents of lung coefficient in three treatment groups were lower and PaO2 was higher than those in BLM group ( P<0. 05 ); compared with BLM group, the contents of ALB, ALP, LDH in the treatment groups reduced on 21 st day ( P<0. 05 );the expression of GSH in BLM group was increased for feedback regulation and higher than the treatment groups and the sham operation group (P<0. 05);(2) some indicators of pulmonary interstitial fibrosis in late stage of IPF:the expressions of HYP, PCⅢand COL4 were reduced after the treatment. There were signifi-cant differences compared with BLM group ( P <0. 05 ) . Conclusions TY501 is valuable for the ther-apy of IPF, the same as the positive drug pirfenidone. TY501 attenuates BLM-induced pulmonary fibrosis, which may be related to the affection of TGF-βpathway and inhibition of MMPs.

Objective To identify microbubbles targeted (MBt) to alpha(v)beta(3) (αvβ3) via biotin-avidin bridge and evaluate the adhesion to human umbilical vein endothelial cells (HUVECs) in vitro.Methods MBt produced via biotin-avidin bridge were validated using fluorescence in vitro.Adhesion of αvβ3-integrin targeted MBt (MBαvβ3) to HUVECs was tested using the parallel plate flow chamber (PPFC) test.Results Bright green fluorescence was observed on the biotinylated microbubbles(MBB) incubated with fluorescein isothiocyanate labeled streptavidin (FITC-SA) and on MBB-SA incubated with FITC labeled biotin.There was no fluorescence seen on non-targeted control microbubbles,MBB incubated with FITC labeled protein A and MBB-SA incubated with FITC labeled protein A. The adherent rate of MBαvβ3 was significantly higher than MBt with non-specific antibody (MBN) in PPFC test,with 9.9±3.1 of MBαvβ3 and 0.8±0.3 of MBN adhered to HUVECs,respectively(P<0.05).Conclusions Avβ3 targeted microbubbles using biotin-avidin bridging method is highly efficient and reliable for HUVECs.

Objective To investigate the usefulness of parametric imaging of contrast-enhanced ultrasound(CEUS) in imaging hepatocellular carcinoma (HCC) using dynamic vascular patterns (DVP). Methods Thirty clinically or pathologically proven HCCs that had undergone CEUS were randomly included. SonoLiver CAP sofeware was used to analyze the CEUS images and reconstruct DVP parametric images. Results The rise time, time to peak and mean transit time were (16. 72±11. 07) s, (29. 92±14. 13) s,(115. 03±90. 91)s in HCC versus (26. 59±9. 60) s, (41.67±12. 59) s, (159.26±123. 74) s in the surrounding liver parenchyma (all P <0. 05). The perfusion index was (90. 41±102. 49) % in HCC versus (54. 10±24. 99)% in surrounding liver parenchyma( P = 0.044). DVP curve and DVP parametric image could both be divided into three types:washout,non-washout and cystic type. The percentages of which were 76.7% (23/30), 20.0% (6/30) and 3.3% (1/30) in DVP curves, respectively, and 66.7% (20/30), 30.0% (9/30) and 3.3% (1/30) in DVP parametric images,respectively. Conclusions Parametric image of CEUS could demonstrates the difference of flow perfusion static between HCC and surrounding liver parenchyma dynamically and directly.