Hepatic encephalopathy is a common metabolic neuropsychiatric syndrome in the development of end-stage liver disease. Since the concept of intestinal-liver-brain axis was proposed, the relationship between the pathogenesis of hepatic encephalopathy and the gut microbiota has been a hot research topic. In recent years, studies have confirmed that gut microbiota is involved in and affects various pathological processes of hepatic encephalopathy. This article combines the latest research progress at home and abroad to elaborate on the research status of regulating gut microbiota and thus interfering with the pathological process of hepatic encephalopathy, hoping to provide new ideas and methods for the intervention of hepatic encephalopathy based on the regulation of gut microbiota.

Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.
Antineoplastic Agents ; Benzamides ; chemistry ; DNA Repair ; Drug Design ; Humans ; Molecular Docking Simulation ; Poly(ADP-ribose) Polymerase Inhibitors ; chemical synthesis ; chemistry ; Poly(ADP-ribose) Polymerases

Objective To understand the situations of home establishments and the related domestic behaviors that causing injuries. Methods A total of 9760 families with regular residents in a community in Shanghai were investigated. Questionnaire was designed bascd on the Guidelines for Conducting Community Surveys on Injuries and Violence and International Classification of External Causes of Injuries. Results Inside the home settings, relative factors were found on issues as fire protection and using of electricity. In terms of household settings, 14.85% of the families had smoke alarm systems in the kitchen; 40.75% had no windows set for emergence. 50% to 70% of the residents had the idea of safe behaviors, including 35.93% of the families stored cleaning products,other chemicals or medical substances in alternative containers, such as used drinking bottle. Only 1.81% of the people being investigated thought that home was also a high risk place where injury might occur and it was placed number 9 in a multiple choice questionnaire. Data from the multiple level model analysis showed that factors as number of family members, space, education, profession etc. were closely related to the situation of home settings and their resident's behaviors. Conclusion Many injury related factors were found related to home establishments and people' s daily behaviors at home which called for interventions to be taken.

Objective To investigate the effect of intrathecal(IT)mibefradil on the mechanical and thermal hyperalgesia following chronic compression of dorsal mot ganglion(CCD)in rats,trying to elucidate the role of T-type calcium channels in the nociceptive signal transmission at spinal level.Methods Forty-eight male SD rats weighing 230-250 g were randomly divided into 6 groups(n=8 each):group Ⅰ sham operation;group Ⅱ CCD;group Ⅲ CCD+normal saline(N.S.)and group Ⅳ,Ⅴ,Ⅵ CCD+mibefradil 50 ?g(Ⅳ),100 ?g (Ⅴ),200 ?g(Ⅵ).The animals were anesthetized with intraperitoneal(IP)1% pentobarbital 40 mg?kg~(-1). Intrathecal catheter was placed according to the technique described by Yaksh et al.Five days after IT catheter placement L_4 and I_5 dorsal root ganglion(DRG)compression(CCD)was performed in group Ⅱ-Ⅵ.In sham operation group(Ⅰ)only L_(4-5) transverse processes and intervertebral foramina were exposed but DRGs were not compressed.In group Ⅳ,Ⅴ,and Ⅵ 5 days after CCD model was established a bolus of mibefradil 50,100 and 200 ?g in 10 ?l NS was given IT.In group Ⅲ NS 10 ?l was given IT instead of mibefradil.Mechanical withdrawal threshold(MWT)using Von Frey filament and thermal withdrawal latency(TWL)using radiant heat applied to the plantar surface were measured before CCD(baseline)and 1,3,5,7,14 and 21 days after CCD in group Ⅰ and Ⅱ and before and 30,60,120,240 and 480 min after IT mibefradil in group Ⅲ-Ⅵ.Results The animals in group Ⅱ(CCD group)developed mechanical and thermal hyperalgesia from the 1st day after operation to the end of the experiment.IT mibefradil 50,100 and 200 ?g can all attenuate both mechanical and thermal hyperalgesia induced by CCD.Conclusion Spinal T-type calcium channel may play an important role in the pathogenesis of neuropathic pain.

Background and Objectives The relationship between left atrial (LA) size and congestive heart failure (CHF) is well recognized;however, there is little information on the association of pulmonary vein (PV) diameter and CHF.The purpose of this study was to investigate the changes of PV and LA sizes in CHF patients by multislice computed tomography (MSCT) angiography using a new 64-slice scanner. Methods and Results We assessed diameters of PVs ostium and LA by 64-slice MSCT with three-dimensional reconstruction in 25 CHF patients and in 26 age- and sex-matched non-CHF controls. Compared with controls, CHF patients showed significant greater diameters of left superior pulmonary vein (LSPV) and right inferior pulmonary vein (RIPV) in both anteriorposterior(AP) and superior-inferior (SI) directions (P＜0.01), significant dilation of right superior pulmonary vein (RSPV) in AP direction (P＜0.05), as well as significant increase of LA transverse, AP, and SI diameters (P＜0.01). Conclusion Significant dilation of PVs with simultaneous LA enlargement was demonstrated in CHF patients. This anatomic and geometric changes may participate in the perpetuation of AF.

Objective To summarize the clinical data of 45 cases of familial adenomatous polyposis(FAP) and the experiences of treatment and diagnosis of FAP. Methods Retrospectively analyzed of the clinical data was made on 45 FAP patients.The choice of operative procedure included total colectomy+ileostomy in 25 cases,subtotal colectomy+rectal polyposis electrocautery in 15,and total colectomy with ileo-anal anastomosis in 5. Results Average age of patients at first diagnosis was 33.5 years. A family history was found in 35 patients. Bleeding, diarrhea, pain are common clinical presentations, and the numbers of polyposis were all more than 100. All patients without malignant change survived for 3-21years;and metastasis of liver was the main cause of death in patients with malignant change. There were age differences between malignant and non malignant group. Conclusions FAP lacks typical clinical presentation, and misdiagnosis is not uncommon. Surgical therapy should be done on an individual basis and according to the actual condition of patients.

Objective To observe the changes of respiratory and hemodynamic functions in children with different age undergoing laparoscopic Nissen's fundoplication(LNF). Methods Thirty-three children with LNF were divided into three groups according to the age: group Ⅰ,1 to 12 months,n=13;group Ⅱ,1 to 3 years old,n=10;and group Ⅲ,4 to 7 years,n=10.Heart rate(HR),mean arterial pressure,Ppeak,compliance of the respiratory system(CRS) and end-tidal carbon dioxide pressure(PETCO2) were recorded 5 min before pneumoperitoneum(T0),10 min(T1),60 min(T2) after pneumoperitoneum and 10 min after deflation(T3),and parameters of blood gas analysis such as PaCO2 were measured at the same time. Results Compared with those at T0,HR,Ppeak,PETCO2 and the difference between PaCO2 and PETCO2(Pa-ETCO2)were significantly increased at T1 and T2,while CRS was significantly decreased.The most significant changes were found in group Ⅰ. Conclusion The changes of respiratory and hemodynamic functions are observed in children undergoing LNF,and anesthesia management should be enhanced for those within 1 to 12 months old who experience the most significant changes.

OBJECTIVETo explore the inhibition and molecular mechanism of icaritin (ICT) combined doxorubicin (DOX) on human osteosarcoma MG-63 cells in vitro.

METHODSThe control group, ICT groups (10, 20, 40, 80, and 160 µmol/L), DOX groups (1, 2, 4, 8, and 16 µg/mL), and combination groups (20 µmol/ L ICT +1 µg/mL DOX, 20 µmol/L ICT +2 µg/mL DOX, 20 µmol/L ICT +4 µg/mL DOX, 40 µmol/L ICT +1 µg/mL DOX, 40 µmol/L ICT +2 µg/mL DOX, 40 µmol/L ICT +4 µg/mL DOX, 80 µmol/L ICT +1 µg/mL DOX, 80 µmol/L ICT +2 µg/mL DOX, 80 µmol/L ICT +4 µg/mL DOX) were set up. Human osteosarcoma MG-63 cells were respectively cultured and their effects on morphological changes were observed using inverted phase contrast microscope after 24-and 48-h intervention. The cell proliferation inhibition rate of each group was de- termined using CCK-8, and IC50 calculated. The MG-63 apoptosis rate was detected using Annexin V-FITC/ PI double dye flow cytometry. Expression levels of bcl-2, caspase-3, and p21 were detected using RT-PCR.

RESULTSICT and DOX could obviously inhibit the proliferation of MG-63 cell. Along with ICT concentration increasing from 10 µmol/L to 160 µmol/L, the cell proliferation inhibition rate also increased gradually from 9.67% ± 3.62% to 89.18% ± 9.66%. The IC50 was 46.93 µmol/L and 3.87 µg/mL respectively. ICT and DOX could cause either early or late stage apoptosis, down-regulate Bcl-2 gene expression, and up-regulate gene expressions of Caspase-3 and p21 respectively (P < 0.05). Aforesaid changes were more obviously seen in combination groups than in lCT groups and DOX groups (P < 0.05).

CONCLUSIONCT combined DOX had additive or synergistic inhibition effect for the proliferation of osteosarcoma MG-63 cells, which might be related with regulating gene expressions of bcl-2, caspase-3, and p21.

Apoptosis ; Bone Neoplasms ; metabolism ; pathology ; Caspase 3 ; metabolism ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Down-Regulation ; Doxorubicin ; pharmacology ; Drug Synergism ; Flavonoids ; pharmacology ; Humans ; Osteosarcoma ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism

Objective To investigate the metabolic alterations in the brain of neonates with HIE and correlate those alterations with clinical grading and prognosis of HIE.Methods Fourty-six eases of full-term neonates diagnosed as HIE clinically were performed MRI and 1~H-MRS,9 healthy neonates without the evidence of asphyxia were studied as controls,1~H-MRS techniques included single voxel proton MRS and two dimensional muhi-voxel chemical shift spectroscopy imaging,point resolved spectroscopy sequence was used for 1~H-MRS.Metabolic changes in the spectroscopy were analyzed in neonates with HIE,and study the relationgship between MRS findings and prognosis.Results(1)The typical 1~H-MRS manifestations of full- term neonates suffering from HIE were as follows:the peaks of Lac were elevated,GLx-? were elevated and NAA were decreased.(2)GLx-?/Cr ratio in control,mild,moderate and severe HIE group was 0.16, 0.21,0.64,and 1.31,respectively.Lac/Cr ratio in control,mild,moderate and severe HIE group was 0.12,0.14,0.19,and 0.26,respectively.There was a significant difference in the ratio of GLx-? and Lac/Cr between HIE group and control group(t=5.01,P

The shape and structure of granules are controlled by the granulation process, which is one of the main factors to determine the nature of the solid dosage forms. In this article, three kinds of granules of a traditional Chinese medicine for improving appetite and promoting digestion, namely, Jianwei Granules, were prepared using granulation technologies as pendular granulation, high speed stirring granulation, and fluidized bed granulation and the powder properties of them were investigated. Meanwhile, synchrotron radiation X-ray computed micro tomography (SR-µCT) was applied to quantitatively determine the irregular internal structures of the granules. The three-dimensional (3D) structure models were obtained by 3D reconstruction, which were more accurately to characterize the three-dimensional structures of the particles through the quantitative data. The models were also used to quantitatively compare the structural differences of granules prepared by different granulation processes with the same formula, so as to characterize how the production process plays a role in the pharmaceutical behaviors of the granules. To focus on the irregularity of the particle structure, the box counting method was used to calculate the fractal dimensions of the granules. The results showed that the fractal dimension is more sensitive to reflect the minor differences in the structure features than the conventional parameters, and capable to specifically distinct granules in structure. It is proved that the fractal dimension could quantitatively characterize the structural information of irregular granules. It is the first time suggested by our research that the fractal dimension difference (Df,c) between two fractal dimension parameters, namely, the volume matrix fractal dimension and the surface matrix fractal dimension, is a new index to characterize granules with irregular structures and evaluate the effects of production processes on the structures of granules as a new indicator for the granulating process control and optimization.
Drugs, Chinese Herbal ; analysis ; Fractals ; Medicine, Chinese Traditional ; Powders ; Quantitative Structure-Activity Relationship ; Synchrotrons ; Technology, Pharmaceutical ; Tomography, X-Ray Computed