Objective: To study the effect of titanium dioxide (TiO2) nanoparticles on intestinal glucose absorption in young rats and its size effect.Methods: In the study, 63 small intestine segments were isolated from 63 Sprague-Dawley rats (SD rats, 4-week-old) to prepare the everted gut sac model.In the first part of our work, the everted sacs were exposed to 0, 50 mg/L TiO2 nanoparticles (24 nm) for 2 h with the presence of a series of glucose concentrations (10, 25, 50, 100, 200, 400, and 800 mmol/L), and the glucose absorbing function of the everted sacs were assessed in the process.On the basis of the work, utilizing the same method, further study was carried out to compare the effects of TiO2 nanoparticles (24 nm) and fine-particles (120 nm) on intestinal glucose absorbing function with the presence of 400 mmol/L glucose and 0, 10, 50, 200 mg/L TiO2.3 intestine segments were used in each group.Results: The cumulative glucose absorption increased with time extension and increased glucose concentration.In the first part of our work, with the presence of 400 mmol/L glucose, the group treated with 50 mg/L TiO2 nanoparticles showed significantly lower cumulative glucose absorption and glucose absorbing rate than the control group at the exposure time of 30 min (tcumulative absorption=3.254, P<0.05;tglucose absorbing rate=3.958, P<0.05), 90 min (tcumulative absorption=3.323, P<0.05;tglucose absorbing rate=3.063, P<0.05) and 120 min (tcumulative absorption=2.834, P<0.05;tglucose absorbing rate=3.002, P<0.05).At other glucose concentrations, statistically significant differences in cumulative glucose absorption or glucose absorbing rates were not found between the TiO2 nanoparticle exposed group and the control group.In the second part of our work, when compared with the control group, no significant downregulations in cumulative glucose absorption or glucose absorbing rates were observed in both TiO2 nano-particle treated group and TiO2 fine particle treated group.Differences between the TiO2 nanoparticle treated group and the TiO2 fine particle treated group were not statistically significant.Conclusion: Short-term exposure to TiO2 nanoparticles may downregulate the intestinal glucose absorbing function in young rats, and the difference with TiO2 fine particlesis is not obvious.

Objective:To compare the effect of TiO 2 nanoparticles on antioxidant function and element content of liver and kidney tissues in young and adult rats .Methods:Forty-eight SD male rats , half in 4-week (youth) old and half in 9-week (adult) old rats, were randomly divided into 8 groups, which were exposed to TiO2 nanoparticles [(75 ±15) nm, anatase] through intragastric administration at 0, 10, 50 and 200 mg/kg body weight every day for 30 days.The liver and kidney tissues were collected for antioxidant function and element content analysis .Results: 200 mg/kg TiO2 nanoparticles exposure significantly increased the liver total superoxide dismutase ( T-SOD ) activity and the kidney reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios in young rats, and significantly decreased the liver Mo, Co, Mn and P contents and the kidney Rb and Na contents in young rats .200 mg/kg TiO2 nanoparticles exposure significantly increased GSH/GSSG ratios and Rb contents and decreased Na con-tents in the liver of adult rats .No significantly difference was found in antioxidant indexes and elements content in the kidney of adult rats between three experimental groups and control group .Conclusion:TiO2 nanoparticles can enhance the antioxidant capacity and decrease the elements content in rat liver and kidney tissues .The liver is the more sensitive target organ and the young animals are more susceptible to TiO2 nanoparticles toxicity by the oral routes .

Biomonitoring can be applied to assess internal exposure and environmental exposure by exposure markers with providing internal exposure to biological characterization and individual exposure information, which is a key tool to evaluate the risk exposure to disease by biological alternation information. With the development of high throughput, broad spectrum and high efficiency screening and detection technology, biomonitoring is defined as traditional biological monitoring (targeted monitoring) and non targeted monitoring analysis (exposomic approaches). An exposomic approach differs from traditional biomonitoring in that it can theoretically include all exposures of potential health significance, whether they are derived from exogenous sources. Both traditional and nontraditional biomonitoring methods should be used to understand the complexity of exposures faced throughout the lifespan. Through hybrid approaches, emerging techniques and the integration of bioinformatics, and developing the detection methods for low abundance chemicals, improving the differentiation ability between endogenous and exogenous chemical, the health outcomes and exposures can be widely recognized and characterized, which can finally contribute to improving the precise prevention and intervention for diseases under the new exposomic model.

Bivalent platinum drugs [Pt(II)] represented by cisplatin are the first-line drugs in clinical application, but they have defects such as severe side-effects, poor bioavailability and drug resistance.Tetravalent platinum [Pt(IV)] complexes, derivatives of Pt(II) with different substitutions in axial positions, can be reduced to Pt(II) under the action of reductants in tumor, and can therefore act as a prodrug of Pt(II).Axial substituents can improve platinum drugs'' pharmacokinetics, selectivity and bioactivity, as well as achieve anti-tumor effect by additional cytotoxic mechanisms other than DNA damage, which can overcome the drug resistance to Pt(II).This review outlines the resistance mechanisms of platinum drugs, including platinum transport, detoxification, autophagy, and DNA repair, etc.It also summarizes the structure-activity relationship, main types and advances of tetravalent platinum prodrugs, as well as possible approach to solve platinum drug resistance.

OBJECTIVETo investigate the clinical efficacy of laparoscopic ventriculoperitoneal shunt with temporary external drainage in the treatment of hydrocephalus.

METHODSFifty-two cases of hydrocephalus randomized into two groups to receive laparoscopic assisted ventriculoperitoneal shunt with temporary external drainage (19 male and 7 female patients) and conventional ventriculoperitoneal shunt (20 male and 6 female patients). The catheterization time in the abdominal cavity, release time of intracranial hypertension, average hospital stay, postoperative pains, and postoperative complications were compared between the two groups.

RESULTSLaparoscopic ventriculoperitoneal shunt with temporary external drainage was performed successfully in all the cases without intraoperative conversion to open surgery. Compared with the conventional ventriculoperitoneal shunt, laparoscopic ventriculoperitoneal shunt with temporary external drainage was associated with significantly shortened catheterization time in the abdominal cavity, release time of intracranial hypertension, and average hospital stay (P<0.01) as well as lowered postoperative pain score at 4, 8, 16, and 24 h after the operation. The pain scores at 48 and 72 h postoperatively were comparable between the two groups. During the follow-up 3 months, the patients receiving laparoscopic ventriculoperitoneal shunt were found to have significantly lower rates of peritoneal end obstruction and abdominal cavity infection than those having conventional shunt (3.8% vs 19.2%, P<0.01; 1.0% vs 23.1%, P<0.01).

CONCLUSIONLaparoscopic ventriculoperitoneal shunt with temporary external drainage is feasible and produces better clinical therapeutic effect for management of hydrocephalus.

Abdominal Cavity ; Adult ; Female ; Humans ; Hydrocephalus ; surgery ; Laparoscopy ; Male ; Treatment Outcome ; Ventriculoperitoneal Shunt ; methods

Objective: To investigate the effects on human peripheral blood erythrocytes of long-term occupational contact with chromate. Methods: A dynamic cohort study was conducted of chromate-exposed workers (343 cases) and non-chromate-exposed workers (73 cases) at a chromate production enterprise who were selected according to specific inclusion and exclusion criteria from 2010 to 2015. Personal information and chromate exposure information were obtained by questionnaire. A generalized estimating equation was employed to analyze the effects on human peripheral blood erythrocytes of long-term occupational contact with chromate, controlling for age, gender, smoking, alcohol consumption and body mass index. Results: The mean ages and working ages of those entering the cohort study were 36.67 ±6.78 and 38.47 ± 7.18, respectively, for the exposure group and 8.39 ± 6.02 and 12.86 ± 8.34, respectively, for the control group. The erythrocyte content [(4.73±0.46), (4.81±0.53), (4.41±0.45)]×10¹²/L in the peripheral blood in the chromate exposure group was lower than that [(4.76±0.42), (4.95±0.45), (4.47±0.39)]×10¹²/L in the control group for the years 2010, 2011, 2012 and 2014 (t values were 0.38, 1.96, 0.92 and 1.21; P values were 0.703, 0.051, 0.358 and 0.227, respectively). The correlations between the years 2010 and 2011, 2011 and 2012, 2012 and 2014, and 2014 and 2015 were 0.667, 0.464,-0.070 and 0.020, respectively (P<0.001). The RR for males and those that consumed alcohol were 0.661 (95% CI: 0.616-0.709) and 0.910 (95% CI: 0.811- 1.201), respectively. Compared with the control group, the risk of reduced erythrocyte levels in the peripheral blood was increased by 0.915 (95% CI: 0.852- 0.982) in the chromate-exposed group. Conclusions The erythrocyte content of peripheral blood was reduced after long-term exposure to chromate. Maleness and alcohol consumption were factors that increased the risk of reduced peripheral blood erythrocytes in the chromate-exposed population.

OBJECTIVE: To screen the serum biomarkers in workers occupationally exposed to titanium dioxide nanoparticles(TiO_2 NPs) using metabolomics technology. METHODS: Using a typical sampling method, 56 workers who have occupationally exposed to TiO_(2 )in a TiO_2 NPs manufacturer were selected as the exposure group and 44 employees without occupational exposure to TiO_2 were selected as the control group. The high performance liquid chromatography-mass spectrometry technology was used to perform non-targeted metabolomics detection. The difference in serum metabolite profiles of the TiO_2 NPs exposure group and the control group were analyzed. Key differential metabolites and potential biomarkers were screened. The sensitivity and specificity of biomarkers were assessed through receiver operating characteristic(ROC) curve.RESULTS: We detected a total of 1 492 mass spectrum peaks in serum samples by serum metabolomics analysis, and 413 well-matched metabolites were obtained after annotation and identification. The results of principal component analysis and orthogonal partial least squares discriminant analysis showed that a total of 296 differentially expressed metabolites were found in the serum of individuals of the exposure group compared with the control group(all P<0.01). Among them the relative expression of metabolites increased in 265 species and decreased in 31 species. The ROC analysis results showed that the area under the ROC curve of five metabolites exceeded 0.900, and these metabolites included tanacetol A,(5 E)-2-hydroxy-4-oxobenzopenta-5-en-1-ylacetic acid, triterpene saponins organic compounds, 9,10,13-trihydroxystearic acid, and liquoric acid. The multiple linear regression analysis showed that the relative expression of all the five metabolites were positively correlated with occupational exposure to TiO_2 NPs after adjusting for the influence of confounding factors such as gender, age, body mass index, smoking and drinking(all P<0.01). CONCLUSION: Occupational exposure to TiO_2 NPs could induce changes in serum metabolite profiles. The metabolites represented by tanacetol A in serum can be used as potential biomarkers for indicating occupational exposure to TiO_2 NPs.

In order to search for new anti-inflammatory agents with strong activity and less toxicity relative to CDDO-Me, the ester prodrugs 2-8 of CDDO-Me were synthesized by treatment of oleanolic acid(OA)with DMF/K2CO3 to generate 1, followed by esterification of 1 with various aliphatic and aromatic carboxylic acids, respectively. All the target compounds showed strong inhibitory effects on LPS-induced NO production in RAW 264. 7 cells. Among them, compounds 2 and 7 possessed the most potent inhibitory effects with IC50=(2. 34±0. 67)and(3. 83±0. 97)nmol/L, respectively. Moreover, MTT assay indicated that all the target compounds(2-8)displayed much weaker anti-proliferative activity against RAW 264. 7 cell lines than CDDO-Me, suggesting that they may be less toxic than CDDO-Me.

The ultrasound endoscopic probes with very small size transducers are normally imaging by focused ultrasound beamforming technology. So the imaging frame rate is not very high, which cannot meet the needs of some clinical applications based on high imaging rate. In recent years, plane-wave ultrafast imaging technology can obtain high image frame rate and guarantee the image quality. In this paper, a plane wave ultra-fast imaging technique based on a home-made small line array ultrasound transducer is presented. Feasibility of the method is verified by simulation estimations and phantom experiments. The results show that for the small size transducer design of plane wave ultrafast imaging, it is necessary to fully consider the combination of the array element width and the number of array elements. So that a good plane wave imaging quality can be obtained. It lays a foundation for the ultra-fast imaging of plane wave in the interventional ultrasound imaging and ultrasound endoscopy.
Phantoms, Imaging ; Transducers ; Ultrasonography ; instrumentation

OBJECTIVE: To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening. METHODS: The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper. RESULTS: It was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen (), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score. CONCLUSIONS A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.
China ; Computer Simulation ; Coronavirus Infections ; diagnosis ; drug therapy ; Drug Repositioning ; methods ; Drugs, Chinese Herbal ; pharmacology ; Glycoproteins ; drug effects ; metabolism ; Humans ; Imaging, Three-Dimensional ; Mass Screening ; methods ; Molecular Docking Simulation ; methods ; Pandemics ; Peptidyl-Dipeptidase A ; drug effects ; Pneumonia, Viral ; diagnosis ; drug therapy ; Protein Binding ; United States ; United States Food and Drug Administration