Relevant literatures on the relationship betw een fluorosis and oxidative stress were reviewed.Based on most of the original papers published in recent years,we can see the increased free radicals and oxidative stress may occur in certain stage of fluoride intoxication,but confirmation of the causality between oxidative stress and fluoride-induced damages still remains much work to do.

Objective: To analyze the death among children under 5 years of age in Huzhou City, Zhejiang Province from 2012 and 2021, so as to provide insights into reduction of mortality among children. Methods: The mortality surveillance data among children under 5 years of age in Huzhou City from 2012 to 2021 were collected from Children Death Report Cards and Surveillance Report among Children under 5 Years of Age, including gender, place of residence, date of death and death diagnosis. The trends in mortality and cause of death were analyzed among children under 5 years of age in Huzhou City from 2012 to 2021. Results: A total of 1 262 deaths occurred among children under 5 years of age in Huzhou City from 2012 to 2021, with mean annual mortality of 4.39‰, and the mortality appeared a tendency towards a decline (χ2trend=132.695, P<0.001). A total of 899 infants died, with mean annual mortality of 3.13‰, and 363 children at ages of 1 to <5 years died, with mean annual mortality of 1.26‰. The mortality appeared a tendency towards a decline among both infants (χ2trend=117.778, P<0.001) and children at ages of 1 to <5 years (χ2trend=19.201, P<0.001). A total of 724 local children died, with mean annual mortality of 3.33‰, and there were 538 deaths among floating children, with mean annual mortality of 7.65‰. The mortality appeared a tendency towards a decline among both local (χ2trend=43.728, P<0.001) and floating children (χ2trend=94.038, P<0.001). The five most common causes of death included preterm birth or low birth weight (207 deaths, 16.40%), drowning (155 deaths, 12.28%), accidental asphyxia (138 deaths, 10.94%), other congenital abnormalities (126 deaths, 9.98%), and congenital heart diseases (113 deaths, 8.95%). Conclusions The mortality appeared a tendency towards a decline among children under 5 years of age in Huzhou City from 2012 to 2021, and preterm birth or low birth weight was the predominant cause of death.

AlM: To study the effects of different concentrations of Coix seed oil on human retinal capillary endothelial cells ( HRCECs ) proliferation and vascular endothelial growth factor ( VEGF) expression in high glucose environment.
METHODS: HRCECs extracted from human fresher eyeball and cultured in vitro, and ultimately used in the experiment were the growth of 3rd ~ 4th cells, the experimental were divided into blank control group, low glucose control group, high glucose control group, high glucose + ( 50ü L/mL, 100ü L/mL, 200ü L/mL ) different concentrations Coix seed oil group. Detecting the multiplication of HRCECs by MTT, the immunocytochemical method was employed to detect the each group HRCECs of VEGF expression.
RESULTS:MTT assay results showed that: different concentrations of coix seed oil acted at HRCECs for 48h, inhibition of cell proliferation was significant difference compared with high glucose control group (P<0. 05). Within 48h showed concentration dependence. There was no statistical difference between the low glucose group and high glucose control group (P>0. 05). lmmunocytochemical assay showed that:50ü L/mL, 100ü L/mL, 200ü L/mL Coix seed oil acted at HRCECs 48h, the expression of VEGF decreased significantly compared with the high glucose control group ( P< 0. 05 ), and in a dose- dependent manner. However, in high glucose control group, the expression of VEGF was obvious higher than that of low glucose control group (P<0. 05).
CONCLUSlON:Coix seed oil can inhibit the HRCECs proliferation and suppress the VEGF expression in high glucose environment.

A simple, rapid and sensitive method was developed for the quantification of tenofovir in plasma of Beagle dogs using HPLC-MS/MS analysis. The analytes tenofovir and internal standard (IS) adefovir were separated on a Zorbax SB-C18 column (3.5 microm, 100 mm x 2.1 mm, Agilent, USA) with mobile phase of methanol/water containing 0.3% formic acid using a gradient elution mode at a flow rate of 0.2 mL x min(-1). The plasma sample preparation was a simple deproteinization by the addition of 20% trichloroacetic acid followed by centrifugation. The detection was performed in positive selected reaction monitoring (SRM) mode with an electrospray ionization (ESI) source. The reactions monitored were m/z 288.1-176.2 for tenofovir and m/z 274.1-162.2 for adefovir (IS). Linear detection responses were obtained for tenofovir ranging from 10 to 5 000 ng x mL(-1). The intra- and inter-day precisions (RSD%) was no more than 6.3% with high recovery and good stability for the quantification, indicating the present method was specific, fast, accurate and reliable. The method was successfully applied to the pharmacokinetic study of two tenofovir agents. Tenofovir dipivoxil fumarate (BP0018, test agent) and tenofovir disoproxil fumarate (reference agent) were orally administrated to 8 Beagle dogs according to the 2 x 2 crossover design. Comparing with the reference agent, the longer MRT and t1/2 were obtained in the group of BP0018, while no significant difference was observed in AUC(0-t), AUC(0-infinity), C(max) and t(max) between them, suggesting that tenofovir dipivoxil fumarate was bioequivalent to the tenofovir disoproxil fumarate in Beagle dogs.

It is valuable to establish a chemical-pharmacokinetic (PK)-pharmacodynamics (PD) fingerprint of traditional Chinese medicine (TCM) for comprehensively understanding the TCM integrated conception and revealing the material foundation. The chemical, metabolic in vitro, and PK/PD in vivo fingerprints of Schisandra chinensis (SC) alcoholic extract were established and comparatively analyzed using HPLC-UV-MS method, rat liver microsomes in vitro and CCl4 intoxicated rats in vivo. Four known effective lignans, schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin, were detected as the standard references in SC alcoholic extract with high concentration. SC alcoholic extract and four lignans when incubated with rat liver microsomes produced several metabolites in NAPDH-dependent manner. Chemical fingerprint of some components with bioactivities were also identified in PK and PD fingerprints in normal and ALI rats that explained the material foundation of SC alcoholic extract for multiple pharmacological effects. Schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin could be considered as the "PK marker" of SC alcoholic extract or its relevant preparations, while two metabolites of the four lignans, 7, 8-dihydroxy-schizandrin and another one (M(W) 432), could be recognized as drug-metabolism (DM) Marker. This work provides experimental data for the further studies of metabolism or material foundation of SC components.

The rat single-pass intestinal perfusion model was applied to study the effect of CYP3A and P-glycoprotein on the absorption of buagafuran in lumen of rats. Buagafuran concentrations in intestinal perfusate and blood in vena mesenterica collected at different time points after perfusion were determined by GC-MS. Permeability coefficient of buagafuran was calculated by the equation [P(lumen) = -(Q/2pirl)Ln(C(out)/C(in)) and P(blood) = (deltaM(B)/deltat)/(2pirl)]. The effects of troleandomycin (TAO, CYP3A inhibitor), cyclosporin A (CYP3A/p-glycoprotein inhibitor) on the absorption of buagafuran in lumen were observed. After rat single-pass intestinal perfusion, the cumulative amount of buagafuran in mesenteric vein of rat was 73.4, 82.9, and 98.3 pmol x cm(-2) and were increased 3.9, 4.6, and 5.6 fold by addition of inhibitor of P-gp (LSN335984), CYP3A (TAO) or P-gp and CYP3A (CsA), respectively. Moreover, the metabolized fraction of buagafuran was decreased by 12%, 11% and 21% with inhibitors. The results suggested that the poor bioavailability of buagafuran was mostly due to the interplay of P-gp and CYP3A on the absorption, transport and metabolism of buagafuran in intestine of rats.

Humans ; Inservice Training ; Occupational Health ; Safety

AIM: To study the feasibility, security a nd validity of the intrapericardial injection with a trans-diaphragmatic approach in chronic heart failure rats and its value in the study of gene therapy for hea rt diseases, and further investigate whether adeno-associated virual gene transf er of sarcoplasmic reticulum Ca 2+-ATPase (SERCA2a) gene can improve ven tricular function in chronic heart failure (HF) rats. METHODS: An animal model of heart failure was obtained by creati ng descending aortic constriction in rats. Recombinant adeno-associated virus, c arrying enhanced green fluorescent protein (EGFP) gene and recombinant adeno-ass ociated virus carrying SERCA2a gene, were respectively injected into pericardium of heart failure rats in different groups (group HF+EGFP and group HF+SERCA2a) by intrapericardial injection with a trans-diaphragmatic approach. After 30 days , hemodynamic parameters were measured and analyzed. Cryosection was analyzed by fluorescence microscopy to examine the expression of green fluorescent protein, and Western blotting was performed to detect the expression of SERCA2a. RESULTS: Green fluorescence was detected in cryosection of the h earts in all rats in group HF+EGFP and the expression of green fluorescent prote in was ubiquitously. The expression of SERCA2a in all rats in group HF+SERCA2a w as more than those in group HF and group HF+EGFP. And overexpression of SERCA2a improved the systolic and diastolic function of heart failure rats significantly and the hemodynamic parameters were similar with those of the controls. CONCLUSION: The intrapericardial injection with a trans-diaphrag matic approach suggests a simple, safe, efficient and cheap technique for the ge ne therapy of chronic heart failure. Gene thransfer of SERCA2a may be a new appr oach for the treatment of chronic heart failure.

Objective:To interpret the main revision of the microbiological examination for nonsterile products:tests for specified microorganisms in Chinese Pharmacopoeia (2015 edition). Methods:The microbiological examination for nonsterile products:tests for specified microorganisms in Chinese Pharmacopoeia (2015 edition) was compared with the relevant content in the 2010 edition, and then the differences were investigated. Results:Microbiological examination for nonsterile products:tests for specified microorganisms in Chinese Pharmacopoeia (2015 edition) had been revised at a comparatively large scale in the inspection items, test method, micro-bial culture system, the quality control concept and so on. Conclusion:Microbial inspection system in Chinese Pharmacopoeia (2015 edition) is gradually improved to become a high standard check system in line with the international standards.

Objective To establish a nerve stem cell model possessing the potentiality of differentiating intoγ-aminobutyric acid neuron-like cells(GABAergic-like cells),and provide eligible investigative vector for study on GABAergic neurons degenerative diseases. Methods Dibutyryl cyclic adenosine monophosphate (dbcAMP)was applied to induce human neuroblastoma SH-SY5Y cells,and the SH-SY5Y cells were divided into control group (0 mmol·L-1 dbcAMP),0.3 mmol·L-1 dbcAMP group,0.6 mmol·L-1 dbcAMP group,1.0 mmol·L-1 dbcAMP group and 2.0 mmol·L-1 dbcAMP group;the morphological changes of SH-SY5Y cells were observed.The Image-Pro Plus 5.0 software was used to measure the length of neurites of the neuron-like cells, and the percentage of the SH-SY5Y cells with neurites longer than 30 μm was calculated. The immunofluorescence cytochemistry technique was utilized to test GAD65 positive cells,and the positive rate of immune response was calculated.Results The results of light microscope observation showed that the cells in control group were polygonal,circular or shuttle type with smooth membrane and clear boundaries. With the increasing of the concentrations of dbcAMP and the prolongation of time,the morphology of SH-SY5Y cells’bodies became smaller with longer processes in dbcAMP groups.The cells interwined each other and showed mature neuron phenotype in 1.0 mmol·L-1 dbcAMP group.Compared with control group(31.4%±4.2%),the percentages of the cell with neurites longer than 30 μm in 0.3, 0.6, 1.0, and 2.0 dbcAMP groups (40.1%± 5.7%, 47.5%± 6.2%, 73.1%±3.2%,and 74.3%± 6.1%)72 h after induction were significantly increased(P<0.05 or P<0.01). Compared with control group (10.2%± 2.1%), the GAD65 positive expression rates in 0.3, 0.6, 1.0,and 2.0 mmol·L-1,dbcAMP groups(22.1%±2.4%,46.9%±3.2%,70.7%±3.4%,and 72.3%±3.7%)72 h after induction were significantly increased(P<0.05 or P<0.01).Conclusion The SH-SY5Y cells have the potentiality of differentiating into GABAergic-like cells, and 1.0 mmol · L-1 is the optimal concentration of dbcAMP.