OBJECTIVE: To investigate the effects of combined inhibition of signal transducer and activator of transcription 3 (STAT3) and hypoxia-inducible factor-1α (HIF-1α) in the enhancement of chemosensitivity of the model of human laryngeal squamous cacinoma in nude mice. METHOD: Model nude mice were divided into six groups randomly: control group(A) , cisplatin group(B) , cisplatin and AG490 group(C) , cisplatin and HIF-1α⁻/⁻ group (D), cisplatin combined AG490 and HIF-1α⁻/⁻ group (E), HIF-1α⁻/⁻ group (F) (only in calculating tumor inhibition rate). 3mg/kg cisplatin was administered by peritoneal injection for 3 days. Then cisplatin and 10 mg/kg AG490 were administered every other day for 12 days. The expression of Ki67 and HIF-1α was detected by immunocytochemical method. Western blot was used to detect the expression of p-STAT3. RESULT: The expression of HIF-1α in group C and group D were lower than that in group B, and there were significant difference respectively (t₁ = 2.782, t₂ = 3.873, P < 0.05); The expression of HIF-1α in group E was lower than that in group C and group D respectively, and there were significant difference respectively (t₁ = 6.140, t₂ = 3.667, P < 0.01). The expression level of p-STAT3 in group C was markedly lower compared with that in group B, and there were significant difference between them (t = 17.840, P < 0.01); There were no difference between the expression level of p-STAT3 in group D and that in group B (t = 0.038, P > 0.05); The expression level of p-STAT3 in group E was significantly lower compared with that in group C and group D respectively (P < 0.01). Tumor inhibition rate of group E was higher than that in group B, group C , as well as group D respectively and there were significant difference respectively (t₁ = 5.509, P < 0.01; t₂ = 3.422, P < 0.05; t₃ = 2.718, P < 0.05 ). Ki67 index of group E was lower than that in group B, group C as well as group D respectively and there were significant difference respectively(t₁ = 8.307, P < 0.01; t₂ = 3.736, P < 0.05; t₃ = 4.524, P < 0.01). CONCLUSION Combined inhibition of STAT3 and HIF-1α could enhance chemo-sensitivity in the model of human laryngeal squamous cacinoma in nude mice.
Animals ; Antineoplastic Agents ; pharmacology ; Carcinoma, Squamous Cell ; drug therapy ; metabolism ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Ki-67 Antigen ; metabolism ; Laryngeal Neoplasms ; drug therapy ; metabolism ; Mice ; Mice, Nude ; Neoplasms, Experimental ; drug therapy ; metabolism ; STAT3 Transcription Factor ; genetics ; metabolism ; Tyrphostins ; pharmacology

OBJECTIVETo dynamically assess drug targeting of Yougui Pill (YP) and Zuogui Pill (ZP) using infrared thermography.

METHODSIn this self-control experiment, five healthy volunteers were recruited. By using infrared thermography 10 to 11 thermal images of different body locations were taken from each participant after they took warm water, YP, ZP, and their dissembled prescriptions at 30, 70, 100, 130, and 160 min, respectively. The heat values in the lower quadrant abdomen, uterus, Du channel, and Shenque (CV8) were statistically analyzed after scanning for 125 times.

RESULTSAdministration of YP and its disassembled prescriptions enhanced the heat value of the locations of the Du channel and Shenque (CV8), but did no enhance the heat value of the lower quadrant abdomen at 30 min. Administration of ZP and its disassembled prescriptions reduced the heat value in the locations of the lower quadrant abdomen, uterus, Du channel, and Shenque (CV8) at each time point.

CONCLUSIONThe drug targeting of ZP and YP focused on the locations of the Du channel and Shenque (CV8), not on the locations of the lower quadrant abdomen or uterus.

Adult ; Drug Delivery Systems ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Infrared Rays ; Thermography ; methods ; Young Adult

OBJECTIVE: To summarize the structural design strategy and safety assessments of rAAV packaging systems. METHODS: Based on the research progress and international review experience of commercial rAAV products, the design strategy and safety assessments of rAAV packaging systems were summarized. The design strategy and safety assessments of rAAV packaging systems were summarized. RESULTS: The scientific evaluation of the pharmaceutical design of rAAV for human should cover multiple aspects, because various types of AAVs differ in tissue selectivity, viral assembly, transgene expression. Meanwhile, the packaging system is diverse, and the production process is complex. CONCLUSION: The considerations referring to the rAAV structure and mechanisms of producing replication-competent AAV are proposed, and we hope to improve the communications between developers and regulators.

Objective To explore the effects of different doses of contrast agent (CA) on types of time-signal intensity curves (TICs) and semi-quantitative parameters after dynamic contrast-enhanced MRI (DCE-MRI) on Walker 256 murine breast tumor model.Methods A total of 12 rats burdened Walker256 breast cancer models were established and divided into 3 groups randomly, 4 in each group.Routine MR and DCE-MRI scans of the rats using Bruker Pharmascan 7T MR scanner were performed.Doses for the 3 groups were 0.2, 0.3, and 0.5 mmol/kg, respectively.MR data, TICs types and semi-quantitative parameters from each different dose group were statistically studied and compared to observe the differences.Results Tumors were enhanced significantly after injection.The types of TICs in all tumors were the Ⅲ pattern which was not influenced by CA doses.Semi-quantitative parameters of first enhancement (Efirst), maximal enhancement (Emax), washout enhancement (Ewash), and signal enhancement ratio (SER) showed statistical differences among the three dose groups (P＜0.05).Semi-quantitative parameters of time to peak (Tpeak) and washout velocity (Vwash) showed no statistical differences among the three dose groups (P＞0.05).Mean signal intensity of each group was highly negatively linear correlated with scan times after the peak (r=-0.972, P=0.000;r=-0.971, P=0.000;r=-0.989, P=0.000).The washout slope (slopewash) showed no statistical differences among the three groups (P＞0.05).Conclusions Injection doses of CA didn't change the TIC type, Tpeak, Vwash, and Slopewash.These parameters are comparable among different medical centers and can be considered as prior parameters to monitor the efficacy of neoadjuvant chemotherapy.

Objective To quantitatively analyze and compare the texture features of thermal and chemical lesions on the porcine striated muscle, in vitro extracted from high-frequency ultrasonograms using computer-assisted image analysis technique, and to investigate the application values. Methods The thermal lesion and chemical lesion were induced in vitro in porcine striated muscle by microwave ablation and anhydrous acetic acid injection, respectively. The two dimension (2D) ultrasonographic ifndings were qualitatively compared between the groups of thermal and chemical lesion models, in which eight textural features in geometric mathematics extracted from 2D ultrasonograms were quantitatively analyzed by a technique of computer-assisted image analysis named multiscale decomposition method of echo intensity of interface relfections. Results As expected, microwave ablation and anhydrous acetic acid caused signiifcant changes of several texture features extracted from ultrasonograms. There were significant differences between the normal group and microwave ablation group in grayscale mean (Mean), irregularity (IRGL) and periodicity of distribution (POD) as follows (Mean: 1.9143±0.2914 vs 1.2334±0.3357, t=-5.306, P=0.000; IRGL: 0.5577±0.0334 vs 0.5092±0.0459, t=-2.957, P=0.007; POD: 0.000 27±0.000 005 vs 0.000 29±0.000 008, t=4.782, P=0.000). There were signiifcant differences between the normal group and anhydrous acetic acid injection group in number of blobs (NOB), size of blobs (SOB) and periodicity of distribution (POD) as follows (NOB: 51.0324±13.6998 vs 31.6042±4.8315, t=4.633, P=0.000; SOB:16.4843±3.9349 vs 25.6230±2.3555, t=6.903, P=0.000;POD:0.000 26±0.000 015 vs 0.000 29±0.000 008, t=-4.459, P=0.000). For each group of injured regions, there were significant differences between the microwave ablation group and anhydrous acetic acid injection group in Mean, IRGL, NOB and SOB as follows (Mean: 1.2664±0.2688 vs 1.9143±0.2914, t=-5.661, P=0.000; IRGL: 0.5220±0.0422 vs 0.5577±0.0334, t=-2.295, P=0.032;NOB:51.0324±13.6998 vs 34.5856±2.6362, t=4.048, P=0.000;SOB:16.4843±3.9349 vs 25.3176±2.3501, t=-6.676, P=0.000). Conclusion Technique of computer-assisted image analysis named multiscale decomposition method of echo intensity of interface relfections, based on multiscale blob features extraction, was useful to differentiate ultrasonic texture features between the groups injured in our study, which established quantitative muscle ultrasound as a practical and reliable tool for the muscle injury diagnosis to distinguish the structural changes induced by different physiochemical factors.

Objective To investigate dental caries in 3-year-old children in Jing′an District of Shanghai and analyze the influence of oral cleaning behavior on caries in children. Methods Six hundread 3-year-old children from 12 kindergartens in Jing′an District, Shanghai were randomly selected by cluster sampling method for oral examination, and a self-administered questionnaire survey on children′s oral cleaning behavior was completed by parents.SPSS 22.0 software package was used for statistical analysis. Results Among the 600 children, the prevalence of dental caries was 42.50%, and the average dmft index was 1.76±2.92.Children who did not brush their teeth had a statistically significant increase in rate of dental caries(χ²=29.995, P < 0.001).Children who brushed their teeth for more than three minutes each time had a statistically significant lower rate of caries(χ²=3.918, P=0.048).Children whose parents helped their children brush their teeth every day had a lower rate of caries than those who brushed teeth by themselves, and the difference was statistically significant (χ²=8.718, P=0.013).Logistic regression analysis showed that age of beginning brushing teeth, times of brushing teeth per day and length of brushing teeth per time were all influence factors for caries in children (P < 0.05). Conclusion For the prevention and control of dental caries in 3-year-old, proper oral cleaning behavior is very important.We should make parents as a priority group for doing oral hygiene in children.Schools should strengthen oral health education for parents.Medical institutions should guide and monitor the effectiveness of oral hygiene in children.It is important to reduce the rate of dental caries in preschool children from three aspects:family, school and medical institutions.

Based on the transcriptome data, we cloned the open reading frame of IiHCT gene from Isatis indigotica, and then performed bioinformatic analysis of the sequence. Further, we detected expression pattern in specific organs and hairy roots treated methyl jasmonate( MeJA) by RT-PCR. The IiHCT gene contains a 1 290 bp open reading frame( ORF) encoding a polypeptide of 430 amino acids. The predicted isoelectric point( pI) was 5.7, a calculated molecular weight was about 47.68 kDa. IiHCT was mainly expressed in stem and undetectable in young root, leaf and flower bud. After the treatment of MeJA, the relative expression level of IiHCT increased rapidly. The expression level of IiHCT was the highest at 4 h and maintained two fold to control during 24 h. In this study, cloning of IiHCT laid the foundation for illustrating the biosynthesis mechanism of phenylpropanoids in I. indigotica.
Acyltransferases ; chemistry ; genetics ; metabolism ; Amino Acid Sequence ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Isatis ; chemistry ; classification ; enzymology ; genetics ; Models, Molecular ; Molecular Sequence Data ; Open Reading Frames ; Phylogeny ; Plant Proteins ; chemistry ; genetics ; metabolism ; Quinic Acid ; metabolism ; Sequence Alignment ; Shikimic Acid ; metabolism

Objective To study the repair function of united endothelial progenitor cells (EPC)transplantation on injured liver endothelium by bone marrow transplantation (BMT) conditioning.Methods C57BL/6 mice were divided into four groups randomly: normal control group, without any treatment; irradiation alone group, administered a total body irradiation(TBI) pretreatment, without BMT; (3) BMT alone group: C57BL/6 mice were infused with bone marrow mononuclearcells (MNC) 5 × 106/only through caudal vein not more than 4 h after the same TBI pretreatment as the irradiation alone group; united transplantation group: receiving the same way as the BMT alone group, but C57BL/6 mice were infused with EPC 5 × 105/only at the same time. Two, 4, 7, 14, and 21 days after the TBI, the changes of the liver weight were observed regularly. The histopathological examination of liver was done at the 4th, 7th, 14th, and 21st day after the TBI. Results In irradiation alone group, BMT alone group and united transplantation group the liver weight began to increase significantly on the day 2 and peaked at 14th day after the TBI, and the peaks were respectively (1.65±0. 15) times (P＜0. 05), (1.61 ±0.06) times (P＜0.05), and (1.11 ±0.40)times (P＜0. 05) of those in normal control group. At the day 14, the liver weight in irradiation alone group, BMT alone group and united transplantation group began to decrease, and on the day 21 the liver weight in united transplantation group had been completely restored to normal level, however the liver weight in irradiation alone group and BMT alone group were still significantly heavier than that in normal control group (P＜0. 05). Liver histopathological examination revealed that there were obvious sinusoidal endothelial cells (SEC) injury, hepatocyte edema and severe inflammatory cell infiltration in irradiation alone group, and on the day 7 the hepatocyte edema and necrosis were significantly worse than before, and almost no alive SEC were found. On the day 14 the injury of SEC in BMT alone group was lighter than before, but on the day 21 the injury had not returned to normal. On the day 7 the injury of SEC, hepatocyte edema and necrosis were alleviated in united transplantation group as compared with irradiation alone group and BMT alone group, and on the day 14 the injury had returned to normal basically. Conclusion The transplantation conditioning could damage recipient liver endothelium and the injury would persist, and united EPC infusion could repair the injured SEC following BMT.

Objective To preliminarily optimize the acupuncture protocol in treating migraine in acute stage. Method Ninety patients with migraine in acute stage were observed, with Visual Analogue Scale (VAS) as the evaluation index and an orthogonal design. Acupoints groups [Taiyang (EX-HN5), Fengchi (GB20), Taiyang (EX-HN5) and Fengchi (GB20)], insertion directions (perpendicular, downward penetration, and backward penetration), stimulation dosage (1 needle, 3 needles, and 5 needles) and acupuncture duration (30 min, 1 h, and 2 h), altogether 4 factors and 3 levels, formed up different acupuncture protocols to observe the analgesic efficacy in treating migraine in acute stage, so as to determine the role of the four factors (Chi-square test), advantage of the 3 levels (multiple comparisons) and the optimal grouping of the 4 factors and 3 levels. Result Acupoints group, insertion direction and stimulation dosage were the major factors in acupuncture analgesia, and the acupuncture duration was the secondary factor (P<0.05). The analgesic effect of Taiyang (EX-HN5) and Fengchi (GB20) was more significant than either Taiyang (EX-HN5) or Fengchi (GB20) (P<0.05). Penetration puncture from Naokong (GB19) towards Fengchi (GB20) (downward penetration) produced a more significant analgesic effect than from Fengchi (GB20) towards Wangu (GB12) and from Tianyou (TE16) towards Fengchi (GB20) (both backward penetration) (P<0.05). Acupuncture with Five needles and 3 needles (parallel horizontal insertion) were superior to that with 1 needle (P<0.05); acupuncture with 5 needles was better than that with 3 needles but without a statistical significance (P>0.05). Needle retaining for 2 h produced a better analgesic effect than retaining for 30 min and 1 h, but without statistical significances (P>0.05). Conclusion Taiyang (EX-HN5) plus Fengchi (GB20), downward penetration acupuncture, 5-needle parallel horizontal acupuncture, and 2-h needle retaining combine an optimal acupuncture protocol in treating migraine in acute stage. Nevertheless, 3-needle parallel acupuncture with 30-60-min needle retaining can also be chosen according to the condition of the patients.

Four screening methods, colorimetric assay, blood-plate hemolysis method, surface tension activ- ity and oil spreading technique were introduced to isolate strains producing bio-demulsifiers from 6 different bacteria source samples. The results of various screening methods were evaluated in this paper. Seventeen demulsifying strains were obtained, which are qualified in demulsification test of kerosene model emulsions. Among them, 5 strains showed high demulsifying ability, achieving 70% plus demulsifying ratio within 24 hours. Petroleum-contaminated soil, excess sludge from biological process treating oilfield produced water and sludge from municipal wastewater treatment plant were the best among all tested sources. Due to the determination limit, the colorimetric assay and blood-plate hemolysis method are not competent to screen bio-demulsifiers strains. The measurement of surface tension and oil spreading method were easy but accu- rate methods to isolate bio-demulsifiers strains. Although demulsification test of model emulsion is an effec- tive technique to target strains with the capability of breaking emulsions, it is sophisticated and time-con- suming. Thus it is recommended to use surface tension and oil spreading methods in pre-screening and vali- date the results in demulsification test with kerosene model emulsions.