ZmPHR1 contributes to drought resistance by modulating phosphate homeostasis in maize.

As an essential macronutrient, phosphorus (P) is often a limiting nutrient because of its low availability and mobility in soils. Drought is a major environmental stress that reduces crop yield. How plants balance and combine P-starvation responses (PSRs) and drought resistance is unclear. In this study, we identified the transcription factor ZmPHR1 as a major regulator of PSRs that modulates phosphate (Pi) signaling and homeostasis. We found that maize zmphr1 mutants had reduced P concentration and were sensitive to Pi starvation, whereas ZmPHR1-OE lines displayed elevated Pi concentration and yields. In addition, 57% of PSR genes and nearly 70% of ZmPHR1-regulated PSR genes in leaves were transcriptionally responsive to drought. Under moderate and early drought conditions, the Pi concentration of maize decreased, and PSR genes were up-regulated before drought-responsive genes. The ZmPHR1-OE lines exhibited drought-resistant phenotypes and reduced stomatal apertures, whereas the opposite was true of the zmphr1 mutants. ZmPT7-OE lines and zmspx3 mutants, which had elevated Pi concentration, also exhibited drought resistance, but zmpt7 mutants were sensitive to drought. Our results suggest that ZmPHR1 plays a central role in integrating Pi and drought signals and that Pi homeostasis improves the ability of maize to combat drought.

Prevalence, Risk Factors, and Prognostic Factors of Primary Malignant Bone Neoplasms with Bone Metastasis at Initial Diagnosis: A Population-Based Study.

Background: Bone metastasis (BM) has been proven to be responsible for the poor prognosis of primary malignant bone neoplasms (PMBNs). We aimed to identify the prevalence, risk factors, and prognostic factors for PMBNs patients with BM based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods: 4,758 patients diagnosed with PMBNs from 2010 to 2018 were selected from the SEER database. All patients were divided into two groups: the BM group or the non-BM group. Pearson's chi-square test and Fisher's exact method were used to assess baseline characteristics, and logistic regression analysis was applied to assess risk factors. In addition, a nomogram was constructed based on the results of Cox regression analysis among 227 patients with BM. The good performance and clinical applicability of the nomogram were tested by the concordance index, operating characteristic curve, area under the curve, calibration curves, and decision curve analysis. Results: 227 (4.8%) patients had metastasis to bone at diagnosis. Primary site outside the extremities (axial: odds ratio, OR = 1.770; others: OR = 1.951), Ewing sarcoma (OR = 2.845), larger tumor size (5-8 cm: OR = 3.403; >8 cm: OR = 5.562), tumor extension beyond the periosteum (OR = 2.477), and regional lymph node metastasis (OR = 2.900) were associated with a higher risk of BM at the initial diagnosis of PMBNs. Five independent prognostic factors were found in the survival analysis: pathological type (chondrosarcoma vs. osteosarcoma: hazard ratio, HR = 0.342; Ewing sarcoma vs. osteosarcoma: HR = 0.592; and chordoma vs. osteosarcoma: HR = 0.015), marital status (HR = 2.457), pulmonary metastasis (HR = 1.934), surgery at the primary site (HR = 0.164), and chemotherapy (HR = 0.084). A nomogram based on these prognostic factors could be a good predictor of cancer-specific survival. Conclusions: We identified the prevalence, risk factors, and prognostic factors correlated with BM in PMBNs patients. The related nomogram could be a practical tool for therapeutic decision-making and individual counseling.

Assessment of Drying Kinetics, Textural and Aroma Attributes of Mentha haplocalyx Leaves during the Hot Air Thin-Layer Drying Process.

Since Mentha haplocalyx leaves are rich in bioactive constitutes, particularly volatile compounds, there are higher demands for high-quality dried medicinal and aromatic peppermint products. This study aimed to assess the drying kinetics of hot air thin layer drying Mentha haplocalyx leaves and exploring the effects of hot air-drying temperatures on the textural properties and sensory quality. According to our results, the Midilli model is the best model representing the hot air-drying process. The effective moisture diffusivity (Deff) and activation energy (Ea) of the hot air-drying process were determined as 7.51 × 10-9-3.03 × 10-8 m2/s and 57.98 KJ/moL, respectively. The changes of textural and aromatic profiles of dried Mentha haplocalyx leaves were subsequently evaluated by the SEM, GC-MS and E-nose technology. Changes in leaf cellular membrane structures were observed in this study, indicating that the loss of moisture content induced the shrinkage of leaf cells during the hot air-drying process. Moreover, the altered profile of volatile compounds was identified at the different drying temperatures. As a result of the GC-MS analysis, increasing the content of D-carvone from 61.89%, 69.25% and 78.2% resulted in drying temperatures of 35 °C, 45 °C and 55 °C, respectively; while a decreasing trend of other volatile compounds, including D-Limonene, cineole and l-caryophyllene was detected as drying temperature elevated. Finally, the aromatic profile was evaluated by E-nose, and results of the flavor radar fingerprint and PCA showed that aromatic profiles were significantly altered by the drying process. The overall results elucidated that the hot air thin layer drying at 35 °C efficiently improved the final quality of dried Mentha haplocalyx leaves by maintaining flavor properties.

[Kinetics and variation of volatile components of Atractylodis Macrocephalae Rhizoma during hot-air drying].

The present study explored the kinetics and variation of volatile components of Atractylodis Macrocephalae Rhizoma during the hot-air drying process to obtain the optimal process parameters under multiple goals such as drying efficiency and drying quality. The dry basis moisture content and drying rate curves along with the change of drying time of Atractylodis Macrocephalae Rhizoma were investigated at five levels of drying air temperatures(30, 40, 50, 60, and 70 ℃). The relationship between moisture ratio and time in the drying process of Atractylodis Macrocephalae Rhizoma was fitted and verified by Midilli model, Page model, Overhults model, Modified Page model, Logaritmic model, Two terms Exponential model, and Newton model. Meanwhile, the effective diffusion coefficient of moisture(D_(eff)) and activation energy(E_a) in Atractylodis Macrocephalae Rhizoma were calculated under different drying air temperatures. GC-MS was used to determine the volatile components and content changes of the fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures. The dry basis moisture content and drying rate of Atractylodis Macrocephalae Rhizoma were closely related to the temperature of the drying medium, and the moisture of the Atractylodis Macrocephalae Rhizoma decreased with the prolonged drying time. As revealed by the drying rate curve, the drying rate increased with the increase in hot air temperature, and the migration of moisture was accelerated. The comparison of the correlation coefficient(R~2), chi-square(χ~2), and root mean standard error(RMSE) of each model indicated that the parameter average of the Midilli model had the highest degree of fit, with R~2=0.999 2, χ~2=8.78×10~(-5), and RMSE=8.20×10~(-3). Besides, the D_(eff) at 30-70 ℃ was in the range of 1.04×10~(-9)-6.28×10~(-9) m~2·s~(-1), and E_a was 37.47 kJ·mol~(-1). The volatile components of fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures were determined by GC-MS, and 18, 18, 18, 17, 17, and 18 compounds were identified respectively, which accounted for more than 84.76% of the volatile components. In conclusion, the hot-air drying of Atractylodis Macrocephalae Rhizoma can be model-fitted and verified and the variation law of the moisture and volatile components of Atractylodis Macrocephalae Rhizoma with temperature is obtained. This study is expected to provide new ideas for exploring the drying characteristics and quality of aromatic Chinese medicine.

Comparing the minimum local anesthetic dose of ropivacaine in real-time ultrasound-guided spinal anesthesia and traditional landmark-guided spinal anesthesia: a randomized controlled trial of knee surgery patients.

BACKGROUND: Through previous studies and clinical practice, we have found that real-time ultrasound-guided (UG) spinal anesthesia (SA) and traditional landmark-guided (LG) SA each require a different minimum local anesthetic dose (MLAD) of ropivacaine. For this study, we used Dixon's up-and-down sequential method to analyze and compare the MLAD of different ropivacaine concentrations required for the UG and LG SA methods. METHODS: A total of 120 patients undergoing knee surgery were consecutively recruited and randomly divided into four groups (30 patients per group). These groups were categorized as follows: Group I: high ropivacaine ultrasound-guided (HRUG), Group II: low ropivacaine ultrasound-guided (LRUG), Group III: high ropivacaine landmark-guided (HRLG), and Group IV: low ropivacaine landmark-guided (LRLG). SA was established by a bolus administration of up-and-down doses of 0.75% or 0.5% plain ropivacaine. Initial doses of 16, 18, 12, and 14 mg were administered to groups I-IV, and after that, increased or decreased by 1.5 mg according to dose effectiveness. Upon identifying the intervertebral puncture level, a lumbar X-ray was performed with metal markers, and actual radiographic findings were identified and compared to the initial markings. RESULTS: For UG groups, the MLAD in the LRUG group was significantly higher than in the HRUG group [20.192 mg (95% CI, 19.256-21.174) versus 17.176 mg (95% CI, 16.276-18.124), respectively; P<0.001]. For LG groups, the MLAD in the LRLG group was significantly higher than in the HLRG group [14.478 mg (95% CI, 13.364-15.500) versus 13.201 mg (95% CI, 11.959-14.571), respectively; P=0.047]. When comparing both high ropivacaine groups (HRGs: I/III) to the low ropivacaine groups (LRGs: II/IV), we found that both UG subgroups (I/II) had a significantly higher MLAD than LG subgroups (III/IV) (P<0.001). US identified L4-5 in up to 90% of cases. Comparatively, palpation was successful in only 33.3% of patients. The rates of cephalad localization by US and palpation were 6.67% vs. 66.67%, respectively (P=0.002). CONCLUSIONS: We found a higher MLAD of ropivacaine was required for UG SA at the L4-5 level due to the method providing a more accurate (less cephalad) localization than traditional LG SA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033158.

Truth-telling, decision-making, and ethics among cancer patients in nursing practice in China.

BACKGROUND: Truth-telling toward terminally ill patients is a challenging ethical issue in healthcare practice. However, there are no existing ethical guidelines or frameworks provided for Chinese nurses in relation to decision-making on truth-telling of terminal illness and the role of nurses thus is not explicit when encountering this issue. OBJECTIVES: The intention of this paper is to provide ethical guidelines or strategies with regards to decision-making on truth-telling of terminal illness for Chinese nurses. METHODS: This paper initially present a case scenario and then critically discuss the ethical issue in association with ethical principles and philosophical theories. Instead of focusing on attitudes toward truth disclosure, it aims to provide strategies regarding this issue for nurses. It highlights and discusses some of the relevant ethical assumptions around the perceived role of nurses in healthcare settings by focusing on nursing ethical virtues, nursing codes of ethics, and philosophical perspectives. And Confucian culture is discussed to explicate that deontology does not consider family-oriented care in China. CONCLUSION: Treating each family individually to explore the family's beliefs and values on this issue is essential in healthcare practice and nurses should tailor their own approach to individual needs regarding truth-telling in different situations. Moreover, the Chinese Code of Ethics should be modified to be more specific and applicable. Finally, a narrative ethics approach should be applied and teamwork between nurses, physicians and families should be established to support cancer patients and to ensure their autonomy and hope. ETHICAL CONSIDERATIONS: This paper was approved by the Ethics Committee of The Second Affiliated Hospital of Guangzhou Medical University. The authors have obtained consent to use the case study and it has been anonymised to preserve the patient's confidentiality.

Sequencing of complete mitochondrial genomes confirms synonymization of Hyalomma asiaticum asiaticum and kozlovi, and advances phylogenetic hypotheses for the Ixodidae.

Phylogeny of hard ticks (Ixodidae) remains unresolved. Mitochondrial genomes (mitogenomes) are increasingly used to resolve phylogenetic controversies, but remain unavailable for the entire large Hyalomma genus. Hyalomma asiaticum is a parasitic tick distributed throughout the Asia. As a result of great morphological variability, two subspecies have been recognised historically; until a morphological data-based synonymization was proposed. However, this hypothesis was never tested using molecular data. Therefore, objectives of this study were to: 1. sequence the first Hyalomma mitogenome; 2. scrutinise the proposed synonymization using molecular data, i.e. complete mitogenomes of both subspecies: H. a. asiaticum and kozlovi; 3. conduct phylogenomic and comparative analyses of all available Ixodidae mitogenomes. Results corroborate the proposed synonymization: the two mitogenomes are almost identical (99.6%). Genomic features of both mitogenomes are standard for Metastriata; which includes the presence of two control regions and all three "Tick-Box" motifs. Gene order and strand distribution are perfectly conserved for the entire Metastriata group. Suspecting compositional biases, we conducted phylogenetic analyses (29 almost complete mitogenomes) using homogeneous and heterogeneous (CAT) models of substitution. The results were congruent, apart from the deep-level topology of prostriate ticks (Ixodes): the homogeneous model produced a monophyletic Ixodes, but the CAT model produced a paraphyletic Ixodes (and thereby Prostriata), divided into Australasian and non-Australasian clades. This topology implies that all metastriate ticks have evolved from the ancestor of the non-Australian branch of prostriate ticks. Metastriata was divided into three clades: 1. Amblyomminae and Rhipicephalinae (Rhipicephalus, Hyalomma, Dermacentor); 2. Haemaphysalinae and Bothriocrotoninae, plus Amblyomma sphenodonti; 3. Amblyomma elaphense, basal to all Metastriata. We conclude that mitogenomes have the potential to resolve the long-standing debate about the evolutionary history of ticks, but heterogeneous evolutionary models should be used to alleviate the effects of compositional heterogeneity on deep-level relationships.

Serological survey of avian influenza virus infection in non-avian wildlife in Xinjiang, China.

We conducted a serological survey to detect antibodies against avian influenza virus (AIV) in Gazella subgutturosa, Canis lupus, Capreolus pygargus, Sus scrofa, Cervus elaphus, Capra ibex, Ovis ammon, Bos grunniens and Pseudois nayaur in Xinjiang, China. Two hundred forty-six sera collected from 2009 to 2013 were assayed for antibodies against H5, H7 and H9 AIVs using hemagglutination inhibition (HI) tests and a pan-influenza competitive ELISA. Across all tested wildlife species, 4.47 % harbored anti-AIV antibodies that were detected by the HI assay. The seroprevalence for each AIV subtype across all species evaluated was 0 % for H5 AIV, 0.81 % for H7 AIV, and 3.66 % for H9 AIV. H7-reactive antibodies were found in Canis lupus (9.09 %) and Ovis ammon (4.55 %). H9-reactive antibodies were found in Gazella subgutturosa (4.55 %), Canis lupus (27.27 %), Pseudois nayaur (23.08 %), and Ovis ammon (4.55 %). The pan-influenza competitive ELISA results closely corresponded to the cumulative prevalence of AIV exposure as measured by subtype-specific HI assays, suggesting that H7 and H9 AIV subtypes predominate in the wildlife species evaluated. These data provide evidence of prior infection with H7 and H9 AIVs in non-avian wildlife in Xinjiang, China.

Effects of Foxp3 gene modified dendritic cells on mouse corneal allograft rejection.

OBJECTIVE: To investigate the effect of Foxp3 gene modified dendritic cells (Foxp3 + DC) on allogeneic T cells proliferation and to study the effect of Foxp3 + DC on corneal allograft rejection. METHODS: Lentivirus-Foxp3 was transfected into DC2.4 cells, as Foxp3 + DC cells. 42 BALB/c mice were randomly divided into: Group A (n = 6), normal group; Group B (n = 12), Group C (n = 12) and Group D (n = 12), allograft groups, were treated with normal saline, DC2.4, Foxp3 + DC by intraperitoneal injection, respectively. RESULTS: Compared with the control group, Foxp3 protein in the Foxp3 + DC cells increased significantly (P < 0.05); the expressions of CD80 and CD86 immunophenotypes of Foxp3 + DC cells decreased significantly (P < 0.05); IL-12 secretion reduced (P < 0.05), but IL-10 secretion was promoted (P < 0.05). The average transplant survival time in Group B was (14.833 ± 1.472) d, and Group C and Group D led to a statistically significant prolongation of transplant survival to (17.667 ± 1.366, 23.000 ± 2.000) d (P < 0.05) respectively. 14 d after transplantation, as compared with Group C and D, the expressions of IFN-γ in grafts markedly increased in Group B. 14 d after transplantation, as compared with Group B, the expressions of Foxp3 mRNA, IDO mRNA in grafts decreased remarkably in Group C and D (P < 0.05); as compared with Group C, the expressions of Foxp3 mRNA, IDO mRNA in grafts decreased remarkably in Group D (P < 0.05). CONCLUSION: Foxp3 + DC cells reduce the expression of costimulatory factors, reduce the secretion of IL-12, promote IL-10 production and inhibit the stimulation of alloreactive T cell proliferation response capacity. Foxp3 + DC cells play important roles in inhibiting corneal allograft immune response and prolonging graft survival time.

Anti-HER-2 anti-CD3 bi-specific antibodies inhibit growth of HCT-116 colorectal carcinoma cells in vitro and in vivo.

OBJECTIVE: This study is conducted to evaluate the effects of anti-HER-2 anti-CD3 bi-specific antibodies(BsAb) on HER-2/neuover-expressing human colorectal carcinoma cells. METHODS: Growth was assessed by MTT assays after exposure of HCT-116 cells to Herceptin, anti-CD3 and BsAb antibodies. Immunocytochemistry was applied to test the HER-2 level of HCT-116. In a nude mouse model, HER-2 CD3 BsAb was combined with effector cells (peripheral blood lymph cells from normal human being) for observations on in Vivo growth of tumors. RESULTS: Compared with the control group, using effector cells combined with anti-CD3 McAb, Herceptin or HER2 CD3 BsAb, tumor cell growth in vitro and in vivo was significantly inhibited (P<0.05), most remarkably in the HER2 CD3 BsAb case. The growth of xenografts with HER2 CD3 BsAb combined with effector cells was also significantly inhibited when compared with the anti-CD3 McAb or Herceptin groups (P<0.05). CONCLUSION: HER-2/neu might be a useful target for immunotherapy in colorectal carcinoma, anti-HER2 anti-CD3 BsAb exerting clear anti-tumor effects.

The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation.

Insulin-stimulated glucose uptake by the glucose transporter GLUT4 plays a central role in whole-body glucose homeostasis, dysregulation of which leads to type 2 diabetes. However, the molecular components and mechanisms regulating insulin-stimulated glucose uptake remain largely unclear. Here, we demonstrate that Axin interacts with the ADP-ribosylase tankyrase 2 (TNKS2) and the kinesin motor protein KIF3A, forming a ternary complex crucial for GLUT4 translocation in response to insulin. Specific knockdown of the individual components of the complex attenuated insulin-stimulated GLUT4 translocation to the plasma membrane. Importantly, TNKS2(-/-) mice exhibit reduced insulin sensitivity and higher blood glucose levels when re-fed after fasting. Mechanistically, we demonstrate that in the absence of insulin, Axin, TNKS and KIF3A are co-localized with GLUT4 on the trans-Golgi network. Insulin treatment suppresses the ADP-ribosylase activity of TNKS, leading to a reduction in ADP ribosylation and ubiquitination of both Axin and TNKS, and a concurrent stabilization of the complex. Inhibition of Akt, the major effector kinase of insulin signaling, abrogates the insulin-mediated complex stabilization. We have thus elucidated a new protein complex that is directly associated with the motor protein kinesin in insulin-stimulated GLUT4 translocation.

Changes in objective vault and effect on vision outcomes after implantable Collamer lens implantation: 1-year follow-up.

PURPOSE: To investigate the changes in vault and the effect on visual outcomes 1 year after implantable Collamer lens (ICL) implantation. METHODS: In this retrospective study, 127 eyes of 66 patients undergoing ICL implantation were examined both before and up to 1 year after the surgery. The examination contents included white-to-white (WTW) diameter, central vault of the ICL (distance between posterior surface of ICL and anterior surface of crystalline lens), refractive error, and wavefront high-order aberration (HOA). All statistical analyses were performed using SPSS 13.0 software. RESULTS: A significant decrease in vault was noted up to 1 month, after which the value stabilized (p=0.001). The moderate vault decreased significantly after the first 3 months postsurgery (paired-samples t test, p<0.05). Low vault showed a tendency to increase and high vault showed a tendency to decrease, but not significantly, over time. There was no statistically significant correlation between the amount of vault and the refractive error (Pearson correlation coefficient R=0.111, p=0.473) and there was a statistically significant correlation between the vault and HOAs (R=0.304, p=0.024). CONCLUSIONS: Implantable Collamer lens vault over the crystalline lens had the tendency toward a slight decrease with time and did not significantly affect the vision outcome 1 year after surgery.

[The observation of the effects of a micromolecular compound J2 on rat corneal allograft using atomic force microscopy].

OBJECTIVE: To study the cell membrane of corneal endothelium with a micromolecular compound J2 in corneal allograft of rat using atomic force microscopy (AFM). METHODS: Cohort study. Subjects were divided into two groups: group A (n = 15): experimental group; group B (n = 15): placebo control group. At the fifth, tenth, fifteen, twentieth, twenty-fifth day after penetrating keratoplasty, the donor implant was separated from receipt bed, one part of which was stained by HE and the others fixed into AFM sample. Amplitude and height images were obtained in the tapping mode with a scan rate of 2 Hz and an integral gain of 0.3 to 0.5. Statistical analysis was performed using single-factor analysis of variance and P value was calculated. RESULTS: The average transplant survival time in group A was (33.12 ± 6.80) d, and those in group B was (18.87 ± 4.19) d. There were significant difference between two group (F = 47.7449, P = 0.00). There were obvious differences on ultrastructure measured by AFM between two groups. At the fifth day after penetrating keratoplasty, regular hexagonal structure of corneal endothelium was observed by AFM in both two group. The diameter of corneal endothelium was about 15 µm, uneven microstructure of cell could be found. The time being, different changes were arose in two group: a clear microstructure could be found in group A, however the microstructure of cell could not be recognized in group B. One way analysis of variance showed that significant differences on parameters (Ra, Rp and Rv) were found between two groups (P < 0.05). At the fifth day after penetrating keratoplasty, group A: Ra (97.64 ± 31.58) nm, Rp (297.79 ± 25.19) nm, Rv (545.55 ± 25.83) nm; group B: Ra (112.61 ± 34.29) nm, Rp (265.06 ± 24.17) nm, Rv (544.41 ± 21.78) nm (Fa = 30.9416, P = 0.0000; Fp = 263.6018, P = 0.0000; Pv = 1.2013, P = 0.2735). At the tenth day after penetrating keratoplasty, group A: Ra (102.98 ± 32.98) nm, Rp (711.38 ± 21.94) nm, Rv (639.89 ± 22.58) nm; group B: Ra (222.85 ± 31.28) nm, Rp (111.22 ± 20.35) nm, Rv (746.49 ± 23.17) nm (Fa = 2086.4535, P = 0.0000; Fp = 53768.4676, P = 0.0000; Pv = 3257.3178, P = 0.0000). At the fifteenth day after penetrating keratoplasty, group A: Ra (87.44 ± 34.97) nm, Rp (344.18 ± 21.09) nm, Rv (482.61 ± 22.27) nm; group B: Ra (197.64 ± 35.72) nm, Rp (510.76 ± 24.98) nm, Rv (545.62 ± 23.17) nm (Fa = 1458.1057, P = 0.0000; Fp = 7788.6963, P = 0.0000; Pv = 1153.2860, P = 0.0000). At the twentieth day after penetrating keratoplasty, group A: Ra (85.85 ± 32.53) nm, Rp (348.69 ± 21.26) nm, Rv (367.65 ± 23.12) nm; group B: Ra (201.36 ± 34.12) nm, Rp (788.58 ± 20.34) nm, Rv (563.33 ± 21.01) nm (Fa = 1801.1215, P = 0.0000; Fp = 67 057.9516, P = 0.0000; Fv = 11 770.2195, P = 0.0000). At the twenty-fifth day after penetrating keratoplasty, group A: Ra (104.97 ± 32.47) nm, Rp (395.05 ± 20.38) nm, Rv (396.17 ± 21.59) nm; group B: Ra (43.85 ± 31.28) nm, Rp (249.88 ± 20.79) nm, Rv (154.88 ± 22.37) nm (Fa = 551.4134, P = 0.0000; Fp = 7458.9255, P = 0.0000; Pv = 18 070.5189, P = 0.0000). CONCLUSIONS: The morphology and ultrastructure of corneal endothelium in group A with J2 were different from group B by observation with AFM. J2 was an effect micromolecular in prevention of corneal allograft rejection.

[Progress in the methods of ocular pharmacokinetics].

Pharmacokinetics can help us to understand the metabolic feature of drugs and it also can instruct the dosage, interval, route and form of drugs used in clinic, guarantee the curative effects and reduce the side effects and toxicity. With the wide range of applications, high sensitivity and specificity, chromatography and immunoassay have been the common methods used in pharmacokinetic study, but the results are one-dimensional, operation is complicated and there are more interference factors. Imaging examination and Raman spectroscopy can be carried out in the ocular pharmacokinetic research non-invasively and continuously in vivo, but only for some specific drug testing. Subject to the restrictions of the devices themselves, specificity and sensitivity are somewhat less. Therefore, it is necessary to chose a suitable method taking into account the drug delivery methods, drug target tissue, drug metabolism characteristics of the selection of suitable methods, or combine with several methods as complementary and validation. In addition, a variety of pharmacokinetic models can also well describe, explain and predict the metabolism of drugs in eyes.

Influence of N(2)O(4) on multifocal electroretinogram in winstar mice.

AIM: To record multifocal electroretinogram from different dosage of N(2)O(4) injected mice. In order to provide a foundation for further study. METHODS: Normal winstar mice which were injected by different dosage of N(2)O(4) were studied for recording multifocal electroretinogram in the same time in the evening after N(2)O(4) injection. RESULTS: The latency and amplitude density of "b" wave of each ring of multifocal electroretinogram was studied. The latency of "b" wave of each ring of multifocal electroretinogram of each group varies to each other. But the difference of the amplitude of "b" wave of multifocal electroretinogram of each ring between each group had no significance. CONCLUSION: Recording multifocal electroretinogram of N(2)O(4) injected mice will give more support for further study in related science and clinic research.

[Inhibitory effect of huangqi and dangshen extraction with pacilitaxel on metastasis and angiogenesis on mouse Lewis lung carcinoma model].

AIM: To study enhance effect of huangqi and dangshen extraction (Shenqi) on pacilitaxel inhibitory metastasis and angiogenesis on mouse Lewis lung carcinoma model. METHODS: Lewis lung carcinoma cells were inoculated into right hind footpad of C57BL/6 mice. Six hour after tumor inoculated, the mice were randomly divided into 3 groups.Shenqi (paclitaxel plus Shenqi) or paclitaxel was intraperitoneally injected in two group since the second day of the establishment of animal model. The third group simply administered with normal saline was set as placebo-control. Tumor volume, quantitation of microvessel density (MVD) in inoculated tumor, the number of metastasis in the lungs and survival analysis were compared in 3 groups. RESULTS: Paclitaxel plus Shenqi can effectively reduced MVD in inoculated tumor and the number of lung metastasis as compared with other two group (P<0.05). The survival time of Shenqi group was also significantly longer (P<0.05). Tumor volume was no statistical difference in three group (P>0.05). CONCLUSION: Shenqi can amplify the paclitaxel effect of anti-angiogenesis and anti-metastasis, enhances the survival time of mice bearing LLC, might has possible therapeutic applications in the treatment of lung cancer.

[Effects of circadian gene mPer1 on therapeutic sensitivity of adriamycin].

OBJECTIVE: To study the effects of mPer1 gene on the response of mammary carcinoma EMT6 cells to Adriamycin in vitro. METHODS: The eukaryotic expression vector pcDNA3. 1 (+)-mPer1 was transfected into the EMT6 cells (EMT6-mPerl). The vector pcDNA3. 1(+) transfect was also performed to serve as the control (EMT6-vect). The transfect efficiency was detected by RT-PCR and Western Blotting. The transfect cells were treated with Adriamycin in vitro. The apoptosis and distribution of cells in the cell cycle were analysed by FCM. The cell proliferation was detected by MTT assay. RT-PCR was used to show the mRNA expression of apoptosis-related genes. RESULTS: The mPerl-transfected EMT6 cells revealed S phase arrest, increased rate of apoptosis [EMT6-vect: (65.65 +/- 0.07)%; EMT6-mPer1: (72.35 +/- 0.57)%], decreased cell proliferation CEMT6-vect: (42.18 +/- 5.73)%; EMT6-mPer1: (53.28 +/- 7.32%)%] and stronger expression of p53 mRNA in RT-PCR (EMT6-vect, 0.48 +/- 0.08; EMT6-mPer1: 1.18 +/- 0.02). CONCLUSION: mPer1 gene can improve the drug sensitivity of this cell line to ADM in vitro.

[Influence of survivin gene repression by RNA interference on the radiosensitivity and chemosensitivity to cisplatin of cervical cancer cell HeLa].

OBJECTIVE: To observe the effect of survivin gene repression by RNA interference (RNAi) on the radiosensitivity and the chemosensitivity to cisplatin of cervical cancer cell HeLa. METHODS: The recombined eukaryotic expression plasmid pSilencer2.1-s2 containing human survivin gene small interference RNA (siRNA) was transfected into human cervical cancer cell line HeLa by using lipofectamine 2000. The expression of survivin gene mRNA and its protein was detected by semi-quantitative RT-PCR and western blot respectively. The changes of caspase-3 activity was assessed by kinase activity test. Cell apoptosis was examined by flow cytometry. The changes of cell radiosensitivity was observed by plate clone formation assay. Cell viability was examined by methyl thiazolyl tetrazolium (MTT) assay and 50% inhibitive concentration (IC(50)) of cisplatin was examined also. RESULTS: Compared with the cells which were transfected with negative control plasmid (HeLa-NC), pure plasmid (HeLa-U6 neo) and un-transfected cells (HeLa), the expression level of survivin gene mRNA and protein declined evidently in the cells transfected with pSilencer2.1-s2 plasmid (HeLa-s2), the expression inhibitory rates were (62.8 +/- 0.3)% and (60.1 +/- 0.5)%; the caspase-3 activity was enhanced and A(405) was 1.261 +/- 0.043 (P < 0.05); the apoptotic rate was increased obviously (29.23 +/- 1.41)% (P < 0.05). At the same dose of radiation, clone formation rate declined significantly (P < 0.05); at the same concentration of cisplatin, cell viability declined sharply and the IC(50) of cisplatin was (0.873 +/- 0.021) microg/ml (P < 0.05). CONCLUSION: Survivin gene repression by RNAi can enhance caspase-3 activity, induce cell apoptosis, significantly increase the radiosensitivity and chemosensitivity to cisplatin in human cervical cancer cell line HeLa.

[Experimental study of target-specific adriamycin nanoparticles in treating tongue squamous cell carcinoma].

PURPOSE: This study was designed to explore the method for increasing the target-specific action of anticancer agent in treating tongue squamous cell carcinoma. METHODS: 30 purebred New Zealand rabbits burdened with tongue squamous cell carcinoma were randomly divided into 2 groups. Group A was treated with adriamycin and group B treated with adriamycin nanoparticles, with 15 animals in each group. The adriamycin and poly (buty1-2-cyanoacrylate)-adriamycin nanoparticles (mean diameter 93.1 nm+/-11.7 nm) with 1 mg/ml in concentration were administered respectively to subjects through super-selective lingual arterial tuber. The dose was 2 mg/kg for each group. 1, 5 and 15 hours after administration, 5 subjects were sacrificed and the tongue, carcinoma in tongue tissue, heart, liver, spleen, kidney and plasma were examined through high performance liquid chromatography (HPLC) to identify the drug concentration. The data then underwent Student's t test. RESULTS: The drug concentration in the tongue and carcinoma in group B were significantly higher than those in group A (P<0.01). The drug concentration in heart, liver, spleen, kidney and plasma of group B were significantly lower than those of group A (P<0.01). CONCLUSION: The super-selective lingual arterial administration of adriamycin nanoparticles can reinforce the target-specific action of anticancer agent, increase the drug concentration within the lesion and decrease it in non-specific organs.

[Expression of A-type atrial natriuretic peptide receptor in the kidneys of renovascular hypertension rats and its implication].

OBJECTIVE: To investigate the expression of A-type atrial natriuretic peptide receptor (ANPR-A) in the kidneys of renovascular hypertension rats and evaluate the significance of the expression. METHODS: The rat model of renovascular hypertension was produced by constricting one lateral renal artery. After the renal artery being constricted for 4 weeks and 8 weeks, the systolic BP of rats was measured with a manometer using the tail-cuff method. Then, the expression of ANPR-A was respectively detected by immunohistochemical technique in the kidneys of the two-kidney, one-clip (2K1C) rats, and the expression level of ANPR-A was semi-quantitatively measured by Mias-2000 computer image analyzer. RESULTS: At 4 weeks after the artery-constricted operation,the expression of ANPR-A increased significantly in 2K1C hypertensive rat glomeruli and decreased significantly in renal tubules, compared with control (P<0.01), but there was no marked change in medullar collecting tubules. At 8 weeks after the artery-constricted operation, the expression of ANPR-A decreased significantly in 2K1C hypertensive rat renal tubules and medullar collecting tubules, compared with control (P<0.01); however, there was weak expression in glomeruli, and no statistically significant difference was seen when compared with control (P>0.05). CONCLUSION: The expression of ANPR-A decreased significantly in kidney tissues of renovascular