Light-Responsive Supramolecular Liquid-Crystalline Metallacycle for Orthogonal Multimode Photopatterning.

The development of multimode photopatterning systems based on supramolecular coordination complexes (SCCs) is considerably attractive in supramolecular chemistry and materials science, because SCCs can serve as promising platforms for the incorporation of multiple functional building blocks. Herein, we report a light-responsive liquid-crystalline metallacycle that is constructed by coordination-driven self-assembly. By exploiting its fascinating liquid crystal features, bright emission properties, and facile photocyclization capability, a unique system with spatially-controlled fluorescence-resonance energy transfer (FRET) is built through the introduction of a photochromic spiropyran derivative, which led to the realization of the first example of a liquid-crystalline metallacycle for orthogonal photopatterning in three-modes, namely holography, fluorescence, and photochromism.

Co-assembled perylene/graphene oxide photosensitive heterobilayer for efficient neuromorphics.

Neuromorphic electronics, which use artificial photosensitive synapses, can emulate biological nervous systems with in-memory sensing and computing abilities. Benefiting from multiple intra/interactions and strong light-matter coupling, two-dimensional heterostructures are promising synaptic materials for photonic synapses. Two primary strategies, including chemical vapor deposition and physical stacking, have been developed for layered heterostructures, but large-scale growth control over wet-chemical synthesis with comprehensive efficiency remains elusive. Here we demonstrate an interfacial coassembly heterobilayer films from perylene and graphene oxide (GO) precursors, which are spontaneously formed at the interface, with uniform bilayer structure of single-crystal perylene and well-stacked GO over centimeters in size. The planar heterostructure device exhibits an ultrahigh specific detectivity of 3.1 × 1013 Jones and ultralow energy consumption of 10-9 W as well as broadband photoperception from 365 to 1550 nm. Moreover, the device shows outstanding photonic synaptic behaviors with a paired-pulse facilitation (PPF) index of 214% in neuroplasticity, the heterosynapse array has the capability of information reinforcement learning and recognition.

Eukaryotic ribosome quality control system: a potential therapeutic target for human diseases.

Protein homeostasis is well accepted as the prerequisite for proper operation of various life activities. As the main apparatus of protein translation, ribosomes play an indispensable role in the maintenance of protein homeostasis. Nevertheless, upon stimulation of various internal and external factors, malfunction of ribosomes may be evident with the excessive production of aberrant proteins, accumulation of which can result in deleterious effects on cellular fate and even cell death. Ribosomopathies are characterized as a series of diseases caused by abnormalities of ribosomal compositions and functions. Correspondingly, cell evolves several ribosome quality control mechanisms in maintaining the quantity and quality of intracellular ribosomes, namely ribosome quality control system (RQCS). Of note, RQCS can tightly monitor the entire process from ribosome biogenesis to its degradation, with the capacity of coping with ribosomal dysfunction, including misassembled ribosomes and incorrectly synthesized ribosomal proteins. In the current literature review, we mainly introduce the RQCS and elaborate on the underlying pathogenesis of several ribosomopathies. With the in-depth understanding of ribosomal dysfunction and molecular basis of RQCS, therapeutic strategy by specifically targeting RQCS remains a promising option in treating patients with ribosomopathies and other ribosome-associated human diseases.

Assessment of Sagittal Spinopelvic Balance in a Population of Normal Chinese Children.

STUDY DESIGN: A retrospective study of 257 normal children at a single center from July 2016 to November 2018 was performed. OBJECTIVE: To evaluate the spinopelvic parameters in a population of normal children and adolescents in mainland China. SUMMARY OF BACKGROUND DATA: Values for sagittal parameters of the spine vary significantly by ages and different population. No study has yet quantified the normal measures for children and adolescents in China, or how these measures compare with other populations. METHODS: Pelvic incidence (PI), sacral slope, pelvic tilt, thoracic kyphosis (TK, T5-T12), lumbar lordosis (LL, L1-S1), and sagittal vertical axis were measured and evaluated by whole spine AP&lateral X-ray images. RESULTS: A total of 257 subjects, including 116 boys (45%) and 141 girls (55%) aged 3 to 12 years, were enrolled. Correlation matrix analysis demonstrated that sagittal balance is strongly correlated with age and Risser sign, including PI, a reported fixed parameter. Further investigation showed that PI could be expressed by the equation PI = 26.243+1.153×age. CONCLUSION: PI was not a fixed but a dynamic parameter in the population under 12-year old. Indeed, PI increases with age and bone maturity in childhood. We also found lower PI, pelvic tilt, and sacral slope compared with published studies of adolescents in other countries. These results may aid in the treatment of patients with spinal deformity, to help them achieve a certain degree of sagittal spinopelvic balance. LEVEL OF EVIDENCE: 2.

Is haemoglobin below 7.0 g/dL an optimal trigger for allogenic red blood cell transfusion in patients admitted to intensive care units? A meta-analysis and systematic review.

OBJECTIVES: We employed a comprehensive systematic review and meta-analysis to assess benefits and risks of a threshold of haemoglobin level below 7 g/dL versus liberal transfusion strategy among critically ill patients, and even patients with septic shock. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We performed systematical searches for relevant randomised controlled trials (RCTs) in the Cochrane Library, EMBASE and PubMed databases up to 1 September 2019. ELIGIBILITY CRITERIA: RCTs among adult intensive care unit (ICU) patients comparing 7 g/dL as restrictive strategy with liberal transfusion were incorporated. DATA EXTRACTION AND SYNTHESIS: The clinical outcomes, including short-term mortality, length of hospital stay, length of ICU stay, myocardial infarction (MI) and ischaemic events, were screened and analysed after data collection. We applied odds ratios (ORs) to analyse dichotomous outcomes and standardised mean differences (SMDs) to analyse continuous outcomes with fixed or random effects models based on heterogeneity evaluation for each outcome. RESULTS: Eight RCTs with 3415 patients were included. Compared with a more liberal threshold, a red blood cell (RBC) transfusion threshold <7 g/dL haemoglobin showed no significant difference in short-term mortality (OR: 0.90, 95% CI: 0.67 to 1.21, p=0.48, I2=53%), length of hospital stay (SMD: -0.11, 95% CI: -0.30 to 0.07, p=0.24, I2=71%), length of ICU stay (SMD: -0.03, 95% CI: -0.14 to 0.08, p=0.54, I2=0%) or ischaemic events (OR: 0.80, 95% CI: 0.43 to 1.48, p=0.48, I2=51%). However, we found that the incidence of MI (OR: 0.54, 95% CI: 0.30 to 0.98, p=0.04, I2=0%) was lower in the group with the threshold <7 g/dL than that with the more liberal threshold. CONCLUSIONS: An RBC transfusion threshold <7 g/dL haemoglobin is incapable of decreasing short-term mortality in ICU patients according to currently published evidences, while it might have potential role in reducing MI incidence.

The Circular RNome of Developmental Retina in Mice.

Circular RNAs (circRNAs) represent a class of noncoding RNAs with a wide expression pattern, and they constitute an important layer of the genome regulatory network. To date, the expression pattern and regulatory potency of circRNAs in the retina, a key part of the central nervous system, are not yet well understood. In this study, RNAs from five stages (E18.5, P1, P7, P14, and P30) of mouse retinal development were sequenced. A total of 9,029 circRNAs were identified. Most circRNAs were expressed in different stages with a specific signature, and their expression patterns were different from those of their host linear transcripts. Some circRNAs could act as sponges for several retinal microRNAs (miRNAs). Furthermore, circTulp4 could function as a competitive endogenous RNA (ceRNA) to regulate target genes. Remarkably, silencing circTulp4 in vivo led to mice having a thin outer nuclear layer (ONL) and defective retinal function. In addition, we found that circRNAs were dysregulated at a much earlier time point than that of disease onset in a retinal degeneration model (rd8 mice). In summary, we provide the first circRNA expression atlas during retinal development and highlight a key biological role for circRNAs in retinal development and degeneration.

Low-intensity pulsed ultrasound promotes spinal fusion by regulating macrophage polarization.

BACKGROUND: Spinal fusion is considered the gold standard procedure for treating spinal degeneration, tumors, and trauma. An inflammatory response is an important part of bone repair. We investigated the polarization change of inflammatory macrophages (M1) and resident macrophages (M2) during low-intensity pulsed ultrasound (LIPUS) treatment. METHODS: Thirty male Sprague Dawley rats (age: 12 weeks; weight: 300 g) were used in the study. A rat spinal fusion model was established by surgical procedures. LIPUS treatment (20 min. d, 5 d/wk) was begun 3 days after surgery. The rats were randomly divided into a control group (5 subgroups, 3 rats in each subgroup) and LIPUS group (5 subgroups, 3 rats in each subgroup), and sacrificed on day 3, 5, 7, 10, and 14 after spinal fusion surgery for further evaluation. Bone volume was measured by micro-CT, fusion region was examined by histological analyses, types of macrophages in the fusion area were examined by immunohistochemical staining. Raw264.7 cells and bone marrow-derived macrophages (BMDM) were used in cell experiments. Cells were divided into a control group and LIPUS group. Flow cytometry was used to examine the rate of resident macrophages, and real-time PCR was used to examine the mRNA expression of anti-inflammation genes. RESULTS: LIPUS promoted spinal fusion and stimulated the transition of F4-80+/Mac-2+ (M1) to F4-80+/Mac-2- (M2), leading to the early appearance of resident macrophages. Cell experiments showed CD206+ macrophages (M2) were significantly increased after LIPUS treatment. M2-related genes and anti-inflammation factors (Arg-1, PPAR-γ, and IL-4) were increased after LIPUS treatment. CONCLUSION: The earlier transition from inflammatory to resident macrophage might be one reason for the positive effect of LIPUS on spinal fusion.

Highly Acylated Anthocyanins from Purple Sweet Potato ( Ipomoea batatas L.) Alleviate Hyperuricemia and Kidney Inflammation in Hyperuricemic Mice: Possible Attenuation Effects on Allopurinol.

Allopurinol is the first-line medication for hyperuricemia treatment. However, severe drug-related adverse effects have often been reported among patients who received allopurinol administration. This study is aimed at evaluating the possible attenuation effects of highly acylated anthocyanins from purple sweet potato (HAA-PSP) on hyperuricemia and kidney inflammation in hyperuricemic mice treated with allopurinol. In comparison with 5 mg kg-1 allopurinol used alone, the combination of 25 mg kg-1 HAA-PSP and 2.5 mg kg-1 allopurinol could not only reduce serum uric acid level in hyperuricemic mice but also attenuate the kidney damage, as indicated by the level of serum biomarkers as well as histopathological examination. The inflammatory response was partially mitigated by inhibiting the protein expression of typical cytokines in the kidney. Our findings provide new evidence for the supplementary therapeutic potential of HAA-PSP with allopurinol on hyperuricemia and inflammation-related syndromes. Moreover, this study provides a theoretical basis for assessing the potential of anthocyanin-rich foods in health.

Cross-cultural Adaptation and Validation of the Simplified-Chinese Version of Neck Bournemouth Questionnaire for Patients in Mainland China.

STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to develop and assess the internal reliability and structure validity of a simplified Chinese version of the Neck Bournemouth Questionnaire (SC-NBQ) for evaluation of patients with nonspecific neck pain (NP) in mainland China. SUMMARY OF BACKGROUND DATA: The NBQ has been cross-culturally translated into several languages with good internal consistency and construct validity to evaluate low back pain and NP. However, the NBQ has been not translated or validated for Chinese-speaking patients. METHODS: The SC-NBQ was developed by standard cross-translation procedures, and completed by 106 patients with nonspecific NP, along with other self-reported questionnaires, including the Neck Disability Index (NDI), Hospital Anxiety and Depression Scale (HADS), Functional Rating Index (FRI), and 36-Item Short Form Health Survey (SF-36). The internal consistency, test-retest reliability, and construct validity of the SC-NBQ were determined. RESULTS: The NBQ was successfully translated into Chinese. All patients completed the SC-NBQ twice, and the other instruments. Score distribution demonstrated that there was no floor or ceiling effects of the SC-NBQ. Cronbach α coefficient (α = 0.89) and intraclass correlation coefficient (ICC = 0.97) showed good internal consistency and test-retest reliability. A good construct validity was shown by strong correlation with HADS (r = 0.75), NDI (r = 0.82), FRI (r = 0.90) and SF-36 physical functioning (r = 0.75), and bodily pain (r = 0.75) subscales. CONCLUSION: The SC-NBQ demonstrated good internal consistency, test-retest reliability, and construct validity, and may be used for the evaluation of NP in Chinese-speaking patients. LEVEL OF EVIDENCE: 2.

Effects of Low-Intensity Pulsed Ultrasound on Knee Osteoarthritis: A Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Osteoarthritis (OA) is a common degeneration disease characterized with joint pain. The aim of the present study was to systemically review the effects of LIPUS on pain relief and functional recovery in patients with knee osteoarthritis (OA). METHODS: PubMed, Embase, and Cochrane Library were searched manually for researches on LIPUS treatment in patients with knee OA from 1945 to July 2017. Two investigators independently selected the studies according to the inclusion and exclusion criteria, extracted the concerned data, and assessed the included studies. Meta-analysis was performed to evaluate VAS, WOMAC, and ambulation speed between control and LIPUS groups. RESULTS: Five studies were selected in this study. Compared with control group, LIPUS group received a decrease of pain intensity with moderate heterogeneity (-0.79, 95% CI, -1.57 to 0.00; I2 = 65%, P = 0.04) by VAS and improvement in knee function by WOMAC (-5.30, 95% CI, -2.88 to -7.71; I2 = 44%, P = 0.17). No significant improvement was found in ambulation speed (0.08 m/s, 95% CI, -0.02 to 0.18 m/s; I2 = 68%, P = 0.03). CONCLUSION: The present study includes 5 high quality randomized controlled trials. The result indicated that LIPUS, used to treat knee OA without any adverse effect, had a beneficial effect on pain relief and knee functional recovery. More evidence is needed to prove whether LIPUS is effective in improving walking ability.

Low-intensity pulsed ultrasound promotes spinal fusion and enhances migration and proliferation of MG63s through sonic hedgehog signaling pathway.

Low-intensity pulsed ultrasound (LIPUS) has been found to accelerate the healing process of spinal fusion via a process closely related to osteoblast differentiation and migration. Sonic hedgehog (Shh) signaling plays an important role in development and homeostasis, including a critical function in bone formation. However, its role in spinal fusion during LIPUS treatment is still unknown. This study showed that LIPUS treatment after spinal fusion surgery increased bone formation. The increased bone mass under LIPUS treatment appeared to result from the increased migration and proliferation of osteoblasts, resulting from upregulation of the Shh signaling pathway. In contrast, inhibition of Shh reduced the migratory and proliferative ability of osteoblast-like MG63 cells and blocked the efficacy of LIPUS treatment.

Cross-cultural validation of simplified Chinese version of spine functional index.

BACKGROUND: No effective constructs were available in mainland China to assess the whole spine function. The SFI was developed to evaluate spinal function based on the concept of a single kinetic chain concept for whole spine. The SFI has been translated to Spanish and Turkish with accepted psychometric properties. It is imperative to introduce the SFI in mainland China and further to explore the measurement properties. METHODS: The English versions of the SFI was cross-culturally translated according to international guidelines. Measurement properties (content validity, construct validity and reliability) were tested in accordance with the COSMIN checklists. A total of 271 patients were included in this study, and 61 participants with neck pain and 64 participants with back pain paid a second visit three to seven days later. Confirmatory factor analysis (CFA) and principal factor analysis (PCA) were applied to test the factor structure. The Functional Rating Index (FRI), Neck Disability Index (NDI), Oswestry Disability Index (ODI), SF-12 and a Visual Analogue Scale (VAS) were employed to evaluate the construct validity. Cronbach's alpha and an intra-class correlation coefficient (ICC) were calculated for internal consistency and reproducibility. RESULTS: The means score of SC-SFI was 63.60 in patients with spinal musculoskeletal disorders. A high response rate was acquired (265/271). No item was removed due to abnormal distribution or low item-total correlation. Results of CFA did not support that one-factor structure was in goodness of fit (CMIN/DF = 3.306, NNFI = 0.687, CFI = 0.756, GFI = 0.771 and RMSEA = 0.092). Yet, PCA suggested a one-factor structure was the best, accounting for 32% of the total variance. For structural validity, the SC-SFI correlated highly with the FRI, NDI, ODI, and PF, BP in SF-12 (r = 0.661, 0.610, 0.750, 0.709, 0.605, respectively). All the a priori hypotheses were verified. The Cronbach's alpha for the SC-SFI was 0.91, and ICC was 0.96 (95% CI, 0.94-0.98). Bland-Altman plot also confirmed excellent test-retest reliability. CONCLUSIONS: The SFI has been culturally adapted into SC-SFI with remarkable clinical acceptance, excellent internal consistency, reproducibility, and construct validity when applied to patients with spinal musculoskeletal disorders. The results of current study suggest that SC-SFI can be applied by physicians and researchers to measure whole-spine functional status in mainland China.

Low-intensity pulsed ultrasound promotes endothelial cell-mediated osteogenesis in a conditioned medium coculture system with osteoblasts.

Angiogenesis plays an important role during bone regeneration. Low-intensity pulsed ultrasound (LIPUS) has been proven to accelerate the process of bone fracture healing. However, the mechanism of the effect of LIPUS on bone regeneration is still unclear. In the present study, we used human umbilical vein endothelial cell (HUVEC) and human osteosarcoma cell (MG-63) to investigate the effect of LIPUS stimulation in an endothelial cell-osteoblast coculture system. At the same time, we used transwell and in vitro angiogenesis assay to observe how LIPUS affects endothelial cells. The results demonstrated that LIPUS could significantly increase the migratory ability and promote tube formation in angiogenesis of HUVECs. Furthermore, LIPUS could significantly elevate the expression of osteogenesis-related genes on osteoblasts such as Runt-related transcription factor 2, alkaline phosphatase, Osteorix, and Cyclin-D1, indicating the pro-osteogenesis effect of LIPUS in our coculture system. In conclusion, endothelial cell is involved in LIPUS-accelerated bone regeneration, the positive effect of LIPUS may be transferred via endothelial cells surrounding fracture healing site.

Characterization and hepatoprotective activity of anthocyanins from purple sweet potato (Ipomoea batatas L. cultivar Eshu No. 8).

The hepatoprotective activity of anthocyanin-rich purple sweet potato extract (APSPE) was demonstrated. Sixty mice were randomly divided into six groups: control group [without carbon tetrachloride (CCl4) or APSPE]; model group (with CCl4 only); positive control group (50 mg/kg body weight silymarin); low-dose group (100 mg/kg body weight APSPE); medium-dose group (200 mg/kg body weight APSPE); and high-dose group (400 mg/kg body weight APSPE). After 10 days intragastric administration of the respective supplements, the mice in all groups except control were injected intraperitoneally with CCl4 (0.15% in arachis oil, 10 mL/kg body weight, intravenous). Twelve hours after CCl4 injection, the mice were measured in terms of liver index, levels of aspartate aminotransferase and alanine aminotransferase in serum, as well as glutathione, superoxide dismutase, and malondialdehyde in liver homogenate. Additionally, the livers of mice were stained with hematoxylin and eosin and sectioned for observation. Nineteen purple sweet potato anthocyanins were identified from the purple sweet potato cultivar Eshu No. 8 and analyzed by liquid chromatography- electrospray ionization-tandem mass spectrometry. Peonidin 3-coumaryl-p-hydroxybenzoyl sophoroside-5-glucoside was first identified in purple sweet potato. The results showed that anthocyanins in Eshu No. 8 had good hepatoprotective activity.

Low-Intensity Pulsed Ultrasound-Induced Spinal Fusion is Coupled with Enhanced Calcitonin Gene-Related Peptide Expression in Rat Model.

Low-intensity pulsed ultrasound (LIPUS) has been found to accelerate fracture healing. In this study, we analyzed the role of calcitonin gene-related peptide (CGRP) in a rat spinal fusion model treated with LIPUS. The results revealed that LIPUS significantly increases bone formation, and the process was coupled with elevated CGRP innervation. CGRP was located in fibrous tissue, closely surrounding the allograft and newly formed cartilage. The density of CGRP peaked at week 3 after surgery in both the control (non-LIPUS-treated) and LIPUS-treated groups. These results suggest that LIPUS might accelerate spinal fusion by promoting sensory nerve fiber innervation.

Effects of anthocyanins from purple sweet potato (Ipomoea batatas L. cultivar Eshu No. 8) on the serum uric acid level and xanthine oxidase activity in hyperuricemic mice.

This study was aimed at evaluating the hypouricemic effect of the anthocyanin-rich purple sweet potato extract (APSPE). In vitro, APSPE has been proved to significantly inhibit XO activity in a dose-dependent manner. In vivo, APSPE could not only inhibit the XO activity in mouse liver, but also reduce the serum uric acid level in hyperuricemic mice and affect the expression of mRNA levels of related renal transporters, such as mURAT1, mGLUT9, mOAT1 and mOCTN2. Moreover, APSPE could effectively regulate BUN and Cr levels to normal and decrease the inflammatory cellular influx in the tubule of the hyperuricemic mice. This study indicates the potential clinical utility of APSPE as a safe and effective anti-hyperuricemia bioactive agent or functional food.

Morphological factors and cardiac doses in whole breast radiation for left-sided breast cancer.

BACKGROUND: To investigate the impact of the breast size, shape, maximum heart depth (MDH), and chest wall hypotenuse (the distance connecting middle point of the sternum and the length of lung draw on the selected transverse CT slice) on the volumetric dose to heart with whole breast irradiation (WBI) of left-sided breast cancer patients. MATERIALS AND METHODS: Fifty-three patients with left-sided breast cancer undergoing adjuvant intensity-modulated radiotherapy (IMRT) were enrolled in the study. The primary breast size and shape, MHD and DCWH (chest wall hypotenuse) were contoured on radiotherapy (RT) planning CT slices. The dose data of hearts were obtained from the dose-volume histograms (DVHs). Data were analyzed by one-way analysis of variance (ANOVA), Student's t-test and linear regression analysis. RESULTS: Breast size was independent of heart dose, whereas breast shape, MHD and DCWH were correlated with heart dose. The shapes of breasts were divided into four types, as the flap type, hemisphere type, cone type and pendulous type with heart mean dose being 491.8±234.6 cGy, 752.7±219.0 cGy, 620.2±275.7 cGy, and 666.1±238.0 cGy, respectively. The flap type of breasts shows a strong statistically reduction in heart dose, compared to others (p=0.008 for V30 of heart). DCWH and MHD were found to be the most important parameters correlating with heart dose in WBI. CONCLUSIONS: More attention should be paid to the heart dose of non-flap type patients. The MHD was found to be the most important parameter to correlate with heart dose in tangential WBI, closely followed by the DCWH, which could help radiation oncologists and physicsts evaluate heart dose and design RT plan in advance.

miR-511 induces the apoptosis of radioresistant lung adenocarcinoma cells by triggering BAX.

Radioresistance is one of the main reasons for the failure of radiotherapy in lung cancer. The present study was conducted to identify the role of miR-511 in suppressing the growth of radioresistant lung adenocarcinoma cells. First, a radioresistant A549/R cell line was generated after prolonged exposure to X-rays for 68 Gy (2 Gy/day, 5 days/week) and the radioresistance was confirmed by wound healing assay. Next, oncogenic TRIB2 was found to be upregulated in the radioresistant A549/R cells when compared to that of the control A549 cells as determined by western blot analysis. As the upstream miRNA, quantitative PCR showed that miR-511 expression was decreased in the radioresistant A549/R cells. Overexpression of miR-511 in miR-511-transfected A549/R cells inhibited cell growth and increased the number of apoptotic cells when compared with the control treatment. Flow cytometric analysis further demonstrated that the growth suppressive effect of miR-511 on A549/R cells was mediated by regulation of the cell cycle, most likely due to a block in the G1-S transition. Finally, our results showed that the expression of BAX was lower in the radioresistant A549/R cells when compared with that in the control A549 cells. After downregulation of TRIB2 by miR-511 treatment, BAX expression was obviously increased in the miR-511-transfected apoptotic A549/R cells when compared to that in the NC-treated or control cultures. In summary, our results revealed that miR-511 regulates the growth of radioresistant A549/R cells by increasing BAX expression through TRIB2, which suggests that miR-511 may be a potential therapeutic molecule for the treatment of radioresistant lung adenocarcinoma.

[Determination of intrinsic alliin dissolution rates with fiber-optic sensing process analysis].

The apparatus for intrinsic dissolution test recorded in United States Pharmacopeia (USP) integrating with fiber-optic drug dissolution test system (FODT) were used to real-time monitor intrinsic dissolution processes of alliin in four media which were water, solution of HCl with pH 1.2, buffer solution of acetate with pH 4.5, and buffer solution of phosphate with pH 6.8. The intrinsic dissolution rate (IDR) and the similarity factor (f2) of two intrinsic dissolution curves with two apparatuses were calculated. The IDR values of alliin with rotating disk system were 28.1.3, 33.55, 28.38 and 30.95 mg x cm(-2) x min(-1) in four media, respectively. And the IDR values of alliin with stationary disk system were 44.16, 47.07, 45.11 and 51.34 mg x cm(-2) x min(-1), respectively. The similarity factors were 56.42, 50.75, 40.30 and 40.64, respectively. The results showed that the intrinsic alliin dissolution rates were much greater than 1 mg x cm(-2) x min(-1). It inferred that alliin dissolution would not be the rate limiting step to absorption.

Phase I study of pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced non-small cell lung cancer.

OBJECTIVES: Concurrent chemoradiotherapy in well-selected locally advanced non-small cell lung cancer (LANSCLC) is considered as standard therapy. However, the choice of anticancer agents is still unresolved. Our objectives were to determine the maximum tolerated dose and recommended dose of pemetrexed in combination with cisplatin, with concurrent late course accelerated hyperfractionated (LCAF) intensity modulated radiotherapy (IMRT) in patients with LANSCLC and to investigate the safety and efficacy. METHODS: The chemotherapy was cisplatin (25 mg/m(2) × 3 days) plus pemetrexed with doses escalating from 400 to 500 mg/m(2). The dose level was increased every 3 patients. The gross tumor volumes of concurrent LCAF IMRT were delineated according to [(18)F] fluorodeoxyglucose positron emission tomography computed tomography imaging. To spare functional lung, single photon emission photography lung perfusion imaging was used to optimize the plans. The total radiation dose was limited such that the V20 of bilateral lung is no more than 35%. RESULTS: Nine patients with LANSCLC were enrolled in this study. The median radiation dose was 70.8 Gy. The response rate was 66.7% with a complete remission rate of 33.3%. Toxicity was mild with only 1 patient experiencing dose limiting toxicity in 500 mg/m(2) level. Obviously, the maximum tolerated dose was not reached as per the definition. As the systemically active chemotherapy dose was reached, further dose escalation was discontinued, and the recommended dose of pemetrexed for a phase II study was 500 mg/m(2). CONCLUSIONS: The combination of pemetrexed and cisplatin with concurrent LCAF IMRT optimized based on single photon emission photography lung perfusion imaging is well tolerated in patients with LANSCLC. Full therapeutic doses of the chemotherapy can be safely administered. The initial results showed signs of efficacy.