High-performance multiplex microvalves fabrication and using for tumor cells staining on a microfluidic chip.

As we all know, microvalve holds great importance for microfluidic manipulation in chip. Herein, a simple method of high-performance multiplex microvalves chip fabrication was reported. In this method, a sandwich structure is established by inserting a polydimethylsiloxane (PDMS) membrane into two glasses, which is cheap and simple without any complex silicon-based device or soft lithography. Taking advantages of both the elasticity of the PDMS and the rigidity of glass, the microvalve chip showed good controls performance and had the ability of multiplex integration. Moreover, aided by a computer design program, this microvalves chip can be performed automatically, showing great potential to develop new highly integrated microfluidic devices. In addition, the fabricated multiplex microvalve chip is further successfully used for staining tumor cells automatically, improving the efficiency of cell identification process and reducing human errors. These results indicate this method opens up new avenues for multiplex microvalves fabrication and its biological application.

Wild-Type P53 Induces Sodium/Iodide Symporter Expression Allowing Radioiodide Therapy in Anaplastic Thyroid Cancer.

AIMS: Anaplastic thyroid cancer(ATC) is one of the most aggressive solid tumors. Mutations in the p53 gene are common in anaplastic thyroid cancer, but the effects of p53 mutations are yet to be elucidated. Here, we investigated the role of p53 in ATC. METHODS: p53 mutation was detect by immunohistochemistry in ATC tissues. Expression of NIS were measured using immunohistochemistry, qRT-PCR, western blot, immunofluorescence in ATC tissues and cell line 8505c. Luciferase reporter assay was performed to examine the effect of wild-type p53 on NIS. Radioiodide uptake assay and flow cytometry analysis were used to detect the role of wild-type p53 on radioiodide uptake.and cell apoptosis in ATC cell line. RESULTS: We showed that the p53 mutation can be detected in ATC tissues. Furthermore, we demonstrated that wild-type p53 transactivated the NIS promoter. In 8505c cells transfected with wild-type p53, treatment with radioiodine resulted in increased radioiodine uptake and increased apoptotic cell death compared with 8505c cells harboring the p53 mutation. CONCLUSION: In summary, transfection with wild-type p53 can increase the therapeutic effect of radioiodine by regulating the expression of the NIS.

Palliative treatment of pelvic bone tumors using radioiodine (125I) brachytherapy.

BACKGROUND: Complete resection of pelvic bone tumors, especially recurrent and metastatic ones, is often impossible to achieve using conventional surgery. This study aimed to assess the benefits and adverse effects of computed tomography (CT)-guided radioiodine (125I) brachytherapy for inoperable recurrent and metastatic bone tumors of the pelvis. METHODS: This was a retrospective study of 22 patients with confirmed pelvic bone tumors (10 females and 12 males; 15-84 years; 21 with primary pelvic tumor and one with pelvic metastasis). CT-guided 125I brachytherapy was performed using 9-21 125I seeds (radioactivity of 0.5-0.7 mCi). Seed implantation was validated by postoperative CT scanning. Complications, pain, survival, and CT-estimated tumor size were carried out to evaluate the therapeutic benefits. RESULTS: Postoperative CT scans revealed satisfactory 125I seed implantation, and the radiation dose delivered to 90% of the target area (D90) was higher than the prescription dose (PD). No obvious complications were observed. Pain was reported by 19 of 22 patients, but 17 reported pain relief after implantation. Follow-up ranged 8-27 (median, 19) months. Tumor size was reduced in 11 patients within 1 month after surgery, nine patients showed no change, and tumor size increased in two patients. Finally, 1- and 2-year survival was 81.8 and 45.5%, respectively; 1- and 2-year local tumor control rates were 59.1 and 36.4%, respectively. CONCLUSIONS: 125I seed implantation significantly reduced bone tumor size and relieved pain, with a low complication rate. These findings suggest that 125I brachytherapy treatment could be a useful palliative approach for pelvic bone tumor treatment.

Gender difference in mobile phone use and the impact of digital device exposure on neck posture.

This cross-sectional study aimed to identify gender differences in the cervical postures when young adults were using mobile phones, as well as the correlations between the postures and the digital devices use (computer and mobile phone). Questionnaires regarding the habits of computer and mobile phone use were administrated to 429 subjects aged from 17 to 33 years old (19.75 ± 2.58 years old). Subjects were instructed to stand habitually and use a mobile phone as in daily life; the sagittal head and cervical postures were measured by head flexion, neck flexion angle and gaze angle. Male participants had a significantly larger head flexion angle (96.41° ± 12.23° vs. 93.57° ± 12.62°, p  =  0.018) and neck flexion angle (51.92°  ±  9.55° vs. 47.09° ± 9.45°, p  <  0.001) than females. There were significant differences in head (F  =  3.62, p  =  0.014) and neck flexion (F  =  3.99, p  =  0.009) between different amounts of computer use. Practitioner Summary: We investigated possible gender differences in head and neck postures of young adults using mobile phones, as well as the potential correlations between these postures and digital device use. We found that males displayed larger head and neck flexion angles than females, which were associated with the amount of computer use.

Simple, effective protein extraction method and proteomics analysis from polyunsaturated fatty acids-producing micro-organisms.

Polyunsaturated fatty acids (PUFAs) are valuable ingredients in the food and pharmaceutical products due to their beneficial influence on human health. Most studies paid attention on the production of PUFAs from oleaginous micro-organisms but seldom on the comparative proteomics of cells. In the study, three methods (i.e., cold shock, acetone precipitation and ethanol precipitation) for lipid removal from crude protein extracts were applied in different PUFAs-producing micro-organisms. Among the selective strains, Schizochytrium was used as an oleaginous strain with high lipid of 60.3 (w/w%) in biomass. The Mortierella alpina and Cunninghamella echinulata were chosen as the low-lipid-content strains with 25.8 (w/w%) and 21.8 (w/w%) of lipid in biomass, respectively. The cold shock resulted as the most effective method for lipid removed, thus obtained higher protein amount for Schizochytrium. Moreover, from the comparative proteomics for the three PUFAs-producing strains, it showed more significant proteins of up or down-regulation were explored under cold shock treatment. Therefore, the essential proteins (i.e., polyunsaturated fatty acid synthase) and regulating proteins were observed. In conclusion, this study provides a valuable and practical approach for analysis of high PUFAs-producing strains at the proteomics level, and would further accelerate the understanding of the metabolic flux in oleaginous micro-organisms.

A preliminary study of the safety and efficacy of radiofrequency ablation with percutaneous kyphoplasty for thoracolumbar vertebral metastatic tumor treatment.

BACKGROUND: Thoracolumbar vertebral metastasis (TVM) affects a large number of cancer patients. However, safe and effective palliative care remains controversial. The aim of the present study was to investigate the safety and efficacy of minimally invasive image-guided radiofrequency ablation (RFA) with percutaneous kyphoplasty (PKP) for TVM treatment. MATERIAL AND METHODS: A retrospective study of 26 patients (mean age: 59.31 ± 11.62 years) was conducted, including 38 vertebral metastases at T11, T12, L1, L2, L3, L4, L5, and S1 with abundant blood vessels. Patients underwent RFA with PKP (4-6 min, 95 ± 5°C, 150 W, effective electrode area of 1.5-2.0 cm) under general anesthesia from February 2005 to January 2009. Electrodes were inserted into the lesions and pre- and post-operative visual analog scale (VAS) scores and X-rays were collected on day 3, week 1, and months 1, 3, and 6. Tumor recurrence and pain level were also evaluated. Safety assessment was conducted based on complications and adverse events. The mean follow-up time was 8.4 ± 2.1 months. RESULTS: A mean of 2.69 ± 0.93 ablation was performed per patient. The ablation procedure required a mean of 15.08 ± 4.64 min, while the injection of bone cement required a mean of 6.73 ± 0.83 min, for a mean total operating time of 47.77 ± 7.13 min. Postoperative VAS scores were significantly lower on day 3, week 1, and months 1, 3, and 6 (P<0.01), without any complications or tumor recurrence. CONCLUSIONS: Image-guided RFA with PKP was safe and effective for TVM treatment when used with careful consideration of bone cement volume/viscosity, injection location, and temperature.

Improving the thermal stability and catalytic activity of ulvan lyase by the combination of FoldX and KnowVolution campaign.

Thermal stability is one of the most important properties of ulvan lyases for their application in algae biomass degradation. The Knowledge gaining directed eVolution (KnowVolution) protein engineering strategy could be employed to improve thermostability of ulvan lyase with less screening effort. Herein, the unfolding free energies (ΔΔG) of the loop region were calculated using FoldX and four sites (D103, G104, T113, Q229) were selected for saturation mutagenesis, resulting in the identification of a favorable single-site mutant Q229M. Subsequently, iteration mutation was carried out with the mutant N57P (previously obtained by our group) to further enhance the performance of ulvan lyase. The results showed that the most beneficial variant N57P/Q229M exhibited a 1.67-fold and 2-fold increase in residual activity compared to the wild type after incubation at 40 °C and 50 °C for 1 h, respectively. In addition, the variant produced 1.06 mg/mL of reducing sugar in 2 h, which was almost four times as much as the wild type. Molecular dynamics simulations revealed that N57P/Q229M mutant enhanced the structural rigidity by augmenting intramolecular hydrogen bonds. Meanwhile, the shorter proton transmission distance between the general base of the enzyme and the substrate contributed to the glycosidic bond breakage. Our research showed that in silico saturation mutagenesis using position scan module in FoldX allowed for faster screening of mutants with improved thermal stability, and combining it with KnowVolution enabled a balanced effect of thermal stability and enzyme activity in protein engineering.

Zoledronate Extends Health Span and Survival via the Mevalonate Pathway in a FOXO-dependent Manner.

Over recent decades, increased longevity has not been paralleled by extended health span, resulting in more years spent with multiple diseases in older age. As such, interventions to improve health span are urgently required. Zoledronate (Zol) is a nitrogen-containing bisphosphonate, which inhibits the farnesyl pyrophosphate synthase enzyme, central to the mevalonate pathway. It is already used clinically to prevent fractures in osteoporotic patients, who have been reported to derive unexpected and unexplained survival benefits. Using Drosophila as a model we determined the effects of Zol on life span, parameters of health span (climbing ability and intestinal dysplasia), and the ability to confer resistance to oxidative stress using a combination of genetically manipulated Drosophila strains and Western blotting. Our study shows that Zol extended life span, improved climbing activity, and reduced intestinal epithelial dysplasia and permeability with age. Mechanistic studies showed that Zol conferred resistance to oxidative stress and reduced accumulation of X-ray-induced DNA damage via inhibition of farnesyl pyrophosphate synthase. Moreover, Zol was associated with inhibition of phosphorylated AKT in the mammalian traget of rapamycin pathway downstream of the mevalonate pathway and required dFOXO for its action, both molecules associated with increased longevity. Taken together, our work indicates that Zol, a drug already widely used to prevent osteoporosis and dosed only once a year, modulates important mechanisms of aging. Its repurposing holds great promise as a treatment to improve health span.

Clinical Manifestations of Polycystic Ovary Syndrome and Associations With the Vaginal Microbiome: A Cross-Sectional Based Exploratory Study.

Background: Previous studies suggest that the vaginal microbiome is associated with polycystic ovary syndrome (PCOS). However, the clinical manifestations of PCOS are heterogeneous. Whether the vaginal microbiome is related with different clinical symptoms was unknown. Materials and Methods: In this cross-sectional study, 89 female patients with PCOS admitted to Zhongda Hospital (Nanjing, China) were included. Basic demographic information, health-related behaviors, clinical manifestations and sex hormone levels were comprehensively recorded for all patients. Vaginal swabs were acquired for microbiota sequencing of the V3-V4 region of the 16S rRNA gene. Results: The prevalence of bacterial vaginitis and vulvovaginal candidiasis was 15.7% and 13.5%, respectively, within the PCOS patients, which were the most important factors affecting the vaginal microbiome (permutational multivariate analysis of variance test, R2 = 0.108, P = 0.001). The vaginal microbiome was associated with specific clinical manifestations of PCOS, including acanthosis nigricans, intermenstrual bleeding, pregnancy history, testosterone level and anti-müllerian hormone level, with P values < 0.05. The abundance of Lactobacillus crispatus was higher (P = 0.010) while that of Lactobacillus iners was lower (P = 0.036) among PCOS patients with elevated testosterone levels. Other potential bacterial biomarkers were not statistically significant after adjusting for confounding factors. No evidence of associations of other common manifestations of PCOS, such as obesity and acne, with the vaginal microbiome was obtained. Conclusion: Vaginal bacterial species among PCOS patients with variable clinical manifestations, especially differences in testosterone levels, are distinct. Further studies are essential to investigate the microbiota and molecular mechanisms underpinning this disease.

Evaluation of Quality of Life Using EORTC QLQ-BM22 in Patients with Bone Metastases after Treatment with Magnetic Resonance Guided Focused Ultrasound.

OBJECTIVE: To reveal the alterations in quality of life (QOL) in bone metastases patients after magnetic resonance guided focused ultrasound (MRgFUS). METHODS: This retrospective study enrolled 26 patients diagnosed with bone metastases. Patients had various primary malignant tumors and tumor lesions in different locations. All patients received MRgFUS for bone metastasis. Each focal spot sonication pulse that was applied to create energy deposition lasted 20 s and was performed at a frequency of 1.05 MHz. The visual analog scale (VAS) was used to measure pain level and the EORTC QLQ-BM22 was applied to evaluate QOL for 12 months. The lower the QLQ-BM22 score, the better the QOL of patients. RESULTS: The painful site subscale of the EORTC QLQ-BM22 was observed without significant change. Significant reductions in the functional subscales were observed after therapy compared with the baseline. The functional interference was reduced significantly during the first 12 months. From the 2-month time point onwards, the pain characteristics subscale also decreased significantly. VAS scores had decreased by 40.8% 1 month after the operation and had decreased 10.9% compared with VAS scores preoperation. Scores for pain characteristics decreased by 28.8% after the operation and the scores were still down by 10.8% 1 year after the treatment. VAS scores indicated a significant reduction in pain over the course of the research until the 12-month time point follow-up compared with the baseline. CONCLUSION: MRgFUS therapy improved the QOL of patients with bone metastasis by relieving bone pain.

Worldwide Research Productivity in the Field of Minimally Invasive Spine Surgery: A 20-year Survey of Publication Activities.

MINI: The time trend for the number of minimally invasive spine surgery articles showed a significant increase over time with an average of 93.23 articles per year. Among all related journals, Spine published the largest number of articles in minimally invasive spine surgery research and was the most popular one in the top five countries. STUDY DESIGN: Bibliometric analysis. OBJECTIVE: This study aimed to reveal the characteristics of world productivity in the field of minimally invasive spine surgery (MISS) research and to provide a general picture for surgeons and researchers. SUMMARY OF BACKGROUND DATA: Significant growth has been observed in the field of MISS research in recent years. However, bibliometric studies concerning the quantity and quality of articles published in MISS journals are scarce. METHODS: All the data concerning MISS in this study originate from the Web of Science (Thomson Reuters, New York, NY) without restrictions. All selected literates were evaluated in the following aspects: publication year, publication journals, author, times cited, Web of Science category, countries/territories. RESULTS: A total number of 2051 articles were published worldwide. The articles published during 2000 to 2015 are more than 11.28 times when compared to those published before 2000. The United States published the largest number of articles (855/2051, 41.7%), followed by Germany (245/2051, 11.9%), South Korea (160/2051, 7.8%), China (147/2051, 7.2%), and Japan (108/2051, 5.2%) and had the highest total citations (16,626). Additionally, the United States had the highest average citations per article (12.14), followed by Japan (11.98), Germany (11.19), South Korea (11.04), and China (10.95). High-income countries published 98.73% of articles, upper-middle-income countries published 0.24% of articles, and middle-income countries published 1.03% of articles. CONCLUSION: The time trend for the number of MISS articles showed a significant increase over time with an average of 93.23 articles per year. The United States was the most productive country and had the highest average citations per article. Among related journals, Spine published the largest number of articles in MISS research and was the most popular one in the top five countries. LEVEL OF EVIDENCE: 5.