Search

Dan Xu,1 Shu-Ting Lu,2 Yu-Shuang Li,2 Aju Baidya,2 Hao Mei,2 Yong He,1 Bo Wu2 1Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, PR China; 2Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, PR China Background: Gliomas are one of the most common types of primary brain tumors. It is usually evaluated by gadolinium(III)-based contrast agents by magnetic resonance imaging (MRI) in the clinic. Methotrexate (MTX), as a type of folate analog that inhibits the enzyme dihydrofolate reductase, is widely used as a chemotherapeutic agent to treat gliomas in the experiment.Purpose: In this study, a novel theranostic agent MTX-DOTA-Gd (MTX-Gd) was synthesized, which integrates magnetic resonance imaging (MRI) with anticancer treatment.Methods: MTX-Gd was synthesized by connecting MTX and Gd through 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The characterization of MTX-Gd was detected by ultraviolet (UV) and infrared spectroscopy (IR). To confirm the antitumor effect of MTX-Gd, the cytotoxicity of MTX-Gd was examined by the MTT assay. The contrast enhancement of the MTX-Gd was measured through MRI in vitro. Then, nude mice bearing C6 tumor xenografts were used to study in vivo imaging capabilities.Results: The ultraviolet-visible-near infrared radiation (UV-NIR) absorption curve indicated that MTX-Gd had a broad absorption in the region of 500-700 nm. The formation of MTX-Gd was confirmed from the characteristic bands of MTX-DOTA-Gd in the 1413 cm-1 (C-N), 1577 cm-1 (-NH2), and 3429 cm-1 (N-H), in the fourier-transform infrared (FTIR) spectra. MTX-Gd showed little difference in the cell viability compared with MTX, except for the highest concentration (270 μM). In vitro, the imaging of MTX-Gd was significantly brighter than Gd-DOTA at the same concentration, and the brightness and signal intensity of MRI were increased followed by the increased concentration of MTX-Gd. And it also showed that MTX was not visualized on MRI. The other images revealed that the concentration of 4 mM MTX-Gd had the same imaging effect with the concentration of 10 mM Gd-DOTA. Then, MTX-Gd was injected in nude mice bearing C6 tumor xenografts through the tail vein. Significant contrast enhancement was observed at the tumor site from 0.5 h to 3 h. The signal of tumor area was strongest at 3 h due to accumulation by size effect of macromolecules.Conclusion: A novel stable and unique theranostic agent(MTX-Gd) was successfully synthesized, and it has good stability, strong anticancer ability and excellent magnetic capacity. The methotrexate component of MTX-Gd, as a chemotherapeutic agent, played an important role in targeted therapies of cancer. The DOTA-Gd component of MTX-Gd performed as the MRI contrast agent. The superior MRI imaging performance and synergetic chemical antineoplastic ability of MTX-Gd was revealed, and it has great potential in the diagnosis and treatment of glioma and potentially other cancers, with prospects of clinical application in the near future. Keywords: methotrexate, gadolinium, glioma, theranostics

Bo Wu,1,* Bing Wan,2,* Shu-Ting Lu,1 Kai Deng,3 Xiao-Qi Li,1 Bao-Lin Wu,1 Yu-Shuang Li,1 Ru-Fang Liao,1 Shi-Wen Huang,3 Hai-Bo Xu1,2 1Department of Radiology, Zhongnan Hospital of Wuhan University, 2Department of Radiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 3Department of Chemistry, Key Laboratory of Biomedical Polymers, Ministry of Education, Wuhan University, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: The major challenge in current clinic contrast agents (CAs) and chemotherapy is the poor tumor selectivity and response. Based on the self-quench property of IR820 at high concentrations, and different contrast effect ability of Gd-DOTA between inner and outer of liposome, we developed “bomb-like” light-triggered CAs (LTCAs) for enhanced CT/MRI/FI multimodal imaging, which can improve the signal-to-noise ratio of tumor tissue specifically. IR820, Iohexol and Gd-chelates were firstly encapsulated into the thermal-sensitive nanocarrier with a high concentration. This will result in protection and fluorescence quenching. Then, the release of CAs was triggered by near-infrared (NIR) light laser irradiation, which will lead to fluorescence and MRI activation and enable imaging of inflammation. In vitro and in vivo experiments demonstrated that LTCAs with 808 nm laser irradiation have shorter T1 relaxation time in MRI and stronger intensity in FI compared to those without irradiation. Additionally, due to the high photothermal conversion efficiency of IR820, the injection of LTCAs was demonstrated to completely inhibit C6 tumor growth in nude mice up to 17 days after NIR laser irradiation. The results indicate that the LTCAs can serve as a promising platform for NIR-activated multimodal imaging and photothermal therapy. Keywords: light triggered, near-infrared light, tumor-specific, multimodal imaging, photothermal therapy, contrast agents

Because parametric values are unknown during initial concept generation, the Axiomatic Design Theory uses the binary design matrix (DM) to represent the coupling relationship between functional requirements and design parameters. However, given an existing product, it would be possible to employ the numerical DM that has more detailed information than the binary DM to help improve the design concept. This paper proposed a two-phase method to create a numerical DM in phase I and manage the functional couplings in phase II for concept improvement of existing product. A decomposition-definition-levelling framework and the Puritan-Bennett’s 0-1-3-9 level rating are employed to evaluate the system impact of each functional coupling to create the numerical DM of an existing design concept. The Design Coupling Sequence (DCS) approach was extended to use the numerical DM to improve this design concept. Compared with other numerical matrices for product development and the structured approach by Su et al., our method is more generic and faster, providing useful details yet still able to maintain the dominance of the high-level couplings.

Conceptual design is the stage where the upstream objectives and downstream constraints meet, so both the ideality and practicality are important in conceptual design. Modularity supports designing complex system while the design can take advantages from the downstream resources. According to Axiomatic Design Theory (ADT), the design with the least complexity is the ideal design, and managing functional coupling sequence can lead to the minimal complexity of design concepts. In this paper, Design Coupling Sequence (DCS) was introduced to bridge the ADT and the modular design. The ‘precedence’ and ‘functional sets’ were defined in DCS to manage the coupled design concepts in order to support the modularity of the design concepts. The ‘precedence’ identified by the level of functional coupling helps realize the sequencing order. The two ‘functional sets’ were defined as the independent U-set: the collection of functionally dependent concepts, and the coupled C-set: the collection of the strongly coupled concepts. The faucet design case study shows how the DCS method and its strategy to decrease relative complexity and increase modularity, and the results between design by extra coupling elimination and design by the existing modules are compared. The DCS method bridges the design theory to design practice.

Abstract Background Signal peptide peptidase (SPP), a member of the presenilin-like intra-membrane cleaving aspartyl protease family, migrates on Blue Native (BN) gels as 100 kDa, 200 kDa and 450 kDa species. SPP has recently been implicated in other non-proteolytic functions such as retro-translocation of MHC Class I molecules and binding of misfolded proteins in the endoplasmic reticulum (ER). These high molecular weight SPP complexes might contain additional proteins that regulate the proteolytic activity of SPP or support its non-catalytic functions. Results In this study, an unbiased iTRAQ-labeling mass spectrometry approach was used to identify SPP-interacting proteins. We found that vigilin, a ubiquitous multi-KH domain containing cytoplasmic protein involved in RNA binding and protein translation control, selectively enriched with SPP. Vigilin interacted with SPP and both proteins co-localized in restricted intracellular domains near the ER, biochemically co-fractionated and were part of the same 450 kDa complex on BN gels. However, vigilin does not alter the protease activity of SPP, suggesting that the SPP-vigilin interaction might be involved in the non-proteolytic functions of SPP. Conclusions We have identified and validated vigilin as a novel interacting partner of SPP that could play an important role in the non-proteolytic functions of SPP. This data adds further weight to the idea that intramembrane-cleaving aspartyl proteases, such as presenilin and SPPs, could have other functions besides the proteolysis of short membrane stubs.

Conjugated polymer sorting is recognized as an efficient and scalable method for the selective extraction of semiconducting single-walled carbon nanotubes (s-SWCNTs). However, this process typically requires the use of nonpolar and aromatic solvents as the dispersion medium, which are petroleum-based and carry significant production hazards. Moreover, there is still potential for improving the efficiency of batch purification. Here, this study presents fluorene-based conjugated polymer that integrates diamines containing ethylene glycol chains (ODA) as linkers within the main chain, to effectively extract s-SWCNTs in bio-renewable solvents. The introduction of ODA segments enhances the solubility in bio-renewable solvents, facilitating effective wrapping of s-SWCNTs in polar environments. Additionally, the ODA within the main chain enhances affinity to s-SWCNTs, thereby contributing to increased yields and purity. The polymer achieves a high sorting yield of 55% and a purity of 99.6% in dispersion of s-SWCNTs in 2-Methyltetrahydrofuran. Thin-film transistor arrays fabricated with sorted s-SWCNTs solution through slot-die coating exhibit average charge carrier mobilities of 20-23 cm 2  V⁻¹ s⁻¹ and high on/off current ratios exceeding 10 5 together with high spatial uniformity. This study highlights the viability of bio-renewable solvents in the sorting process, paving the way for the eco-friendly approach to the purification of SWCNTs., (© 2024 Wiley‐VCH GmbH.)

Background: Dysfunction of the glymphatic system in the brain in different stages of altered glucose metabolism and its influencing factors are not well characterized., Aim: To investigate the function of the glymphatic system and its clinical correlates in patients with different glucose metabolism states, the present study employed diffusion tensor imaging along the perivascular space (DTI-ALPS) index., Methods: Sample size was calculated using the pwr package in R software. This cross-sectional study enrolled 22 patients with normal glucose metabolism (NGM), 20 patients with prediabetes, and 22 patients with type 2 diabetes mellitus (T2DM). A 3.0T magnetic resonance imaging was used to evaluate the function of the glymphatic system. The mini-mental state examination (MMSE ) was used to assess general cognitive function. The DTI-ALPS index of bilateral basal ganglia and the mean DTI-ALPS index was calculated. Further, the correlation between DTI-ALPS and clinical features was assessed., Results: The left-side, right-side, and mean DTI-ALPS index in the T2DM group were significantly lower than that in the NGM group. The right-side DTI-ALPS and mean DTI-ALPS index in the T2DM group were significantly lower than those in the prediabetes group. DTI-ALPS index lateralization was not observed. The MMSE score in the T2DM group was significantly lower than that in the NGM and prediabetes group. After controlling for sex, the left-side DTI-ALPS and mean DTI-ALPS index in the prediabetes group were positively correlated with 2-hour postprandial blood glucose level; the left-side DTI-ALPS index was negatively correlated with total cholesterol and low-density lipoprotein level. The right-side DTI-ALPS and mean DTI-ALPS index were negatively correlated with the glycosylated hemoglobin level and waist-to-hip ratio in the prediabetes group. The left-side, right-side, and mean DTI-ALPS index in the T2DM group were positively correlated with height. The left-side and mean DTI-ALPS index in the T2DM group were negatively correlated with high-density lipoprotein levels., Conclusion: Cerebral glymphatic system dysfunction may mainly occur in the T2DM stage. Various clinical variables were found to affect the DTI-ALPS index in different glucose metabolism states. This study enhances our understanding of the pathophysiology of diabetic brain damage and provides some potential biological evidence for its early diagnosis., Competing Interests: Conflict-of-interest statement: The authors declare that this study was conducted without any business or financial relationship that could be interpreted as a potential conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Syk is a tumor suppressor gene in some solid tumors. Currently, it remains unknown how Syk gene hypermethylation is controlled by DNA methyltransferase (DNMT) and p53. In colorectal cancer HCT116 cells, we found that protein and mRNA levels of Syk were much higher in WT than in p53 -/- cells. Both p53 inhibitor PFT-α and p53 silencing can reduce the protein and mRNA expression of Syk in WT cells, while DNMT inhibitor 5-Aza-2'-dC can increase Syk expression in p53 -/- cells. Interestingly, the DNMT expression in p53 -/- HCT116 cells was higher than that in WT cells. PFT-α can not only enhance Syk gene methylation but also increase DNMT1 protein and mRNA levels in WT HCT116 cells. In metastatic lung cancer cell lines A549 and PC9, which express WT p53 and gain function of p53, respectively, PFT-α can also downregulate Syk mRNA and protein expression. However, the Syk methylation level was increased by PFT-α in A549 but not in PC9 cells. Likewise, 5-Aza-2'-dC transcriptionally increased Syk gene expression in A549 cells, but not in PC9 cells. In summary methylation of Syk promoter requires DNMT1, and p53 can upregulate Syk expression via downregulation of DNMT1 at the transcriptional level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To introduce a case of a uterus "hernia-like" myoma within the uterine cavity that was successfully treated with hysteroscopy., Design: Step-by-step explanation of the case and surgical procedure using a video and slides. The Medical Ethics Committee of Women and Children's Hospital of Chongqing Medical University approved the study and decided for this video to be exempt from formal approval, and informed consent was obtained from the patient., Setting: Hospital., Patient(s): A 37-year-old woman, gravida 1, para 1, with a history of secondary infertility for 2 years and heavy menstrual bleeding for 7 months, which eventually resulted in anemia, was diagnosed with a type 1 (International Federation of Gynecology and Obstetrics leiomyoma subclassification system) myoma approximately 4 cm in diameter using ultrasonography. Her hemoglobin level was 8.6 g/dL (11.5-15.0 g/dL), red blood cell count was 3.6 ×10-12/L (3.8-5.1 ×10-12/L), and hematocrit was 26.7% (35%-45%)., Intervention(s): Hysteroscopic myomectomy with bipolar resectoscope and transabdominal ultrasound guidance was used to resect the hernia-like myoma. Blunt dissection combined with oxytocin (20 U I.V.) and uterine dilation pressure reduction was used to induce the hernial content (myoma) protrusion into the uterine cavity., Main Outcome Measure(s): The hernia-like myoma was completely resected by hysteroscopy, and all symptoms disappeared., Result(s): The hernia-like myoma was successfully and completely resected by hysteroscopy. The operative time was 37 minutes. No surgical-related or anesthesia-related complications occurred. During the follow-up period, the patient had regular menstrual cycles without hypermenorrhea, and her anemia had improved. The 5-month follow-up ultrasound examination and hysteroscopy revealed that the uterine cavity had recovered well. The patient conceived 7 months after the procedure and delivered at term (39 weeks 1 day) via cesarean section., Conclusion(s): A hernia-like myoma covered with endometrium is a degenerative myoma that herniates into the myometrium and forms a hernia sac-like defect. Hysteroscopy is an effective and feasible method for treating hernia-like myoma., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Large area skin trauma has always been a great challenge for both patients and clinicians. Exosomes originating from human adipose-derived mesenchymal stem cells (hADSCs) have been a novel promising cell-free treatment in cutaneous damage repair. Nevertheless, the low retention rate of exosomes post-transplantation in vivo remains a significant challenge in clinical applications. Herein, we purposed to explore the potential clinical application roles of hADSCs-Exos encapsulated in functional PF-127 hydrogel in wound healing., Methods: hADSCs-Exos were isolated from human hADSCs by ultracentrifugation. An injectable, biocompatible, and thermo-sensitive hydrogel Pluronic F-127 hydrogel was employed to encapsulate allogeneic hADSCs-Exos, and this complex was topically applied to a full-thickness cutaneous wound in mice. On different days post-transplantation, the mice were sacrificed, and the skin tissue was excised for histological and immunohistochemical analysis., Results: Compared with hADSCs-Exos or PF-127 only, PF-127/hADSCs-Exos complexes enhanced skin wound healing, promoted re-epithelialization, increased expression of Ki67, α-SMA, and CD31, facilitated collagen synthesis (Collagen I, Collagen III), up-regulated expression of skin barrier proteins (KRT1, AQP3), and reduced inflammation (IL-6, TNF-α, CD68, CD206). By using PF-127/hADSCs-Exos complexes, hADSCs-Exos can be administrated at lower doses frequency while maintaining the same therapeutic effects., Conclusion: Administration of hADSCs-Exos in PF-127 improves the efficiency of exosome delivery, maintains the bioactivity of hADSCs-Exos, and optimizes the performance of hADSCs-Exos. Thus, this biomaterial-based exosome will be a promising treatment approach for the cutaneous rejuvenation of skin wounds., (© 2022. The Author(s).)

Introduction and Hypothesis: To present a novel technique to remove intravesical eroded mesh through a 3-mm trocar-assisted cystoscopy., Methods: First, a 3-mm trocar was inserted into the bladder under ultrasound guidance after the bladder had been infused with 600 ml normal saline. Second, we inserted the forceps through the trocar into the bladder and pulled the mesh through the 3-mm trocar. Last, cystoscopic scissors were used to remove the eroded mesh completely., Results: The patient was managed adequately in the inpatient department. The urethral catheter was left in situ for 3 days, and the patient was discharged within 5 days., Conclusion: Surgery under 3-mm trocar-assisted cystoscopy offers the advantage of lower risk of morbidity and complications compared to other surgical techniques. It is an effective and feasible procedure for treatment of synthetic mesh erosion into the bladder after TVM surgery., (© 2022. The International Urogynecological Association.)

Purpose: The pedal-based power meter has its advantages, so it has become a popular monitoring tool in cycling. This study aimed to examine the validity of the Favero Assioma Duo power pedal system (FAD) in comparison with the SRM, which is considered the gold standard under maximal-effort cycling conditions, and a widely used cycling test, the 20-minute Functional Threshold Test., Methods: Fourteen male adolescent cyclists completed a series of cycling intervals including 5, 15, 30, 60, 240, 600, and 1200 seconds (20-min Functional Threshold Test) with their maximal-effort performance on 2 separate days. Power output data were collected from the FAD and the SRM for analysis., Results: Extremely strong correlations and excellent intraclass correlation coefficients (ICCs) were found between the power output values registered with the FAD and the SRM overall (r > .999, ICC = .996) and each power test (r > .98, ICC > .91). A low bias was found in power tests of longer durations (-3.2% at 240-s test, -3.3% at 600-s test, and -3.1% at 20-min Functional Threshold Test), while the bias augmented in shorter intervals (-2.7% at 5-s test, -3.6% at 15-s test, and -2.6% at 30-s test and -3.3% at 60-s test). A regression equation was proposed as y = -2.943 + 0.976x to diminish the bias (-0.2 W) with increased r value (>.98) and ICC (>.98)., Conclusion: The FAD appears to be a valid tool for the measures of maximal-effort performance. The recorded power value reflects the true value with proposed regression equation.

Introduction: The most frequently prescribed first-line treatment for limited (mild-to-moderate) psoriasis is topical corticosteroids, which are associated with several adverse effects with long term use. Benvitimod is an aryl hydrocarbon receptor immunomodulator that is both efficacious and tolerable for use in patients with mild to severe psoriasis with a body surface area (BSA) range of 1-20%., Areas Covered: In this review, the authors conducted a PubMed and Google Scholar search of key words and a review of clinical trials. They discuss the targeted mechanism of action for psoriasis, efficacy and safety profile of topical benvitimod, and its indications. Benvitimod affects key regulators of psoriasis, including proinflammatory markers and skin barrier proteins. Benvitimod is well-tolerated in patients with mild to severe plaque psoriasis. Treatment-emergent adverse events (TEAEs) include pruritus, contact dermatitis, and folliculitis; however, the majority of TEAEs were mild to moderate in severity, and most resolved without further treatment. A limitation of this study includes a small number of trials due to the dr' novelty., Expert Opinion: Benvitimod may serve as a good alternative for psoriatic patients who desire a nonsteroidal topical option. The usefulness of benvitimod may be limited by prior authorizations that discourage healthcare providers from prescribing the medication and poor outcomes.

In order to comprehensively explore multitarget mechanism and key active compounds of Artemisia argyi essential oil (AAEO) in the treatment of pressure injuries (PIs), we analyzed the biological functions and pathways involved in the intersection targets of AAEO and PIs based on network pharmacology, and the affinity of AAEO active compounds and core targets was verified by molecular docking finally. In our study, we first screened 54 effective components according to the relative content and biological activity. In total, 103 targets related to active compounds of AAEO and 2760 targets associated with PIs were obtained, respectively, and 50 key targets were overlapped by Venny 2.1.0. The construction of key targets-compounds network was achieved by the STRING database and Cytoscape 3.7.2 software. GO analysis from Matespace shows that GO results are mainly enriched in biological processes, including adrenergic receptor activity, neurotransmitter clearance, and neurotransmitter metabolic process. KEGG analysis by the David and Kobas website shows that the key targets can achieve the treatment on PIs through a pathway in cancer, PI3K-Akt signaling pathway, human immunodeficiency virus 1 infection, MAPK signaling pathway, Wnt signaling pathway, etc. In addition, molecular docking results from the CB-Dock server indicated that active compounds of AAEO had good activity docking with the first 10 key targets. In conclusion, the potential targets and regulatory molecular mechanisms of AAEO in the treatment of PIs were analyzed by network pharmacology and molecular docking. AAEO can cure PIs through the synergistic effect of multicomponent, multitarget, and multipathway, providing a theoretical basis and new direction for further study., Competing Interests: All authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Shu-ting Lu et al.)

Background: Endometriosis of the uterine body can be manifested as diffuse solid lesions or cystic lesions. The former is common, while the latter is rare, especially for cystic adenomyosis larger than 5 cm., Case Presentation: A 30-year-old woman was admitted for severe and worsening dysmenorrhea. Ultrasound examination revealed a rare well-circumscribed cystic lesion about 5.5 × 4 × 5.0 cm. CA-125 level was slightly elevated. She accepted laparoscopic surgery and the adenomyotic tissues were excised. The histopathology of the specimen demonstrated the endometrial glands in the walls of cysts and an area of extensive hemorrhage can be seen in the inner wall of cyst. The patient made a good recovery after surgery and her symptoms complete resoluted., Conclusions: This is a rare case of a cystic adenomyotic lesion that was treated by laparoscopic surgery.

Background: Cutaneous wound healing and regeneration have become a recognized health challenge in the world, which causes severe damage to the mental and physical health of patients. Human adipose-derived mesenchymal stem cells (hADSC) play an essential role in wound healing via their paracrine function. Exosomes secreted by hADSC may contribute to this progress. In this study, we investigated the potential clinical application roles of hADSC and hADSC-derived exosomes (hADSC-Exo) in cutaneous wound healing., Methods: hADSC-Exo was isolated from human hADSC by ultracentrifugation. Mice were subjected to a full-thickness skin biopsy experiment and treated with either control vehicle or hADSC or hADSC-Exo by smearing administration (sm) or subcutaneous administration (sc) or intravenous administration (iv). The efficacy of hADSC and hADSC-Exo on wound healing was evaluated by measuring wound closure rates, histological analysis., Results: Combined application of local hADSC-Exo smearing and hADSC/hADSC-Exo intravenous administration offered the additional benefit of promoting wound healing, accelerating re-epithelialization, reducing scar widths, and enhancing angiogenesis and collagen synthesis. Either topical application of hADSC-Exo or systemic administration with hADSC/hADSC-Exo appeared more effective in stimulating cell proliferation, inhibiting cell apoptosis and inflammation, and promoting skin elasticity and barrier integrity, with increased genes expression of PCNA, VEGF, collagen III, Filaggrin, Loricrin, and AQP3, with decreased genes expression of TNF-alpha., Conclusion: Our findings suggest that the combined administration of hADSC/hADSC-Exo can facilitate cutaneous wound healing and reduce scar formation. These data provide the first evidence for the feasibility of smearing of hADSC-Exo as a cell-free therapy in treating cutaneous wounds, and the potential clinical value of combined administration of hADSC/hADSC-Exo.

Objectives: To evaluate the safety of low-dose tanezumab in the treatment of knee or hip osteoarthritis (OA)., Methods: Databases were searched up to September 2019 for phase III randomized controlled trials (RCTs). Eleven phase III RCTs comprising 11,455 patients were eligible. The pooled estimates of safety outcomes were assessed and expressed using relative risks (RRs) and 95% confidence intervals with a random-effects model., Results: Tanezumab significantly increased the incidence of rapidly progressive OA (RPOA; RR = 9.07, 95% CI = 1.21-67.90, P = 0.03) and abnormal peripheral sensation (APS; RR = 2.68, 95% CI = 1.64-4.37, P < 0.00001) compared with placebo. No significant difference was found in terms of incidence of total joint replacement (TJR; RR = 1.13, 95% CI = 0.76-1.68, P = 0.55) or withdrawal due to adverse effects (AEs; RR = 1.26, 95% CI = 0.79-2.00, P = 0.33). The tanezumab group showed a statistically higher incidence of RPOA (RR = 3.96, 95% CI = 2.23-7.04, P < 0.00001) and APS (RR = 1.2, 95% CI = 1.44-2.56, P < 0.00001) compared with the nonsteroidal anti-inflammatory drugs and opioids group. No significant difference was found in terms of TJR (RR = 1.51, 95% CI = 0.65-3.47, P = 0.33) and withdrawal (RR = 0.54, 95% CI = 0.20-1.40, P = 0.20). Subgroup analysis revealed that 2.5 mg of tanezumab did not show an advantage over 5 mg of tanezumab in reducing AEs., Conclusions: These results demonstrate that RPOA and APS should be the most concerning AEs when using tanezumab in OA patients. Additional data are needed to define the optimal dose to minimize risk and to determine the optimal subjects to receive this treatment., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Shunt infection is a common complication while treating hydrocephalus. The antibiotic-impregnated shunt catheter (AISC) was designed to reduce shunt infection rate. A meta-analysis was conducted to study the effectiveness of AISCs in reduction of shunt infection in terms of age, follow-up time and high-risk patient population., Methods: This study reviewed literature from three databases including PubMed, EMBASE, and Cochrane Library (from 2000 to March 2019). Clinical studies from controlled trials for shunt operation were included in this analysis. A subgroup analysis was performed based on the patient's age, follow-up time and high-risk population. The fixed effect in RevMan 5.3 software (Cochrane Collaboration) was used for this meta-analysis., Results: This study included 19 controlled clinical trials including 10105 operations. The analysis demonstrated that AISC could reduce the infection rate in shunt surgery compared to standard shunt catheter (non-AISC) from 8.13% to 4.09% (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.40-0.58; p=0.01; I2=46%). Subgroup analysis of different age groups showed that AISC had significant antimicrobial effects in all three groups (adult, infant, and adolescent). Follow-up time analysis showed that AISC was effective in preventing early shunt infections (within 6 months after implant). AISC is more effective in high-risk population (OR, 0.24; 95% CI, 0.14-0.40; p=0.60; I2=0%) than in general patient population., Conclusion: The results of meta-analysis indicated that AISC is an effective method for reducing shunt infection. We recommend that AISC should be considered for use in infants and high-risk groups. For adult patients, the choice for AISC could be determined based on the treatment cost.

Differential diagnosis between inflammatory mass and malignant glioma is of great significance to patients, which is the basis for developing accurate individualized treatment. Due to the lack of non-invasive imaging characterization methods in the clinical application, the current diagnosis grading of glioma mainly depended on the pathological biopsy, which is complicated and risky. This study aims to develop a non-invasive imaging differential diagnosis method of glioma based on the reduction activated strategy of intracellular aggregation of sensitive superparamagnetic Fe 3 O 4 nanoparticles (SIONPs). In vitro and in vivo magnetic resonance imaging results indicated that SIONPs could specifically increase the T 2 relaxation rate and enhance MR imaging in tumor with redox microenvironment by the response-aggregation in the tumorous site. In vivo experiments also demonstrate that the substantial improvement of T2-weighted imaging contrast could be used to differentiate inflammatory mass and malignant glioma. The reduction-active MR imaging contrast agent offers a new paradigm for designing "smart" MR imaging probes of differential diagnosis of the tumor., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Meta-analysis to evaluate complications in the use of autogenous bone and bone substitutes and to compare bone substitutes, specifically HA, polyetheretherketone (PEEK) and titanium materials. Methods: Search of PubMed, Cochrane, Embase and Google scholar to identify all citations from 2010 to 2019 reporting complications regarding materials used in cranioplasty. Results: 20 of 2266 articles met the inclusion criteria, including a total of 2913 patients. The odds of overall complication were significantly higher in the autogenous bone group ( n  = 214/644 procedures, 33.2%) than the bone substitute groups ( n  = 116/436 procedures, 26.7%, CI 1.29-2.35, p < 0.05). In bone substitutes groups, there was no significant difference in overall complication rate between HA and Ti (OR, 1.2; 95% CI, 0.47-3.14, p  = 0.69). PEEK has lower overall complication rates (OR, 0.51; 95% CI, 0.30-0.87, p  = 0.01) and lower implant exposure rates (OR, 0.17; 95% CI, 0.06-0.53, p  = 0.002) than Ti, but there was no significant difference in infection rates and postoperative hematoma rates. Conclusions: Cranioplasty is associated with high overall complication rates with the use of autologous bone grafts compared with bone substitutes. PEEK has a relatively low overall complication rates in substitutes groups, but still high infection rates and postoperative hematoma rates. Thus, autologous bone grafts should only be used selectively, and prospective long-term studies are needed to further refine a better material in cranioplasty.

Neuronal GABAergic responses switch from excitatory to inhibitory at an early postnatal period in rodents. The timing of this switch is controlled by intracellular Cl- concentrations, but factors determining local levels of cation-chloride cotransporters remain elusive. Here, we report that local abundance of the chloride importer NKCC1 and timely emergence of GABAergic inhibition are modulated by proteasome distribution, which is mediated through interactions of proteasomes with the adaptor Ecm29 and the axon initial segment (AIS) scaffold protein ankyrin G. Mechanistically, both the Ecm29 N-terminal domain and an intact AIS structure are required for transport and tethering of proteasomes in the AIS region. In mice, Ecm29 knockout (KO) in neurons increases the density of NKCC1 protein in the AIS region, a change that positively correlates with a delay in the GABAergic response switch. Phenotypically, Ecm29 KO mice showed increased firing frequency of action potentials at early postnatal ages and were hypersusceptible to chemically induced convulsive seizures. Finally, Ecm29 KO neurons exhibited accelerated AIS developmental positioning, reflecting a perturbed AIS morphological plastic response to hyperexcitability arising from proteasome inhibition, a phenotype rescued by ectopic Ecm29 expression or NKCC1 inhibition. Together, our findings support the idea that neuronal maturation requires regulation of proteasomal distribution controlled by Ecm29., (© 2020 Lee et al.)

In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24 months. Micro-CT analysis showed that the implanted stent was able to maintain structural integrity after 6 months, while its disintegration occurred after 9 months of implantation. After 24 months of implantation, approximately 28 ± 13 vol% of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24 months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24 months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications. STATEMENT OF SIGNIFICANCE: Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: Ultrasound-guided venipuncture and tip location by intracavitary electrocardiogram have many advantages during the insertion of peripherally inserted central catheters, both in terms of safety and cost-effectiveness. Recently, a new tip-conductive peripherally inserted central catheters and new Doppler ultrasound device integrated with intracavitary electrocardiogram have been introduced into clinical practice in China. A randomized multicenter study (clinical trial no. NCT03230357) was performed to verify the feasibility and accuracy of intracavitary electrocardiogram, as performed with this new peripherally inserted central catheters and device., Methods: Our study enrolled a total of 2250 adult patients in 10 different Chinese hospitals. The patients were randomly assigned to either the study group (intracavitary electrocardiogram) or the control group (anatomical landmark guidance) in a 2:1 allocation. Ultrasound was used in both groups for venipuncture and tip navigation. All patients underwent chest X-ray after the procedure to verify the position of the catheter tip., Results: No insertion-related complications were reported in either group. In the study group, first-attempt successful tip location was 91.7% (95% confidence interval: 90.3%-93.1%), significantly higher than 78.9% (95% confidence interval: 76.0%-81.9%) observed in the control group (p < 0.001). As evaluated by post-procedural chest X-ray, tip location in the study group had a sensitivity of 99.3% (95% confidence interval: 98.8%-99.7%), significantly higher than 86.8% (95% confidence interval: 84.4%-89.2%) observed in the anatomical landmark group (p < 0.001)., Conclusion: These results indicated that during peripherally inserted central catheters insertion in adult patients, tip location with intracavitary electrocardiogram guidance, as carried out by a new tip-conductive peripherally inserted central catheters and intracavitary electrocardiogram integrated ultrasound device, was more effective and more accurate than tip location using anatomical landmarks.

Background: MicroRNA molecules have been identified to play key roles in a broad range of physiological and pathological processes. Polymorphisms in the corresponding sequence space are likely to make a significant con-tribution to phenotypic variation. The aim of this study was to evaluate the pre-miR-146a C/G (rs2910164) and pre-miR-499 T/C (rs3746444) polymorphisms and their putative association with inflammatory markers in AF in Han Chinese., Methods: A total of 123 participants were enrolled, 65 AF patients were confirmed with electrocardiogram (ECG) or dynamic electrocardiography, 58 normal individuals were assigned to the control group., Results: Genotypes of the pre-miR-146a C/G (rs2910164) and pre-miR-499 T/C (rs3746444) polymorphisms were distinguished using the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The distribution of the pre-miR-146a C/G (rs2910164) genotypes CC, CG, and GG was 33.85%, 52.31%, and 13.84% in the AF group and 37.93%, 51.72%, and 10.35% in the controls, respectively. There was no significant difference in either genotype frequency distributions (p = 0.7973) or allele frequency distributions (p = 0.5411) between these two groups. The distribution of the pre-miR-499 T/C (rs3746444) genotypes TT, TC, and CC was 72.41%, 22.41%, and 5.18% in the controls and 49.23%, 38.46%, and 12.31% in AF subjects, respec-tively (p = 0.0296). The frequency of the C allele in the AF group was significantly higher than that in the control group (31.54% vs. 16.38%, p = 0.0057). Compared with the TT genotype, the C allele carriers (TC+CC genotypes) had a 2.7070-fold increased risk of AF. After being adjusted for age, gender, leucocytes, left atrial dimension, left ventricular ejection fraction, serum levels of lipids, and inflammatory markers, the association persisted (adjusted OR = 2.3387, 95% CI =1.1094 - 4.9300, p = 0.0280). Individuals with TC+CC genotype in pre-miR-499 T/C (rs3746444) had greater serum levels of IL-6 and hs-CRP than did patients with the TT genotype., Conclusions: Our data support that the pre-miR-499 T/C (rs3746444) polymorphism is associated with AF, and the C allele has increased risk for AF in Han Chinese.

Single-component nanomaterials such as bismuth (Bi) based on nanoparticles (NPs) intrinsically having both diagnostic and therapeutic capabilities are widely needed in biomedical fields. However, their design and fabrication still face enormous challenges. Here, a kind of pure Bi NPs with ultrahigh X-ray attenuation coeffcient was developed and evaluated as a simple but powerful theranostic nanomaterals and potent light-to-heat conversion efficiency for photoacuostic imaging (PAI)/photothermal therapy (PTT) in this study. The prepared pure Bi NPs showed excellent photothermal performance and the temperature of NPs solution (1 mg/mL) increased to 70 °C under near-infrared light irradiation within 4 min. The pure Bi NPs showed obvious enhancement effect both in X-ray computed tomography (CT) and PA imaging modalities in vivo . In addition, the glioma growth was efficiently suppressed by the pure Bi NPs after 808 nm laser irradiation, while maintained the biosafety and low toxicity. Thus, it is notable that this type of Bi nanomaterial has great potential in multi-imaging guided cancer treatment.

Effective hemostasis is vital to reduce the pain and mortality of patients, and the research and development of hemostatic materials are prerequisite for effective hemostasis. Chitosan (CS), with good biodegradability, biocompatibility and non-toxicity, has been widely applied in bio-medicine, the chemical industry, the food industry and cosmetics. The excellent hemostatic properties of CS have been extensively studied. As a result, chitosan-based composite hemostatic materials have been emerging. In this review, the hemostatic mechanism of chitosan is briefly discussed, and then the progress of research on chitosan-based composite hemostatic materials with multiple forms such as films, sponges, hydrogels, particles and fibers are introduced. Finally, future perspectives of chitosan-based composite hemostatic materials are given. The objective of this review is to provide a reference for further research and development of effective hemostatic materials.

Multifunctional nanomaterials with simple structure and good biosafety, integrating multimodal imaging and therapeutic functions, can facilitate the development of clinical cancer treatments. Here, a simple but powerful pure bismuth based nanoparticle (Gd-PEG-Bi NPs) was developed from pure Bi NPs and gadolinium-diethylenetriaminepentaacetic acid-bis-tetradecylamide, which not only shows high quality MRI/CT/PAI triple-modal imaging, but can also be a potent photothermal therapy agent under the guidance of the triple-modal imaging. The Gd-PEG-Bi NPs showed good stability and excellent biocompatibility. In vitro and in vivo study demonstrated that Gd-PEG-Bi NPs have ultrahigh X-ray attenuation coefficient, short T1 relaxation time in MRI, and strong PAI signal. Following the imaging diagnosis, the excellent light-to-heat conversion efficiency of Gd-PEG-Bi NPs was capable of suppressing the tumor growth effectively under near-infrared laser radiation in vivo. Such multifunctional nanoparticles were ideal candidates for cancer diagnosis and treatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Neurite initiation is the first step in neuronal development and occurs spontaneously in soft tissue environments. Although the mechanisms regulating the morphology of migratory cells on rigid substrates in cell culture are widely known, how soft environments modulate neurite initiation remains elusive. Using hydrogel cultures, pharmacologic inhibition, and genetic approaches, we reveal that paxillin-linked endocytosis and adhesion are components of a bistable switch controlling neurite initiation in a substrate modulus-dependent manner. On soft substrates, most paxillin binds to endocytic factors and facilitates vesicle invagination, elevating neuritogenic Rac1 activity and expression of genes encoding the endocytic machinery. By contrast, on rigid substrates, cells develop extensive adhesions, increase RhoA activity and sequester paxillin from the endocytic machinery, thereby delaying neurite initiation. Our results highlight paxillin as a core molecule in substrate modulus-controlled morphogenesis and define a mechanism whereby neuronal cells respond to environments exhibiting varying mechanical properties.

In recent years, there has been increasing interest in developing a multifunctional nanoscale platform for cancer monitoring and chemotherapy. However, there is still a big challenge for current clinic contrast agents to improve their poor tumor selectivity and response. Herein, we report a new kind of Gd complex and folate-coated redox-sensitive lipid-polymer hybrid nanoparticle (Gd-FLPNP) for tumor-targeted magnetic resonance imaging and therapy. Gd-FLPNPs can simultaneously accomplish diagnostic imaging, and specific targeting and controlled release of doxorubicin (DOX). They exhibit good monodispersity, excellent size stability, and a well-defined core-shell structure. Paramagnetic nanoparticles based on gadolinium-diethylenetriaminepentaacetic acid-bis-cetylamine have paramagnetic properties with an approximately two-fold enhancement in the longitudinal relaxivity compared to clinical used Magnevist. For targeted and reduction-sensitive drug delivery, Gd-FLPNPs released DOX faster and enhanced cell uptake in vitro, and exhibited better antitumor effect both in vitro and in vivo., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Porphyrin derivatives have been widely applied in MR imaging and photodynamic cancer therapy. We here report a novel Gd/Pt bifunctionalized porphyrin derivative (Gd/Pt-P1) for MRI-guided chemo-photodynamic cancer therapy. Gd/Pt-P1 was prepared from tetra(4-pyridyl) porphyrin (P1) via step by step coordination to cisplatin and gadolinium (Gd(iii)). Gd/Pt-P1 showed a particularly high synergetic chemo-photodynamic antitumor effect in vivo with a tumor inhibition rate (TIR) of 96.6% and excellent MR imaging performance.

Codelivery is a promising strategy to overcome the limitations of single chemotherapeutic agents in cancer treatment. Despite progress, codelivery of two or more different functional drugs to increase anticancer efficiency still remains a challenge. Here, reduction-sensitive lipid-polymer hybrid nanoparticles (LPNPs) drug delivery system composed of monomethoxy-poly(ethylene glycol)- S - S -hexadecyl (mPEG- S - S -C 16 ), soybean lecithin, and poly(D,L-lactide-co-glycolide) (PLGA) was used for codelivery of doxorubicin (DOX) and a Chinese herb extract triptolide (TPL). Hydrophobic DOX and TPL could be successfully loaded in LPNPs by self-assembly. More importantly, drug release and cellular uptake experiments demonstrated that the two drugs were reduction sensitive, released simultaneously from LPNPs, and taken up effectively by the tumor cells. DOX/TPL-coloaded LPNPs (DOX/TPL-LPNPs) exhibited a high level of synergistic activation with low combination index (CI) in vitro and in vivo. Moreover, the highest synergistic therapeutic effect was achieved at the ratio of 1:0.2 DOX/TPL. Further experiments showed that TPL enhanced the uptake of DOX by human oral cavity squamous cell carcinoma cells (KB cells). Overall, DOX/TPL-coencapsulated reduction-sensitive nanoparticles will be a promising strategy for cancer treatment., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The aim of the present study was to investigate the effects of phosphorylated osteopontin (p-OPN) on apoptosis and pro-inflammatory cytokine expression in human knee osteoarthritis (OA) chondrocytes. Human knee OA chondrocytes obtained from patients who underwent total knee arthroplasty were treated with p-OPN, OPN or buffer. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) and western blot analysis were used to assess the expression levels of proinflammatory factors, including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6 and nuclear factor (NF)-κB. Apoptosis of human knee OA chondrocytes was detected by Annexin V-fluorescein isothiocyanate/propidium iodide flow cytometry. Compared with the controls, chondrocytes treated with OPN exhibited higher mRNA and protein expression levels of proinflammatory factors (IL-1β, TNF-α, IL-6 and NF-κB), and a higher percentage of apoptotic chondrocytes. Furthermore, chondrocytes treated with p-OPN exhibited the highest mRNA and protein expression levels of proinflammatory factors (IL-1β, TNF-α, IL-6, NF-κB) and the highest percentage of apoptotic chondrocytes. p-OPN induces chondrocyte apoptosis and proinflammatory factor release, which suggests that p-OPN may contribute to OA pathogenesis, and inhibition of p-OPN may provide a novel effective strategy to slow or halt OA progression.

Novel dual-ratiometric fluorescent electrospun (ES) nanofibers featuring high sensitivity for pH and ferric ion (Fe(3+)) were prepared using binary blends of poly(2-hydroxyethyl methacrylate-co-N-methylolacrylamide-co-nitrobenzoxadiazolyl derivative) (poly(HEMA-co-NMA-co-NBD)) and a spirolactam rhodamine derivative (SRhBOH) by employing a single-capillary spinneret. The HEMA, NMA, and NBD moieties were designed to exhibit hydrophilic properties, chemical cross-linking, and fluorescence (fluorescence resonance energy transfer (FRET) donor), respectively. The fluorescence emission of SRhBOH was highly selective for pH and Fe(3+); when SRhBOH detected acidic media and Fe(3+), the spirocyclic form of SRhBOH, which is nonfluorescent, was transformed into the opened cyclic form and exhibited strong fluorescence emission. The emission colors of ES nanofibers in acidic or Fe(3+) aqueous solutions changed from green to red because of FRET from NBD (donor) to SRhBOH (acceptor). The off/on switching of the FRET process was modulated by adjusting the SRhBOH blending ratio, pH, and Fe(3+) concentration. Poly(HEMA-co-NMA-co-NBD) ES fibers blended with 20% SRhBOH showed high sensitivity in sensing Fe(3+) and pH because of the substantial 57 nm red shift in emission as well as substantial reversible dual photoluminescence. The prepared FRET-based dual-ratiometric fluorescent ES nanofibrous membranes can be used as "naked eye" sensors and have potential for application in multifunctional environment sensing devices.

Objective: To observe the hemodynamic change and reperfusion injury cause by transient hepatic venous occlusion and transient hepatic inflow occlusion in rats., Methods: The rat liver was divided into 3 different areas: the ischemia reperfusion (IR) area: the inflow of the right superior lobe was clamped for half an hour; the non-isolated lobe congestive reperfusion (NIL-CR) area: the outflow of the right median lobe was clamped for half an hour; and the isolated lobe congestive reperfusion (IL-CR) area: the outflow of the left lobe was clamped for half an hour. The flux value and the oxygen saturation of microcirculation were monitored before at clamping for 30 minutes, and on 1 day, 3 days ,and 7 days after reperfusion. The hepatic damage and Suzuki's score were evaluated., Results: After clamping for 30 minutes, the flux value in the IR area was significantly higher than in NIL-CR area (P<0.01) and IL-CR area (P<0.01), the oxygen saturation in the IR area was significantly higher than in NIL-CR area (P<0.01) and IL-CR area (P<0.05). Compared with IR area, both NIL-CR area and IL-CR area were found having more severe liver damage in terms of Suzuki's score in early postoperative period (at clamping for 30 minutes and on 1 day, P<0.01). However, there was no significant difference between NIL-CR area and IL-CR area in flux value, oxygen saturation, and Suzuki's score (P>0.05)., Conclusions: Hepatic venous occlusion can more effectively decrease the blood perfrusion and oxygen saturation; thus, compared to the IR, CR can result in more severe liver damage. The presence of normal liver tissue around the congestion area can not influence liver damage in transient hepatic venous occlusion.

This study investigates the risk factors in railway reconstruction project through complete literature reviews on construction project risks and scrutinizing experiences and challenges of railway reconstructions in Taiwan. Based on the identified risk factors, an assessing framework based on the fuzzy multicriteria decision-making (fuzzy MCDM) approach to help construction agencies build awareness of the critical risk factors on the execution of railway reconstruction project, measure the impact and occurrence likelihood for these risk factors. Subjectivity, uncertainty and vagueness within the assessment process are dealt with using linguistic variables parameterized by trapezoid fuzzy numbers. By multiplying the degree of impact and the occurrence likelihood of risk factors, estimated severity values of each identified risk factor are determined. Based on the assessment results, the construction agencies were informed of what risks should be noticed and what they should do to avoid the risks. That is, it enables construction agencies of railway reconstruction to plan the appropriate risk responses/strategies to increase the opportunity of project success and effectiveness.

Objective: To evaluate the factors that might affect the putative survival benefit from pre-operative neoadjuvant chemotherapy (NAC) in patients with early stage bulky cervical cancer., Methods: A retrospective review for 304 patients with stage IB(2)/IIA(2) cervical cancer was performed. Two groups were made according to pre-operative NAC or not: NAC group (n=154) and primary surgery group (PST, n=150). Recurrence risks and survival were analyzed., Results: The total response rate was 72.1%. For those NAC-responders, NAC decreased the ratio of lymphovascular space invasion (0 vs. 4.7%, p=0.022; 0 vs. 3.3%, p=0.052), deep stromal invasion (19.8% vs. 53.5%, p=0.000; 19.8% vs. 29.3%, p=0.08), lymph node metastasis (8.1% vs. 25.6%, p=0.004; 8.1% vs. 17.3%, p=0.031), and the need of adjuvant radiotherapy (5.5% vs. 30.2%, p=0.000; 5.4% vs. 15.3%, p=0.012), whereas improve 5-year PFS rate (94% vs. 86%, p=0.041; 94% vs. 80%, p=0.089) and 5-year OS rate (96% vs. 86%, p=0.015; 96% vs. 82%, p=0.05), as compared with non-responders and PST. Multivariate analysis suggested that the response to NAC is an independent prognostic factor of PFS (HR 0.221, 95% CI 0.048-1.022, p=0.053) and OS (HR 0.126, 95% CI 0.016-1.000, p=0.05); as compared, stage IIA disease demonstrates negative impact upon PFS (HR 4.778, 95% CI 1.490-15.317, p=0.009) and OS (HR 4.142, 95% CI 1.258-13.639, p=0.019)., Conclusion: Responsiveness of NAC before surgery might be an independent prognostic factor for the patients with early stage bulky cervical cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The microbial activity in soils was a critical factor governing the degradation of organic micro-pollutants. The present study was conducted to analyze the effects of soil organic matter on the development of degradation potentials for polycyclic aromatic hydrocarbons (PAHs). Most of the degradation kinetics for PAHs by the indigenous microorganisms developed in soils can be fitted with the Logistic growth models. The microbial activities were relatively lower in the soils with the lowest and highest organic matter content, which were likely due to the nutrition limit and PAH sequestration. The microbial activities developed in humic acid (HA) were much higher than those developed in humin, which was demonstrated to be able to sequester organic pollutants stronger. The results suggested that the nutrition support and sequestration were the two major mechanisms, that soil organic matter influenced the development of microbial PAHs degradation potentials., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Microwave-induced corneal endothelial damage was reported to have a low threshold (2.6 W/kg), and vasoactive ophthalmologic medications lowered the threshold by a factor of 10-0.26 W/kg. In an attempt to confirm these observations, four adult male Rhesus monkeys (Macaca mulatta) under propofol anesthesia were exposed to pulsed microwaves in the far field of a 2.8 GHz signal (1.43 +/- 0.06 micros pulse width, 34 Hz pulse repetition frequency, 13.0 mW/cm(2) spatial and temporal average, and 464 W/cm(2) spatial and temporal peak (291 W/cm(2) square wave equivalent) power densities). Corneal-specific absorption rate was 5.07 W/kg (0.39 W/kg/mW/cm(2)). The exposure resulted in a 1.0-1.2 degrees C increase in eyelid temperature. In Experiment I, exposures were 4 h/day, 3 days/week for 3 weeks (nine exposures and 36 h total). In Experiment II, these subjects were pretreated with 0.5% Timolol maleate and 0.005% Xalatan(R) followed by 3 or 7 4-h pulsed microwave exposures. Under ketamine-xylazine anesthesia, a non-contact specular microscope was used to obtain corneal endothelium images, corneal endothelial cell density, and pachymetry at the center and four peripheral areas of the cornea. Ophthalmologic measurements were done before and 7, 30, 90, and 180 days after exposures. Pulsed microwave exposure did not cause alterations in corneal endothelial cell density and corneal thickness with or without ophthalmologic drugs. Therefore, previously reported changes in the cornea exposed to pulsed microwaves were not confirmed at exposure levels that are more than an order of magnitude higher.

Objective: To investigate the effect of handportable mobiletelephone microwave radiation on rat central nervous system by setting up rat model., Methods: 80 healthy male SD rats (weighed about 200 g) were divided into 4 groups at random: control, radiation, decranium, decranium + radiation. TUNEL method was adopted used to detect the apoptosis of neurons after irradiation, then immunohistochemistry was used to detect Bcl-2, Bax expression in all brain tissue., Results: TUNEL positive rate, Bax and Bcl-2 positive cell numbers could be found in decranium + radiation group [(26.45 +/- 9.27)%, (23.5 +/- 3.58), (11.1 +/- 2.55) respectively]. There were significant differences among control [(9.59 +/- 2.55)%, 14.2 +/- 2.46, 7.0 +/- 1.14 respectively], decranium group [(9.52 +/- 1.93)%, 15.5 +/- 1.77, 7.4 +/- 1.76], radiation group [(10.04 +/- 3.62)%, 15.9 +/- 2.02, 7.2 +/- 1.07] (P < 0.01). But the difference was not found in the ratio of Bax to Bcl-2., Conclusion: Microwave radiation did not affect the intact rat, but did promote the occurrence of neuron apoptosis in cranial defect rat. Bax, Bcl-2 gene participated in regulation of apoptosis. The intact cranium may be an important factor to protect the neurons against handportable mobiletelephone microwave radiation to some extent.

We studied the retinal effects of 1.25 GHz high peak power microwaves in Rhesus monkeys. Preexposure fundus photographs, retinal angiograms, and electroretinograms (ERG) were obtained to screen for normal ocular structure and function and, after exposure, as endpoints of the study. Histopathology of the retina was an additional endpoint. Seventeen monkeys were randomly assigned to receive sham exposure or pulsed microwave exposures. Microwaves were delivered anteriorly to the face at 0, 4.3, 8.4, or 20.2 W/kg spatially and temporally averaged retinal specific absorption rates (R-SAR). The pulse characteristics were 1.04 MW ( approximately 1.30 MW/kg temporal peak R-SAR), 5.59 micros pulse length at 0, 0.59, 1. 18, and 2.79 Hz pulse repetition rates. Exposure was 4 h per day and 3 days per week for 3 weeks, for a total of nine exposures. The preexposure and postexposure fundus pictures and angiograms were all within normal limits. The response of cone photoreceptors to light flash was enhanced in monkeys exposed at 8.4 or 20.2 W/kg R-SAR, but not in monkeys exposed at 4.3 W/kg R-SAR. Scotopic (rod) response, maximum (combined cone and rod) response, and Naka-Rushton R(max) and log K of scotopic b-waves were all within normal range. Retinal histopathology revealed the presence of enhanced glycogen storage in photoreceptors among sham (2/5), 8.4 W/kg (3/3), and 20.2 W/kg (2/5) exposed monkeys, while enhanced glycogen storage was not observed in the 4.3 W/kg (0/4) exposed group. Supranormal cone photoreceptor b-wave was R-SAR dependent and may be an early indicator of mild injury. However no evidence of degenerative changes and ERG depression was seen. We concluded that retinal injury is very unlikely at 4 W/kg. Functional changes that occur at higher R-SAR are probably reversible since we saw no evidence of histopathologic correlation with ERG changes. Bioelectromagnetics 21:439-454, 2000. Published 2000 Wiley-Liss, Inc.

The ultrawide-band (UWB) electromagnetic pulses are used as a new modality in radar technology. Biological effects of extremely high peak E-field, fast rise time, ultrashort pulse width, and ultrawide band have not been investigated heretofore due to the lack of animal exposure facilities. A new biological effects database is needed to establish personnel protection guidelines for these new type of radiofrequency radiation. Functional indices of the cardiovascular system (heart rate, systolic, mean, and diastolic pressures) were selected to represent biological end points that may be susceptible to the UWB radiation. A noninvasive tail-cuff photoelectric sensor sphygmomanometer was used. Male Wistar-Kyoto rats were subjected to sham exposure, 0.5-kHz (93 kV/m, 180 ps rise time, 1.00 ns pulse width, whole-body averaged specific absorption rate, SAR = 70 mW/kg) or a 1-kHz (85 kV/m, 200 ps rise time, 1.03 ns pulse width, SAR = 121 mW/kg) UWB fields in a tapered parallel plate GTEM cell for 6 min. Cardiovascular functions were evaluated from 45 min to 4 weeks after exposures. Significant decrease in arterial blood pressures (hypotension) was found. In contrast, heart rate was not altered by these exposures. The UWB radiation-induced hypotension was a robust, consistent, and persistent effect.

The pharmacological effects of laurotetanine on rat isolated thoracic aorta were examined. The contraction of aortic rings caused by high potassium (60 mM) and cumulative concentrations of calcium (0.03-3 mM) was inhibited by 3-50 microM laurotetanine in a dose-dependent manner with an IC50 value of 19.8 +/- 3.6 microM (n = 6) in a 1 mM Ca2+ medium. The phenylephrine (3 microM)-induced contraction was also inhibited by laurotetranine. Its effect was more marked on the tonic contraction than on the phasic contraction and was not easily washed-out. On addition of laurotetanine during the tonic contraction, relaxation could also be observed. This relaxing effect was not antagonized by indomethacin (20 microM) and was still seen in denuded aorta or in the presence of nifedipine (1 microM). The caffeine (20 mM)-induced contraction was not affected by laurotetanine. cAMP and cGMP levels of aorta were not changed by laurotetanine. It is concluded that laurotetanine relaxed the rat thoracic aorta mainly by suppressing the Ca2+ influx through both voltage- and receptor-operated calcium channels.

Microwave evoked body movements were studied in mice. A resonant cavity was used to provide head and neck exposure of the mouse to pulsed and gated continuous wave (CW) 1.25 GHz microwaves. No difference in response to pulsed and gated CW stimuli of equal average power was found. The incidence of the microwave evoked body movements increased proportionally with specific absorption (dose) when the whole-body average specific absorption rate was at a constant level (7300 W/kg). Under a constant average specific absorption rate, the response incidence reached a plateau at 0.9 kJ/kg. For doses higher than 0.9 kJ/kg, response incidence was proportional to the specific absorption rate and reached a plateau at 900 W/kg. Body movements could be evoked by a single microwave pulse. The lowest whole-body specific absorption (SA) tested was 0.18 kJ/kg, and the corresponding brain SA was 0.29 kJ/kg. Bulk heating potentials of these SAs were less than 0.1 degree C. For doses higher than 0.9 kJ/kg, the response incidence was also proportional to subcutaneous temperature increment and subcutaneous heating rate. The extrapolated absolute thresholds (0% incidence) were 1.21 degrees C temperature increment and 0.24 degree C/s heating rate. Due to high subcutaneous heating rates, these microwaves must be perceived by the mouse as an intense thermal sensation but not a pain sensation because the temperature increment was well below the threshold for thermal pain. Results of the present study should be considered in promulgation of personnel protection guideline against high peak power but low average power microwaves.