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AAA domain containing 3A (ATAD3A) is a nucleus-encoded mitochondrial protein with vital function in communication between endoplasmic reticulum (ER) and mitochondria which is participated in cancer metastasis. Here we show that elevated ATAD3A expression is clinically associated with poor 5-year disease-free survival in patients with colorectal cancer (CRC), especially high-risk CRC patients who received adjuvant chemotherapy. Our results indicated ATAD3A is significantly upregulated to reduce chemotherapy-induced cancer cell death. We found that knockdown of ATAD3A leads to dysregulation in protein processing for inducing ER stress by RNA sequencing (RNA-seq). In response to chemotherapy-induced ER stress, ATAD3A interacts with elevated GRP78 protein to assist protein folding and alleviate ER stress for cancer cell survival. This reduction of ER stress leads to reduce the surface exposure of calreticulin, which is the initiator of immunogenic cell death and antitumor immunity. However, silencing of ATAD3A enhances cell death, triggers the feasibility of chemotherapy-induced ER stress for antitumor immunity, increases infiltration of T lymphocytes and delays tumor regrowth in vitro and in vivo. Clinically, CRC patients with less ATAD3A have high density of CD45+ intratumoral infiltrating lymphocytes (TILs) and memory CD45RO+ TILs. Taken together, our results suggest that pharmacologic targeting to ATAD3A might be a potential therapeutic strategy to enhance antitumor immunity for CRC patients who received adjuvant chemotherapy.

Propose: The proposed deep learning model with a mask region–based convolutional neural network (Mask R-CNN) can predict choroidal thickness automatically. Changes in choroidal thickness with age can be detected with manual measurements. In this study, we aimed to investigate choroidal thickness in healthy eyes by utilizing the Mask R-CNN model. Methods: A total of 68 eyes from 57 participants without significant ocular disease were recruited. The participants were allocated to one of three groups according to their age and underwent spectral domain optical coherence tomography (SD-OCT) centered on the fovea. Physicians labelled the choroidal contours in all the OCT sequences. We applied the Mask R-CNN model for automatic segmentation. Comparisons of choroidal thicknesses were conducted according to age and prediction accuracy. Results: Older age groups had thinner choroids, according to the automatic segmentation results; the mean choroidal thickness was 253.7 ± 41.9 μm in the youngest group, 206.8 ± 35.4 μm in the middle-aged group, and 152.5 ± 45.7 μm in the oldest group (p < 0.01). Measurements obtained using physician sketches demonstrated similar trends. We observed a significant negative correlation between choroidal thickness and age (p < 0.01). The prediction error was lower and less variable in choroids that were thinner than the cutoff point of 280 μm. Conclusion: The mean choroidal thickness decreased with age in healthy subjects. The Mask R-CNN model can accurately predict choroidal thickness, especially choroids thinner than 280 μm. This model can enable exploring larger and more varied choroid datasets comprehensively, automatically, and conveniently.

Failure to follow the "Five Rights" and interruptions during medication administration are the two most common factors underlying nurse-related medication errors.This study was designed to examine the effectiveness in terms of improving nurses' medication administration self-efficacy and recognition of medication errors of an online objective structured video examination (OSVE) intervention focused on the "Five Rights" and "management of interruptions during medication administration".A quasi-experimental pretest-posttest research design with a respondent-driven sampling method was employed. One hundred and twelve nurses finished the online survey. Instruments included the self-efficacy of medication administration questionnaire and four online medication error OSVEs addressing the issue of medication error recognition. The intervention was an acute medication behavior OSVE. Paired t-tests were used to assess the pre-test / post-test differences between variables.The mean age of the 112 survey respondents was 27.21 years, and the mean years of working experience was 4.67. The mean self-efficacy of medication administration score, which was 38.88 (SD = 4.45) at baseline, increased significantly to 41.69 (SD = 4.58) at post-test (t = 7.11, p.001). Similarly, the mean score for recognition of medication errors was 10.71 (SD = 7.16) at pre-test and significantly higher (15.32; SD = 4.94) at post-test (t = 5.90, p.001).The online OSVE may be used to improve the recognition of medication errors and self-efficacy of medication administration in nurses. Future research is needed to examine the effect of this intervention in enhancing the safety of medication administration in actual clinical practice settings.線上客觀結構式影像測試於提升護理人員給藥自我效能與辨認給藥錯誤行為之成效.「三讀五對」及給藥過程被干擾是導致護理人員給藥錯誤的最常見原因。.探討線上「三讀五對」與「給藥過程干擾處理」的給藥客觀結構式影像測試（objective structured video examinations, OSVE）介入於提升護理人員給藥自我效能與辨認給藥錯誤行為之成效。.採類實驗前測、後測研究設計，以同伴推動抽樣法共招募112位護理人員參與本線上研究。研究工具包括給藥自我效能問卷、四個給藥錯誤行為OSVE及其對應之辨認給藥錯誤行為問題，介入措施為一個正確給藥行為OSVE。成對樣本t檢定用以分析二個變項在前測與後測的差異。.112位研究樣本的平均年齡為27.21歲，平均工作年資為4.67年，給藥自我效能於前測得分為38.88（SD = 4.45），後測得分為41.69（SD = 4.58），二者達顯著差異（t = 7.11, p.001）；辨認給藥錯誤行為前測得分為10.71（SD = 7.16），後測得分為15.32（SD = 4.94），二者也呈顯著差異（t = 5.90, p.001）。.線上給藥OSVE可立即提升臨床護理人員辨認給藥錯誤行為的正確性，並提高自我效能，未來研究需探討其在提升實際給藥安全的成效。.

Background : Restless legs syndrome (RLS) has been thought to increase the risk of hypertension, cardiovascular events, and all-cause mortality. Periodic limb movements in sleep (PLMS) can be observed in most patients with RLS. Using non-invasive physiologic measurement and analysis, including heart rate variability (HRV) analysis, we aimed to investigate sleep quality and sleep state stability. Method : A total of 53 healthy controls and 15 patients with RLS and PLMS were recruited. Patients with other sleep-related disorders such as obstructive sleep apnea (OSA) and major depressive disorder (MDD) were excluded. Each subject was evaluated using sleep and mood questionnaires and had to undergo polysomnography (PSG). HRV analysis was applied to assess autonomic function and analyze correlations with the severity of periodic leg movements (PLM). The power of different brainwaves was analyzed using electroencephalogram (EEG). Electromyogram (EMG) was also used to explore the temporal correlation between changes in HRV and leg movement events. Results : Compared with healthy controls, PLMS group had not only poorer perceived sleep and mood questionnaires scales but also reductions in parasympathetic-related HRV indices and increases in sympathetic-related HRV parameters. The changes were in proportion to the severity of PLM. Brainwaves and sleep stage which indicate “deep sleep” decreased in the PLMS group. There were no significant temporal correlations between changes in HRV and leg movement events. Conclusions : Our findings suggest that patients with RLS and PLMS have poorer subjective sleep and mood scales. Besides, objective sleep quality including HRV analysis and brainwaves analysis revealed reduced parasympathetic tone, increased sympathetic tone, and sleep disturbance, which reveal the possibility of a higher risk for secondary disease.

Heme oxygenase (HO)-1 is an inducible stress response protein and well known to protect cells and tissues against injury. Despite its important function in cytoprotection against physiological stress, the role of HO-1 in embryonic stem cell (ESC) differentiation remains largely unknown. We showed previously that induced pluripotent stem (iPS) cells that lack HO-1 are more sensitive to oxidant stress-induced cell death and more prone to lose pluripotent markers upon LIF withdrawal. To elucidate the role of HO-1 in ESC differentiation and to rule out the controversy of potential gene flaws in iPS cells, we derived and established mouse HO-1 knockout ESC lines from HO-1 knockout blastocysts. Using wild type D3 and HO-1 knockout ESCs in the 3-dimensional embryoid body (EB) differentiation model, we showed that at an early time point during EB development, an absence of HO-1 led to enhanced ROS level, concomitant with increased expressions of master mesodermal regulator brachyury and endodermal marker GATA6. In addition, critical smooth muscle cell (SMC) transcription factor serum response factor and its coactivator myocardin were enhanced. Furthermore, HO-1 deficiency increased Smad2 in ESCs and EBs, revealing a role of HO-1 in controlling Smad2 level. Smad2 not only mediates mesendoderm differentiation of mouse ESCs but also SMC development. Collectively, loss of HO-1 resulted in higher level of mesodermal and SMC regulators, leading to accelerated and enhanced SMC marker SM α-actin expression. Our results reveal a previously unrecognized function of HO-1 in regulating SMC gene expressions during ESC-EB development. More importantly, our findings may provide a novel strategy in enhancing ESC differentiation toward SMC lineage., Graphical abstract fx1, Highlights • Loss of HO-1 in ESCs promotes adipogenesis but reduces osteogenesis. • During early EB development, loss of HO-1 results in robust induction of brachyury. • During early EB development, lack of HO-1 leads to enhanced ROS level. • Loss of HO-1 increases SMC transcription factor SRF and cofactor myocardin. • HO-1 deficiency promotes mesodermal SMC differentiation during EB development.

Dysfunctional mitochondria have been shown to enhance cancer cell proliferation, reduce apoptosis, and increase chemoresistance. Chemoresistance develops in nearly all patients with colorectal cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. However, the effect of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission on chemoresistance in colorectal cancer is unclear. Here, we found that the release of high-mobility group box 1 protein (HMGB1) in conditioned medium from dying cells by chemotherapeutic drugs and resistant cells, which triggered Drp1 phosphorylation via its receptor for advanced glycation end product (RAGE). RAGE signals ERK1/2 activation to phosphorylate Drp1 at residue S616 triggerring autophagy for chemoresistance and regrowth in the surviving cancer cells. Abolishment of Drp1 phosphorylation by HMGB1 inhibitor and RAGE blocker significantly enhance sensitivity to the chemotherapeutic treatment by suppressing autophagy. Furthermore, patients with high phospho-Drp1Ser616 are associated with high risk on developing tumor relapse, poor 5-year disease-free survival (DFS) and 5-year overall survival (OS) after neoadjuvant chemoradiotherapy (neoCRT) treatment in locally advanced rectal cancer (LARC). Moreover, patients with RAGE-G82S polymorphism (rs2070600) are associated with high phospho-Drp1Ser616 within tumor microenvironment. These findings suggest that the release of HMGB1 from dying cancer cells enhances chemoresistance and regrowth via RAGE-mediated ERK/Drp1 phosphorylation.

Myeloid leukemia cells maintain a high intracellular ROS level and use redox signals for survival. The metabolism of ROS also affects cell fate, including cell death and differentiation. Superoxide dismutases (SODs) are major antioxidant enzymes that have high levels of expression in myeloid leukemia cells. However, the role of SODs in the regulation of myeloid leukemia cells' biological function is still unclear. To investigate the function of SODs in myeloid leukemia cell death and differentiation, we used myeloid leukemia cell lines K562, MEG-01, TF-1, and HEL cells for this study. We found that PMA-induced megakaryocytic differentiation in myeloid leukemia cells is accompanied by cell death and SOD1 down-regulation, while SOD2 expression is not affected. The role of SOD1 is verified when ATN-224, a SOD1 specific inhibitor, inhibits cell proliferation and promotes cell death in myeloid leukemia cells without PMA treatment. Moreover, inhibition or silencing of SODs further increases cell death and decreases polyploidization induced by PMA while they were partially reversed by SOD1 overexpression. Thus, SOD1 expression is required for myeloid leukemia cell fate determination. In addition, the knockdown of PKD2 reduces cell death and promotes polyploidization induced by PMA. PMA/PKD2-mediated necrosis via PARP cleavage involves both SOD1-dependent and -independent pathways. Finally, ATN-224 enhanced the inhibition of cell proliferation by Ara-C. Taken together, the results demonstrate that SOD1 regulates cell death and differentiation in myeloid leukemia cells. ATN-224 may be beneficial for myeloid leukemia therapy.

Esophageal carcinoma (EC) is one of the most aggressive cancer types worldwide. However, the underlying genomic events of EC are not fully understood. It is becoming evident that long non-coding RNAs (lncRNAs) play vital roles in tumorgenesis, metastasis, prognosis and diagnosis. Accumulating EC-related lncRNAs have been verified to involve in various biological processes through diverse functions including signal, decoy, scaffold and guide. However, the molecular mechanism of lncRNAs in EC has not been fully explored. In this review, we outline the functions and underlying mechanism of EC-related lncRNAs to pave the way for identification of novel potential biomarkers for EC.

Oxidative stress-induced growth inhibitor 1 (OSGIN1), a tumor suppressor, inhibits cell proliferation and induces cell death. N-6 and n-3 PUFAs protect against breast cancer, but the molecular mechanisms of this effect are not clear. We investigated the effect of n-6 and n-3 PUFAs on OSGIN1 expression and whether OSGIN1 is involved in PUFA-induced apoptosis in breast cancer cells. We used 100 μM of n-6 PUFAs including arachidonic acid, linoleic acid, and gamma-linolenic acid and n-3 PUFAs including alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid (DHA). Only DHA significantly induced OSGIN1 protein and mRNA expression. DHA triggered reactive oxygen species (ROS) generation and nuclear translocation of Nrf2. LY294002, a PI3K inhibitor, suppressed DHA-induced OSGIN1 protein expression and nuclear accumulation of Nrf2. Nrf2 knockdown attenuated DHA-induced OSGIN1 expression. N-Acetyl-l-cysteine, a ROS scavenger, abrogated the DHA-induced increases in Akt phosphorylation, Nrf2 nuclear accumulation, and OSGIN1 expression. DHA induced the Bax/Bcl-2 ratio, mitochondrial accumulation of OSGIN1 and p53, and cytochrome c release; knockdown of OSGIN1 diminished these effects. In conclusion, induction of OSGIN1 by DHA is at least partially associated with increased ROS production, which activates PI3K/Akt/Nrf2 signaling. Induction of OSGIN1 may be involved in DHA-induced apoptosis in breast cancer cells.

From 1989 to 1996, we treated 18 cases (10 males, eight females; average age 48.2 years) of failed ankle arthrodesis by revision of ankle arthrodesis and followed their progress for at least two years. The average time interval between original surgery and revision was 17.3 months. Revisions were needed due to infection in one case, nonunion in 10 cases, and malalignment in seven cases. The salvage operations included debridement in the infected case, refreshed pseudoarthrosis in nonunion cases, and corrective osteotomy in malalignment cases. Sixteen cases were fixed by crossed screws with internal compression, one infected case was fixed by an external fixator, and one case with bone loss was fixed with buttress plate. The average follow-up period was 40.4 months. There was one nonunion and two delayed unions, with an ultimate fusion rate of 94%. The average AOFAS ankle-hindfoot score was 70.9 at final follow up. There was one excellent result (5.6%), five good results (27.8%), 11 fair results (61%), and one poor result (5.6%), and the overall results were poorer compared with our series of primary arthrodesis. The time to fusion also took longer in the revision cases (average 2.7 months in primary cases and 4.8 months in revision cases). Fusion techniques that ensure solid union in a functional position are essential. If an ankle arthrodesis fails, however, revision is a salvage procedure that can achieve an acceptable result.

Aging and age-related health problems are major issues of concern for community health services. Yoga is an exercise with both physiological and psychological effects on aging. Although many studies have assessed the effectiveness of yoga in the elderly, little information is available in the literature to support empirical conclusions.This review synthesizes and characterizes findings related to the effects of yoga on depression and quality of sleep in the elderly.Researchers used keywords including yoga, elderly, aged / older adult, depression, sleep, and quality to search 6 electronic databases for relevant studies published prior to March 2013. Inclusion and exclusion criteria were used to screen identified study abstracts. The Jadad scale appraised the quality of identified studies.Seven studies met the inclusion criteria. Five studies found significant changes in participant depression symptoms after doing yoga. Three studies found significant effects on the quality of sleep of participants after 6 months of doing yoga.Yoga significantly reduced the depressive symptoms of elderly participants and improved their quality of sleep after 6 months. Findings were similar for elderly living in institutions and in the community. However, the majority of participants in the assessed studies were women characterized by a high level of social participation and proactive participation in health promotion activities. Future studies should broaden the scope of research to address different aging populations and use long-term cohort observations in order to better elicit the effectiveness of yoga and to develop strategies to introduce yoga into daily activities.瑜珈於老年人憂鬱及睡眠品質之系統性文獻回顧老年健康議題，隨人口老化逐年上升而倍備受重視。瑜珈對促進老年健康之身心運動，雖有多位學者曾探討老年人執行瑜珈的成效，但文獻中鮮少提供具體實證性結論。本文經由系統性文獻回顧，整合及探討瑜珈運用於老年人憂鬱及睡眠品質之成效。搜尋六個中英文資料庫，使用關鍵字瑜珈（yoga）、老年人（elderly, aged, or older adult）、憂鬱（depression）、睡眠品質（sleep and quality）進行搜尋，時間至2013年3月前，於摘要為根據篩選納入及排除條件，並以modified Jadad score評定文獻品質。最後納入七篇文獻，其中有五篇文獻顯示在執行瑜珈後老年人的憂鬱症狀有顯著改善；三篇測量睡眠品質文獻，顯示瑜珈課程六個月後睡眠品質達到顯著改善。不論居住於機構或社區的老人，其憂鬱症狀及睡眠品質在執行六個月瑜珈後皆有顯著性改善。但由於受試者大多為女性、社會參與度高及具有健康促進的觀念者，建議未來可針對不同族群老年人進行探討，此外，亦建議進行世代研究，長期觀察瑜珈者的身心狀態，藉以了解瑜珈應用於老年人之效益，使老年人能將運動與日常生活結合。

Objective— The introduction of 4 transcription factors—c-MYC, OCT3/4, SOX2, and KLF4—can reprogram somatic cells back to pluripotency. However, some of the factors used are oncogenic, making therapeutic application unfeasible. Although the use of adult stem cells expressing high endogenous levels of some of these factors allows for reprogramming with fewer exogenous genes, such cells are rare and may have accumulated genetic mutations. Our goal was to reprogram human somatic cells without oncogenic factors. We found that high endogenous expression of KLF4 in human umbilical vein endothelial cells (HUVECs) allows for generation of induced pluripotent stem cells (iPSCs) with just 2 nononcogenic factors, OCT3/4 and SOX2 . Methods and Results— HUVECs were infected with lentivirus containing OCT4 and SOX2 for generation of iPSCs. These 2-factor HUVEC iPSCs were morphologically similar to embryonic stem cells, express endogenous pluripotency markers postreprogramming, and can differentiate toward lineages of all 3 germ layers both in vitro and in vivo. Conclusion— iPSCs can be generated from HUVECs with only 2 nononcogenic factors. The use of fetal cells for reprogramming without oncogenic factors may provide an efficient in vitro model for human iPSC research, as well as a novel source for possible therapeutic use.

BACKGROUND. The role of elective and therapeutic selective neck dissection in patients with early stage cancer of the oral tongue remains controversial. The purpose was to investigate the role of neck treatment in the management of this condition. METHODS. A total of 380 patients with cT1-2N0 oral tongue cancer were retrospectively reviewed. Patients were staged by means of computed tomography (CT) or magnetic resonance imaging (MRI) scans. A total of 324 patients received elective neck dissection (END), whereas 56 participants received observation (OBS). In all, 287 patients received supraomohyoid neck dissection (SOND), whereas 37 patients received modified radical neck dissection (MRND). Overall survival (OS) and neck control rates (NCR) were investigated according to the treatment modality. RESULTS. In the END group the occult metastasis (OM) rates in cervical lymph nodes were 5.2% for cT1 lesions and 14.6% for cT2 lesion (P = .005). The 5-year OS (P = .029) and NCR rates (P = .001) were significantly better in the END group compared with the OBS group. Patients who received MRND had a better 5-year NCR compared with SOND, albeit not significantly (91.4% vs 85.3%, P = .415). Multivariate analysis showed that END and stage were independent predictors of both NCR and OS. CONCLUSIONS. END should be performed routinely in patients with early-stage oral tongue cancer, even in the presence of negative neck by CT scans and MRI. Cancer 2008. © 2008 American Cancer Society

Tetrahydrofuran (THF) has commonly been used to deliver carotenoids to cells but the use of THF is associated with cytotoxicity and low uptake efficiency of carotenoids. Here, we used fetal bovine serum (FBS) as the delivery vehicle for lycopene in comparison with THF, THF containing 0·0025 % butylated hydroxytoluene (THF/BHT), methyl-β-cyclodextrin (M-β-CD) and micelles in two human prostate cancer cell lines, DU145 and PC-3. Lycopene (10 mm) solubilized in THF/BHT and then diluted in FBS at ratios of 5 and 10 gave the highest lycopene uptake in DU145 cells. Using a dilution factor of 10, we found that lycopene (10 μm) carried in FBS in a cell-free system led to significantly less loss of lycopene than in THF, THF/BHT and M-β-CD within 24 h of incubation. Lycopene solubilized in micelles was more stable than that in FBS within 24 h, but the micelle itself led to marked cytotoxicity to DU145 cells. Lycopene at 10 μm in FBS led to significantly higher uptake of lycopene in both cell lines than that in THF, THF/BHT or M-β-CD within 24 h of incubation. When FBS was replaced with lipoprotein-deficient serum, the uptake of lycopene by DU145 cells was markedly decreased and was not significantly different from that of THF or THF/BHT. These results demonstrate that FBS is superior to THF, THF/BHT, M-β-CD and micelles as a delivery vehicle for lycopene in prostate cell lines and that the lipoprotein of FBS is likely responsible for the improved stability and cellular uptake of lycopene.

Purpose: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). Methods and Materials: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapy or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8 –72.8 Gy). Cisplatin-based regimens were used for chemotherapy. Results: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT significantly improved survival (3-year RFS with ECS and with CCRT 48.2% vs. without CCRT 15%, p 0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. Conclusions: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present. © 2007 Elsevier Inc. Tongue neoplasms, Combined modality therapy, Radiotherapy, Concurrent chemotherapy.

Chronic progressive external ophthalmoplegia (CPEO) syndrome is one of the mitochondrial diseases caused by large-scale deletions in mitochondrial DNA (mtDNA) that impair the respiratory function of mitochondria and result in decreased production of ATP in affected tissues. In order to investigate whether CPEO-associated mtDNA mutations (i.e., 4,366-bp and 4,977-bp large-scale deletions) render human cells more vulnerable to apoptosis, we constructed cybrids carrying the deleted mtDNA. Assays for cell viability, DNA fragmentation, cytochrome c release, and caspase 3 activation revealed that UV irradiation at 20 J/m 2 triggered apoptosis in all the cybrids. This treatment also produced elevated intracellular levels of reactive oxygen species (ROS). The rate of UV-induced cell death was more pronounced in the cybrids harboring mtDNA deletions than in the control cybrid with wild-type mtDNA. Subsequently, we evaluated the effect of coenzyme Q 1 0 on the UV-triggered apoptosis. The results showed that after pretreatment of the cybrids with 100 μM coenzyme Q 1 0 the UV-induced cell damage (i.e., ROS production and activation of caspase 3) was significantly reduced. Taken together, these findings suggest that large-scale deletions of mtDNA increased the susceptibility of human cells to the UV-triggered apoptosis and that coenzyme Q 1 0 mitigated the damage; hence, it might potentially serve as a therapeutic agent to treat mitochondrial diseases resulting from mtDNA deletions.

Distant metastasis is an important issue for nasopharyngeal carcinoma (NPC). The potential value of PET using 18F-FDG has not been well defined. This prospective study investigated the impact of 18F-FDG PET in NPC patients with stage M0 disease.From April 2001 to June 2003, 140 NPC patients (118 primary and 22 primary recurrent) with stage M0 (negative results from chest radiography, liver sonography, and whole-body bone scanning) underwent 18F-FDG PET to check for distant metastases. Confirmatory MRI or CT was performed if any abnormal 18F-FDG uptake was found at distant sites. The distant lesion was confirmed pathologically, if feasible, and was followed up clinically and with imaging for at least 6 mo.18F-FDG PET detected 26 true-positive metastatic sites in 18 (12.9%) of the 140 patients, among whom 14 had primary and 4 had recurrent tumors. The patient-based sensitivity and specificity of 18F-FDG PET for distant metastases were 100% and 86.9%, respectively. Mediastinal lymph nodes (n = 8) were the most common sites, followed by lung, liver, and bone (n = 5 each) and by other lymph nodes (n = 3). In patients with primary tumors, advanced nodal status (N2-3) was a statistically significant variable associated with development of distant metastases (P = 0.044). For recurrent NPC, neither age, sex, initial tumor stage, grade of differentiation, nor nodal stage showed a statistically significant difference between patients with and patients without distant metastases.18F-FDG PET is valuable in avoiding aggressive locoregional radiotherapy in some NPC patients by the revelation of occult distant metastases, especially in patients with primary disease at a nodal stage of N2-3.

We have treated 56 patients (56 ankles) for symptomatic chronic lateral ankle instability by the surgical reconstruction procedure. The operation included lateral shift of the entire lateral capsule-ligament complex, suture to anterior border of fibula, and reinforcement by an elevated periosteal flap of distal fibula. These patients were reviewed at a mean period of 3.1 years (range, 9 months to 5 years) after the operation. There were 29 males and 27 females with an average age of 29 years (range, 16-49 years). The clinical results were graded according to the AOFAS Ankle-Hindfoot scales. There were 35 patients who were excellent (above 90 points), 16 who were good (between 76 and 90 points), 4 who were fair (between 60 and 75 points), and 1 who was poor (below 60 points). The excellent and good results amounted to 91.1% (51/56). Therefore, we concluded that symptomatic chronic lateral ankle instability could be successfully managed with this easy and effective surgical reconstruction method.

Third-harmonic generation (THG) microscopy has been reported to provide intrinsic contrast in elastic fibers, cytoplasmic membrane, nucleus, actin filaments, lipid bodies, hemoglobin, and melanin in human skin. For advanced molecular imaging, exogenous contrast agents are developed for a higher structural or molecular specificity. We demonstrate the potential of the commonly adopted tattoo dye as a THG contrast agent for in vivo optical biopsy of human skin. Spectroscopy and microscopy experiments were performed on cultured cells with tattoo dyes, in tattooed mouse skin, and in tattooed human skin to demonstrate the THG enhancement effect. Compared with other absorbing dyes or nanoparticles used as exogenous THG contrast agents, tattoo dyes are widely adopted in human skin so that future clinical biocompatibility evaluation is relatively achievable. Combined with the demonstrated THG enhancement effect, tattoo dyes show their promise for future clinical imaging applications.