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A high-pass sigma-delta modulator (HPSDM) is proposed for electrocardiography (ECG) signal acquisition system. The HPSDM is implemented using operational amplifier (op-amp) sharing and programmable feedforward coefficients. The op-amp sharing is adopted to reduce the quantity of amplifiers because they dominate the power consumption of the HPSDM. In addition, given that the magnitude of the ECG is dependent on different persons, programmable feedforward coefficients are utilized to extend the dynamic range of the HPSDM to fit the actual application. The proposed HPSDM is fabricated in a 0.18-μm standard CMOS process. Measurement results reveal that the proposed HPSDM has a signal-to-noise and distortion ratio (SNDR) of 54.5 dB and a power consumption of 2.25 μW under a 1.2 V supply voltage and achieves a figure of merit (FoM) of 12.96 pJ/conv. Moreover, the proposed HPSDM has an SNDR of 64.8 dB and a power consumption of 5.2 μW under a 1.8 V supply voltage and achieves a FoM of 9.15 pJ/conv due to the op-amp sharing technique. Under the 1.2 V and 1.8 V supply voltages, the dynamic range of the HPSDM is extended to approximately 12 dB due to the technique of programmable feedforward coefficients.

Artificial intelligence models implemented in power-efficient Internet-of-Things (IoT) devices have accuracy degradation due to limited power consumption. To mitigate the accuracy loss on IoT devices, an edge-server joint inference system is introduced. On the edge-server inference system, allocate more workloads to the server end can mitigate accuracy loss, but data transmission contributes to the power consumption of the edge device. Thus, in this article, we present a novel two-stage method to allocate workloads to the server or the edge to maximize inference accuracy under a power constraint. In the first stage, we present a clusterwise threshold-based method for estimating the trustworthiness of a prediction made at the edge. In the second stage, we further determine the workload allocation of a trustworthy image based on the probability of the top 1 prediction and the power constraint. In addition, we propose a fine-tuning process to the pretrained model at the edge for achieving better accuracy. In the experiments, we apply the proposed method to several well-known deep neural network models. The results show that the proposed method can improve inference accuracy up to 3.93% under a specific power constraint compared to previous methods.

BACKGROUND/AIM The aim of this study was to examine the role of caspase-8 rs3834129 polymorphism on colorectal cancer (CRC) risk in Taiwanese CRC patients and healthy controls. MATERIALS AND METHODS The caspase-8 rs3834129 (-652 6N insertion/deletion) polymorphic genotypes were analyzed in 362 patients with CRC and the same number of age- and gender-matched healthy subjects. The interaction of caspase-8 rs3834129 genotypes with personal behaviors and clinicopathological features were also examined. RESULTS The percentage of variants ID and DD for caspase-8 rs3834129 genotype were 37.6 and 5.8% in CRC group and 39.0 and 6.6% in the control group, respectively (p for trend=0.7987). The allelic frequency distribution analysis showed that caspase-8 rs3834129 D allele conferred a non-significant lower susceptibility for CRC compared with I allele (OR=0.92, 95%CI=0.74-1.20, p=0.5063). There was no obvious link between caspase-8 rs3834129 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No statistically significant correlation was observed between caspase-8 rs3834129 genotypic distribution and age, gender, tumor size, location or metastasis status. CONCLUSION Overall, caspase-8 rs3834129 genotypes may not serve as predictors for CRC risk or prognosis.

Epilepsy is a common clinical disease. Severe epilepsy can be life-threatening in certain unexpected conditions, so it is important to detect seizures instantly with a wearable device and to provide treatment within the golden window. The observation of the electroencephalography (EEG) signal is an imperative method to assist correct epilepsy diagnosis. To detect and classify EEG signals, a convolutional neural network (CNN) is an intuitive and appropriate method that borrows expertise from neurologists. However, the computational cost of training and inference on artificial intelligence (AI)-based solutions make software-only and hardware-only solutions incompetent for real-time monitoring on embedded devices. Hence, this study proposes three key contributions for the challenge, namely, an algorithm framework to provide real-time epilepsy detection, a dedicated coprocessor chip implementing this framework to enable real time epilepsy detection to offload and accelerate detection algorithm, and a custom interface with the coprocessor and reduced instruction set computer-V (RISC-V) instructions to reconfigure the coprocessor and transfer data. The epilepsy detection framework is implemented in 11-layer CNN. The proposed epilepsy detection algorithm performs 97.8% accuracy for floating-point and 93.5% for fixed-point operations through animal experiments with lab rats. The RISC-V CNN coprocessor is fabricated in the TSMC 0.18-μm CMOS process. For each classification, the coprocessor consumes 51 nJ/class. and 0.9 µJ/class. energy on data transfer and inference, respectively. The detection latency on the chip is 0.012 s. With the integration of the hardware coprocessor, AI algorithms can be applied to epilepsy detection for real-time monitoring.

TIMP metallopeptidase inhibitor 1 (TIMP-1) has been identified as a multifunctional molecule with divergent functions. It participates in wound healing and regeneration, cell morphology and survival, tumor metastasis, angiogenesis, and inflammatory responses. An imbalance of Matrix Metalloproteinase/TIMP regulation has been implicated in several inflammatory diseases. TIMP-1 could be considered an important regulator in the process of liver fibrosis and bile duct degeneration. Thus, we aimed to determine the role of TIMP-1 in a rat model of Common Bile Duct Ligation (CBDL). Male Sprague-Dawley rats were divided into several groups, including those with/ without CBDL surgery and those with/without amiodarone or simvastatin administration. Amiodarone/simvastatin treatment was given at a daily dose of 15 mg/kg and 18 mg/kg by means of intergalactic gavage, which began 7 days prior to CBDL induction. Two weeks after surgery, the animals in each group were sacrificed and hepatocyte degeneration severity was examined using histological morphologies. Large-scale array for secretory factors is intended for the purpose of finding key functional protein after CBDL. The hepatic level of miR-21 was determined through Taqman miRNA analysis. Furthermore, the TIMP-1 level in liver tissue was also visualized by histological stain. Liver injury and fibrosis were founded in CBDL rats based upon histopathological examination and serum biochemical analysis. Hepatic miR-21 and TIMP-1 were significantly up-regulated in CBDL rats, while being slightly rescued in response to amiodarone or simvastatin treatment. Up-regulation of miR-21 and TIMP-1 may result in the progression of hepatic cirrhosis after bile duct obstruction. Drug intervention for cirrhosis, like the use of statin, may function via similar mechanisms.

With the success of deep learning, many neural network models have been proposed and applied to various applications. In several applications, the devices used to implement the complicated models have limited power resources, and thus aggressive optimization techniques are often applied for saving power. However, some optimization techniques, such as voltage scaling and multiple threshold voltages, may increase the probability of error occurrence due to slow signal propagation, which increases the path delay in a circuit and fails some input patterns. Although neural network models are considered to have some error tolerance, the prediction accuracy could be significantly affected, when there are a large number of errors. Thus, in this paper, we propose a scheme to mitigate the errors caused by slow signal propagation. Since the delay of multipliers dominates the critical path, we consider the patterns significantly altered by the slow signal propagation in a multiplier. We propose two methods, weight distribution and error-aware quantization to prevent the patterns from failure. Since we modify a neural network on the software side and it is unnecessary to re-design the hardware structure. The experimental results show that the proposed scheme is effective for several neural network models. It can improve the network accuracy by up to 27% under the consideration of slow signal propagation.

Background: Experiments were conducted on the assumption that vivid chondrogenesis would be boosted in vivo following previously preliminary chondrogenesis in a mesenchymal stem cell (MSC)-rich entire umbilical cord (UC) in vitro. Methods: Virtual 3-D tracheal grafts were generated by using a profile obtained by scanning the native trachea of the listed porcine. Although the ultimate goal was the acquisition of a living specimen beyond a 3-week survival period, the empirical results did not meet our criteria until the 10(th) experiment, ending with the sacrifice of the animal. The categories retrospectively evolved from post-transplant modification due to porcine death using 4 different methods of implantation in chronological order. For each group, we collected details on graft construction, clinical outcomes, and results from both gross and histology examinations. Results: Three animals died due to tracheal complications: one died from graft crush, and two died secondary to erosion of the larger graft into the great vessels. It appeared that the remaining 7 died of tracheal stenosis from granulation tissue. Ectopic de novo growth of neocartilage was found in three porcine subjects. In the nearby tissues, we detected neocartilage near the anastomosis containing interim vesicles of the vascular canals (VCs), perichondrial papillae (PPs) and preresorptive layers (PRLs), which were investigated during the infancy of cartilage development and were first unveiled in the tracheal cartilage. Conclusions: 3-D-printed anatomically precise grafts could not provide successful transplantation with stent-sparing anastomosis; nonetheless, de novo cartilage regeneration in situ appears to be promising for tracheal graft adaptability. Further graft refinement and strategies for managing granulated tissues are still needed to improve graft outcomes.

AIM Metalloproteinase 2 (MMP2) is a multi-functional protein which has been shown to be up-regulated in patients with oral cancer, especially those with lymph node metastasis. However, the association of MMP2 genotype with oral cancer risk or metastatic behavior is unknown. This study aimed to evaluate the role of MMP2 promoter 1306 and -735 genotypes in the risk of oral cancer and metastasis. MATERIALS AND METHODS In this case-control study, MMP2 promoter 1306 (rs243865) and -735 (rs2285053) genotypes and their interaction with consumption of areca, cigarettes, and alcohol in determining oral cancer risk were investigated among 788 patients with oral cancer and 956 gender-matched healthy controls. In addition, their role in oral cancer metastasis were also examined. RESULTS The distribution of CC, CT and TT for MMP2 promoter 1306 genotype was 79.0, 20.1 and 0.9% in the oral cancer group and 68.7, 29.2 and 2.1% in the non-cancer control group, respectively (p for trend=4.3E-6). The allelic frequency distributions showed that the variant T allele of MMP2 promoter 1306 conferred lower oral cancer susceptibility than the wild-type C allele (odds ratio=0.61, 95% confidence interval=0.50-0.75, p=1.1E-6). As for the MMP2 -735 genotypes, there was no differential distribution in genotypic or allelic frequencies. The variant CT and TT genotypes were also associated with lower metastasis rates within 5 years among the patients with oral cancer (odds ratio=0.34, 95% confidence interval=0.15-0.80, p=0.0102). CONCLUSION The CT and TT genotypes of MMP2 promoter 1306 may have a protective effect on oral cancer susceptibility and metastasis risk within 5 years for Taiwanese. They may serve as predictive markers for oral cancer in precise medical practice.

Background/Aim: The genomic role of human mouse double minute 2 (MDM2) in colorectal cancer (CRC) is unclear, therefore, our study aimed to evaluate the contribution of MDM2 genotype to the risk of CRC in Taiwan. Materials and Methods: In this case–control study, MDM2 SNP309 T to G (rs2279744) genotypes were determined and their association with CRC risk were investigated among 362 patients with CRC and 362 age- and gender-matched healthy controls in central Taiwan. In addition, the interaction of MDM2 SNP309 genotypes with personal behaviors and clinicopathological features were also examined. Results: The percentage of variant GG for the MDM2 SNP309 genotype was 30.9% in the CRC group and 24.0% in the control group, respectively (odds ratio (OR)=1.78, 95% confidence interval (CI)=1.25-2.86, p=0.0057). The allelic frequency distribution analysis showed that the variant G allele of MDM2 SNP309 conferred a significantly increased susceptibility to CRC compared with the wild-type T allele (OR=1.32, 95% CI=1.14-1.69, p=0.0062). As for the gene-lifestyle interaction, there was an obvious joint effect of MDM2 SNP309 GG genotype on the risk of CRC among ever-smokers and non-alcohol drinkers, but not non-smoker or alcohol drinker subgroups. No statistically significant correlation was observed between MDM2 SNP309 genotypic distributions and age, gender, tumor size, location or metastasis status. Conclusion: The genotypes of MDM2 SNP309 may allow forr early detection of and predictor for CRC risk, especially among smokers and non-alcohol drinkers, but not for prognosis. The combined effects of MDM2 SNP309 and other genes (such as matrix metalloproteinases) on CRC susceptibility and prognosis, should also be taken into consideration in the era of precision medicine.

Liver cirrhosis is a major cause of liver cancer. Traditionally, the diagnosis of stages of liver cirrhosis depends on doctors’ examination of large numbers of images acquired from clinical specimens, which is a relatively time-consuming and labor-intensive task. To avoid this extensive effort and possible error of human judgment, it is necessary to develop an automatic system to recognize the liver scar stages based on clinical liver tissue section images. In this study, a tissue section image-based liver scar stage (TSILSS) diagnosis system is proposed to detect liver scar stages. In this system, a local cross-thresholding method is provided to separate the scar liver tissues from normal liver tissues on a liver tissue section image. Moreover, a two-layer recognition algorithm is presented to identify the scar stage of liver tissue. Furthermore, a parameter decider genetic algorithm is proposed to determine the most suitable values of the parameters used in the TSILSS diagnosis system. The experimental results show that in segmenting scar tissues and normal tissues on liver cirrhosis images, the average precision, average recall rate, and average F-measure that the TSILSS diagnosis system obtains are greater than 94%, and the average accuracy is close to 90%. The TSILSS diagnosis system can help doctors recognize the liver tissue scar stage more efficiently.

Background/Aim: Metalloproteinases (MMPs) are a family of multifunctional proteins reported to be overexpressed in several types of cancers. However, the contribution of MMP8 genotype to oral cancer has not been elucidated. In this study, we focused on the contribution of polymorphisms in the promoter region of MMP-8 (C-799T) and two non-synonymous polymorphisms (Val436Ala and Lys460Thr) to Taiwanese oral cancer. Materials and Methods: In this case-control study, MMP-8 genotype, was examined among 788 patients with oral cancer and 956 gender- and age-matched healthy controls regarding its potential to determine oral cancer risk. Results: The distributions of MMP-8 C-799T, Val436Ala and Lys460Thr genotypes were not different between the oral cancer and non-cancer control groups. We also analyzed the allelic frequency distributions and no significant difference was found. As for gene-environment interaction analysis, there was an increased risk for smokers, alcohol drinkers or betel quid chewers with variant MMP-8 C-799T or Val436Ala genotypes. Conclusion: Our findings suggest that the polymorphisms at MMP-8 C-799T or Val436Ala may not play a major role in mediating personal risk of oral cancer; however, the detailed mechanisms require further investigation.

AIM Bladder cancer is the sixth most common cancer worldwide and its incidence is particularly high in many developed regions including southwestern Taiwan. However, the genetic contribution to the etiology of bladder cancer is not well-understood. The aim of this study was to evaluate the association of the enhancer of zeste homolog 2 (EZH2) genotypes with Taiwan bladder cancer risk. MATERIALS AND METHODS Three polymorphic variants of EZH2 were analyzed regarding their association with bladder cancer risk, and three hundred and seventy-five patients with bladder cancer and same number of age- and gender-matched healthy controls recruited were genotyped by the PCR-RFLP method. RESULTS Among the three polymorphic sites examined, the genotypes of EZH2 rs887569 (C to T), but not rs41277434 (A to C) or rs3757441 (T to C), were positively associated with bladder cancer risk (p for trend =0.0146). Individuals with the EZH2 rs887569 TT genotypes were associated with decreased cancer risk than those with wild-type CC genotype. The stratified analyses showed that EZH2 rs887569 TT genotypes had protective effects on non-smokers but obviously not on smokers. CONCLUSION Our findings provide evidence that the T allele of EZH2 rs887569 may be associated with the lower risk of bladder cancer development, especially among non-smokers.

Background: The use of a nonthermal plasma (NTP) jet in the treatment of living tissue has been the subject of considerable interest in the field of medical technology, and has the potential to reduce the recovery time of open wounds. We aimed to investigate the wound-healing process by clinical observation, blood tests, and expression of cell adhesion markers and reactive oxygen species in NTP jet-treated rats. Methods: This study utilized Sprague-Dawley (SD) rats as experimental subjects, and wounds measuring 2 cm × 2 cm were produced on the animals' backs. The experimental group was treated with NTP for 5 min/d for 4 weeks. The NTP was injected in a diffused manner into the cage housing the rats. The SD rats that had not received plasma treatment were designated as the control group. Blood was drawn on Postoperative Day 2, Day 4, and at 3 months. An immunohistochemical stain of E-cadherin and 4-hydroxy-2-nonenal (4-HNE), a reactive oxygen species marker, were evaluated and quantified for analysis using a CMYK color model. Results: A total of 35 SD rats were included in the study (25 in the NTP group and 10 in the control group). Low dose plasma treatment shortened the wound-healing time without damaging organs. In the NTP group, the white blood cell counts at Day 2 post-NTP treatment was not increased significantly more than that in the control group. After quantification of immunohistochemical staining, 4-HNE was increased at Day 14 compared with Day 7 (16.16 ± 12.81% vs. 55.11 ± 8.11%, p

Aim Arsenic trioxide (As2O3), known as pi-shuang and the most toxic compound in traditional Chinese medicine, has been used as an antitumor agent for thousands of years. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural phenol that has significant anti-bacterial, anti-fungaI and antiaging activities. Our study aimed to examine the combined anticancer effects of As2O3 and resveratrol against human neuroblastoma SK-N-SH cells, and elucidate the underlying intracellular signaling. Materials and methods SK-N-SH cells were treated with an extremely low-dose (2-4 μM) of As2O3 alone or combined with 75 μg/ml resveratrol for further comparisons. Cell viability, apoptotic signaling as well as synergistic cytotoxic effects were estimated using the MTT assay, microscopy observation, flow cytometric analysis for loss of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS), and typical quantitative western blotting analysis. Student's t-test, and one- and two-way analysis of variance (ANOVA) were used for examination of significant differences. Results The combined treatment was more effective than single treatment of As2O3 or resveratrol alone in suppressing cell viability, which correlated with the elevation of ROS levels. The intracellular mechanisms of cytotoxicity of As2O3 plus resveratrol were revealed as ROS accumulation and relative decrease of MMP, leading to activation of caspase-3 and -9, but not of caspase-1, -7 and-8. Combination treatment reduced the expression of B-cell lymphoma 2 (BCL2), BH3 interacting domain death agonist (BID), and BCL-x/L. Conclusion Combined treatment at extremely low concentration of two agents from natural products, As2O3 and resveratrol, has high potential as a cocktail of anticancer drugs for neuroblastoma.

Metalloproteinase 2 (MMP2) is a multi-functional protein which has been shown to be up-regulated in patients with oral cancer, especially those with lymph node metastasis. However, the association of MMP2 genotype with oral cancer risk or metastatic behavior is unknown. This study aimed to evaluate the role of MMP2 promoter 1306 and -735 genotypes in the risk of oral cancer and metastasis.In this case-control study, MMP2 promoter 1306 (rs243865) and -735 (rs2285053) genotypes and their interaction with consumption of areca, cigarettes, and alcohol in determining oral cancer risk were investigated among 788 patients with oral cancer and 956 gender-matched healthy controls. In addition, their role in oral cancer metastasis were also examined.The distribution of CC, CT and TT for MMP2 promoter 1306 genotype was 79.0, 20.1 and 0.9% in the oral cancer group and 68.7, 29.2 and 2.1% in the non-cancer control group, respectively (p for trend=4.3E-6). The allelic frequency distributions showed that the variant T allele of MMP2 promoter 1306 conferred lower oral cancer susceptibility than the wild-type C allele (odds ratio=0.61, 95% confidence interval=0.50-0.75, p=1.1E-6). As for the MMP2 -735 genotypes, there was no differential distribution in genotypic or allelic frequencies. The variant CT and TT genotypes were also associated with lower metastasis rates within 5 years among the patients with oral cancer (odds ratio=0.34, 95% confidence interval=0.15-0.80, p=0.0102).The CT and TT genotypes of MMP2 promoter 1306 may have a protective effect on oral cancer susceptibility and metastasis risk within 5 years for Taiwanese. They may serve as predictive markers for oral cancer in precise medical practice.

Background/aim Matrix metalloproteinases (MMPs) play important roles in inflammation and carcinogenesis, but the genotypic role of MMP-7 has never been investigated in colorectal cancer (CRC) among the Taiwanese. Therefore, in this study we aimed to evaluate the contribution of MMP-7 genotypes to the risk of CRC in Taiwan. Materials and methods In this case-control study, MMP-7 A-181G and C-153T promoter genotypes were determined and their association with CRC risk were investigated among 362 CRC patients and 362 age- and gender-matched healthy controls. In addition, the interaction of MMP-7 genotypes and personal behaviors were also examined. Results The percentages of variant AG and GG for MMP-7 A-181G genotypes were 10.5% and 1.7% in the CRC group and 11.9% and 2.2% in the control group, respectively (p for trend=0.7145). The allelic frequency distribution analysis showed that the variant G allele of MMP-7 A-181G conferred a slight but non-significant decreased CRC susceptibility to the wild-type C allele (odds ratio (OR)=0.86, 95% confidence interval (CI)=0.64-1.31, p=0.37). Taiwanese all harbour the CC genotype at MMP-7 C-153T. As for the gene-lifestyle interaction, there were no obvious joint effects of MMP-7 A-181G genotype on the risk of CRC among ever smoker, alcohol drinker, non-smoker or non-drinker subgroups. No statistically significant correlation was observed between MMP-7 A-181G genotypic distributions and age, gender, tumor size, location or metastasis status. Conclusion The genotypes of MMP-7 A-181G may play an indirect role in determining personal susceptibility to CRC and prognosis. The further genotyping work on MMP-7 and other genes (such as other MMPs, oncogenes and tumor suppression genes) on CRC susceptibility and prognosis, should be taken into consideration spontaneously in the precision medicine era.

Identifying parasite species and their stage is very important in scrutinizing the properties of malaria, and preventing as well as diagnosing it. Unfortunately, it is a labor-intensive and time-consuming task. Moreover, the diagnosis accuracy heavily depends on the experience and skill of the technician, whose training is expensive. Developing a computer-aided system is thus necessary for identifying parasite species and their stage for malaria diagnosis. Extracting the infected erythrocytes and parasites from a blood smear image is essential for such as system. The present study proposes an automatic malaria parasite detector for segmenting parasites and malaria-infected erythrocytes from a blood smear image. This detector can objectively and efficiently help a doctor diagnose malaria. Experimental results show that the proposed detector performs well in segmenting parasites and malaria-infected erythrocytes from a blood smear image taken under a microscope.

Background/aim Matrix metalloproteinases (MMPs) play a critical role in inflammation and carcinogenesis, and the expression of mRNA MMP7 in oral squamous cell carcinoma tissues was higher than in the oral lichen planus or normal oral mucosa. However, the genotypic role of MMP7 has never been examined in oral cancer. Therefore, in the current study we aimed to examine the contribution of genotypic variants in the promoter region of MMP7 (A-181G and C-153T) to oral cancer risk in Taiwan. Materials and methods In this hospital-based case-control study, 788 patients with oral cancer and 956 gender-and age-matched healthy controls were genotyped for MMP7 A-181G and C-153T via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Results The distribution pattern of AA, AG and GG for MMP7 promoter A-181G genotype was 88.2, 10.4 and 1.4% in the oral cancer patient group and 89.0, 9.3 and 1.7% in the healthy control group, respectively (p for trend=0.6779), non-significantly differentially distributed between the two groups. There is no polymorphic genotype for MMP7 C-153T among Taiwanese. The comparisons in allelic frequency distribution also support the findings that G allele may not be the risk determinant allele for oral cancer. There is no interaction between the genotypes of MMP7 with age, gender, smoking, alcohol or betel quid consumption on oral cancer risk. Conclusion Our results indicate that the MMP7 promoter genotypes only play an indirect role in determining the personal susceptibility to oral cancer in Taiwan.

Background/Aim: Pterygium is composed of proliferating fibrovascular tissue, and its formation and progression are closely related to the homeostasis of the extracellular microenvironment. However, few studies have examined the contribution of matrix metalloproteinases (MMP) to either diagnostic or prognostic potential in pterygium. In this study, we investigated the contribution of a polymorphism in the promoter region of MMP-8 (-799C/T) and two non-synonymous polymorphisms (Val436Ala and Lys460Thr) to pterygium. Materials and Methods: In this study, 134 patients with pterygium and 268 non-cancer controls patients were collected and the MMP-8 -799C/T, Val436Ala and Lys460Thr polymorphic genotypes of each subject were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The results showed that the three polymorphisms investigated were not significantly associated with risk of pterygium. In addition, the stratified analysis showed that there was no interaction between MMP-8 genotype with age or gender on pterygium risk determination. Conclusion: Polymorphisms at MMP-8 -799C/T, Val436Ala and Lys460Thr may not mainly contribute to determining personal susceptibility to pterygium in the Taiwanese examined.

Background: In this study, we investigated the effects of treating dental implants made from titanium with argon based non-thermal plasma, immediately before insertion on implant stability and bone formation. Biodegradable sandblasting and acid etching had been previously used to modify the surface of the implants. Methods: To obtain data for 4-time points in triplicate with references, a total of 36 dental implants were divided into 2 groups; 18 implants served as the experimental group and received a spray containing non-thermal plasma, while the other 18 implants served as controls. Two treated and two untreated implants were each inserted in the jaws of 9 beagle dogs. After periods of 4, 8, and 12 weeks, the Implant Stability Quotient scores were determined and histometric values obtained. Results: Plasma spray treatment increased the healing time slightly during the early recovery period (4th to 8th week, p = 0.1595 and 0.1041, respectively), but was not profoundly effective in the later recovery stage (12th week, p = 0.4942). Both non-decalcified histometric measurements and bone growth analysis showed no statistically significant differences between the plasma spray group and the controls at 4, 8, and 12 weeks. Conclusion: Non-thermal plasma did not enhance the stability of the implants nor did it increase bone formation in our animal models. Keywords: Biodegradable sandblasting, Bone formation, Dental implant, Etching, Non-thermal plasma

Rationale: Diabetic retinopathy is characterized by vasopermeability, vascular leakage, inflammation, blood–retinal barrier breakdown, capillary degeneration, and neovascularization. However, the mechanisms underlying the association between diabetes mellitus and progression retinopathy remain unclear. Objective: TPL2 (tumor progression locus 2), a serine-threonine protein kinase, exerts a pathological effect on vascular angiogenesis. This study investigated the role of N ε -(carboxymethyl)lysine, a major advanced glycation end products, and the involved TPL2-related molecular signals in diabetic retinopathy using models of in vitro and in vivo and human samples. Methods and Results: Serum N ε -(carboxymethyl)lysine levels and TPL2 kinase activity were significantly increased in clinical patients and experimental animals with diabetic retinopathy. Intravitreal administration of pharmacological blocker or neutralizing antibody inhibited TPL2 and effectively suppressed the pathological characteristics of retinopathy in streptozotocin-induced diabetic animal models. Intravitreal VEGF (vascular endothelial growth factor) neutralization also suppressed the diabetic retinopathy in diabetic animal models. Mechanistic studies in primary human umbilical vein endothelial cells and primary retinal microvascular endothelial cells from streptozotocin-diabetic rats, db/db mice, and samples from patients with diabetic retinopathy revealed a positive parallel correlation between N ε -(carboxymethyl)lysine and the TPL2/chemokine SDF1α (stromal cell–derived factor-α) axis that is dependent on endoplasmic reticulum stress-related molecules, especially ATF4 (activating transcription factor-4). Conclusions: This study demonstrates that inhibiting the N ε -(carboxymethyl)lysine-induced TPL2/ATF4/SDF1α axis can effectively prevent diabetes mellitus–mediated retinal microvascular dysfunction. This signaling axis may include the therapeutic potential for other diseases involving pathological neovascularization or macular edema.

It has been previously proposed that genetic variations on DNA repair genes confer susceptibility to cancer and the DNA repair gene Xeroderma Pigmentosum Group D (XPD) is thought to play the role of a helicase during excision repair and transcription. We investigated three genotypes of XPD, at promoter -114 (rs3810366), Asp312Asn (rs1799793) and Lys751Gln (rs13181), regarding their association with colorectal cancer susceptibility in a Taiwanese population.In total, 362 patients with colorectal cancer and 362 gender- and age-matched healthy controls were genotyped by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP), and their XPD genotypes' association with colorectal cancer risk was investigated.The genotypes of XPD Asp312Asn (p=0.2493), Lys751Gln (p=0.7547) and promoter -114 (p=0.8702), were not associated with susceptibility for colorectal cancer. The Chi-square test revealed that the variant alleles of XPD Asp312Asn, Lys751Gln and promoter -114 was not associated with susceptibility for colorectal cancer either [p=0.1330, 0.3888 and 0.8740; odds ratio (OR)=1.20, 0.83 and 0.98; 95% confidence interval (95%CI)=0.95-1.52, 0.54-1.27 and 0.80-1.21, respectively]. The risk of A/G and A/A genotypes have no association with cancer risk among non-alcohol drinkers (OR=1.24, 95%, CI=0.90-1.72, p=0.2103) or alcohol drinkers (OR=1.51, 95% CI=0.64-3.55, p=0.4648). There exists no obvious contribution of XPD genotypes to tumor size (p=0.3531), location (p=0.3006) and lymph node metastasis (p=0.1061).Asp312Asn, Lys751Gln and promoter -114 of the XPD gene were not found to be adequate predictive markers for colorectal cancer risk in Taiwan.

Polyetheretherketone (PEEK), which has biomechanical performance similar to that of human cancellous bone, is used widely as a spinal implant material. However, its bioinertness and hydrophobic surface properties result in poor osseointegration. This study applies a novel modification method, arc ion plating (AIP), that produces a highly osteoblast compatible titanium dioxide (TiO2) coatings on a PEEK substrate. This PEEK with TiO2coating (TiO2/PEEK) was implanted into the femurs of New Zealand white male rabbits to evaluate itsin vivoperformance by the push-out test and histological observation. Analytical results show that AIP can prepare TiO2coatings on bullet-shaped PEEK substrates as implant materials. After prolonged implantation in rabbits, no signs of inflammation existed. Newly regenerated bone formed more prominently with the TiO2/PEEK implant by histological observation. The shear strength of the bone/implant interface increases as implantation period increases. Most importantly, bone bonding performance of the TiO2/PEEK implant was superior to that of bare PEEK. The rutile-TiO2coatings achieved better osseointegration than the anatase-TiO2coatings. Therefore, AIP-TiO2can serve as a novel surface modification method on PEEK for spinal interbody fusion cages.