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BACKGROUND We aimed to explore the risk factors that affect the serum concentration of sodium valproate (VPA-Na) in patients with epilepsy and to provide references for the rationale of the use of VPA-Na. MATERIAL AND METHODS The enzyme-multiplied immunoassay technique was used to determine the serum VPA-NA concentrations of 109 patients, and the results were retrospectively analyzed and summarized. A multivariate logistic regression model was used to analyze substandard serum VPA-Na concentrations. RESULTS Fifty-six patients (51.38%) treated with VPA-Na tablets were within the effective treatment range of 50-100 μg/mL, while 53 patients (48.62%) were out of the treatment range. The results indicated that the standard-reaching rate of serum drug concentration in the juvenile group was higher than that in the adult and elderly groups; the standard-reaching rates of serum drug concentrations in the low-dose group and the intermediate-dose group were lower than that in the high-dose group; and the standard-reaching rate of serum drug concentration in the group receiving carbapenems in combination was lower than that in the non-combination group; all differences were statistically significant. The combination with carbapenems and enzyme inducers was an independent risk factor for VPA-Na serum concentration below the target level in hospitalized patients. CONCLUSIONS To improve clinical efficacy and reduce the occurrence of adverse reactions, there is a need for therapeutic drug monitoring of VPA-Na. Moreover, individual administration should be implemented when VPA-Na tablets are used in the treatment of epilepsy because of the significant fluctuation in VPA-Na blood concentration.

Expressional changes of pain-associated genes in primary sensory neurons of DRG are critical for neuropathic pain genesis. DNA methyltransferase (DNMT)-triggered DNA methylation silences gene expression. We show here that DNMT1, a canonical maintenance methyltransferase, acts as the de novo DNMT and is required for neuropathic pain genesis likely through repressing at least DRG Kcna2 gene expression in male mice. Peripheral nerve injury upregulated DNMT1 expression in the injured DRG through the transcription factor cAMP response element binding protein-triggered transcriptional activation of Dnmt1 gene. Blocking this upregulation prevented nerve injury-induced DNA methylation within the promoter and 5'-untranslated region of Kcna2 gene, rescued Kcna2 expression and total Kv current, attenuated hyperexcitability in the injured DRG neurons, and alleviated nerve injury-induced pain hypersensitivities. Given that Kcna2 is a key player in neuropathic pain, our findings suggest that DRG DNMT1 may be a potential target for neuropathic pain management.SIGNIFICANCE STATEMENT In the present study, we reported that DNMT1, a canonical DNA maintenance methyltransferase, is upregulated via the activation of the transcription factor CREB in the injured DRG after peripheral nerve injury. This upregulation was responsible for nerve injury-induced de novo DNA methylation within the promoter and 5'-untranslated region of the Kcna2 gene, reductions in Kcna2 expression and Kv current and increases in neuronal excitability in the injured DRG. Since pharmacological inhibition or genetic knockdown of DRG DNMT1 alleviated nerve injury-induced pain hypersensitivities, DRG DNMT1 contributes to neuropathic pain genesis partially through repression of DRG Kcna2 gene expression.

Peripheral nerve injury increased the expression of the DNA methyltransferase 3A (Dnmt3a) mRNA and its encoding Dnmt3a protein in injured dorsal root ganglia (DRG). This increase is considered as an endogenous instigator in neuropathic pain genesis through epigenetic silencing of pain-associated genes (such as Oprm1) in injured DRG. However, how DRG DNMT3a is increased following peripheral nerve injury is still elusive. We reported here that peripheral nerve injury caused by the fifth spinal nerve ligation (SNL) downregulated microRNA (miR)-143 expression in injured DRG. This downregulation was required for SNL-induced DRG Dnmt3a increase as rescuing miR-143 downregulation through microinjection of miR-143 mimics into injured DRG blocked the SNL-induced increase in Dnmt3a and restored the SNL-induced decreases in Oprm1 mRNA and its encoding mu opioid receptor (MOR) in injured DRG, impaired spinal cord central sensitization and neuropathic pain, and improved morphine analgesic effects following SNL. Mimicking SNL-induced DRG miR-143 downregulation through DRG microinjection of miR143 inhibitors in naive rats increased the expression of Dnmt3a and reduced the expression of Oprm1 mRNA and MOR in injected DRG and produced neuropathic pain-like symptoms. These findings suggest that miR-143 is a negative regulator in Dnmt3a expression in the DRG under neuropathic pain conditions and may be a potential target for therapeutic management of neuropathic pain.

Nerve injury‐induced change in gene expression in primary sensory neurons of dorsal root ganglion (DRG) is critical for neuropathic pain genesis. N6‐methyladenosine (m6A) modification of RNA represents an additional layer of gene regulation. Here, it is reported that peripheral nerve injury increases the expression of the m6A demethylase fat‐mass and obesity‐associated proteins (FTO) in the injured DRG via the activation of Runx1, a transcription factor that binds to the Fto gene promoter. Mimicking this increase erases m6A in euchromatic histone lysine methyltransferase 2 (Ehmt2) mRNA (encoding the histone methyltransferase G9a) and elevates the level of G9a in DRG and leads to neuropathic pain symptoms. Conversely, blocking this increase reverses a loss of m6A sites in Ehmt2 mRNA and destabilizes the nerve injury‐induced G9a upregulation in the injured DRG and alleviates nerve injury‐associated pain hypersensitivities. FTO contributes to neuropathic pain likely through stabilizing nerve injury‐induced upregulation of G9a, a neuropathic pain initiator, in primary sensory neurons., This study explores the m6A epitranscriptional mechanism of neuropathic pain. Peripheral nerve injury produces the Runx1‐triggered FTO upregulation in the dorsal root ganglion (DRG). This upregulation contributes to nerve injury‐induced pain hypersensitivity through erasing Ehmt2 mRNA m6A, stabilizing Ehmt2 mRNA/G9a expression, and silencing mu opioid receptor expression in the injured DRG. FTO may be a new target for neuropathic pain treatment.

The transmission of normal sensory and/or acute noxious information requires intact expression of pain-associated genes within the pain pathways of nervous system. Expressional changes of these genes after peripheral nerve injury are also critical for neuropathic pain induction and maintenance. Methyl-CpG-binding domain protein 1 (MBD1), an epigenetic repressor, regulates gene transcriptional activity. We report here that MBD1 in the primary sensory neurons of DRG is critical for the genesis of acute pain and neuropathic pain as DRG MBD1-deficient mice exhibit the reduced responses to acute mechanical, heat, cold, and capsaicin stimuli and the blunted nerve injury-induced pain hypersensitivities. Furthermore, DRG overexpression of MBD1 leads to spontaneous pain and evoked pain hypersensitivities in the WT mice and restores acute pain sensitivities in the MBD1-deficient mice. Mechanistically, MDB1 repressesOprm1andKcna2gene expression by recruiting DNA methyltransferase DNMT3a into these two gene promoters in the DRG neurons. DRG MBD1 is likely a key player under the conditions of acute pain and neuropathic pain.SIGNIFICANCE STATEMENTIn the present study, we revealed that the mice with deficiency of methyl-CpG-binding domain protein 1 (MBD1), an epigenetic repressor, in the DRG displayed the reduced responses to acute noxious stimuli and the blunted neuropathic pain. We also showed that DRG overexpression of MBD1 produced the hypersensitivities to noxious stimuli in the WT mice and rescued acute pain sensitivities in the MBD1-deficient mice. We have also provided the evidence that MDB1 repressesOprm1andKcna2gene expression by recruiting DNA methyltransferase DNMT3a into these two gene promoters in the DRG neurons. DRG MBD1 may participate in the genesis of acute pain and neuropathic pain likely through regulating DNMT3a-controlledOprm1andKcna2gene expression in the DRG neurons.

Opioids are the gold standard for pharmacological treatment of neuropathic pain, but their analgesic effects are unsatisfactory in part due to nerve injury-induced downregulation of opioid receptors in dorsal root ganglia (DRG) neurons. How nerve injury drives such downregulation remains elusive. DNA methyltransferase-(DNMT-) triggered DNA methylation represses gene expression. We show here that blocking the nerve injury-induced increase in DRG DNMT3a (a de novo DNMT) rescued the expression of Oprm1 and Oprk1 mRNAs and their respective encoding mu opioid receptor (MOR) and kappa opioid receptor (KOR) proteins in the injured DRG. Blocking this increase also prevented the nerve injury-induced increase in DNA methylation in the promoter and 5′-untranslated region of the Oprm1 gene in the injured DRG, restored morphine or loperamide (a peripheral acting MOR preferring agonist) analgesic effects, and attenuated the development of their analgesic tolerance under neuropathic pain conditions. Mimicking this increase reduced the expression of Oprm1 and Oprk1 mRNAs and their coding MOR and KOR in DRG and augmented MOR-gated neurotransmitter release from the primary afferents. Mechanistically, DNMT3a regulation of Oprm1 gene expression required the methyl-CpG-binding protein 1, MBD1, as MBD1 knockout resulted in the decreased binding of DNMT3a to the Oprm1 gene promoter and blocked the DNMT3a-triggered repression of Oprm1 gene expression in DRG neurons. These data suggest that DNMT3a is required for nerve injury-induced and MBD1-mediated epigenetic silencing of the MOR and KOR in the injured DRG. DNMT3a inhibition may serve as a promising adjuvant therapy for opioid use in neuropathic pain management.

Nerve injury induces changes in gene transcription in dorsal root ganglion (DRG) neurons, which may contribute to nerve injury-induced neuropathic pain. DNA methylation represses gene expression. Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor 1. Blocking this increase prevents nerve injury-induced methylation of the voltage-dependent potassium (Kv) channel subunit Kcna2 promoter region and rescues Kcna2 expression in the injured DRG and attenuates neuropathic pain. Conversely, in the absence of nerve injury, mimicking this increase reduces the Kcna2 promoter activity, diminishes Kcna2 expression, decreases Kv current, increases excitability in DRG neurons and leads to spinal cord central sensitization and neuropathic pain symptoms. These findings suggest that DNMT3a may contribute to neuropathic pain by repressing Kcna2 expression in the DRG.

Neuropathic pain genesis is related to gene alterations in the dorsal root ganglion (DRG) after peripheral nerve injury. Transcription factors control gene expression. In this study, we investigated whether octamer transcription factor 1 (OCT1), a transcription factor, contributed to neuropathic pain caused by chronic constriction injury (CCI) of the sciatic nerve. Chronic constriction injury produced a time-dependent increase in the level of OCT1 protein in the ipsilateral L4/5 DRG, but not in the spinal cord. Blocking this increase through microinjection of OCT1 siRNA into the ipsilateral L4/5 DRG attenuated the initiation and maintenance of CCI-induced mechanical allodynia, heat hyperalgesia, and cold allodynia and improved morphine analgesia after CCI, without affecting basal responses to acute mechanical, heat, and cold stimuli as well as locomotor functions. Mimicking this increase through microinjection of recombinant adeno-associated virus 5 harboring full-length OCT1 into the unilateral L4/5 DRG led to marked mechanical allodynia, heat hyperalgesia, and cold allodynia in naive rats. Mechanistically, OCT1 participated in CCI-induced increases in Dnmt3a mRNA and its protein and DNMT3a-mediated decreases in Oprm1 and Kcna2 mRNAs and their proteins in the injured DRG. These findings indicate that OCT1 may participate in neuropathic pain at least in part by transcriptionally activating Dnmt3a and subsequently epigenetic silencing of Oprm1 and Kcan2 in the DRG. OCT1 may serve as a potential target for therapeutic treatments against neuropathic pain.

Nerve injury induces changes in gene transcription in dorsal root ganglion (DRG) neurons, which may contribute to nerve injury-induced neuropathic pain. DNA methylation represses gene expression. Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor 1. Blocking this increase prevents nerve injury-induced methylation of the voltage-dependent potassium (Kv) channel subunit Kcna2 promoter region and rescues Kcna2 expression in the injured DRG and attenuates neuropathic pain. Conversely, in the absence of nerve injury, mimicking this increase reduces the Kcna2 promoter activity, diminishes Kcna2 expression, decreases Kv current, increases excitability in DRG neurons and leads to spinal cord central sensitization and neuropathic pain symptoms. These findings suggest that DNMT3a may contribute to neuropathic pain by repressing Kcna2 expression in the DRG., Transcriptional changes occur in the dorsal root ganglion in response to nerve injury and may contribute to neuropathic pain. Here the authors show that the DNA methyltransferase DNMT3a is upregulated in rodents following nerve injury, and may contribute to pain-like behaviour by decreasing expression of the voltage-gated potassium channel Kv1.2.

Neuropathic pain is associated with gene expression changes within the dorsal root ganglion (DRG) after peripheral nerve injury, which involves epigenetic mechanisms. Coactivator-associated arginine methyltransferase 1 (CARM1), an epigenetic activator, regulates gene transcriptional activity by protein posttranslational modifications. However, whether CARM1 plays an essential role in the development and maintenance of neuropathic pain is unknown. We report here that peripheral nerve injury induced the upregulation of the mRNA and protein expression of CARM1 in the injured DRG, and blocking its expression through small interfering RNA (siRNA) in the injured DRG attenuated the development and maintenance of neuropathic pain. Furthermore, pharmacological inhibition of CARM1 mitigated peripheral nerve injury-induced mechanical allodynia and thermal hyperalgesia. Given that CARM1 inhibition or knockdown attenuated the induction and maintenance of neuropathic pain after peripheral nerve injury, our findings suggest that CARM1 may serve as a promising therapeutic target for neuropathic pain treatment in clinical applications.

To assess the diagnostic value of dual-energy (DE) computed tomography pulmonary angiography (CTPA) for acute pulmonary embolism (PE) using a helical DE scan mode with rapid kVp switching.Seventy-six patients with suspected acute PE underwent DE CTPA. Two readers independently assessed and measured the iodine maps. CTPA images were assessed for the presence, location, and degree of PE as the standard of reference. Iodine maps were used to identify the perfusion defect (PD), and the diagnostic accuracy of iodine maps was calculated. The iodine concentrations of PDs and normal lung parenchyma were also measured and compared.A per-patient analysis showed the 84.6% sensitivity and 96.0% specificity of iodine map for PE, and on per-segment analysis, the sensitivity and specificity for PE were 82.9% and 99.6%, respectively. Intraobserver and interobserver variability correlations were excellent, with k values from 0.806 to 1.000. Quantitative analysis showed there was a significant difference for iodine concentration between circumscribed/patchy PDs or wedge-shaped PDs consistent with PE and normal lung parenchyma (P.05). The intraobserver reliability of reader 1 was from 0.928 to 0.997, and reader 2 was from 0.912 to 0.995. And, the interobserver reliability between two readers was from 0.967 to 0.999.CTPA based on DE scanning with rapid kVp switching can provide both morphologic analysis and quantitative evaluation of PD related to acute PE in addition to standard CTPA data. Quantification of iodine concentration may be helpful for identifying the presence or absence of PE.

Changes in gene transcription in the dorsal root ganglion (DRG) after nerve trauma contribute to the genesis of neuropathic pain. We report that peripheral nerve trauma caused by chronic constriction injury (CCI) increased the abundance of the transcription factor C/EBPβ (CCAAT/enhancer binding protein β) in the DRG. Blocking this increase mitigated the development and maintenance of CCI-induced mechanical, thermal, and cold pain hypersensitivities without affecting basal responses to acute pain and locomotor activity. Conversely, mimicking this increase produced hypersensitivity to mechanical, thermal, or cold pain. In the ipsilateral DRG, C/EBPβ promoted a decrease in the abundance of the voltage-gated potassium channel subunit Kv1.2 and μ opioid receptor (MOR) at the mRNA and protein levels, which would be predicted to increase excitability in the ipsilateral DRG neurons and reduce the efficacy of morphine analgesia. These effects required C/EPBβ-mediated transcriptional activation of Ehmt2 (euchromatic histone-lysine N-methyltransferase 2), which encodes G9a, an epigenetic silencer of the genes encoding Kv1.2 and MOR. Blocking the increase in C/EBPβ in the DRG improved morphine analgesia after CCI. These results suggest that C/EBPβ is an endogenous initiator of neuropathic pain and could be a potential target for the prevention and treatment of this disorder.

To evaluate the impact of reduced-radiation dual-energy (DE) protocols using 320-detector row computed tomography on the differentiation of urinary calculus components.A total of 58 urinary calculi were placed into the same phantom and underwent DE scanning with 320-detector row computed tomography. Each calculus was scanned 4 times with the DE protocols using 135 kV and 80 kV tube voltage and different tube current combinations, including 100 mA and 570 mA (group A), 50 mA and 290 mA (group B), 30 mA and 170 mA (group C), and 10 mA and 60 mA (group D). The acquisition data of all 4 groups were then analyzed by stone DE analysis software, and the results were compared with x-ray diffraction analysis. Noise, contrast-to-noise ratio, and radiation dose were compared.Calculi were correctly identified in 56 of 58 stones (96.6%) using group A and B protocols. However, only 35 stones (60.3%) and 16 stones (27.6%) were correctly diagnosed using group C and D protocols, respectively. Mean noise increased significantly and mean contrast-to-noise ratio decreased significantly from groups A to D (P.05). In addition, the effective dose decreased markedly from groups A to D at 3.78, 1.81, 1.07, and 0.37 mSv, respectively.Decreasing the DE tube currents from 100 mA and 570 mA to 50 mA and 290 mA resulted in 96.6% accuracy for urinary calculus component analysis while reducing patient radiation exposure to 1.81 mSv. Further reduction of tube currents may compromise diagnostic accuracy.

This paper focuses on free vibration analysis of corrugated-core sandwich plates (CSP) via a meshfree Galerkin method based on a first-order shear deformation theory (FSDT). A CSP is considered as a composite structure of three members — two face sheets at the top and the bottom, and one corrugated sheet in the middle of the structure. The face sheets are taken as isotropic plates, and the corrugated sheet is approximated by an orthotropic plate that has different elastic properties along the two perpendicular directions. Dynamic equations of the members are given by the meshfree Galerkin method based on the FSDT. After overcoming the difficulty to implement the displacement compatibility conditions among the members, the governing equation for the entire CSP is obtained by superposing the dynamic equations of the members. The meshfree characteristic of the proposed method guarantee that no meshes are used in deriving the dynamic equations, therefore the proposed method is more flexible in studying problems for which remeshing is inevitable with the finite element methods. The approximation of the corrugated sheet with an orthotropic plate also simplifies the analysis without much loss of precision. A few selected examples are studied to demonstrate the accuracy and convergence of the proposed method. The results obtained for these examples are compared with the ANSYS solutions. Good agreement is evident for all cases.

This systematic review and meta-analysis assesses whether concurrent chemoradiotherapy is associated with improvement in survival outcomes for patients with locoregionally advanced nasopharyngeal carcinoma., Key Points Question Is induction chemotherapy or adjuvant chemotherapy associated with additional survival benefit in locoregionally advanced nasopharyngeal carcinoma? Findings In a systematic review and meta-analysis of 28 randomized clinical trials of 8036 patients, concurrent chemoradiotherapy was associated with substantial improvement in survival outcomes for patients with locoregionally advanced nasopharyngeal carcinoma. Survival benefit was also associated with the addition of induction chemotherapy but not adjuvant chemotherapy to concurrent chemoradiotherapy. Meaning For locoregionally advanced nasopharyngeal carcinoma, concurrent chemoradiotherapy should be recommended as the standard treatment strategy, with the addition of induction chemotherapy but not adjuvant chemotherapy., Importance The role of induction chemotherapy (IC) or adjuvant chemotherapy (AC) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains controversial. Objectives To update meta-analyses on the association of survival outcomes with IC and AC regimens in patients with locoregionally advanced NPC and assess whether the current evidence is conclusive by a trial sequential analysis (TSA) approach. Data Sources PubMed, Embase, and Web of Science were searched for articles published from inception until June 1, 2019. Study Selection Randomized clinical trials that assessed the efficacy of radiotherapy with or without chemotherapy among previously untreated patients and patients with nondistant metastatic NPC. Data Extraction and Synthesis Data were extracted by 2 investigators from each trial independently and synthesized by the 2 investigators. All trial results were combined and analyzed by a fixed- or random-effects model. Main Outcomes and Measures Overall survival (OS), progression-free survival (PFS), distant metastasis–free survival (DMFS), and locoregional recurrence-free survival (LRFS). Results A total of 8036 patients (median age, 46.5 years; 5872 [73.1%] male) from 28 randomized clinical trials were included in the analysis. Pooled analyses revealed that concurrent chemoradiotherapy (CCRT) was significantly associated with improved OS, PFS, DMFS, and LRFS compared with radiotherapy across all subgroups. The TSA confirmed the treatment outcomes of CCRT compared with radiotherapy. The additional IC regimen was associated with an improvement in OS (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95), PFS (HR, 0.73; 95% CI, 0.64-0.84), DMFS (HR, 0.67; 95% CI, 0.59-0.78), and LRFS (HR, 0.74; 95% CI, 0.64-0.85). These findings were consistent in subgroup analyses of multicenter trials with sample sizes greater than 250, years of survival rate of 5 or greater, median follow-up longer than 5 years, or low risk of bias. However, the additional AC regimen was not associated with a survival benefit in OS (HR, 0.98; 95% CI, 0.78-1.23), PFS (HR, 0.86; 95% CI, 0.70-1.07), DMFS (HR, 0.84; 95% CI, 0.64-1.10), or LRFS (HR, 0.80, 95% CI, 0.59-1.09). The TSA provided sound evidence on the additional benefit of IC but not AC. Conclusions and Relevance These data suggest a significant association of survival outcomes with CCRT in patients with locoregionally advanced NPC. The addition of IC instead of AC could achieve survival benefits. The potential therapeutic gain of AC should be explored in the future.

The data-acquisition of temperature is widely used in industrial control, household appliances, medical care, and other important areas often using the data acquisition. For industry, household appliances, and other unsuitable for the traditional wireless data acquisition situation, this paper presents a wireless system of data acquisition of temperature based on radio frequency, and the system can avoid a cable transmission’s the inherent high-cost, long production cycle, the restricted number of transceiver devices such shortcomings . This paper presents the principle, the major flow chart, features system which is mainly made up of MCU ATmega8 and RF chip nF905. Experiments show that this is the accurately and efficiently system of temperature data wireless acquisition and transmission.

Because of the growth in cloud computing and manturity of virtualization technology, many enterprises are virtualizing their servers to increase server utilization and lower costs. However, the complex network topology arising from virtualization makes clouds vulnerable, and security breaches have occurred on cloud computing platforms in recent years. Therefore, a comprehensive mechanism for detecting and preventing malicious traffic is necessary. We propose a network intrusion detection system that is based on a virtualization platform. This system, developed from a multipattern based network traffic classifier, collects packets from the virtual network environment and analyzes their content by using deep packet inspection for identifying malicious network traffic and intrusion attempts. We improve the intrusion detection features of the network traffic classifier and deploy it on a Xen virtualization platform. Our system can be combined with the Linux Netfilter framework to monitor inter-virtual-machine communications in the virtualization platform. It efficiently inspects packets and instantly protects the cloud computing environment from malicious traffic.

Background Obstructed nephropathy is a common complication of several disease processes. Accurate evaluation of the functional status of the obstructed kidney is important to achieve a good outcome. The purpose of this study was to investigate renal cortical and medullary perfusion changes associated with unilateral ureteral obstruction (UUO) using whole-organ perfusion imaging with 320-detector row computed tomography (CT). Methodology/Principle Findings Sixty-four patients with UUO underwent whole-organ CT perfusion imaging. Patients were divided into 3 groups, mild, moderate, and severe, based on hydronephrosis severity. Twenty sex- and age-matched patients without renal disease, who referred to abdominal CT, were chosen as control subjects. Mean cortical and medullary perfusion parameters of obstructed and contralateral kidneys were compared, and mean perfusion ratios between obstructed and contralateral kidneys were calculated and compared. Mean cortical or medullary blood flow (BF) and blood volume (BV) of the obstructed kidneys in the moderate UUO and BF, BV, and clearance (CL) in the severe UUO were significantly lower than those of the contralateral kidneys (p < 0.05). The mean cortical or medullary BF of the obstructed kidney in the moderate UUO, and BF, BV, and CL in the severe UUO were significantly lower than those of the kidneys in control subjects (p < 0.05). Mean cortical or medullary BF of the non-obstructed kidneys in the severe UUO were statistically greater than that of normal kidneys in control subjects (p < 0.05). An inverse correlation was observed between cortical and medullary perfusion ratios and grades of hydronephosis (p < 0.01). Conclusions/Significance Perfusion measurements of the whole kidney can be obtained with 320-detector row CT, and estimated perfusion ratios have potential for quantitatively evaluating UUO renal injury grades.

This study aims to examine the incidence and risk factors of bilateral breast cancer in area with low incidence rate. A total of 120 and 1902 women with bilateral and unilateral breast cancers were enrolled; various factors, including those concerning their medical history and life style, were extracted. Using Kaplan-Meier method, we calculate the cumulative incidence of contralateral breast cancer. The results show as follows. The cumulative incidences of contralateral breast cancer at 1, 3, 5 years after diagnosis of first breast cancer were 1.15, 1.94, and 2.97%, respectively. The statistically significant risk factors included menopause (Hazard Ratio (HR) =1.56, (1.00-2.42)), invasive lobular carcinoma (HR=2.98, (1.35-6.56)), receiving chemotherapy (HR=2.21, (1.43-3.42)) and/or radiotherapy (HR=3.32, (2.19-5.05) and a protective factor was tamoxifen therapy (HR=0.5 (0.34-0.74). Size of the second occurred tumour (2.97 cm) tended to be smaller than the first one (3.58 cm) with borderline statistical significance (p=0.0731). Comparing to the existing data on Western countries, we find a higher risk for developing contralateral breast cancer in Taiwan where a low incidence of first breast cancer rate with early age diagnosis is noted. It suggests that first primary breast tumour with early age of onset and lobular carcinoma are found more likely to develop bilateral breast cancers.

Based on the first-order shear deformation theory (FSDT) and the moving least-squares approximation, a new meshless model to study the geometric nonlinear problem of ribbed rectangular plates is presented. Considering the plate and the ribs separately, the displacement field, the stress, and strain of the plate and the ribs are obtained according to the moving least-squares approximation, the von Karman large deflection theory, and the FSDT. The ribs are attached to the plate by considering the displacement compatible condition along the connections between the ribs and the plate. The virtual strain energy formulation of the plate and the ribs is derived separately, and the nonlinear equilibrium equation of the entire ribbed plate is given by the virtual work principle. In the new meshless model for ribbed plates, there is no limitation to the rib position; for example, the ribs need not to be placed along the mesh lines of the plate as they need to be in FEM, and the change of rib positions will not lead to remeshing of the plate. The proposed model is compared with the FEM models from pieces of literature and ANSYS in several numerical examples, which proves the accuracy of the model.

The aim of our study was to determine whether Urografin has the potential to offer surgeons a way of differentiating complete from partial small bowel obstruction and whether partial small bowel obstruction can be treated nonoperatively. Altogether 116 patients who had postoperative small bowel obstructions without any toxic signs underwent Urografin studies. Urografin (40 ml) mixed with 40 ml of distilled water was administrated either orally or via nasogastric tube to each patient. Serial plain abdominal radiographs were taken 2, 4, and 8 hours later. A total of 74 patients (63.8%) whose contrast medium reached the colon within the first 8 hours were considered to have partial obstruction and were successfully treated with intravenous hydration and nasogastric decompression. The remaining 42 patients (36.2%) in whom the contrast medium failed to reach the colon within the first 8 hours were regarded as having complete obstruction, and 34 of those patients (81.0%) underwent surgery; 8 (19.0%) received conservative treatment. Adhesion bands with complete bowel obstruction were observed in all 34 patients (100.0%) during laparotomy. Regardless of the presence of an air-fluid level on a plain abdominal radiograph or abdominal pain, a liquid diet followed by a soft diet could be given to those patients whose Urografin emptied into the colon. All the patients with partial bowel obstruction were treated successfully with nonoperative methods. The presence of Urografin in the colon within 8 hours of ingestion as an indicator for nonoperative treatment had a sensitivity of 90.2%, a specificity of 100%, and an accuracy of 93. 1%. Urografin, a safe and reliable water-soluble contrast medium, can be used to differentiate partial intestinal obstruction from complete intestinal obstruction. Early oral intake was found to be a major advantage of Urografin use in this study, and the potential of Urografin use to shorten the period of conservative treatment for postoperative small bowel obstruction needs further investigation.

Background It has been suggested that p53 plays an important part in gastric carcinogenesis but the data remain inconclusive. Methods Alteration of the tumour suppressor gene p53 was prospectively investigated by immunohistochemistry in 168 primary gastric cancers. Results Positive staining, indicative of gene mutations, was detected in 34 tumours (20·2 per cent). No correlation was observed between expression of p53 and various clinicopathological factors, including age, sex, tumour site, gross type, tumour size, depth of invasion, lymph node metastases, distant metastases, and tumour node metastasis stage. However, p53 overexpression was different between intestinal and diffuse type gastric cancer. Survival analysis revealed a significant survival disadvantage of p53 expression in diffuse type gastric cancer (P = 0·039) but not in the intestinal type. Multivariate analysis of all 168 patients revealed that independent predictors of recurrent disease included age, invasion depth and nodal involvement but not p53 expression. Conclusion The presence of p53 overexpression may identify a subset of more aggressive tumours with a poor prognosis in diffuse type gastric cancer.

We conducted a prospective study to evaluate the value of abdominal sonography in the diagnosis of acute appendicitis and determine the need for abdominal sonography before operation. Altogether 191 patients with clinically diagnosed or suspected appendicitis underwent an abdominal sonography examination performed by a staff surgeon before operation. The sonographic findings are classified into three categories: appendicitis, other diseases, or normal screening. A total of 158 patients (82.7%) with positive findings of appendicitis proceeded to surgery; 18 patients (9.4%) were found to have other diseases, and they were treated for their conditions; and 15 patients (7.9%) with normal screening were discharged from the hospital and were reevaluated 2 weeks later. Only one patient had a false-negative finding. Of the 158 patients undergoing operation, 143 (90.5%) were proved to have appendicitis by the pathologic reports. A total of 32 negative appendectomies (16.8%) were prevented after sonographic examination. Abdominal sonography for detecting acute appendicitis had a sensitivity of 99.3%, a specificity of 68.1%, an accuracy of 91.6%, a positive predictive value of 90.5%, and a negative predictive value of 97.0%. The value of meticulous history-taking, physical examination, and laboratory tests cannot be overemphasized. Our experience suggests that patients with clinically diagnosed or suspected acute appendicitis should routinely undergo abdominal sonography examination, performed by an experienced surgeon, to further decrease the negative appendectomy rates.

To evaluate the prognosis of patients with gastric stump cancer after previous distal gastrectomy for benign gastroduodenal disease, we compared 25 patients with resected gastric remnant cancer with 143 patients with primary cancer in the upper third of the stomach. The histopathological differences between gastric remnant cancer and primary cancer were not significant, except for esophageal invasion. The percentage of esophageal invasion in gastric remnant cancer is 16%, significantly lower than 56.6% in primary cancer. The overall 5-year survival rates were 46% and 25% for patients with resected remnant cancer (n = 25) and resected primary cancer (n = 143), respectively, and there was no statistical difference between the two groups. The 5-year survival rates for gastric remnant cancer with stage I or II and primary cancer with the same stages were 89% (n = 11) and 39% (n = 50), a statistically significant (p < 0.02) difference. On contrast, the 5-year survival rate for gastric remnant cancer with stage III or IV was 0%, which was significantly worse than 17% for primary cancer with the same stages (p < 0.05). The prognosis of gastric remnant cancer is better than that of primary cancer in the upper third of the stomach at its early stages, but it is worse at its late stages. An aggressive resection is recommended for gastric stump cancer.

To compare and characterize retrospectively the clinicopathologic features of gastric cancers with and without previous Helicobacter pylori infection, we determined the preoperative seropositivity of H. pylori in 151 patients who had undergone gastric resection for primary gastric adenocarcinoma between 1988 and 1993. The overall seroprevalence of H. pylori was 60.9%. H. pylori-positive gastric cancers were frequently associated (p

To investigate the significance of the number of node metastases in gastric cancer and its relationship to traditional anatomical classification, 305 patients who underwent a radical gastrectomy and extended lymphadenectomy (R3/4) with curative intent were reviewed. Lymph node metastases was found in 191 (62.6%) patients. The incidence of lymph node metastases was closely related to the depth of cancer invasion as well as the extent of lymph node group involvement. The frequency of metastases in different lymph node locations was related to the location of the primary tumor. The 3-year survival rates for patients with node involvement and without were 42.1 and 92.3%, respectively. In node number analysis, the distribution of the N1 group and the N4 group involvement was rather characteristic and could be predicted from a node number4 or12. The predictability of N2 and N3 involvement from node numbers 4-8 and 9-12 was less satisfactory. On the whole, patients with a metastatic node number4 could be considered to be N1 and had a relative good prognosis. Patients with node number 4-10 could be considered as N2 and10 as an incurable disease with distant metastases. Both had a poor prognosis. The data suggest that lymph node number represents the biologic behavior of cancer instead of the anatomic consideration of conventional N stage. The number of metastatic lymph node number is a good prognostic indicator with similar predicting power as the conventional node stage.

Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction of opioid receptors in the first-order sensory neurons of dorsal root ganglia. G9a is a repressor of gene expression. We found that nerve injury-induced increases in G9a and its catalyzed repressive marker H3K9m2 are responsible for epigenetic silencing of Oprm1, Oprk1, and Oprd1 genes in the injured dorsal root ganglia. Blocking these increases rescued dorsal root ganglia Oprm1, Oprk1, and Oprd1 gene expression and morphine or loperamide analgesia and prevented the development of morphine or loperamide-induced analgesic tolerance under neuropathic pain conditions. Conversely, mimicking these increases reduced the expression of three opioid receptors and promoted the mu opioid receptor-gated release of primary afferent neurotransmitters. Mechanistically, nerve injury-induced increases in the binding activity of G9a and H3K9me2 to the Oprm1 gene were associated with the reduced binding of cyclic AMP response element binding protein to the Oprm1 gene. These findings suggest that G9a participates in the nerve injury-induced reduction of the Oprm1 gene likely through G9a-triggered blockage in the access of cyclic AMP response element binding protein to this gene.

Gastrostomy commonly is performed for patients who have esophageal stenosis or difficulty in swallowing. The fact that most patients who require a gastrostomy are malnourished or debilitated urges surgeons to seek a safe and simple procedure. Percutaneous endoscopic gastrostomy (PEG) was introduced into clinical use and recommended as the procedure of choice in the 1980s. However, for patients with obstruction of the oroesophageal canal, PEG was not possible, and only traditional open gastrostomy could be considered. We describe a technique for placement of a gastrostomy tube under laparoscopic guidance. The technique is simple and easily mastered, requires equipment routinely used in laparoscopic surgery, and can be used by surgeons without gastroendoscopic experience. When performed properly, the method is simple, economical, and reliable.

The lymphocytes and their subsets were determined in the peripheral blood of 62 gastric cancer patients and 68 controls using fluorescent conjugated monoclonal antibodies and flow cytometry (FACScan method). A significant increase in the total number of white blood cells from gastric cancer patients was noted in comparison to controls, but the percentage of lymphocytes was the same. The percentage of suppressor (cytotoxic) T cells (CD8) showed no difference in all stages of gastric cancer patients evaluated, but the percentage of helper (inducer) T cells (CD4) and the CD4/ CD8 ratio decreased significantly in the advanced stages III and IV. Depression of the CD4/CD8 ratio was well correlated with tumor invasion, lymph node metastasis, and tumor size but not with sex, age, tumor location, gross type, or histologic differentiation. It appeared that the immune defect of gastric cancer patients was associated with the afferent arm (CD4) and worsened as the disease advanced. These results suggest that immunotherapy to stimulate the deficient immune system may play an important part in the multimodality treatment of patients with advanced gastric cancer. © Wiley-Liss, Inc.

Twelve patients underwent stapled hemorrhoidectomies on an outpatient basis at Cathay General Hospital. This paper describes the preliminary evaluation of a new hemorrhoidectomy technique involving the use of Endo GIA 30. Our goal was to show that stapled hemorrhoidectomies could be tolerated well in an outpatient setting with shortened procedure duration and minimal patient discomfort. We found that stapled hemorrhoidectomy is a technique than can be effectively used in an ambulatory surgical setting with good patient tolerance and acceptance.

The paper mainly studies the designs of LA, LS and LAS codes. Then it makes simulation for theirs auto-correlation functions and cross-correlation functions. Simulation and analysis show that, LAS code has zero cross-correlation in the "Zero Interference Window", and has only an impulse auto-correlation in the "Zero Interference Window", and these excellent features help to eliminate ACI, MAI and ISI, thus it increases the system capacity largely. So it has more large potential than traditional codes

Since polymer spherulites were observed using optical microscopy and single polymer crystals were prepared from solution,1,2 the internal structure of polymer spherulites has been investigated widely with electron microscopy.3-9 For most crystalline polymers, it is generally accepted that spherulites are developed from a single crystal through unidirectional growth, and the spherical shape is attained through continuous splaying apart and occasional branching of lamellae,5 though there are ongoing debates concerning the details of the branching in the literature. More recently, atomic force microscopy (AFM) has been utilized to study the organization of spherulites and the crystallization process of polymers.10,11 A copolymer, poly(bisphenol A-co-octane),12 was synthesized with the following structure

This article offers the analysis of electromagnetic compatibility of high frequency switching power supply by finite element method of harmonic balance theoretically. Finite element method of harmonic balance is different from traditional time-domain finite element method and transient analysis method. Finite element method of harmonic balance produces solution using linear synthesis of sine function and represents wave figure using coefficient of sine function. It combines steady-state response of finite element method directly in frequency domain solution electromagnetic field. The experiment has proved finite element method of harmonic balance is generally more effective than traditional time-domain method.

Occult breast carcinoma presenting with axillary metastases is a difficult clinical problem. Mammography is recommended as the diagnostic tool for detecting breast masses, but is very insensitive. In two consecutive patients with nonpalpable carcinoma of the breast, the detection of breast lesions was made by color Doppler sonography. The sensitivity of the technique makes it a useful diagnostic aid in patients with negative mammograms.

In this prospective study, the authors examined 50 patients with breast tumors (malignant, n = 32; benign, n = 18) to investigate the correlation between color Doppler flow mapping and histopathological findings and to evaluate the clinical significance of color Doppler mapping. Among the 32 patients with breast cancer, color Doppler signals were detected in 24 patients (75%). The maximum flow velocities varied from 5 to 34 cm/sec, with 16 (67%) of them above 15 cm/sec. Among the 18 patients with benign tumors, color Doppler signals could be detected in 7 (39%). The maximum flow velocity varied from 3 to 30 cm/sec but was over 15 cm/sec in only two patients (28%). Histological studies revealed that color Doppler signals detected by Doppler sonography correlated with disordered neovascularization penetrating the lesion from its periphery, consisting of thin-walled blood vessels and large arteriovenous shunts. Although large tumors tend to have high Doppler flow, there is no significant correlation between the maximum flow velocity and tumor size. There is also no significant correlation between the detection of high flow color Doppler signals and the age, receptor status, tumor size, lymph node metastases, or clinical stage of patients with breast cancer. However, there is a positive association (p < 0.05) between nodal metastases and higher tumor flow velocity in T1 (≤ 2 cm) breast tumors, but not in larger tumors. It is concluded that color Doppler is useful in the assessment of tumor vascularity but is of limited value in the differentiation of benign from malignant lesions. However, the presence of color Doppler signals in Tl breast cancer suggesting early dissemination of the cancer might be of important clinical significance in detecting those small, apparently early, but aggressive tumors with poor prognosis.

A retrospective study of 954 resectable gastric cancers in a single institute of Taiwan from 1971 to 1990 was performed to evaluate improvements in gastric cancer surgery. The patients were divided into four time periods representing an overall experience of progressive implementation of aggressive resection and increased extent of systematic lymph node dissection. The clinicopathologic data and survival rates were statistically compared and the significance of the extent of resection on survival analyzed. A significant increase in the proportion of upper one-third tumors (from 14.8% to 20.4%) and a decrease in the incidence of intestinal type (73.6% to 41.5%) was found within the overall period. The proportion of patients with early gastric cancer increased from 11.5% to 19.4%. Patients who underwent total gastrectomy and combined visceral resection increased from 13.7% to 27.4% and 19.8% to 41.1%, respectively. An increase of both total dissected lymph, node number and the incidence of detected lymph node metastases in early gastric cancer were associated with more extensive lymphadenectomy. An improved 5-year survival rate following aggressive resection was found for all stages except stage IV and T4 lesions, and the surgical mortality decreased from 5.5% to 2.0%. Patients with earlier stage lesions benefited more from radical resection, especially those with stage II and T2 lesions. Systematic lymph node dissection increased the 5-year survival of patients by about 10% for stage III or T3 lesions, but not for patients with stage IV or T4 lesions. Multivariate analysis confirmed the significance of the improved technique of lymphadenectomy on the prognosis of gastric cancer following resection in Taiwan. In conclusion, a changing pattern of gastric cancer epidemiology in Taiwan is documented. A decrease in surgical mortality indicates that curative resection with extensive lymph node dissection can be safely performed. Although potential for increasing survival by upstaging remains, radical gastrectomy with extended lymphadenectomy could be adopted for gastric cancer resection with possibly more adequate control of locoregional disease.

The preoperative seropositivity of Helicobacter pylori was determined in 128 patients who had undergone gastrectomy for primary gastric adenocarcinoma during the past 5 years. The overall seroprevalence of H. pylori was 64 per cent. Gastric cancers positive for H. pylori were associated with tumours located in the lower third of the stomach which were of localized type (Borrmann I and II) (P < 0.05), but not with age, sex, blood type, tumour size, invasion depth, lymph node metastases, histological type, DNA ploidy or type of surgery. The cumulative 5-year survival curves after surgical resection were significantly better in patients who were positive for H. pylori. Multivariate analysis revealed that seropositivity for H. pylori was not an independent prognostic factor. Pathological tumour node metastasis staging was the only prognostic indicator. Better prognosis for those with H. pylori-seropositive gastric cancer may be attributed to the more advanced stage of H. pylori-seronegative gastric cancers. The potential role of H. pylori in gastric cancer carcinogenesis and its biological significance warrant further investigation.

Tumor growth and metastases require the development of new vessels (angiogenesis). Angiogenesis, assessed by microvessel count using immunocytochemical stain of endothelial cells, has been shown to predict metastases and correlate with early death. Recently developed color Doppler mapping can detect the "tumor flow signals" in breast cancer and help to distinguish it from benign lesions. The question is, does this tumor vascularization assessed by color Doppler mapping correlate with the angiogenesis assessed by immunocytochemistry?Eighty-four patients admitted for breast surgery were studied. The final diagnosis was made by pathology for 52 malignancies and 32 benign lesions. The color Doppler mapping of the breast lesion was made preoperatively. The following parameters were assessed: (a) vessel location (peripheral or central); (b) density of color Doppler signals; and (c) maximum systolic velocity. Tumor angiogenesis was assessed by microvessel count under light microscopy using the platelet/endothelial cell adhesion molecule antibodies (CD31) method. The correlation between maximum velocity and microvessel count of breast cancer was examined. The clinical significance of maximum flow velocity of breast cancer with various clinicopathologic factors was assessed.Color signals were detected in 48 cases of 52 malignancies (92%). All tumors demonstrated signals at the periphery of the lesion but in only 13 (27%) were the signals detected within the tumor. Color signals were scored as + + or + + + in 44 (92%) patients. Pulsed wave blood flow was shown in all these 48 tumors, with maximum velocities varying from 4 to 36 cm/s. Among the 32 benign lesions, color signals were detected in 10 (31%) and all were peripheral and scored subjectively as +. Evaluation of these color Doppler mapping parameters shows no significant correlation with microvessel counts using CD31 monoclonal antibodies. However, there was a positive association (p0.05) between nodal metastases and higher tumor flow velocity in T1 (2 cm) breast tumors but not in larger tumors.Although the color Doppler mapping has been shown to be useful in distinguishing benign from malignant breast lesions, the intensity of signal and velocity of flow had no correlation with the extent of angiogenesis of breast cancer. The presence of high-flow tumor signal in early breast carcinoma is significantly associated with the presence of axillary lymph node metastases.

The clonogenic patterns of three human pulmonary adenocarcinoma cell lines (PC-9, PC-13 and PC-14) were studied by human tumor clonogenic assay (HTCA), and factors which could influence the results of tests for the chemosensitivity of these tumor cells to cisplatin in HTCA were determined. The results showed that each tumor cell line had a characteristic clonogenic pattern. The time intervals for the cells to grow to the plateau phase varied from 9 to 16 days, depending on the cell line and number of cells plated. The number of cells plated could substantially influence the results of chemosensitivity tests. The percentage of surviving colonies increased markedly if too many cells (usually 5 X 10(4) or more/plate) were plated. For continuous exposure, the results of chemosensitivity tests were rather stable after 7 days of incubation in each cell line, especially when fewer than 2 X 10(4) cells/plate were plated. For 1-hour exposure, the incubation periods for the results to become stable varied from 7 to 16 days depending on the cell type, number of cells plated and drug concentration. It was stressed that for the correct evaluation of the chemosensitivity of cultured cell lines in HTCA, the clonogenic pattern of each tumor cell line should be checked in detail before further experiments are conducted. The higher the concentration and the longer the exposure time, the more strongly cis-diamminedichloroplatinum (CDDP) suppressed the colony growth in each of the three cell lines in HTCA, and it was recommended that CDDP should be used clinically in such a way as to maintain a high serum level of the active form of CDDP for a long time.

This article reports an experience on subemergent separation of xyphoomphaloischiopagus tetrapus conjoined twins in the newborn period when survival of one of the twins was threatened by a severely malformed counterpart.

Eight cases of colon perforation due to amebiasis, proved pathologically and surgically in the National Taiwan University Hospital, occurred during a ten-year period from 1959 to 1969. Colon perforation was found in 6% of the hospitalized patients with amebiasis. Because of the variability of the clinical picture, accurate diagnosis was commonly delayed. The sites of perforations were most frequently found at cecum, ascending colon, and sigmoid colon. Multiple perforations were noted in six out of eight cases. Surgical procedures used in this series included drainage, proximal enterostomy, exteriorization of the perforated colon, and segmental resection followed by exteriorization of both ends. All except patient 2 died. In case 2, direct exteriorization of the perforated cecum was performed with a complete cure.

A patient with massive ascites associated with a pseudocyst of the pancreas after blunt abdominal injury is reported. A review of the literature reveals twenty-four similar cases. The most reasonable explanation of the etiology of ascites appears to be chronic leakage from a disrupted pancreatic duct or pseudocyst. Diagnosis is based on the finding of an elevated amylase and protein content in ascitic fluid. Surgical excision with drainage of the damaged pancreas or pseudocyst is the treatment of choice.