A Rapid and Feasible 1H-NMR Quantification Method of Ephedrine Alkaloids in Ephedra Herbal Preparations.

A highly specific and sensitive proton nuclear magnetic resonance (1H-NMR) method has been developed for the quantification of ephedrine alkaloid derivatives in Ephedra herbal commercial prescriptions. At the region of δ 4.0 to 5.0 ppm in the 1H NMR spectrum, the characteristic signals are separated well from each other, and six analogues in total, methylephedrine (ME), ephedrine (EP), norephedrine (NE), norpseudoephedrine (NP), pseudoephedrine (PE), and methylpseudoephedrine (MP) could be identified. The quantities of these compounds are calculated by the relative ratio of the integral values of the target peak for each compound to the known concentrations of the internal standard anthracene. The present method allows for a rapid and simple quantification of ephedrine alkaloid derivatives in Ephedra-related commercial prescriptions without any preliminary purification steps and standard compounds, and accordingly it can be a powerful tool to verify different Ephedra species. In comparison to conventional chromatographic methods, the advantages of this method include the fact that no standard compounds are required, the quantification can be directly performed on the crude extracts, a better selectivity for various ephedrine alkaloid derivatives, and the fact that a very significant time-gain may be achieved.

Ethnic disparity in prevalence and associated risk factors of myopia in adolescents.

BACKGROUND/PURPOSE: To examine ethnic disparity in prevalence and associated factors of myopia in adolescents using the Unites States National Health and Nutrition Examination Survey (NHANES) dataset. METHODS: Participants who were aged 12-19 years were included from NHANES (1999-2008). Logistic regression analyses were applied to identify risk factors associated with myopia after stratification by race. RESULTS: A total of 9,960 participants were included in the prevalence analysis, and 6,571 in the risk factor analysis. Other race (excluded Mexican American, other Hispanic, non-Hispanic white, non-Hispanic black) participants had the highest frequency of myopia (42.77%). Multivariate analyses of the whole population suggested that the odds of myopia were significantly lower in participants with household smokers (odds ratio [OR] = 0.79, 95% confidence interval [CI]: 0.66-0.97), and significantly greater in Mexican American race (OR = 1.28, 95% CI: 1.01-1.62), other Hispanic (OR = 1.79, 95% CI: 1.10-2.92) and in participants with senior high school graduate education (OR = 1.79, 95% CI: 1.01-3.18), watched 2 hours of television daily (OR = 1.27, 95% CI: 1.02-1.59), used the computer for 1 hour daily (OR = 1.276, 95% CI: 1.02-1.57). When examined by race/ethnicity, 1 hour of computer use increased the odds of myopia in the non-Hispanic White group, in Mexican Americans a higher family poverty income ratio and 2 hours of television time was associated with myopia, and in the Other Hispanic group, a higher family poverty income ratio was associated with myopia, while males and those with a higher sugar had a lower risk of myopia. CONCLUSION: Risk factors for myopia vary with race/ethnicity.

Relenza-Induced Acute Myopia Change.

PURPOSE: To report a case of a patient with a notable side effect to Relenza, an anti-influenza virus medication, who also developed acute transient myopia. CASE REPORT: A 31-year-old woman was diagnosed as having seasonal influenza and treated with Relenza. However, an allergic reaction and blurred vision caused by a transient myopic change were noted after she received Relenza treatment. Relenza-induced acute transient myopia had never been reported. The possible mechanisms include (1) ciliary spasm, (2) lens edema, (3) ciliary body and/or choroidal effusion. Fortunately, the drug-induced myopic change mostly resolved spontaneously after discontinuation of the drug and had a benign course. CONCLUSIONS: Patients suspected of having drug-induced myopia should be examined by an internist for a systemic allergic reaction and referred to an optometrist or an ophthalmologist for further special examinations such as A-scan, B-scan, and ultrasound biomicroscopy. Optometrists and ophthalmologists should keep in mind and be aware of the possible ocular side effect (myopic change) of Relenza and warn patients of this potential condition.

USP24-i-101 targeting of USP24 activates autophagy to inhibit drug resistance acquired during cancer therapy.

Drug resistance in cancer therapy is the major reason for poor prognosis. Addressing this clinically unmet issue is important and urgent. In this study, we found that targeting USP24 by the specific USP24 inhibitors, USP24-i and its analogues, dramatically activated autophagy in the interphase and mitotic periods of lung cancer cells by inhibiting E2F4 and TRAF6, respectively. USP24 functional knockout, USP24C1695A, or targeting USP24 by USP24-i-101 inhibited drug resistance and activated autophagy in gefitinib-induced drug-resistant mice with doxycycline-induced EGFRL858R lung cancer, but this effect was abolished after inhibition of autophagy, indicating that targeting USP24-mediated induction of autophagy is required for inhibition of drug resistance. Genomic instability and PD-L1 levels were increased in drug resistant lung cancer cells and were inhibited by USP24-i-101 treatment or knockdown of USP24. In addition, inhibition of autophagy by bafilomycin-A1 significantly abolished the effect of USP24-i-101 on maintaining genomic integrity, decreasing PD-L1 and inhibiting drug resistance acquired in chemotherapy or targeted therapy. In summary, an increase in the expression of USP24 in cancer cells is beneficial for the induction of drug resistance and targeting USP24 by USP24-i-101 optimized from USP24-i inhibits drug resistance acquired during cancer therapy by increasing PD-L1 protein degradation and genomic stability in an autophagy induction-dependent manner.

Impact of pathological nodal staging and tumour differentiation on survival and postoperative radiotherapy in completely resected stage IIIA Non-small-cell lung cancer.

BACKGROUND: Tumour differentiation is an important index for adjuvant therapy in many cancers; however, non-small cell lung cancer (NSCLC) is an exception. Furthermore, postoperative radiotherapy (PORT) is controversial in patients with NSCLC with N0-1 and N2 disease. We aimed to evaluate the impact of tumour-related factors on overall survival (OS), cancer-specific survival (CSS), and distant control (DC) in patients with completely resected stage IIIA NSCLC. MATERIALS AND METHODS: Patients with stage IIIA non-metastatic NSCLC who underwent complete resection and adjuvant chemotherapy were identified from the Taiwan Cancer Registry (January 2007-December 2017). Logistic regression analysis was performed to determine the factors associated with PORT. Survival and relapse outcomes were compared using log-rank tests and Cox regression analysis. Sensitivity analysis was performed using propensity score-matched pairs. RESULTS: In total, 1,897 patients were included and stratified according to PORT use (PORT vs. non-PORT). After adjusting for covariates, PORT was not found to be associated with improved survival outcomes. In patients with poorly differentiated tumours and N2 disease, absolute benefits for OS (adjusted hazard ratio [aHR] 0.76), CSS (aHR 0.80), and DC (aHR 0.74) were observed. Multivariable hazard models of propensity score-matched pN2 disease and poorly differentiated tumour subgroups also showed significant survival benefit with PORT treatment. CONCLUSIONS: Patients with poorly differentiated tumours and receiving PORT for pN2 disease showed a lower risk of distant recurrence and more favourable survival outcomes in stage IIIA NSCLC with R0 resection.

The feasibility study of using multiple partial volumetric-modulated arcs therapy in early stage left-sided breast cancer patients.

The purpose of this study was to assess the feasibility of using a multiple partial volumetric-modulated arcs therapy (MP-VMAT) technique on the left breast irradiation and to evaluate the dosimetry and treatment efficiency. Ten patients with left-sided breast cancer who had been treated by whole breast irradiation were selected for the treatment plan evaluation by using six partial volumetric modulated arcs. Each arc consisted of a 50° gantry rotation. The planning target volumes and the normal organs, including the right breast, the bilateral lungs, left ventricle, heart, and unspecified tissue, were contoured on the CT images. Dose-volume histograms were generated and the delivery time for each arc was recorded. The PTV received greater than 95% of the V(95) for all cases, and the maximum dose was within ± 1% of 110% of the prescription dose. The mean homogeneity index (HI) was 10.61 ± 0.99, and mean conformity index (CI) was 1.21 ± 0.03. The mean dose, V(5), V(10), V(25), and V(30) of the heart were 7.61 ± 1.38 Gy, 59.73% ± 15.87%, 24.39%± 6.82%, 2.52%± 1.11%, and 1.57% ± 0.71%, respectively. The volume of the left ventricle receiving 25 Gy was 5.15% ± 2.23%. The total lung mean dose was 5.57 ± 0.36 Gy, with V(5) of 25.39% ± 3.88% and V(20) of 5.66% ± 0.89%. The right breast received a mean dose of 2.13 ± 0.22 Gy, with V(5) of 1.83% ± 1.22% and V(10) of 0.04% ± 0.12%. The mean dose of unspecified tissue was 5.34 ± 0.37 Gy and V(5) was 22.23% ± 1.57%. The volume of the unspecified tissue receiving 50 Gy was 0.50% ± 0.14%. The mean delivery time for each arc was 13.9 seconds. The average MU among ten patients was 511 MU (range 443 to 594 MUs). The MP-VMAT technique for the left-sided breast cancer patients achieved adequate target dose coverage while maintaining low doses to organs-at-risk, and therefore reduced the potential for induction of second malignancy and side effects. The highly efficient treatment delivery would be beneficial for improving patient throughput, providing patient comfort, and achieving precise treatment with the breathing control system.

Optimizing surgical outcome of auricular keloid with a novel multimodal approach.

Various treatments are available for auricular keloids, but none has an absolute advantage. A practical and safe therapy to optimize the surgical outcome for auricular keloids is needed. We adopted a multimodal treatment of surgical enucleation, core fillet flap reconstruction, intraoperative corticosteroid injection, and immediate postoperative radiotherapy. There were no routine intralesional corticosteroid injections during follow-up. Keloid recurrences, complications, and risk factors for recurrences were analyzed. The outcome was compared with other published literatures. 45 auricular keloids were included in this study. 85.7% were female with an average age of 27.1 ± 7.5 years, and averaged size was 1.8 × 1.2 ± 0.9 × 0.6 cm. 71.1% were located at ear helix with 28.9% at the ear lobe. Nine keloids were classified as Chang-Park classification type I, 30 for type II, two for type III, and four for IV. The average radiation dosage was 1578.6 cGy. The recurrence rate was 6.7% at an average 24.1-month follow-up. There were no complications of surgery, radiotherapy, and intralesional corticosteroid injection. Our recurrence rate was lower than those in mono-adjuvant therapies of intraoperative corticosteroid injection or radiotherapy. This one-session multimodal approach optimizes treating auricular keloids with a low recurrence rate and minimal post-radiation and long-term corticosteroid injection-related complications.

Long-Term Survival Effect of the Interval between Postoperative Chemotherapy and Radiotherapy in Patients with Completely Resected Pathological N2 Non-Small-Cell Lung Cancer.

(1) Purpose: To investigate the effects of the time interval between initiation of adjuvant chemotherapy and radiotherapy on survival outcomes in patients with completely resected stage IIIA pN2 non-small-cell lung cancer (NSCLC); (2) Methods: Data on 2515 patients with completely resected stage IIIA pN2 NSCLC in 2007-2017 were extracted from the Taiwan Cancer Registry Database. The survival outcomes in patients who underwent concurrent chemoradiotherapy (CCRT) and sequential chemotherapy and radiotherapy (SCRT) with either a short (SCRT1) or long (SCRT2) interval between treatments were estimated using Kaplan-Meier, Cox regression, and propensity score matching (PSM); (3) Results: Multivariate analyses of OS showed that SCRT2 (hazard ratio [HR] 0.64, p = 0.017) was associated with improved overall survival (OS). After PSM, the median OS periods were 64 and 75 months in the SCRT1 and SCRT2 groups, respectively, which differed significantly from that of 58 months in the CCRT group (p = 0.003). In elderly patients, SCRT2 significantly improved survival relative to CCRT before PSM (p = 0.024) and after PSM (p = 0.002); (4) Conclusions: A longer interval between initiation of adjuvant chemotherapy and postoperative radiotherapy (PORT; SCRT2) improved OS relative to CCRT; the benefits were greater in elderly patients (age >60 years).

The factor influencing the rate of ROSC for nontraumatic OHCA in New Taipei city.

ABSTRACT: Return of spontaneous circulation (ROSC) from out-of-hospital cardiac arrest (OHCA) is critical for the Emergency Medical Services System. When compared to other developed countries, Taiwan has lower rate of ROSC in OHCA patients.We conducted a retrospective study of cardiac arrest using The Emergency Medical Service Dispatching Center in Northern Taiwan and The Prehospital Care System of New Taipei City Paramedic Service. Patients suffering from nontraumatic OHCA between August of 2019 to February of 2020 were included. We analyzed the cardiopulmonary resuscitation (CPR) quality parameters such as chest compression interruptions, bystander CPR, shockable rhythm, CPR interruption, chest compression fraction (CCF) average, patient transportation in buildings, and adrenaline injection during CPR. Multivariable logistic regression analysis was performed to assess the relationship between potential independent variables and ROSC.In our study, we involved 1265 subjects suffering from nontraumatic OHCA, among which 587 patients met inclusion criteria. We identified that CCF> 0.8, chest compression interruption greater than 3 times, and patient transportation in the building were the most critical factors influencing ROSC. However, patient transportation in a building was identified as a dependent predictor variable (P = .4752).We concluded that CCF > 0.8 and chest compression interruption greater than 3 times were essential factors affecting the CPR ROSC rate. The most significant reason for suboptimal CCF and CPR interruption is patient transportation in a building. Improving the latter point could facilitate high-quality CPR.

Comparisons within the Rice GA 2-Oxidase Gene Family Revealed Three Dominant Paralogs and a Functional Attenuated Gene that Led to the Identification of Four Amino Acid Variants Associated with GA Deactivation Capability.

BACKGROUND: GA 2-oxidases (GA2oxs) are involved in regulating GA homeostasis in plants by inactivating bioactive GAs through 2ß-hydroxylation. Rice GA2oxs are encoded by a family of 10 genes; some of them have been characterized, but no comprehensive comparisons for all these genes have been conducted. RESULTS: Rice plants with nine functional GA2oxs were demonstrated in the present study, and these genes not only were differentially expressed but also revealed various capabilities for GA deactivation based on their height-reducing effects in transgenic plants. Compared to that of wild-type plants, the relative plant height (RPH) of transgenic plants was scored to estimate their reducing effects, and 8.3% to 59.5% RPH was observed. Phylogenetic analysis of class I GA2ox genes revealed two functionally distinct clades in the Poaceae. The OsGA2ox3, 4, and 8 genes belonging to clade A showed the most severe effect (8.3% to 8.7% RPH) on plant height reduction, whereas the OsGA2ox7 gene belonging to clade B showed the least severe effect (59.5% RPH). The clade A OsGA2ox3 gene contained two conserved C186/C194 amino acids that were crucial for enzymatic activity. In the present study, these amino acids were replaced with OsGA2ox7-conserved arginine (C186R) and proline (C194P), respectively, or simultaneously (C186R/C194P) to demonstrate their importance in planta. Another two amino acids, Q220 and Y274, conserved in OsGA2ox3 were substituted with glutamic acid (E) and phenylalanine (F), respectively, or simultaneously to show their significance in planta. In addition, through sequence divergence, RNA expression profile and GA deactivation capability analyses, we proposed that OsGA2ox1, OsGA2ox3 and OsGA2ox6 function as the predominant paralogs in each of their respective classes. CONCLUSIONS: This study demonstrates rice has nine functional GA2oxs and the class I GA2ox genes are divided into two functionally distinct clades. Among them, the OsGA2ox7 of clade B is a functional attenuated gene and the OsGA2ox1, OsGA2ox3 and OsGA2ox6 are the three predominant paralogs in the family.

Magnetic resonance imaging-derived radiomic signature predicts locoregional failure after organ preservation therapy in patients with hypopharyngeal squamous cell carcinoma.

BACKGROUND AND PURPOSE: To develop and validate a magnetic resonance imaging (MRI)-derived radiomic signature (RS) for the prediction of 1-year locoregional failure (LRF) in patients with hypopharyngeal squamous cell carcinoma (HPSCC) who received organ preservation therapy (OPT). MATERIAL AND METHODS: A total of 800 MRI-based features of pretreatment tumors were obtained from 116 patients with HPSCC who received OPT from two independent cohorts. The least absolute shrinkage and selection operator regression model were used to select the features used to develop the RS. Harrell's C-index and corrected C-index were used to evaluate the discriminative ability of RS. The Youden index was used to select the optimal cut-point for risk category. RESULTS: The RS yielded 1000 times bootstrapping corrected C-index of 0.8036 and 0.78235 in the experimental (n = 82) and validation cohorts (n = 34), respectively. With respect to the subgroup of patients with stage III/IV and cT4 disease, the RS also showed good predictive performance with corrected C-indices of 0.760 and 0.754, respectively. The dichotomized risk category using an RS of 0.0326 as the cut-off value yielded a 1-year LRF predictive accuracy of 79.27%, 79.41%, 76.74%, and 71.15% in the experimental, validation, stage III/IV, and cT4a cohorts, respectively. The low-risk group was associated with a significantly better progression-free laryngectomy-free and overall survival outcome in two independent institutions, stage III/IV, and cT4a cohorts. CONCLUSION: The RS-based model provides a novel and convenient approach for the prediction of the 1-year LRF and survival outcome in patients with HPSCC who received OPT.

Outcomes for Cervical Cancer Patients Treated With Radiation in High-Volume and Low-Volume Hospitals.

PURPOSE: To investigate the effects of different hospital patient loads on the standard of care and treatment outcomes of patients with cervical cancer treated primarily with radiation therapy and to identify factors that may contribute to survival differences among hospitals. METHODS AND MATERIALS: We used the Taiwan Cancer Registry database to extract data on a total of 2582 International Federation of Gynecology and Obstetrics stage IB to IVA patients with uterine cervical cancer diagnosed from 2007 to 2013 who underwent primarily curative radiation therapy (with or without chemotherapy). We explored associations among hospital patient loads, clinical parameters, the type of care given, and survival. RESULTS: Patients who received treatment at hospitals with small and medium patient loads (≤5 cases annually) were older and had more advanced-stage disease than other patients. Positive associations were evident between the use of chemotherapy and brachytherapy and hospital patient load. Patients treated at hospitals with large patient loads (>5 cases annually) experienced better overall survival than those treated at hospitals with small or medium patient loads (P < .001). Stepwise addition of variables to multivariable analyses indicated that greater use of chemotherapy and brachytherapy were major contributors to the better survival of patients treated at hospitals with large patient loads. However, larger hospital patient load per se (>5 vs ≤5 cases annually) was also independently prognostic for better survival of patients with bulky tumors or advanced-stage disease. CONCLUSIONS: We found that the inferior survival rate of patients with cervical cancer treated at hospitals with smaller patient loads was attributable not only to a lower standard of care in such hospitals but also to the smaller patient load. Our findings indicate how treatment should be improved in hospitals with small and medium patient loads.

The prognostic impact of overall treatment time on disease outcome in uterine cervical cancer patients treated primarily with concomitant chemoradiotherapy: a nationwide Taiwanese cohort study.

The importance of the overall treatment time (OTT) has a paradoxical status in the current era of concomitant chemoradiotherapy. The main objective of this nationwide study was to evaluate the correlation between overall treatment duration and clinical outcome in cervical cancer patients treated primarily with curative concurrent chemoradiotherapy (CCRT). In this population-based cohort study, 2,594 patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I-IVA uterine cervical cancer were studied. Univariate and multivariate analyses of prognostic factors were analyzed using Cox's proportional hazards models. The median irradiation duration was 59 days. Significant prognostic factors related to poor cancer-specific survival (CSS) and overall survival (OS) included old age, non-squamous cell cancer type, high-grade histology, increased tumor size, advanced FIGO stage, and prolonged OTT. After multivariate analysis, prolonged treatment time remained as a significant factor for poor CSS (hazard ratio, HR = 1.33; p < 0.001) and OS (HR = 1.15; p = 0.05). Further subgroup analysis showed that the 5-year OS rates after a treatment time of ≤ 56 days compared with > 56 days in patients with FIGO stages I-IIB and III-IVA were 70% and 65% (p = 0.002) compared with 43% and 42% (p = 0.67), respectively. Inconclusion, completion of CCRT within 8 weeks is recommended, particularly for patients with FIGO stage I-IIB disease.

Upper eyelid granuloma: a rare delayed-onset complication secondary to cosmetic filler injection on forehead.

A 72-year-old Taiwanese woman had the history of cosmetic cryopreserved autologous fat injection on her forehead ~21 years ago and was referred to our oculoplastic clinic and presented with multiple painless mass, which she had for 4 years, on both upper eyelids. Histopathology confirmed the diagnosis of foreign body granuloma on both upper eyelids. Clinicians should be aware of the potential complication of granuloma reaction and migration even many years after the injection. We advise that autologous fat injection should be performed solely by trained physicians and it should be made known that there is a possible occurrence of migration.

A study on fluidized bed combustion characteristics of corncob in three different combustion modes.

This paper presents results obtained from corncob combustion in a pilot scale vortexing fluidized bed combustor (VFBC). Three combustion modes including direct combustion, staged combustion and flue gas recirculation (FGR) combustion were employed, and their combustion and pollutant emission characteristics were studied. In addition, the effects of combustion fraction and bed temperature on pollutant emission characteristics were investigated. The experimental results show that the combustion fractions vary with different combustion modes, resulting in different CO and NO emission characteristics. Staged and FGR combustions can reduce the NO emission concentration. Under similar working condition, NO concentration decreases by 30% in FGR mode, while 15% in staged mode compared with direct mode.

Helicobacter pylori infection concomitant with metabolic syndrome further increase risk of colorectal adenomas.

AIM: To investigate the association of colorectal adenomas with both Helicobacter pylori (H. pylori) infection and metabolic syndrome. METHODS: Using a cross-sectional hospital-based study, we analyzed physical examination data from 9311 healthy subjects with overnight physical examinations performed between January 2004 and December 2006. Examined data included gender, age, life style, anthropometric measurements, blood pressure, biochemical and hematological studies, H. pylori infection detected by esophagogastroduodenoscopy and biopsy urease tests, and colorectal adenomas detected with a complete total colonoscopy. RESULTS: The prevalence values for H. pylori infection, metabolic syndrome, and colorectal adenoma were 39.2%, 18.7%, and 20.7%, respectively. Colorectal adenoma risk factors included male gender [odd ratio (OR): 2.005, 95% confidence interval (CI): 1.740-2.310, P < 0.001], advanced age (OR: 1.046, 95% CI: 1.040-1.052, P < 0.001), smoking (OR: 1.377, 95% CI: 1.146-1.654, P = 0.001), increased body fat (OR: 1.016, 95% CI: 1.007-1.026, P = 0.001), higher white blood cell count (OR: 1.038, 95% CI: 1.005-1.073, P = 0.025), H. pylori infection (OR: 1.366, 95% CI: 1.230-1.517, P < 0.001), and metabolic syndrome (OR: 1.408, 95% CI: 1.231-1.610, P < 0.001). In addition, concomitant H. pylori infection with metabolic syndrome further increased the probability of colorectal adenomas. CONCLUSION: Our study revealed H. pylori infection with concomitant metabolic syndrome might further increase the risk of colorectal adenomas.

Effect of alkyl properties and head groups of cationic surfactants on retention of cesium by organoclays.

Cationic surfactants modified clays exhibit high sorptive capability toward anionic radionuclides but retention of cationic radionuclides was concurrently reduced. In this study, organoclays were synthesized by intercalating a variety of primary/quaternary alkylammonium species (NH(2)R/(CH(3))(3)N(+)RBr(-), where R = benzyl, dodecyl, and octadecyl) into bentonite MX-80. The effect of surfactant's properties on enhancing or limiting cationic sorption capability was investigated by performing Cs sorption experiments. Experimental results were analyzed using the MINEQL+ software by considering Cs uptake by structural and edge sorption sites. Bentonites that were intercalated with primary alkylammonium surfactants had a higher sorptive capacity than those intercalated with quaternary alkylammonium surfactants. Samples intercalated with octadecyl-bearing surfactants had the lowest sorption rate. XRD and FTIR analyses revealed that each organoclay had a characteristic arrangement of alkyl chains. The cation retention of organoclays was dominated by the extent of hydrophobic interactions affected by the local distribution and arrangement of surfactants. The intercalated primary alkylammoniun surfactants tended to transform into local clusters with a high packing density, leaving more structural sites available for Cs uptake. In contrast, the NH(3)R(+)-surfactants tended to form a denser monolayer over clay surface, inhibiting the retention of Cs at structural sites.