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Yi-Jan Wu,1,2 Shu-Sen Chang,3 Hsien-Yi Chen,4 Kai-Fan Tsai,2,5 Wen-Chin Lee,2,5 I-Kuan Wang,6,7 Chern-Horng Lee,8 Chao-Yu Chen,1,2 Shou-Hsuan Liu,1,2 Cheng-Hao Weng,1,2 Wen-Hung Huang,1,2 Ching-Wei Hsu,1,2 Tzung-Hai Yen1,2 1Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan City, Taiwan; 3Institute of Health Behaviors and Community Sciences, Department of Public Health, College of Public Health, National Taiwan University, Taipei City, Taiwan; 4Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan; 5Division of Nephrology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Branch, Kaohsiung City, Taiwan; 6Department of Nephrology, China Medical University Hospital, Taichung City, Taiwan; 7College of Medicine, China Medical University, Taichung City, Taiwan; 8Division of General Internal Medicine and Geriatrics, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, TaiwanCorrespondence: Tzung-Hai Yen, Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou Branch, 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan, Tel +886 3 3281200 ext 8181, Fax +886 3 3282173, Email m19570@cgmh.org.twBackground and Purpose: There is an overall paucity of data regarding the human toxicity of chlorpyrifos and cypermethrin pesticide mixture. Both organophosphate and pyrethroid insecticides are metabolized by carboxylesterases. Thus, its pesticide combination, organophosphates may boost the toxicity of pyrethroids via inhibited its detoxification by carboxylesterases. This study examined the clinical course, laboratory tests, and outcomes of patients with chlorpyrifos, cypermethrin or their pesticide mixture poisoning, and to determine what association, if any, might exist between these findings.Patients and Methods: Between 2000 and 2021, 121 patients poisoned with chlorpyrifos, cypermethrin, or their pesticide mixture were treated at Chang Gung Memorial Hospital. Patients were categorized as chlorpyrifos (n=82), cypermethrin (n=27) or chlorpyrifos and cypermethrin (n=12) groups. Demographic, clinical, laboratory and mortality data were collected for analysis.Results: The patients experienced a broad range of clinical symptoms, including aspiration pneumonia (44.6%), salivation (42.5%), acute respiratory failure (41.3%), acute kidney injury (13.9%), seizures (7.5%), hypotension (2.6%), etc. Leukocytosis (12,700± 6600 /uL) and elevated serum C-reactive protein level (36.8± 50.4 mg/L) were common. The acute respiratory failure rate was 41.3%, comprising 48.8% in chlorpyrifos, 11.1% in cypermethrin as well as 58.3% in chlorpyrifos and cypermethrin poisoning. Patients with chlorpyrifos and cypermethrin pesticide mixture poisoning suffered higher rates of acute respiratory failure (P=0.001) and salivation (P=0.001), but lower Glasgow Coma Scale score (P=0.011) and serum cholinesterase level (P< 0.001) than other groups. A total of 17 (14.0%) patients expired. The mortality rate was 14.0%, including 17.1% in chlorpyrifos, 3.7% in cypermethrin as well as 16.7% in chlorpyrifos and cypermethrin poisoning. No significant differences in mortality rate were noted (P=0.214).Conclusion: Chlorpyrifos pesticide accounted for the major toxicity of the pesticide mixture. While the data show a higher rate of respiratory failure in the chlorpyrifos and cypermethrin pesticide mixture group than others, other measures of toxicity such as mortality and length of stay were not increased.Keywords: chlorpyrifos, cypermethrin, pesticide mixture, poisoning, acute respiratory failure, mortality

Pei-Ching Chang,1 Chia-Lin Hsu,2 Shao-Yu Tai,2 Aileen I Tsai,2 I-Kuan Wang,3 Cheng-Hao Weng,4 Wen-Hung Huang,4 Ching-Wei Hsu,4 Tzung-Hai Yen4–6 1Department of Pediatric Dentistry, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Pediatric Dentistry, Chang Gung Memorial Hospital, Linkou, Taiwan; 3Department of Nephrology, China Medical University Hospital and College of Medicine, China Medical University, Taichung, Taiwan; 4Department of Nephrology and Clinical Poison Center, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Linkou, Taiwan; 5Kidney Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan; 6Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou, TaiwanCorrespondence: Tzung-Hai YenDepartment of Nephrology and Clinical Poison Center, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, 199 Tung Hwa North Road, Taipei 105, TaiwanTel +886 3 3281200 ext 8181Fax +886 3 3282173Email m19570@adm.cgmh.org.twPurpose: A consensus about the pathogenesis of torus palatinus (TP) in patients receiving dialysis still eludes the scientific community. This prospective observational study investigated the epidemiology of TP in peritoneal dialysis and hemodialysis patients and analyzed the influences of multiple pathogenic factors such as mineral and bone disorders, genetic, environmental or nutritional triggers, progression of age, heredity, climatologic or biomechanical causes, and hyperparathyroidism on the formation of TP.Methods: Between 2013 and 2016, a total of 575 chronic dialysis patients (441 on hemodialysis and 134 on peritoneal dialysis) were recruited from Chang Gung Memorial Hospital, Taiwan. Patients were stratified into two groups based on the presence (n = 179) or absence (n = 396) of TP. Demographic, oral examination, laboratory, and dialysis data were collected for analysis. Student’s t-test was used to analyze the quantitative variables and Chi-square or Fisher’s exact test for categorical variables. Univariate binary logistic regression analysis was conducted to determine the predictors for TP and multivariate binary logistic regression analysis to identify significant associated factors.Results: The prevalence of TP in dialysis patients in this study was 31.1% (28.3% for hemodialysis and 40.3% for peritoneal dialysis). Patients with TP were younger (54.6 ± 13.4 versus 58.9 ± 14.7 years, P = 0.001) and mostly female (60.3 versus 41.2%, P < 0.001). Most TP cases (55.3%) were small in size (< 2 cm), with the flat shape (56.4%) being the most common followed by the spindle (17.9%), nodular (17.3%), and lobular (8.4%) shapes. A longer duration of dialysis was associated with TP ≥ 2 cm than with TP < 2 cm (94.4 ± 85.9 versus 72.8 ± 59.1 months, P = 0.048). Multivariate logistic regression revealed that female gender (odds ratio 2.108, 95% confidence interval 1.455– 3.055, P < 0.001) and younger age (odds ratio 0.982; 95% confidence interval 0.969– 0.994, P = 0.005) were significant predictors for TP.Conclusion: The prevalence of TP in chronic dialysis patients is 31.1%, higher in patients receiving peritoneal dialysis (40.3%) than hemodialysis (28.3%). Female gender and younger age are significant predictors associated with TP.Keywords: end-stage renal disease, hemodialysis, peritoneal dialysis, torus palatinus

Ching-Chih Hu,1,2 Cheng-Hao Weng,2,3 Liang-Che Chang,4 Chih-Lang Lin,1,2 Yen-Ting Chen,1 Ching-Fang Hu,5 Man-Chin Hua,2,6 Li-Wei Chen,1 Rong-Nan Chien2,7 1Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan; 2College of Medicine, Chang Gung University, Linkou, Taiwan; 3Department of Nephrology and Poison Center, Chang Gung Memorial Hospital, Linkou, Taiwan; 4Department of Pathology, Chang Gung Memorial Hospital, Keelung, Taiwan; 5Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung, Taiwan; 6Department of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan; 7Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Linkou, Taiwan Purpose: Eradication of chronic hepatitis C virus (HCV) after interferon-based therapy and its association with the reduction of risk of hepatocellular carcinoma (HCC) in HCV-infected patients with advanced fibrosis is controversial. The study is aimed to develop a simple scoring model for HCC prediction among advanced fibrotic chronic hepatitis C (CHC) patients after pegylated interferon (pegIFN) and ribavirin (RBV) therapy. Patients and methods: We enrolled 271 biopsy-proven CHC patients with advanced fibrosis between 2003 and 2016, and divided them into non-HCC (n=211) and HCC (n=60) groups. The median observation duration was 6.0 years (range: 0.9–12.6 years). Results: The HCC prevalence after pegIFN and RBV therapy in CHC patients with sustained virologic response (SVR) and without SVR was 14.7% and 32.2%, respectively. Multivariate Cox regression showed age ≥59.5 years old at initiation of therapy (HR: 2.542, 95% CI: 1.390–4.650, P=0.002), pretreatment total bilirubin ≥1.1 mg/dL (HR: 2.630, 95% CI: 1.420–4.871, P=0.002), pretreatment platelet counts

Cheng-Hao Weng,1,2 Ching-Wei Hsu,1,2 Ching-Chih Hu,2,3 Tzung-Hai Yen,1,2 Ming-Jen Chan,1,2 Wen-Hung Huang1,2 1Department of Nephrology and Division of Clinical Toxicology, Chang Gung Memorial Hospital, Linkou Medical Center, 2Department of Medicine, Chang Gung University College of Medicine, Taoyuan, 3Department of Hepatogastroenterology and Liver Research Unit, Chang Gung Memorial Hospital, Keelung, Taiwan Abstract: Although uremic pruritus (UP) is a common and annoying symptom for end-stage renal disease patients on hemodialysis (HD) and peritoneal dialysis, its pathogenesis is poorly understood. However, systemic inflammation is one of the possible pathogenesis of UP, and blood lead level (BLL) has been noted to be associated with inflammation and nutritional status in long-term HD patients. There might be an interaction or association, therefore, between BLL and UP through systemic inflammation. We analyzed cross-sectional data among 866 participants. All of the 866 patients in this study were stratified into groups with low-normal (20 µg/dL). The associations between UP and BLL and the clinical data were analyzed. Multivariate logistic regression demonstrated that HD duration, non-anuria, log ferritin, serum low-density lipoprotein, log BLL, high-normal BLL, and high BLL were associated with UP. In conclusion, BLL was positively associated with UP. Keywords: blood lead levels, uremic pruritus, hemodialysis

Ching-Chung Hsiao,1,* Cheng-Hao Weng,1,2,* Yi-Jung Li,1 Hsin-Hsu Wu,1,2 Yung-Chang Chen,1 Yu-Ming Chen,1 Hsiang-Hao Hsu,1 Ya-Chung Tian1 1Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Taipei, 2Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan *These authors contributed equally to this work Abstract: Hemodialysis (HD) patients are more susceptible to infective endocarditis (IE) due to the increased risk of bacterial invasion through intravascular access. However, it remains unclear whether the causative organisms and outcomes of IE in HD patients differ from those in non-HD patients. This study clarified the differences in clinical presentation and outcomes between HD and non-HD patients. At our hospital, we performed a retrospective study of 39 HD and 51 non-HD patients with echocardiography-confirmed IE between June 2000 and February 2007. No differences in sex, intravenous drug use, previous diagnosis of congestive heart failure, and previous valvular surgery were observed between these two groups. The number of patients with diabetic mellitus in these two groups was significantly different (28.2% HD vs 5.9% non-HD patients). The C-reactive protein levels in the two groups were not significantly different. By contrast, the erythrocyte sedimentation rate was significantly higher in the HD patients (HD vs non-HD: 87.2±33.32 vs 52.96±28.19). The incidence of IE involving the mitral valve (MV; 45.1%) or the aortic valve (AV; 43.1%) was similar among the non-HD patients, whereas a preference of IE involving the MV (79.5%) over the AV (15.4%) was noted among the HD patients. The HD patients had a significantly higher Staphylococcus aureus infection rate (HD: 46.2%; non-HD: 27.5%). The proportion of methicillin-resistant S. aureus (MRSA; 83.8%) infection accounting for S. aureus IE in the HD group was higher than that (28.6%) in the non-HD group. The in-hospital mortality rate did not differ between the two groups. In conclusion, compared with non-HD patients, a propensity of IE involving the MV and a higher MRSA infection rate were observed in HD patients. The in-hospital mortality rate of echocardiography-confirmed IE did not differ between the two groups. Keywords: infective endocarditis, hemodialysis, mitral valve, aortic valve, Staphylococcus aureus

Chao-Yu Chen,1,2,* Ming-Hui Liu,3,* Ching-Wei Hsu,1,2 Cheng-Hao Weng,1,2 Tzung-Hai Yen,1,2 Wen-Hung Huang1,2 1Department of Nephrology and Division of Clinical Toxicology and Toxicology Laboratory, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan, Republic of China; 2Chang Gung University College of Medicine, Taoyuan, Taiwan, Republic of China; 3Department of Pediatric Dentistry, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, Republic of China *These authors contributed equally to this work Abstract: Patients undergoing hemodialysis (HD) have significantly higher mean blood lead levels (BLLs) than those in healthy individuals. Because elementary lead can be found in particulate matter with a diameter of

Ching-Wei Hsu,1–3 Cheng-Hao Weng,1–3 Cheng-Chia Lee,1–3 Dan-Tzu Lin-Tan,1–3 Pao-Hsien Chu,3,4 Kuan-Hsing Chen,1–3 Tzung-Hai Yen,1–3 Wen-Hung Huang1–3 1Department of Nephrology, Division of Clinical Toxicology, Chang Gung Memorial Hospital, Taipei, Taiwan, ROC; 2Department of Nephrology, Division of Clinical Toxicology, Linkou Medical Center, Taoyuan, Taiwan, ROC; 3Chang Gung University and School of Medicine, Taoyuan, Taiwan, ROC; 4Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan, ROC Background: Acute heart failure (AHF) is a serious condition that is associated with increased mortality in critically ill patients. Previous studies indicated that environmental exposure to cadmium increases mortality of general populations. However, the relationship of cadmium exposure and mortality is unclear for AHF patients.Materials and methods: A total of 153 patients with AHF in intensive care units (ICUs) met the inclusion criteria and were followed up for 6 months. Demographic data, AHF etiology, hematological and biochemical data, and hospital mortality were recorded. The scores of two predictive systems (Sequential Organ Failure Assessment [SOFA], Acute Physiology and Chronic Health Evaluation II [APACHE II]) for mortality in critically ill patients were calculated, and urinary cadmium levels were recorded.Results: At the end of the follow-up period, the mortality rate was 24.8%. The survivors (n=115) had higher urinary cadmium levels on day 1 (D1UCd) of ICU admission than non-survivors (n=38). A multiple linear regression analysis revealed a positive correlation between D1UCd and acute kidney injury, but a negative correlation between D1UCd and the level of serum albumin. A multivariate Cox analysis indicated that D1UCd was an independent predictor of mortality in AHF patients. For each increment of 1 µg of D1UCd, the hazard ratio for ICU mortality was 1.20 (95% confidence interval [CI]: 1.09–1.32, P

Ming-Hui Liu,1,* Ming-Jen Chan,2,* Ching-Wei Hsu,2,3 Cheng-Hao Weng,2,3 Tzung-Hai Yen,2,3 Wen-Hung Huang2,3 1Department of Pediatric Dentistry, 2Department of Nephrology and Division of Clinical Toxicology and Toxicology Laboratory, Chang Gung Memorial Hospital, Linkou Medical Center, 3Chang Gung University College of Medicine, Taoyuan, Taiwan, Republic of China *These authors contributed equally to this work Abstract: Uremic pruritus (UP) is a common and incapacitating symptom in patients undergoing hemodialysis (HD). The pathogenesis of UP is multifactorial and complex. Particulate matter (PM), a major air pollutant, is a mixture of particles with various chemical compositions. PM is associated with several allergic diseases, including dermatitis. To assess the role of PM (PM with a diameter of

Ching-Wei Hsu,1–3 Cheng-Hao Weng,1–3 Cheng-Chia Lee,1–3 Dan-Tzu Lin-Tan,1–3 Kuan-Hsing Chen,1–3 Tzung-Hai Yen,1–3 Wen-Hung Huang1–3 1Department of Nephrology, Division of Clinical Toxicology, Chang Gung Memorial Hospital, Taipei, Taiwan, Republic of China; 2Department of Nephrology, Division of Clinical Toxicology, Linkou Medical Center, Taoyuan, Taiwan, Republic of China; 3Department of Medicine, Chang Gung University College of Medicine, Taoyuan, Taiwan, Republic of China Background: The National Kidney Foundation–Kidney Disease Outcomes Quality Initiative recommends that the serum aluminum level (SAL) should be below 20 µg/L for patients with maintenance hemodialysis (MHD). However, serum aluminum may have toxic effects on MHD patients even when it is in the apparently acceptable range (below 20 µg/L).Methods: The Medical Ethics Committee approved this study. Initially, 954 MHD patients in dialysis centers were recruited. A total of 901 patients met the inclusion criteria and were followed-up for 1 year. Patients were stratified by SAL into four equal-sized groups: first quartile (13 µg/L). Demographic, biochemical, and dialysis-related data were obtained for analyses. A linear regression model was applied to identify factors associated with SAL. Cox proportional hazard model was used to determine the significance of variables in prediction of mortality.Results: Only 9.3% of MHD patients had SALs of 20 µg/L or more. At the end of the follow-up, 54 patients (6%) died, and the main cause of death was cardiovascular disease. Kaplan–Meier survival analysis showed that patients in the fourth SAL quartile had higher mortality than those in the first SAL quartile (log rank test, χ2=13.47, P=0.004). Using the first quartile as reference, Cox multivariate analysis indicated that patients in the third quartile (hazard ratio =1.31, 95% confidence interval =1.12–1.53, P=0.038) and the fourth quartile (hazard ratio =3.19, 95% confidence interval =1.08–8.62, P=0.048) had increased risk of all-cause mortality.Conclusion: This study demonstrates that SAL, even when in an apparently acceptable range (below 20 µg/L), is associated with increased mortality in MHD patients. The findings suggest that avoiding exposure of aluminum as much as possible is warranted for MHD patients. Keywords: aluminum, mortality, hemodialysis

Wen-Hung Huang,1,2 Ching-Wei Hsu,1,2 Ching-Chih Hu,3 Tzung-Hai Yen,1,2 Cheng-Hao Weng1,2 1Department of Nephrology, Division of Clinical Toxicology, Chang Gung Memorial Hospital, Linkou Medical Center, Gueishan, Taiwan, Republic of China; 2Department of Medicine, Chang Gung University College of Medicine, Taoyuan, Taiwan, Republic of China; 3Department of Hepatogastroenterology and Liver Research Unit, Chang Gung Memorial Hospital, Keelung, Taiwan, Republic of China Introduction: Predialysis hypotension has been noted to be a predictor of mortality in hemodialysis (HD) patients. Previous studies evaluating the impact of predialysis hypotension on the mortality of HD patients did not exclude patients with diabetes mellitus (DM) or cardiovascular disease.Methods: Eight hundred and sixty-six patients on maintenance HD were recruited. Clinical parameters were recorded and subjected to the analysis of predictors of predialysis hypotension and mortality.Results: Multivariate logistic regression analyses indicated that DM (odds ratio [OR]: 0.439, P=0.002), hypertension history (OR: 0.634, P=0.022), Kt/V Daugirdas (OR: 2.545, P=0.001), anuria (OR: 2.313, P=0.002), serum phosphate (OR: 0.833, P=0.010), and serum triglyceride (OR: 1.002, P=0.012) were associated with predialysis hypotension. Multivariate Cox regression analysis showed that age (P

Cheng-Hao Weng,1,2 Ching-Chih Hu,3 Tzung-Hai Yen,1,2 Wen-Hung Huang1,2 1Department of Nephrology, Division of Clinical Toxicology, Chang Gung Memorial Hospital, Linkou, 2College of Medicine, Chang Gung University, Taoyuan, 3Liver Research Unit, Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan Background: Secondary hyperparathyroidism (SHPT) is a major disorder in patients with chronic renal disease with or without dialysis. Air pollution has been confirmed as being associated with increased incidence of human morbidity and mortality. To our knowledge, investigating air pollution as a dialysis-unrelated factor for SHPT in patients undergoing dialysis is limited. We developed this study to assess the effect of air pollution and other important risk factors on SHPT in patients undergoing peritoneal dialysis (PD). Materials and methods: We recruited a total of 141 patients who did not have diabetes mellitus, were nonsmokers, and were undergoing PD in this cross-sectional study. We analyzed the difference in air quality based on the patients’ living areas. We estimated demographic, hematological, nutritional, inflammatory, biochemical, air pollutant, and dialysis-related data based on this cross-sectional study. Subgroup analysis of the relationship between air pollutants and the clinical variables and having or not having hyperparathyroidism (HPT) (intact parathyroid hormone level ≥180 pg/dL) was also performed. Results: A total of 141 patients undergoing PD (30 men and 111 women) were enrolled in the study. Sixty-eight patients had SHPT. In a binary logistic regression, high environmental CO exposure (odds ratio [OR] 3.22, 95% confidence interval [CI] 1.42–7.28; P=0.005), serum phosphate levels (OR 1.66, 95% CI 1.17–2.37; P=0.005), hypoalbuminemia (OR 3.76, 95% CI 1.29–10.94; P=0.015), and use of calcitriol (OR 8.25, 95% CI 3.43–19.85; P

Chen-Yen Lee,1,* Eileen Kevyn Chang,1,* Ja-Liang Lin,1 Cheng-Hao Weng,1 Shen-Yang Lee,1 Kuo-Chang Juan,1 Huang-Yu Yang,1 Chemin Lin,2 Shwu-Hua Lee,2 I-Kwan Wang,3 Tzung-Hai Yen1 1Department of Nephrology and Division of Clinical Toxicology, 2Department of Psychiatry, Chang Gung Memorial Hospital and Chang Gung University, Taipei, Taiwan; 3Department of Nephrology, China Medical University Hospital and China Medical University, Taichung, Taiwan *These authors contributed equally to this work Introduction: Methanol poisoning continues to be a serious public health issue in Taiwan, but very little work has been done to study the outcomes of methanol toxicity in the Asian population. In this study, we examined the value of multiple clinical variables in predicting mortality after methanol exposure. Methods: We performed a retrospective observational study on patients with acute poisoning who were admitted to the Chang Gung Memorial Hospital over a period of 9 years (2000–2008). Out of the 6,347 patients, only 32 suffered methanol intoxication. The demographic, clinical, laboratory, and mortality data were obtained for analysis. Results: Most patients were middle aged (46.1±13.8 years), male (87.5%), and habitual alcohol consumers (75.0%). All the poisonings were from an oral exposure (96.9%), except for one case of intentionally injected methanol (3.1%). After a latent period of 9.3±10.1 hours, many patients began to experience hypothermia (50.0%), hypotension (15.6%), renal failure (59.4%), respiratory failure (50.0%), and consciousness disturbance (Glasgow coma scale [GCS] score 10.5±5.4). Notably, the majority of patients were treated with ethanol antidote (59.4%) and hemodialysis (58.1%). The remaining 41.6% of patients did not meet the indications for ethanol therapy. At the end of analysis, there were six (18.8%), 15 (46.9%), and eleven (34.4%) patients alive, alive with chronic complications, and dead, respectively. In a multivariate Cox regression model, it was revealed that the GCS score (odds ratio [OR] 0.816, 95% confidence interval [CI] 0.682–0.976) (P=0.026), hypothermia (OR 168.686, 95% CI 2.685–10,595.977) (P=0.015), and serum creatinine level (OR 4.799, 95% CI 1.321–17.440) (P=0.017) were significant risk factors associated with mortality. Conclusion: The outcomes (mortality rate 34.4%) of the Taiwanese patients subjected to intensive detoxification protocols were comparable with published data from other international poison centers. Furthermore, the analytical results indicate that GCS score, hypothermia, and serum creatinine level help predict mortality after methanol poisoning. Keywords: wood alcohol, intoxication, ethanol, hemodialysis, mortality

Hsiao-Hui Chen,1 Ja-Liang Lin,1 Wen-Hung Huang,1 Cheng-Hao Weng,1 Shen-Yang Lee,1 Ching-Wei Hsu,1 Kuan-Hsing Chen,1 I-Kuan Wang,2 Chih-Chia Liang,2 Chiz-Tzung Chang,2 Tzung-Hai Yen1 1Department of Nephrology and Division of Clinical Toxicology, Chang Gung Memorial Hospital and Chang Gung University, Taipei, Taiwan; 2Department of Nephrology, China Medical University Hospital and China Medical University, Taichung, Taiwan Background: Data on the spectrum of corrosive injury to the esophagus after paraquat or glyphosate-surfactant ingestion are sparse in the literature and confined to case studies and brief reports. Therefore, this study aimed to examine the clinical features, degrees of esophageal injury, and clinical outcomes after paraquat or glyphosate herbicide ingestion, and sought to determine what association, if any, may exist between these findings. Methods: We performed an observational study on 47 patients with paraquat or glyphosate ingestion who underwent endoscopic evaluation over a period of 11 years (2000–2011). Results: Corrosive esophageal injuries were classified as grade 1 in 14 (glyphosate-surfactant) and three (paraquat), grade 2a in nine (glyphosate-surfactant) and 18 (paraquat), and grade 2b in one (glyphosate-surfactant) and two (paraquat) patients. No patients had grade 0, 3a, or 3b esophageal injuries. Therefore, the severity of corrosive injury was more severe in the paraquat group (P = 0.005). After toxin ingestion, systemic toxicity occurred, with rapid development of systemic complications in many cases. Neurologic complications occurred more frequently in the glyphosate-surfactant group (29.2% versus 0%, P = 0.005), although respiratory failure (4.2% versus 34.8%, P = 0.008), hepatitis (12.5% versus 52.2%, P = 0.004), and renal failure (20.8% versus 52.2%, P = 0.025) developed more frequently in the paraquat group. Patients with glyphosate poisoning had shorter hospital stays than patients with paraquat poisoning (13.3 ± 15.1 days versus 26.8 ± 10.2 days, P = 0.001). Nevertheless, there was no significant difference in mortality rate between the glyphosate-surfactant and paraquat groups (8.3% versus 13.0%, P = 0.601). We ultimately found that patients with grade 2b esophageal injury suffered from a greater incidence of respiratory (100.0% versus 5.9%, P = 0.001) and gastrointestinal (66.7% versus 11.8%, P = 0.034) complications than patients with grade 1 injury, regardless of herbicide type. Conclusion: Paraquat and glyphosate are mild caustic agents that produce esophageal injuries of grades 1, 2a, and 2b only. Our data also suggest a potential relationship between the degree of esophageal injury and systemic complications. Keywords: paraquat, glyphosate-surfactant, poisoning, suicide, esophageal injury

The existing roofing system in tropical climates is not adapting to the worsening climate, along with the demand for sustainable building design; this study introduced a pioneering cool roof system to reform the traditional roofing system. The pioneering cool roof system is composed of white reflective coating, hollow foamed concrete roof (HFCR) tile, and a sustainable active reflective insulation (RI) system. Despite the complex integrated roof technologies, the study adopted 3D CFD numerical simulation for an in-depth and frontier thermal distribution analysis and fluid flow presentation. The outcomes of the numerical model were compared with field measurements for validation purposes, which resulted in just a 3.31% error. The internal attic was 35.64 °C despite the roof exterior achieving 54.59 °C after receiving an average 680 W/m2 solar radiation source. After the heat flux was hugely terminated by the HFCR tile and sustainable active RI system, the heat flux magnitude attained in the internal attic was 1.0822 W/m2, and the active RI system removed 96.29% of heat flux excellently. Meanwhile, the proposed roofing design's energy-saving performance was 27.5%.

Objective To establish a model of combined injury of thermal radiation and blast wave of gas explosion in closed pipeline, and investigate the characteristics of important organ injury induced by burn-blast combined injury in rats. Methods A total of 72 male SD rats (aged 8~10 weeks, weighing 200~10 g) were randomly divided into control group and mild and severe injured groups. After the model rats were inflicted with blast wave and thermal radiation, their physical parameters were detected and measured. The respiratory function of the survival rats was tested. In 24 h later, arterial blood gas analysis, blood biochemical tests, and detection for serum inflammatory factors and lung injury related protein levels were performed, and the pathological changes in the lung tissue and trachea were observed. Results The peak range of explosive blast wave overpressure was 209~493 kPa, and the temperature was 152~258 ℃. The mortality rate was 8.3% in the mild group and 53.1% in the severe group. Compared with the control group, longer inspiratory time (Ti) and relaxation time (Tr) and larger tidal volume (TV)(P < 0.05), while lower respiratory frequency (f) were observed in the 2 injured groups within 6 h after injury (P < 0.05). At 24 h after injury, the values of partial pressure of carbon dioxide (PaCO2), residual base value (BE) and bicarbonate (HCO3-) were increased significantly (P < 0.05), while partial pressure of oxygen (PaO2) was decreased (P < 0.05). The serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBI) and total bile acid (TBA) were notably elevated (P < 0.05). So were the levels of IL-1 β, TNF-α and IL-6 (P < 0.01). Various severities of hyperemia foci and inflammation in the tracheal mucosa were observed in the injured rats. The incidence of lung injury was high, and the pathological manifestations were dot-shaped hemorrhage to diffuse hemorrhage of the whole lobe, rupture of alveolar septum, thickening of septum, and infiltration of red blood cells and inflammatory cells. The levels of serum lung injury-related proteins were significantly increased (P < 0.05). Conclusion A rat model which can highly simulate mild to severe burn-blast combined injury is constructed, which can meet the needs for rat model in study of explosive burn-blast compound injury. The main characteristics of the injury are lung injury, respiratory dysfunction, liver damage and secondary infection.

Rotating detonation engines (RDEs) have attracted significant attention in the aerospace field due to their high thermal cycle efficiency. This study explores the characteristics of rotating detonation in gas-solid mixed fuel within an air atmosphere. A theoretical detonation model for gas-solid mixed-phase fuel is developed in a cylindrical coordinate system. Using the three-dimensional conservation element and solution element (CE/SE) method, numerical simulations of the detonation process in a disc combustor are conducted in three dimensions. The flow field structure during the stable propagation of gas-solid mixed-phase rotating detonation waves is calculated. Subsequently, the analysis is conducted on the distribution characteristics of thermodynamic parameters in the detonation flow field, the distribution of chemical reaction zone, and the characteristics of wave system following the rotating detonation wave. The research results demonstrate that micron-sized coal powder can undergo a rapid reaction and support the stable propagation of rotating detonation waves with the assistance of hydrogen. However, due to the flat structural characteristics of the disc combustor and the non-premixed injection mode, the wave front of detonation wave appears as an irregular surface. The difference in the ability of coal powder and hydrogen jet to penetrate the air layer leads to the separation of the chemical reaction zone of the gas-solid mixed fuel, ultimately supporting the stable propagation of rotating detonation wave in the form of a dual reaction zone. The irregular surface structure of the rotating detonation wave leads to multiple reflections in the flat combustor, consequently causing the regular appearance of multiple reflected shock waves after the detonation wave.

The penetration of increasing solar gain towards the building deteriorates the building's thermal quality and raises cooling demand. In particular, the roof receives the most solar gain. The roof system reformation is urged to improve the roof system's heat capacity and conserve building energy. This paper introduced a novel cool roofing system to replace the traditional roof system. The proposed novel cool roofing applications merged: (i) lightweight foam concrete, (ii) hollow concrete slab, (iii) white cooling paint and (iv) active reflective insulation system powered by solar energy. The discovery of the proposed system was evaluated with experimental chambers exposed to the outdoor environment. Under intense sunlight, the internal roof surface was 30.6 % cooler (50.5 °C to 35.0 °C). The mean attic temperature achieved was 33.9 °C under a field where the daily maximum recorded surrounding temperature is 43.0 °C. In contrast with a bare roof at 41.9 °C, the proposed design demonstrated a 19.2 % lower solar gain, achieving a sub-ambient structure. Besides that, the cooling demand simulation generated similar cooling demand savings (20 %). Significantly, this comprehensive cool roofing system exhibited a considerable and constructive outcome in cooling the buildings by achieving sustainable development to create a better and more environmental future for all.

Human leukocyte antigen (HLA) restriction of conventional T-cell targeting introduces complexity in generating T-cell therapy strategies for patients with cancer with diverse HLA-backgrounds. A subpopulation of atypical, major histocompatibility complex-I related protein 1 (MR1)-restricted T-cells, distinctive from mucosal-associated invariant T-cells (MAITs), was recently identified recognizing currently unidentified MR1-presented cancer-specific metabolites. It is hypothesized that the MC.7.G5 MR1T-clone has potential as a pan-cancer, pan-population T-cell immunotherapy approach. These cells are irresponsive to healthy tissue while conferring T-cell receptor(TCR) dependent, HLA-independent cytotoxicity to a wide range of adult cancers. Studies so far are limited to adult malignancies. Here, we investigated the potential of MR1-targeting cellular therapy strategies in pediatric cancer. Bulk RNA sequencing data of primary pediatric tumors were analyzed to assess MR1 expression. In vitro pediatric tumor models were subsequently screened to evaluate their susceptibility to engineered MC.7.G5 TCR-expressing T-cells. Targeting capacity was correlated with qPCR-based MR1 mRNA and protein overexpression. RNA expression of MR1 in primary pediatric tumors varied widely within and between tumor entities. Notably, embryonal tumors exhibited significantly lower MR1 expression than other pediatric tumors. In line with this, most screened embryonal tumors displayed resistance to MR1T-targeting in vitro. MR1T susceptibility was observed particularly in pediatric leukemia and diffuse midline glioma models. This study demonstrates potential of MC.7.G5 MR1T-cell immunotherapy in pediatric leukemias and diffuse midline glioma, while activity against embryonal tumors was limited. The dismal prognosis associated with relapsed/refractory leukemias and high-grade brain tumors highlights the promise to improve survival rates of children with these cancers.

Objective To study the feasibility and effectiveness of quantitative evaluation of retinal function in blind patients with retinitis pigmentosa (RP) by chromatic pupillometry. Methods A total of 46 blind RP patients (81 eyes) who met the legal blindness standard admitted in our department from January 2022 to December 2022 were recruited in this study.According to their best-corrected visual acuity, they were divided into the no form perception (NFP) group, faint form perception (FFP) group, and form perception (FP) group.Another 18 healthy volunteers (18 eyes) were enrolled as controls.The subjects received routine ophthalmic examinations such as color fundus photography, optical coherence tomography (OCT), fundus autofluorescence (FAF), and flash visual evoked potential (FVEP).The thickness of the outer nuclear layer of OCT, vertical diameter of the FAF high fluorescence area, and amplitude of FVEP P2 were collected.Then chromatic pupillometry was performed.The light stimulation mode of low-intensity blue light was conducted to activate rods, and of high-intensity red light to activate cones.The evaluation indexes included transient pupil construction amplitude (TPCA), latency, maximal contraction velocity (MCV), and contraction duration. Results Under the mode of low-intensity blue light stimulation, more than half of the blind RP patients had rods pupil light reaction disappeared.Under the mode of high-intensity red light stimulation, the blind RP patients though retained pupil response of cone cells to light mostly but the response was significantly weakened.Compared with the control group, the TPCA and MCV of the cones'pupillary responses were significantly lower (P < 0.05), and the contraction latency was obviously higher (P < 0.05) in all RP blind groups.The NFP group had significantly lower TPCA and MCV and higher contraction latency when compared with the FP group (both P < 0.05).Positively correlations were observed in the TPCA and MCV of the cones'pupillary responses with the thickness of the outer nuclear layer of the retina, the vertical diameter of autofluorescence, and the amplitude of the FVEP P2 wave, respectively (P < 0.05).The latency of contraction was significantly negatively correlated with the thickness of the outer nuclear layer of the retina and the amplitude of FVEP P2 wave (P < 0.05). Conclusion Chromatic pupillometry can quantitatively distinguish the difference in retinal function between blind RP patients with and without formal perceptual vision.The changes in chromatic pupillometric results are consistent with the changes in retinal morphology and function.

Abstract Background Gene fusions are important cancer drivers in pediatric cancer and their accurate detection is essential for diagnosis and treatment. Clinical decision-making requires high confidence and precision of detection. Recent developments show RNA sequencing (RNA-seq) is promising for genome-wide detection of fusion products but hindered by many false positives that require extensive manual curation and impede discovery of pathogenic fusions. Methods We developed Fusion-sq to overcome existing disadvantages of detecting gene fusions. Fusion-sq integrates and “fuses” evidence from RNA-seq and whole genome sequencing (WGS) using intron–exon gene structure to identify tumor-specific protein coding gene fusions. Fusion-sq was then applied to the data generated from a pediatric pan-cancer cohort of 128 patients by WGS and RNA sequencing. Results In a pediatric pan-cancer cohort of 128 patients, we identified 155 high confidence tumor-specific gene fusions and their underlying structural variants (SVs). This includes all clinically relevant fusions known to be present in this cohort (30 patients). Fusion-sq distinguishes healthy-occurring from tumor-specific fusions and resolves fusions in amplified regions and copy number unstable genomes. A high gene fusion burden is associated with copy number instability. We identified 27 potentially pathogenic fusions involving oncogenes or tumor-suppressor genes characterized by underlying SVs, in some cases leading to expression changes indicative of activating or disruptive effects. Conclusions Our results indicate how clinically relevant and potentially pathogenic gene fusions can be identified and their functional effects investigated by combining WGS and RNA-seq. Integrating RNA fusion predictions with underlying SVs advances fusion detection beyond extensive manual filtering. Taken together, we developed a method for identifying candidate gene fusions that is suitable for precision oncology applications. Our method provides multi-omics evidence for assessing the pathogenicity of tumor-specific gene fusions for future clinical decision making.

Abstract The loss‐of‐function of the proprotein convertase subtilisin–kexin type 9 (Pcsk9) gene has been associated with significant reductions in plasma serum low‐density lipoprotein cholesterol (LDL‐C) levels. Both CRISPR/Cas9 and CRISPR‐based editor‐mediated Pcsk9 inactivation have successfully lowered plasma LDL‐C and PCSK9 levels in preclinical models. Despite the promising preclinical results, these studies did not report how vehicle‐mediated CRISPR delivery inactivating Pcsk9 affected low‐density lipoprotein receptor recycling in vitro or ex vivo. Extracellular vesicles (EVs) have shown promise as a biocompatible delivery vehicle, and CRISPR/Cas9 ribonucleoprotein (RNP) has been demonstrated to mediate safe genome editing. Therefore, we investigated EV‐mediated RNP targeting of the Pcsk9 gene ex vivo in primary mouse hepatocytes. We engineered EVs with the rapamycin‐interacting heterodimer FK506‐binding protein (FKBP12) to contain its binding partner, the T82L mutant FKBP12‐rapamycin binding (FRB) domain, fused to the Cas9 protein. By integrating the vesicular stomatitis virus glycoprotein on the EV membrane, the engineered Cas9 EVs were used for intracellular CRISPR/Cas9 RNP delivery, achieving genome editing with an efficacy of ±28.1% in Cas9 stoplight reporter cells. Administration of Cas9 EVs in mouse hepatocytes successfully inactivated the Pcsk9 gene, leading to a reduction in Pcsk9 mRNA and increased uptake of the low‐density lipoprotein receptor and LDL‐C. These readouts can be used in future experiments to assess the efficacy of vehicle‐mediated delivery of genome editing technologies targeting Pcsk9. The ex vivo data could be a step towards reducing animal testing and serve as a precursor to future in vivo studies for EV‐mediated CRISPR/Cas9 RNP delivery targeting Pcsk9.

Objective To summarize the clinical and imaging characteristics with Dandy-Walker syndrome (DWS) in children before and after peritoneal shunt. Methods and Results All 6 children with DWS admitted to Fujian Sanbo Funeng Brain Hospital from January 2016 to January 2023 were selected as the objects of observation, including one case of Dandy-Walker malformation (DWM) and 5 cases of Dandy- Walker variant (DWV). Before surgery, the main manifestations were cerebellar vermis defect, upward movement of the tentorial and sinusional area, severe dilatation of the fourth ventricle, posterior cranial fossa cystic lesions, supratentorial ventricle dilatation and hydrocephalus (one case); or cerebellar vermis dysplasia, cerebellar hemisphere compression, the fourth ventricle dilatation, posterior cranial fossa cystic lesions, supratentorial ventricle dilatation and hydrocephalus (5 cases). Right lateral ventriculoperitoneal shunt (2 cases) or posterior cranial fossa cyst-peritoneal shunt (4 cases) were performed, and the operations were successful without surgery - related complications. After 2.31-7.00 years of follow - up, 6 cases of hydrocephalus and posterior cranial fossa cystic malformation were gradually relieved, 3 cases of good prognosis, cerebral hemisphere and cerebellum development, speech, movement and intelligence normal; there were 3 children with general prognosis, including cerebellar disequilibrium symptoms (one case), autism, claustrophobia (one case), and speech, motor and intellectual disorders (one case) complicated with neurocutaneous melanosis. Conclusions The brain structure of the children with DWS presented with hydrocephalus can be well developed after the hydrocephalus is corrected by single shunt. Among them, the cerebellar vermis of the DWV is well developed, while the development of the DWM presented with cerebellar vermis defect needs to be observed in more cases.

In this study, an axicon metalens comprising a large central disc surrounded by nanoposts for energy harvesting in composite metal-oxide semiconductor sensors was designed, fabricated, and experimentally characterized. The main role of the central disc is focusing light; the nanoposts of various diameters deflect light to form a Bessel-like beam. The spatial distribution of the optical transmission was measured using micro-hyperspectral imaging. The axicon metalens concentrates the light to the sensitive area of the sensor and also harvests light from adjacent pixels. After adding an axicon metalens, the normalized peak transmission is up to 250% at λ = 700 nm as compared to a blank TiO2 film. The experimental results had fair agreement with the finite-difference-time-domain simulation. The ultra-broadband energy-harvesting performance of the sensor suggests that it could be applied in surveillance and Internet of Things applications.

ObjectiveTo investigate a suspected outbreak of healthcare-associated infection （HAI） caused by carbapenem-resistant Klebsiella pneumonia （CRKP） in a secondary grade-A hospital， analyze the infection source and transmission route， and put forward corresponding preventive and control measures.MethodsEpidemiological investigation was conducted on 5 patients with CRKP infection in department of neurosurgery during December 23‒30， 2021. Specimens were collected with the environmental microbiology monitoring procedure. CRKP isolated from the environmental samples were analyzed by multilocus sequence typing （MLST） method. Comprehensive measures were taken to control the CRKP infection.ResultsThe 5 infected patients were located in 3 rooms， and all were diagnosed as HAI. The antimicrobial susceptibility testing results from the specimens of 3 CRKP infected patients were the same. Through environmental microbiology monitoring， CRKP strains were detected from the faucet handle and sink specimens in 3 rooms. The results of MLST analysis showed that the faucet handle and sink specimens in room 2 and 3 were ST11 type. The environmental specimen in room 1 was ST23 type. The suspected outbreak was effectively controlled after comprehensive interventions.ConclusionHAI suspected outbreak might be caused by the environmental contamination from the pathogens of CRKP-infected patients as well as the contaminated hands of medical staff and accompanying family members. Strengthening the publicity， education and management of medical staff and accompanying staff， early identification of infection outbreaks， and timely comprehensive control measures are the keys to controlling multidrug-resistant nosocomial infection outbreaks.

ObjectiveTo analyze the clinical characteristics of 151 local COVID-19 patients in Shanghai， 2022.MethodsThe clinical data of 151 COVID-19 patients admitted to a district-level designated hospital in Shanghai from April 13 to May 10， 2022 were reviewed， and their clinical manifestations， laboratory tests， lung imaging， treatment and outcomes were analyzed.ResultsThe 151 patients ranged from 3 to 97 years old， with a median age of 72 years. Most of them were clustered cases in the communities and families. The main clinical types were mild （95 cases， 62.9%） and general （47 cases， 31.1%）. Most of the 9 severe/critical patients （6.0%） were elderly and complicated with multiple comorbidities. The proportion of people who had not been vaccinated was as high as 66.9%， and the proportion of those among severe/critically ill patients who had not been vaccinated was even higher. The most common first symptoms were expectoration in 71 cases （47.0%）， fever in 51 cases （33.8%） and dry cough in 30 cases （19.9%）. The counts of white blood cells and neutrophils in mild or general group were mostly normal or decreased， and in the severe/critical group increased significantly （P

Abstract Background Basal cell carcinoma (BCC) is one of the most common malignancies in the world. The frequency of histopathological subtypes and the distribution on the body of BCC has been well documented. Less has been written on the nature of secondary tumours. The genetics of BCC is starting to be understood, particularly with the advent of newer medical treatments (hedgehog inhibitors). Objectives To determine if primary basal cell carcinoma histopathological subtype predicts secondary tumour subtype, as well as their anatomical distribution. Methods A retrospective case series of patients over the age of 18 was performed from 2009 to 2014, with at least two separate diagnoses of BCC. Results In 394 identified patients, a total of 1355 BCCs arose in the cohort over the 6‐year study period. The number of secondary BCCs per patient ranged from 2 to 19 tumours. Nodular BCC was the most likely to reoccur in secondary tumours (53.3%), followed by mixed subtypes (45.7%). Conclusions Within our study, we did find a predisposition for secondary BCCs to be of the same histopathological subtype as the primary, particularly with respect to nodular and mixed tumours. Furthermore, we found that secondary tumours were also more likely to occur on the same anatomical site as the primary tumour. We are only just beginning to under the genetic mutations involved in subtype formation.

Supply Chain Management (SCM) is increasingly complex and dynamic. Radio frequency identification (RFID) and the Internet of Things (IoT) are expected to play a significant role in fulfilling customer requirements in the supply chain. In this work, the integration of RFID with IoT is called RFID-IoT. RFID-IoT strives to develop automated sensing, seamless, interoperable and highly secure systems by connecting IoT devices through the internet. In this paper, the authors have systematically reviewed the selected literature on the application of RFID-IoT in supply chain management. The contribution of this paper is to review the current state-of-the-art literature and potential trend on the application of RFID-IoT in SCM. There is a need for an in-depth, comprehensive analysis of up-to-date literature to help enhance the management system efficiency, maximize productivity, and minimize cost. This work also explores the current challenges of the reviewed papers in RFID-IoT implementation in the supply chain. The conceptual framework model has been conducted from four major critical SCM perspectives: product manufacturing, shipping and distribution, inventory and retail shop. In the future, this review's highlighted insights and recommendations will hopefully lead to increased efforts toward developing RFID-IoT technologies.

Interleukin-8 (IL-8), a member of the CXC chemokine family, is an important mediator of immune responses in the innate immune system. Recent studies have confirmed that IL-8 is significantly elevated in a variety of tumor tissues, including breast, nasopharyngeal, colorectal and gastric tumors, and also in the serum of patients suffering from these cancers. The level of IL-8 is correlated to the TNM staging and prognosis of cancer patients. Researches have shown that IL-8 is an indispensable inflammatory and immunosuppressive factor in the tumor microenvironment, capable of promoting tumor progression, angiogenesis and the recruitment of immune suppressor cells, as well as suppressing immune responses against tumor growth. It is also closely related to the drug resistance of tumors. This article provides a review on the application of targeted therapies related to IL-8 and the progress in combining these therapies with other anti-tumor treatments.

Background: There is considerable evidence on the benefits of endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) within 6 h after symptom onset. However, uncertainties remain regarding EVT efficacy beyond 6 h after symptom onset. We undertook a meta-analysis to assess the efficacy and safety of EVT in patients with AIS >6 h after symptom onset.Methods: We searched PubMed, EMBASE, and Chinese Biomedical through July 2019. We included studies involving early (≤6 h) vs. delayed (>6 h) EVT in selected patients with AIS, based on radiological evaluation criteria. Functional independence, successful recanalization, mortality, and symptomatic intracranial hemorrhage (sICH) rates were assessed.Results: Eight articles, with 3,265 patients who had undergone early EVT and 1,078 patients who had received delayed EVT, were included in the meta-analysis. Patients treated with early EVT showed a similar proportion of functional independence at 90 days [odds ratio (OR) = 1.14, 95% confidence interval (CI) = 0.926–1.397, P = 0.219; I2 = 36.2%, P = 0.128] as those treated with delayed EVT. Delayed EVT was also associated with no significant difference in mortality (OR = 1.015, 95% CI = 0.852–1.209; P = 0.871; I2 = 0.0%, P = 0.527), successful recanalization (OR = 1.255, 95% CI = 0.923–1.705; P = 0.147; I2 = 60.5%, P = 0.009), and sICH (OR = 0.976, 95% CI = 0.737–1.293; P = 0.871; I2 = 0.0%, P = 0.742) rates compared with early EVT.Conclusions: Among selected patients with AIS, delayed EVT showed comparable outcomes in functional independence, recanalization, mortality, and sICH rates compared with early EVT.

Global energy demand is rising due to the rapid development and adoption of new technologies in every sector. Hence, there is a need to introduce a clean energy source that does not cause damage to the environment. Aluminium-air battery with its high theoretical specific volumetric capacity is an exciting alternative for post-lithium energy storage and has been at the forefront of energy research for years. However, the conventional aqueous electrolyte-based aluminium-air battery with bulky liquid storage, parasitic corrosion of aluminium in contact with the electrolyte, and formation of a passive oxide or hydroxide layer has precluded its widespread application. In order to achieve successful simplification and cost-effectiveness, a novel idea of a polypropylene-based aluminium-air battery is proposed. In this work, a polypropylene-based aluminium-air battery was constructed using aluminium foil as an anode, carbon fiber cloth as an air-cathode, and Polypropylene and Kimwipes as the separator. The effects of the electrolyte concentration on the aluminium-air battery were investigated and analyzed using various discharge currents. The study showed that the performance of the polypropylene separator is better than that of the Kimwipes separator. The battery capacity is negatively correlated with the concentrations of the electrolyte. At a discharge current of 30 mA, the aluminium-air battery has a specific capacity of 375 mAh g−1 when 1 M of potassium hydroxide was used as electrolyte.

Gaussia luciferase (GLuc) is a secreted protein with significant potential for use as a reporter of gene expression in bacterial pathogenicity studies. To date there are relatively few examples of its use in bacteriology. In this study we show that GLuc can be functionally expressed in the human pathogen Staphylococcus aureus and furthermore show that it can be used as a biosensor for the agr quorum sensing (QS) system which employs autoinducing peptides to control virulence. GLuc was linked to the P3 promoter of the S. aureusagr operon. Biosensor strains were validated by evaluation of chemical agent-mediated activation and inhibition of agr. Use of GLuc enabled quantitative assessment of agr activity. This demonstrates the utility of Gaussia luciferase for in vitro monitoring of agr activation and inhibition.

Leucine-rich repeat-containing G protein-coupled receptors 4–6 (LGR4–LGR6) are receptors for R-spondins, potent Wnt agonists that exert profound trophic effects on Wnt-driven stem cells compartments. We present crystal structures of a signaling-competent fragment of R-spondin 1 (Rspo1) at a resolution of 2.0 Å and its complex with the LGR5 ectodomain at a resolution of 3.2 Å. Ecto-LGR5 binds Rspo1 at its concave leucine-rich-repeat (LRR) surface, forming a dimeric 2:2 complex. Fully conserved residues on LGR4–LGR6 explain promiscuous binding of R-spondins. A phenylalanine clamp formed by Rspo1 Phe106 and Phe110 pinches Ala190 of LGR5 and is critical for binding. Mutations related to congenital anonychia reduce signaling, but not binding of Rspo1 to LGR5. Furthermore, antibody binding to the extended loop of the C-terminal LRR cap of LGR5 activates signaling in a ligand-independent manner. Thus, our data reveal binding of R-spondins to conserved sites on LGR4–LGR6 and, in analogy to FSHR and related receptors, suggest a direct signaling role for LGR4–LGR6 in addition to its formation of Wnt receptor and coreceptor complexes.

In human sperm motility analysis, sperm segmentation plays an important role to determine the location of multiple sperms. To ensure an improved segmentation result, the Laplacian of Gaussian filter is implemented as a kernel in a pre-processing step before applying the image segmentation process to automatically segment and detect human spermatozoa. This study proposes an intersecting cortical model (ICM), which was derived from several visual cortex models, to segment the sperm head region. However, the proposed method suffered from parameter selection; thus, the ICM network is optimised using particle swarm optimization where feature mutual information is introduced as the new fitness function. The final results showed that the proposed method is more accurate and robust than four state-of-the-art segmentation methods. The proposed method resulted in rates of 98.14%, 98.82%, 86.46% and 99.81% in accuracy, sensitivity, specificity and precision, respectively, after testing with 1200 sperms. The proposed algorithm is expected to be implemented in analysing sperm motility because of the robustness and capability of this algorithm.

Stearoyl-coenzyme A desaturase (SCD) is an endoplasmic reticulum (ER) protein that catalyzes the Δ9-cis desaturation of saturated fatty acids. Mice with targeted disruption in SCD1 (Scd1−/−) have significant reduction in the tissue content of triglycerides, suggesting that monounsaturated fatty acids endogenously synthesized by SCD1 are important for triglyceride synthesis. Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) is the enzyme that catalyzes the final reaction in the synthesis of triglycerides. The lack of DGAT2, one of the two DGAT isoforms, results in almost a complete loss of tissue triglycerides. We hypothesize that SCD1 participates in triglyceride synthesis by providing a more accessible pool of monounsaturated fatty acids through substrate channeling. In this study, we test whether SCD1 is proximal to DGAT2 by colocalization study with confocal microscopy, coimmunoprecipitation, and fluorescence resonance energy transfer using HeLa cells as the model of study. All of the results suggest that SCD1 and DGAT2 are located very close to each other in the ER, which is a very important criterion for the channeling of substrate. By performing subcellular fractionation using mouse livers, we also show, for the first time, that SCD is present in the mitochondria-associated membrane.

Particles of sub-micron size possess significant capacity to adsorb organic molecules from aqueous media. Semiconductor photocatalysts in particle form could potentially be utilized for dye removal through either physical adsorption or photo-induced chemical process. The photocatalytic and adsorption capabilities of Cu2O particles with various exposed crystal facets have been studied through separate adsorption capacity test and photocatalytic degradation test. These crystals display unique cubic, octahedral, rhombic dodecahedral, and truncated polyhedral shapes due to specifically exposed crystal facet(s). For comparison, Cu2O particles with no clear exposed facets were also prepared. The current work confirms that the surface charge critically affects the adsorption performance of the synthesized Cu2O particles. The octahedral shaped Cu2O particles, with exposed {111} facets, possess the best adsorption capability of methyl orange (MO) dye due to the strongest positive surface charge among the different types of particles. In addition, we also found that the adsorption of MO follows the Langmuir monolayer mechanism. The octahedral particles also performed the best in photocatalytic dye degradation of MO under visible light irradiation because of the assistance from dye absorption. On top of the photocatalytic study, the stability of these Cu2O particles during the photocatalytic processes was also investigated. Cu(OH)2 and CuO are the likely corrosion products found on the particle surface after the photocorrosion in MO solution. By adding hole scavengers in the solution, the photocorrosion of Cu2O was greatly reduced. This observation confirms that the photocatalytically generated holes were responsible for the photocorrosion of Cu2O.

Zinc RING finger 3 (ZNRF3) and its homolog RING finger 43 (RNF43) antagonize Wnt signaling in adult stem cells by ubiquitinating Frizzled receptors (FZD), which leads to endocytosis of the Wnt receptor. Conversely, binding of ZNRF3/RNF43 to LGR4-6 - R-spondin blocks Frizzled ubiquitination and enhances Wnt signaling. Here, we present crystal structures of the ZNRF3 ectodomain and its complex with R-spondin 1 (RSPO1). ZNRF3 binds RSPO1 and LGR5-RSPO1 with micromolar affinity via RSPO1 furin-like 1 (Fu1) domain. Anonychia-related mutations in RSPO4 support the importance of the observed interface. The ZNRF3-RSPO1 structure resembles that of LGR5-RSPO1-RNF43, though Fu2 of RSPO1 is variably oriented. The ZNRF3-binding site overlaps with trans-interactions observed in 2:2 LGR5-RSPO1 complexes, thus binding of ZNRF3/RNF43 would disrupt such an arrangement. Sequence conservation suggests a single ligand-binding site on ZNRF3, consistent with the proposed competing binding role of ZNRF3/RNF43 in Wnt signaling.

Abstract Background Sequence and structural elements in the 3'-untranslated region (UTR) of Japanese encephalitis virus (JEV) are known to regulate translation and replication. We previously reported an abundant accumulation of small subgenomic flaviviral RNA (sfRNA) which is collinear with the highly conserved regions of the 3'-UTR in JEV-infected cells. However, function of the sfRNA in JEV life cycle remains unknown. Results Northern blot and real-time RT-PCR analyses indicated that the sfRNA becomes apparent at the time point at which minus-strand RNA (antigenome) reaches a plateau suggesting a role for sfRNA in the regulation of antigenome synthesis. Transfection of minus-sense sfRNA into JEV-infected cells, in order to counter the effects of plus-sense sfRNA, resulted in higher levels of antigenome suggesting that the presence of the sfRNA inhibits antigenome synthesis. Trans-acting effect of sfRNA on JEV translation was studied using a reporter mRNA containing the luciferase gene fused to partial coding regions of JEV and flanked by the respective JEV UTRs. In vivo and in vitro translation revealed that sfRNA inhibited JEV translation. Conclusions Our results indicate that sfRNA modulates viral translation and replication in trans.

Abstract Background Irpex lacteus, a versatile lignin-degrading fungus with various extracellular enzymes, has been widely used for biological pretreatment. However, most studies have focused on the change of substrate structure after biological pretreatment, and the effect of these changes on the enzymatic hydrolysis, but the effect of byproducts from biological pretreatment process on subsequent enzymatic hydrolysis is not well understood. Methods We developed a biological pretreatment process with I. lacteus that can produce stimulatory byproducts that enhance the enzymatic hydrolysis of cornstalks. Results The maximum hydrolysis yield of glucan (82%) was obtained after pretreatment for 28 days. The maximum reducing sugar yield decreased from 313.5 to 200.1 mg/g raw cornstalks after water-soluble byproducts of biological pretreatment were removed from pretreated cornstalks. The effect of byproducts on enzymatic hydrolysis was also investigated. We found that the hydrolysis efficiency of commercial cellulase preparation on cornstalks could be improved by water extracts from bio-pretreated cornstalks with hydrolytic enzyme activity and iron-reducing activity. Conclusion The key finding suggested that byproducts from biological pretreatment play important roles in enhancing downstream hydrolysis, which might be attributable to hydrolytic enzymes and iron-reducing compounds produced by I. lacteus.

Abstract Background Registered data can provide valuable information regarding blindness. The purpose of this study was to evaluate the main causes and 3-year incidence of registered blindness in Jing-An district in Shanghai, China. Methods Data from the blindness registry (age, gender and cause of visual disability) were collected and analyzed. The prevalence of blindness for 2003, 2007, 2009 and the 3-year incidence of blindness were calculated. Results The reported blindness increased significantly from 113.7 per 100,000 in 2003 to 145.8 per 100,000 in 2006 to 165.9 per 100,000 in 2009 (P < 0.05, P < 0.05, respectively). Age significantly affects prevalence; the odd ratios (OR) were 2.57 in the 30 y - 49 y range (P < 0.001), 7.27 in the 50 y - 69 y range (P < 0.001) and 21.2 in the ≥ 70 y (P < 0.001). The 3-year incidence increased from 32.3 per 100,000 in 2001-2003 to 34.2 per 100,000 in 2004-2006 to 40.8 per 100,000 in 2007-2009. The causes of new blindness registered in 2001-2009 were myopic macular degeneration (19.4%), followed by glaucoma (17.7%), age-related macular degeneration (11.8%), optical nerve atrophy (9.4%), retinitis pigmentosa (8.6%), diabetic retinopathy (7.8%) and corneal opacity (5.8%). Conclusions The 3-year incidence and prevalence of registered blindness increased in the past 9 years. The leading causes of new blindness were myopic macular degeneration, glaucoma and age-related macular degeneration. The pattern of causes has changed little in the past 9 years and is different from other locations in China. The pattern is similar to that of Taiwan, Hongkong, and Western countries.

Abstract In the present study, we explore the role of apoptosis signal-regulating kinase 1 (ASK1) in denbinobin-induced apoptosis in human lung adenocarcinoma (A549) cells. Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative mutant (ASK1DN), two antioxidants (N-acetyl-L-cysteine (NAC) and glutathione (GSH)), a c-Jun N-terminal kinase (JNK) inhibitor (SP600125), and an activator protein-1 (AP-1) inhibitor (curcumin). Treatment of A549 cells with denbinobin caused increases in ASK1 activity and reactive oxygen species (ROS) production, and these effects were inhibited by NAC and GSH. Stimulation of A549 cells with denbinobin caused JNK activation; this effect was markedly inhibited by NAC, GSH, and ASK1DN. Denbinobin induced c-Jun phosphorylation, the formation of an AP-1-specific DNA-protein complex, and Bim expression. Bim knockdown using a bim short interfering RNA strategy also reduced denbinobin-induced A549 cell apoptosis. The denbinobin-mediated increases in c-Jun phosphorylation and Bim expression were inhibited by NAC, GSH, SP600125, ASK1DN, JNK1DN, and JNK2DN. These results suggest that denbinobin might activate ASK1 through ROS production to cause JNK/AP-1 activation, which in turn induces Bim expression, and ultimately results in A549 cell apoptosis.

Objective: To investigate whether semaglutide increases the risk of non-arteritic anterior ischemic optic neuropathy (NAION) in the general population., Design: This retrospective cohort study utilized a de-identified global electronic medical records database. The enrollment period was extended from January 2017 to August 2023, with observations concluding in August 2024., Participants: This study included individuals with type 2 diabetes mellitus (T2DM) or obesity. They were further categorized into T2DM-only, obesity-only, and T2DM with obesity groups to assess the differences among these subgroups. The effects of semaglutide were compared with those of glucose-lowering or weight loss medications other than glucagon-like peptide receptor agonists., Methods: Patient data were obtained from 160 healthcare organizations across 21 countries. Outcomes were evaluated at one, two, and three years of follow-up. A 1:1 propensity score matching was performed to balance age, sex, body mass index, hemoglobin A1C, medications, and underlying comorbidities. Cox regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI)., Main Outcome Measures: The occurrence of NAION., Results: The final analysis included 37,245 participants with T2DM-only, 33,537 participants with obesity-only, and 64,989 participants with both T2DM and obesity. The results indicated that the administration of semaglutide was not associated with the development of NAION in the T2DM-only group (1 year follow-up: HR, 2.32; 95% CI, 0.60-8.97; 2 years: HR, 2.31; 95% CI, 0.86-6.17; 3 years: HR, 1.51; 95% CI, 0.71-3.25), the obesity-only group (1 year follow-up: HR, 0.25; 95% CI, 0.03-2.28; 2 years: HR, 0.44; 95% CI, 0.09-2.21; 3 years: HR, 0.44; 95% CI, 0.09-2.21), and the T2DM with obesity group (1 year follow-up: HR, 0.81; 95% CI, 0.42-1.57; 2 years: HR, 1.2; 95% CI, 0.74-1.94; 3 years: HR, 1.19; 95% CI, 0.78-1.82)., Conclusions: The findings suggest that semaglutide may not be associated with an increased risk of NAION in the general population. Therefore, avoidance of semaglutide based solely on concerns regarding the risk of NAION may not be warranted, as its potential benefits for blood glucose control and cardiovascular health likely outweigh its potential risks., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To estimate the risk of Alzheimer's disease (AD) associated with long-term use of topical glaucoma medications among middle-aged and older glaucoma patients, and compare the AD risk among various glaucoma subtypes., Methods: This nationwide population-based cohort study utilized insurance claims data from Taiwan's National Health Insurance Research Database between 2008 and 2019. Participants were adults aged 45 years or older either with a diagnosis of glaucoma or without. Those with glaucoma must have received single antiglaucomatous medication (including α2-adrenergic agonists, cholinergic agonists, beta-blockers, prostaglandin analogs, and pilocarpine) for over 90 days. Those with pre-existing AD diagnoses prior to the index date were excluded., Results: A total of 202,000 participants were included in the study, with 101,000 in each group (glaucoma and control groups). Glaucoma patients on topical alpha-2 adrenergic agonist monotherapy exhibited a significantly higher AD risk (aHR 1.15, 95% CI = 1.01-1.31) compared to those on beta-blockers. Glaucoma was further categorized into primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), primary angle-closure glaucoma (PACG), and unspecified glaucoma. Irrespective of the type of glaucoma, individuals with glaucoma had a significantly higher risk of AD compared to those without glaucoma (POAG: aHR 1.23, 95% CI = 1.08-1.40; NTG: aHR 1.49, 95% CI = 1.19-1.85; PACG: aHR 1.35, 95% CI = 1.19-1.52; unspecified glaucoma: aHR 1.36, 95% CI = 1.23-1.50)., Conclusions: Topical alpha-2 adrenergic agonists might pose increased AD risk in individuals with glaucoma compared to beta-blockers. Accordingly, their utilization should be undertaken judiciously, especially in middle-aged and older populations. Our findings also indicate glaucoma may increase the risk of AD regardless of glaucoma subtype., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: Previous studies implied that different types of statins may pose divergent impacts on the risk of glaucoma onset. This study aimed to comprehensively evaluate the effects of various statins on the risk of glaucoma occurrence., Methods: PubMed, Cochrane CENTRAL, Embase, and Web of Science were searched from February 1994 to February 2024. We included studies that investigated the effects of various types of statins, fibrates, ezetimibe, cholestyramine, niacin, PCSK9 inhibitors, omega-3 fatty acids, and any cholesterol-lowering medications on glaucoma onset or progression. The revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0) and the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-1) tool were used to assess the quality of randomized controlled trials (RCTs) and non-RCTs, respectively. The frequentist network meta-analysis framework was utilized to evaluate the comparative effectiveness, with the random effects model applied., Results: This network meta-analysis comprised 12 studies, encompassing 262,217 individuals and including cholesterol-lowering medications such as statins, fibrates, ezetimibe, cholestyramine, niacin, and omega-3 fatty acids. Our findings demonstrate that comparing to the placebo, rosuvastatin (risk ratio [RR], 1.23; 95% confidence interval [CI], 1.03 to 1.46), simvastatin (RR, 1.21; 95% CI, 1.02 to 1.43), and pravastatin (RR, 1.20; 95% CI, 1.01 to 1.43) increased the risk of glaucoma onset with statistical significance., Conclusion: Rosuvastatin, simvastatin, and pravastatin were each associated with a significantly increased risk of glaucoma onset. We advise medical practitioners to exercise caution when prescribing these specific statins for patients who are at risk of developing glaucoma., Key Messages: What is known Previous studies have suggested a link between statins and the risk of developing glaucoma. However, there is still ongoing debate regarding the specific effects of each type of statin on the onset of glaucoma. What is new This network meta-analysis comprehensively evaluated the effects of various statins on the risk of glaucoma onset. Rosuvastatin, simvastatin, and pravastatin were associated with a significantly increased risk of glaucoma onset., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The available data on anticoagulation therapy in real-world primary care settings for atrial fibrillation (AF) patients at high risk of stroke is limited., Objective: To evaluate anticoagulation therapy and elucidate the factors associated with the selection between direct oral anticoagulants (DOACs) and warfarin., Design and Participants: This is a retrospective cohort study that included patients ≥ 18 years old at a large primary care outpatient group, a network of twenty clinics in the northeast United States between January 4, 2021 - January 4, 2023., Main Measures: Oral anticoagulation therapy in AF patients with high risk of stroke (CHA 2 DS 2 -VASc score of ≥ 2 in men or ≥ 3 in women)., Key Results: Among the 3,118 adult patients with AF and high risk of stroke (median age 77.90, IQR 71.66-84.50 years; male 57.6%), we found that older age (aOR 1.40, p = 0.003), greater BMI (25-29.9: aOR 1.32, p = 0.048; ≥ 30 aOR 1.42, p = 0.010), and taking more than five medications (aOR 2.28, p < 0.001) were more likely to be on an oral anticoagulant. Among those taking an OAC, having Medicare as the sole coverage (aOR 0.53, p = 0.032), male gender (aOR 0.69, p = 0.011), worse renal function (aOR 0.80, p = 0.021), and higher CHA 2 DS 2 -VASc score (aOR 0.88, p = 0.024) are more likely to be on warfarin than a DOAC. Patients taking more than five medications daily (6-10 medications: aOR 1.92, p = 0.013; ≥ 16: aOR = 2.10, p = 0.006) were more likely to be on an anticoagulant and may receive a DOAC over warfarin., Conclusions: AF with high stroke risk adult patients are more likely to be on an oral anticoagulant if they are older, having BMI ≥ 25, or taking more than five medications. Medicare as the sole coverage, male gender, worse renal function, and higher CHA 2 DS 2 -VASc scores are factors associated with greater warfarin usage, while patients taking over five daily medications are more likely to be prescribed DOACs., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Rationale: This case report presents a challenging medical scenario involving a young adult male who exhibited an unusual combination of symptoms, including abrupt weight loss, declining renal function, proteinuria, and concurrent onset of diabetes mellitus. Remarkably, the patient had no previous medical history or family history of similar conditions, necessitating a comprehensive investigation., Patient Concerns: On March 10, 2021, a 25-year-old male sought medical attention due to the aforementioned symptoms. Initial assessments revealed stage 5 chronic kidney disease, with elevated blood urea nitrogen (BUN) and serum creatinine (Cr) levels, as well as significant proteinuria. The only notable physical finding was obesity, and renal ultrasound showed normal-sized kidneys without cysts., Diagnosis: A treatment plan was initiated to stabilize creatinine levels, including medications such as Glimepiride, Glyxambi, Bisoprolol, Amlodipine, and Valsartan. However, despite diligent medication management, proteinuria persisted, prompting further evaluation. A renal biopsy was performed on April 12th, 2023, leading to the diagnosis of glomerulocystic kidney disease with early-stage changes indicative of diabetic nephropathy., Interventions: The patient continues to receive ongoing care and follow-up at our outpatient clinic to optimize therapeutic interventions and elucidate the underlying etiology of this complex clinical scenario., Outcomes: Ongoing investigations and therapeutic interventions are crucial to understand the underlying cause and optimize patient care in this intricate clinical scenario., Lessons: This case underscores the complexity of diagnosing and managing a young adult presenting with concurrent renal dysfunction, proteinuria, and diabetes mellitus in the absence of prior underlying conditions. It highlights the importance of comprehensive evaluation and ongoing care in such challenging cases., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)