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A novel actinobacterium strain, HUAS 14-6 T , was isolated from the healthy leaves of Camellia oleifera collected from Changde City, Hunan Province, China. Strain HUAS 14-6 T produced tight spiral spore chains consisting of oval or spherical spores with a smooth surface. 16S rRNA gene sequence analysis revealed that strain HUAS 14-6 T belonged to the genus Streptomyces and shared highest similarity to Streptomyces bungoensis DSM 41781 T (99.72%). Phylogenetic analysis based on 16S rRNA gene sequences indicated strain HUAS 14-6 T was in a clade with S. bungoensis DSM 41781 T . However, the ANIm and dDDH between strain HUAS 14-6 T and S. bungoensis DSM 41781 T were 88.16% and 31.2%, respectively, far less than the species-level thresholds. Phylogenetic trees based on the five housekeeping genes (atpD, gyrB, recA, rpoB and trpB) showed that strain HUAS 14-6 T formed a separate branch, indicating that this strain could belong to a potential new species. Pairwise MLSA distances between strain HUAS 14-6 T and all type strains exhibiting 16S rRNA gene sequence similarities of ≥98.7% to it were much higher than the maximum range of 0.014 recommended for delineating a new Streptomyces species. Based on polyphasic taxonomic study, HUAS 14-6 T represents a novel species within the genus Streptomyces for which the name Streptomyces albidocamelliae sp. nov. is proposed. The type strain is HUAS 14-6 T (=MCCC 1K08365 T =JCM 35920 T )., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Study Objective: This study aimed to investigate the effect of liposomal bupivacaine in transversus abdominis plane block (TAP) on recovery quality after cesarean delivery., Design: A randomized trial., Setting: An operating room, a post-anesthesia care unit, and a hospital ward., Patients: A total of 147 women scheduled for cesarean delivery under spinal anesthesia were enrolled and randomized to receive a TAP block with plain bupivacaine (bupivacaine group), liposomal bupivacaine (liposomal group), or a mixture of plain bupivacaine and liposomal bupivacaine (mixture group)., Interventions: The bupivacaine group received bilateral TAP blocks with plain bupivacaine 50 mg alone. The liposomal group received bilateral TAP blocks with liposomal bupivacaine 266 mg alone. The mixture group received bilateral TAP blocks with plain bupivacaine 50 mg followed by liposomal bupivacaine 266 mg., Measurements: The primary outcome was the Quality of Recovery-15 (QoR - 15) score assessed 24 h postoperatively. Secondary outcomes encompassed the QoR - 15 score at 48 h post-surgery, the VAS pain score at rest and with movement at 24, 48, and 72 h postoperatively, opioid consumption within the 0-24 h and 24-48 h periods following surgery, as well as patient's satisfaction with analgesic., Main Results: The QoR - 15 score at 24 h postoperatively was significantly higher in both the liposomal group and the mixture group compared to the bupivacaine group. Specifically, the QoR - 15 score for the liposomal group versus the bupivacaine group (median [IQR]: 120 [107, 128] vs. 109 [104, 120]; median difference, 7; 95 % CI, 2 to 13; P = 0.011) and for the mixture group versus the bupivacaine group (median [IQR]: 122 [112, 128] vs. 109 [104, 120]; median difference, 9; 95 % CI, 4 to 14; P = 0.001). The QoR - 15 score in both the liposomal group and the mixture group were also higher than those in the bupivacaine group at 48 h postoperatively, though the difference was not clinically meaningful. Additionally, both the liposomal and mixture groups exhibited lower pain score at 24 h and 48 h postoperatively compared to the bupivacaine group, but no significant clinical differences were achieved in either pain scores or opioid consumption. Patients in both the liposomal and mixture groups reported higher satisfaction score with analgesia than those in the bupivacaine group., Conclusions: TAP block using either liposomal bupivacaine or a mixture of plain bupivacaine and liposomal bupivacaine provided superior quality of recovery at 24 h after cesarean delivery compared to using plain bupivacaine alone., Competing Interests: Declaration of competing interest The author(s) declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

In recent years, there has been a gradual increase in the prevalence of drug-resistant bacteria, primarily attributed to the widespread use of antibiotics. This has resulted in heightened mortality rates, morbidity, and exorbitant healthcare costs associated with antibiotic-resistant bacterial infections. In order to mitigate the spread of antibiotic-resistant bacteria, environmental disinfection plays a crucial role. Ultraviolet radiation C (UVC) light disinfection has emerged as a potent technique to limit the transmission of nosocomial pathogens and prevent healthcare-associated infections. Different types of high-touch surfaces were used. A serial disinfected experiment with different 222 nm UVC dosages was conducted on clinically isolated antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus species (VRE), carbapenem-resistant Escherichia coli (CREC), carbapenem-resistant Klebsiella pneumonia (CRKP), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA) on different material surfaces. The bactericidal efficacy was evaluated by The Clinical & Laboratory Standards Institute (CLSI) guidelines. 222 nm UVC irradiation had a potent bactericidal efficacy on clinical antibiotic-resistant bacteria on different high-touch surfaces that are commonly found in the environment and healthcare facilities. 222 nm UVC irradiation time was tested from 10 s to 1 h. Different surfaces affect the efficiency of 222 nm UVC. The more adsorptive a material is, the higher the dosage of 222 nm UVC irradiation energy is required for effective disinfection. The use of 222 nm UVC lamps for disinfection on different materials has been shown to be a useful method. However, it is crucial to pay attention to the energy required for effective sterilization., Importance: This study is crucial, providing compelling evidence on Far-ultraviolet radiation C (Far-UVC) light's efficacy against clinically significant antibiotic-resistant bacteria-a pressing issue in microbiology and infection control. Our research employs antibiotic-resistant strains from clinically isolated bacteria, emphasizing real-world relevance. Simultaneously, we assess Far-UVC light (222 nm) across diverse material surfaces commonly found in clinical settings. This dual approach ensures practical applicability and broad relevance. Our comprehensive setup and rigorous methodologies unequivocally demonstrate Far-UVC light's potency in combating antibiotic-resistant bacteria. Since 222 nm far-UVC has a disinfection capability and is harmless to mammalian cells, this dual effectiveness positions Far-UVC as a secure tool for infection control, with potential applications in healthcare settings, mitigating antibiotic-resistant bacteria spread, and reducing healthcare-associated infections.

Abstract: Background: Early prediction of sepsis onset is crucial for reducing mortality and the overall cost burden of sepsis treatment. Currently, few effective and accurate prediction tools are available for sepsis. Hence, in this study, we developed an effective sepsis clinical decision support system (S-CDSS) to assist emergency physicians to predict sepsis. Methods: This study included patients who had visited the emergency department (ED) of Taipei Tzu Chi Hospital, Taiwan, between January 1, 2020, and June 31, 2022. The patients were divided into a derivation cohort (n = 70,758) and a validation cohort (n = 27,545). The derivation cohort was subjected to 6-fold stratified cross-validation, reserving 20% of the data (n = 11,793) for model testing. The primary study outcome was a sepsis prediction ( International Classification of Diseases , Tenth Revision , Clinical Modification ) before discharge from the ED. The S-CDSS incorporated the LightGBM algorithm to ensure timely and accurate prediction of sepsis. The validation cohort was subjected to multivariate logistic regression to identify the associations of S-CDSS-based high- and medium-risk alerts with clinical outcomes in the overall patient cohort. For each clinical outcome in high- and medium-risk patients, we calculated the sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and accuracy of S-CDSS-based predictions. Results: The S-CDSS was integrated into our hospital information system. The system featured three risk warning labels (red, yellow, and white, indicating high, medium, and low risks, respectively) to alert emergency physicians. The sensitivity and specificity of the S-CDSS in the derivation cohort were 86.9% and 92.5%, respectively. In the validation cohort, high- and medium-risk alerts were significantly associated with all clinical outcomes, exhibiting high prediction specificity for intubation, general ward admission, intensive care unit admission, ED mortality, and in-hospital mortality (93.29%, 97.32%, 94.03%, 93.04%, and 93.97%, respectively). Conclusion: Our findings suggest that the S-CDSS can effectively identify patients with suspected sepsis in the ED. Furthermore, S-CDSS-based predictions appear to be strongly associated with clinical outcomes in patients with sepsis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

The taxonomic relationship between Streptomyces violarus and Streptomyces violaceus was reevaluated using a polyphasic taxonomic approach in this work. Phylogenetic analysis based on 16S rRNA gene sequences indicated that Streptomyces violarus JCM 4534  T was closely related to Streptomyces arenae ISP 5293  T . However, phylogenetic analysis based on five house-keeping gene (atpD, gyrB, recA, rpoB and trpB) showed that the evolutionary neighbor of Streptomyces violarus JCM 4534  T was Streptomyces violaceus CGMCC 4.1456  T , suggesting that there was a close genetic relationship between these two strains. The average nucleotide identity and digital DNA-DNA hybridization values between them were 97.0 and 72.9%, respectively, greater than the 96.7 and 70% cut-off points recommended for delineating a Streptomyces species. This result indicated that they belonged to the same genomic species which was also verified by a comprehensive comparison of phenotypic and chemotaxonomic characteristics between Streptomyces violarus JCM 4534  T and Streptomyces violaceus CGMCC 4.1456  T . According to all these data and the rule of priority in nomenclature, it is proposed the Streptomyces violarus (Artamonova and Krassilnikov 1960) Pridham 1970 is a later heterotypic synonym of Streptomyces violaceus (Rossi Doria 1891) Waksman 1953. In addition, based on dDDH, Streptomyces violaceus and Streptomyces violarus are simultaneously designated as two different subspecies, i.e., Streptomyces violaceus subsp. violaceus and Streptomyces violaceus subsp. violarus., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A novel actinobacterium, strain HUAS 3 T , was isolated from the rhizosphere soil of Cathaya argyrophylla collected in Hunan Province, PR China. Strain HUAS 3 T contained meso -diaminopimelic acid in the cell-wall peptidoglycan. The dominant menaquinones were MK-9(H 4 ), MK-9(H 6 ), MK-10(H 2 ) and MK-9(H 4 ). The polar lipids consisted of diphosphatidylglycerol, phospholipids, phosphatidylethanolamine, phosphatidylglycerol, phosphotidylinositol and phosphatidylinositol mannosides. The main cellular fatty acids (>5.0 %) were C 17 : 1  ω8 c , iso-C 16 : 0 , C 18 : 1  ω9 c , iso-C 15 : 0 , C 16 : 0 and summed feature 3 (C 16 : 1  ω6 c and/or C 16 : 1  ω7 c ). The DNA G+C content of the novel strain's genome sequence, consisting of 7 196 442 bp, was 72.8 mol%. The full-length 16S rRNA gene sequence analysis indicated that strain HUAS 3 T belonged to the genus Micromonospora and showed highest similarities to Micromonospora fluminis A38 T (99.44 %), Micromonospora echinospora DSM 43816 T (99.23 %), Micromonospora tulbaghiae DSM 45142 T (99.23 %), Micromonospora solifontis PPF5-17 T (99.16 %) and Micromonospora endolithica DSM 44398 T (98.96 %). Phylogenetic trees based on 16S rRNA gene sequences showed that strain HUAS 3 T was closely related to M. fluminis A38 T , M. tulbaghiae DSM 45142 T and M. solifontis PPF5-17 T . The phylogenomic tree revealed that strain HUAS 3 T was closely related to Micromonospora pallida DSM 43817 T . However, the average nucleotide identity (ANIb/ANIm) and the digital DNA-DNA hybridization values between them were 84.75 /88.16 and 30.80 %, respectively, far less than the 95-96 and 70 % cut-off points recommended for delineating species. Furthermore, strain HUAS 3 T was distinct from the type strain of M. pallida in terms of phenotypic and chemotaxonomic characteristics. In summary, strain HUAS 3 T represents a novel Micromonospora species, for which the name Micromonospora cathayae sp. nov. is proposed. The type strain is HUAS 3 T (=MCCC 1K08599 T =JCM 36275 T ).

Two actinomycete strains, designated MG62 T and CRLD-Y-1, were isolated from rhizosphere soil of Koelreuteria paniculata and healthy leaves of Xanthium sibiricum , respectively, in Hunan province, PR China. They could produce abundant aerial mycelia that generated rod-shaped spores with spiny surfaces. Morphological features of the two strains are typical of the genus Streptomyces . Strains MG62 T and CRLD-Y-1 exhibited 99.93 % 16S rRNA gene sequence similarity. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between them were 99.99 and 100 %, respectively, suggesting that they belonged to the same species. 16S rRNA gene sequences analysis revealed that the two strains belonged to the genus Streptomyces and showed highest similarities to Streptomyces violarus NBRC 13104 T (99.07-99.29 %) and Streptomyces arenae ISP 5293 T (99.21-99.35 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strains MG62 T and CRLD-Y-1 were closely related to S. violarus NBRC 13104 T and S. arenae ISP 5293 T . However, the ANI, dDDH and multilocus sequence analysis evolutionary distance values between the two strains and their relatives provide a robust basis upon which to verify strains MG62 T and CRLD-Y-1 as representing a novel species. Moreover, a comprehensive comparison of phenotypic and chemotaxonomic characteristics further confirmed that the two strains were distinct from their relatives. Based on all these data above, strains MG62 T and CRLD-Y-1 should represent a novel Streptomyces species, for which the name Streptomyces koelreuteriae sp. nov. is proposed. The type strain is MG62 T (=JCM 34747 T =MCCC 1K06175 T ).

Background: Healthcare-associated COVID-19 infections caused by SARS-CoV-2 have increased morbidity and mortality. Hospitals and skilled nursing facilities (SNFs) have been challenged by infection control and management., Methods: This case study presents an outbreak investigation in a COVID-19-designated hospital and a hospital-based SNF. Real-time polymerase chain reaction (PCR) and other studies were performed on samples obtained from SNF residents, hospital patients, and healthcare workers (HCWs). The results of the laboratory tests and field epidemiological data were analyzed. Genome sequencing and phylogenetic analysis of SARS-CoV-2 were performed to identify the associations between cases. The tracer gas was released and recorded by a thermal imaging camera to investigate the spatial relations within clusters., Results: During the outbreak, 29 COVID-19 infections in 3 clusters were identified through hospital-wide, risk-guided, and symptom-driven PCR tests. This included 12 HCWs, 5 patients, and 12 SNF residents who had been hospitalized for at least 14 days. Serology tests did not identify any cases among the PCR-negative individuals. The phylogenetic analysis revealed that viral strains from the 3 clusters shared a common mutation of G3994T and were phylogenetically related, which suggested that this outbreak had a common source rather than multiple introductions from the community. Linked cases exhibited vertical spatial distribution, and the sulfur hexafluoride release test confirmed a potential airborne transmission., Conclusions: This report addressed the advantage of a multi-disciplinary team in outbreak investigation. Identifying an airborne transmission within an outbreak highlighted the importance of regular maintenance of ventilation systems., Competing Interests: Declaration of competing interest All authors denied any financial and personal conflict of interest that could inappropriately influence this article., (Copyright © 2023. Published by Elsevier B.V.)

Since April 2022, waves of SARS-CoV-2 Omicron variant cases have surfaced in Taiwan and spread throughout the island. Using high-throughput sequencing of the SARS-CoV-2 genome, we analyzed 2,405 PCR-positive swab samples from 2,339 persons and identified the Omicron BA.2.3.7 variant as a major lineage within recent community outbreaks in Taiwan.

Background/purpose: This study aimed to investigate the in vitro susceptibilities of carbapenem-non-susceptible Pseudomonas aeruginosa (CNSPA) and Acinetobacter baumannii (CNSAB) isolates to cefiderocol, novel β-lactamase inhibitor (BLI) combinations, new tetracycline analogues, and other comparative antibiotics., Methods: In total, 405 non-duplicate bacteremic CNSPA (n = 150) and CNSAB (n = 255) isolates were collected from 16 hospitals in Taiwan between 2018 and 2020. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibilities were interpreted according to the relevant guidelines or in accordance with results of previous studies and non-species-related pharmacokinetic/pharmacodynamic data., Results: Among the isolates tested, cefiderocol demonstrated potent in vitro activity against CNSPA (MIC 50/90 , 0.25/1 mg/L; 100% of isolates were inhibited at ≤4 mg/L) and CNSAB (MIC 50/90 , 0.5/2 mg/L; 94.9% of isolates were inhibited at ≤4 mg/L) isolates. More than 80% of CNSPA isolates were susceptible to cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and amikacin, based on breakpoints established by the Clinical and Laboratory Standards Institute. Activities of new BLI combinations varied significantly. Tetracycline analogues, including tigecycline (MIC 50/90 , 1/2 mg/L; 92.5% of CNSAB isolates were inhibited at ≤2 mg/L) and eravacycline (MIC 50/90 , 0.5/1 mg/L; 99.6% of CNSAB isolates were inhibited at ≤2 mg/L) exhibited more potent in vitro activity against CNSAB than omadacycline (MIC 50/90 , 4/8 mg/L)., Conclusions: The spread of CNSPA and CNSAB poses a major challenge to global health. Significant resistance be developed even before a novel agent becomes commercially available. The development of on-site antimicrobial susceptibility tests for these novel agents is of great clinical importance., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

The aim of the current study was to evaluate the subchronic toxicity of GmDREB3 gene modified wheat in the third generation rats. SPF Wistar rats were fed with transgenic wheat diet (Gm), parental wheat diet (Jimai22) and AIN-93 rodent diet (Control), respectively, for two generations, to produce the third generation rats which were used for this study. The selected fresh weaned offspring rats (20/sex/group) were given the same diet as their parents for 13 weeks. No toxicity-related changes were observed in rats fed with Gm diet in the following respects: clinical signs, body weights, body weight gains, food consumption, food utilization rate, urinalysis, hematology, serum biochemistry and histopathology. The results from the present study demonstrated that 13 weeks consumption of Gm wheat did not cause any adverse effects in the third generation rats when compared with the corresponding Jimai22 wheat.

Background/purpose: Streptococcus pneumoniae causes pneumonia and other invasive diseases, and is a leading cause of mortality in the elderly population. The present study aimed to provide current antimicrobial resistance and epidemiological profiles of S. pneumoniae infections in Taiwan., Methods: A total of 252 nonduplicate S. pneumoniae isolates were collected from patients admitted to 16 hospitals in Taiwan between January 2017 and December 2019, and were analyzed. The minimum inhibitory concentration of antibiotics was determined using the Vitek 2 automated system for antimicrobial susceptibility testing. Furthermore, epidemiological profiles of S. pneumoniae infections were analyzed., Results: Among the strains analyzed, 88% were recognized as invasive pneumococcal strains. According to the Clinical and Laboratory Standards Institute criteria for non-meningitis, the prevalence of penicillin-non-susceptible S. pneumoniae demonstrated a declining trend from 43.6% in 2017 to 17.2% in 2019. However, the rate of penicillin-non-susceptible S. pneumoniae was 85.7% based on the criteria for meningitis. Furthermore, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7% based on the criteria for meningitis. Isolates demonstrated higher susceptibility toward doripenem and ertapenem than toward meropenem and imipenem. An increased rate of non-susceptibility toward levofloxacin was observed in southern Taiwan (15.1%) and elderly patients (≥65 years; 11.4%). Most isolates were susceptible to vancomycin and linezolid., Conclusion: Empirical treatment with ceftriaxone monotherapy for pneumococcal meningitis should be carefully monitored owing to its high non-susceptibility rate. The susceptibility rates of most isolates to penicillin (used for treating non-meningitis pneumococcal diseases), carbapenems (ertapenem and doripenem), respiratory quinolones (moxifloxacin and levofloxacin), vancomycin, and linezolid suggested the potential of these antibiotics in treating pneumococcal diseases in Taiwan., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021. Published by Elsevier B.V.)

Malvids is one of the largest clades of rosids, includes 58 families and exhibits remarkable morphological and ecological diversity. Here, we report a high-quality chromosome-level genome assembly for Euscaphis japonica, an early-diverging species within malvids. Genome-based phylogenetic analysis suggests that the unstable phylogenetic position of E. japonica may result from incomplete lineage sorting and hybridization event during the diversification of the ancestral population of malvids. Euscaphis japonica experienced two polyploidization events: the ancient whole genome triplication event shared with most eudicots (commonly known as the γ event) and a more recent whole genome duplication event, unique to E. japonica. By resequencing 101 samples from 11 populations, we speculate that the temperature has led to the differentiation of the evergreen and deciduous of E. japonica and the completely different population histories of these two groups. In total, 1012 candidate positively selected genes in the evergreen were detected, some of which are involved in flower and fruit development. We found that reddening and dehiscence of the E. japonica pericarp and long fruit-hanging time promoted the reproduction of E. japonica populations, and revealed the expression patterns of genes related to fruit reddening, dehiscence and abscission. The key genes involved in pentacyclic triterpene synthesis in E. japonica were identified, and different expression patterns of these genes may contribute to pentacyclic triterpene diversification. Our work sheds light on the evolution of E. japonica and malvids, particularly on the diversification of E. japonica and the genetic basis for their fruit dehiscence and abscission., (© 2021 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Objectives: The aim of this study was to investigate the trends in serotypes and in vitro antimicrobial susceptibility of Streptococcus pneumoniae causing adult invasive pneumococcal disease (IPD) to dalbavancin, telavancin, tedizolid, eravacycline, omadacycline and other comparator antibiotics from 2017-2020 following implementation of the 13-valent pneumococcal conjugate vaccine (PCV-13) and during the COVID-19 (coronavirus disease 2019) pandemic., Methods: During the study period, 237 S. pneumoniae isolates were collected from non-duplicate patients, covering 15.0% of IPD cases in Taiwan. Antimicrobial susceptibility testing was performed using a Sensititre® system. A latex agglutination method (ImmuLex™ Pneumotest Kit) was used to determine serotypes., Results: Susceptibility rates were high for vancomycin (100%), teicoplanin (100%) and linezolid (100%), followed by ceftaroline (non-meningitis) (98.3%), moxifloxacin (94.9%) and quinupristin/dalfopristin (89.9%). MIC 50 and MIC 90 values of dalbavancin, telavancin, tedizolid, eravacycline and omadacycline were generally low. Non-vaccine serotype 23A was the leading cause of IPD across the adult age range. Isolates of serotype 15B were slightly fewer than those of PCV-13 serotypes in patients aged ≥65 years. The overall case fatality rate was 15.2% (36/237) but was especially high for non-PCV-13 serotype 15B (21.4%; 3/14). Vaccine coverage was 44.7% for PCV-13 and 49.4% for the 23-valent pneumococcal polysaccharide vaccine (PPSV-23), but was 57% for both PCV-13 and PPSV-23., Conclusion: The incidence of IPD was stationary after PCV-13 introduction and only dramatically decreased in the COVID-19 pandemic in 2020. The MIC 50 and MIC 90 values of dalbavancin, telavancin, tedizolid, eravacycline, omadacycline were generally low for S. pneumoniae causing adult IPD., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study examined the susceptibility of carbapenem-nonsusceptible Enterobacterales (CNSE) to cefiderocol, cefepime/zidebactam, cefepime/enmetazobactam, omadacycline, eravacycline and other comparative agents. Non-duplicate Enterobacterales isolates from 16 Taiwanese hospitals were evaluated. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibility results were interpreted based on relevant guidelines. In total, 201 CNSE isolates were investigated, including 26 Escherichia coli isolates and 175 Klebsiella pneumoniae isolates. Carbapenemase genes were detected in 15.4% (n=4) of E. coli isolates and 47.4% (n=83) of K. pneumoniae isolates, with the most common being bla KPC (79.3%, 69/87), followed by bla OXA-48-like (13.8%, 12/87). Cefiderocol was the most active agent against CNSE; only 3.8% (n=1) of E. coli isolates and 4.6% (n=8) of K. pneumoniae isolates were not susceptible to cefiderocol. Among the carbapenem-resistant E. coli and K. pneumoniae isolates, 88.5% (n=23) and 93.7% (n=164), respectively, were susceptible to ceftazidime/avibactam. For cefepime/zidebactam, 23 (88.5%) E. coli isolates and 155 (88.6%) K. pneumoniae isolates had MICs ≤2/2 mg/L. For cefepime/enmetazobactam, 22 (84.6%) E. coli isolates and 85 (48.6%) K. pneumoniae isolates had MICs ≤2/8 mg/L. The higher MICs of K. pneumoniae against cefepime/enmetazobactam were due to only one (1.5%) of the 67 bla KPC -carrying isolates being susceptible. MICs of omadacycline were significantly higher than those of eravacycline and tigecycline. In summary, cefiderocol, ceftazidime/avibactam and cefepime/zidebactam were more effective against carbapenem-nonsusceptible E. coli and K. pneumoniae than other drugs, highlighting their potential as valuable therapeutics., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

To discover effective drugs for COVID-19 treatment amongst already clinically approved drugs, we developed a high throughput screening assay for SARS-CoV-2 virus entry inhibitors using SARS2-S pseudotyped virus. An approved drug library of 1800 small molecular drugs was screened for SARS2 entry inhibitors and 15 active drugs were identified as specific SARS2-S pseudovirus entry inhibitors. Antiviral tests using native SARS-CoV-2 virus in Vero E6 cells confirmed that 7 of these drugs (clemastine, amiodarone, trimeprazine, bosutinib, toremifene, flupenthixol, and azelastine) significantly inhibited SARS2 replication, reducing supernatant viral RNA load with a promising level of activity. Three of the drugs were classified as histamine receptor antagonists with clemastine showing the strongest anti-SARS2 activity (EC 50  = 0.95 ± 0.83 µM). Our work suggests that these 7 drugs could enter into further in vivo studies and clinical investigations for COVID-19 treatment., (© 2020. CPS and SIMM.)

Multicenter surveillance of antimicrobial susceptibility was performed for 235 vancomycin-resistant Enterococcus faecium (VREfm) isolates from 18 Taiwanese hospitals. The minimum inhibitory concentrations (MICs) of eravacycline, omadacycline, lipoglycopeptides, and other comparator antibiotics were determined using the broth microdilution method. Nearly all isolates of VREfm were not susceptible to teicoplanin, dalbavancin, and telavancin, with susceptibility rates of 0.5%, 1.7% and 0.5%, respectively. Tigecycline and eravacycline were active against 93.2% and 89.7% of the VREfm isolates, respectively. Moreover, the susceptibility rates of quinupristin/dalfopristin, tedizolid, and linezolid were 59.1%, 84.2%, and 77.4%, respectively. Additionally, 94% of the VREfm isolates were classified as susceptible to daptomycin, and the MICs of omadacycline required to inhibit VREfm growth by 50% and 90% were 0.12 and 0.5 mg/L, respectively. Susceptibility rates of VREfm isolates to synthetic tetracyclines and daptomycin were slightly lower and to oxazolidinone-class antibiotics were much lower in Taiwan than those in other parts of the world. Continuous monitoring of VREfm resistance to novel antibiotics, including synthetic tetracyclines, oxazolidinone-class antibiotics, and daptomycin, is needed in Taiwan., (Copyright © 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

The occurrence and characterization of carbapenemase-producing Enterobacteriaceae from companion animals in Guangzhou, China, are investigated. Six isolates (2.3%, 6/257) were positive for bla NDM-5 , that is, one Enterobacter cloacae , one Citrobacter freundii , and four Escherichia coli . Three E. coli isolates obtained from the same animal hospital were ST410 and showed identical pulse field gel electrophoresis pattern, resistance profiles, and resistance genes. bla NDM-5 was located on IncX3 ( n  = 5) and IncK2 ( n  = 1) plasmid, respectively. The presence of carbapenemase-producing Enterobacteriaceae among companion animals needs continued surveillance.

Background: World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP)., Methods: AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort., Results: By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1-2) and 33.1% as serious (Grade 3-5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75-169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually., Conclusions: Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

Background: In recent years, intraoperative radiotherapy (IORT) has been increasingly used for the treatment of rectal cancer. However, the efficacy and safety of IORT for the treatment of rectal cancer are still controversial., Aim: To evaluate the value of IORT for patients with rectal cancer., Methods: We searched PubMed, Embase, Cochrane Library, Web of Science databases, and conference abstracts and included randomized controlled trials and observational studies on IORT vs non-IORT for rectal cancer. Dichotomous variables were evaluated by odds ratio (OR) and 95% confidence interval (CI), hazard ratio (HR) and 95%CI was used as a summary statistic of survival outcomes. Statistical analyses were performed using Stata V.15.0 and Review Manager 5.3 software., Results: In this study, 3 randomized controlled studies and 12 observational studies were included with a total of 1460 patients, who are mainly residents of Europe, the United States, and Asia. Our results did not show significant differences in 5-year overall survival (HR = 0.80, 95%CI = 0.60-1.06; P = 0.126); 5-year disease-free survival (HR = 0.94, 95%CI = 0.73-1.22; P = 0.650); abscess (OR = 1.10, 95%CI = 0.67-1.80; P = 0.713), fistulae (OR = 0.79, 95%CI = 0.33-1.89; P = 0.600); wound complication (OR = 1.21, 95%CI = 0.62-2.36; P = 0.575); anastomotic leakage (OR = 1.09, 95%CI = 0.59-2.02; P = 0.775); and neurogenic bladder dysfunction (OR = 0.69, 95%CI = 0.31-1.55; P = 0.369). However, the meta-analysis of 5-year local control was significantly different (OR = 3.07, 95%CI = 1.66-5.66; P = 0.000)., Conclusion: The advantage of IORT is mainly reflected in 5-year local control, but it is not statistically significant for 5-year overall survival, 5-year disease-free survival, and complications., Competing Interests: Conflict-of-interest statement: No conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

A multicenter collection of bacteremic isolates of Escherichia coli ( n = 423), Klebsiella pneumoniae ( n = 372), Pseudomonas aeruginosa ( n = 300), and Acinetobacter baumannii complex ( n = 199) was analyzed for susceptibility. Xpert Carba-R assay and sequencing for mcr genes were performed for carbapenem- or colistin-resistant isolates. Nineteen (67.8%) carbapenem-resistant K. pneumoniae ( n = 28) and one (20%) carbapenem-resistant E. coli ( n  = 5) isolate harbored bla KPC ( n = 17), bla OXA-48 ( n  = 2), and bla VIM ( n = 1) genes., (Copyright © 2020 American Society for Microbiology.)

Since the outbreak of novel coronavirus pneumonia (COVID-19) in December 2019, more than 2,500,000 people worldwide have been diagnosed with SARS-CoV-2 as of April 22. In response to this epidemic, China has issued seven trial versions of diagnosis and treatment protocol for COVID-19. According to the information that we have collected so far, this article provides an overview of potential therapeutic drugs and compounds with much attention, including favipiravir and hydroxychloroquine, as well as traditional Chinese medicine, which have been reported with good clinical treatment effects. Moreover, with further understanding of SARS-CoV-2 virus, new drugs targeting specific SARS-CoV-2 viral components arise and investigations on these novel anti-SARS-CoV-2 agents are also reviewed.

Background: Patients with heterotaxy syndrome (HS), commonly associated with hyposplenism and complex congenital heart disease (CCHD), require multiple-stage single ventricle type operation for long-term survival. Although a higher risk of community-acquired sepsis and mortality rate was reported in CCHD with HS compared with those without HS, whether the risk of postoperative severe bacterial infection (SBI) is higher in patients with HS remains unknown., Method: All patients with CCHD (with and without HS) born between 2001 and 2013 who received cardiac surgery between 2001 and 2018 were enrolled. We analyzed the epidemiology and risk of postoperative SBI in this CCHD cohort., Result: In total, 101 patients of CCHD with HS and 164 patients without HS were enrolled. The mean postoperative nosocomial SBI rate was 0.73/100 patient-days in patients with HS and 0.56/100 patient-days in patients without HS (P = 0.13). Multivariate Cox regression analysis demonstrated that the most critical risk factor for postoperative SBI was postoperative intubation >14 days. Preoperative risk factors, including a nonstandard surgical procedure and multiple surgeries, but not HS, were associated with an increased risk of postoperative nosocomial SBI. The pathogens of infection were also similar between these 2 groups., Conclusion: Although commonly associated with hyposplenism, patients with HS have similar postoperative SBI risk and pathogens as those with CCHD alone.

Background: Nationwide newborn screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency has been implemented in Taiwan since 1987 and the G6PD enzyme activity levels were applied for diagnosis confirmation. As the reference value of G6PD enzyme activity was not available for infants aged 7-90 days, this study was performed to determine the enzyme level in different genotypes., Methods: Between January 1, 2016 and June 30, 2017, 410 term infants aged 7-90 days old visiting National Taiwan University Hospital Hsinchu branch were enrolled. The comparisons of G6PD enzyme activities among genotype groups were performed., Results: G6PD enzyme activity was negatively correlated with age (R = -0.212, p = 0.01). For infants under 30 days of age, the G6PD enzyme activity levels were 1.4 ± 0.9 U/g Hb in hemizygotes (n = 76), 6.5 ± 2.0 U/g Hb in heterozygotes (n = 47), and 13.6 ± 3.7 U/g Hb in those without G6PD mutations (n = 70). Among infants more than 30 days old, G6PD enzyme activity levels were 0.9 ± 0.5 U/g Hb in hemizygotes (n = 46), 6.0 ± 2.7 U/g Hb in heterozygotes (n = 23), and 11.7 ± 3.4 U/g Hb in those without G6PD mutations (n = 148). G6PD levels differed significantly among the groups defined by genotypes., Conclusion: We determined G6PD enzyme activity levels in infants aged between 7 and 90 days in Taiwan. Completing the reference data and determining the cutoff values for different G6PD deficiency disease statuses will help pediatricians to make accurate diagnoses., (Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Multicentre surveillance of antimicrobial susceptibility of clinically important Gram-negative bacteria (GNB) from 16 Taiwanese hospitals was performed. Escherichia coli (n = 398), Klebsiella pneumoniae (n = 346), Pseudomonas aeruginosa (n = 252) and Acinetobacter baumannii complex (ABC) (n = 188) bloodstream isolates, non-typhoidal Salmonella (n = 230) and Shigella flexneri (n = 18) from various sources were collected. Antimicrobial MICs were determined using broth microdilution. Genes encoding K. pneumoniae carbapenemases (KPCs), New Delhi metallo-β-lactamases (NDMs), Verona integron-encoded metallo-β-lactamase (VIM), OXA-48-like carbapenemase (OXA-48) as well as mcr-1-5 genes were detected by molecular methods. Rates of carbapenem non-susceptibility were 2.8%, 9.0%, 0.4%, 0%, 10.3% and 48.8% for E. coli, K. pneumoniae, Salmonella, Shigella, P. aeruginosa and ABC, respectively. For carbapenemases, one (0.3%) E. coli harboured bla NDM-1 . Fifteen (4.3%), two (0.6%) and two (0.6%) K. pneumoniae contained bla KPC , bla OXA-48 and bla VIM , respectively. Two (0.5%) E. coli and fourteen (4.0%) K. pneumoniae were non-wild-type according to the colistin MIC. Among Enterobacteriaceae with a colistin MIC ≥ 2 mg/L, mcr-1 was detected in one E. coli, two K. pneumoniae and three Salmonella spp. All three mcr-1-positive Salmonella isolates were collected from community-acquired infections; none of the six mcr-1-positive Enterobacteriaceae were carbapenem-resistant. Carbapenem resistance has increased among clinically important GNB, especially among hospital-acquired infections. bla KPC , especially the bla KPC-2 variant, was detected in approximately one-half of the carbapenem-resistant K. pneumoniae isolates in this study. Although resistance rates to colistin remained low among Enterobacteriaceae, the finding of mcr-1 from different species raises concern of potential dissemination., (Copyright © 2019. Published by Elsevier B.V.)

The purpose of this study was to investigate the occurrence of plasmid-mediated colistin resistance gene mcr-1 in Enterobacteriaceae isolates from companion animals in Guangzhou, China. Enterobacteriaceae isolated from 180 samples collected from cats and dogs were screened for mcr-1 by PCR and sequencing. MCR-1-producing isolates were further characterized by multilocus sequence typing and pulsed-field gel electrophoresis (PFGE). Plasmid characterization was performed by conjugation, replicon typing, S1-PFGE, and Southern blot hybridization. Plasmid pHN6DS2 as a representative IncN1-IncHI2/ST3 plasmid from ST93 E. coli was fully sequenced. pHN6DS2-like plasmids were screened by PCR-mapping and sequencing. The mcr-1 gene was detected in 6.25% (8/128) Escherichia coli isolates, of which, five belonged to E. coli ST93 and had identical PFGE patterns, resistance profiles and resistance genes. mcr-1 genes were located on ∼244.4 kb plasmids ( n = 6), ∼70 kb plasmids, and ∼60 kb plasmids, respectively. Among them, five mcr-1 -carrying plasmids were successfully transferred to recipient by conjugation experiments, and were classified as IncN1-IncHI2/ST3 (∼244.4 kb, n = 4, all obtained from E. coli ST93), and IncI2 (∼70 kb, n = 1), respectively. Plasmid pHN6DS2 contained a typical IncHI2-type backbone, with IncN1 segment (Δ repA- Iterons I- gshB -ΔIS 1294 ) inserted into the multiresistance region, and was similar to other mcr-1 -carrying IncHI2/ST3 plasmids from Enterobacteriaceae isolates of various origins in China. The remaining five mcr-1 -bearing plasmids with sizes of ∼244.4 kb were identified to be pHN6DS2-like plasmids. In conclusion, clonal spread of ST93 E. coli isolates was occurred in companion animals in Guangzhou, China.

Sophorae Flavescentis Radix (Sophora flavescens Ait., SFR) and Sophorae Tonkinensis Radix et Rhizoma (S. tonkinensis Gapnep., STR) are two commonly used traditional Chinese medicines from Sophora (Leguminosae) plants, which are believed to possess similar bioactive components with entirely different clinical applications. In order to find out the characteristic chemical constituents potentially leading to the unique medicinal properties claimed for each of the two closely related TCMs, an HPLC fingerprint method was developed for analyses of the alkaloid and flavonoid constituents of SFR and STR, respectively, which were further evaluated and compared through similarity calculation and hierarchical clustering analysis (HCA). The results from the present study showed that the alkaloid fingerprints of the two herbs were similar, with many components co-existing in both drugs and various batches of samples from different species being mixed together in the HCA dendrogram. However, their flavonoid constituents were totally different with specific fingerprints being yielded for each herb, and further HCA analysis showed that the tested samples could almost be clearly divided into two groups based on their origins of species. The results from the present study indicated that the flavonoid constituents could serve as the differentially diagnostic constituents of SFR and STR and might potentially attributed to their distinct therapeutic effects., (Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Objectives: We investigated the in vitro antimicrobial susceptibilities of clinically important Gram-negative bacteria (GNB) from 16 major teaching hospitals in Taiwan in 2017., Materials and Methods: Escherichia coli (n=686) and Klebsiella pneumoniae bloodstream isolates (n=673), non-typhoid Salmonella (NTS; n=221) from various sources, Shigella species (n=21) from fecal samples, and Neisseria gonorrhoeae (n=129) from the genitourinary tract were collected. Antibiotic minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. Alleles encoding K. pneumoniae carbapenemases (KPCs), New Delhi metallo-β-lactamases (NDMs), Verona integron-encoded metallo-β-lactamase, imipenemase, OXA-48-like , and mcr -1-5 genes were detected by molecular methods in Enterobacteriaceae isolates., Results: Five (0.7%) E. coli isolates harbored mcr -1 alleles. Twenty-four (3.6%), seven (1.0%), four (0.6%), and one (0.15%) K. pneumoniae isolates contained bla KPC , bla OXA-48-like , mcr -1, and bla NDM , respectively. Three (1.4%) NTS and no Shigella isolates harbored mcr -1 genes. Seventy-one (10.5%) K. pneumoniae isolates displayed non-susceptibility (NS) to carbapenem agent(s). Phenotypically extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae isolates showed significantly higher rates of ertapenem, tigecycline, and ceftolozane-tazobactam (CLZ- TAZ) NS (40.2%, 16.3%, and 71%-80%, respectively) than E. coli isolates exhibiting ESBL phenotypes (5.4%, 0.7%, and 18%-28%, respectively). All phenotypically ESBL-producing E. coli isolates were ceftazidime-avibactam (CAZ-AVB) susceptible. Two (8.3%) KPC-producing K. pneumoniae isolates showed CAZ-AVB NS. Hospital-acquired K. pneumoniae isolates were significantly less susceptible to ertapenem and CLZ-TAZ than hospital-acquired E. coli isolates., Conclusion: Third-generation cephalosporins remain the optimal choice for treating NTS, Shigella , and gonococcal infections in Taiwan. Hospital-acquired and phenotypically ESBL-producing K. pneumoniae are a heavy resistance burden in Taiwan., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease (IBD) characterized by complicated and relapsing inflammation in the gastrointestinal tract. SM934 is a water-soluble artemisinin analogue that shows anti-inflammatory and immuno-regulatory effects. In this study, we investigated the effects of SM934 on UC both in vivo and in vitro. A mouse model of colitis was established in mice by oral administration of 5% dextran sulfate sodium (DSS). SM934 (3, 10 mg/kg per day, ig) was administered to the mice for 10 days. After the mice were sacrificed, colons, spleens and mesenteric lymph nodes (MLNs) were collected for analyses. We showed that SM934 administration restored DSS-induced body weight loss, colon shortening, injury and inflammation scores. Furthermore, SM934 administration significantly decreased the disease activity index (DAI), histopathological scores, and myeloperoxidase (MPO) activities in colonic tissues. Moreover, SM934 administration dose-dependently decreased the mRNA and protein levels of DSS-induced pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), and the percentage of macrophages and neutrophils in colon tissues. The effects of SM934 on LPS-stimulated RAW 264.7 cells and THP-1-derived macrophages were examined in vitro. Treatment with SM934 (0.8, 8, 80 μmol/L) dose-dependently decreased the production of pro-inflammatory mediators in LPS-stimulated RAW264.7 cells and THP-1-derived macrophages via inhibiting activation of the NF-κB signaling. Our results reveal the protective effects of SM934 on DSS-induced colitis can be attributed to its suppressing effects on neutrophils and macrophages and its inhibitory role in the NF-κB signaling, suggests that SM934 might be a potential effective drug for ulcerative colitis.

Background: This study aimed to analyze the stage-situation depression and anxiety as well as independent influential factors in patients with postsurgical gastroparesis syndrome (PGS) and to provide dependent indications for treatment., Patients and Methods: The self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used to test the depression and anxiety of 53 patients with PGS, who were treated in the Department of Gastroenterological Surgery of Gansu Provincial Hospital from January 2012 to October 2016. A comparison between the SDS or SAS scores of patients with PGS and without PGS was undertaken; then, we retrospectively analyzed the factors influencing depression and anxiety in PGS patients., Results: The patients with PGS' mean scores of depression and anxiety were 49.92±11.37 and 50.91±6.57, respectively, which were higher than that of patients without PGS in the Chinese population ( P <0.05). The results of multivariate logistic regression analysis indicated that the independent influential factors of depression and anxiety in patients with PGS included course of disease, pancreatic juice leakage, preoperative outflow tract obstruction, postoperative abdominal infection, and anastomotic complication ( P <0.05). Patients with a disease course longer than 30 days; with pancreatic juice leakage; and who suffered from preoperative outflow tract obstruction, postoperative abdominal infection, and anastomotic complication had higher ratios of depression and anxiety., Conclusion: Depression and anxiety are clearly evident in patients with PGS, and we should pay attention to this phenomenon and provide appropriate treatment., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Parkinson's disease (PD) is a complex and heterogeneous neurological condition characterised mainly by bradykinesia, resting tremor, rigidity and postural instability, symptoms that together comprise the parkinsonian syndrome. Non-motor symptoms preceding and following clinical onset are also helpful diagnostic markers revealing a widespread and progressive pathology. Many other neurological conditions also include parkinsonism as primary or secondary symptom, confounding their diagnosis and treatment. Although overall disease course and end-stage pathological examination single out these conditions, the significant overlaps suggest that they are part of a continuous disease spectrum. Recent genetic discoveries support this idea because mutations in a few genes (α-synuclein, LRRK2 , tau) can cause partially overlapping pathologies. Additionally, mutations in causative genes and environmental toxins identify protein homeostasis and the mitochondria as key mediators of degeneration of dopaminergic circuits in the basal ganglia. The evolving mechanistic insight into the pathophysiology of PD and related conditions will contribute to the development of targeted and effective symptomatic treatments into disease-modifying therapies that will reduce the burden of these dreadful conditions., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The aim of the study was to investigate the efficacy of homemade tolcapone in treatment of patients with Parkinson's disease (PD). Eighty patients with PD were subjected to randomized, double-blind, placebo-controlled and parallel-group study. PD patients were randomly divided into the tolcapone treatment group (41 cases) and placebo group (39 cases). Each patient received 1 pill of tolcapone or placebo, 3 times per day for 26 weeks. Efficacy was evaluated using the internationally used unified Parkinson's disease rating scale (UPDRS) scoring system for PD symptoms. After the treatment for 26 weeks, the cognitive function, tremor, muscle stiffness, voluntary movement and autonomic nerve symptoms were compared between the two groups using UPDRS scores. Compared with the placebo group, cognitive function, muscle stiffness and voluntary movement reduction were significantly improved in patients of the tolcapone group (P<0.05). However, no significant differences in UPDRS scores of autonomic nerve symptoms and tremor were found between two groups after treatment (P>0.05). Tolcapone, a catechol- O -methyl transferase (COMT) inhibitor, can improve the motor function of patients with PD, especially exercise and muscle stiffness. Tolcapone can also improve the cognitive function of patients.

Background: Infection is a major complication in pediatric patients with acute lymphoblastic leukemia during chemotherapy. In this study, the infection characteristics were determined and risk factors analyzed based on the Taiwan Pediatric Oncology Group (TPOG) acute lymphoblastic leukemia (ALL) protocol., Procedure: We retrospectively reviewed fever events during chemotherapy in 252 patients treated during two consecutive clinical trials at a single institution between 1997 and 2012. Patients were classified as standard, high, and very high risk by treatment regimen according to the TPOG definitions. We analyzed the characteristics and risk factors for infection., Results: Fever occurred in 219 patients (86.9%) with a mean of 2.74 episodes per person. The fever events comprised 64% febrile neutropenia, 39% clinically documented infections, and 44% microbiologically documented infections. The microbiologically documented infections were mostly noted during the induction phase and increased in very high risk patients (89 vs. 24% and 46% in standard-risk and high-risk patients, respectively). Younger age and higher risk (high-risk and very high risk groups) were risk factors for fever and microbiologic and bloodstream infections. Female gender and obesity were additive risk factors for urinary tract infection (odds ratios = 3.52 and 3.24, P < 0.001 and P = 0.004, respectively)., Conclusions: Infections developed primarily during the induction phase, for which younger age and higher risk by treatment regimen were risk factors. Female gender and obesity were additive risk factors for urinary tract infection., (© 2017 Wiley Periodicals, Inc.)

Opioid analgesics remain the first choice for the treatment of moderate to severe pain, but they are also notorious for their respiratory depression and addictive effects. This study focused on the pharmacology of a novel opioid receptor mixed agonist DPI-125 and attempted to elucidate the relationship between the δ-, μ- and κ-receptor potency ratio and respiratory depression and abuse liability. Five diarylmethylpiperazine compounds (DPI-125, DPI-3290, DPI-130, KUST202 and KUST13T02) were selected for this study. PKA fluorescence redistribution assays in CHO cells individually expressing δ-, μ- or κ-receptors were used to measure the agonist potency. The respiratory safety profiles were estimated in rats by the ratio of ED 50 (pCO 2 increase)/ED 50 (antinociception). The abuse liability of DPI-125 was evaluated with a self-administration model in rhesus monkeys. The observed agonist potencies of DPI-125 for δ-, μ- and κ-opioid receptors were 4.29±0.36, 11.10±3.04, and 16.57±4.14 nmol/L, respectively. The other four compounds were also mixed agonists with varying potencies. DPI-125 exhibited a high respiratory safety profile, clearly related to its high δ-receptor potency. The ratio of the EC 50 potencies for the μ- and δ-receptors was found to be positively correlated with the respiratory safety ratio. DPI-125 has similar potencies for μ- and κ-receptors, which is likely the reason for its reduced abuse potential. Our results demonstrate that the opioid receptor mixed agonist DPI-125 is safer and less addictive than traditional μ-agonist analgesics. These findings suggest that the development of δ>μ∼κ opioid receptor mixed agonists is feasible, and such compounds could represent a promising class of potent analgesics with wider therapeutic windows.

Pulmonary fibrosis, a progressive and lethal lung disease, is a major therapeutic challenge for which new therapeutic strategies are warranted. Schisandrin B (Sch B) and Glycyrrhizic acid (GA) are the principal active ingredients of Schisandra chinensis and Glycyrrhiza glabra respectively, which have been reported to protect against lung injures. The present study was aimed at exploring the combinatorial therapeutic effects on bleomycin-induced pulmonary fibrosis. Lung fibrotic injuries were induced in mice by a single intratracheal instillation of 5mg/kg bleomycin (BLM). Then, these mice were administered with Sch B (100mg/kg) or/and GA (75mg/kg) for 28days. BLM-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, pro-inflammatory cytokine release, and oxidative stress damages in lung tissues were attenuated to a higher degree by combinatorial treatment than by treatment of the individual agents. The expression of TGF-β1 and the phosphorylation of its downstream target, Smad2 were enhanced by BLM, but weakened by Sch B or/and GA. Furthermore, the significant overexpression of NADPH oxidase 4 (NOX4) was observed in BLM-induced pulmonary fibrosis, which was inhibited by Sch B or/and GA. Our study reveals that the synergistic protection by Sch B and GA against BLM-induced pulmonary fibrosis is correlated to its anti-inflammatory, anti-oxidative and anti-fibrotic properties, involving inhibition of TGF-β1/Smad2 signaling pathways and overexpression of NOX4., (Copyright © 2017 Elsevier B.V. All rights reserved.)

BackgroundPneumococcal vaccines, including pneumococcal polysaccharide vaccine (PPV) and pneumococcal conjugated vaccine (PCV), are crucial in preventing invasive pneumococcal diseases. We analyzed the pneumococcal vaccination rate, efficacy, and durability in patients with heterotaxy.MethodsAll patients with heterotaxy and CCHD who were followed up at our institution between 2010 and 2015 were included. Pneumococcal vaccine status and geometric mean concentration (GMC) of serotypes 6B, 14, 19F, and 23F were analyzed. Splenic function was considered abnormal when the percentage of IgM memory B cell was less than 1%.ResultsThe GMCs of the four serotypes did not differ significantly between patients with heterotaxy and those with CCHD; the GMCs were also not affected by abnormal splenic function. Most patients had GMCs >0.35 μg/ml (protection level) 4-5 years after either PPV or PCV injection; however, it may decay gradually in some serotypes. In addition, 21.4% of 42 patients with heterotaxy did not receive pneumococcal vaccine, and none completely adhered to the vaccine guidelines.ConclusionsVaccine efficacy was acceptable, even in patients with abnormal splenic function. In some patients, the durability of PPV and PCV decreased with time, highlighting the importance of booster doses. Vaccination rate in patients with heterotaxy is unsatisfactory.

Background: Influenza virus infection is a major threat to human health. Small interfering RNA (siRNA) is a promising approach for the prevention and treatment of viral infections. In this study, we constructed a series of DNA vector-based short hairpin RNAs (shRNAs) that target various genes of the influenza A virus using the polymerase III U6-RNA promoter to prevent influenza virus infection in vitro and in a mouse model., Results: Three sets of DNA vector-based shRNA, two targeting genes encoding the polymerase acidic protein (PA) and one targeting polymerase basic protein 2 (PB2), efficiently inhibited the replication of influenza virus A/WSN/33(H1N1) in vitro. We also successfully prevented influenza virus A/WSN/33(H1N1) infection in a C57BL/6 mouse model by intratracheal delivery of anti-PB2 shRNA., Conclusions: Our findings suggest that the PB2-targeting shRNA plasmid showed potential for use as an RNAi-based therapeutic for influenza virus infection.

Contact tracing and seroepidemiologic studies were done after a premature baby contracted pertussis in a children's hospital. No infection source was confirmed. Four (3.5%) healthcare providers were positive for anti-pertussis IgM, while only 23% (26/113) were positive for IgG in a following survey. Pertussis vaccination for healthcare providers is needed.

Objective: To observe the influence of electroacupuncture stimulation (EA) of "Neiguan" (PC 6)/"Lieque" (LU 7) on ST segment of electrocardiogram (ECG) and the expression of myocardiac chloride channel (CLC)-2 and calcium (Ca 2+ )-activated chloride channel accessory (CLCA) proteins in acute myocardial ischemia (AMI) mice, so as to explore its mechanisms underlying improvement of AMI., Methods: Thirty ASIC 3 -/- knock out mice were randomly divided into control, AMI model, EA-Neiguan (PC 6), EA-Lieque (LU 7) and EA-non-acupoint groups. The AMI model was induced by multiple subcuta-neous injection of isoprenaline (ISO, 0.5 g/L, 20 mg/kg). EA was applied to bilateral PC 6, LU 7, or non-acupoint[the mid-point between "Tianshu" (ST 25) and "Shenque" (CV 8)] for 20 min, once daily for 7 days. The ST segment of ECG of the standard Ⅱlimb-lead was recorded using a PowerLab data acquisition device, the change of myocardial histology observed by using microscope after HE staining, the activity of serum superoxide dismutase (SOD) detected using Colorimetric method, and the expression of CLC-2 and CLCA proteins of the left ventricle myocardium detected by Western blot., Results: Outcomes of HE staining showed that the ischemic injury (sarcoplasm swelling and necrosis, etc.) of the left ventrical myocardial tissue after mo-deling was relatively milder in the EA-PC 6 group, not in the EA-non-acupoint group. The SOD activity was significantly lower in the model group than in the control group ( P <0.01), and obviously increased in the EA-PC 6 group( P <0.01), but not in the EA-non-acupoint group ( P >0.05). The expression levels of myocardial CLC-2 and CLCA proteins were significantly up-regulated in the model group compared with the control group ( P <0.01) and markedly down-regulated in the EA-PC 6 group (not in the EA-non-acupoint group) in comparison with the model group( P <0.01), suggesting a specificity of effects of EA-PC 6 in improving myocardial injury and down-regulating CLC-2 and CLCA protein expression., Conclusions: EA of "Neiguan" (PC 6) can effectively suppress the increase of expression of CLC-2 and CLCA proteins in the left ventricle myocardium, which may contribute to its effect in relieving myocardial injury in mice.

Objective: To compare the risk of respiratory syncytial virus (RSV)-associated hospitalization and analyze the epidemiology of RSV infection in patients with cyanotic and acyanotic congenital heart disease (CHD), we analyzed the nationwide health insurance database from 2005-2010., Study Design: This study included 1050 patients with cyanotic CHD and 7077 patients with acyanotic CHD. Patients with acyanotic CHD were further classified into hemodynamically significant (hs)-acyanotic and non-hs-acyanotic groups according to whether they underwent surgery or took at least 2 anticongestive medications., Results: RSV-associated hospitalization was higher in the cyanotic group than in hs-acyanotic and non-hs-acyanotic groups both before 1 year of age (4.8% vs 2.1% vs 1.5%, P < .001) and between 1 and 2 years of age (0.9% vs 0.56% vs 0.14%, P = .003). The hospitalization duration, intensive care, ventilator support prevalence, hospitalization cost, and mortality rate were significantly higher in the cyanotic group than in the other 2 groups. Logistic regression revealed that cyanotic CHD was the most significant risk factor for the ventilator support and RSV-associated mortality. In both patients with cyanotic and acyanotic CHD, RSV-associated hospitalization rate was higher in patients aged younger than 1 year and in spring and autumn in Taiwan, a subtropical country., Conclusions: The results show that patients with cyanotic CHD have a higher risk of severe RSV infection than do those with acyanotic CHD. RSV prophylaxis is more important and may reduce costs more for patients with cyanotic CHD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Patients with heterotaxy syndrome, commonly associated with complex congenital heart disease (CHD), exhibit a higher risk of severe bacterial infection (SBI). We sought to define the change of a novel immunologic marker, the immunoglobulin M (IgM) memory B-cell percentage, and its association with SBI., Methods: We enrolled 46 (M/F 29/17) heterotaxy syndrome patients (42 right atrial isomerism (RAI) and 4 left atrial isomerism (LAI)) aged > 1 y during the period 2010-2012 in a tertiary care center. We analyzed IgM(+)CD27(+) memory B-cell percentages. Patients with simple and complex CHD served as controls., Results: The mean IgM memory B-cell percentages were the lowest in the heterotaxy syndrome group, compared with those in complex and simple CHD groups (1.8 ± 2.1 vs. 3.9 ± 3.2 vs. 5.1 ± 4.7, P < 0.001). In the heterotaxy syndrome group, 41.3% had low IgM memory B-cell percentages (<1% of B cells). Seven had a history of community-acquired SBI and 85.7% of these had low IgM memory B-cell percentages, which was the only significant factors related to community-acquired SBI (P = 0.028)., Conclusion: The memory B cell and IgM memory B-cell percentages are low in patients with heterotaxy syndrome, and the presence of IgM memory B-cell percentage < 1% correlates with community-acquired SBI.

During the hepatitis B virus (HBV) life cycle, nucleocapsid assembly is essential for HBV replication. Both RNA reverse transcription and DNA replication occur within the HBV nucleocapsid. HBV nucleocapsid is consisted of core protein (HBcAg), whose carboxy-terminal domain (CTD) contains an Arg-rich domain (ARD). The ARD of HBcAg does contribute to the encapsidation of pregenomic RNA (pgRNA). Previously, we reported a small-molecule, NZ-4, which dramatically reduced the HBV DNA level in an in vitro cell setting. Here, we explore the possible mechanisms by which NZ-4 inhibits HBV function. As an HBV inhibitor, NZ-4 leads to the formation of genome-free capsids, including a new population of capsid that runs faster on agarose gels. NZ-4's activity was dependent on the presence of the ARD I, containing at least one positively charged amino acid. NZ-4 might provide a new option for further development of HBV therapeutics for the treatment of chronic hepatitis B., (Copyright © 2015. Published by Elsevier B.V.)

Background: Central line-associated bloodstream infection (CLABSI) is a serious complication in hematology-oncology patients. This study aimed to analyze the prevalence of CLABSI and the effectiveness of antimicrobial lock therapy (ALT) in pediatric patients., Methods: BSIs of all pediatric hematology-oncology patients admitted to a children's hospital between January 2009 and December 2013 were reviewed. The United States National Healthcare Safety Network and Infectious Diseases Society of America guidelines were used to define CLABSI and catheter-related BSI (CRBSI). The incidence, laboratory and microbiology characteristics, poor outcome, and effectiveness of ALT were analyzed., Results: There were 246 cases of CLABSI in 146 patients (mean age, 10.0 years), including 66 (26.8%) cases of CRBSI. The incidence of CLABSI was 4.49/1000 catheter-days, and the infection was responsible for 32.9% of the complications these patients developed and 9.3% of contributable mortality. Patients with acute myeloid leukemia had the highest infection density (5.36/1000 patient-days). Enterobacteriaceae (40.2%) and coagulase-negative staphylococci (CoNS; 20.7%) were the predominant pathogens. In multivariate analysis, older age, male sex, elevated C-reactive protein, acute lymphoblastic leukemia, and candidemia were associated with poor outcome. The success rate of ALT was 58.6% (17/29) for the treatment of CoNS and 78.3% (29/37) for Enterobacteriaceae infections. Patients with candidemia (n = 18) had the highest mortality (33.4%) and catheter removal rate (66.7%). Chlorhexidine as the disinfectant decreased the 1-year CLABSI rate from 13.7/1000 to 8.4/1000 catheter-days (p = 0.02)., Conclusion: CoNS and Enterobacteriaceae are the predominant pathogens in CLABSI among pediatric hematology-oncology patients. ALT is effective and showed no significant side effect. New disinfection practice and infection control measures can decrease CLABSI., (Copyright © 2014. Published by Elsevier B.V.)

In this study, the leaf anatomical characteristics and transpiration rate of one-year-old seedlings from three study areas including Qingyuan of Zhejiang Province, Dongkou and Jingzhou of Hunan Province were investigated using a pot planting experiment in which relative soil water content was kept as 75%-80% (control), 55%-60% (mild drought stress), 45%-50% (moderate drought stress), 30%-35% (severe drought stress), respectively. The results showed that drought stress significantly reduced the total thickness of the seedling leaves, the thickness of their upper and lower epidermis and the thickness of palisade tissue. The ratio of the palisade tissue to spongy tissue, stomatal length and width also decreased significantly, while the stomatal density increased significantly as the drought stress became more intense. The treatments of drought stress had no significant effect on the thickness of the main veins of the leaves although their xylem thickness varied depending on the seedlings from the different study sites. The change of leaf structure caused the change of physiological function. As drought stress was intensified, the transpiration rate of C. gilva seedlings decreased significantly. The ratio of the palisade tissue to spongy tissue, the thickness of the lower epidermis and stomatal density of the seedlings from Dongkou of Hunan Province were significantly greater, while the transpiration rate was significantly lower than those from other two study sites for all the drought stress treatments, implying that the C. gilva seedlings from Dongkou of Hunan Province had a stronger drought-resistance ability.

Here we first identified a novel pyridazinone derivative, compound 3711, as a nonnucleosidic hepatitis B virus (HBV) inhibitor in a cell model system. 3711 decreased extracellular HBV DNA levels by 50% (50% inhibitory concentration [IC50]) at 1.5 ± 0.2 μM and intracellular DNA levels at 1.9 ± 0.1 μM, which demonstrated antiviral activity at levels far below those associated with toxicity. Both the 3TC/ETV dually resistant L180M/M204I mutant and the adefovir (ADV)-resistant A181T/N236T mutant were as susceptible to 3711 as wild-type HBV. 3711 treatment induced the formation of genome-free capsids, a portion of which migrated faster on 1.8% native agarose gel. The induced genome-free capsids sedimented more slowly in isopycnic CsCl gradient centrifugation without significant morphological changes. 3711 treatment decreased levels of HBV DNA contained in both secreted enveloped virion and naked virus particles in supernatant. 3711 could interfere with capsid formation of the core protein (Cp) assembly domain. A Cp V124W mutant, which strengthens capsid interdimer interactions, recapitulated the effect of 3711 on capsid assembly. Pyridazinone derivative 3711, a novel chemical entity and HBV inhibitor, may provide a new opportunity to combat chronic HBV infection., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Objective: To investigate the etiologies and antibiotic susceptibility of community-acquired bacteremia in infants in a medical center in northern Taiwan., Methods: We conducted a retrospective analysis of all blood cultures from infants in the National Taiwan University Hospital from 2002 to 2011 to find community-acquired bacteremia. Common pathogens, antibiotic resistance, and outcome were analyzed., Results: During the study period, 25,628 blood cultures were collected, and 3.4% of the cultures were positive, of which 15.9% were categorized as community-acquired bacteremia. In the age group of 0-6-days, the leading causative organisms were group B streptococcus (41.7%) and Escherichia coli (30.6%). In the 7-90-days and 4-6-months groups, the most common pathogens were E. coli (44.1%, 45.5%, respectively) and group B streptococcus (32.4%, 13.6%, respectively). For infants aged 7-12 months, the most common pathogens were Salmonella species (51.1%) and E. coli (12.8%). The overall mortality rate of community-acquired bacteremia was 6%. Urinary tract infection was the concomitant diagnosis among 52.4% of infants with E. coli bacteremia. Meningitis was found in 33.3% of infants with group B streptococcus bacteremia. Listeria monocytogenes bacteremia was identified in three infants, one of whom had meningitis. Penicillin resistance was found in 4% of group B streptococcus and ampicillin resistance in 71% of E. coli., Conclusion: Our study provides updated etiological data on community-acquired bacteremia in infants in northern Taiwan. Group B streptococcus and E. coli remained the leading pathogens in infants aged 6 months or younger and Salmonella species for those older than 6 months., (Copyright © 2013. Published by Elsevier B.V.)

This study aims to explore the safety and efficacy of intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) in elderly (≥80 years old) acute ischemic stroke (AIS) patients. The clinical data of patients who were treated in Tianjin Huanhu Hospital from June 2012 to November 2013 were retrospectively analyzed; among them, 404 patients had received IVT with rt-PA and 200 patients had not received IVT. Among ≥80-year-old patients, 204 had received IVT and 200 had not. And the 404 patients who had received IVT were divided into two subgroups: elderly (≥80 years of age; n = 204) and controls (<80 years old; n = 200). The incidence of intracranial hemorrhage (ICH) and symptomatic intracranial hemorrhage, case fatality rate, and other prognostic indicators were compared. Among all ≥80-year-old patients, the IVT subgroup had significantly superior good outcome rates than the non-IVT subgroup at 24-h and 3-month along with significantly lower case fatality rate. But for the patients those who had received IVT, the incidence of ICH and the 7-day case fatality rate were not significantly increased in both the elderly and control subgroups. The 24-h and 3-month good outcome rates were not significantly different between these two subgroups as well. IVT with rt-PA is a safe and effective treatment for ≥80-year-old AIS patients.