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Kuo-Sheng Liu,1 Ching-Wei Kao,2 Yuan-Yun Tseng,3 Shih-Kuang Chen,4 Yu-Ting Lin,4 Chia-Jung Lu,4,5 Shih-Jung Liu4,5 1Department of Thoracic and Cardiovascular Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Anesthesiology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 3Department of Neurosurgery, New Taipei Municipal Tu-Cheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City, Taiwan; 4Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan; 5Department of Orthopedic Surgery, Bone and Joint Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, TaiwanCorrespondence: Shih-Jung LiuBiomaterials Lab, Mechanical Engineering, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, TaiwanTel +886-3-2118166Fax +886-3-2118558Email shihjung@mail.cgu.edu.twBackground: Postoperative tissue adhesion is a major concern for most surgeons and is a nearly unpreventable complication after abdominal or pelvic surgeries. This study explored the use of sandwich-structured antimicrobial agents, analgesics, and human epidermal growth factor (hEGF)-incorporated anti-adhesive poly(lactic-co-glycolic acid) nanofibrous membranes for surgical wounds.Materials and Methods: Electrospinning and co-axial electrospinning techniques were utilized in fabricating the membranes. After spinning, the properties of the prepared membranes were assessed. Additionally, high-performance liquid chromatography and enzyme-linked immunosorbent assays were utilized in assessing the in vitro and in vivo liberation profiles of the pharmaceuticals and the hEGF from the membranes.Results: The measured data suggest that the degradable anti-adhesive membranes discharged high levels of vancomycin/ceftazidime, ketorolac, and hEGF in vitro for more than 30, 24, and 27 days, respectively. The in vivo assessment in a rat laparotomy model indicated no adhesion in the peritoneal cavity at 14 days post-operation, demonstrating the anti-adhesive capability of the sandwich-structured nanofibrous membranes. The nanofibers also released effective levels of vancomycin, ceftazidime, and ketorolac for more than 28 days in vivo. Histological examination revealed no adverse effects.Conclusion: The outcomes of this study implied that the anti-adhesive nanofibers with sustained release of antimicrobial agents, analgesics, and growth factors might offer postoperative pain relief and infection control, as well as promote postoperative healing of surgical wounds.Keywords: nanofibrous anti-adhesive membrane, poly(lactic-co-glycolic acid), extended release, vancomycin, ceftazidime, ketorolac, hEGF

Ching-Wei Kao,1,2 Yuan-Yun Tseng,3,4 Kuo-Sheng Liu,5 Yen-Wei Liu,5 Jin-Chung Chen,6 Hong-Lin He,7 Yi-Chuan Kau,8 Shih-Jung Liu2,91Department of Anesthesiology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan; 3Division of Neurosurgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; 4Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 5Department of Thoracic and Cardiovascular Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Graduate Institute of Biomedical Science, Chang Gung University, Taoyuan, Taiwan; 7Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan; 8Department of Anesthesiology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 9Department of Orthopedic Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, TaiwanBackground: This study exploited sheath-core-structured lidocaine/human EGF (hEGF)-loaded anti-adhesive poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibrous films for surgical wounds via a co-axial electrospinning technique.Materials and methods: After spinning, the properties of the co-axially spun membranes were characterized by scanning electron microscopy, laser-scanning confocal microscopy, Fourier Transform Infrared spectrometry, water contact angle measurements, and tensile tests. Furthermore, a HPLC analysis and an ELISA evaluated the in vitro and in vivo release curves of lidocaine and hEGF from the films.Results: PLGA anti-adhesion nanofibers eluted high levels of lidocaine and hEGF for over 32 and 27 days, respectively, in vitro. The in vivo evaluation of post-surgery recovery in a rat model demonstrated that no adhesion was noticed in tissues at 2 weeks after surgery illustrating the anti-adhesive performance of the sheath-core-structured nanofibers. Nanofibrous films effectively released lidocaine and hEGF for >2 weeks in vivo. In addition, rats implanted with the lidocaine/hEGF nanofibrous membranes exhibited greater activities than the control demonstrating the pain relief efficacy of the films.Conclusion: The empirical outcomes suggested that the anti-adhesive nanofibrous films with extended release of lidocaine and hEGF offer post-operative pain relief and wound healing.Keywords: sheath-core nanofiber, anti-adhesive membrane, sustained elution, lidocaine, hEGF

Cheng-Hung Lee,1 Ming-Jer Hsieh,1 Kuo-Sheng Liu,2,3 Che-Wei Cheng,3 Shang-Hung Chang,1 Shih-Jung Liu,3,4 Chao-Jan Wang,5 Ming-Yi Hsu,5 Kuo-Chun Hung,1 Yung-Hsin Yeh,1 Wei-Jan Chen,1 I-Chang Hsieh,1 Jyuhn-Huarng Juang,6 Ming-Shien Wen1 1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Tao-Yuan, Taiwan; 2Department of Cardiovascular Surgery, Chang Gung Memorial Hospital-Linkou, Tao-Yuan, Taiwan; 3Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 4Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan; 5Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan; 6Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, Tao-Yuan, Taiwan Objective: The current treatment of atherosclerotic coronary heart disease with limus-eluting stents can lead to incomplete endothelialization and substantial impairment of arterial healing relative to treatment with bare-metal stents. The sustained and local delivery of ticagrelor, a reversibly binding P2Y12 receptor inhibitor, using hybrid biodegradable nanofibers/stents, was developed to reduce neointimal formation and endothelial dysfunction.Methods: In this investigation, a solution of ticagrelor, poly(D,L)-lactide-co-glycolide, and hexafluoro isopropanol was electrospun to fabricate ticagrelor-eluting nanofibrous drug-eluting stents. The in vitro and in vivo ticagrelor concentrations were measured using a high-performance liquid chromatography assay. The effectiveness of ticagrelor-eluting stents was examined relative to that of sirolimus-eluting stents. Results: Adequate ticagrelor levels were detected for four weeks in vitro. Less HES5-positive labeling was found near the ticagrelor-eluting stented vessels (0.33±0.12) than close to the sirolimus-eluting stented vessels (0.57±0.15) (p

Yin-Kai Chao,1 Cheng-Hung Lee,2 Kuo-Sheng Liu,1 Yi-Chuan Wang,3 Chih-Wei Wang,4 Shih-Jung Liu3 1Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan; 4Department of Pathology, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan Background: Inadequate intrapleural drug concentrations caused by poor penetration of systemic antibiotics into the pleural cavity is a major cause of treatment failure in empyema. Herein, we describe a novel antibiotic-eluting pigtail catheter coated with electrospun nanofibers used for the sustained release of bactericidal concentrations of penicillin in the pleural space.Methods: Electrospun nanofibers prepared using polylactide-polyglycolide copolymer and penicillin G sodium dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol were used to coat the surface of an Fr6 pigtail catheter. The in vitro patterns of drug release were tested by placing the catheter in phosphate-buffered saline. In vivo studies were performed using rabbits treated with penicillin either intrapleurally (Group 1, 20 mg delivered through the catheter) or systemically (Group 2, intramuscular injection, 10 mg/kg). Penicillin concentrations in the serum and pleural fluid were then measured and compared.Results: In vitro studies revealed a burst release of penicillin (10% of the total dose) occurring in the first 24 hours, followed by a sustained release in the subsequent 30 days. Intrapleural drug levels were significantly higher in Group 1 than in Group 2 (P

Kuo-Sheng Liu,1 Cheng-Hung Lee,2 Yi-Chuan Wang,3 Shih-Jung Liu3 1Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan; 2Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; 3Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan Abstract: This study describes novel biodegradable, drug-eluting nanofiber-loaded vascular prosthetic grafts that provide local and sustained delivery of vancomycin to surrounding tissues. Biodegradable nanofibers were prepared by first dissolving poly(D,L)-lactide-co-glycolide and vancomycin in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution was then electrospun into nanofibers onto the surface of vascular prostheses. The in vitro release rates of the pharmaceutical from the nanofiber-loaded prostheses was characterized using an elution method and a high-performance liquid chromatography assay. Experimental results indicated that the drug-eluting prosthetic grafts released high concentrations of vancomycin in vitro (well above the minimum inhibitory concentration) for more than 30 days. In addition, the in vivo release behavior of the drug-eluting grafts implanted in the subcutaneous pocket of rabbits was also documented. The drug-eluting grafts developed in this work have potential applications in assisting the treatment of vascular prosthesis infection and resisting reinfection when an infected graft is to be exchanged. Keywords: drug-eluting prosthetic graft, vascular prosthesis infection, release characteristics

Electromagnetic shielding fabric (ESF) is a novel electromagnetic shielding product with portability, flexibility, and good mechanical properties. However, the existing ESFs suffer from poor washing fastness of coating and poor comfort performance in terms of hand-feel characteristic. In this study, a core layer-coated yarn (CLCY) was successfully spun using a carboxylic acid-functionalized multi-walled carbon nanotube/polypyrrole/Fe3O4 composite suspension with polyvinyl butyral as an adhesive agent. To better explore the properties, the original fabric and treated fabrics, viz., core layer-coated fabric (CLCF) and surface layer-coated fabric (SLCF), were characterized by several methods. Scanning electron microscopic observations revealed that the coating was on the core layer in CLCF. In addition, the Fourier-transform infrared spectroscopy and X-ray diffraction spectroscopy results revealed that the composition of the coating corresponds with that in the multi-composite suspension. Moreover, the coating of CLCY formed a conductive path with good conductivity in the core layer, but the conductivity of the coating on the surface layer of SLCF deteriorated sharply after washing. Further, compared with the original fabric and SLCF, CLCF has highest breaking strength (after 10 washes), and keeps a relatively good hand-feel characteristic. Finally, the evaluated electromagnetic interference shielding characteristics reveal that the fastness of coating affects the electromagnetic shielding effectiveness, suggesting that the wrapped protection of outside staple fibers in CLCF reduce the loss of coating in the core layer during washing. However, the coating on the surface layer in SLCF could be washed away easily. [ABSTRACT FROM AUTHOR]

Background: A predominate azole-resistant Candida tropicalis clade 4 genotype causing candidemia has been detected in not only Taiwan but also China, Singapore, and Australia. It can also be detected on fruit surfaces. In addition to determining distribution and drug susceptibilities of pathogenic yeasts in environments of intensive care units of 25 hospitals in Taiwan, we would also like to investigate whether the azole-resistant C. tropicalis exists in Taiwan's hospital environment., Methods: The swabs of hospital environments were collected from August to November in 2020 and were cultured for yeasts. The yeasts were identified by rDNA sequence and the antifungal susceptibilities of those isolates were determined by the broth microdilution method., Results: The average yeast-culture rate of hospitals was 9.4% (217/2299). Sinks had the highest yeast-positive culture rate (32.7%), followed by bedside tables (28.9%), floors (26.0%), water-dispenser buttons (23.8%), and TV controller/touch panels (19.0%). Of 262 identified isolates, Candida parapsilosis was the most common species, accounting for 22.1%, followed by Filobasidium uniguttulatum (18.3%), Candida albicans (9.5%), C. tropicalis (8.0%), Candida glabrata (Nakaseomyces glabratus) (6.9%), and 30 other species (35.1%). Of the 21 C. tropicalis isolates from 11 units in 9 hospitals, 15 diploid sequence types (DSTs) were identified. The two DST506 fluconazole-resistant ones belonged to clade 4., Conclusion: We detected not only various pathogenic yeast species but also the predominant clade 4 genotype of azole-resistant C. tropicalis. Our findings highlight and re-emphasize the importance of regular cleaning and disinfection practices., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Crochetage sign is a specific electrocardiographic manifestation of ostium secundum atrial septal defects (ASDs), which is associated with the severity of the left-to-right shunt. Herein, we reported a case of selective his bundle pacing (S-HBP) that eliminated crochetage sign in a patient with ostium secundum ASD., Case Summary: A 77-year-old man was admitted with a 2-year history of chest tightness and shortness of breath. Transthoracic echocardiography revealed an ostium secundum ASD. Twelve-lead electrocardiogram revealed atrial fibrillation with a prolonged relative risk interval, incomplete right bundle branch block, and crochetage sign. The patient was diagnosed with an ostium secundum ASD, atrial fibrillation with a second-degree atrioventricular block, and heart failure. The patient was treated with selective his bundle pacemaker implantation. After the procedure, crochetage sign disappeared during his bundle pacing on the electrocardiogram., Conclusion: S-HBP eliminated crochetage sign on electrocardiogram. Crochetage sign may be a manifestation of a conduction system disorder., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Rotavirus vaccine has not been included in the Hong Kong Government's Childhood Immunisation Programme. This randomised controlled trial examined whether a simple intervention package can increase rotavirus vaccine uptake in Hong Kong children., Methods: Postpartum mothers were recruited from two public hospitals in Hong Kong and randomly allocated into three groups using block randomisation, with block sizes kept unknown to investigators and research staff. Control-subjects received public rotavirus information. Subjects in intervention group 1 additionally received: key rotavirus information with a hyperlink to a webpage showing private clinics providing rotavirus vaccines and guidance on searching the clinics, and vaccination reminders. Subjects in intervention group 2 received the same intervention as group 1, plus tokens to receive free rotavirus vaccines at specific health centres. Rotavirus vaccination status was collected when children were approximately 8 months old. Maternal attitudes towards rotavirus vaccine were assessed at enrolment and at the end of the study. This trial has been registered in the Chinese Clinical Trial Register (Ref.:ChiCTR2000039791)., Findings: From 16 February to 30 July 2021, 788 eligible mothers were recruited and randomly allocated to control group (n = 263), intervention group 1 (n = 263), and intervention group 2 (n = 262). The full intervention package (intervention group 2 relative to control group) increased rotavirus vaccine uptake by 1.7 times (95% confidence interval [CI] = 1.49-1.97) or by 33 percent-points (from 48% to 81% uptake). Provision of key rotavirus information with vaccination reminders (intervention group 1 relative to control group) and removal of financial barrier (intervention group 2 relative to intervention group 1) increased uptake by 1.17 times (95% CI = 0.99-1.38) or 8 percent-points, and by 1.46 times (95% CI = 1.29-1.66) or 25 percent-points, respectively., Interpretation: A multiple-component intervention package, and in particular providing free vaccine, could increase the uptake of rotavirus vaccine in Hong Kong children. The impact of the intervention package was greatest in low-income families, emphasising the importance of removing financial barriers to vaccination to promote equity. Incorporating rotavirus vaccine into the routine CIP could further protect more young children from rotavirus infection and improve equity., Funding: This work was supported by the Health and Medical Research Fund by the Health Bureau, Government of Hong Kong SAR [Ref.: 19180202]., Competing Interests: EASN received travel and accommodation support by meeting organizers to conferences and meetings (MasterClass in Vaccinology in Taipei, Taiwan in November 2023; and 9th Asian Vaccine Conference in Cebu, Philippines in November 2023), and honorarium was paid to The Chinese University of Hong Kong for participation in the MSD organised Asia Pacific Pediatrics Vaccines Regional Group Input Meeting in July 2023., (© 2024 The Author(s).)

Background: The objective was to evaluate the efficacy of introducing less invasive surfactant administration (LISA) for management of preterm neonates with respiratory distress syndrome (RDS)., Methods: This was a retrospective cohort study identifying preterm neonates with RDS born between 2017 and 2022 in a tertiary neonatal unit, where LISA was introduced in January 2020. Time trend analysis comparing cohort of neonates born before (2017-2020) and after LISA introduction (2020-2022) was performed. The primary outcomes were incidence and severity of bronchopulmonary dysplasia (BPD). Multivariable regression models were used to estimate the association between introducing LISA to RDS management and health and safety outcomes., Results: In total, 261 neonates with RDS were included (114 born after LISA was introduced). Neonates receiving invasive surfactant administration had lower gestational age, birth weight, lower Apgar scores, and higher oxygen requirement, compared to those receiving LISA. In the time trend analysis, introduction of LISA was associated with lower incidence of BPD (odds ratio (95% confidence interval) 0.34 (0.16, 0.72)), and lower severity of BPD (0.31 (0.16, 0.59)). Pre- and post-LISA period showed similar treatment safety profiles., Conclusion: Introduction of LISA was associated with improved prognosis in neonates with RDS in Hong Kong., Competing Interests: Declaration of competing interest All authors have disclosed no conflicts of interest., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

C-type lectins play a crucial role as pathogen-recognition receptors for the dengue virus, which is responsible for causing both dengue fever (DF) and dengue hemorrhagic fever (DHF). DHF is a serious illness caused by the dengue virus, which exists in four different serotypes: DEN-1, DEN-2, DEN-3, and DEN-4. We conducted a genetic association study, during a significant DEN-2 outbreak in southern Taiwan, to explore how variations in the neck-region length of L-SIGN (also known as CD209L, CD299, or CLEC4M) impact the severity of dengue infection. PCR genotyping was utilized to identify polymorphisms in variable-number tandem repeats. We constructed L-SIGN variants containing either 7- or 9-tandem repeats and transfected these constructs into K562 and U937 cells, and cytokine and chemokine levels were evaluated using enzyme-linked immunosorbent assays (ELISAs) following DEN-2 virus infection. The L-SIGN allele 9 was observed to correlate with a heightened risk of developing DHF. Subsequent results revealed that the 9-tandem repeat was linked to elevated viral load alongside predominant T-helper 2 (Th2) cell responses (IL-4 and IL-10) in K562 and U937 cells. Transfecting K562 cells in vitro with L-SIGN variants containing 7- and 9-tandem repeats confirmed that the 9-tandem repeat transfectants facilitated a higher dengue viral load accompanied by increased cytokine production (MCP-1, IL-6, and IL-8). Considering the higher prevalence of DHF and an increased frequency of the L-SIGN neck's 9-tandem repeat in the Taiwanese population, individuals with the 9-tandem repeat may necessitate more stringent protection against mosquito bites during dengue outbreaks in Taiwan., Competing Interests: The authors declare no conflicts of interest.

Background: Dexmedetomidine is known to prolong the analgesic duration of spinal anesthesia, but it can be challenging to achieve further extension without opioids. Therefore, this study aimed to investigate a novel analgesic strategy using dexmedetomidine as an adjuvant to spinal-epidural anesthesia for elective cesarean surgery., Methods: The study was a randomized, double-blind, controlled trial conducted at a single center. Sixty parturients who underwent elective cesarean were randomly assigned to either group C or group D. Group D received an intrathecal injection of 12.5 mg ropivacaine and 5 μg dexmedetomidine followed by continuous epidural patient-controlled analgesia (PCA) infusion with a total volume of 100 ml, containing 0.2 % ropivacaine and 0.5 μg/kg dexmedetomidine. Group C received an intrathecal injection of 12.5 mg ropivacaine with an equivalent saline placebo followed by a similar PCA infusion, containing 0.2 % ropivacaine and an equivalent saline placebo., Results: The primary outcome was visual analog scale score on movement at 24 h after surgery. The results showed that the rest and motion pain scores in group D were significantly lower than those in group C at 6 h, 12 h, and 24 h after surgery ( P  < 0.05), with the differences at 24 h were 5.0 (5.0, 5.0)in group D versus 5.0 (5.0, 6.0) in group C ( P  = 0.04). Additionally, the time to the first PCA in group D was significantly longer than that in group C ( P  < 0.05), as well as the time of sensory and motor recovery., Conclusions: Whole-course application of dexmedetomidine as an adjuvant to spinal-epidural anesthesia could effectively extend the analgesic duration of ropivacaine to 24 h following elective cesarean surgery., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Th22 cells are a newly identified subpopulation of CD4 + T lymphocytes distinct from Th1, Th2, and Th17 cells, which secretes mainly interleukin-22 (IL-22), in addition to a variety of other cytokines. The function of Th22 cells in tumors is mainly realized through IL-22, which can activate JAK/STAT and MAPK cell signaling pathways, thereby regulating the anti-tumor immune response of the body. The main function of Th22 cells is to participate in mucosal defense, tissue repair, and wound healing. However, controversial data have shown that overexpression of IL-22 can lead to pathological changes under inflammatory conditions and tumor progression. In this review, we searched the PubMed and Web of Science databases for articles and reviews published before May 6, 2022, using the keywords "Th22 cells, T helper 22 cells, cancer, tumor", and conducted a comprehensive review of the relevant literature. In addition, this article offers an overview of the relevant findings on the function of Th22 cells in tumors published in recent years, along with a more comprehensive analysis of the functions and mechanisms of Th22 cells in tumors. This article will hopefully inspire new future directions in the research on cancer therapy., Competing Interests: None., (AJCR Copyright © 2023.)

The impact of the immune response on the therapeutical efficacy of neoadjuvant chemotherapy for breast cancer remains largely unknown. To characterize the role of regulatory T cells (CD4 + CD25 + CD127 low Treg), T lymphocyte subsets (CD3 + , CD4 + , CD4 + /CD8 + ) and NK cells in neoadjuvant chemotherapy, we investigated the correlation patterns of these immune cell subsets with the progression of breast cancer. A total of 120 breast cancer patients receiving neoadjuvant chemotherapy in Nanjing Maternal and Child Health Hospital from May 2019 to November 2021 were retrospectively collected as the breast cancer group, and 46 healthy women were selected as the control group. The number of regulatory T cells, T lymphocyte subsets and NK cells in the peripheral blood were analyzed by flow cytometry. Compared with the control group, CD3 + , CD4 + , CD4 + /CD8 + ratio and NK cells were significantly decreased in patients with breast cancer ( P < 0.05), while the levels of Treg and CD8 + cells were significantly increased ( P < 0.05). In addition, the status of the immune response among breast cancer patients at different clinical stages was obviously different. In higher tumor stages, the level of CD3 + , CD4 + , CD4 + /CD8 + ratio and NK cell were reduced, while the level of Treg and CD8 + T cells gradually increased. Furthermore, we found a lower percentage of CD3 + , CD4 + , CD4 + /CD8 + and NK cells in association with lymph node metastasis, accompanied by a higher number of CD8 + T cells. Interestingly, after treatment with neoadjuvant chemotherapy, the levels of Tregs, CD3 + , CD4 + and CD4 + /CD8 + ratio of patients were all upregulated compared with the levels before treatment, indicating the recovery of cytotoxic lymphocytes and a consolidation of the immunosuppressive microenvironment at the same time ( P < 0.05 ). Immune dysfunction is commonly observed in breast cancer patients, which is closely associated with tumor progression and lymph node metastasis. Neoadjuvant chemotherapy was found to highly influence the number of T lymphocytes and improve the immune function of T lymphocyte subsets in breast cancer patients. At the same time, as immunosuppressive cells, the proportion of Tregs (CD4 + CD25 + CD127 low Treg) also increased after treatment with neoadjuvant chemotherapy. Our results provide guidance for the development of new combination strategies during neoadjuvant chemotherapy to reverse the immunosuppressive microenvironment and achieve better clinical outcomes., Competing Interests: None., (AJCR Copyright © 2023.)

Pseudorabies (PR) and classical swine fever (CSF) are economically important infectious diseases in pigs. Most pig farms in China are vaccinated against these two diseases. Gene-deleted pseudorabies virus (PRV) can be used to develop promising and economical multivalent live attenuated viral vector vaccines. It has been reported that recombinant PRV can express a truncated E2 protein (1-338 aa), but it has not been reported that recombinant PRV can express a full-length E2 protein. We constructed nine groups of E2 proteins with different expression forms and found that the E2 protein could be expressed in vitro only when the transmembrane region of E2 was removed and the signal peptide was added. Analysis of the transmembrane region of E2 revealed that the high hydrophobicity of the E2 transmembrane region was the main reason for its inability to express. By mutating an amino acid to reduce the hydrophobicity of the transmembrane region, it was found that the full-length mutant of E2 (E2FL-muta3 or E2FL-muta4) could be expressed. The expressed full-length mutant E2 could also localize to the cell membrane. Mice immunized with a PRV vector vaccine expressing E2FL-muta3 or E2FL-muta4 developed specific cellular immunity to the E2 protein and stimulated higher levels of E2 antibody than mice immunized with a PRV vector expressing truncated E2. After immunizing the rabbits, the lethal challenge by PRV-ZJ2013 and the febrile response elicited by CSFV were simultaneously prevented. These results suggest that rPRV-dTK/gE-E2FL-muta4 is a promising bivalent vaccine against CSFV and PRV infections., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Natriuretic peptides, which are produced by the heart, bind to natriuretic peptide receptor A (NPR1 encoded by natriuretic peptide receptor 1 gene) and cause vasodilation and natriuresis. Thus, they serve an important role in regulating blood pressure. In the present study, microinjection of CRISPR associated protein 9/single guide RNA into fertilized C57BL/6N mouse eggs was performed to generate filial generation zero (F0) Npr1 knockout homozygous mice (Npr1 -/- ). F0 mice mated with wild-type (WT) mice to obtain F1 Npr1 knockout heterozygous mice with stable heredity (Npr1 +/- ). F1 self-hybridization was used to expand the population of heterozygous mice (Npr1 +/- ). The present study performed echocardiography to investigate the impact of NPR1 gene knockdown on cardiac function. Compared with those in the WT group (C57BL/6N male mice), the left ventricular ejection fraction, myocardial contractility and renal sodium and potassium excretion and creatinine-clearance rates were decreased, indicating that Npr1 knockdown induced cardiac and renal dysfunction. In addition, expression of serum glucocorticoid-regulated kinase 1 (SGK1) increased significantly compared with that in WT mice. However, glucocorticoids (dexamethasone) upregulated NPR1 and inhibited SGK1 and alleviated cardiac and renal dysfunction caused by Npr1 gene heterozygosity. SGK1 inhibitor GSK650394 ameliorate cardiorenal syndrome by suppressing SGK1. Briefly, glucocorticoids inhibited SGK1 by upregulating NPR1, thereby ameliorating cardiorenal impairment caused by Npr1 gene heterozygosity. The present findings provided novel insight into the understanding of cardiorenal syndrome and suggested that glucocorticoids targeting the NPR1/SGK1 pathway may be a potential therapeutic target to treat cardiorenal syndrome., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Huang et al.)

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 had reported over 676 million cases by March 2023. The main aim of this study is to investigate whether the levels of anti-S and anti-N antibodies could precisely indicate the degree of protection against SARS-CoV-2 and affect the probability or time of contracting COVID-19. In this study, a serosurveillance study was conducted in healthcare workers (HCWs) at a regional hospital in Taiwan to evaluate their antibody levels based on infection and vaccination status. Of 245 HCWs enrolled, all have been vaccinated prior to infection. Of these, 85 participants were infected by SARS-CoV-2, while 160 participants were not infected at the time of blood sample collection. The level of anti-SARS-CoV-2 S antibody was significantly higher in the infected HCWs than in the non-infected participants ( p < 0.001). It is worth noting that the mean duration between the administration of the last dose of the vaccine and the occurrence of SARS-CoV-2 infection was 5.61 ± 2.95 months. Our follow-up survey revealed that the non-infected group had significantly higher levels of antibodies compared to the infected group (all p < 0.001). In conclusion, this study suggests that the level of antibodies could serve as a reflection of the protective efficacy against SARS-CoV-2 infection. It has the implication for vaccine decision-making policies in the future.

There is scarce evidence about the surgeon learning curve of acute type A aortic dissection surgery and whether the optimal procedure number exists when training a cardiovascular surgeon. A total of 704 patients with acute type A aortic dissection surgery performed by 17 junior surgeons who can identify their first career surgery from January 1, 2005, to December 31, 2018, are included. The surgeon experience volume is defined as the cumulative number of acute type A aortic dissection surgery of the surgeon since January 1, 2005. The primary outcome was in-hospital mortality. The possibility of non-linearity and cutoffs for surgeon experience volume level was explored using a restricted cubic spline model. The results revealed that more surgeon experience volume is significantly correlated to a lower in-hospital mortality rate (r = - 0.58, P = 0.010). The RCS model shows for an operator who reaches 25 cumulative volumes of acute type A aortic dissection surgery, the average in-hospital mortality rate of the patients can be below 10%. Furthermore, the longer duration from the 1st to 25th operations of the surgeon is significantly correlated to a higher average in-hospital mortality rate of the patients (r = 0.61, p = 0.045). Acute type A aortic dissection surgery has a prominent learning curve in terms of improving clinical outcomes. The findings suggest fostering high-volume surgeons at high-volume hospitals can achieve optimal clinical outcomes., (© 2023. The Author(s).)

Background: Esophageal cancer (EC) incidence rates overall have declined in recent decades; however, the two main subtypes, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), show divergent secular trends., Methods: Age-adjusted EC incidence rates were calculated using data from the Surveillance Epidemiology and End Results (SEER) 12 Program. We examined secular trends from 1992 to 2019 overall and by age group, sex, race/ethnicity, tumor location, and SEER registry. Joinpoint regression was used to compute annual percent changes (APC) and average annual percent changes (AAPC). We used age-period-cohort models to examine the potential impact of period and birth cohort effects on trends., Results: Between 1992 and 2019, overall EC incidence rates declined by 0.54% annually (95% confidence interval [CI]: -0.75%, -0.33%). While ESCC rates declined linearly throughout the study period (AAPC = -2.85; 95%CI: -3.05%, -2.65%), EAC rates increased by over 5% annually from 1992 to 2000 (APC = 5.17; 95%CI: 3.28%, 7.10%), before stabilizing from 2000 to 2019 (APC = 0.22; 95%CI: -0.16%, 0.60%). Trends in ESCC and EAC varied by age group, sex, and race/ethnicity. Relative to ESCC rates among cohorts born circa 1950, the rates were 81% lower in cohorts born circa 1985 (rate ratio, 0.19; 95%CI: 0.04, 0.96). For EAC, rates have remained stable across successive birth cohorts since 1950., Conclusions: We observed linear declines in EC rates overall and for ESCC across age, sex, and race/ethnicity subgroups, but an inconsistent pattern for EAC. The trends in EAC cohorts born after 1955 were stable and suggest that EAC rates may have peaked in the U.S.

Background: To determine the relationship between hospital surgical volume and mortality risk and valve repair rate in infective endocarditis (IE) surgery., Methods: Using the Taiwan National Health Insurance Research Database, 3873 patients were identified who underwent surgery between 2000 and 2013. The cumulative hospital volume of valve surgery for IE was calculated, and patients were divided into 4 subgroups according to the quartile. Outcomes were mortality and valve repair rate and the cut point of referral excellence., Results: The distribution of IE surgery has been shifting to lower-volume hospitals over the years. The global disease severity (Charlson Comorbidity Index score) of patients was greater in the lowest-volume hospital than in the highest-volume hospital (2.4 vs 2.0). The crude in-hospital mortality rate was 15.8% and 9.4% for the lowest- and highest-volume hospitals, respectively, with a significant difference (adjusted odds ratio: 1.86, 95% confidence interval: 1.22-2.85) after adjustment of baseline characteristics including the Charlson Comorbidity Index score. The mitral valve repair rate increased with the increase in cumulative volume. During a mean follow-up period of 4.4 years, 324 (41.9%) and 254 (30.9%) patients died in the lowest- and highest-volume subgroups, respectively, and the difference was significant (adjusted hazard ratio: 1.59, 95% confidence interval: 1.21-2.10)., Conclusions: A higher cumulative volume of IE surgery is associated with a lower risk of mortality and a higher likelihood of successful mitral valve repair. Therefore, interfacility transfer to a high-volume hospital may improve outcomes of IE surgery., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Nowadays, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), whose infectivity is awfully strong, has been a major global threat to the public health. Since lung is the major target of SARS-CoV-2, the infection can lead to respiratory distress syndrome (RDS), multiple organ failure (MOF), and even death. The studies on viral structure and infection mechanism have found that angiotensin-converting enzyme 2 (ACE2), a pivotal enzyme affecting the organ-targeting in the RAS system, is the receptor of the SARS-CoV-2 virus. Currently, the detection of SARSCoV-2 is mainly achieved using open plate real-time reverse-transcription polymerase chain reaction (RT-PCR). While open plate method has some limitations, such as a high false-negative rate, cumbersome manual operation, aerosol pollution and leakage risks. Therefore, a convenient method to rapidly detect SARS-CoV-2 virus is urgently and extremely required for timely epidemic control with the limited resources. In this review, the current real-time methods and principles for novel coronavirus detection are summarized, with the aim to provide a reference for real-time screening of coronavirus in areas with insufficient detection capacity and inadequate medical resources. The development and establishment of a rapid, simple, sensitive and specific system to detect SARS-CoV-2 is of vital importance for distinct diagnosis and effective treatment of the virus, especially in the flu season., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

More and more studies have proved that there are a small number of cells with self-renewal and differentiation ability in breast tumors, namely breast cancer stem cells. Such cells play a key role in the initiation, development and migration of breast tumors. The properties of breast tumor stem cells are regulated by a range of intracellular and extracellular factors, including important signaling pathways, transcription factors, non-coding RNAs, and cytokines such as Hedgehog, Wnt, Notch, microRNA93, microRNA100, and IL-6. Tumor microenvironment (such as mesenchymal stem cells, macrophages and cytokines) plays an important role in the regulation of breast tumor stem cells. Using the keywords including "breast cancer stem cells", "signal pathway", "chemotherapy tolerance", and "non-coding RNA", "triple negative breast cancer", "inhibitors", this study retrieved the original articles and reviews published before October 3, 2021, from PubMed and WEB OF SCI database and this study performed a comprehensive review of them. After treatment, there is a correlation between the metastasis-prone nature and recurrence with breast cancer stem cells. The signaling pathway of breast cancer stem cells plays a significant role in activating the function of breast cancer cells, regulating the differentiation of breast cancer cells and controlling the division of breast cancer cells. This imbalance leads to the uncontrolled growth and development of breast cancer cells. Targeted therapy that blocks the corresponding pathway may become a new perspective for breast cancer treatment. In addition, corresponding therapeutic strategies can be used according to the expression characteristics of different molecular types of breast cancer stem cells. For ER-positive breast cancer, simultaneous endocrine therapy and targeted therapy of tumor stem cells may improve the efficacy of endocrine therapy. Trastuzumab therapy significantly reduces the risk of recurrence of HER2-positive breast cancer. For drug-resistant patients, combination therapy is required due to the different phenotypes of epithelial-mesenchymal transforming tumor stem cells. This study briefly reviews the research progress of breast cancer stem cell-related signaling pathways and their inhibitors, in order to provide a reference for breast cancer patients to obtain more effective clinical treatment., Competing Interests: None., (AJCR Copyright © 2022.)

Objective: Thoracic endovascular aortic repair (TEVAR) can be complicated by a type Ia endoleak. However, its natural history remains unclear. This report describes the natural history and midterm outcome of conservatively treated type Ia endoleaks in the proximal aorta., Methods: Between 2007 and 2015, 395 patients underwent TEVAR at our institution. Only TEVARs landing proximally at landing zones 0, 1, and 2 were included (221/395). Type Ia endoleak's flow was classified as "fast" or "slow" based on the time needed to visualize the aneurysmal sac during arteriogram., Results: The median follow-up was 4.1 years. Aortic dissection, thoracic aortic aneurysm, and traumatic aortic injury were the most common indications for TEVAR; the incidence of type Ia endoleak was not statistically different. Forty-seven patients (21.3%) had a type Ia endoleak. TEVAR landing proximally at zone 1 increased the odds of developing a type Ia endoleak (odds ratio, 2.8; 95% confidence interval, 1.3-5.9; P = .0072). The 30-day mortality and the overall survival was not influenced by the development of immediate-type Ia endoleak. In 34 (72.3%) patients, the endoleak resolved spontaneously. Ninety-four percent of these patients had a SlowE (n = 32/34). All of spontaneous resolutions occurred before the end of the first postoperative year., Conclusions: SlowE tends to resolve within 1 year after TEVAR. Initial conservative treatment seems to be a reasonable approach in patients with SlowE., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

A novel hybrid biodegradable Nuss bar model was developed to surgically correct the pectus excavatum and reduce the associated pain during treatment. The scheme consisted of a three-dimensional (3D) printed biodegradable polylactide (PLA) Nuss bar as the surgical implant and electrospun polylactide-polyglycolide (PLGA) nanofibers loaded with lidocaine and ketorolac as the analgesic agents. The degradation rate and mechanical properties of the PLA Nuss bars were characterized after submersion in a buffered mixture for different time periods. In addition, the in vivo biocompatibility of the integrated PLA Nuss bars/analgesic-loaded PLGA nanofibers was assessed using a rabbit chest wall model. The outcomes of this work suggest that integration of PLA Nuss bar and PLGA/analgesic nanofibers could successfully enhance the results of pectus excavatum treatment in the animal model. The histological analysis also demonstrated good biocompatibility of the PLA Nuss bars with animal tissues. Eventually, the 3D printed biodegradable Nuss bars may have a potential role in pectus excavatum treatment in humans.

No study has evaluated the effect of dexmedetomidine in patients who received surgery for type A aortic dissection. This is the first study to evaluate the effect of dexmedetomidine in aortic dissection patients. This study was executed using data from the Chang Gung Research Database in Taiwan. The CGRD contains the multi-institutional standardized electronic medical records from seven Chang Gung Memorial hospitals, the largest medical system in Taiwan. We retrospectively evaluate patients who received surgery for acute type A aortic dissection between January 2014 and December 2018. Overall, 511 patients were included, of whom 104 has received dexmedetomidine infusion in the postoperative period. One-to-two propensity score-matching yielded 86 cases in the dexmedetomidine group and 158 cases in the non-dexmedetomidine group. The in-hospital mortality and composite outcome including all-cause mortality, acute kidney injury, delirium, postoperative atrial fibrillation, and respiratory failure, were considered primary outcomes. The in-hospital mortality and composite outcome were similar between groups. The risk of Acute Kidney Injury Network stage 3 acute kidney injury was significantly lower in the dexmedetomidine group than in the non-dexmedetomidine group (8.1% vs 19.0%; OR, 0.38; 95% CI, 0.17-0.86; p = 0.020. The risk of newly-onset dialysis was also significantly lower in the dexmedetomidine group than in the non-dexmedetomidine group (4.7% vs 13.3%; OR, 0.32; 95% CI, 0.11-0.90; p = 0.031). Post-operative dexmedetomidine infusion significantly reduced the rate of severe acute kidney injury and newly-onset dialysis in patients who received surgery for acute type A aortic dissection., (© 2022. The Author(s).)

Much of our understanding of bacterial behavior stems from studies in liquid culture. In nature, however, bacteria frequently live in densely packed spatially-structured communities. How does spatial structure affect bacterial cooperative behaviors? In this work, we examine rhamnolipid production-a cooperative and virulent behavior of Pseudomonas aeruginosa. Here we show that, in striking contrast to well-mixed liquid culture, rhamnolipid gene expression in spatially-structured colonies is strongly associated with colony specific growth rate, and is impacted by perturbation with diffusible quorum signals. To interpret these findings, we construct a data-driven statistical inference model which captures a length-scale of bacterial interaction that develops over time. Finally, we find that perturbation of P. aeruginosa swarms with quorum signals preserves the cooperating genotype in competition, rather than creating opportunities for cheaters. Overall, our data demonstrate that the complex response to spatial localization is key to preserving bacterial cooperative behaviors., (© 2022. The Author(s).)

NMR is a noninvasive, molecular-level spectroscopic technique widely used for chemical characterization. However, it lacks the sensitivity to probe the small number of spins at surfaces and interfaces. Here, we use nitrogen vacancy (NV) centers in diamond as quantum sensors to optically detect NMR signals from chemically modified thin films. To demonstrate the method's capabilities, aluminum oxide layers, common supports in catalysis and materials science, are prepared by atomic layer deposition and are subsequently functionalized by phosphonate chemistry to form self-assembled monolayers. The surface NV-NMR technique detects spatially resolved NMR signals from the monolayer, indicates chemical binding, and quantifies molecular coverage. In addition, it can monitor in real time the formation kinetics at the solid-liquid interface. With our approach, we show that NV quantum sensors are a surface-sensitive NMR tool with femtomole sensitivity for in situ analysis in catalysis, materials, and biological research., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

Coronavirus disease 2019 (COVID-19) is now a major public health problem worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is extremely strong. One major target of the virus is the lung, which can lead to death due to the development of respiratory distress syndrome and even multiple system organ failure. The possible pathophysiology by which SARS-CoV-2 affects the object is by way of the receptor, angiotensin-converting enzyme 2 (ACE2). From the study of the viral structure and infection mechanisms, researchers have discovered that the ACE2 acts as a receptor for SARS-CoV-2. According to previous studies, ACE2 is one of the key enzymes in the RAS system. Physiological functions can be found in angiosarcomas and in the kidney, liver, intestine and so on. Whether SARS-CoV-2 infection leads to male fertility impairment has recently received attention. Nevertheless, the association between SARS-CoV-2 infection and reproductive health is currently poorly understood. Using key words including "SARS-CoV-2", "reproductive health", "ACE2" and "2019-nCoV", we retrieved original articles and reviews from the PubMed and WEB OF SCI databases published before December 16, 2020 and performed a thorough review of them. Compared with females, we discovered that infected person with SARS-CoV-2 was higher in males. Men who were infected with SARS-CoV-2 may be easy to suffer from impaired reproductive health. These investigations would help for a comprehensive grasp of the relationship between SARS-CoV-2 infection and reproductive health., Competing Interests: None., (AJTR Copyright © 2021.)

Background: Health care providers who care for patients with CKD must be able to provide effective counseling about a kidney-friendly diet. Nutrition is underemphasized in medical curricula, and the kidney diet is one of the most challenging diets. We hypothesized that participation in an experiential educational program in kidney diet would result in improved knowledge of the underlying principles behind it and provide concrete examples of how to explain this diet to patients., Methods: The first part of this study was a knowledge assessment administered to all US nephrology fellows during the 2020 National Board of Medical Examiners Nephrology In-Training Examination. We later opened the assessment to a broader, global audience via social media. Respondents included trainees, practicing nephrologists, dieticians, and other health professionals. Participants self-identified willingness to participate in the second part of the study, the Kidney Diet Challenge (KDC). The 5-day challenge included daily webinars by experts in nutrition. Daily surveys captured self-reported adherence to the diet. Social media was used to engage with participants. All participants received a follow-up knowledge assessment., Results: Among the nephrology fellows ( n =317), the median pretest score was 2 out of 5 (40%) questions correct, and results did not differ by year of training ( P =0.31). Of the participants ( n =70) who completed the 5-day challenge and responded to the post-challenge survey, the distribution of the number of correct answers improved after the KDC (median [25th, 75th percentile]: 3 [2, 3] versus 3 [2, 4]; P <0.001). Statistics from our official hashtag for this study (#kidneydietchallenge) showed that we achieved 406,241 reaches and 1,004,799 impressions, with a total of 974 posts using this hashtag., Conclusions: The KDC is an immersive, experiential educational tool that enabled a global population to learn how to counsel their patients better about adherence to a complex kidney diet., Competing Interests: W.E. Mitch reports other interests/relationships with the American Diabetes Association, American Heart Association, American Society of Nephrology, International Society of Nephrology, and National Kidney Foundation but does not receive compensation from these organizations. K. Pivert reports current employment by the American Society of Nephrology and the Journal of Neurosurgery Publishing Group. R. Raghavan reports consultancy agreements with PriMed and honoraria from GlaxoSmithKline and Reata Pharmaceuticals. B. Shusterman reports consultancy agreements with SOMA Strategies; ownership interest with Davita, Sanderling Dialysis, The Cooking Doc, LLC, and US Renal; and partnership with the American Kidney Fund. C. Yuan reports being an administrator and member of the Nephrology Education Research and Development Consortium (https://nerdc.org). All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Stent implantation impairs local endothelial function and may be associated with subsequent adverse cardiovascular events. Telmisartan, an angiotensin II receptor blocker that has unique peroxisome proliferator-activated-receptor-gamma-mediated effects on cardiovascular disease, has been shown to enhance endothelial function and limit neointimal hyperplasia. This study utilized hybrid biodegradable/stent nanofibers to facilitate sustained and local delivery of telmisartan to injured arterial vessels. Telmisartan and poly(d,l)-lactide- co -glycolide (PLGA) (75:25) were dissolved in hexafluoroisopropyl alcohol and electrospun into biodegradable nanofibrous tubes which were coated onto metal stents. By releasing 20% of the loaded telmisartan in 30 days, these hybrid biodegradable/stent telmisartan-loaded nanofibers increased the migration of endothelial progenitor cells in vitro, promoted endothelialization, and reduced intimal hyperplasia. As such, this work provides insights into the use of PLGA nanofibers for treating patients with an increased risk of stent restenosis.

An optimal antimicrobial regimen for the treatment of patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI) is currently unavailable. This study aimed to identify the appropriate antibiotics and the risk factors of all-cause mortality for CRKP BSI patients. This retrospective cohort study included the hospitalized patients with CRKP BSI. Primary outcome was 30-day all-cause mortality. Cox regression analysis was used to evaluate the risk factors of 30-day mortality. A total of 89 patients were included with a 30-day mortality of 52.1%. A total of 52 (58.4%) patients were treated with appropriate antimicrobial regimens and 58 (65.2%) isolates carried bla KPC-2 genes. Microbiologic eradication within 7 days (adjusted hazard ratio [HR] = 0.09, p < 0.001), platelet count (per 1 × 10 4 /mm 3 , adjusted HR = 0.95, p = 0.002), and Pitt bacteremia scores (adjusted HR = 1.40, p < 0.001) were independently associated with 30-day all-cause mortality. No effective antimicrobial regimens were identified. In conclusion, risk factors of 30-day mortality in patients with CRKP BSI included microbiologic eradication > 7 days, lower platelet count, and a higher Pitt bacteremia score. These findings render a new insight into the clinical landscape of CRKP BSI.

Recent years have seen a rising incidence of male infertility, mostly caused by the decline of sperm quality. The ratio of infertile males to infertile females has escalated from 3:7 in 2013 to current 5:5, which turns male infertility into the research focus of reproductive medicine. This study aimed to clarify the effect of reproductive tract infection by ureaplasma urealyticum (UU) and chlamydia trachomatis (CT) on the DNA integrity and routine semen parameters of infertile males. A retrospective study was performed. A total of 259 infertile males who were treated at the Andrological Laboratory Examination and Reproductive Medicine Center in our hospital were analyzed. qRT-PCR was used to examine the infection status of CT and UU. According to the eligibility criteria, we evaluated the semen parameters and biochemical data of 253 men. Based on the results of PCR, the subjects were divided into four groups: Group I (CT positive, 63 cases), Group II (UU positive, 60 cases), Group III (CT positive and UU positive, 62 cases), and Group IV (no infection, 68 cases). DNA fragmentation index (DFI), sperm count, vitality and morphology, elastase level, seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) were assessed. Compared to Group IV, three groups (Group I, Group II and Group III) showed difference in semen volume, proportion of sperm with normal morphology, sperm motility, progressive motility, and vitality (P < 0.05). Compared to Group IV, Group II and Group III showed difference in DFI (P < 0.05). Compared to Group IV, Group II and Group III showed difference in elastase level (P < 0.05). VCL, VSL, VAP, WOB, ROS, TM, HDS showed differences between groups of abnormal/normal WBC (*P < 0.01).UU infection significantly increased the level of seminal leukocytes only in Group II, but not in the other three groups, indicating that UU is a factor to increase the level of seminal leukocytes. Compared with the normal leukocyte group, there were significant differences in total motility, forward motility and normal sperm ratio between the two groups. The proportion of sperm with abnormal morphology (mostly in the head) showed obvious difference between groups of high and normal seminal leukocytic levels. At the same time, in this study, SCGE and SCD verified that leukocytes could damage sperm DNA by increasing ROS, which ultimately affects male fertility.

Objective: Several serum biomarkers have been investigated for their potential as diagnostic tools in aortic disease; however, no study has investigated the association between serum biomarkers and outcomes after aortic surgery. This study explored the predictive ability of serum soluble lumican in postoperative outcomes after aortic surgery., Methods: In total, 58 patients receiving aortic surgery for aortic dissection or aneurysm at Linkou Chang Gung Memorial Hospital in Taiwan in December 2011-September 2018 were enrolled. Blood samples were collected immediately upon patients' arrival in the intensive care unit after aortic surgery. The diagnostic properties of soluble lumican levels were assessed by performing receiver operating characteristic (ROC) curve analysis. The confidence interval (CI) of the area under the ROC curve (AUC) was measured using DeLong's nonparametric method and the optimal cutoff was determined using the Youden index., Results: The serum soluble lumican level distinguished prolonged ventilation (AUC, 73.5%; 95% CI, 57.7%-89.3%) and hospital stay for >30 days (AUC, 78.2%; 95% CI, 61.6%-94.7%). The optimal cutoffs of prolonged ventilation and hospital stay for >30 days were 1.547 and 5.992 ng/mL, respectively. The sensitivity and specificity were respectively 100% (95% CI, 71.5%-100%) and 40.4% (95% CI, 26.4%-55.7%) for prolonged ventilation and 58% (95% 27.7%-84.8%) and 91.3% (95% CI, 79.2%-97.6%) for hospital stay for >30 days., Conclusions: The serum soluble lumican level can be a potential prognostic factor for predicting poor postoperative outcomes after aortic surgery. However, more studies are warranted in the future., Competing Interests: No conflicts of interest for all authors

Background Octogenarians (≥80 years old) are high-risk patients for acute aortic dissection (AAD) surgery. However, no population-based study has investigated the late outcomes of AAD surgery in octogenarians. This study aimed to investigate the late outcomes of AAD surgery in octogenarians. Methods and Results A total of 3998 patients who received AAD surgery from 2005 to 2013 were identified from the Taiwan National Health Insurance Research Database. In-hospital complications and late outcomes including all-cause mortality, major adverse cardiac and cerebrovascular event, respiratory failure, and redo aortic surgery were evaluated. The risks of late outcomes between octogenarians and nonoctogenarians were compared using the multivariable Cox proportional hazard model or Fine and Gray competing model. The numbers of the octogenarians who underwent type A and B AAD surgeries were 206 (6%; 206/3423) and 79 (13.7%; 79/575), respectively. Compared with the nonoctogenarians, the type A octogenarians had higher risks of in-hospital mortality and several in-hospital complications, whereas the type B octogenarians did not. Furthermore, compared with the nonoctogenarians, the type A octogenarians had a higher risk of all-cause mortality (61.7% vs 32.5%; hazard ratio [HR], 2.35; 95% CI, 1.95-2.84) and a higher cumulative incidence of major adverse cardiac and cerebrovascular event and respiratory failure, and the type B octogenarians demonstrated a higher risk of all-cause mortality (44.3% vs 30.4%; HR, 1.74; 95% CI, 1.18-2.55). The octogenarians receiving AAD surgeries had higher mortality rates than the normal octogenarian population. Conclusions Octogenarians receiving AAD surgeries exhibit worse late outcomes than nonoctogenarian counterparts.

Endovascular aneurysm repair (EVAR) and thoracic endovascular aortic repair (TEVAR) are effective and minimally invasive treatment options for high-risk surgical candidates. Nevertheless, knowledge about the management of aortic stent graft therapy in chronic kidney disease (CKD) is scarce. This study aimed to examine outcomes after EVAR and TEVAR in patients with CKD.Utilizing data from the Taiwan National Health Insurance Research Database, we retrospectively assessed patients who underwent EVAR and TEVAR therapy between January 1, 2006, and December 31, 2013. Patients were divided into CKD and non-CKD groups. Outcomes were in-hospital mortality, all-cause mortality, readmission, heart failure, and major adverse cardiac and cerebrovascular events.There were 1019 patients in either group after matching. The CKD group had a higher in-hospital mortality rate than the non-CKD group (15.2% vs 8.3%, respectively; odds ratio, 1.92; 95% confidence interval [CI], 1.46-2.54). Patients with CKD had higher risks of all-cause mortality including in-hospital death (46.1% vs 33.1%; hazard ratio [HR], 1.61; 95% CI, 1.35-1.92), readmission rate (62.6% vs 55.0%; subdistribution HR [SHR], 1.61; 95% CI, 1.32-1.69), redo stent (7.8% vs 6.2%; SHR, 1.50; 95% CI, 1.09-2.07), and major adverse cardiac and cerebrovascular events (13.3% vs 8.8%; SHR, 1.50; 95% CI, 1.15-1.95). The subgroup analysis did not demonstrate a variation in mortality between the TEVAR and EVAR cohorts (P for interaction = .725). The dialysis group had higher risks of all-cause mortality and readmission than the CKD without dialysis and non-CKD groups.Among EVAR/TEVAR recipients, CKD was independently associated with higher in-hospital mortality, postoperative complication, and all-cause mortality rates. Patients with end-stage renal disease on dialysis had worse outcomes than those in the CKD non-dialysis and non-CKD groups.

Pressure injury is the most important issue facing paralysis patients and the elderly, especially in long-term care or nursing. A new interfacial pressure sensing system combined with a flexible textile-based pressure sensor array and a real-time readout system improved by the Kalman filter is proposed to monitor interfacial pressure progress in the cardiac operation. With the design of the Kalman filter and parameter optimization, noise immunity can be improved by approximately 72%. Additionally, cardiac operation patients were selected to test this developed system for the direct correlation between pressure injury and interfacial pressure for the first time. The pressure progress of the operation time was recorded and presented with the visible data by time- and 2-dimension-dependent characteristics. In the data for 47 cardiac operation patients, an extreme body mass index (BMI) and significantly increased pressure after 2 h are the top 2 factors associated with the occurrence of pressure injury. This methodology can be used to prevent high interfacial pressure in high-risk patients before and during operation. It can be suggested that this system, integrated with air mattresses, can improve the quality of care and reduce the burden of the workforce and medical cost, especially for pressure injury.

A 63-year-old diabetic smoker with alcoholism was the first mortality case of coronavirus disease 2019 (COVID-19) in Taiwan. As concurrently infected with Klebsiella pneumoniae and subsequently with Klebsiella aerogenes, he was exposed by a national survey of patients with critically influenza-negative pneumonia. We recommend COVID-19 screening for patients with severe flu-like syndrome and protecting health-care workers from being infected., (Copyright © 2020. Published by Elsevier B.V.)

Brain abscesses are emergent and life-threating despite advances in modern neurosurgical techniques and antibiotics. The present study explores the efficacy of vancomycin embedded to 50:50 poly(lactic- co -glycolide acid) (PLGA) microparticles in the treatment of brain abscess. The vancomycin embedded microparticles (VMPs) were stereotactically introduced into the cerebral parenchyma in Staphylococcus aureus bacteria- induced brain abscess-bearing rats. Experimental rats were divided into three groups: group A (n = 13; no treatment), group B (n = 14; daily vancomycin injection (5 mg intraperitoneally), and group C (n = 12; stereotactic introduction of VMPs into the abscess cavity). Group C exhibited no inflammatory response and significantly increased survival and reduced mean abscess volumes ( p <0.001) at the eighth week, compared with other groups. Vancomycin delivery via a biodegradable PLGA vehicle can easily attain Area Under the Curve (AUC)/minimum inhibitory concentration (MIC) ratios of ≥400, and strengthens the therapeutic efficacy of antibiotics without provoking any potential toxicity. Biodegradable VMPs are a safe and sustainable drug delivery vehicle for the treatment of brain abscess., Competing Interests: The authors declare no competing financial interest.

Unexplained fever is one of the most common and difficult diagnostic problems faced daily by clinicians. This study evaluated the differences in health service utilization, health care expenditures, and quality of care provided to patients with unexplained fever before and after global budget (GB) implementation in Taiwan.The National Health Insurance Research Database was used for analyzing the health care expenditures and quality of care before and after implementation of the GB system. Patients diagnosed as having unexplained fever during 2000-2001 were recruited; their 2000-2001 and 2004-2005 data were considered baseline and postintervention data, respectively.Data of 259 patients with unexplained fever were analyzed. The mean lengths of stay (LOSs) before and after GB system implementation were 4.22 ± 0.35 days and 5.29 ± 0.70 days, respectively. The mean costs of different health care expenditures before and after implementation of the GB system were as follows: the mean diagnostic, drug, therapy, and total costs increased respectively from New Taiwan Dollar (NT$) 1440.05 ± NT$97.43, NT$3249.90 ± NT$1108.27, NT$421.03 ± NT$100.03, and NT$13,866.77 ± NT$2,114.95 before GB system implementation to NT$2224.34 ± NT$238.36, NT$4272.31 ± NT$1466.90, NT$2217.03 ± NT$672.20, and NT$22,856.41 ± NT$4,196.28 after implementation. The mean rates of revisiting the emergency department within 3 days and readmission within 14 days increased respectively from 10.5% ± 2.7% and 8.3% ± 2.4% before implementation to 6.3% ± 2.2% and 4.0% ± 1.7% after implementation.GB significantly increased LOS and incremental total costs for patients with unexplained fever; but improved the quality of care.

Ganoderma sinense is a Chinese unique medicinal fungus that has been used in folk medicine for thousands of years. Polysaccharides are considered to be biologically active ingredients due to their immune-modulating functions. Previously we found that GSP-2, a new polysaccharide isolated from Ganoderma sinense, exerts an immunomodulatory effect in human peripheral blood mononuclear cells but the underlying mechanism is unclear. The present study aimed to investigate how GSP-2 triggers immunologic responses and the implicated signaling pathways. GSP-2 effects were investigated both in a macrophagic cell line, RAW264.7, and in primary macrophages. Moreover, the molecular basis of GSP-2 recognition by immune cells, and the consequent activation of signaling cascades, were explored by employing recombinant human HEK293-TLR-Blue clones, individually overexpressing various Toll-like receptors. GSP-2 dose-dependently induced the overexpression of Toll-like receptor 4 (TLR4) but did not affect the expression of other TLRs. Moreover, GSP-2 induced TNFα secretion in primary macrophages from wild-type, but not TLR4-knockout mice. In addition, GSP-2 upregulated TLR4 protein expression and activated the MAPK pathway in RAW246.7 macrophages. Finally, GSP-2 induced the production of the cytokines TNFα, IL1β, and IL6. Our data demonstrated that GSP-2 was specifically recognized by TLR4, promoting cytokine secretion and immune modulation in macrophages., Competing Interests: The authors have declared that no competing interests exist.

A facile and diversity-oriented synthetic strategy toward aminocyclitol natural products from inexpensive C 2 -symmetric l-tartaric acid was developed. The pivotal epoxide was used as a common intermediate to accomplish eight diverse target molecules in six to eleven steps. Various allyl-amine-type conduramines were synthesized in a diastereoselective manner. Heck arylation was explored to construct a phenanthridone ring in a concise synthesis of (+)-lycoricidine. In addition, a highly efficient formal synthesis of (-)-laminitol was developed.

To investigate the incidence, outcomes, and risk factors of postoperative acute respiratory distress syndrome (ARDS) in patients undergoing surgical repair for acute type A aortic dissection.This retrospective study involved 270 patients who underwent surgical repair for acute type A aortic dissection between January 2009 and December 2015. Data on clinical characteristics and outcomes were collected. Patients who immediately died after surgery and with preoperative myocardial dysfunction were excluded. The included patients were divided into the ARDS (ARDS patients who met the Berlin definition) and non-ARDS groups. Primary outcome was postoperative ARDS, according to the 2012 Berlin definition for ARDS and was reviewed by 2 qualified physicians with expertise in critical care and cardiac surgery. Outcomes of interest were the incidence and severity of risk factors for ARDS in this population, and perioperative outcomes and survival rates were compared with patients with or without ARDS.A total of 233 adult patients were enrolled into this study; of these, 37 patients (15.9%) had ARDS. Three, 20, and 14 patients had mild, moderate, and severe ARDS, respectively, according to the Berlin definition, with no significant difference in age, sex, and underlying disease. The ARDS group had lower mean oxygenation index (OI) than the non-ARDS group in the first 3 days post-surgery and demonstrated an improvement in lung function after the fourth day. Postoperative complication risks were higher in the ARDS group than in the non-ARDS group. However, no significant difference was observed in in-hospital mortality between the 2 groups (10.8% vs 5.6%, P = .268). Additionally, there was also no significant difference in the 3-year mortality rate between the 2 groups (P of log-rank test = .274). Postoperative hemoglobin level (odds ratio [OR]: 0.78; 95% confidence interval [CI]: 0.62-0.99) and perioperative blood transfusion volume (OR: 1.07; 95% CI: 1.03-1.12) were associated with ARDS risk.Postoperative ARDS after type A aortic dissection repair surgery was associated with risks of postoperative complications but not with risk of in-hospital mortality or 3-year mortality. A higher perioperative blood transfusion volume and a lower postoperative hemoglobin level may be risk factors for ARDS.

Reactivation of hepatitis B virus (HBV) is a potentially fatal complication of immunosuppressive therapy, and can occur in individuals who are hepatitis B surface antigen (HBsAg) negative but positive for hepatitis B core antibody (anti-HBc). While anti-HBc positivity indicates prior HBV exposure, it may also reflect clearance of HBsAg, but with viral persistence at low intrahepatic replicative and transcriptional levels. 1 HBV reactivation can still occur during intense immunosuppression, including B cell-depleting therapy with anti-CD20 antibodies 2 and hematopoietic stem cell transplantation. 3 While prevention via antiviral prophylaxis is recommended, it remains uncertain, from a global perspective, if this is an ideal and cost-effective strategy. An alternative is regular HBV DNA monitoring. 4 However, this approach is problematic in resource-constrained regions, where the logistics of sample collection, transportation, and molecular analysis in dedicated facilities poses challenges. 5 We aimed to evaluate the effectiveness of simple monitoring strategies using routine liver biochemistry and serum HBsAg in preventing HBV-related complications during anti-CD20 therapy., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Preoperative renal dysfunction is associated with mortality in patients who undergo coronary artery bypass graft and valve surgery. However, the role of preoperative renal dysfunction in type A aortic dissection (TAAD) remains unclear. This study aimed to evaluate the impact of preoperative renal dysfunction on the outcome of surgical intervention in patients with TAAD.We retrospectively studied the outcomes of 159 patients with TAAD who were treated at a tertiary referral hospital between 2005 and 2010. The demographics and surgical details of patients were analyzed according to their renal function. Risk factors for outcomes were analyzed using multivariable logistic regression. Thirty-two of the patients (20.1%) had preoperative serum creatinine of 1.5 mg/dL or more. The multivariable logistic regression model revealed independent risk factors of in-hospital mortality to be renal dysfunction (odds ratio [OR], 3.79; 95% confidence interval [CI], 1.64-8.77), preoperative shock (OR, 8.75; 95% CI, 2.83-27.02), and bypass time (OR, 1.008; 95% CI, 1.003-1.013). In addition, patients with renal dysfunction exhibited a lower 90-day survival rate than did patients without the condition (P of log-rank test = .005).Preoperative renal dysfunction may have a critical role in the surgical outcomes of patients with TAAD. Additional large-scale investigations are warranted.