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Chang-chun Cao,1,* Da-wei Chen,2,* Jing Li,2 Meng-qing Ma,2 Yu-bao Chen,3 Yi-zhi Cao,4 Xi Hua,2 Wei Shao,1 Xin Wan2 1Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; 2Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; 3Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; 4The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China *These authors contributed equally to this work Purpose: Previous studies have described the incidence, risk factors, and outcomes for patients with acute exacerbations of COPD (AECOPD) developing acute kidney injury (AKI). However, little is known about the differences between community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) in patients with AECOPD. Thus, in this study, we compared prevalence, risk factors, and outcomes for these patients with CA-AKI and HA-AKI. Patients and methods: This study was conducted from January 2014 to January 2017, and data from adult inpatients with AECOPD were analyzed retrospectively. A total of 1,768 patients were included, 280 patients were identified with CA-AKI and 97 patients were with HA-AKI. Results: Prevalence of CA-AKI was 15.8% and that of HA-AKI was 5.5%, giving an overall AKI prevalence of 21.3%. Patients with CA-AKI had a higher prevalence of chronic kidney disease (CKD) and lower prevalence of chronic cor pulmonale than patients with HA-AKI. Risk factors for developing HA-AKI and CA-AKI were similar, such as being elderly, requirement for mechanical ventilation, and a history of coronary artery disease and CKD. Patients with HA-AKI were more likely to have stage 3 AKI and worse short-term outcomes. In comparison with patients with CA-AKI, those with HA-AKI were more likely to require non-invasive mechanical ventilation (31.3% versus 16.8%; P = 0.003) and had a longer duration of mechanical ventilation (11 days versus 8 days; P = 0.020), longer hospitalization (14 days versus 12 days; P = 0.038), and higher inpatient mortality (32.0% versus 13.2%; P < 0.001). Patients with HA-AKI had worse (multivariate-adjusted) inpatient survival than those with CA-AKI (hazard ratio, 1.7 [95% confidence interval, 1.03–2.81; P = 0.038] for the HA-AKI group). Conclusion: AKI was common in patients with AECOPD requiring hospitalization. CA-AKI was more common than HA-AKI but otherwise demonstrated similar demographics and risk factors. Nevertheless, patients with HA-AKI had worse short-term outcomes. Keywords: acute exacerbation of COPD, community-acquired acute kidney injury, hospital-acquired acute kidney injury, short-term outcomes

Dawei Chen,1,2,* Chenyue Zhang,3,* Jiamao Lin,4 Xinyu Song,2,4 Haiyong Wang4 1Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, 2School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, 3Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 4Department of Internal Medicine-Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, People’s Republic of China *These authors contributed equally to this work Aim: The aim of this study was to analyze the diagnostic and prognostic values of the circular RNA (circRNA) hsa_circ_0128298 in hepatocellular carcinoma (HCC). Patients and methods: The global circRNA expression was measured using circRNA microarray using three pairs of cancer and noncancerous tissues from HCC patients. The microarray analysis revealed that two circRNAs were differentially expressed in the three pairs of cancerous and noncancerous tissues. The higher levels of two representative circRNAs, such as hsa_circ_0128298 and hsa_circ_0091582, were further confirmed by real-time polymerase chain reaction. In addition, the association between the expression level of hsa_circ_0128298 and the clinicopathological features of patients with HCC was further analyzed. The clinical diagnosis value was confirmed by receiver operating characteristic (ROC) curve analysis. Independent prognostic factors of patient outcome were identified using the Cox regression model. The survival data were analyzed by the Kaplan–Meier method, and the differences were evaluated using log-rank tests. Two-sided P-values

Qing Chen,1,* Miaomiao Long,2,* Lipeng Qiu,3 Mengqin Zhu,3 Zhen Li,1 Mingxi Qiao,1 Haiyang Hu,1 Xiuli Zhao,1 Dawei Chen1 1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 2Department of Research and Development, Nanjing Chia Tai Tianqing Pharmaceutical Group Co. Ltd, Nanjing, 3Department of Pharmaceutics, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, People’s Republic of China *These authors contributed equally to this work Abstract: To improve the targeting efficacy of hyaluronic acid (HA)-based micelles, pH-sensitive mixed micelles based on HA-g-poly(L-histidine) (PHis) and d-α-tocopheryl polyethylene glycol 2000 copolymers were prepared and decorated with human epidermal growth factor receptor 2 (Her2) peptide, a tumor cell-specific peptide ligand, on their surface. The doxorubicin-loaded micelles (HA-PHis/peptide–d-α-tocopheryl polyethylene glycol 2000 mixed micelles [PHTM]) were characterized to have a unimodal size distribution and pH-dependent drug release pattern. In vitro tumor targeting studies demonstrated that PHTM exhibited the pronounced cytotoxicity and efficient internalization in MDA-MB-231 cells overexpressing CD44 and Her2 receptors. In vivo investigation into micelles in MDA-MB-231 tumor-bearing mice confirmed that PTHM could reach the tumor site more effectively and exert excellent tumor killing activity. In general, Her2 peptide decoration can enhance the selective cytotoxicity and antitumor activity of HA-based micelles. Keywords: Her2 peptide, hyaluronic acid, poly(L-histidine), targeted delivery, antitumor efficacy

Jie Zhang,1 Dan Liu,1 Mengjun Zhang,1 Yuqi Sun,1,2 Xiaojun Zhang,1 Guannan Guan,1 Xiuli Zhao,1 Mingxi Qiao,1 Dawei Chen,1 Haiyang Hu1 1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 2Department of Pharmaceutics, School of Pharmacy, Liaoning Medical University, Jinzhou, Liaoning Province, People’s Republic of China Abstract: Polyamidoamine dendrimers, which can deliver drugs and genetic materials to resistant cells, are attracting increased research attention, but their transportation behavior in resistant cells remains unclear. In this paper, we performed a systematic analysis of the cellular uptake, intracellular transportation, and efflux of PAMAM-NH2 dendrimers in multidrug-resistant breast cancer cells (MCF-7/ADR cells) using sensitive breast cancer cells (MCF-7 cells) as the control. We found that the uptake rate of PAMAM-NH2 was much lower and exocytosis of PAMAM-NH2 was much greater in MCF-7/ADR cells than in MCF-7 cells due to the elimination of PAMAM-NH2 from P-glycoprotein and the multidrug resistance-associated protein in MCF-7/ADR cells. Macropinocytosis played a more important role in its uptake in MCF-7/ADR cells than in MCF-7 cells. PAMAM-NH2 aggregated and became more degraded in the lysosomal vesicles of the MCF-7/ADR cells than in those of the MCF-7 cells. The endoplasmic reticulum and Golgi complex were found to participate in the exocytosis rather than endocytosis process of PAMAM-NH2 in both types of cells. Our findings clearly showed the intracellular transportation process of PAMAM-NH2 in MCF-7/ADR cells and provided a guide of using PAMAM-NH2 as a drug and gene vector in resistant cells. Keywords: PAMAM dendrimers, multidrug resistance, endocytosis, intracellular transportation, exocytosis

Liang Cheng,1,* Fa-Zhen Huang,1,2,* Li-Fang Cheng,1 Ya-Qin Zhu,1 Qing Hu,1 Ling Li,1 Lin Wei1, Da-Wei Chen1 1Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu Province, 2Department of Pharmacy, Central Hospital of Zaozhuang Minging Group, Zaozhuang, Shandong Province, People's Republic of China *These authors contributed equally to this work Abstract: Non-small cell lung cancer (NSCLC) is a serious threat to human health, and 40%–80% of NSCLCs express high levels of epidermal growth factor receptor (EGFR). GE11 is a novel peptide and exhibits high affinity for EGFR binding. The aim of this study was to construct and evaluate GE11-modified liposomes for targeted drug delivery to EGFR-positive NSCLC. Doxorubicin, a broad-spectrum antitumor agent, was chosen as the payload. GE11 was conjugated to the distal end of DSPE-PEG2000-Mal by an addition reaction with a conjugation efficiency above 90%. Doxorubicin-loaded liposomes containing GE11 (GE11-LP/DOX) at densities ranging from 0% to 15% were prepared by combination of a thin film hydration method and a post insertion method. Irrespective of GE11 density, the physicochemical properties of these targeted liposomes, including particle size, zeta potential, and drug entrapment efficiency, were nearly identical. Interestingly, the cytotoxic effect of the liposomes on A549 tumor cells was closely related to GE11 density, and liposomes with 10% GE11 had the highest tumor cell killing activity and a 2.6-fold lower half maximal inhibitory concentration than that of the nontargeted counterpart (PEG-LP/DOX). Fluorescence microscopy and flow cytometry analysis revealed that GE11 significantly increased cellular uptake of the liposomes, which could be ascribed to specific EGFR-mediated endocytosis. It was found that multiple endocytic pathways were involved in entry of GE11-LP/DOX into cells, but GE11 assisted in cellular internalization mainly via the clathrin-mediated endocytosis pathway. Importantly, the GE11-modified liposomes showed enhanced accumulation and prolonged retention in tumor tissue, as evidenced by a 2.2-fold stronger mean fluorescence intensity in tumor tissue than the unmodified liposomes at 24 hours. In summary, GE11-modified liposomes may be a promising platform for targeted delivery of chemotherapeutic drugs in NSCLC. Keywords: epidermal growth factor receptor, nanosized carrier, targeted drug delivery, cellular uptake mechanism, in vivo imaging

Yuan-Yuan Diao1,2,*, Hao-Ying Li3,*, Ying-Hua Fu4, Min Han1, Yu-Lan Hu1, Hong-Liang Jiang5, Yasuo Tsutsumi6, Qi-Chun Wei7, Da-Wei Chen2, Jian-Qing Gao1 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou; 2School of Pharmacy, Shenyang Pharmaceutical University, Shenyang; 3Biomanufacturing Research Centre, Department of Mechanical and Electrical Engineering, Soochow University, Suzhou; 4Department of Pharmaceutics, Jiaxing University College of Medicine, Jiaxing; 5Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People's Republic of China; 6Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan; 7Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, Zhejiang University School of Medicine, Hangzhou, People's Republic of China, *These authors contributed equally to this workBackground: Multidrug resistance remains a major obstacle to successful cancer chemotherapy. Some chemical multidrug resistance inhibitors, such as ciclosporin and verapamil, have been reported to reverse resistance in tumor cells. However, the accompanying side effects have limited their clinical application. In this study, we have developed a novel drug delivery system, ie, a polyethyleneglycol-polycaprolactone (PEG-PCL) copolymer micelle encapsulating doxorubicin, in order to circumvent drug resistance in adriamycin-resistant K562 tumor cells.Methods: Doxorubicin-loaded diblock copolymer PEG-PCL micelles were developed, and the physicochemical properties of these micelles, and accumulation and cytotoxicity of doxorubicin in adriamycin-resistant K562 tumor cells were studied.Results: Doxorubicin-loaded micelles were prepared using a solvent evaporation method with a diameter of 36 nm and a zeta potential of +13.8 mV. The entrapment efficiency of doxorubicin was 48.6% ± 2.3%. The micelles showed sustained release, increased uptake, and cellular cytotoxicity, as well as decreased efflux of doxorubicin in adriamycin-resistant K562 tumor cells.Conclusion: This study suggests that PEG-PCL micelles have the potential to reverse multidrug resistance in tumor cells.Keywords: doxorubicin, polyethylene glycol, polycaprolactone, adriamycin-resistant K562 tumor cells, multidrug resistance, micelles

Objectives: Demonstrate initial results using Khan Kinetic Treatment [KKTTM] as a low back pain [LBP] treatment option. Methods: A self-reported functional assessment, LBP questionnaire, and pain medication dose were used as the outcome measures for 48 matched subjects randomly split into two groups [treatment and control]. The treatment group underwent a treatment period consisting of several individual KKTTM treatments over a few weeks period, while the control group continued conventional treatment. A paired t-test analyzed the functional assessment scores and a two group by two LBP score [positive or non-positive] McNemar's test was used for the LBP questionnaires. Pain medication dose analysis consisted of a two group by two pain medication dose outcome [same or reduced] McNemar's test. Results: Compared to a control group, the treatment group lowered both their self-recorded LBP scores [P < 0.001] and showed a strong positive trend to lower their pain medication dose [P = 0.054]. Only the range of motion assessment questionnaire [range of motion, overall activity, and recreation/work activities] detected changes in these measurements [P = 0.046, P = 0.061, P = 0.052, respectively]. Conclusions: Although we await blinded and randomized placebo controlled trials, initial results suggest thatKKTTMmay be an effective treatment for LBP, may increase the range of motion, and may decrease the need for pain relieving medication. [ABSTRACT FROM AUTHOR]

The most common source of information on workforce in the United States is the Bureau of Labor Statistics (BLS), a branch of the Department of Labor. In 1998, 14 public health workforce titles were added to the BLS Standard Occupational Classification (SOC) system. While this was a constructive step, it is not a 'quick fix,' because these additional titles do not solve the longstanding problems inherent in capturing accurate PH workforce data. As is true for all currently available sources, BLS statistics capture a limited segment of public health's broadly defined and multidisciplinary workforce. A standard system of data collection is needed to guide planning to sustain the present and future workforce. Revision of the 1998 SOC in preparation for the 2010 Census is now underway. This presents an opportunity for the public health community to act on prior recommendations regarding workforce data and advocate for more inclusive enumeration of public health occupations that can inform policies and planning for the current and future workforce. [ABSTRACT FROM AUTHOR]

Inferior alveolar nerve blockade is one of the most common, yet technically difficult local procedures performed. Inadvertent injury to the inferior alveolar or lingual nerve, resulting in persistent anesthesia, paresthesias, loss of taste, or pain in the distribution of these nerves, is more common than once thought. We report on two cases of lingual nerve injury during routine inferior alveolar nerve blockade. These cases are consistent with the hypotheses that direct nerve trauma, whether by nerve-needle contact or compression by anesthetic bolus, and the neurotoxic effects of specific anesthetic preparations may produce long term nerve damage. When this damage occurs to the pain-sensing A-delta and C-fibers, symptoms may resemble those seen in complex regional pain syndrome. [ABSTRACT FROM AUTHOR]

Yung-Heng Hsu,1,2 Dave Wei-Chih Chen,1 Chun-Der Tai,3 Ying-Chao Chou,1,2 Shih-Jung Liu,2 Steve Wen-Neng Ueng,1 Err-Cheng Chan4 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, 2Department of Mechanical Engineering, Chang Gung University, Guishan Township, 3Graduate Institute of Medical Mechatronics, Chang Gung University, Guishan Township, 4School of Medical Technology, Chang Gung University, Guishan Township, Taiwan Abstract: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L)-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration) for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics. Keywords: biodegradable nanofiber-enveloped plates, electrospinning, antibiotics, release characteristics

Dave Wei-Chih Chen1,2, Jun-Yi Liao3, Shih-Jung Liu2, Err-Cheng Chan41Department of Orthopedic Surgery, Chang Gung Memorial Hospital, 2Department of Mechanical Engineering, 3Graduate Institute of Medical Mechatronics, 4School of Medical Technology, Chang Gung University, Kwei-San, Tao-Yuan, TaiwanBackground: The purpose of this study was to develop novel sandwich-structured nanofibrous membranes to provide sustained-release delivery of vancomycin, gentamicin, and lidocaine for repair of infected wounds.Methods: To prepare the biodegradable membranes, poly(D, L)-lactide-co-glycolide (PLGA), collagen, and various pharmaceuticals, including vancomycin, gentamicin, and lidocaine, were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into sandwich-structured membranes with PLGA/collagen as the surface layers and PLGA/drugs as the core. An elution method and a high-pressure liquid chromatography assay were used to characterize in vivo and in vitro drug release from the membranes. In addition, repair of infected wounds in rats was studied. Histological examination of epithelialization and granulation at the wound site was also performed.Results: The biodegradable nanofibrous membranes released large amounts of vancomycin and gentamicin (well above the minimum inhibition concentration) and lidocaine in vivo for more than 3 weeks. A bacterial inhibition test was carried out to determine the relative activity of the antibiotics released. The bioactivity ranged from 40% to 100%. The nanofibrous membranes were functionally active in treating infected wounds, and were very effective as accelerators in early-stage wound healing.Conclusion: Using the electrospinning technique, we will be able to manufacture biodegradable, biomimetic, nanofibrous, extracellular membranes for long-term delivery of various drugs.Keywords: nanofibrous, sandwich-structured, drug-eluting membranes, electrospinning, release characteristics, repair, wound infection

Objectives: Microvascular free tissue transfer (MVFTT) for head and neck reconstruction is infrequently performed in pediatric patients. There is a paucity of data on perioperative airway management in pediatric MVFTT, such as the need for tracheostomy, which can pose higher morbidity to young patients due to potential long-term effects on the softer, more pliable laryngotracheal cartilage. Our objective was to report airway outcomes on pediatric patients undergoing MVFTT after segmental mandibulectomy with or without tracheostomy., Methods: Retrospective chart review of pediatric patients who underwent MVFTT reconstruction after segmental mandibulectomy at a tertiary care center from 2014 to 2023. Demographic variables, surgical characteristics, and hospital clinical outcomes were recorded. Statistical analyses were performed with JMP Pro, Version 16.0.0 (2021) SAS Institute Inc., Cary, NC, 1989-2021., Results: Ten patients (median age 11.5 years old, IQR: 9.0-13.3) underwent fibular free flap reconstruction. Mandibular pathologies included 3 ameloblastoma, 2 mesenchymal chondrosarcoma, 2 desmoplastic fibroma, 1 Ewing sarcoma, 1 chondroblastic osteosarcoma, and 1 desmoid tumor. Two patients received upfront tracheostomy at time of initial surgery for a subtotal mandibulectomy and a sub-hemimandibulectomy, respectively. Both patients were decannulated within 1 week after surgery and prior to discharge. The median ICU and hospital length of stay for patients who underwent tracheostomy was 3.5 days [IQR: 3.0-4.0] and 8.5 days [IQR: 8.0-9.0] respectively. Of the remaining 8 patients without tracheostomy, surgical defects were hemimandibulectomy and anterior subtotal mandibulectomy. Median intubation duration was 1.0 day [IQR: 1.0-2.5]. The median ICU and hospital length of stay for these patients were 3.0 days [IQR: 2.0-6.3] and 8.5 days [IQR: 7.3-13.0], respectively. No patient had to be reintubated for respiratory failure following extubation or had long-term airway complications during the follow-up period., Conclusions: Fibular free flap reconstruction without tracheostomy can be feasible in pediatric patients with mandibular defects, which can potentially reduce hospital resources required for fresh tracheostomy care needs and avoid additional surgical morbidity. Further studies in larger populations and prospective approaches are warranted., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Higher center and surgeon volume correspond to better outcomes for patients with thyroid cancer. This study aims to investigate how a hospital's safety-net burden, the proportion of a hospital's patients who are insured by state Medicaid plans or are uninsured, influences the outcomes of high-volume (HV) surgeons. Methods: We performed a retrospective cohort study of all patients who underwent surgery for thyroid cancer in California from 1999 to 2017. We stratified treating facilities by the proportion of Medicaid-type and indigent payors into safety-net burden quartiles. We compared the perioperative and oncologic outcomes of HV surgeons (annual case volume ≥10) for patients undergoing total thyroidectomy across safety-net burden quartiles. A mixed-effects regression model controlled for surgeon random effects and fixed effects of patient and tumor characteristics. Results: Our sample comprised 42,347 patients (78% female, median age 50), of whom 13,848 (32%) were treated by HV surgeons ( n = 276). Compared to patients of lower-volume surgeons, patients of HV surgeons were more likely to be White, from the upper quartiles of socioeconomic status and well insured (all p < 0.001). HV surgeons in each hospital's safety-net burden quartile displayed similar case number distributions. Compared to patients treated by HV surgeons at Q1 (lowest safety-net burden) hospitals, those treated by HV surgeons at Q4 (highest safety-net burden) hospitals had higher absolute risks of endocrine complications (+7%, p = 0.007), airway complications (+6%, p = 0.004), disease-specific mortality (+1.3%, p = 0.046), and all-cause mortality during the study period (+3%, p = 0.046) in multivariable analysis. Conclusion: The performance of HV thyroid cancer surgeons differs by a hospital's safety-net burden, with patients treated at high safety-net burden hospitals experiencing higher rates of operative complications, disease-specific mortality, and all-cause mortality. Having a HV surgeon alone may be insufficient to provide optimal short- and long-term outcomes for patients with thyroid cancer.

Competing Interests: Declaration of competing interest 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.

This paper reports on the novel composite membrane electrolytes used in Zn/MnO 2 , Al/MnO 2 , Al/air, and zinc/air electrochemical devices. The composite membranes were made using poly(vinyl alcohol), poly(acrylic acid), and a sulfonated polypropylene/polyethylene separator to enhance the electrochemical characteristics and dimensional stability of the solid electrolyte membranes. The ionic conductivity was improved significantly by the amount of acrylic acid incorporated into the polymer systems. In general, the ionic conductivity was also enhanced gradually as the testing temperature increased from 20 to 80 °C. Porous zinc gel electrodes and pure aluminum plates were used as the anodes, while porous carbon air electrodes or porous MnO 2 electrodes were used as the cathodes. The cyclic voltammetry properties and electrochemical impedance characteristics were investigated to evaluate the cell behavior and electrochemical properties of these prototype cells. The results showed that these prototype cells had a low bulk resistance, a high cell power density, and a unique device stability. The Al/MnO 2 cell achieved a density of 110 mW cm -2 at the designated current density for the discharge tests, while the other cells also exhibited good values in the range of 70-100 mW cm -2 . Furthermore, the Zn/air cell consisting of the PVA/PAA = 10:5 composite membrane revealed an excellent discharge capacity of 1507 mAh. This represented a very high anode utilization of 95.7% at the C/10 rate.

Erythrocytosis moderately enhances the oxygen-carrying capacity of the blood and is considered a characteristic response of individuals adapting from low-altitude regions to high-altitude regions. Nevertheless, erythrocytosis can also turn excessive and result in maladaptive syndromes, such as high altitude polycythemia (HAPC). The increased differentiation or proliferation of erythroid cells in the bone marrow may be a crucial factor leading to accumulation of peripheral erythroid cells. However, the mechanism of erythroid regulation within the bone marrow of high-altitude erythrocytosis remains insufficiently systematically observed. We utilized single-cell transcription sequencing to characterize bone marrow cells following chronic hypoxic exposure and found that bone marrow erythrocytosis is associated with the accumulation of Baso-E, Poly-E, and Ortho-E cells at the terminal stage of erythroid lineage differentiation. Through analysis of differential gene expression and localization in differentiated cells within the erythroid lineage, we confirmed that DDIT4 expression was localized in advanced differentiated erythroblast including Baso-E, Poly-E and Ortho-E, its expression was significantly enhanced by hypoxia exposure. We demonstrated that overexpression of DDIT4 could promote K562 cell differentiation, and through the IP pull-down interaction protein profile, we found that DDIT4 might participate in regulating the cell cycle by interacting with SIPA1 to promote the proliferation of erythroid cells and may be involved in HAPC., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship, and/orpublication of this article., (Copyright © 2024. Published by Elsevier Inc.)

Background: Total knee arthroplasty (TKA) is an effective treatment for knee osteoarthritis; however, early readmissions due to complications are common. This study assessed the ability of the hemoglobin-to-red cell distribution width ratio (HRR), hemoglobin-to-monocyte ratio (HMR), and hemoglobin-to-leukocyte ratio (HLR) to predict readmission within 14 days after TKA., Methods: Data from the Chang Gung Medical Research Database (CGRD) from 2014 to 2022 were retrospectively analyzed. Patients ≥ 20 years old who underwent primary TKA were eligible for inclusion. Patients with incomplete data on the indices of interest or follow-up < 14 days were excluded. Patient demographic, clinical, and comorbidity data were collected. Logistic regression was utilized to determine the associations between HRR, HMR, and HLR and 14-day readmission., Results: Data from 1,137 patients were analyzed. Multivariable analysis revealed that a higher HMR was significantly associated with lower 14-day readmission risk (adjusted OR [aOR] = 0.72, 95% confidence interval [CI]: 0.51-0.997), an HMR ≥ 2.18 (optimal cutoff value) was predictive of a significantly lower 14-day readmission risk (aOR = 0.61, 95% CI: 0.39-0.96). The composite indicator, HRR-HMR-HLR score, derived from the 3 indices assessed, was significantly associated with a lower 14-day readmission risk (score 2 vs. score 0: aOR = 0.51, 95% CI: 0.27-0.98; score 3 vs. score 0: aOR = 0.37, 95% CI: 0.17-0.82)., Conclusions: High HMR and the HRR-HMR-HLR score are independently associated with a lower 14-day readmission risk after TKA. Implementing these indices into clinical practice may enhance postoperative management., (© 2024. The Author(s).)

Epimedium is widely used in traditional Chinese medicine and contains rich bioactive compounds. These compounds often have a methyl group at their 4'-OH position catalyzed by methyltransferases. Therefore, studying methyltransferases in Epimedium plants is of great significance. In this study, a flavonol methyltransferase, EpOMT4, was isolated from Epimedium pseudowushanense B.L. Guo. The recombinant enzyme regiospecifically transferred a methyl group to the 4'-OH position of 8-prenylkaempferol forming icaritin. The study demonstrates that enzymatic methylation of flavonoids in Epimedium plants holds significant potential and could provide a promising alternative method for the biosynthetic production of bioactive methylated prenylflavonoids.

Background and Objectives: Despite general acceptance that corticosteroid therapy (CST) should be withheld before biopsy for suspected primary central nervous system lymphoma (PCNSL), there remains conflicting evidence surrounding the precise impact of preoperative CST on the histopathological diagnosis. The objective of this systematic review and meta-analysis was to describe and quantify the effects of preoperative CST on the diagnostic accuracy of biopsies for PCNSL., Methods: Primary articles were screened from Ovid MEDLINE, Embase, Web of Science, and Scopus databases. Meta-analysis was performed for immunocompetent patients with histologically confirmed PCNSL. Subgroup and regression analyses were performed to assess the effects of biopsy type, CST duration, dose, and preoperative taper on the diagnostic accuracy. In addition, the sensitivity of cerebrospinal fluid (CSF) analyses for PCNSL was assessed., Results: Nineteen studies, comprising 1226 patients (45% female; mean age: 60.3 years), were included. Preoperative CST increased the risk of nondiagnostic biopsy with a relative risk (RR) of 2.1 (95% CI: 1.1-4.1). In the stereotactic biopsy subgroup, the RR for nondiagnostic biopsy was 3.0 (95% CI: 1.2-7.5). CST taper, duration, and dose did not significantly influence diagnostic biopsy rates. The sensitivity of CSF cytology, including flow cytometry, for PCNSL was 8.0% (95% CI: 6.0%-10.7%)., Conclusion: Our results suggest that preoperative CST reduces the diagnostic yield of stereotactic biopsies for PCNSL. We found no evidence that tapering CST before biopsy improves diagnostic rates. CSF analysis currently has a poor sensitivity for the diagnosis of PCNSL., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Lifelong hematopoiesis is sustained by crosstalk between hematopoietic stem and progenitor cells (HSPCs) and specialized bone marrow niches. Acute myeloid leukemia (AML) upends that balance, as leukemic blasts secrete factors that remodel the bone marrow into a self-reinforcing leukemic niche. The inflammatory secretome behind this compartmental adaptation accounts for a progressive decline in hematopoietic function that leads to diagnosis and persists through early treatment. Not surprisingly, the mediators of an acute inflammatory injury and HSPC suppression have attracted much attention in an effort to alleviate morbidity and improve outcomes. HSPCs typically recover during disease remission and re-expand in the bone marrow (BM), but little is known about potentially lasting consequences for stem cells and progenitors. We recently showed that AML-experienced HSPCs actively participate in the inflammatory process during leukemic progression. HSPCs are constituent components of the innate immune system, and elegant studies of infection and experimental inflammation over the past decade have described the generation of an adoptively transferable, innate immune memory. Building on this paradigm, we discuss the potential translational relevance of a durable legacy in AML-experienced HSPC.

Phospholipids can act as antioxidants in food. In this study, egg yolk phospholipids (EPL) and sunflower oil were utilized in making chili oil, and proton nuclear magnetic resonance spectroscopy was employed to quantify the concentrations of fatty acyl groups, carotenoids, capsaicinoids in chili oil according to their specific signals in the spectra. The results showed that the changes in the concentrations of fatty acyl groups in the control samples were greater than those in the EPL-treated samples at the same frying temperature, while the contents of carotenoids and capsaicinoids were significantly lower than those of the EPL-treated samples when fried at 150 °C (p < 0.05). Two-way ANOVA indicated that frying temperature and EPL treatment, as well as their interaction had significant impacts on the thermal-oxidative stability of chili oil (p < 0.05). The results suggest that EPL may act as antioxidants during frying, and EPL can improve the thermal-oxidative stability of chili oil., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Carbodicarbenes are strong C-donor ligands, which have found numerous applications in organometallic and main group element chemistry. Herein, we report a structurally distinct carbodicarbene ligand, which is formed by dinitrogenative coupling of a Fischer carbene complex with an N-heterocyclic diazoolefin. The resulting carbonyl complex serves as a stable source for the mixed Arduengo-Fischer carbodicarbene ligand. Facile ligand transfer reactions were demonstrated to occur with gold(I), copper(I), palladium(II), and rhodium(I) complexes., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: For patients with thyroid cancer, distant metastasis is a significant predictor of poor outcome. Since distant metastasis occurs in less than 10% of patients with differentiated thyroid cancer, correlates of survival in this vulnerable patient population remain understudied. This study aimed to identify prognostic groups among patients with differentiated thyroid cancer and distant metastases and to determine the role of, and interactions between, patient and tumor characteristics in determining survival. Methods: We identified adult patients diagnosed with differentiated thyroid cancer with distant metastases from the U.S. SEER-17 cancer registry (2010-2019). Analyses were performed using Cox proportional hazards regression, survival trees, and random survival forest. Relative importance of patient and tumor factors important for disease-specific and overall survival was assessed based on the random survival forest analyses. Results: Cohort consisted of 2411 patients with differentiated thyroid cancer with distant metastases followed for a median of 62 months. Most common histopathologic subtype (86.0%) was papillary thyroid cancer, and the most common sites of distant metastasis were the lungs (33.7%) and bone (18.9%). Cox proportional hazards model illustrated significant associations between survival and the following: patient age ( p < 0.001), tumor size ( p < 0.01), and site of distant metastasis ( p < 0.05). Survival tree analyses identified three distinct prognostic groups based on disease-specific survival (DSS) (5-year survival of the prognostic groups was 92%, 64%, and 41%; p < 0.001) and four distinct prognostic groups based on overall survival (OS) (5-year survival of the prognostic groups was 96%, 84%, 57%, and 31%; p < 0.001). The first split in the survival trees for DSS and OS was by age at diagnosis (≤57 years vs. ≥58 years) with subsequent splits based on presence/absence of lung metastases, tumor size (≤4 cm vs. >4 cm), and patient age. A total of 558 patients (23.1%) died from thyroid cancer, and 757 patients (31.4%) died from all causes during the study period. Conclusions: This study identifies distinct prognostic groups for patients with differentiated thyroid cancer with distant metastases and highlights the importance of patient age, lung metastases, and tumor size for determining both disease-specific and overall survival. These findings inform risk stratification and treatment decision-making in this understudied patient population.

Importance: Racial and ethnic disparities have been observed in the outpatient visit rates for specialist care, including cancer care; however, little is known about patients' experience at the critical step of attempting to access new clinic appointments for cancer care., Objective: To determine simulated English-speaking, Spanish-speaking, and Mandarin-speaking patient callers' ability to access new clinic appointments for 3 cancer types (colon, lung, and thyroid cancer) that disproportionately impact Hispanic and Asian populations., Design, Setting, and Participants: This cross-sectional audit study was conducted between November 2021 and March 2023 using 479 clinic telephone numbers that were provided by the hospital general information personnel at 143 hospitals located across 12 US states. Using standardized scripts, trained research personnel assigned to the roles of English-speaking, Spanish-speaking, and Mandarin-speaking patients called the telephone number for a clinic that treats colon, lung, or thyroid cancer to inquire about a new clinic appointment. Data analysis was conducted from June to September 2023., Main Outcomes and Measures: The primary outcome was whether the simulated patient caller was able to access cancer care (binary variable, yes or no), which was defined to include being provided with a clinic appointment date or scheduling information. Multivariable logistic regression analysis was performed to determine factors independently associated with simulated patient callers being able to access cancer care., Results: Of 985 total calls (399 English calls; 302 Spanish calls; 284 Mandarin calls), simulated patient callers accessed cancer care in 409 calls (41.5%). Differences were observed based on language type, with simulated English-speaking patient callers significantly more likely to access cancer care compared with simulated Spanish-speaking and Mandarin-speaking patient callers (English, 245 calls [61.4%]; Spanish, 110 calls [36.4%]; Mandarin, 54 calls [19.0%]; P < .001). A substantial number of calls ended due to linguistic barriers (291 of 586 Spanish or Mandarin calls [49.7%]) and workflow barriers (239 of 985 calls [24.3%]). Compared with English-speaking simulated patient callers, the odds of accessing cancer care were lower for Spanish-speaking simulated patient callers (adjusted odds ratio [aOR], 0.34; 95% CI, 0.25-0.46) and Mandarin-speaking simulated patient callers (aOR, 0.13; 95% CI, 0.09-0.19). Compared with contacting clinics affiliated with teaching hospitals, callers had lower odds of accessing cancer care when contacting clinics that were affiliated with nonteaching hospitals (aOR, 0.53; 95% CI, 0.40-0.70)., Conclusions and Relevance: In this cross-sectional audit study, simulated patient callers encountered substantial barriers when attempting to access clinic appointments for cancer care. These findings suggest that interventions focused on mitigating these barriers are necessary to increase access to cancer care for all patients.

Soil heavy metal contamination has become a global environmental issue, which threaten soil quality, food security and human health. Symphytum officinale L. have exhibited high tolerance and restoration capacity to heavy metals (HMs) stress. However, little is known about the mechanisms of HMs in S. officinale. In this study, transcriptomic and physiological changes of S. officinale response to different HMs (Pb, Cd and Zn) were analyzed and investigated the key genes and pathways involved in HMs uptake patterns. The results showed that phenotypic effects are not significant, and antioxidant enzyme activities were all upregulated. Transcriptome analysis indicated that 1247 differential genes were up-regulated, and 1963 differential genes were down-regulated under Cd stress, while 3752 differential genes were up-regulated, and 7197 differential genes were down-regulated under Pb stress; and 527 differential genes were up-regulated; and 722 differential genes were down-regulated under Zn stress. Based on their expression, we preliminarily speculate that different HMs resistance of S. officinale may be regulated by the differential expression of key genes. These results provide a theoretical basis for determining the exact expression of genes in plants under different heavy metal stress, the processes involved molecular pathways, and how they can be efficiently utilized to improve plant tolerance to toxic metals and improve phytoremediation efficiency., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the occult nodal disease rate and whether elective regional lymph node dissection (RLND) confers any 10-year overall survival (OS) in cN0 intermediate-grade mucoepidermoid carcinoma (MEC) of the parotid gland., Materials & Methods: The National Cancer Database was reviewed from 2004 to 2016 on adults with cT1-4aN0M0 intermediate-grade parotid MEC undergoing resection with/without RLND. Comparisons between patients with and without RLND were made. Occult nodal rate and 10-year overall survival (OS) were determined., Results: Out of 898 included patients with cN0 intermediate grade parotid MEC undergoing elective RLND, the occult nodal rate was 7.6%. This was significantly different from low-grade (3.9%) and high-grade (25.7%) cN0 disease. When stratified by pT-classification, marginal differences were identified between low-grade and intermediate-grade tumors, whereas high-grade tumors demonstrated increased occult nodal disease with low T-stage (pT1-pT2, 20.4% vs. 5.1%) and high T-stage (pT3-pT4a, 32.1% vs. 17.6%). Patients undergoing elective RLND were more often treated at an academic facility (53.8% vs. 41.2%), had higher pT3-pT4 tumors (19.2% vs. 10.4%), and more frequently underwent total/radical parotidectomy (46.0% vs. 29.9%) with adjuvant radiation therapy (53.8% vs. 41.0%) Cox-proportional hazard modeling did not identify RLND, regardless if stratified by nodal yield or pT-classification, nor nodal positivity as significant predictors of 10-year OS., Conclusions: The occult nodal disease in intermediate-grade parotid MEC is low and similar to low-grade. Elective RLND may have a limited impact on OS, though its effect on locoregional control remains unknown., Level of Evidence: III., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Inflammation in the bone marrow (BM) microenvironment is a constitutive component of leukemogenesis in acute myeloid leukemia (AML). Current evidence suggests that both leukemic blasts and stroma secrete proinflammatory factors that actively suppress the function of healthy hematopoietic stem and progenitor cells (HSPCs). HSPCs are also cellular components of the innate immune system, and we reasoned that they may actively propagate the inflammation in the leukemic niche. In two separate congenic models of AML we confirm by evaluation of the BM plasma secretome and HSPC-selective single-cell RNA sequencing (scRNA-Seq) that multipotent progenitors and long-lived stem cells adopt inflammatory gene expression programs, even at low leukemic infiltration of the BM. In particular, we observe interferon gamma (IFN-γ) pathway activation, along with secretion of its chemokine target, CXCL10. We show that AML-derived nanometer-sized extracellular vesicles (EV AML ) are sufficient to trigger this inflammatory HSPC response, both in vitro and in vivo. Altogether, our studies indicate that HSPCs are an unrecognized component of the inflammatory adaptation of the BM by leukemic cells. The pro-inflammatory conversion and long-lived presence of HSPCs in the BM along with their regenerative re-expansion during remission may impact clonal selection and disease evolution., (© 2024. The Author(s).)

From September 2019 to October 2020, pathogenetic analysis of three patients clinically diagnosed as transfusion-related acute lung injury (TRALI) caused by human leukocyte antibodies was conducted by Guangzhou Blood Centre, including 2 males and 1 female, aged 56, 50 and 20 years old, respectively. Solid phase agglutination, anti-human globulin test and flow cytometry method were used to detect the presence of antibodies against patients. Sequencing-based human leukocyte antigen (HLA-SBT) typing technique was used to detect the human leukocyte antigen (HLA) genotypes of patients. Lifecodes single antigen class Ⅰ/Ⅱ kit (LSA-Ⅰ/Ⅱ) were used to detect the specificity of HLA-class Ⅰ and class Ⅱ antibodies in donor blood by Luminex 200 liquid suspension chip system. The HLA specific antibodies and corresponding epitopes in donors were also analyzed. The results showed that　HLA class Ⅰ or class Ⅱ specific antibodies against TRALI patients were detected in the blood donors. The plasma of donor 3 received by patient 1 contained antibodies against the patient's HLA-DRB1*09∶01 antigen, and the epitopes mediating the antibody reaction of the donor and recipient were 70R, 31I, 70QA. There were antibodies against the HLA-A*11∶02, HLA-A*11∶01, DRB1*12∶02, and DRB1*09∶01 antigens of patient 2 in the plasma of donor 4, and the associated antigenic epitopes were 151AHA, 57V, and 16Y. Antibodies against the HLA-DRB1*14∶04, DRB1*11∶01, and DPB1*05∶01 antigens of patient 3 were present in the plasma of donor 6 and donor 7, and the associated epitopes were 96HK, 140TV, 13SE, and 111K.　Three cases of TRALI were confirmed to be caused by HLA antibodies through laboratory analysis, and human leukocyte antibody detection should be paid attention in clinically suspected cases of TRALI, and targeted diagnosis and treatment should be given.

Octahedral coordination cages of the general formula [Pd 6 L 12 ](BF 4 ) 12 were obtained by combining [Pd(CH 3 CN) 4 ](BF 4 ) 2 with heteroditopic N-donor ligands. Four different ligands were employed. These ligands have 3-pyridyl donor groups at one end and 4-pyridyl, imidazolyl, or triazolyl donor groups at the other end. According to a geometric analysis, cages with a cis configuration at the six metal centers should be preferred (" cis rule"). This prediction was corroborated by spectroscopic data and crystallographic analyses. Limitations of the " cis rule" were also encountered, and possible explanations are discussed.

Background: There have been documented racial and ethnic disparities in the care and clinical outcomes of patients with thyroid disease., Context: Key to improving disparities in thyroid care is understanding the context for racial and ethnic disparities, which includes acknowledging and addressing social determinants of health. Thyroid disease diagnosis, treatment, and survivorship care are impacted by patient- and system-level factors, including socioeconomic status and economic stability, language, education, health literacy, and health care systems and health policy. The relationship between these factors and downstream clinical outcomes is intricate and complex, underscoring the need for a multifaceted approach to mitigate these disparities., Conclusion: Understanding the factors that contribute to disparities in thyroid disease is critically important. There is a need for future targeted and multilevel interventions to address these disparities, while considering societal, health care, clinician, and patient perspectives., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Low back pain (LBP) is a leading cause of long-term disability globally. Intervertebral disk degeneration (IVDD) is mainly responsible for discogenic pain in LBP-affected young patients. There is no effective therapy to reverse disease severity and IVDD progression. This study investigates the effect of human peripheral blood-derived mononuclear cells (PBMCs) on pain relief and life quality improvement in IVDD patients. The enriched monocytes of the PBMCs could differentiate into CD14 and CD206 double-positive M2 macrophages in vitro . Preclinical evidence in rats showed that the transplanted PBMCs exhibited anti-inflammatory and moderate tissue-repair effects on controlling IVDD progress in the rat model. The PBMCs significantly steered the aggrecan and type II collagen expressions and attenuated the pro-inflammatory cytokines in the affected disk. Based on the animal results, 36 patients with chronic low back pain (CLBP) were included in clinical trials. The control group was conservative care only, and the experimental group was platelet-rich plasma (PRP) and PBMCs intradiscal injections. We first confirmed the single lumbar disk causing the discogenic pain by provocative discography or magnetic resonance imaging (MRI). Discogenic LBP participants received one intradiscal injection of autologous PBMCs and followed for 6 months. Our clinical trial showed that patients' LBP and disability were significantly ameliorated after the PBMCs transplantation rather than PRP. These preclinical and pilot clinical studies indicate that intradiscal injection of the enriched PBMCs might be a feasible and potential cell therapy to control pain and disability in IVDD patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors have the following competing interests. The technology transfer office of National Chung Hsing University has received consultancy, speaker fees, and research grants on behalf of H-LS from Duogenic StemCells Corporation and Hualien Tzu Chi Medical Center. F-HW, C-YH, and C-IS are employees of Duogenic StemCells Corporation. F-HW, C-YH, C-IS, H-LS, and C-LL are shareholders of Duogenic StemCells Corporation. Y-HC, M-HH, S-CK, Y-HK, C-HC, and D-WCC have no conflict of interest with respect to the research, authorship, and publication of this article. Patents, products in development, and marketing products are associated with this research.

Short-chain dehydrogenase/reductases (SDRs) belong to the NAD(P)(H)-dependent oxidoreductase superfamily, which have various functions of catalyzing oxidation/reduction reactions and have been generally used as powerful biocatalysts in the production of pharmaceuticals. In this study, ScSDR1 and ScSDR2, two new SDRs have been identified and characterized from Stachybotrys chartarum 3.5365. Substrate scope investigation revealed that both of the enzymes possessed the ability to oxidize β -OH to ketone specifically, and exhibited substrate promiscuity and high stereo-selectivity for efficiently catalyzing the structurally different prochiral ketones to chiral alcohols. These findings not only suggest that ScSDR1 and ScSDR2 might be potent synthetic tools in drug research and development, but also provide good examples for further engineered enzymes with higher efficiency and stereo-selectivity.

Objective: In the last decade, new systemic treatment options have been made available for patients with advanced thyroid cancer. However, little is known about the real-world utilization of these systemic therapies., Methods: We used Optum's de-identified Clinformatics® Data Mart Database to characterize trends in the use of 15 systemic therapies that are available for the treatment of advanced thyroid cancer between 2013 and 2021. Joinpoint regression was used to calculate annual percentage changes in the use of systemic therapy by patients' race/ethnicity. The sequence of therapies was determined by the date of prescription claims., Results: Between 2013 and 2021, the annual number of patients treated for advanced thyroid cancer with systemic therapy increased from 45 patients in 2013 to 114 patients in 2021 (N of total cohort = 885). Most patients were female (54.7%) and non-Hispanic White (62.1%). Between 2013 and 2021, there was a significant decrease in the proportion of non-Hispanic White patients treated for advanced thyroid cancer with systemic therapy (annual percentage change -3.9%, 95% confidence intervals, -6.0% to -1.8%). Since its approval by the US Food and Drug Administration (FDA) in 2015, lenvatinib remains the most frequently prescribed first-line therapy for the treatment of radioiodine-refractory thyroid cancer (48.8% of patients between 2017 and 2021). Between 2017 and 2021, most patients (79.7%) were initiated on 1 of the 10 FDA-approved agents and 81.7% received only a first-line therapy., Conclusions: Between 2013 and 2021, the use of systemic treatment options for advanced thyroid cancer increased significantly, largely driven by the prescription of lenvatinib following its approval by the FDA in 2015, with an increasing trend for use in non-White patients., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)

Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly-metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase-expressing (S18-1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI-related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5-8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR., (© 2023 Wiley Periodicals LLC.)

Egg yolk phospholipids (PLs) extracted by organic solvent are prone to oxidation, while they are quite stable in egg yolk. This study was to verify the decisive role of lutein (naturally present in egg yolk) on the oxidative stability of PLs by constructing liposome. The liposome samples were heated at 100 °C for 10 min, and then the oxidation products of the liposome samples were analyzed by 1 H NMR and GC-MS. The results showed that the concentrations of most of the oxidation products in the PLs-liposomes sample were significantly higher than those in the PLs&lutein-liposomes sample. Therefore, lutein could protect egg yolk PLs from oxidation, thus inhibiting the formation of lipid-derived volatile compounds. As those lipid-derived volatile compounds are the key fatty note odorants, this study has confirmed that the removal of lutein is the determining factor in using egg yolk PLs as an ideal precursor of fatty note odorants., Competing Interests: The authors declare that they have no conflict of interest.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 Author(s).)

Purpose: Our study aimed to determine the impact of a novel technique of anesthesia administration on the clinical outcomes and complications in geriatric patients with severe systemic disease undergoing hip surgery., Methods: We retrospectively identified patients aged > 65 years with severe systemic disease that was a constant of life [American Society of Anesthesiologists (ASA) IV] who underwent surgery for hip fracture between January 2018 and January 2020. The patients were divided into two groups: Group I [fascia iliaca compartment block plus propofol-based total intravenous anesthesia (FICB + TIVA)] and Group II [general anesthesia (GA)]. The primary outcomes were 30-day and 1-year mortality. The secondary outcomes included length of hospital stay, length of intensive care unit (ICU) stay, postoperative morbidity, Visual Analog Scale score, and consumption of analgesics., Results: There was no significant difference in the 30-day mortality (5 vs. 3.8%, p = 0.85) and 1-year mortality (15 vs. 12%, p = 0.73) between the groups. Group I had significantly lower ICU requirements (p = 0.01) and shorter lengths of ICU stay (p < 0.001) and hospital stay (p < 0.001). Moreover, a smaller proportion of patients in Group I required postoperative morphine or oral opiates., Conclusion: Geriatric patients who underwent hip surgery under FICB + TIVA required fewer ICU admissions, shorter lengths of ICU and hospital stay, and had lesser postoperative opioid consumption than those who were under GA. Hence, we recommend the novel FICB + TIVA technique for hip fracture surgery in geriatric patients with poor general health status and high surgical risks (ASA IV)., (© 2023. The Author(s).)

Didymocarpussubpalmatinervis W.T.Wang was shown to be conspecific with Petrocodonlithophilus Y.M.Shui, W.H.Chen & Mich.Möller, by checking original literature, examining specimens, tracing specimen collecting history, and conducting field surveys. The results show morphological characteristics and geographical distribution overlaps between these two species. The transfer of Didymocarpussubpalmatinervis to Petrocodon as a new combination with Petrocodonsubpalmatinervis (W.T.Wang) F.Wen & Z.L.Li is proposed here, and P.lithophilus is synonymized with P.subpalmatinervis . Color photographs and essential information are also provided, including a detailed comparison of description, distribution, habitat, and the proposed IUCN conservation status., Competing Interests: The authors have declared that no competing interests exist., (Zheng-Long Li, Zhang-Jie Huang, Da-Wei Chen, Xin Hong, Fang Wen.)

In the present study, the antimicrobial peptide nisin was successfully conjugated onto the surface of sulfonated polyetheretherketone (SPEEK), which was decorated with graphene oxide (GO) to investigate its biofilm resistance and antibacterial properties. The PEEK was activated with sulfuric acid, resulting in a porous structure. The GO deposition fully covered the porous SPEEK specimen. The nisin conjugation was accomplished using the crosslinker 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) through a dip-coating method. The surface micrographs of the SPEEK-GO-nisin sample indicated that nisin formed discrete islets on the flat GO surface, allowing both the GO and nisin to perform a bactericidal effect. The developed materials were tested for bactericidal efficacy against Staphylococcus aureus ( S. aureus ). The SPEEK-GO-nisin sample had the highest antibacterial activity with an inhibition zone diameter of 27 mm, which was larger than those of the SPEEK-nisin (19 mm) and SPEEK-GO (10 mm) samples. Conversely, no inhibitory zone was observed for the PEEK and SPEEK samples. The surface micrographs of the bacteria-loaded SPEEK-GO-nisin sample demonstrated no bacterial adhesion and no biofilm formation. The SPEEK-nisin and SPEEK-GO samples showed some bacterial attachment, whereas the pure PEEK and SPEEK samples had abundant bacterial colonies and thick biofilm formation. These results confirmed the good biofilm resistance and antibacterial efficacy of the SPEEK-GO-nisin sample, which is promising for implantable orthopedic applications.

Background: Patients with limited English proficiency, a vulnerable patient population, remain understudied in the literature addressing cancer disparities. Although it is well documented that language discordance between patients and physicians negatively impacts the quality of patient care, little is known about how patients' preferred spoken language impacts their access to cancer care., Patients and Methods: Between November 2021 and June 2022, we conducted an audit study of 144 hospitals located across 12 demographically diverse states. Using a standardized script, trained investigators assigned to the roles of English-speaking, Spanish-speaking, and Mandarin-speaking patients called the hospital general information telephone line seeking to access care for 3 cancer types that disproportionately impact Hispanic and Asian populations (colon, lung, and thyroid cancer). Primary outcome was whether the simulated patient caller was provided with the next steps to access cancer care, defined as clinic number or clinic transfer. We used chi-square tests and logistic regression analysis to test for associations between the primary outcome and language type, region type, hospital teaching status, and cancer care requested. We used multivariable logistic regression analysis to determine factors associated with simulated patient callers being provided the next steps., Results: Of the 1,296 calls, 52.9% (n=686) resulted in simulated patient callers being provided next steps to access cancer care. Simulated non-English-speaking (vs English-speaking) patient callers were less likely to be provided with the next steps (Mandarin, 27.5%; Spanish, 37.7%; English, 93.5%; P<.001). Multivariable logistic regression found significant associations of the primary outcome with language spoken (Mandarin: odds ratio [OR], 0.02 [95% CI, 0.01-0.04] and Spanish: OR, 0.04 [95% CI, 0.02-0.06] vs English) and hospital teaching status (nonteaching: OR, 0.43 [95% CI, 0.32-0.56] vs teaching)., Conclusions: Linguistic disparities exist in access to cancer care for non-English-speaking patients, emphasizing the need for focused interventions to mitigate systems-level communication barriers.

Anhydroicaritin ( 1a ), baohuoside ( 1b ) and icariin ( 1c ) were recognized as major pharmacologically active ingredients of Epimedium plants. Their primary means of acquisition were chemical isolation from plants. However, it suffers from low yield, environmental pollution and shortage of plants. Herein, to remedy these problems, biosynthesis was explored to obtain the three active ingredients. Fortunately, with SfFPT as 8-prenyltransferase, EpPF3RT and Ep7GT as glycosyltransferases, kaempferide ( 1 ) was transferred to 1a , 1b and 1c enzymatically. Thus, we report the details of this method. This approach represents a promising environmental friendly alternative for the production of these compounds from an abundant analogue.

Retinal ganglion cell (RGC) neurodegeneration in glaucoma is not prevented by controlling the elevated intraocular pressure alone. Neuroprotective gene therapy approaches could be an essential part of a combination treatment. Five cell adhesion peptide (CAP)-gemini surfactants (18-7N(p 1 - 5 )-18) were synthesized as building blocks for brain-derived neurotrophic factor (BDNF) gene carrier nanoparticles (CAP-NPXs). The composition of CAP-NPXs was optimized, physicochemically characterized and evaluated for in vitro transfection efficiency (TE) in A7 astrocytes, 3D retinal neurospheres and for gene expression in vivo in CD1 mice using RFP reporter gene and BDNF levels after intravitreal (IVT) injection. The IgSF-binding 18-7N(p FASNKL )-18 pNPXs treated cells demonstrated 1.4-fold higher TE compared to integrin-binding 18-7N(p RGD )-18 pNPXs and parent 18-7NH-18 NPXs with overall viability between 86 and 95%. The 18-7N(p FASNKL )-18 pNPXs selectively transfected RGCs in 3D MiEye8 neurospheres. In the in vivo CD1 mouse model 18-7N(p FASNKL )-18 pNPXs administered by IVT injection delivered tdTomato/BDNF plasmid to retinal cells and produced higher gene expression than the 18-7N(p RGD )-18 pNPXs, the parent 18-7NH-18 NPXs and Lipofectamine® 3000 as demonstrated by confocal microscopy of whole mount retinas. The BDNF gene expression, assessed by ELISA, showed significantly high levels of BDNF with 18-7N(p FASNKL )-18 (422.60 ± 42.60 pg/eye), followed by 18-7N(p RGD )-18 pNPXs (230.62 ± 24.47 pg/eye), 18-7NH-18 NPXs (245.90 ± 39.72 pg/eye), Lipofectamine® 3000 (199.99 ± 29.90 pg/eye) and untreated controls (131.33 ± 20.30 pg/eye). In summary, the 18-7N(p FASNKL )-18 pNPXs induced 3.4-fold higher BDNF level compared to controls and 2-fold higher than 18-7N(p RGD )-18 pNPXs. The in vivo efficacy of 18-7N(p FASNKL )-18 NPXs to produce BDNF at pharmacologically relevant levels supports further studies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

For thyroid cancer clinical trials, the inclusion of participants from diverse patient populations is uniquely important given existing racial/ethnic disparities in thyroid cancer care. Since 2011, a paradigm shift has occurred in the treatment of advanced thyroid cancer with the approval of multiple systemic therapies by the US Food and Drug Administration based on their use in the clinical trials setting. Although these clinical trials recruited patients from up to 164 sites in 25 countries, the inclusion of racial/ethnic minority patients remained low. In this mini-review, we provide an overview of barriers to accessing cancer clinical trials, framed in the context of why patients with thyroid cancer may be uniquely vulnerable. Multilevel interventions and increased funding for thyroid cancer research are necessary to increase access to and recruitment of under-represented patient populations into thyroid cancer clinical trials., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

The past 5-10 years have brought in a new era in the care of patients with thyroid cancer, with the introduction of transformative diagnostic and management options. Several international ultrasound-based thyroid nodule risk stratification systems have been developed with the goal of reducing unnecessary biopsies. Less invasive alternatives to surgery for low-risk thyroid cancer, such as active surveillance and minimally invasive interventions, are being explored. New systemic therapies are now available for patients with advanced thyroid cancer. However, in the setting of these advances, disparities exist in the diagnosis and management of thyroid cancer. As new management options are becoming available for thyroid cancer, it is essential to support population-based studies and randomised clinical trials that will inform evidence-based clinical practice guidelines on the management of thyroid cancer, and to include diverse patient populations in research to better understand and subsequently address existing barriers to equitable thyroid cancer care., Competing Interests: Declaration of interests We declare no competing interests. Editorial note: The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations., (Copyright © 2023 Elsevier Ltd. All rights reserved.)