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Shu Li,1 Fu-Zheng Guo,2 Xiu-Juan Zhao,1 Qi Wang,3 Hui Wang,3 You-Zhong An,1 Feng-Xue Zhu1,21Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Trauma Centre, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaPurpose: Active surveillance of carbapenem-resistant Enterobacteriaceae (CRE) may contribute to the decline of the infection rate. Individualized active surveillance of CRE could cost less than screening all patients. However, the impact of individualized active surveillance on the CRE infection rate in intensive care units (ICUs) has not been well described.Patients and methods: We retrospectively studied the clinical data of all patients admitted in the ICUs of a tertiary-care hospital in China from 2015 to 2017 during two periods, before and after the implementation of individualized active surveillance. During period 1 (January 2015–April 2016), no screening protocol was used. During period 2 (May 2016–December 2017), we implemented active CRE screening for selected patients according to their clinical characteristics. The trend of CRE rate infection was analyzed by a joinpoint regression model, and multivariate analysis was performed to analyze the association of active surveillance, Acute Physiology and Chronic Health Evaluation (APACHE) II score, prior antimicrobial use, length of mechanical ventilation (MV) before infection, and other risk factors with CRE infection rate.Results: A total of 5,372 patients were included. After assessing the patients’ clinical characteristics, 72.3% (3,882/5,372) were considered to be at high risk of CRE infection. During period 1, the infection percent of CRE increased by 13.04% every month (95% CI: 5.2–21.5). During period 2, the infection rate decreased (monthly percent change, −3.57%; 95% CI −6.9 to −0.1, P

Yu-Lin Zhong,1,* Rui-Yang Hu,2,* Yuan-Zhi He,3 Xiao-Tong Li,3 Zi-Cong Li,4 Xin Huang1 1Department of Ophthalmology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, People’s Republic of China; 2School of Ophthalmology and Optometry, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 3Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 4Department of Radiology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zi-Cong Li, Department of radiology, Jiangxi Provincial People’s Hospital, No. 152, Ai Guo Road, Dong Hu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Email 39652858@qq.com Xin Huang, Department of ophthalmology, Jiangxi Provincial People’s Hospital, No. 152, Ai Guo Road, Dong Hu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 15879215294, Email 334966891@qq.comBackground: This study aims to explore changes in white matter function and network connectivity in individuals with DR.Methods: This study included 46 patients with DR and 43 age- and gender-matched healthy control (HC) participants were enrolled in the study. The aim was to investigate inter-group differences in white matter (WM) function and to analyze changes in the WM network among DR patients.Results: Increased degree centrality (DC) values were observed in the middle cerebellar peduncle and genu of the corpus callosum, while higher fractional amplitude of low-frequency fluctuations (fALFF) values were found in the left superior corona radiata, right anterior corona radiata, and right superior longitudinal fasciculus. Conversely, reduced regional homogeneity (ReHo) values were noted in the left posterior thalamic radiation among patients with DR compared to HC, with statistical correction applied The SVM classification accuracy for distinguishing between DR and HC patients based on WM measures indicated values of 81.52%, 80.43%, and 89.13% for DC, fALFF, and ReHo, respectively, with respective area under the curve (AUC) values of 0.87, 0.85, and 0.93. Furthermore, alterations were detected within specific brain regions including the body of corpus callosum (BCC), splenium of corpus callosum (SCC), genu of corpus callosum (GCC), left posterior thalamic radiation (PTR), right anterior corona radiata (ACR), and right posterior corona radiata (PCR) in the DR group compared to HCs, with an intra-network decrease in connectivity. Interestingly, the left superior longitudinal fasciculus (SLF) within the DR group exhibited an intra-network increase compared to the HC group.Conclusion: DR exhibited abnormal white matter functional alterations, particularly affecting the fiber pathways linking the visual network to the sensory-motor network.Keywords: diabetic retinopathy, degree centrality, DC, fractional amplitude of low-frequency fluctuation, fALFF, regional homogeneity, ReHo, independent component analysis, ICA

Yun-Mei Yu, Yuan-Zhu Long,* Zhao-Qiong Zhu* Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuan-Zhu Long; Zhao-Qiong Zhu, Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, No. 149 Dalian Road, Zunyi, Guizhou, 563000, People’s Republic of China, Email 125682383@qq.com; zhuzhaoqiong@zmu.edu.cnAbstract: Local anesthetics, particularly amide types, play a crucial role in perioperative anesthesia to alleviate pain and manage chronic, long-term pain, with their brief effect period remaining a universal challenge that needs resolution. There is a high anticipation for creating materials that maintain prolonged effectiveness of local anesthetics through a straightforward administration technique. Chitosan is the most typical natural amino polymer, which is highly reactive and easy to modify. It has been widely and deeply used in the field of medicine. At present, it is mainly used in tissue regeneration and repair, hemostasis and wound healing, antibacterial and anti-infection, disease diagnosis and treatment detection, and drug delivery. In the field of anesthesia, chitosan is regarded as a potential perfect carrier for the sustained release of amide local anesthetics. This document aims to analyze the current application of chitosan as a prolonged-release substance in amide-type local anesthetics, encapsulate the associated research advancements, and subsequently investigate the practicality and prospects of its medical uses.Keywords: extended-release carrier, chitosan, amide local anesthetics, duration of action

Dong-Mei Guan,1,* Yuan-Zhuang Shan,1,* Hao-Tian Zhao,2 Ying Meng,2 Zhong-Rui Yan,2 Hai-Lin Zhang2 1Shandong University of Tradition Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Department of Neurology, Jining No.1 People’s Hospital, Jining, Shandong, People’s Republic of China*These authors contributed equally to this studyCorrespondence: Hai-Lin Zhang, Department of Neurology, Jining No.1 People’s Hospital, No. 6 of Healthy Road, Rencheng District, Jining, Shandong, 272000, People’s Republic of China, Tel +86 176 6130 0365, Email zhanghailin_zhl@126.comBackground: Hemiplegic migraine, a less common variant of migraine, is the focus of this paper. Within the scope of this study, we present a case of hemiplegic migraine that bears the potential for misdiagnosis, particularly as encephalitis.Brief introduction to the Disease: The patient developed a right-sided headache a day prior to admission, accompanied by fever, nausea, vomiting, and left-sided limb weakness. On the fourth day, the patient experienced a grand mal epilepsy, marked by unconsciousness, leftward deviation of both eyes, limb convulsions, and foaming at the mouth. Cerebrospinal fluid analysis revealed no apparent abnormalities, Electroencephalography showed abnormal slow waves, imaging studies indicated swelling and meningeal thickening in the right cortex, and genetic testing identified a heterozygous mutation in the ATPIA2 gene. The diagnosis was hemiplegic migraine, and the patient received symptomatic supportive treatment, leading to improvement and subsequent discharge. Flunarizine and sodium valproate were prescribed post-discharge, and the patient achieved complete recovery after a one-month follow-up.Conclusion: Apart from experiencing headaches, patients with hemiplegic migraine may exhibit additional symptoms like fever, epilepsy, and hemiplegia. These manifestations warrant clinical attention, and if deemed necessary, genetic testing should be conducted, and this is an autosomal dominant pattern.Keywords: ATP1A2 gene mutation, encephalitis, migraine, hemiplegic migraine, swelling of the cortex

Yong Chen,1 Mang He,1 Si-Jin Zhao,2 Yan-Juan Chen,1 Yong-Qiao Zhang,2 Xiao-Long Chen,2 Chuan-Jie Yang,2 Yu-Zhuo Luo,2 Kutty Selva Nandakumar,3 Zhou-Xiong Xing,4 Mei Tian1 1Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 2Undergraduate Students of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 3Docent, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; 4Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of ChinaCorrespondence: Mei Tian; Zhou-Xiong Xing, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi City, Guizhou Province, People’s Republic of China, Email 348820517@qq.com; xingzhouxiong111@126.comPurpose: To investigate the clinical value of adding Jin-gu-lian (JGL) capsules into rheumatoid arthritis (RA) treatment by examining its impact on disease activity and quality of life (QoL) through a real-world study (RWS).Patients and methods: RWS was conducted to compare the inflammatory markers, including IgM-RF, ESR, and CRP, between RA patients treated with only Western medicine (reference group) and Western medicine plus JGL (study group) during one-year follow-up. The clinical data was acquired from the hospital information system (HIS). Telephone call-based follow-up on QoL (SF-36) and accompanying symptoms, including gastrointestinal complaints, attacks of pneumonia, herpes zoster, URTIs, UTIs, and LTBIs. Finally, the anti-rheumatic drugs given to both groups were also compared. RWS was further validated for its feasibility by performing studies with hydroxychloroquine (HCQ) treatment, which is a commonly used anti-rheumatic drug for RA with mild effect.Results: The study group failed to show a significant effect on inflammatory markers, especially on the CRP levels, indicating no additional clinical value of supplementing with JGL. Similarly, at the endpoint, no significant differences between the two groups on QoL and related symptoms were observed. Our study suggests that the patients in the study group might need more anti-rheumatic drugs to fill the treatment insufficiency, and the application ratio of NSAIDs would be significantly higher than the reference group. By conducting this study on HCQ treatment, the positive aspects of controlling disease activity and reducing NSAIDs application were found, which demonstrates the utility of performing the RWS to evaluate the effect of JGL.Conclusion: Adding JGL did not significantly improve the clinical efficacy of RA treatment by this RWS. Folk herbal prescriptions such as JGL are suggested to underwent strict clinical trials before application.Keywords: real-world study, rheumatoid arthritis, traditional Chinese medicine, disease activity, hydroxychloroquine

Houriah Y Nukaly,1 Raghad A Aljuhani,1 Mahinar M Alhartani,1 Yosra Z Alhindi,2 Uzma Asif,1 Asim M Alshanberi,1,3 Safaa M Alsanosi2 1General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia; 2Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 3Department of Community Medicine and Pilgrims Health Care, Umm Alqura University, Makkah, Saudi ArabiaCorrespondence: Safaa M Alsanosi, Email smsanosi@uqu.edu.saIntroduction: The World Health Organization (WHO) has placed great importance on providing thorough, hands-on training to medical students regarding responsible and appropriate antibiotic prescription. Accordingly, this study aims to gain a better perspective on the knowledge of antibiotic use and resistance among medical students in Jeddah, Saudi Arabia.Methods: A questionnaire-based cross-sectional study was conducted among medical students in Jeddah, Saudi Arabia, from 1 September to 30 November 2023. The categorical variables are presented as frequencies and percentages. Mann–Whitney and Kruskal–Wallis tests were used to compare the outcomes, and generalised linear regression models were constructed to predict the students’ knowledge of antibiotics and antibiotic resistance. A p-value of < 0.05 was taken to indicate statistical significance.Results: The study included a total of 353 medical students. First-year medical students represented 28.60% of the participants, while females represented 76.80%. Most participants (92.40%) agreed that antibiotics are effective against bacteria, whereas only 25.20% agreed about antibiotics’ effectiveness against viruses. More than half of the participants (53.80%) believed that bacterial infections can be resolved without antibiotics. A significant majority (78.20%) agreed that the unnecessary use of antibiotics makes them less effective. More than half of the participants (56.90%) acknowledged that infections caused by resistant bacteria are increasing in Saudi Arabia, and two-thirds (75.10%) believed that healthcare workers could effectively reduce antibiotic resistance in Saudi Arabia. Male students had low knowledge about antibiotics [Beta = − 1.429, 95% CI (− 2.618, − 0.241), P value = 0.019].Conclusion: Improving the curriculum by incorporating topics like resistance mechanisms and responsible antibiotic usage can address the knowledge gap among male students. This comprehensive training, utilizing various educational methods, is essential for fostering responsible antibiotic practices among future healthcare professionals.Keywords: antibiotic use, antibiotic resistance, medical students, Saudi Arabia

Hamsah S Alqashqri,1 Ahmed Siddiqi,2 Halah T Albar,3 Enas H Alfalogy,1,4 Nahla H Hariri,1 Yosra Z Alhindi,5 Asim M Alshanberi,1 Safaa M Alsanosi,5 Alaa H Falemban5 1Department of Community Medicine and Pilgrims Health Care, Faculty of Medicine, Umm Al Qura University, Makkah, Saudi Arabia; 2Department of Internal Medicine, National Guard Hospital, Jeddah, Saudi Arabia; 3Department of Physiology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 4Family Medicine, Faculty of Medicine, Suez-Canal University, Ismailia, Egypt; 5Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al Qura University, Makkah, Saudi ArabiaCorrespondence: Alaa H Falemban, Email ahfalemban@uqu.edu.saIntroduction: As a result of the physiological decline in renal function that comes with age and the common failure to recognise renal insufficiency, older adults aged 65 and above are at increased risk of receiving medications that are inappropriate for their level of renal function which in turn lead to increased risk of adverse effects. Little is known about how many older adults receive medications that are inappropriate for their level of renal function. This study aimed to determine the prevalence of renally inappropriate medications in elderly adults by reviewing patient files and evaluating the appropriateness of medication doses relative to renal function in patients aged ≥ 65 years at inpatient healthcare departments.Methods: A retrospective cross-sectional study of patients aged ≥ 65 years was conducted, covering cases from 2015 to 2021. Patient’s medical records were reviewed, their renal function and medications lists were evaluated, determined whether they had been prescribed at least one renally inappropriate medication based on drug-dosing recommendations for different degrees of renal function.Results: A total of 317 elderly inpatients were included, 10% of whom had received inappropriate doses relative to their renal function. Glomerular filtration rate was associated with inappropriate dosing in this study. Of the patients CKD stage 5, 36.8% had at least one drug administered at an inappropriate dose, while this figure was 6.5% among the patients at CKD stage 1; this difference was statistically significant (p = 0.001).Conclusion: A notable portion of older adults may be at risk of adverse effects due to inappropriate medication dosing related to their renal function. Further studies with large samples, drug use analyses based on comprehensive geriatric references and a prioritisation of actual outcomes over potential outcomes are needed to further determine elderly adults’ exposure to inappropriate drugs.Keywords: older adults, geriatric, inappropriate medication, healthcare outcomes, elderly inpatients, renally inappropriate medication, physiological decline, healthcare evaluation, insufficiency

Qi Wang,1,&ast; Xiao-Xiang Jiang,1,&ast; Yan-Zhen Que,2,&ast; Xiao-Ying Wan,2 Chao-Qin Lin1 1Department of Gynecology, Fujian Maternity and Child Health Hospital, Fujian Provincial Key Laboratory of Women and Children’s Critical Diseases Research, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Gynecology and Obstetrics, Shaxian General Hospital, Sanming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao-Qin Lin, Department of Gynecology, Fujian Maternity and Child Health Hospital, 18 Dao-Shan Street, Gu-Lou District, Fuzhou, 350000, People’s Republic of China, Tel +8613950422970, Email lcqfjsfy@126.com Xiao-Xiang Jiang, Department of Gynecology, Fujian Maternity and Child Health Hospital, Fujian Provincial Key Laboratory of Women and Children’s Critical Diseases Research, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China, Email 19959179535@163.comPurpose: With China’s rapidly aging population and the rising proportion of obese people, an increase in the number of women suffering from urinary incontinence (UI) is to be expected. In order to identify high-risk groups before leakage occurs, we aimed to develop and validate a model to predict the risk of stress UI (SUI) in rural women.Patients and methods: This study included women aged 20– 70 years in rural Fujian who participated in an epidemiologic survey of female UI conducted between June and October 2022. Subsequently the data was randomly divided into training and validation sets in a ratio of 7:3. Univariate and multivariate logistic regression analyses were used to identify independent risk factors as well as to further construct a nomogram for risk prediction. Finally, concordance index (C-index), calibration curve and decision curve analysis were applied to evaluate the performance of the predictive models.Results: A total of 5290 rural females were enrolled, of whom 771 (14.6%) had SUI. Age, body mass index (BMI), postmenopausal status, number of vaginal deliveries, vaginal delivery of large infant, constipation and family history of pelvic organ prolapse (POP) and SUI were included in the nomogram. C-index of this prediction model for the training and validation sets was 0.835 (95% confidence interval [CI] = 0.818– 0.851) and 0.829 (95% CI = 0.796– 0.858), respectively, and the calibration curves and decision analysis curves for both the training and validation sets showed that the model was well-calibrated and had a positive net benefit.Conclusion: This model accurately estimated the SUI risk of rural women in Fujian, which may serve as an effective primary screening tool for the early identification of SUI risk and provide a basis for further implementation of individualized early intervention. Moreover, the model is concise and intuitive, which makes it more operational for rural women with scarce medical resources.Keywords: stress urinary incontinence, rural women, risk factors, nomogram, predict model

Alexandr Ceasovschih,1,2,&ast; Victorița Șorodoc,1,2 Serghei Covantsev,3,&ast; Anastasia Balta,1,2,&ast; Jamol Uzokov,4,&ast; Sergio E Kaiser,5 Abdallah Almaghraby,6 C&abreve;t&abreve;lina Lionte,1,2 Cristian St&abreve;tescu,1,7 Radu A Sasc&abreve;u,1,7 Viviana Onofrei,1,8 Raluca Ecaterina Haliga,1,2,&ast; Alexandra Stoica,1,2,&ast; Cristina Bologa,1,2 Ștefan Ailoaei,7 Yusuf Ziya &Scedil;ener,9 Nicholas G Kounis,10 Laurențiu Șorodoc1,2 1Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania; 2 2nd Internal Medicine Department, “Sf. Spiridon” Clinical Emergency Hospital, Iasi, Romania; 3Department of Research and Clinical Development, Botkin Hospital, Moscow, Russia; 4Department of Cardiology, Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation, Tashkent, Uzbekistan; 5Discipline of Clinical and Experimental Pathophysiology, Rio de Janeiro State University, Rio de Janeiro, Brazil; 6Department of Cardiology, Ibrahim Bin Hamad Obaidallah Hospital, Ras Al Khaimah, United Arab Emirates; 7Department of Cardiology, “Prof. Dr. George I.M. Georgescu” Cardiovascular Diseases Institute, Iasi, Romania; 8Department of Cardiology, “Sf. Spiridon” Clinical Emergency Hospital, Iasi, Romania; 9Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkiye; 10Department of Internal Medicine, Division of Cardiology, University of Patras Medical School, Patras, Greece&ast;These authors contributed equally to this workCorrespondence: Victorița Șorodoc, 2nd Internal Medicine Department, “Sf. Spiridon” Clinical Emergency Hospital, Independentei 1 Street, Iasi, 700106, Romania, Tel +40232 240 822, Email vivisorodoc@yahoo.com Viviana Onofrei, Cardiology Department, “Sf. Spiridon” Clinical Emergency Hospital, Independentei 1 Street, Iasi, 700106, Romania, Email onofreiviviana@gmail.comAbstract: Despite the noteworthy advancements and the introduction of new technologies in diagnostic tools for cardiovascular disorders, the electrocardiogram (ECG) remains a reliable, easily accessible, and affordable tool to use. In addition to its crucial role in cardiac emergencies, ECG can be considered a very useful ancillary tool for the diagnosis of many non-cardiac diseases as well. In this narrative review, we aimed to explore the potential contributions of ECG for the diagnosis of non-cardiac diseases such as stroke, migraine, pancreatitis, Kounis syndrome, hypothermia, esophageal disorders, pulmonary embolism, pulmonary diseases, electrolyte disturbances, anemia, coronavirus disease 2019, different intoxications and pregnancy.Keywords: electrocardiography, electrocardiogram, features, non-cardiac diseases, ECG

Yang Fu,&ast; Xiao-Qin Huang,&ast; Hang-Bo Qu, Yan Zhi Ge, Xuan-Liang Ru Department of Orthopedics, Zhejiang Hospital, Hangzhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuan-Liang Ru, Department of Orthopedics, Zhejiang Hospital, No. 1229 Gudun Road, Hangzhou, Zhejiang Province, 310013, People’s Republic of China, Tel +86-133-3612-4875, Email zjyyrxl@qq.comBackground: Intervertebral disc degeneration (IVDD) is the main cause of low back pain (LBP), but the specific regulatory factors, pathways and specific molecular mechanisms remain unclear.Methods: We identified and quantitatively analyzed Pfirrmann Grade II (n=3) and Pfirrmann Grade IV (n=3) pulposus samples via MRI. The differential abundance of proteins in the samples was determined and quantitatively analyzed by relative and absolute quantitative analysis of the isotope marker levels combined with the liquid chromatography–tandem mass spectrometry (LC‒MSMS/MS).Results: A total of 70 proteins (30 significantly increased proteins (> 1.2-fold change) and 40 significantly decreased proteins (< 0.8-fold change)) showed different levels among the groups. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO) enrichment analyses and Western blot analysis showed that CYCS, RAC1, and PSMD14 may play important roles in IVDD and that Epstein‒Barr virus infection, viral myocarditis, colorectal cancer, nonalcoholic fatty liver disease (NAFLD) and amyotrophic lateral sclerosis (ALS) are the main pathways involved in IVDD.Conclusion: CYCS, RAC1 and PSMD14 may play important roles in IVDD, and Epstein‒Barr virus infection, viral myocarditis, colorectal cancer, NAFLD and ALS may be the main pathways involved in IVDD.Keywords: TMT, LC‒MS/MS, proteomics, low back pain, nucleus pulposus

Yun-Zhu Wu,1,2 Qing-Yun Song1,2 1Department of Diagnostic Ultrasound, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Chengdu, People’s Republic of ChinaCorrespondence: Qing-Yun Song, Department of Diagnostic Ultrasound, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China, Email huaxi2chaoshengsqy@163.comBackground: Placental infarction refers to a localized area of ischemic villous necrosis resulting from the interruption of maternal blood flow to the intervillous space, which can be attributed to spasm, stenosis, or occlusion of the decidual spiral artery caused by systemic or localized maternal vascular disease. The presence of large placental infarcts may pose significant risks to fetal well-being, including intrauterine growth retardation, fetal distress, and even fetal demise. Although placental infarction is commonly identified during postnatal pathological examinations, its prenatal diagnosis through ultrasound remains challenging and has been rarely reported.Case Presentation: This report presents a case of acute placental infarction diagnosed by prenatal ultrasound using Superb Micro-vascular Imaging (SMI) technology. At 23 weeks’ gestation, the ultrasound revealed that the placenta was attached to the left lateral and posterior walls of the uterus, showing localized thickening. Within this area of thickening, there were observed inhomogeneous hypoechoic regions. Superb Micro-vascular Imaging (SMI) revealed an abnormal echogenic region within the thickened placental tissue that lacked microvascular blood flow signals, but showed surrounding vascularity. Visually, this elliptical-shaped echogenic region enveloped by microvascular blood flow. From the 29th weeks of gestation onward, ultrasound suggested that the fetus was small for gestational age. A live baby weighing 2360g was delivered by cesarean section at 37 weeks’ gestation. The placenta was approximately 20× 18 × 3 cm with large grayish-yellow infarcts.Conclusion: SMI allows rapid screening of large placental infarcts and easy detection of regions without normal vessel trees, thereby reducing missed diagnoses. Infarct area is easily measured by measuring the area surrounded by small blood vessels, especially in acute placental infarction, which is very helpful in accurately determining infarct size.Keywords: SMI, placental infarction, prenatal ultrasound diagnosis

Recently, the electrical switching of antiferromagnetic (AFM) order has been intensively investigated because of its application potential in data storage technology. Herein, we report the current switching of the AFM Néel vector in epitaxial Pd/CoO films as a function of temperature. Using combined measurements of Hall resistance (HR) and x-ray magnetic linear dichroism (XMLD) below and above the AFM Néel temperature, we unambiguously identified both magnetic and nonmagnetic contributions to the current-induced HR change. Through magnetic field-induced HR measurements, we quantitatively determined the percentage of current-induced CoO spin switching. Further, we showed that the thermal effect dominated the CoO magnetic switching more in samples with a thinner Pd layer and that samples with a thicker CoO layer required higher thermal activation for current-induced magnetic switching. These results provide a clear and comprehensive picture of current-induced AFM spin switching across the AFM Néel temperature.

Using element-resolved x-ray magnetic circular dichroism (XMCD) and x-ray magnetic linear dichroism (XMLD) measurements, we determined the spin orientations of Ni, CoO and Fe films in Ni/CoO/Fe films grown on a curved MgO(0 0 1) substrate. We find that the vicinal surface of MgO(0 0 1) substrate results in a spin canting towards out-of-plane direction in the Ni and CoO films as a result of the interfacial coupling. The Ni spin canting angle increases monotonically with the vicinal angle in the studied range of 0–17° and the CoO spin canting angle increases more rapidly towards saturation only at a few degrees of the vicinal angle. The uniaxial magnetic anisotropy induced in the Ni layer by the Ni/CoO interfacial coupling is quantitatively determined and is shown to increase monotonically with the vicinal angle. Our result provides a new pathway for tailoring the spin orientation by modifying the substrate surface symmetry in combining with the ferromagnetic/antiferromagnetic interfacial interaction in thin-film based spintronic devices.

Guang Zeng,1,&ast; Yong-Zhi Jin,1,&ast; Yi Huang,1 Jun-Sheng Hu,1 Meng-Fan Li,2 Ming Tian,3 Jun Lu,4 Rong Huang1 1Department of General Surgery, Putuo Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People’s Republic of China; 2Department of General Surgery, LiQun Hospital, Shanghai, 200333, People’s Republic of China; 3Department of Burn, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of China; 4Department of Endocrinology, Putuo Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Lu; Rong Huang, Email lujundoctor@163.com; huangrongsci@163.comBackground: The pathological damage mechanism of type 2 diabetes (T2D) and macroangiopathy is extremely complex, and T2D and arteriosclerosis obliterans have different biological behaviors and clinical features. To explore the mechanism of lower extremity arteriosclerosis occlusion (LEAOD) in T2D patients, we utilized RNA-seq to identify unique gene expression signatures of T2D and LEAOD through transcriptomic analysis.Methods: We obtained blood samples and performed RNA sequencing from four patients with T2D, five of whom had LEAOD. Another six age- and gender-matched blood samples from healthy volunteers were used for control. By exploring the general and specific differential expression analysis after transcriptome sequencing, specific gene expression patterns of T2D and LEAOD were verified.Results: Transcriptome analysis found differentially expressed genes in T2D, and T2D + LEAOD (vs normal) separately, of which 35/486 (T2D/T2D + LEAOD) were up-regulated and 1290/2970 (T2D/T2D + LEAOD) were down-regulated. A strong overlap of 571 genes across T2D, LEAOD, and coexisting conditions was mainly involved in extracellular exosomes and the transcription process. By exploring the sex difference gene expression features between T2D, T2D + LEAOD, and healthy controls, we noticed that sex chromosome-associated genes do not participate in the sexual dimorphism gene expression profiles of T2D and LEAOD. Protein–Protein Interaction Network analysis and drug target prediction provided the drug candidates to treat T2D and LEAOD.Conclusion: This study provides some evidence at the transcript level to uncover the association of T2D with LEAOD. The screened hub genes and predicted target drugs may be therapeutic targets.Keywords: type 2 diabetes mellitus, lower extremity arterial disease, gene expression profile, hub gene

Ying Wei,1 Yan-Zhi Wang,2 Ying Li,1 Ling Liu,1 Ting-Ting Sui,2 Yuan Li1 1Department II of Anorectal Department, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 2Department I of Anorectal Department, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of ChinaCorrespondence: Ying Wei, Department II of Anorectal Department, China-Japan Friendship Hospital, No. 2, Sakura East Street, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-01053236548, Email Yingwei_2023@163.comObjective: To explore the effect of comprehensive nursing on pain relief, comfort and burden of family care of infantile anal fistula.Methods: This was a randomized, double-blind, controlled clinical trial. A total of 106 cases of children with anal fistula from January 2021 to December 2021 were selected and divided into observation group and control group, there were 53 cases in each group. The control group were underwent with routine nursing intervention. The observation group were underwent with video health education, peer support, music relaxation training, physiotherapy and auricular point pressing on the basis of routine nursing therapy and other measures (comprehensive nursing). The wound healing time, comfort score, complication rate and family care burden of two groups were compared.Results: After intervention, the scores of pain degree in the observation group were significantly lower than those in the control group (4.02 ± 0.85 vs 5.89 ± 2.36, p < 0.05), and the scores of comfort degree in the observation group were higher than those in the control group (70.23 ± 5.98 vs 46.88 ± 5.23, p < 0.05). After intervention, the wound healing time of the observation group was shorter than that of the control group (3.98 ± 0.63 vs 5.77 ± 1.02, p < 0.05), and the crying times of the observation group were less than that of the control group (1.22 ± 0.26 vs 4.02 ± 0.48, p < 0.05). After intervention, the total scores of family members’ care load in the observation group were significantly lower than those in the control group (37.26 ± 4.78 vs 55.99 ± 5.02, p < 0.05).Conclusion: Comprehensive nursing can effectively promote wound healing in infantile anal fistula, reduce pain, prompt children’s comfort, reduce the number of children crying, and reduce the burden of care for children’s families.Keywords: comprehensive nursing, infantile anal fistula, comfort, complications, family care burden

Wen-Jie Cong,1,&ast; Zhi-Peng Liu,2,&ast; Yi-Xin Liang,2 Sheng-Lie Ye,2 Zhong-Ming Cai,2 Hao-Man Chen,2 Cheng-Wei Liao,2 Qun-Li Lin,3 Ren-Qian Feng,2 Xu-Dong Zhou,4 Yan-Zhi Wu,2 Le-Qiu Sun,5 Xue-Rong Huang,6 Man-Man Zhang,7 Gui-Qian Huang,8 Bei-Lei Zhu7 1Department of Acupuncture and Physiotherapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2The First Clinical School, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Neurology, Yongjia People’s Hospital, Wenzhou, Zhejiang, People’s Republic of China; 4Department of Neurology, Pingyang People’s Hospital, Wenzhou, Zhejiang, People’s Republic of China; 5Department of Neurology, Affiliated Yueqing Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 6Department of Neurology, Ruian People’s Hospital, Wenzhou, Zhejiang, People’s Republic of China; 7Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang People’s Republic of China; 8School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bei-Lei Zhu, Tel +86 13567896076, Email doczbl@163.comPurpose: To explore the predictive value of nutritional risk for all-cause death and functional outcomes among elderly acute stroke patients.Patients and Methods: A total of 479 elderly acute stroke patients were enrolled in this study. The nutritional risk of patients was screened by the GNRI and NRS-2002. The primary outcome was all-cause death, and the secondary outcome was poor prognosis defined as a modified Rankin Scale (mRS) score ≥ 3.Results: Based on the NRS-2002, patients with nutritional risk had a higher risk of all-cause death at 3 months (adjusted OR: 3.642, 95% CI 1.046~12.689) and at 3 years (adjusted OR: 2.266, 95% CI 1.259~4.076) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.748, 95% CI 1.518~4.972. Based on the GNRI, compared to those without nutritional risk, patients with mild malnutrition also had a higher risk of all-cause death at 3 months (adjusted OR: 7.186, 95% CI 1.550~33.315) and at 3 years (adjusted OR: 2.255, 95% CI 1.211~4.199) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 1.947, 95% CI 1.030~3.680), so patients with moderate and severe malnutrition had a higher risk of all-cause death at 3 months (adjusted OR: 6.535, 95% CI 1.380~30.945) and at 3 years (adjusted OR: 2.498, 95% CI 1.301~4.799) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.213, 95% CI 1.144~4.279).Conclusion: Nutritional risk increases the risk of poor short-term and long-term outcomes in elderly patients with acute stroke. For elderly stroke patients, we should pay attention to early nutritional risk screening, and effective intervention should be provided to improve the prognosis of such patients.Keywords: acute stroke, malnutrition, nutritional screening, all-cause death, GNRI, NRS-2002

Yin Dong,1,&ast; Ming-Jing Li,2,&ast; Yan-Zhu Hong,3 Wen-Jie Li4 1Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 4Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan-Zhu Hong, Xiamen University, No. 422, Siming South Road, Siming District, Xiamen, Fujian, 361005, People’s Republic of China, Tel +86 13671617025, Email hongyanzhu2020@sina.com Wen-Jie Li, Shanghai University of Traditional Chinese Medicine, No. 1200 Cai-lun Road, Pudong District, Shanghai, 201203, People’s Republic of China, Tel +86 15397687742, Email liwenjie@shutcm.edu.cnAbstract: Dysmenorrhea, classified as primary dysmenorrhea and secondary dysmenorrhea, is a common gynecological symptom that seriously affects female daily life. At present, studies on dysmenorrhea are numerous and complex. To better reflect the trend and innovative progress of dysmenorrhea-related research, this study screened papers on the Web of Science from January 1, 1992, to December 31, 2022. A total of 1012 papers were selected and analyzed for their affiliated countries, institutions, authors, keywords, etc. China is the country with the most academic output, Beijing University of Traditional Chinese Medicine is the most influential institution, and Yang Jie, from Chengdu University of Traditional Chinese Medicine, China, is the scholar with the most papers. We consider that the current research focus is on pathogenesis, treatment, epidemiology, and self-management. With increasing research on functional connectivity between dysmenorrhea and various brain regions, functional connectivity has gradually become the forefront of research. We hope our study can promote the further study of dysmenorrhea.Keywords: pathogenesis, treatment, management, traditional Chinese medicine

Hong Huang, Nai-Qing Hu, Jun-Yun Yang, Yu-Luan Xiang, Yuan-Zhao Zhu, Qian-Ru Du, Xue-Yan Yin, Jin-lin Lv, Li-Hua Li Department of Gerontology, The First Affiliated Hospital of Dali University, Dali, Yunnan Province, 671000, People’s Republic of ChinaCorrespondence: Li-Hua Li, Department of Gerontology, The First Affiliated Hospital of Dali University, Jiashibo Road 32, Dali, 671000, People’s Republic of China, Tel +86-872-2205663, Fax +86-872-2201096, Email lilihuayncn@163.comBackground: Non-valvular atrial fibrillation (NVAF) is associated with increased stroke in elderly populations, yet anticoagulant therapy is underutilized. We analyzed clinical characteristics and anticoagulation treatment rates of elderly NVAF patients hospitalized in Dali, China, to identify potential contributing factors.Methods: We collected data for 155 elderly patients with NVAF aged ≥ 60 years, from July 01, 2020, to December 31, 2021. We analyzed the awareness rate, clinical characteristics, and anticoagulant treatment rate of atrial fibrillation (AF), and identified factors influencing treatment. Patients were followed up one year after discharge to assess vital status, cardiovascular events, and anticoagulation therapy status.Results: Among 155 patients, 52.26% were female, and the average age was 75.77 years. The awareness rate of AF was 47.74% at admission, and only 21.94% received anticoagulant therapy. After discharge, the rate of anticoagulant therapy significantly increased to 70.97%, and 89.09% used new oral anticoagulants. Thromboembolic history and persistent AF predicted anticoagulant therapy at discharge, while male gender, previous bleeding history, and antiplatelet therapy predicted non-anticoagulant therapy. Out of 133 patients who completed a one-year follow-up, 23.31% died, 3.01% had strokes, and 3.01% experienced bleeding. Anticoagulant therapy decreased to 51.96% during the follow-up year.Conclusion: Our findings highlight the low awareness rate and anticoagulant treatment rate, and high mortality among elderly NVAF patients in Dali. The development of comprehensive intervention strategies is critical to standardize AF management and improve prognosis.Keywords: non-valvular atrial fibrillation, awareness rate of atrial fibrillation, anticoagulant therapy, stroke, all-cause death

Han Wu,&ast; Yang Zheng,&ast; Dan-Ni Liu, Xiao-Xia Liu, Qun-Di Yang, Qiu-Yun Su, Ying-Quan Wang, Yu-Zhuo Wang, Xue-Na La, Yan Shi,&ast; Chen Fu&ast; Division of Noncommunicable Diseases and Injury, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Shi; Chen Fu, Tel +86-21-62758710, Email shiyan@scdc.sh.cn; fuchen@scdc.sh.cnPurpose: This study aimed to investigate the relationship between sleep duration (SD) and stroke, and examine the effects of SD on stroke with or without metabolic syndrome (Mets) and its components among the adult residents in Shanghai, China.Participants and Methods: A total of 20,245 participants (51.72% male, mean age 44.66 years) were included from Shanghai Chronic Disease and Risk Factors Surveillance (SCDRFS) in 2017. The weighted logistic regressions were performed to examine the associations between SD and stroke in different status of Mets and its components.Results: The mean SD was 7.51± 0.03 h/d. After adjusting for all the potential factors, SD< 6 h/d (OR=1.73, 95% CI: 1.35– 2.20) or ≥ 10 h/d (OR=1.66, 95% CI: 1.08– 2.57) was significantly positively associated with stoke in the total participants; moreover, in the non-Mets group, only SD< 6 h/d (OR=1.77, 95% CI: 1.19, 2.64) significantly increased the risk of stroke; while, in the Mets group, SD< 6 h/d (OR=1.80, 95% CI:1.17– 2.76) and ≥ 10 h/d (OR=1.97, 95% CI: 1.00– 3.88) both had a positive significantly association with stoke. In addition, the effects of SD< 6 h/d on stroke were more pronounced among those with high WC (OR=2.24, 95% CI: 1.40– 3.58) and high TG (OR=2.60, 95% CI: 1.86– 3.62), and the effects of SD≥ 10 h/d on stroke were more evident among those with high TG (OR=2.28, 95% CI: 1.02– 5.08) and high FBG (OR=2.58, 95% CI: 1.30– 5.10).Conclusion: Both short and long SD were significantly positively associated with stroke in the total participants, and the associations were stronger in the Mets group; conversely, in the non-Mets group, only short SD was significantly positively associated with stroke, and no significant association was observed between long SD and stroke. Therefore, more precise sleep measures may be needed to prevent stroke according to the different status of Mets.Keywords: sleep duration, metabolic syndrome, stroke, Shanghai

Qi Wang,1,&ast; Yan-Zhen Que,2,&ast; Xiao-Ying Wan,2 Chao-Qin Lin1 1Department of Gynecology, Fujian Provincial Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Gynecology and Obstetrics, Shaxian General Hospital, Sanming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao-Qin Lin, Department of Gynecology, Fujian Provincial Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Dao-shan street, Gu-lou District, Fuzhou, 350000, People’s Republic of China, Tel +8613950422970, Email lcqfjsfy@126.comPurpose: To investigate the prevalence, risk factors, and impact on quality of life (QOL) of female urinary incontinence (UI) in a region of southeastern China.Patients and Methods: This cross-sectional study, conducted between June 2022 and March 2023, included 9584 women aged 20– 70 years who completed a standardized questionnaire through face-to-face interviews. This sample size represents almost 10% of the population in the target area.Results: The prevalence of female UI was found to be 24.8%, with stress UI being the most common subtype (12.7%), followed by mixed UI (8.0%) and urgency UI (4.1%). Notably, the prevalence of UI increased progressively with age and body mass index (BMI). The study also revealed several risk factors for UI, including urban residence, postmenopausal status, multiple vaginal deliveries, instrumental vaginal deliveries, previous delivery of macrosomia, and prior history of pelvic floor surgery as determined by multivariate analysis. Furthermore, the study showed that 89.5% of women who reported UI experienced varying degrees of negative impact on their QOL. The incontinence quality of life (I-QOL) scale had an average score of 79.70± 19.03, which decreased with increasing severity of UI. Despite the adverse effects on QOL, only 20.6% of women with UI had sought medical help.Conclusion: UI is common among women in the survey area. UI has been observed to have varying degrees of adverse effects on the QOL of those affected, but most of them do not seek treatment for several reasons, highlighting the urgent need for health authorities to develop effective UI intervention strategies.Keywords: female urinary incontinence, epidemiology, prevalence, risk factors, quality of life, Southern Chinese

Abstract Brassica napus, a versatile crop with significant socioeconomic importance, serves as a valuable source of nutrition for humans and animals while also being utilized in biodiesel production. The expansion potential of B. napus is profoundly influenced by climatic variations, yet there remains a scarcity of studies investigating the correlation between climatic factors and its distribution. This research employs CLIMEX to identify the current and future ecological niches of B. napus under the RCP 8.5 emission scenario, utilizing the Access 1.0 and CNRM-CM5 models for the time frame of 2040–2059. Additionally, a sensitivity analysis of parameters was conducted to determine the primary climatic factors affecting B. napus distribution and model responsiveness. The simulated outcomes demonstrate a satisfactory alignment with the known current distribution of B. napus, with 98% of occurrence records classified as having medium to high climatic suitability. However, the species displays high sensitivity to thermal parameters, thereby suggesting that temperature increases could trigger shifts in suitable and unsuitable areas for B. napus, impacting regions such as Canada, China, Brazil, and the United States.

Yi Zhen Tan,1 Lucy R Thomsen,1 Nensi Shrestha,1 Adalberto Camisasca,2 Silvia Giordani,2 Rhonda Rosengren1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, 9016, New Zealand; 2School of Chemical Sciences, Dublin City University, Glasnevin, Dublin, D09 NA55, IrelandCorrespondence: Rhonda Rosengren, Department of Pharmacology and Toxicology, 18 Frederick Street, Dunedin, 9016, New Zealand, Tel +64 3 479 9141, Fax +64 3 479 9140, Email rhonda.rosengren@otago.ac.nzBackground: A nanoscale drug carrier could have a variety of therapeutic and diagnostic uses provided that the carrier is biocompatible in vivo. Carbon nano-onions (CNOs) have shown promising results as a nanocarrier for drug delivery. However, the systemic effect of CNOs in rodents is unknown. Therefore, we investigated the toxicity of CNOs following intravenous administration in female BALB/c mice.Results: Single or repeated administration of oxi-CNOs (125, 250 or 500 μg) did not affect mouse behavior or organ weight and there was also no evidence of hepatotoxicity or nephrotoxicity. Histological examination of organ slices revealed a significant dose-dependent accumulation of CNO aggregates in the spleen, liver and lungs (p< 0.05, ANOVA), with a trace amount of aggregates appearing in the kidneys. However, CNO aggregates in the liver did not affect CYP450 enzymes, as total hepatic CYP450 as well as CYP3A catalytic activity, as meased by erythromycin N-demethylation, and protein levels showed no significant changes between the treatment groups compared to vehicle control. CNOs also failed to act as competitive inhibitors of CYP3A in vitro in both mouse and human liver microsomes. Furthermore, CNOs did not cause oxidative stress, as indicated by the unchanged malondialdehyde levels and superoxide dismutase activity in liver microsomes and organ homogenates.Conclusion: This study provides the first evidence that short-term intravenous administration of oxi-CNOs is non-toxic to female mice and thus could be a promising novel and safe drug carrier.Keywords: carbon nano-onions, drug carriers, intravenous administration, toxicity, accumulation, drug metabolism, oxidative stress

Yi-Zhou Feng,1,&ast; Jun-Tao Chen,1,2,&ast; Zhen-Yu Hu,1,&ast; Gao-Xia Liu,1 Yu-Shun Zhou,1 Ping Zhang,1 Ai-Xi Su,1 Shuai Yang,1 Yue-Ming Zhang,1 Ru-Meng Wei,1 Gui-Hai Chen1 1Department of Neurology (Sleep Disorders), Chaohu Hospital of Anhui Medical University, Hefei, Anhui, 238000, People’s Republic of China; 2Department of Neurology, Shangyu People’s Hospital of Shaoxing, Shaoxing, Zhejiang, 312000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gui-Hai Chen, Department of Neurology (Sleep Disorders), Chaohu Hospital of Anhui Medical University, Hefei, Anhui, 238000, People’s Republic of China, Tel +86-13956094425, Email doctorcgh@163.comPurpose: To investigate changes and links of stress and high sleep reactivity (H-SR) on the macro-structure and orderliness of sleep and cortisol levels in good sleepers (GS).Patients and Methods: Sixty-two GS (18– 40 years old) were recruited, with 32 in the stress group and 30 in the control group. Each group was further divided into H-SR and low SR subgroups based on the Ford Insomnia Response to Stress Test. All participants completed two nights of polysomnography in a sleep laboratory. Before conducting polysomnography on the second night, the stress group completed the Trier Social Stress Test and saliva was collected.Results: The duration of NREM sleep stages 1, 2 (N1, N2) and rapid eye movement sleep (REM) decreased, and the values of approximate entropy, sample entropy, fuzzy entropy, and multiscale entropy increased under stress and SR effects. Stress increased rapid eye movement density, and H-SR increased cortisol reactivity.Conclusion: Stress can damage the sleep and increase cortisol release in GS, especially those with H-SR. N1, N2 and REM sleep are more easily affected, while NREM sleep stage 3 sleep is relatively stable.Keywords: cortisol, entropy, insomnia, polysomnography, sleep reactivity, stress

Xiang-Zhe Shi,1,2 Sheng Zhao,3 Yan Wang,1,2 Meng-Yao Wang,1,2 Su-Wen Su,1,2 Yan-Zhao Wu,3 Chen Xiong1,2 1The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; 2The Key Laboratory of Pharmacology and Toxicology for New Drugs, Department of Pharmacology, Hebei Medical University, Shijiazhung, 050017, People’s Republic of China; 3Department of Otorhinolaryngology-Head and Neck Surgery, 4th Hospital of Hebei Medical University, Shijiazhuang, 050011, People’s Republic of ChinaCorrespondence: Chen Xiong; Yan-Zhao Wu, Email bearmorning@sina.com; wyz315@163.comIntroduction: Anaplastic thyroid carcinoma (ATC) is the most lethal thyroid carcinoma. Doxorubicin (DOX) is the only drug approved for anaplastic thyroid cancer treatment, but its clinical use is restricted due to irreversible tissue toxicity. Berberine (BER), an isoquinoline alkaloid extracted from Coptidis Rhizoma, has been proposed to have antitumor activity in many cancers. However, the underlying mechanisms by which BER regulates apoptosis and autophagy in ATC remain unclear. Thus, the present study aimed to assess the therapeutic effect of BER in human ATC cell lines CAL-62 and BHT-101 as well as the underlying mechanisms. In addition, we assessed the antitumor effects of a combination of BER and DOX in ATC cells.Methods: The cell viability of CAL-62 and BTH-101 with treatment of BER for different hours was measured by CCK-8 assay, and cell apoptosis was assessed by clone formation assay and flow cytometric analysis. The protein levels of apoptosis protein, autophagy-related proteins and PI3K/AKT/mTORpathway were determined Using Western blot. Autophagy in cells was observed with GFP-LC3 plasmid using confocal fluorescent microscopy. Flow cytometry was used to detect intracellular ROS.Results: The present results showed that BER significantly inhibited cell growth and induced apoptosis in ATC cells. BER treatment also significantly upregulated the expression of LC3B-II and increased the number of GFP-LC3 puncta in ATC cells. Inhibition of autophagy by 3-methyladenine (3-MA) suppressed BER-induced autophagic cell death. Moreover, BER induced the generation of reactive oxygen species (ROS). Mechanistically, we demonstrated that BER regulated the autophagy and apoptosis of human ATC cells through the PI3K/AKT/mTOR pathways. Furthermore, BER and DOX cooperated to promote apoptosis and autophagy in ATC cells.Conclusion: Taken together, the present findings indicated that BER induces apoptosis and autophagic cell death by activating ROS and regulating the PI3K/AKT/mTOR signaling pathway.Keywords: anaplastic thyroid carcinoma, berberine, autophagy, apoptosis, PI3K/AKT/mTOR, reactive oxygen species

Li Fang,1,2 Chun-Hao Li,1,3 Qian Zhang,1,3 Tian-Jiao Jiang,1,3 Yuan Liu,1,2 Feng-Po Shi,1,3 Peng Yu,1,3 Liang Yu,1,3 Ai-Ping Chen,1,3 Tao Li,1,3 Yu-Zhu Wan,1,3 Li Shi1,3 1Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Otolaryngology Head & Neck Surgery, The Second People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of China; 3Department of Allergy, Shandong Second Provincial General Hospital, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Tao Li; Yu-Zhu Wan, Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Duanxing West Road, Jinan, Shandong, 250033, People’s Republic of China, Tel +86 531 83086279 ; +86 531 83086280, Fax +86 531 87980304, Email ltwfmc@163.com; wanyuzhu001@126.comBackground: Mounting research indicates that brain-derived neurotrophic factor (BDNF), has great potential to increase neuro-hyperresponsiveness and airway resistance in airway allergic disease. The expression level of BDNF has been found to be notably elevated in lung/nasal lavage (NAL) fluid. However, the expression and position of BDNF in ciliated cells with allergic rhinitis remains unclear.Methods: Nasal mucosal cells were collected from patients with allergic rhinitis (AR) and mice which were performed under different allergen challenge time, then observed the expression and position of BDNF located in ciliated cells through the immunofluorescence staining. Nasal mucosa, serum and NAL fluid were collected also. The expression level of BDNF and IL-4/5/13 were detected by RT-PCR. The expressions of BDNF (in serum and NAL fluid), and total-IgE, ovalbumin sIgE (in serum) were detected by ELISA.Results: We found that MFI of BDNF in AR group’s ciliated cells was obviously lower than that in the control group, and a negative correlation was discovered between MFI and VAS score. It can be roughly divided into 5 patterns according to its location in the cytoplasm of ciliated cells. In the mouse model, the expressions of BDNF in serum and NAL fluid increased temporarily after allergen stimulation. The MFI of BDNF in ciliated cells displayed an initial increase followed by a subsequent decrease.Conclusion: Our study shows for the first time that, the expression and localization of BNDF were observed in the human nasal ciliated epithelial cells of allergic rhinitis, and the expression of level was less than the control group under the persistent state of allergy. BDNF expression in ciliated cells was transient increased after allergen stimulation and decreased to normal level after 24h in mouse model of allergic rhinitis. This might be the possible source of the transient increase of BNDF in serum and NAL fluid.Keywords: allergic rhinitis, BDNF, ciliated cell, NAL fluid

Hao Huang,1,&ast; Peng-Yang Yu,1,&ast; Chen Wei,2 Yang-Wei Li,3 Li-Jie Liang,1 Yu-Zhang Liu,1 Li-Na Liu,1 Bai-Jun Fang,1 Yao-Mei Wang1 1Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China; 2Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China; 3Central Laboratory, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yao-Mei Wang; Bai-Jun Fang, Email wangyaomeiwym9@126.com; bjfdr_sea@163.comObjective: To examine the clinical characteristics and anemia-related factors in patients with newly diagnosed multiple myeloma (NDMM), as well as the effect and mechanism of erythroblastic islands (EBIs) and EBI macrophages in NDMM patients with anemia.Methods: We collected and analyzed clinical data to find anemia-related factors. Using flow cytometry, the numbers and ratios of erythroblasts and EBI macrophages were determined. RNA sequencing (RNA-seq) was used to determine the differences of EBI macrophages in NDMM patients with or without anemia.Results: Based on the clinical characteristics of NDMM patients with anemia, MCV, abnormal levels of albumin, osteolytic lesions, and Durie-Salmon (DS) stage are risk factors for anemia. Patients with anemia have fewer erythroblasts, erythroblastic islands (EBIs), and EBI macrophages in their bone marrow than patients without anemia. RNA-seq analysis of EBI macrophages from the bone marrow of patients with and without anemia revealed that macrophages from patients with anemia are impaired and tend to promote the production of interleukin-6, which has been demonstrated to be an essential survival factor of myeloma cells and protects them from apoptosis.Conclusion: In NDMM patients with anemia, EBI macrophages are impaired, which causes anemia in those patients. Our finding highlights the significance of EBI macrophages in anemia in NDMM patients and provides a new strategy for recovery from anemia in these patients.Keywords: anemia, central macrophages, erythroblastic islands, erythropoiesis, multiple myeloma

The ability to alloy different elements is critical for property tuning and materials discovery. However, general alloying at the nanoscale remains extremely challenging due to strong immiscibility and easy oxidation, particularly for early transition metals that are highly reactive. Here, we report nanoscale alloying using a high-temperature- and high-entropy-based strategy (T∗ΔSmix) to significantly expand the possible alloys and include early transition metals. While high-temperature synthesis favors alloy formation and metal reduction, the high-entropy compositional design is critical to further extending the alloying to strongly repelling combinations (e.g., Au-W) and easily oxidized elements (e.g., Zr). In particular, we explicitly characterized a record 15-element nanoalloy, which showed a solid-solution structure featuring localized strain and lattice distortions as a result of extreme mixing. Our study significantly broadens available compositions of nanoalloys and provides clear guidelines by utilizing the less-explored entropic chemistry.

Carbon monoxide (CO) adsorption on ultrathin fcc Fe films is known to result in the rotation of magnetization from out-of-plane to in-plane. By imaging in real time the magnetic domain structure of perpendicularly magnetized Fe/(2 ML)Ni/Cu(100) films during exposure to CO, we demonstrate that the effect of adsorption on the magnetic properties occurs in two distinct stages. Initially, when CO bonds preferentially on bridge sites, perpendicular magnetic anisotropy is enhanced. Later, when on-top adsorption dominates, magnetization rotates towards in-plane in agreement with previous studies. This CO-induced spin reorientation transition (SRT) is not reversible by annealing, as CO desorption would require high temperature cycles which yield permanent structural changes in the metal films. This study demonstrates the existence of a novel non-monotonic behavior of the magnetic anisotropy as a function of adsorbate coverage. The influence of CO on ultrathin film magnetism in real time near critical points, where the anisotropy balance is extremely sensitive to small variations, reveals the previously elusive complexity of this adsorbate induced SRT.

Hua-Man Wu,1,2,&ast; Zhi-Jun Wang,1,&ast; Chao-Hong Cheng,1 Tong Su,1 Jing Wang,1 Ye-Zhou Li,3 Qiao-Jun Wang,4 Fei Han,4 Rui Chen1,4 1Department of Respiratory, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Zigong First People’s Hospital, Zigong, Sichuan, People’s Republic of China; 3School of Medicine, the University of Manchester, Manchester, UK; 4Department of Sleeping Center, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Chen, Department of Respiratory/Department of Sleeping Center, the Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, People’s Republic of China, Tel +86(0512)67784857, Email chenruigood@126.comPurpose: Obstructive sleep apnea hypopnea syndrome (OSAHS) can lead to cognitive impairment, though few studies have so far examined hypercapnia as its causal mechanism, due to the invasive nature of conventional arterial CO2 measurement. The study aims to investigate the effects of daytime hypercapnia on working memory in young and middle-aged patients with OSAHS.Patients and Methods: This prospective study screened 218 patients and eventually recruited 131 patients (aged 25– 60 years) with polysomnography (PSG)-diagnosed OSAHS. Using a cut-off of 45mmHg daytime transcutaneous partial pressure of carbon dioxide (PtcCO2), 86 patients were assigned into the normocapnic group and 45 patients into the hypercapnic group. Working memory was evaluated using the Digit Span Backward Test (DSB) and the Cambridge Neuropsychological Test Automated Battery.Results: Compared with the normocapnic group, the hypercapnic group performed worse in verbal, visual, and spatial working memory tasks. PtcCO2≥ 45mmHg was an independent predictor for lower DSB scores (OR=4.057), lower accuracy in the immediate Pattern Recognition Memory (OR=2.600), delayed Pattern Recognition Memory (OR=2.766) and Spatial Recognition Memory (OR=2.722) tasks, lower Spatial Span scores (OR=4.795), and more between errors in the Spatial Working Memory task (OR=2.734 and 2.558, respectively). Notably, PSG indicators of hypoxia and sleep fragmentation did not predict task performance.Conclusion: Hypercapnia may be plays an important role in working memory impairment in patients with OSAHS, perhaps more so than hypoxia and sleep fragmentation. Routine CO2 monitoring in these patients could prove of utility in clinical practices.Keywords: hypercapnia, obstructive, sleep apnea, working memory

We describe an extension of the most recent version of the Planck Catalogue of Compact Sources (PCCS2), produced using a new multi-band Bayesian Extraction and Estimation Package (BeeP). BeeP assumes that the compact sources present in PCCS2 at 857 GHz have a dust-like spectral energy distribution (SED), which leads to emission at both lower and higher frequencies, and adjusts the parameters of the source and its SED to fit the emission observed in Planck's three highest frequency channels at 353, 545, and 857 GHz, as well as the IRIS map at 3000 GHz. In order to reduce confusion regarding diffuse cirrus emission, BeeP's data model includes a description of the background emission surrounding each source, and it adjusts the confidence in the source parameter extraction based on the statistical properties of the spatial distribution of the background emission. BeeP produces the following three new sets of parameters for each source: (a) fits to a modified blackbody (MBB) thermal emission model of the source; (b) SED-independent source flux densities at each frequency considered; and (c) fits to an MBB model of the background in which the source is embedded. BeeP also calculates, for each source, a reliability parameter, which takes into account confusion due to the surrounding cirrus. This parameter can be used to extract sub-samples of high-frequency sources with statistically well-understood properties. We define a high-reliability subset (BeeP/base), containing 26 083 sources (54.1% of the total PCCS2 catalogue), the majority of which have no information on reliability in the PCCS2. We describe the characteristics of this specific high-quality subset of PCCS2 and its validation against other data sets, specifically for: the sub-sample of PCCS2 located in low-cirrus areas; the Planck Catalogue of Galactic Cold Clumps; the Herschel GAMA15-field catalogue; and the temperature-and spectral-index-reconstructed dust maps obtained with Planck's Generalized Needlet Internal Linear Combination method. The results of the BeeP extension of PCCS2, which are made publicly available via the Planck Legacy Archive, will enable the study of the thermal properties of well-defined samples of compact Galactic and extragalactic dusty sources.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.

Understanding spin textures in magnetic systems is extremely important to the spintronics and it is vital to extrapolate the magnetic Hamiltonian parameters through the experimentally determined spin. It can provide a better complementary link between theories and experimental results. We demonstrate deep learning can quantify the magnetic Hamiltonian from magnetic domain images. To train the deep neural network, we generated domain configurations with Monte Carlo method. The errors from the estimations was analyzed with statistical methods and confirmed the network was successfully trained to relate the Hamiltonian parameters with magnetic structure characteristics. The network was applied to estimate experimentally observed domain images. The results are consistent with the reported results, which verifies the effectiveness of our methods. On the basis of our study, we anticipate that the deep learning techniques make a bridge to connect the experimental and theoretical approaches not only in magnetism but also throughout any scientific research.

Magnetic skyrmions are topological spin textures, which usually exist in noncentrosymmetric materials where the crystal inversion symmetry breaking generates the so-called Dzyaloshinskii-Moriya interaction. This requirement unfortunately excludes many important magnetic material classes, including the recently found two-dimensional van der Waals (vdW) magnetic materials, which offer unprecedented opportunities for spintronic technology. Using photoemission electron microscopy and Lorentz transmission electron microscopy, we investigated and stabilized Néel-type magnetic skyrmion in vdW ferromagnetic Fe3GeTe2 on top of (Co/Pd) n in which the Fe3GeTe2 has a centrosymmetric crystal structure. We demonstrate that the magnetic coupling between the Fe3GeTe2 and the (Co/Pd) n could create skyrmions in Fe3GeTe2 without the need of an external magnetic field. Our results open exciting opportunities in spintronic research and the engineering of topologically protected nanoscale features by expanding the group of skyrmion host materials to include these previously unknown vdW magnets.

Magnetic skyrmions are topological spin textures, which usually exist in noncentrosymmetric materials where the crystal inversion symmetry breaking generates the so-called Dzyaloshinskii-Moriya interaction. This requirement unfortunately excludes many important magnetic material classes, including the recently found two-dimensional van der Waals (vdW) magnetic materials, which offer unprecedented opportunities for spintronic technology. Using photoemission electron microscopy and Lorentz transmission electron microscopy, we investigated and stabilized Néel-type magnetic skyrmion in vdW ferromagnetic Fe3GeTe2 on top of (Co/Pd) n in which the Fe3GeTe2 has a centrosymmetric crystal structure. We demonstrate that the magnetic coupling between the Fe3GeTe2 and the (Co/Pd) n could create skyrmions in Fe3GeTe2 without the need of an external magnetic field. Our results open exciting opportunities in spintronic research and the engineering of topologically protected nanoscale features by expanding the group of skyrmion host materials to include these previously unknown vdW magnets.

Analysis of the Planck 2018 data set indicates that the statistical properties of the cosmic microwave background (CMB) temperature anisotropies are in excellent agreement with previous studies using the 2013 and 2015 data releases. In particular, they are consistent with the Gaussian predictions of the ΛCDM cosmological model, yet also confirm the presence of several so-called "anomalies"on large angular scales. The novelty of the current study, however, lies in being a first attempt at a comprehensive analysis of the statistics of the polarization signal over all angular scales, using either maps of the Stokes parameters, Q and U, or the E-mode signal derived from these using a new methodology (which we describe in an appendix). Although remarkable progress has been made in reducing the systematic effects that contaminated the 2015 polarization maps on large angular scales, it is still the case that residual systematics (and our ability to simulate them) can limit some tests of non-Gaussianity and isotropy. However, a detailed set of null tests applied to the maps indicates that these issues do not dominate the analysis on intermediate and large angular scales (i.e., ℓ 400). In this regime, no unambiguous detections of cosmological non-Gaussianity, or of anomalies corresponding to those seen in temperature, are claimed. Notably, the stacking of CMB polarization signals centred on the positions of temperature hot and cold spots exhibits excellent agreement with the ΛCDM cosmological model, and also gives a clear indication of how Planck provides state-of-the-art measurements of CMB temperature and polarization on degree scales.

We present full-sky maps of the cosmic microwave background (CMB) and polarized synchrotron and thermal dust emission, derived from the third set of Planck frequency maps. These products have significantly lower contamination from instrumental systematic effects than previous versions. The methodologies used to derive these maps follow closely those described in earlier papers, adopting four methods (Commander, NILC, SEVEM, and SMICA) to extract the CMB component, as well as three methods (Commander, GNILC, and SMICA) to extract astrophysical components. Our revised CMB temperature maps agree with corresponding products in the Planck 2015 delivery, whereas the polarization maps exhibit significantly lower large-scale power, reflecting the improved data processing described in companion papers; however, the noise properties of the resulting data products are complicated, and the best available end-to-end simulations exhibit relative biases with respect to the data at the few percent level. Using these maps, we are for the first time able to fit the spectral index of thermal dust independently over 3° regions. We derive a conservative estimate of the mean spectral index of polarized thermal dust emission of βd = 1.55 ± 0.05, where the uncertainty marginalizes both over all known systematic uncertainties and different estimation techniques. For polarized synchrotron emission, we find a mean spectral index of βs = -3.1 ± 0.1, consistent with previously reported measurements. We note that the current data processing does not allow for construction of unbiased single-bolometer maps, and this limits our ability to extract CO emission and correlated components. The foreground results for intensity derived in this paper therefore do not supersede corresponding Planck 2015 products. For polarization the new results supersede the corresponding 2015 products in all respects.

We present a final description of the data-processing pipeline for the Planck Low Frequency Instrument (LFI), implemented for the 2018 data release. Several improvements have been made with respect to the previous release, especially in the calibration process and in the correction of instrumental features such as the effects of nonlinearity in the response of the analogue-to-digital converters. We provide a brief pedagogical introduction to the complete pipeline, as well as a detailed description of the important changes implemented. Self-consistency of the pipeline is demonstrated using dedicated simulations and null tests. We present the final version of the LFI full sky maps at 30, 44, and 70 GHz, both in temperature and polarization, together with a refined estimate of the solar dipole and a final assessment of the main LFI instrumental parameters.

We analyse the Planck full-mission cosmic microwave background (CMB) temperature and E-mode polarization maps to obtain constraints on primordial non-Gaussianity (NG). We compare estimates obtained from separable template-fitting, binned, and optimal modal bispectrum estimators, finding consistent values for the local, equilateral, and orthogonal bispectrum amplitudes. Our combined temperature and polarization analysis produces the following final results: flocalNL= -0.9 ± 5.1; fequilNL= -26 ± 47; and forthoNL= -38 ± 24 (68% CL, statistical). These results include low-multipole (4 ≤ ℓ < 40) polarization data that are not included in our previous analysis. The results also pass an extensive battery of tests (with additional tests regarding foreground residuals compared to 2015), and they are stable with respect to our 2015 measurements (with small fluctuations, at the level of a fraction of a standard deviation, which is consistent with changes in data processing). Polarizationonly bispectra display a significant improvement in robustness; they can now be used independently to set primordial NG constraints with a sensitivity comparable to WMAP temperature-based results and they give excellent agreement. In addition to the analysis of the standard local, equilateral, and orthogonal bispectrum shapes, we consider a large number of additional cases, such as scale-dependent feature and resonance bispectra, isocurvature primordial NG, and parity-breaking models, where we also place tight constraints but do not detect any signal. The nonprimordial lensing bispectrum is, however, detected with an improved significance compared to 2015, excluding the null hypothesis at 3.5σ. Beyond estimates of individual shape amplitudes, we also present model-independent reconstructions and analyses of the Planck CMB bispectrum. Our final constraint on the local primordial trispectrum shape is glocalNL= (-5.8 ± 6.5) × 104(68% CL, statistical), while constraints for other trispectrum shapes are also determined. Exploiting the tight limits on various bispectrum and trispectrum shapes, we constrain the parameter space of different early-Universe scenarios that generate primordial NG, including general single-field models of inflation, multi-field models (e.g. curvaton models), models of inflation with axion fields producing parity-violation bispectra in the tensor sector, and inflationary models involving vector-like fields with directionally-dependent bispectra. Our results provide a high-precision test for structure-formation scenarios, showing complete agreement with the basic picture of the CDM cosmology regarding the statistics of the initial conditions, with cosmic structures arising from adiabatic, passive, Gaussian, and primordial seed perturbations.

This paper presents the High Frequency Instrument (HFI) data processing procedures for the Planck 2018 release. Major improvements in mapmaking have been achieved since the previous Planck 2015 release, many of which were used and described already in an intermediate paper dedicated to the Planck polarized data at low multipoles. These improvements enabled the first significant measurement of the reionization optical depth parameter using Planck-HFI data. This paper presents an extensive analysis of systematic effects, including the use of end-to-end simulations to facilitate their removal and characterize the residuals. The polarized data, which presented a number of known problems in the 2015 Planck release, are very significantly improved, especially the leakage from intensity to polarization. Calibration, based on the cosmic microwave background (CMB) dipole, is now extremely accurate and in the frequency range 100-353 GHz reduces intensity-to-polarization leakage caused by calibration mismatch. The Solar dipole direction has been determined in the three lowest HFI frequency channels to within one arc minute, and its amplitude has an absolute uncertainty smaller than 0.35 μK, an accuracy of order 10-4. This is a major legacy from the Planck HFI for future CMB experiments. The removal of bandpass leakage has been improved for the main high-frequency foregrounds by extracting the bandpass-mismatch coefficients for each detector as part of the mapmaking process; these values in turn improve the intensity maps. This is a major change in the philosophy of "frequency maps", which are now computed from single detector data, all adjusted to the same average bandpass response for the main foregrounds. End-to-end simulations have been shown to reproduce very well the relative gain calibration of detectors, as well as drifts within a frequency induced by the residuals of the main systematic effect (analogue-to-digital convertor non-linearity residuals). Using these simulations, we have been able to measure and correct the small frequency calibration bias induced by this systematic effect at the 10-4 level. There is no detectable sign of a residual calibration bias between the first and second acoustic peaks in the CMB channels, at the 10-3 level.

We report on the implications for cosmic inflation of the 2018 release of the Planck cosmic microwave background (CMB) anisotropy measurements. The results are fully consistent with those reported using the data from the two previous Planck cosmological releases, but have smaller uncertainties thanks to improvements in the characterization of polarization at low and high multipoles. Planck temperature, polarization, and lensing data determine the spectral index of scalar perturbations to be ns = 0.9649 ± 0.0042 at 68% CL. We find no evidence for a scale dependence of ns, either as a running or as a running of the running. The Universe is found to be consistent with spatial flatness with a precision of 0.4% at 95% CL by combining Planck with a compilation of baryon acoustic oscillation data. The Planck 95% CL upper limit on the tensor-to-scalar ratio, r0.002 < 0.10, is further tightened by combining with the BICEP2/Keck Array BK15 data to obtain r0.002 < 0.056. In the framework of standard single-field inflationary models with Einstein gravity, these results imply that: (a) the predictions of slow-roll models with a concave potential, V″(φ) < 0, are increasingly favoured by the data; and (b) based on two different methods for reconstructing the inflaton potential, we find no evidence for dynamics beyond slow roll. Three different methods for the non-parametric reconstruction of the primordial power spectrum consistently confirm a pure power law in the range of comoving scales 0.005 Mpc-1 k 0.2 Mpc-1. A complementary analysis also finds no evidence for theoretically motivated parameterized features in the Planck power spectra. For the case of oscillatory features that are logarithmic or linear in k, this result is further strengthened by a new combined analysis including the Planck bispectrum data. The new Planck polarization data provide a stringent test of the adiabaticity of the initial conditions for the cosmological fluctuations. In correlated, mixed adiabatic and isocurvature models, the non-adiabatic contribution to the observed CMB temperature variance is constrained to 1.3%, 1.7%, and 1.7% at 95% CL for cold dark matter, neutrino density, and neutrino velocity, respectively. Planck power spectra plus lensing set constraints on the amplitude of compensated cold dark matter-baryon isocurvature perturbations that are consistent with current complementary measurements. The polarization data also provide improved constraints on inflationary models that predict a small statistically anisotropic quadupolar modulation of the primordial fluctuations. However, the polarization data do not support physical models for a scale-dependent dipolar modulation. All these findings support the key predictions of the standard single-field inflationary models, which will be further tested by future cosmological observations.

The study of polarized dust emission has become entwined with the analysis of the cosmic microwave background (CMB) polarization in the quest for the curl-like B-mode polarization from primordial gravitational waves and the low-multipole E-mode polarization associated with the reionization of the Universe. We used the new Planck PR3 maps to characterize Galactic dust emission at high latitudes as a foreground to the CMB polarization and use end-to-end simulations to compute uncertainties and assess the statistical significance of our measurements. We present Planck EE, BB, and TE power spectra of dust polarization at 353 GHz for a set of six nested high-Galactic-latitude sky regions covering from 24 to 71% of the sky. We present power-law fits to the angular power spectra, yielding evidence for statistically significant variations of the exponents over sky regions and a difference between the values for the EE and BB spectra, which for the largest sky region are αEE = -2.42 ± 0.02 and αBB = -2.54 ± 0.02, respectively. The spectra show that the TE correlation and E/B power asymmetry discovered by Planck extend to low multipoles that were not included in earlier Planck polarization papers due to residual data systematics. We also report evidence for a positive TB dust signal. Combining data from Planck and WMAP, we have determined the amplitudes and spectral energy distributions (SEDs) of polarized foregrounds, including the correlation between dust and synchrotron polarized emission, for the six sky regions as a function of multipole. This quantifies the challenge of the component-separation procedure that is required for measuring the low-ℓ reionization CMB E-mode signal and detecting the reionization and recombination peaks of primordial CMB B modes. The SED of polarized dust emission is fit well by a single-temperature modified black-body emission law from 353 GHz to below 70 GHz. For a dust temperature of 19.6 K, the mean dust spectral index for dust polarization is βdP = 1.53±0.02. The difference between indices for polarization and total intensity is βdP-βdI = 0.05±0.03. By fitting multi-frequency cross-spectra between Planck data at 100, 143, 217, and 353 GHz, we examine the correlation of the dust polarization maps across frequency. We find no evidence for a loss of correlation and provide lower limits to the correlation ratio that are tighter than values we derive from the correlation of the 217- and 353 GHz maps alone. If the Planck limit on decorrelation for the largest sky region applies to the smaller sky regions observed by sub-orbital experiments, then frequency decorrelation of dust polarization might not be a problem for CMB experiments aiming at a primordial B-mode detection limit on the tensor-to-scalar ratio r≃ 0.01 at the recombination peak. However, the Planck sensitivity precludes identifying how difficult the component-separation problem will be for more ambitious experiments targeting lower limits on r.

We present measurements of the cosmic microwave background (CMB) lensing potential using the final Planck 2018 temperature and polarization data. Using polarization maps filtered to account for the noise anisotropy, we increase the significance of the detection of lensing in the polarization maps from 5σ to 9σ. Combined with temperature, lensing is detected at 40σ. We present an extensive set of tests of the robustness of the lensingpotential power spectrum, and construct a minimum-variance estimator likelihood over lensing multipoles 8 ≤ L ≤ 400 (extending the range to lower L compared to 2015), which we use to constrain cosmological parameters. We find good consistency between lensing constraints and the results from the Planck CMB power spectra within the σCDM model. Combined with baryon density and other weak priors, the lensing analysis alone constrains σ8Ω0.25m= 0.589 ± 0.020 (1σ errors). Also combining with baryon acoustic oscillation data, we find tight individual parameter constraints, σ8 = 0.811 ± 0.019, H0 = 67.9+1.2-1.3km s-1Mpc-1, and m = 0.303+0.016-0.018. Combining with Planck CMB power spectrum data, we measure σ8 to better than 1% precision, finding σ8 = 0.811 ± 0.006. CMB lensing reconstruction data are complementary to galaxy lensing data at lower redshift, having a different degeneracy direction in σ8 - m space; we find consistency with the lensing results from the Dark Energy Survey, and give combined lensing-only parameter constraints that are tighter than joint results using galaxy clustering. Using the Planck cosmic infrared background (CIB) maps as an additional tracer of high-redshift matter, we make a combined Planck-only estimate of the lensing potential over 60% of the sky with considerably more small-scale signal.We additionally demonstrate delensing of the Planck power spectra using the joint and individual lensing potential estimates, detecting a maximum removal of 40% of the lensing-induced power in all spectra. The improvement in the sharpening of the acoustic peaks by including both CIB and the quadratic lensing reconstruction is detected at high significance.

Observations of the submillimetre emission from Galactic dust, in both total intensity I and polarization, have received tremendous interest thanks to the Planck full-sky maps. In this paper we make use of such full-sky maps of dust polarized emission produced from the third public release of Planck data. As the basis for expanding on astrophysical studies of the polarized thermal emission from Galactic dust, we present full-sky maps of the dust polarization fraction p, polarization angle ψ, and dispersion function of polarization angles «. The joint distribution (one-point statistics) of p and NH confirms that the mean and maximum polarization fractions decrease with increasing NH. The uncertainty on the maximum observed polarization fraction, pmax = 22.0-1.4+3.5% at 353 GHz and 80′ resolution, is dominated by the uncertainty on the Galactic emission zero level in total intensity, in particular towards diffuse lines of sight at high Galactic latitudes. Furthermore, the inverse behaviour between p and « found earlier is seen to be present at high latitudes. This follows the «p-1 relationship expected from models of the polarized sky (including numerical simulations of magnetohydrodynamical turbulence) that include effects from only the topology of the turbulent magnetic field, but otherwise have uniform alignment and dust properties. Thus, the statistical properties of p, ψ, and « for the most part reflect the structure of the Galactic magnetic field. Nevertheless, we search for potential signatures of varying grain alignment and dust properties. First, we analyse the product map « × p, looking for residual trends. While the polarization fraction p decreases by a factor of 3-4 between NH = 1020 cm-2 and NH = 2 × 1022 cm-2, out of the Galactic plane, this product « × p only decreases by about 25%. Because « is independent of the grain alignment efficiency, this demonstrates that the systematic decrease in p with NH is determined mostly by the magnetic-field structure and not by a drop in grain alignment. This systematic trend is observed both in the diffuse interstellar medium (ISM) and in molecular clouds of the Gould Belt. Second, we look for a dependence of polarization properties on the dust temperature, as we would expect from the radiative alignment torque (RAT) theory. We find no systematic trend of « × p with the dust temperature Td, whether in the diffuse ISM or in the molecular clouds of the Gould Belt. In the diffuse ISM, lines of sight with high polarization fraction p and low polarization angle dispersion « tend, on the contrary, to have colder dust than lines of sight with low p and high «. We also compare the Planck thermal dust polarization with starlight polarization data in the visible at high Galactic latitudes. The agreement in polarization angles is remarkable, and is consistent with what we expect from the noise and the observed dispersion of polarization angles in the visible on the scale of the Planck beam. The two polarization emission-to-extinction ratios, RP/p and RS/V, which primarily characterize dust optical properties, have only a weak dependence on the column density, and converge towards the values previously determined for translucent lines of sight. We also determine an upper limit for the polarization fraction in extinction, pV/E(B - V), of 13% at high Galactic latitude, compatible with the polarization fraction p ≈ 20% observed at 353 GHz. Taken together, these results provide strong constraints for models of Galactic dust in diffuse gas.

We describe the legacy Planck cosmic microwave background (CMB) likelihoods derived from the 2018 data release. The overall approach is similar in spirit to the one retained for the 2013 and 2015 data release, with a hybrid method using different approximations at low (ℓ < 30) and high (ℓ ≥ 30) multipoles, implementing several methodological and data-analysis refinements compared to previous releases. With more realistic simulations, and better correction and modelling of systematic effects, we can now make full use of the CMB polarization observed in the High Frequency Instrument (HFI) channels. The low-multipole EE cross-spectra from the 100 GHz and 143 GHz data give a constraint on the λCDM reionization optical-depth parameter τ to better than 15% (in combination with the TT low-ℓ data and the high-ℓ temperature and polarization data), tightening constraints on all parameters with posterior distributions correlated with τ. We also update the weaker constraint on τ from the joint TEB likelihood using the Low Frequency Instrument (LFI) channels, which was used in 2015 as part of our baseline analysis. At higher multipoles, the CMB temperature spectrum and likelihood are very similar to previous releases. A better model of the temperature-to-polarization leakage and corrections for the effective calibrations of the polarization channels (i.e., the polarization efficiencies) allow us to make full use of polarization spectra, improving the λCDM constraints on the parameters θMC, ωc, ωb, and H0 by more than 30%, and ns by more than 20% compared to TT-only constraints. Extensive tests on the robustness of the modelling of the polarization data demonstrate good consistency, with some residual modelling uncertainties. At high multipoles, we are now limited mainly by the accuracy of the polarization efficiency modelling. Using our various tests, simulations, and comparison between different high-multipole likelihood implementations, we estimate the consistency of the results to be better than the 0.5σ level on the λCDM parameters, as well as classical single-parameter extensions for the joint likelihood (to be compared to the 0.3σ levels we achieved in 2015 for the temperature data alone on λCDM only). Minor curiosities already present in the previous releases remain, such as the differences between the best-fit λCDM parameters for the ℓ < 800 and ℓ > 800 ranges of the power spectrum, or the preference for more smoothing of the power-spectrum peaks than predicted in λCDM fits. These are shown to be driven by the temperature power spectrum and are not significantly modified by the inclusion of the polarization data. Overall, the legacy Planck CMB likelihoods provide a robust tool for constraining the cosmological model and represent a reference for future CMB observations.