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Cui Ying Wei,1,* Zhong Ming He,2,* Han Yan,3 Jing Li,3 Pei An,3 Long Zhao,3 Li Nong Ji,4 Zhan Cheng Gao,3 Xiao Song Dong,3 Fang Han3 1Department of Endocrinology, First Affiliated Hospital, Baotou Medical College, Baotou, Inner Mongolia, People’s Republic of China; 2Department of Pulmonary Medicine, Karamay Central Hospital, Karamay, Xinjiang, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 4Department of Endocrinology, Peking University People’s Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao Song DongDepartment of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of ChinaTel/Fax +86-10-88324207Email dongxiaosong@pkuph.edu.cnPurpose: The study aimed at assessing glucose control measured with a continuous glucose monitoring system (CGMS) before and after short-term continuous positive airway pressure (CPAP).Materials and Methods: Twenty-four type 2 diabetic patients (T2DM) with Obstructive sleep apnea syndrome (OSAS) (mean age 55.0 ± 9.0 years; BMI 29.5 ± 5.2 kg/m2) were admitted and kept under diet control for 2 days, then underwent 2 overnight polysomnographies: a diagnostic study and one with CPAP titration. Then they were treated by CPAP during sleep for the following three nights. Participants were divided into subgroup D (only diet control) and subgroup M (with DM medication). CGMS was utilized over the last five days. Glucose control was also assessed with plasma insulin and a clinical measure of insulin resistance (HOMA-IR) index.Results: The mean (±SD) apnea-hypopnea index (AHI) at diagnostic polysomnography was 51.2 ± 22.4 (range 10– 88) events/h. CPAP treatment in the subjects with OSAS resulted in the index of oxygenation desaturations being reduced from 33.3 ± 20.1 to 1.1 ± 1.6 (P =0.00). CGMS showed mean 24-hours glucose values significantly lower after CPAP treatment than at baseline in both subgroups (7.97± 1.31 vs 7.52± 0.94, P=0.033 in subgroup D; and 7.72± 1.51 vs 7.17± 1.21, P=0.05 in subgroup M), as the fasting plasma insulin levels and HOMA-IR were also decreased significantly after CPAP treatment (13.0 ± 7.5μU/mL vs 10.8 ± 5.4μU/mL, P=0.044; and 4.2 ± 2.2 vs 3.1± 1.7, P=0.003, respectively). Standard deviation (SD) and mean amplitude of glucose excursions (MAGE) were also decreased in the subgroup D (1.91 ± 1.10 vs 1.61 ± 1.20, P=0.014; 1.26 ± 1.13 vs 1.01 ± 0.98, P=0.008, respectively) only.Conclusion: Short-term CPAP treatment in OSAS with type 2 diabetic patients is accompanied by a decrease in blood glucose level and improved insulin sensitivity. Glucose variability was reduced but only in the patients with diet control.Keywords: type 2 diabetes mellitus, obstructive sleep apnea syndrome, continuous positive airway pressure, continuous glucose monitoring system, glucose variability, HOMA-IR

Chronic hepatitis B virus (HBV) infection is a major risk factor for liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Despite advances in understanding HBV-related liver diseases, effective therapeutic strategies remain limited. Macrophage migration inhibitory factor (MIF) has been implicated in various inflammatory and fibrotic conditions, but its role in HBV-induced liver fibrosis has not been fully explored. This study investigates the involvement of MIF in liver fibrosis and evaluates its potential as a therapeutic target. We found that MIF expression was significantly elevated in hepatic stellate cells (HSCs) following stimulation with HBVcc (HBV cell culture) or HBV surface antigen (HBsAg). Through its receptor CD74, MIF enhanced the TGF-β/SMAD signaling pathway, promoting HSC activation and liver fibrosis progression. Histological analysis revealed higher MIF and CD74 expression in HBsAg-positive individuals compared to HBsAg-negative controls. Moreover, MIF expression correlated with the activation of fibrosis markers, including α-SMA and TGF-β-related proteins. Inhibition of MIF with the specific inhibitor ISO-1 attenuated fibrosis progression, suggesting that targeting MIF could offer a promising approach for treating HBV-related liver fibrosis. Our findings underscore the critical role of the MIF/CD74 axis in liver fibrosis and provide a basis for future therapeutic strategies targeting MIF in chronic liver diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To analyze the clinical features of COVID-19 infection in hospitalized immunocompromised patients in comparison with immunocompetent patients. Methods: A single-center retrospective observational study was conducted on 213 inpatients diagnosed with COVID-19 in the Peking University People's Hospital between December 2022 and October 2023. They were divided into an immunocompromised group (102 patients, 47.9%) and an immunocompetent group(111 patients, 52.1%), and clinical data were compared between the two groups. The immunocompromised group was further divided into death group (18 cases, 17.6%) and non-death group (84 cases, 82.4%). The differences in laboratory examination findings were compared. Further analysis was performed on the lymphocyte subset differences between the death group(10 patients, 9.8%) and the non-death group (36 patients, 35.3%) with complete data. Results: The proportion of severe and critical cases and the mortality rate, were significantly higher in the immunocompromised group than the immunocompetent group (47.1% vs . 40.5%, 18.6% vs . 9.0%, 17.6% vs . 9.0%, P< 0.05). The immunocompromised group had lower vaccination rate (26.5% vs . 44.1%, P <0.05). Hypertension, kidney disease and infections were more common in the immunocompromised group (63.7% vs . 48.6%, 30.4% vs . 9.0%, 49.0% vs . 19.8%, all P <0.05). CT findings of consolidation (40.2% vs . 18.9%), rate of antiviral treatment (48.0% vs . 30.6%) and the positive duration of viral nucleic acid [median 14(7.0, 19.3) days vs . 9(7.0, 18.0) days] were higher in the immunocomprised group (all P <0.05). Lactate dehydrogenase (LDH), procalcitonin (PCT), interleukin-6 (IL-6) and ferritin were higher in the immunocompromised group than those in the immunocompetent group (all P <0.05). In the death group, neutrophils (NEU), C-reactive protein (CRP), PCT, IL-6, ferritin and D-dimer were higher, while lymphocytes (LY), CD4 + T-cells, CD8 + T-cells, B-cell counts and hemoglobin (HGB) were significantly lower than those in the non-death group (all P <0.05). Conclusions: More than 60% of patients in the immunocompromised group were classified as severe or critical type, with a higher mortality rate and decreased ability to clear severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Decreases in total lymphocytes, CD4 + T lymphocytes, CD8 + T lymphocytes, and B lymphocytes, along with elevated levels of procalcitonin, ferritin, and D-dimer, indicated poor prognosis.

Background: Osteosarcoma (OS) is a common malignancy among adolescents and children, characterized by a high propensity for metastasis and resistance to chemotherapy., Aims: This study aimed to investigate the role of COL12A1, a gene often overexpressed in various cancers and associated with poor prognosis, in the progression of OS and explore the underlying mechanisms., Methods: The expression pattern and potential function of COL12A1 in OS were evaluated using bioinformatics analyses, clinical sample examination, and OS cell lines. Various assays, including transwell, CCK-8, flow cytometry, and wound healing, were performed to assess the impact of COL12A1 on OS cell growth, cell cycle progression, apoptosis, invasion, and migration. Western blot analysis was conducted to investigate markers associated with the FAK/PI3K/AKT/mTOR pathway., Results: COL12A1 expression was significantly elevated in OS tissues and cells. Upregulation of COL12A1 promoted cell growth, accelerated cell cycle progression, and enhanced migration and invasion while inhibiting apoptosis. Conversely, the knockdown of COL12A1 had the opposite effect. Additionally, COL12A1 overexpression increased the phosphorylation of components in the FAK/PI3K/AKT/mTOR pathway. The FAK inhibitor Y15 mitigated the effects of COL12A1 overexpression on cell apoptosis, invasion, proliferation, and the FAK/PI3K/AKT/mTOR pathway in OS., Conclusion: Our findings indicated that COL12A1 enhanced OS development by activating the FAK/PI3K/AKT/mTOR pathway, suggesting that COL12A1 could serve as a valuable biomarker for the prediction and identification of OS patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: To investigate the outcomes of cochlear implantation in Mandarin-speaking cochlear implant (CI) users with single-sided deafness (SSD). Methods: This study was a single-center prospective cohort study. Eleven Mandarin-speaking adult SSD patients who underwent CI implantation at Capital Medical University Beijing Tongren Hospital from August 2020 to October 2021 were recruited, including 6 males and 5 females, with the age ranging from 24 to 50 years old. In a sound field with 7 loudspeakers distributed at 180°, we measured root-mean-square error(RMSE)in SSD patients at the preoperative, 1-month, 3-month, 6-month, and 12-month after switch-on to assess the improvement of sound source localization. The Mandarin Speech Perception (MSP) was used in the sound field to test the speech reception threshold (SRT) of SSD patients under different signal-to-noise locations in a steady-state noise under conditions of CI off and CI on, to reflect the head shadow effect(S SSD N NH ), binaural summation effect(S 0 N 0 ) and squelch effect(S 0 N SSD ). The Tinnitus Handicap Inventory (THI) and the Visual Analogue Scale (VAS) were used to assess changes in tinnitus severity and tinnitus loudness in SSD patients at each time point. The Speech, Spatial and Qualities of Hearing Scale(SSQ) and the Nijmegen Cochlear Implantation Scale (NCIQ) were used to assess the subjective benefits of spatial speech perception and quality of life in SSD patients after cochlear implantation. SPSS 19.0 software was used for statistical analysis. Results: SSD patients showed a significant improvement in the poorer ear in hearing thresholds with CI-on compared with CI-off; The ability to localize the sound source was significantly improved, with statistically significant differences in RMSE at each follow-up time compared with the preoperative period ( P <0.05). In the S SSD N NH condition, which reflects the head shadow effect, the SRT in binaural hearing was significantly improved by 6.5 dB compared with unaided condition, and the difference was statistically significant ( t =6.25, P =0.001). However, there was no significant improvement in SRT between the binaural hearing condition and unaided conditions in the S 0 N 0 and S 0 N SSD conditions ( P >0.05). The total score of THI and three dimensions were significant decreased ( P <0.05). Tinnitus VAS scores were significantly lower in binaural hearing compared to the unaided condition ( P <0.001). The total score of SSQ, and the scores of speech and spatial dimensions were significant improved in binaural hearing compared to the unaided condition ( P <0.001). There was no statistical difference in NCIQ questionnaire scores between preoperative and postoperative ( P >0.05), and only the self-efficacy subscore showed a significant increase( Z =-2.497, P =0.013). Conclusion: CI could help Mandarin-speaking SSD patients restore binaural hearing to some extent, improve sound localization and speech recognition in noise. In addition, CI in SSD patients could suppress tinnitus, reduce the loudness of tinnitus, and improve subjective perceptions of spatial hearing and quality of life.

Objectives: To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision. Methods: In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People's Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group ( n =39) and non-tumor residual group ( n =30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ 2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results: The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs . 61.9%(13/21), χ 2 =7.838, P= 0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor ( OR =16.852, 95% CI : 1.819 to 156.130, P =0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions: BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.

Breast cancer, especially the aggressive triple-negative subtype, poses a serious health threat to women. Unfortunately, effective targets are lacking, leading to a grim prognosis. Research highlights the crucial role of c-MYC overexpression in this form of cancer. Current inhibitors targeting c-MYC focus on stabilizing its G-quadruplex (G4) structure in the promoter region. They can inhibit the expression of c-MYC , which is highly expressed in triple-negative breast cancer (TNBC), and then regulate the apoptosis of breast cancer cells induced by intracellular ROS. However, the clinical prospects for the application of such inhibitors are not promising. In this research, we designed and synthesized 29 acridone derivatives. These compounds were assessed for their impact on intracellular ROS levels and cell activity, followed by comprehensive QSAR analysis and molecular docking. Compound N 8 stood out, significantly increasing ROS levels and demonstrating potent anti-tumor activity in the TNBC cell line, with excellent selectivity shown in the docking results. This study suggests that acridone derivatives could stabilize the c-MYC G4 structure. Among these compounds, the small molecule N 8 shows promising effects and deserves further investigation.

We retrospectively analyzed a rare case of giant pleural tuberculoma. The patient was a female, 62 years old, admitted to hospital for intermittent fever and hemoptysis. The CT scan of the chest and abdomen showed a mass in the right thoracic cavity, and the uneven surface of the bilateral fallopian tubes. Routine blood tests showed a decrease in platelets, white blood cells, and hemoglobin. The mass in the chest was finally confirmed as a tuberculoma by biopsy. The patient was diagnosed with tuberculosis more than 9 years ago and had been treated with anti-tuberculosis drugs for more than 9 years, which caused damage to the liver, bone marrow and other organs, and led to the drug-resistant tuberculosis, making diagnosis and treatment more complex.

Objective: To investigate the chronic respiratory symptoms and pulmonary function of adult residents in 3 towns of Hongtong County, Shanxi Province, and to explore their risk factors. Methods: The investigation of chronic respiratory symptoms and lung function status of adult residents in Hongdong County is based on the regional population of the entire county in Hongdong County. The project was initiated by the Science and Technology Department of Linfen City and coordinated by the Hongdong County Government. The investigation will be conducted in 3 townships in Hongdong County, Linfen City, Shanxi Province from April to November 2021: Demographic characteristics, respiratory symptoms, smoking dust exposure and other personal history were collected through questionnaires. Physical examination, routine blood tests and lung function tests were also performed on each individual. SPSS 22.0 software was used to conduct t test, χ 2 test, ANOVA or Kruskal-Wallis test for statistical analysis of the collected information. Results: 10 945 subjects aged 18-102 years were included in the analysis, of whom 3 754 (34.3%) were male, 1 222 (11.2%) had a history of dust exposure, 7 164 (65.5%) had used straw and firewood as cooking fuel, and 3 296 (30.1%) had a history of smoking. Among the participants, 394 (3.6%), 339 (3.1%), and 1 543 (14.1%) had respiratory symptoms such as chronic cough, sputum, and dyspnea. Statistics showed that the population with chronic respiratory symptoms was more elderly and had a smoking history, and the incidence of chronic respiratory symptoms was higher in those who smoked more than 40 packs a year (all P <0.05). Men with a history of dust exposure were more likely to suffer from chronic cough and expectoration, while emaciation and biofuel use for more than 40 years were more likely to suffer from chronic expectoration and dyspnea (all P <0.05). The median values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC in 1 second were 2.19 L/s, 3.24 L and 69.16%, respectively. Among them, the lung function of 5 801 (53.0%) respondents was lower than the expected value. The median FEV1/FVC decreased with the increase of age. The FEV1/FVC of people over 40 years old with smoking history was lower, the dust exposure history of people with decreased lung function was more than that of people with normal lung function, and the incidence of chronic expectoration and dyspnea was higher in people with decreased lung function (all P <0.05). The absolute value and ratio of eosinophils in patients with decreased ventilation function over 60 years old were significantly higher than those with normal ventilation function, but the level of body mass index (BMI) was lower (all P <0.05). Conclusion: In Hongdong County, Shanxi Province, grassroots residents have poor medical awareness, low lung function examination rate, chronic respiratory symptoms and lung function decline are associated with more risk factors. Primary medical institutions need to formulate prevention strategies and carry out lung function detection according to the actual situation, focusing on monitoring and follow-up of high-risk groups to achieve early and timely prevention, diagnosis and treatment of chronic obstructive pulmonary disease.

Polyhydroxyalkanoates (PHAs) are a family of natural microbial biopolyesters with the same basic chemical structure and diverse side chain groups. Based on their excellent biodegradability, biocompatibility, thermoplastic properties and diversity, PHAs are highly promising medical biomaterials and elements of medical devices for applications in tissue engineering and drug delivery. However, due to the high cost of biotechnological production, most PHAs have yet to be applied in the clinic and have only been studied at laboratory scale. This review focuses on the biosynthesis, diversity, physical properties, biodegradability and biosafety of PHAs. We also discuss optimization strategies for improved microbial production of commercial PHAs via novel synthetic biology tools. Moreover, we also systematically summarize various medical devices based on PHAs and related design approaches for medical applications, including tissue repair and drug delivery. The main degradation product of PHAs, 3-hydroxybutyrate (3HB), is recognized as a new functional molecule for cancer therapy and immune regulation. Although PHAs still account for only a small percentage of medical polymers, up-and-coming novel medical PHA devices will enter the clinical translation stage in the next few years.

Objective: To explore the clinical features of IgG4-related lung disease. Methods: The clinical data of 60 patients diagnosed with IgG4-related lung disease in Peking University People's Hospital from February 2012 to May 2021 were retrospectively collected. Analysis was made to explore the features of clinical manifestation, laboratory, imaging, prognosis and other characteristics of the disease. Results: A total of 60 patients were included, with 40 males, age of (58.2±12.9) years, an age of onset of (57.1±13.2) years, and 31.7% (19 cases) of the patients had a history of allergic disease. 36.7% (22 cases) of the patients had respiratory symptoms during the disease. 94.6% (53/56) of patients had serum IgG4>1.35 g/L, 24.1% (14/58) of patients had increased eosinophils, 79.2% (38/48) of patients had increased IgE level, and 53.7% (29/54) of patients had decreased C3 or C4. Common imaging findings included nodular changes (38 cases, 63.3%), mediastinal and/or hilar lymphadenopathy (34 cases, 56.7%), and ground glass opacities (31 cases, 51.7%). Fifty-three cases (88.3%) showed two or more imaging changes. The pathological examination of the patient was mainly characterized by lymphoplasmacytic infiltration and fibrosis, with only one case of phlebitis obliterans. Compared with the asymptomatic group (38 cases), patients with respiratory symptoms (22 cases) showed higher level of serum total IgG and eosinophils (43.2 vs 17.8 g/L, 0.30×10 9 /L vs 0.14×10 9 /L, P <0.05), lower proportion of allergic diseases, and higher proportion of consolidation shadows on chest CT ( P <0.05). There were no significant differences in serum IgG4, IgE, complement levels, and imaging outcomes after treatment between the two groups ( P >0.05). Conclusions: The clinical manifestations of IgG4-related lung disease are atypical, and asymptomatic patients account for a high proportion. The imaging of the disease is highly heterogeneous, and patients are prone to show coexisted multiple imaging changes. The main clinical features and imaging outcomes of patients with and without respiratory symptoms are not significantly different.

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering (TE) and regenerative medicine. In contrast to conventional biomaterials or synthetic materials, biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix (ECM). Additionally, such materials have mechanical adaptability, microstructure interconnectivity, and inherent bioactivity, making them ideal for the design of living implants for specific applications in TE and regenerative medicine. This paper provides an overview for recent progress of biomimetic natural biomaterials (BNBMs), including advances in their preparation, functionality, potential applications and future challenges. We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM. Moreover, we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications. Finally, we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field., (© 2023. The Author(s).)

Cryptococcus gattii often causes meningitis, but rarely causes pulmonary infections. Here, we reported a patient with asymptomatic pulmonary cryptococcosis caused by Cryptococcus gattii . The patient presented to the thoracic surgery department with an isolated pulmonary nodule that had been present for three years and underwent a thoracoscopic pulmonary wedge resection. Postoperative pathology was consistent with Cryptococcus gattii infection. Although the incidence of Cryptococcus gattii infection is lower than that of Cryptococcus neoformans , the neurological involvement is common and has severe complications. In this report, the risk factors, symptoms, diagnosis, treatment, and prognosis of Cryptococcus gattii pneumonia were discussed to improve clinical awareness of this disease.

Legionella pneumophila is an intracellular pathogen causing pneumonia in humans. In February 2022, Legionnaires' disease caused by L. pneumophila strain Corby in a patient with lung adenocarcinoma was identified for the first time in China. This paper includes the case report and phenotypic and genomic analysis of the Corby (ICDC) strain. Its biological characteristics were evaluated by antibiotic sensitivity testing and cytology experiments, and genomic analysis was performed to understand its genetic evolution. The patient's clinical manifestations included cough, fever, pulmonary infiltration, and significantly decreased activity endurance. After empirical antimicrobial therapy, infection indicators decreased. The Corby (ICDC) strain was susceptible to nine antibiotics and exhibited strong intracellular proliferation ability. A phylogenetic tree showed that the Corby (ICDC) strain was closely related to the Corby strain, but under the pressure of a complex environment, its genome had undergone more rearrangement and inversion. The type IF CRISPR-Cas system was identified in its genome, and spacer analysis indicated that it had been invaded by several foreign plasmids, bacteria, and viruses during evolution. Legionnaires' disease caused by L. pneumophila strain Corby may be ignored in China, and it is urgent to improve long-term monitoring and investigation of aquatic environments and patients with respiratory infections to prevent a large-scale outbreak of Legionnaires' disease.

Community-acquired pneumonia (CAP) is the third leading cause of death worldwide and one of the most commonly infectious diseases. Its epidemiological characteristics vary with host and immune status, and corresponding pathogen spectrums migrate over time and space distribution. Meanwhile, with the outbreak of COVID-19, some unconventional treatment strategies are on the rise. This article reviewed the epidemiological characteristics, pathogen spectrum and treatment direction of CAP in China over the years, and aimed to provide guidance for the diagnosis and treatment of CAP in clinical practice.

Vascular endothelial cells and oxidation reduction system play an important role in the pathogenesis of atherosclerosis (AS). If these conditions are disordered, it will inevitably lead to plaque formation and even rupture. Astragaloside IV (AsIV) and salvianolic acid B (Sal B) are the main active ingredients of Astragalus membranaceus and Salvia miltiorrhiza, respectively, and found to ameliorate vascular endothelial dysfunction and protect against oxidative stress in recent studies. However, it is still unknown if the combination of AsIV and Sal B (AsIV + Sal B) can inhibit the development of plaque through amplifying the protective effect of vascular endothelial cells and anti-oxidative stress effect. To clarify the role of AsIV + Sal B in AS, we observed the efficacy of each group (Control, Model, AsIV, Sal B, and AsIV + Sal B) by biomolecular assays, such as observing the pathological morphology of the aorta by oil red O staining, evaluating the level of oxidative stress and endothelial cells in the serum by the Elisa test, and analyzing the changes of all small molecule metabolites in liver tissue by UPLC-QTOF-MS. Results showed that AsIV, Sal B and AsIV + Sal B decreased the deposition of lipid in the arterial wall, so as to exert the effect of anti-oxidant stress and vascular endothelial protection, where the inhibitory effect of AsIV + Sal B was the most obvious. Metabonomics analysis showed that Sal B regulated the metabolic pathways of arginine and proline. AsIV regulated glycerol metabolism and saturated fatty acid biosynthesis metabolism. AsIV + Sal B is mainly related to the regulation of the citrate cycle (TCA cycle), alanine, aspartic acid, and glutamate metabolism, cysteine, and methionine metabolism. Succinic acid and methionine are synergistic metabolites that exert an enhancing effect when AsIV and Sal B were used in combination. In conclusion, we demonstrated that AsIV acompanied with Sal B can be successfully used for anti-oxidative stress and vascular endothelial protection of AS, and succinic acid and methionine are the synergistic metabolites., (Copyright © 2022 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Massoia lactone could be released from liamocins produced by Aureobasidium melanogenum M39. The obtained Massoia lactone was very stable and highly active against many fungal crop pathogens which cause many plant diseases and food unsafety. Massoia lactone treatment not only could effectively inhibit their hyphal growth and spore germination, but also caused pore formation in cell membrane, reduction of ergosterol content, rise in intracellular ROS levels, and leakage of intracellular components, consequently leading to cellular necrosis and cell death. The direct contact of Massoia lactone with Fusarium graminearum spores could stop the development of Fusarium head blight symptom in the diseased wheats. Therefore, Massoia lactone could be a promising candidate for development as an effective and green bio-fungicide because of its high anti-fungal activity and the multiplicity of mode of its action., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: 18 F-FDG PET/CT has an important role in the evaluation of fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Our study was to investigate the current status of the inclusion of 18 F-FDG PET/CT within FUO/ IUO diagnostic work-up and evaluate the cost-effectiveness of it in China., Methods: A total of 741 FUO/IUO patients admitted to our hospital from January 2012 to December 2019 were retrospectively reviewed. The clinical characteristic, medical expenses to reach diagnosis and the proportion of definite etiological diagnosis achieved upon hospital discharge were compared between patients examined by 18 F-FDG PET/CT ( 18 F-FDG PET/CT group) and patients not examined by 18 F-FDG PET/CT (non- 18 F-FDG PET/CT group)., Results: The mean age, proportion of critically-ill patients, proportion of rheumatologic diseases, the number of examinations and hospitalisation days to reach diagnosis in the 18 F-FDG PET/CT group were significantly higher than those in the non- 18 F-FDG PET/CT group. The mean medical costs of 18 F-FDG PET/CT group were significantly higher than those of non- 18 F-FDG PET/CT group, whereas the proportion of definite etiological diagnosis achieved upon hospital discharge of 18 F-FDG PET/CT group was significantly higher than that of non- 18 F-FDG PET/CT group. The mean hospitalisation days and mean medical costs before diagnosis were significantly lower in patients who undertook 18 F-FDG PET/CT ≤ 7 days after hospital admission than those in patients who undertook 18 F-FDG PET/CT > 7 days after hospital admission., Conclusions: 18 F-FDG PET/CT is mostly used in critically-ill and hard-to-diagnose FUO/IUO patients currently in China, which may conceal its cost-effective advantage. While the early use of 18 F-FDG PET/CT according to patient characteristics and etiological clues could help to reduce hospitalization stay, limit medical costs, thus producing its diagnostic effect to the great extent., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To clarify the clinical characteristics of influenza pneumonia in the elderly patients and the relationship between D-dimer and the severity of influenza pneumonia., Methods: In the study, 52 hospitalized patients older than 65 years with confirmed influenza pneumonia diagnosed in Peking University People's Hospital on 5 consecutive influenza seasons from 2014 were retrospectively analyzed. General information, clinical symptoms, laboratory data, treatment methods and prognosis of the patients were collected. The relationship between D-dimer and pneumonia severity was analyzed, and receiver operating characteristic (ROC) curve was used to evaluate the predictive value of D-dimer., Results: Among the 52 patients, 31 were male (31/52, 59.6%), the average age was (77.1±7.4) years, and 19 of them (36.5%) were diagnosed with severe pneumonia. About 70% patients presenting with fever. In the severe group, the patients were more likely to complain of dyspnea than in the non-severe group (14/19, 73.7% vs . 10/33, 30.3%, P =0.004), severe pneumonia group had higher level of CURB-65 (confusion, urea, respiratory rate, blood pressure, and age>65), pneumonia severity index (PSI), C-reactive protein, urea nitrogen, lactate dehydrogenase, fasting glucose, and D-dimer ( P value was 0.004, < 0.001, < 0.001, 0.003, 0.038, 0.018, and < 0.001, respectively), albumin was lower than that in the non-severe group [(35.8±5.6) g/L vs . (38.9±3.5) g/L, t =-2.348, P =0.018]. There was a significant positive correlation between the D-dimer at the first admission and PSI score ( r =0.540, 95% CI : 0.302 to 0.714, P < 0.001), while a significant negative correlation with PaO 2 /FiO 2 ( r =-0.559, 95% CI : -0.726 to -0.330, P < 0.001). Area under the curve of D-dimer was 0.765 (95% CI : 0.627 to 0.872). Area under the curve of PSI was 0.843 (95% CI : 0.716 to 0.929). There was no statistically significant difference in test efficacy between the two ( Z =2.360, P =0.174). D-dimer level over 1 225 μg/L had a positive predict value for influenza pneumonia in hospital death with a sensitivity of 76.92% and a specificity of 74.36%., Conclusion: Influenza pneumonia in the elderly always has atypical symptoms, dyspnea is a prominent feature in severe cases, D-dimer level is associated with the severity of influenza pneumonia, and greater than 1 200 μg/L has a good predictive value for in-hospital death in the elderly.

H1N1 and H3N2 are the two most common subtypes of swine influenza virus (SIV). They not only endanger the pig industry, but are also a huge risk of zoonotic diseases. However, the molecular mechanism and regulatory network of pigs (hosts) against influenza virus infection are still unclear. In this study, porcine alveolar macrophage cell (3D4/21) models infected by swine influenza virus (H1N1 and H3N2) were constructed. The expression profiles of miRNAs, mRNAs, lncRNAs and circRNAs after H1N1 and H3N2 infected 3D4/21 cells were revealed in this study. Then, two ceRNAs (TCONS&#95;00166432-miR10391-MAN2A1 and novel&#95;circ&#95;0004733-miR10391-MAN2A1) that regulated H1N1 and H3N2 infection in 3D4/21 cells were verified by the methods of bioinformatics analysis, gene overexpression, gene interference, real-time quantitative PCR (qPCR), dual luciferase activity assay and RNA immunoprecipitation (RIP). In addition, the important candidate molecules (miR-10391, TCONS&#95;00166432, and novel&#95;circ&#95;0004733) were identified by qPCR and enzyme linked immunosorbent assay (ELISA). Finally, the regulatory effect and possible molecular mechanism of the target gene MAN2A1 were identified by the methods of gene interference, qPCR, Western blot and ELISA. The results of this study suggested that TCONS&#95;00166432 and novel&#95;circ&#95;0004733 could competitively bind miR-10391 to target the MAN2A1 gene to regulate swine influenza virus infecting 3D4/21 cells. This study reported for the first time the ceRNA networks involved in the regulation of the swine influenza virus infecting 3D4/21 cells, which provided a new insight into the molecular mechanism of 3D4/21 cells against swine influenza virus infection.

Objective: To investigate the clinical features and pathogenesis of spontaneous regression of lymphoma involving the respiratory system. Methods: Two cases of pulmonary lymphoma which regressed spontaneously were reported. Literatures with"spontaneous regression, lymphoma""spontaneous remission, lymphoma"published before February 2020 were searched in Wanfang, CNKI and Pubmed database. And cases with respiratory system involvement of lymphoma which regressed spontaneously were analyzed. A total of 22 cases were finally retrieved. There were 6 males and 16 females, with an average age of (62.5±16.8) years. Results: Common symptoms included dyspnea, cough, expectoration, fever and weakness. Imaging examination showed that any parts in respiratory system could be involved. The proportion of invasive and indolent lymphomas was approximately similar. The time interval between diagnosis of lymphoma and first sign of spontaneous regression of the disease was from 2 weeks to 1 year. Spontaneous regression of the disease could sustain from 50 days to 60 months. Moreover, 78.6% of patients achieved complete remission in their courses of treatment, and some patients showed wax and wane phenomena. Conclusions: Spontaneous regression of lymphoma may occur in any part of the respiratory system. When a patient exhibits spontaneous regression of pulmonary lesions, lymphoma should be considered in the differential diagnoses. Pathology study is needed to achieve a definitive diagnosis. Misdiagnosis and delayed diagnosis related to empirical treatment of antibiotics and corticosteroid should be avoided.

Objective: To explore the epidemiological and clinical characteristics of COVID-19 reinfection cases. Methods: The published COVID-19 reinfection cases were reviewed and the relevant data were extracted, including the baseline characteristics of patients, the results of antibody tests, and the whole-genome sequencing results of the viral strains. Results: We reviewed 29 reinfection cases in 20 reports from 14 countries. The age of re-infected patients ranged from 21 to 90 years (median 53 years), and there was no significant difference in gender distribution. Among the 29 patients, 11 were health care workers, 6 received immunosuppressive drugs (including glucocorticoids), 17 presented more severe symptoms than their primary infections and 5 (all aged over 80 years) died. The interval of the two infections was usually less than 60 days when the patients were infected by the same viral strain,while the interval was much longer (median 78.5 days) when the patients were infected by different viral strains. Nine patients had negative antibody test results or low antibody titers when the reinfections were confirmed, and 5 of them had negative antibody test results even during the initial infection. Conclusions: Virus-specific antibodies had a protective effect against COVID-19 reinfection for the majority of the population, however, this effect may decrease over time. Occupational exposure, low levels of antibodies, or an inability to produce antibodies may be the main risk factors for reinfection. Advanced age was a major risk factor for a poor prognosis. Effective personal prevention and social distancing were still essential for the prevention of reinfection.

Spinal cord injury is a highly disabled neurological disease, and there is still a lack of effective treatments. Studies have proved that olfactory ensheathing cells are one of the ideal seed cells for promoting nerve regeneration after spinal cord injury. Olfactory ensheathing cells can promote axonal germination and elongation through secretion, interaction with astrocytes, regulation of inflammatory reaction, migration characteristics, myelination, anti-oxidation, lipid regulation and other channels. Thus olfactory ensheathing cells play the role of neuroprotection and nerve repair. In recent years, some studies have used bioengineering, tissue engineering, reprogramming and other technologies to enhance the efficacy of olfactoryensheathing cells from different aspects, thereby providing new therapeutic strategies for optimizing the cell therapy of spinal cord injury. This article will summarize the mechanism of olfactory ensheathing cells in repairing spinal cord injury, and review the progress of optimizing strategy of olfactory ensheathing cells in treating spinal cord injury recently, so as to provide new research ideas for the further developing the repair potential of olfactory ensheathing cells and optimize the cell therapy effect of spinal cord injury.

Recently, ultrathin localized spoof surface plasmon (LSSP) resonators are found to have intrinsic defects of relatively low quality factors (Q-factors) because of unavoidable material and radiation losses. In this paper, multilayer structures of planar-circular-grating resonators and their magnetic-coupling schemes are proposed to achieve effective excitation of high-Q LSSPs modes. By adopting the multilayer structures with air between the layers, the power dissipation effected by both material and radiation losses is significantly suppressed. Experimental results show that the Q-factors could reach more than 200 and the excitation efficiencies could reach more than 90%. Numerical simulations show the distribution of the electromagnetic field and illustrate the principle of magnetic coupling. Besides, the Q-factors of resonators with different structural parameters were measured and analyzed. This study aims to provide some inspirations on planar gyro-devices and to improve the performance of existing applications, such as sensors and filters.

Although tumor necrosis factor α (TNF-α)-mediated inflammation significantly impacts osteoporosis, the mechanisms underlying the osteogenic differentiation defects of bone marrow-derived mesenchymal stem cells (BM-MSCs) caused by TNF-α remain poorly understood. We found that TNF-α stimulation of murine BM-MSCs significantly upregulated the expression levels of several microRNAs (miRNAs), including let-7f-5p, but this increase was significantly reversed by treatment with the kinase inhibitor BAY 11-7082. To study gain- or loss of function, we transfected cells with an miRNA inhibitor or miRNA mimic. We then demonstrated that let-7f-5p impaired osteogenic differentiation of BM-MSCs in the absence and presence of TNF-α, as evidenced by alkaline phosphatase and alizarin red staining as well as quantitative assays of the mRNA levels of bone formation marker genes in differentiated BM-MSCs. Moreover, let-7f-5p targets the 3' untranslated region of Nucleoside diphosphate kinase 4 (Nme4) mRNA and negatively regulates Nme4 expression in mouse BM-MSCs. Ectopic expression of Nme4 completely reversed the inhibitory effects of the let-7f-5p mimic on osteogenic differentiation of mouse BM-MSCs. Furthermore, inhibition of let-7f-5p or overexpression of Nme4 in BM-MSCs restored in-vivo bone formation in an ovariectomized animal model. Collectively, our work indicates that let-7f-5p is involved in TNF-α-mediated reduction of BM-MSC osteogenesis via targeting Nme4.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by arteriovenous malformations in the skin and mucous membranes. We enrolled a large pedigree comprising 32 living members, and screened for mutations responsible for HHT., Methods: We performed whole-exome sequencing to identify novel mutations in the pedigree after excluding three previously reported HHT-related genes using Sanger sequencing. We then performed in silico functional analysis of candidate mutations that were obtained using a variant filtering strategy to identify mutations responsible for HHT., Results: After screening the HHT-related genes, activin A receptor-like type 1 (ACVRL1), endoglin (ENG), and SMAD family member 4 (SMAD4), we did not detect any co-segregated mutations in this pedigree. Whole-exome sequencing analysis of 7 members and Sanger sequencing analysis of 16 additional members identified a mutation (c.784A > G) in the NSF attachment protein gamma (NAPG) gene that co-segregated with the disease. Functional prediction showed that the mutation was deleterious and might change the conformational stability of the NAPG protein., Conclusions: NAPG c.784A > G may potentially lead to HHT. These results expand the current understanding of the genetic contributions to HHT pathogenesis.

Background: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines., Methods: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19., Results: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004)., Conclusions: The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

To investigate the clinical significance of serum soluble programmed cell death ligand-1 (PD-L1) in adult patients with community-acquired pneumonia (CAP). A total of 44 CAP patients, 54 severe CAP patients and 30 healthy volunteers were recruited in this study. Serum soluble PD-L1 were detected. Univariate and multivariate regression analyses were used to assess the influence of multiple clinical variables on prognosis. Serum soluble PD-L1 level in severe CAP group was 98.20(57.94, 128.90) ng/L, which was significantly higher than that in the CAP group [59.32(33.55, 92.58) ng/L] and healthy controls [20.44(12.15, 36.20) ng/L] (all P <0.001). PD-L1 level was positively correlated with CRUB-65( r =0.481, P <0.001) and the pneumonia severity index (PSI) score ( r =0.442, P <0.001). Univariate regression analysis showed that CURB-65 ( HR =2.544, 95% CI 1.324-4.889, P =0.005), PSI score ( HR =1.036, 95% CI 1.012-1.061, P =0.004), soluble PD-L1( HR =1.013, 95% CI 1.001-1.026, P =0.041) were risk factors of mortality during hospitalization. Multivariate regression analysis suggested that PSI score ( HR =1.042, 95% CI 1.012-1.073, P =0.005), soluble PD-L1 ( HR =1.011, 95% CI 1.002-1.071, P =0.020) were independent predictors for mortality risk in CAP patients. CAP patients with soluble PD-L1≥98.20 ng/L had a significantly lower survival rate than those with soluble PD-L1<98.20 ng/L ( P =0.033). In conclusion, this study indicates that serum soluble PD-L1 level in CAP patients is correlated with the survival prognosis.

In this study, the interactions between spin wave (SW) and stacked domain walls in a magnetic nanostrip are investigated via micromagnetic simulation. It is found that under the excitation of SW, the metastable TWVW structure consisting of a transverse wall (TW) and a vortex wall (VW) may transform into a 360° wall or may completely annihilate depending on the frequency and amplitude of the SW. In contrast, stacked TWs (STWs) structure shows good robustness. Similar to a single TW, the STWs can be moved by SW and the inside TWs exhibit coherent motions. Notably, the frequency dependence of STWs' velocity demonstrates obvious emergence, shift and disappearance of the resonant peaks. Such changes are found to be in accordance with SW reflection, which thus agrees with the mechanism of linear momentum transfer torque (LMTT). In concern with the SW transmission through STWs, we show that by varying TWs number and SW frequency, a wide range of transmission efficiency η can be obtained. At certain frequencies, η may increase with TWs number and may go beyond 100%, which indicates a lowered attenuation by STWs. On the other hand, the phase shift of the transmitted SW always increases linearly with the TWs number and can be resonantly enhanced at frequencies same as that of TWs normal modes. Mapping of SW reveals that the phase shift is a result of fast propagation of SW through TWs. The fast propagation and the low attenuation of SW through STWs suggests that STWs may serve as an excellent SW channel. Meanwhile, the induced STWs motion and the controlled SW transmission and phase shift by STWs also promises great uses of STWs in future magnonic devices and domain wall devices.

Background: The current outbreak of coronavirus disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, Hubei, China, spreads across national and international borders., Methods: We prospectively collected medical records of 14 health care workers (HCWs) who were infected with SARS-CoV-2, in neurosurgery department of Wuhan Union Hospital, China., Results: Among the 14 HCWs, 12 were conformed cases, the other 2 were suspected cases. Most of them were either exposed to the two index patients or infected coworkers, without knowing they were COVID-19 patients. There were 4 male and 10 female infected HCWs in this cohort, whose mean age was 36 years (SD, 6 years). The main symptoms included myalgia or fatigue (100%), fever (86%) and dry cough (71%). On admission, 79% of infected HCWs showed leucopenia and 43% lymphopenia. Reduced complement C3 could be seen in 57% of the infected HCWs and IL-6 was significantly elevated in 86% of them. The proportion of lymphocytes subsets, concentrations of immunoglobulins, complement C4, IL-2, IL-4, IL-10, TNF-α and IFN-γ were within normal range in these 14 infected HCWs. The most frequent findings on pulmonary computed tomographic images were bilateral multifocal ground-glass opacifications (86%)., Conclusions: Human-to-human transmission of COVID-19 pneumonia has occurred among HCWs, and most of these infected HCWs with confirmed COVID-19 are mild cases. Our data suggest that in the epidemic area of COVID-19, stringent and urgent surveillance and infection-control measures should be implemented to protect doctors and nurses from COVID-19 infection., Competing Interests: The authors declare that they have no competing interests., (© 2020 Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC.)

Liamocins, as the secondary metabolites synthesized and secreted by Aureobasidium spp., consist of a single mannitol or a single arabitol head group partially O-acylated with three 3,5-dihydroxydecanoic ester groups or directly esterified with three or four 3,5-dihydroxydecanoic ester tails. Very recently, the whole synthetic pathway of liamocins in A. melanogenum 6-1-2 has been elucidated. It was found that the promoter sequences of all the genes related to liamocin synthesis in A. melanogenum 6-1-2 had stress regulatory elements with core sequences of AGGGG or CCCCT. Therefore, expression of all the genes would be regulated by the Msn2. In this study, it was found that removal of the single one MSN2 gene in A. melanogenum 6-1-2 made the mutant decrease yield of extracellular liamocin by 92.28 %, while complementation of the MSN2 gene in the mutant rendered liamocin synthesis to be restored. When A. melanogenum 6-1-2 was cultured in the liamocin fermentation medium with high glucose and low nitrogen, the Msn2 was localized in the nucleus and positively regulated the expression of the genes related to liamocin biosynthesis. Furthermore, when the key BCY1 gene encoding regulatory subunit of the cAMP-PKA signaling pathway in A. melanogenum 6-1-2 was knocked out, the amount of extracellular liamocins synthesized by the mutant was decreased by 96.73 % and the Msn2 was localized in the cytoplasm. Similarly, when the key HOG1 gene in the HOG1 signaling pathway was deleted, liamocin biosynthesis in the knockout strain was decreased by 98.09 %. However, it was found that the Hog1 may be one part of the general transcription complex to regulate the transcription of the MSN2 gene, leading to the reduced Msn2 and liamocin synthesis in the mutant. In addition, the key TOR1 gene and SNF1 gene in the TOR1 signaling pathway and the SNF1 signaling pathway were not involved in the regulation of the Msn2 activity and liamocin synthesis. It was concluded that the transcriptional activator Msn2, the HOG1 signaling pathway and the cAMP-PKA signaling pathway were involved in the regulation of liamocin biosynthesis and production., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) poses distinct clinical challenges due to extensively drug resistant (XDR) phenotype, and sequence type (ST) 11 is the most dominant blaKPC-2-bearing CP-Kp clone in China. The purpose of this current retrospective study was to explore the genetic factors associated with the success of XDR CP-Kp ST11 strains circulated in the intensive care unit (ICU) of a Chinese tertiary hospital., Methods: Six ST11 XDR CP-Kp strains were identified between May and December 2014 and validated by minimum inhibitory concentration examination, polymerase chain reaction, and pyrosequencing. The six ST11 XDR CP-Kp, as well as three multi-drug resistant (MDR) and four susceptible strains, were sequenced using single-molecule real-time method. Comprehensively structural and functional analysis based on comparative genomics was performed to identify genomic characteristics of the XDR ST11 CP-Kp strains., Results: We found that ST11 XDR blaKPC-2-bearing CP-Kp strains isolated from inpatients spread in the ICU of the hospital. Functionally, genes associated with information storage and processing of the ST11 XDR CP-Kp strains were more abundant than those of MDR and susceptible strains, especially genes correlative with mobile genetic elements (MGEs) such as transposons and prophages. Structurally, eleven large-scale genetic regions taken for the unique genome in these ST11 XDR CP-Kp strains were identified as MGEs including transposons, integrons, prophages, genomic islands, and integrative and conjugative elements. Three of them were located on plasmids and eight on chromosomes; five of them were with antimicrobial resistance genes and eight with adaptation associated genes. Notably, a new blaKPC-2-bearing ΔΔTn1721-blaKPC-2 transposon, probably transposed and truncated from ΔTn1721-blaKPC-2 by IS903D and ISKpn8, was identified in all six ST11 XDR CP-Kp strains., Conclusion: Our findings suggested that together with clonal spread, MGEs identified uniquely in the ST11 XDR CP-Kp strains might contribute to their formidable adaptability, which facilitated their widespread dissemination in hospital.

The solute carrier 4 (SLC4) family is a class of cell membranes transporters involved in base transport that plays crucial roles in diverse physiological processes. In our study, 15 slc4 genes were identified and annotated in spotted sea bass, including five members of Cl - /HCO 3 - exchangers, eight genes coding Na + -dependent HCO 3 - transporters, and two copies of Na + -coupled borate transporters. The gene sequence and structure, chromosomal and syntenic arrangement, phylogenetic and evolution profiles were analyzed. Results showed that the slc4 gene in teleosts obviously expanded compared with higher vertebrates, arising from teleost-specific whole genome duplication event. Most gene sites of slc4 in spotted sea bass were under strong purifying selection during evolution, while positive selection sites were only detected in slc4a1b , slc4a8 , and slc4a10b . Additionally, qRT-PCR results showed that different slc4 genes exhibited distinct branchial expression patterns after alkalinity and salinity stresses, of which the strongly responsive members may play essential roles during these physiological processes. Our study provides the systemic overview of the slc4 gene family in spotted sea bass and enables a better understanding for the evolution of this family and further deciphering the biological roles in maintaining ion and acid-base homeostasis in teleosts., Competing Interests: The authors declare no conflict of interest.

The effect of bromide and iodide on the transformation of humic acid (HA) and algal organic matter (AOM), and the formation of disinfection by-products (DBPs) during UV/chlorination were investigated. Experimental results indicated that the halides effectively inhibited mineralization, with multiple changes in organic molecule transformation due to differences in formation and speciation of reactive halogen species and free halogen. As a consequence, bromide and iodide also played important roles in DBP formation. The DBP yields in HA-containing water during UV/chlorination decreased in the order of iodide loaded > freshwater ≫ bromide loaded, whereas DBP formation in AOM-containing water decreased remarkably with halides added (freshwater > bromide loaded ≫ iodide loaded) at high UV fluence. Moreover, Pearson correlation analysis exhibited weaker correlation between DBPs and water parameters in AOM-containing water, while DBPs in HA-containing water exhibited better correlation with water parameters. For both simulated waters, the theoretical toxicity was calculated and peaked in bromide-containing water, whereas the calculated toxicity in iodide-containing water was comparable or slightly higher than that in freshwater. Therefore, UV/chlorine treatment may achieve good quality water with reduced DBP-associated toxicity in freshwater or iodide-containing water (iodide only), but careful consideration is needed when purifying source waters containing bromide (bromide only), especially for AOM/bromide-containing water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The fundamental problem of domain wall (DW) inertia-the property that gives to inertial behaviors remains unclear in the physics of magnetic solitons. To understand its nature as well as to achieve accurate DW positioning and efficient manipulation of domain wall motion (DWM), spin wave (SW) pulse-induced DW transient effect is studied both numerically and theoretically in a magnetic nanostrip. It is shown for the first time that there occurs inevitable deceleration/automotion after SW pulse, which indicates nonzero DW inertia. The induced DWM is revealed to relate to two factors: energy storing within DW and out-of-plane tilting of DW. To explain the DWM dynamics, a one-dimensional collective model is developed to account for the excitation of spin wave pulse. The model successfully bridges DW energy, DW tilting and DW displacement and provides descriptions in accordance with numerical findings. It is made clear that the DW automotion hence DW inertia originate from the process of DW relaxation toward equilibrium. The DW inertia is expressed in terms of effective mass and turns out to be a time-dependent function with damping constant α as the governing parameter, which opposes the nature of intrinsic mass. For case containing multiple DWs, the total effective mass is shown to concern the reached velocity and stored energy of DWs instead of the number of DWs, which is against common intuition., (© 2020 IOP Publishing Ltd.)

So far, it has been still unknown how liamocins are biosynthesized, regulated, transported and secreted. In this study, a highly reducing polyketide synthase (HR-PKS), a mannitol-1-phosphate dehydrogenase (MPDH), a mannitol dehydrogenase (MtDH), an arabitol dehydrogenase (ArDH) and an esterase (Est1) were found to be closely related to core biosynthesis of extracellular liamocins in Aureobasidium melanogenum 6-1-2. The HR-PKS was responsible for biosynthesis of 3,5-dihydroxydecanoic acid. The MPDH and MtDH were implicated in mannitol biosynthesis and the ArDH was involved in arabitol biosynthesis. The Est1 catalyzed ester bond formation of them. A phosphopantetheine transferase (PPTase) activated the HR-PKS and a transcriptional activator Ga11 activated expression of the PKS1 gene. Therefore, deletion of the PKS1 gene, all the three genes encoding MPDH, MtDH and ArDH, the EST1, the gene responsible for PPTase and the gene for Ga11 made all the disruptants (Δpks13, Δpta13, Δest1, Δp12 and Δg11) totally lose the ability to produce any liamocins. A GLTP gene encoding a glycolipid transporter and a MDR1 gene encoding an ABC transporter took part in transport and secretion of the produced liamocins into medium. Removal of the GLTP gene and the MDR1 gene resulted in a Δgltp1 mutant and a Δmdr16 mutant, respectively, that lost the partial ability to secrete liamocins, but which cells were swollen and intracellular lipid accumulation was greatly enhanced. Hydrolysis of liamocins released 3,5-dihydroxydecanoic acid, mannitol, arabitol and acetic acid. We proposed a core biosynthesis pathway, regulation, transport and secretion of liamocins in A. melanogenum., (© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

At the end of 2019, sporadic and clustered case with "pneumonia of unknown origin" emerged in Wuhan, Hubei province. The causative pathogen was quickly confirmed as "2019-nCoV" . The epidemic soon spread throughout the country and became a pandemic in over a month. Government and medical institutions across the country mobilized all kinds of resources and took a variety of measures to actively treat patients and stop the epidemic. Based on current studies, the author summarized the clinical characteristics and evolution of the novel viral pneumonia, and proposed the key points of diagnosis and treatment, the scientific management of both confirmed and suspected cases, and the scientific management of disease prevention and control.

This study compared the degradation of dissolved organic matter (DOM) by UV/chlorine advanced oxidation processes (AOPs) with emerging ultraviolet light-emitting diode (UV-LED, 275 nm) and traditional low pressure UV (LPUV, 254 nm) as UV sources. Excitation emission matrix-parallel factor (EEM-PARAFAC) analysis and two-dimensional (2D) correlation gel permeation chromatograph were applied to explore the evolutions of DOM during oxidation processes. The degradation behaviors of DOM indicated by UV absorbance at 254 nm (UV 254 ), dissolved organic carbon (DOC), and fluorophores fitted the pseudo-first-order kinetics well. The removal efficiency of DOM was similar under UV-LED and LPUV irradiation alone. However, UV-LED exhibited much higher degradation rates (increased by 29-160%) than LPUV regardless of the tracking variables during UV/chlorine processes. For three PARAFAC components, humic-like fluorescences were preferentially degraded by UV/chlorine oxidation compared with protein-like fluorescence potentially due to the differences of electronic moieties and molecular weight (MW). The decline in UV 254 , DOC, and fluorophores increased with increasing chlorine dosage; linear correlations between those indicators were observed during the two AOPs. Moreover, UV-LED/chlorine could achieve greater extents of MW change. Our study demonstrated that UV-LED could be a superior alternative for the future selection of UV source in the UV/chlorine process., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To explore the expression and clinical significance of chemokine ligand 18 (CCL18) in Bronchoalveolar Lavage Fluid (BALF) of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). Methods: From January 2016 to June 2017, BALF of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD group), patients with dermatomyositis-associated interstitial lung disease (DM-ILD group), and patients with primary Sjögren syndrome-associated interstitial lung disease (pSS-ILD group) of Peking University People's Hospital were collected. According to the prognosis of each group of patients during hospitalization, they were divided into the discharged and the died. Besides, 30 patients without ILD served as a control group. Levels of CCL18 in BALF of all patients were tested by enzyme linked immunosorbent assay (ELISA). Cells in BALF of RA-ILD group, DM-ILD group and pSS-ILD group were collected and analyzed by absolute different cell counts. Results of high-resolution CT (HRCT) of these three groups were scored. In addition, the area under the curve (AUC) of CCL18 in predicting mortality during hospitalization was calculated. Results: A total of 38 patients with RA-ILD, 54 patients with DM-ILD, and 35 patients with pSS-ILD were enrolled. Levels of CCL18 of those discharged patients of RA-ILD, DM-ILD, and pSS-ILD groups were 8.27(3.62, 14.36), 11.04 (5.86, 17.38), 5.25(2.68, 8.21) μg/L, respectively, which were all significantly higher than that of the control group [2.54(1.26, 3.66) μg/L, all P< 0.05]. Furthermore, levels of CCL18 of those deceased patients of RA-ILD and DM-ILD groups were 18.28 (13.82, 22.39), 18.81 (16.29, 22.90) μg/L, which were significantly higher than that of the discharged patients of same group (all P< 0.05). Levels of CCL18 were positively correlated with lymphocyte percentage in BALF of RA-ILD, DM-ILD and pSS-ILD groups ( r= 0.4356, 0.4029, 0.3939, respectively, all P< 0.05). Besides, levels of CCL18 were significantly correlated with HRCT scores of RA-ILD and DM-ILD groups ( r= 0.4242, 0.3319, respectively, both P< 0.05). Areas under the curve (AUCs) of CCL18 to predict mortality during hospitalization of RA-ILD and DM-ILD groups were 0.860, 0.851, respectively. Conclusions: Levels of CCL18 are elevated in BALF of CTD-ILD patients, and may be correlated with the severity and prognosis during hospitalization. CCL18 might be served as an indicator of the severity and prognosis of CTD-ILD.

Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

The efficiency of the ultraviolet (UV)/chlorine process strongly depends on UV wavelength because chlorine photolysis and its subsequent radical formation are highly wavelength-dependent. This study compared the degradation of humic acid (HA) during the UV/chlorine process by low pressure mercury lamp (LPUV, 254 nm) and ultraviolet light-emitting diode (UV-LED, 275 and 310 nm). The results indicated that HA degradation followed the pseudo-first-order kinetics, and the fluence-based degradation rate constants (k obs ) were significantly affected by UV wavelength and solution pH. HA degradation decreased greatly with increasing solution pH during the UV/chlorine process at 254 nm, while the opposite trend was observed at 275 and 310 nm. In the meantime, k obs decreased in the order of 275 nm > 254 nm > 310 nm at pH > 7.0. The changes of chlorine molar absorption coefficients at different UV wavelengths resulted in the variation of chlorine photodecay rates (k obs, chlorine ), and the synergistic effects of k obs, chlorine and chlorine quantum yields (Φ chlorine ) affected HA reduction. The formation of disinfection by-products (DBPs) during the UV/chlorine process was also evaluated. A significant suppression on DBP formation and DBP-associated calculated theoretical cytotoxicity were observed at 275 nm high UV fluence and alkaline pHs. These findings in this study demonstrate that UV wavelength at 275 nm is more suitable for HA degradation by the UV/chlorine advanced oxidation process in practical applications., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To investigate multilineage-differentiating stress-enduring (Muse) by immunomagnetic bead screening from Wharton's jelly mesenchymal stromal cells(WJ-MSCs), and explore transplantation of Muse cell for safety and effectivensess of sub acute cord injury in rats., Methods: Donated Wharton's Jelly-mesenchymal stromal cells (WJ-MSCs) were successfully derived from a human umbilical cord by a series of procedures namely physical isolation of Wharton's Jelly from cord membrane, collagenase and trypsin treatment and density gradient centrifugation. Magnetic activated cell sorting was performed to specifically select SSEA3+ Muse cells, and flow cytometry and immunocytochemistry were used to identify further. In vivo, spinal cord contusion injury model in rats was induced by NYU-III impactor, and were randomly divided and equally into four groups, namely group A (sham), group B (control), group C (Non-Muse cells transplantation) and group D (Muse cells transplantation). Laminectomy was conducted in group A but no spinal cord contusion injury. Laminectomy and cord injury were performed in group B, C and D, 10 g trip rod was freely falling down from 12.5 mm. Two weeks later, group B, C and D were received PBS injection, Non-Muse cells transplantation and Muse cells transplantation respectively, four-point injection were performed in each cord with totally 4×10⁵ cells. BBB scores were evaluated on 1 day, 1, 2, 3, 4, 5 and 6 week after injury. Four weeks after cell transplantation, the rats were sacrificed, and immunohistochemistry were carried out to observe survival, migration and differentiation of the injected cells., Results: The expression of CD105, CD90 and CD73 were over 99.5% in the derived WJ-MSCs population, but CD45 and CD14 were lower than 0.5%, positive rate of SSEA3+ was 1.46% under flow cytometer, However, after MACS sorting, the percentage of 92.0% Muse cells expressed SSEA3 and CD105, and immunohistochemistry results of SSEA3 showed typically membrane morphology with special processes. In vivo, BBB scores was 21 in group A at different time points. One-way ANOVA and LSD analysis showed that BBB scores in group C and D were significantly higher than that in group B ( P =0.004, 0.002), but there was no significantly difference between group C and D. Further intra-group paired t test showed that BBB score was significantly higher at 4 weeks than that 3 weeks in group C ( P =0.005). However, in group D, BBB scores were significantly higher at 4 and 6 week than those at 3 and 5 weeks, P values were 0.005 and 0.016 respectively. Immunohistochemistry results showed that both Muse cells and Non-Muse cells could survive for 4 weeks in rats and they migrated from the four-point injection to injury site. But there showed more Muse cells survival than Non-Muse cells in the cord., Conclusions: Immunomagnetic bead screening is efficient to select large number of purified SSEA3+ Muse cells. Muse cells could survive and target-migrate in injured cord to improve BBB scores continuously. Muse cells are a novel kind of seed cells in the spinal cord injury treatment., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Objective: To better understand the clinical features of human adenovirus type 7 (hAdV7) pneumonia and to identify whether there is a variation in the genome of the strain (CHN/BeiJing/2018) isolated during the small-scale epidemic. Method: Forty-two patients were diagnosed with hAdV7 pneumonia between October 27th, 2017 and February 28th, 2018. They were all males with an average age of (21±2) years. Demographic and clinical data were reviewed and analyzed in detail. The nucleic acid of the epidemic strain was extracted from a bronchoalveolar lavage fluid sample. Whole genome sequencing (WGS) was then performed and sequences were compared with other hAdV7 strains distributed globally. Phylogenetic tree analysis was conducted based on whole genome sequences of the epidemic strain. Results: Thirty-eight cases with hAdV7 pneumonia presented with influenza-like symptoms (90.5%) at the onset and 36 cases developed fever (85.7%), followed by cough (97.6%), expectoration (90.5%) and chest pain (28.6%). Five cases presented with tonsillitis(11.9%) and 4 had transient hemoptysis (9.5%), while 3 patients reported dyspnea (7.1%). Moist rales were only heard in 3 patients (7.1%). Notably elevated creatine kinase (CK) concentrations were observed in 8 patients (19.1%), but all returned to normal after treatment. Four cases developed hypoxemia (9.5%), but none of them progressed to respiratory failure or acute respiratory distress syndrome (ARDS). Chest CT imaging showed bilateral patchy parenchymal opacities with a random distribution with or without consolidation. Ten patients were co-infected with influenza virus (23.8%), while 32 patients developed atypical pneumonia (76.2%). Genomic analysis revealed that the strain isolated during this epidemic was 99% similar to the known hAdV7 strains (19BOVLB/Volgograd/Rus/2014 and 0901HZ/ShX/CHN/2009). Phylogenetic tree analysis suggested that the strain was closely related to the hAdV7 strain isolated in Jingmen China in 2012. Conclusions: Cases with hAdV7 pneumonia were generally mild. Symptomatic treatment was sufficient for a favorable prognosis. A good genome stability of the hAdV7 strain was observed, indicating that hAdV7 could remain stable for a long period and cause continuing sporadic cases and clusters.

Pulsed ultraviolet (UV) irradiation has presented enhanced inactivation efficiency in water disinfection and food decontamination. As an emerging UV source, UV light-emitting diodes (UV-LEDs) are an attractive alternative for pulsed irradiation because they can be turned on and off with a high and adjustable frequency. In this study, disinfection efficiencies of pulsed and continuous UV-LED irradiation were compared for Escherichia coli (E. coli) inactivation in water using a high power 285 nm LED and low power 265 and 280 nm LEDs. Factors including various duty cycles, pulse frequencies and UV irradiances were evaluated. The log-inactivation of E. coli increased substantially as the duty cycle decreased from 100% to 5% at the same UV dose. For 265 and 280 nm LEDs, the log-inactivation enhancements of pulsed UV irradiation were similar. When a higher irradiance was applied, the energy efficiency enhancement of pulsed UV irradiation became more obvious. The log-inactivation of E. coli enhanced remarkably using high current pulsed irradiation of 280 nm LEDs. Compared to continuous UV irradiation, pulsed UV-LED irradiation is an attractive alternative for E. coli inactivation in water considering energy efficiency., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To study and measure the anatomic structure of lumbar vertebral endplate structure in healthy adults by computed tomography(CT) technique in order to provide a useful guidance for the optimal design and clinical application of lumbar prostheses., Methods: Sixty healthy adults (male and female equals) were recruited for full-waist CT scan after signing the informed consent form in the imaging department of the Second Affiliated Hospital of Xi'an Jiaotong University. The scanning data was imported into the computer aided software Mimics 16.0 for 3D reconstruction and measurement. The acquisition indexes included median sagittal diameter, maximum coronal diameter, concavity depth, median sagittal depression angle, coronal depression angle and so on. Finally, the collected data were statistically analyzed by the statistical software., Results: The median sagittal diameter and the maximum coronal diameter of the upper and lower endplates were not only different between the different sexes( P <0.05), but also were increased with the increase of the lumbar spine sequence. The concavity depth of upper and lower endplates had no gender differences( P >0.05), but had a little change from L₁ to L₅, fluctuating from 1.5 to 2.0 mm and from 2.2 to 3.9 mm, respectively. In the same sequence, the concavity depth of lower endplate in males was greater than that of upper endplate, and the difference was statistically significant( P <0.05), but there was no significant difference in the concavity depth of upper and lower endplate in females( P >0.05). Sagittal concavity angle and coronal concavity angle of upper and lower endplates changed slightly with the increase of vertebral order, and there was no gender difference in sagittal and coronal concavity angle of most vertebral sequences ( P >0.05). Statistics showed that the largest concavity near the caudal lumbar endplate was located on the dorsal side of the endplate plane., Conclusions: The anatomical structure of the lumbar endplate is very complicated. It is important to master the anatomical parameters of the endplate and make full use of CT before operation for the development and clinical application of the lumbar prosthesis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

Ultraviolet (UV) irradiation has been widely used in drinking water treatment processes, but its influence on the formation of disinfection by-products (DBPs), especially the emerging iodinated trihalomethanes (I-THMs) during post-chloramination remains unclear. This study evaluated the impact of low pressure (LP) UV treatment on the formation of I-THMs during post-chloramination through two pathways. The first pathway is through the transition of DOM structure and composition during UV-chloramination, resulting significant increase of I-THM formation with increasing UV dosage in different dissolved organic matter (DOM)-containing water (49.7%-90.5% at 1160 mJ/cm 2 ). With the application of excitation emission matrix-parallel factor analysis (EEM-PARAFAC), we found that I-THM formation in UV-chloraminated water correlated well with two ratios of three PARAFAC humic-like components (C3/C2 and C1/C2, R 2  = 0.958-1.000), suggesting that the ratios of fluorescent components can be used as reliable indicators for I-THM formation. Moreover, the shift in these fluorescent components is crucial for I-THM formation during UV-chloramination. Another pathway for UV irradiation to affect I-THM formation during post-chloramination is through the transformation of iodine species. Large amounts of reactive iodine species (HOI/I 2 and I 3 - ) can be generated directly in the mixed iodine system by UV light, leading to the enhancement of iodine utilization factor (IUF) (up to 0.040) after post-chloramination. These results suggest that UV application to DOM-containing water may induce changes in organic precursors and iodine species so as to enhance I-THM formation during post-chloramination., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: To summarize the computed tomography angiography(CTA) features of Dieulafoy disease of the bronchus. Methods: The clinical, imaging and pathological data of Dieulafoy disease of the bronchus diagnosed in our hospital from July 4, 2010 to June 20, 2016 were retrospectively analyzed, and the CTA imaging features of the abnormal bronchial arteries were summarized. Results: There were 6 cases of bronchial Dieulafoy disease, 5 males and 1 female, with an average age of (55±15) years. Three cases had smoking history, and 2 cases had underlying diseases such as tuberculosis and acute myeloid leukemia. The common manifestations were hemoptysis, fever and pneumonia. Three patients got CTA examination, and bronchial arteries of Dieulafoy disease of the bronchus were circuitous and dilated, with the vascular diameter lager than 2 mm, no gradual narrowing but sudden truncation. Some circuitous vessels went into bronchial lumen as nodules. The bronchoscopy biopsy of 2 cases of bronchial nodules led to severe hemorrhage, with one death and one survival by successful management. Conclusions: Bronchial arteries of Dieulafoy disease of the bronchus were circuitous and dilated, and some circuitous vessels went into bronchial lumen as nodules, this demonstration can be used to diagnose Dieulafoy disease of the bronchus. For patients with hemoptysis, bronchial biopsy should only be performed after CTA examination if this disease is suspected.