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Background: Infection with Neisseria gonorrhoeae in adults usually leads to vaginitis and acute urethritis, and infection through the birth canal in newborns can lead to acute neonatal conjunctivitis. In view of certain factors such as a high missed detection rate of N.gonorrhoeae from staining microscopy method, the time-consuming nature and limited sensitivity of bacterial culture method, complicated and inability of absolute quantification from the ordinary PCR method., Methods: This study aims to establish a ddPCR system to detect N.gonorrhoeae in a absolute quantification, high specificity, high stability and accurate way. We selected the pgi1 gene as the target gene for the detection of N.gonorrhoeae., Results: The amplification efficiency was good in the ddPCR reaction, and the whole detection process could be completed in 94 min. It has a high sensitivity of up to 5.8 pg/μL. With a high specificity, no positive microdroplets were detected in 9 negative control pathogens in this experiment. In addition, ddPCR detection of N.gonorrhoeae has good repeatability, and the calculated CV is 4.2 %., Conclusions: DdPCR detection technology has the characteristics of absolute quantification, high stability, high specificity and high accuracy of N.gonorrhoeae. It can promote the accuracy of the detecting of N.gonorrhoeae, providing a more scientific basis for clinical diagnosis and treatment., 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 paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Eight previously undescribed cevanine-type steroidal alkaloids, cirrhosinones I-N and cirrhosinols A-B, along with five known analogs, were isolated from the bulbs of Fritillaria cirrhosa D. Don. Their structures were elucidated on the basis of comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and single-crystal X-ray diffraction analyses. All compounds revealed weak NO inhibitory activities in the LPS-stimulated NR8383 cells at the concentration of 20 μM, with inhibition ratios ranging from 5.1% to 14.3%., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Pulmonary embolisms (PEs) exhibit clinical features similar to those of acute coronary syndrome (ACS), including electrocardiographic abnormalities and elevated troponin levels, which frequently lead to misdiagnoses in emergency situations., Case Presentation: Here, we report a case of PE coinciding with chronic coronary syndrome in which the patient's condition was obscured by symptoms mimicking ACS. A 68-year-old female with syncope presented to the hospital. Upon admission, she was found to have elevated troponin levels and an electrocardiogram showing ST-segment changes across multiple leads, which initially led to a diagnosis of ACS. Emergency coronary arteriography revealed occlusion of the posterior branches of the left ventricle of the right coronary artery, but based on the complexity of the intervention, the occlusion was considered chronic rather than acute. On the 3rd day after admission, the patient experienced recurrent chest tightness and shortness of breath, which was confirmed as acute PE by emergency computed tomography pulmonary angiography. Following standardized anticoagulation treatment, the patient improved and was subsequently discharged., Conclusions: This case report highlights the importance of recognizing the nonspecific features of PE. Clinicians should be vigilant when identifying other clinical features that are difficult to explain accompanying the expected disease, and it is necessary to carefully identify the causes to prevent missed diagnoses or misdiagnoses., (© 2024. The Author(s).)

Introduction: Malnutrition is strongly associated with heart failure (HF); however, the causal link remains unclear. We used Mendelian randomization (MR) to infer causal associations between different nutritional assessment phenotypes and HF and to analyze whether these associations were mediated by common HF risk factors., Methods: Two-sample bidirectional MR was used to infer causal associations between nutritional assessment phenotypes and HF. Mutual influences between different nutritional assessment phenotypes and potential correlations were estimated using multivariate MR methods. Two-step MR was used to quantify the mediating effects of common HF risk factors on the causal associations., Results: Three phenotypes were positively associated with the development of HF: waist circumference (WC) (odds ratio [OR] = 1.74; 95% confidence interval [CI], 1.60-1.90; P  = 3.95 × 10 -39 ), body mass index (BMI) (OR = 1.70; 95%CI, 1.60-1.80; P  = 1.35 × 10 -73 ), and whole body fat mass (WBFM) (OR = 1.54; 95%CI, 1.44-1.65; P  = 4.82 × 10 -37 ). Multivariate MR indicated that WBFM remained positively associated with HF after conditioning on BMI and WC (OR = 2.05; 95%CI, 1.27-3.31; P  = 0.003). Three phenotypes were negatively correlated with the development of HF: usual walking pace (UWP) (OR = 0.40; 95%CI, 0.27-0.60; P  = 8.41 × 10 -6 ), educational attainment (EA) (OR = 0.73; 95%CI, 0.67-0.79; P  = 2.27 × 10 -13 ), and total cholesterol (TC) (OR = 0.90; 95%CI, 0.84-0.96; P  = 4.22 × 10 -3 ). There was a bidirectional causality between HF and UWP (Effect estimate = -0.03; 95%CI, -0.05 to -0.01; P  = 1.95 × 10 -3 ). Mediation analysis showed that common risk factors for HF (hypertension, coronary artery disease, cardiomyopathy, and valvular heart disease) mediated these causal associations (all P  < 0.05)., Conclusions: BMI, WC, and WBFM are potential risk factors for HF, and the correlation between WBFM and HF was significantly stronger than that between BMI and WC, and HF. EA, UWP, and TC are potential protective factors against HF. Common risk factors for HF mediate these causal pathways. Early identification of potential risk or protective factors for HF patients from the dimension of nutritional status is expected to further improve patient outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Using highly sensitive and selective in situ techniques to investigate the dynamics of intermediates formation is key to better understand reaction mechanisms. However, investigating the early stages of solid-state reactions/transformations is still challenging. Here we introduce in situ fluorescence spectroscopy to observe the evolution of intermediates during a two-step [2 + 2] photocycloaddition process in a coordination polymer platform. The structural changes and kinetics of each step under ultraviolet light irradiation versus time are accompanied by the gradual increase-decrease of intensity and blue-shift of the fluorescence spectra from the crystals. Monitoring the fluorescence behavior using a laser scanning confocal microscope can directly visualize the inhomogeneity of the photocycloaddition reaction in a single crystal. Theoretical calculations allow us to rationalize the fluorescence behavior of these compounds. We provide a convenient strategy for visualizing the solid-state photocycloaddition dynamics using fluorescence spectroscopy and open an avenue for kinetic studies of a variety of fast reactions., (© 2023. The Author(s).)

Although interlocked three-dimensional molecules display unique properties associated with their spatial structures, their synthesis and study of their host-guest properties remain challenging. We report the formation of a novel [2]catenane, [Et 4 N]@[(Tp*WS 3 Cu 3 Cl) 2 ( cis -bpype) 3 ] 2 (OTf) 5 ([Et 4 N][ 1 ](OTf) 5 ), by self-assembly of the cluster node [Tp*WS 3 Cu 3 Cl] + and the organic linker ( Z )-1,2-diphenyl-1,2-bis(4-(pyridin-4-yl)phenyl)ethene ( cis -bpype). Single-crystal X-ray and NMR analyses established that [ 1 ] 4+ is formed by the interpenetration of two cluster-organic cages. Unique cation-in-cation host-guest complexes were observed with this catenane. The crystalline, empty catenane was formed by taking advantage of the electrostatic repulsion-induced weak binding of the host. Encapsulation experiments also reveal that the empty catenane can adaptively encapsulate cations such as [Et 4 N] + and [Pr 4 N] + in the cross cavity but is unable to encapsulate [Bu 4 N] + and [Me 4 N] + , although the size of the latter is compatible with that of the cavity. Theoretical calculations and volume analysis allow to unravel the ingenious role of catenane structures and the interplay between electrostatic repulsion and attractive noncovalent interactions for size-specific recognition behavior in host-guest systems involving species with similar electric charges.

Due to its high reactivity and oxidative strength, singlet oxygen ( 1 O 2 ) is used in a variety of fields including organic synthesis, biomedicine, photodynamic therapy and materials science. Despite its importance, the controlled trapping and release of 1 O 2 is extremely challenging. Herein, we describe a one-dimensional coordination polymer, CP1, which upon irradiation with visible light, transforms 3 O 2 (triplet oxygen) to 1 O 2 . CP1 consists of Cd II centers bridged by 9,10-bis((E)-2-(pyridin-4-yl)vinyl)anthracene ligands which undergo a [4+2] cycloaddition reaction with 1 O 2 , resulting in the generation of CP1- 1 O 2 . Using microwave irradiation, CP1- 1 O 2 displays efficient release of 1 O 2 , over a period of 30 s. In addition, CP1 exhibits enhanced fluorescence and has an oxygen detection limit of 97.4 ppm. Theoretical calculations reveal that the fluorescence behaviour is dominated by unique through-space conjugation. In addition to describing a highly efficient approach for the trapping and controlled release of 1 O 2 , using coordination polymers, this work also provides encouragement for the development of efficient fluorescent oxygen sensors., (© 2023 Wiley-VCH GmbH.)

Rationale: The purpose of this article is to discuss the characteristics, diagnosis, treatment, and outcomes of cases of multiple coronary embolism (CE) highly suspected to be caused by a dislodged aneurysm of the ventricular membranous septum (AVMS) thrombus., Patient Concerns: A 35-year-old man was rushed to the Chest Pain Center of Taicang TCM Hospital Affiliated to Nanjing University of Chinese Medicine for sudden onset of chest pain. The patient had severe and persistent chest pain without relief, accompanied by sweating throughout the body., Diagnosis: An electrocardiogram showed ST-segment elevation in the inferior wall leads, and blood tests suggested elevated troponin I levels. The initial diagnosis was acute ST-segment elevation myocardial infarction. Emergency coronary angiography revealed complete occlusion of the first diagonal branch, thrombolysis in myocardial infarction grade 0 flow, and smooth remaining vessels. Complete occlusion of the left anterior descending artery unexpectedly occurred during interventional treatment. Postoperative cardiac ultrasonography revealed the presence of a thrombus within the AVMS and in the apical portion of the heart. The final diagnosis was a CE., Interventions: Intraoperatively, the diagonal branch occluded segment was dilated with a balloon and intracoronary administration of tirofiban and nitroglycerin. Postoperatively, antithrombotic therapy (aspirin, clopidogrel, and rivaroxaban) was administered., Outcomes: Ten days after admission, a repeat coronary angiography showed complete restoration of left anterior descending artery flow on its own, balloon dilation was again performed on the diagonal branch, and flow was restored to thrombolysis in myocardial infarction grade 1. Six months later, the intracardiac thrombus disappeared on repeat cardiac ultrasound., Lessons: AVMS is a potential source of embolism in patients with CE. CE has features that distinguish it from atherosclerosis, and a timely and correct diagnosis can help improve patient clinical outcomes., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Klebsiella pneumoniae is listed by the WHO as a priority pathogen of extreme importance that can cause serious consequences in clinical settings. Due to its increasing multidrug resistance all over the world, K. pneumoniae has the potential to cause extremely difficult-to-treat infections. Therefore, rapid and accurate identification of multidrug-resistant K. pneumoniae in clinical diagnosis is important for its prevention and infection control. However, the limitations of conventional and molecular methods significantly hindered the timely diagnosis of the pathogen. As a label-free, noninvasive, and low-cost method, surface-enhanced Raman scattering (SERS) spectroscopy has been extensively studied for its application potentials in the diagnosis of microbial pathogens. In this study, we isolated and cultured 121 K. pneumoniae strains from clinical samples with different drug resistance profiles, which included polymyxin-resistant K. pneumoniae (PRKP; n  = 21), carbapenem-resistant K. pneumoniae, (CRKP; n  = 50), and carbapenem-sensitive K. pneumoniae (CSKP; n  = 50). For each strain, a total of 64 SERS spectra were generated for the enhancement of data reproducibility, which were then computationally analyzed via the convolutional neural network (CNN). According to the results, the deep learning model CNN plus attention mechanism could achieve a prediction accuracy as high as 99.46%, with robustness score of 5-fold cross-validation at 98.87%. Taken together, our results confirmed the accuracy and robustness of SERS spectroscopy in the prediction of drug resistance of K. pneumoniae strains with the assistance of deep learning algorithms, which successfully discriminated and predicted PRKP, CRKP, and CSKP strains. IMPORTANCE This study focuses on the simultaneous discrimination and prediction of Klebsiella pneumoniae strains with carbapenem-sensitive, carbapenem-resistant, and polymyxin-resistant phenotypes. The implementation of CNN plus an attention mechanism makes the highest prediction accuracy at 99.46%, which confirms the diagnostic potential of the combination of SERS spectroscopy with the deep learning algorithm for antibacterial susceptibility testing in clinical settings.

Introduction: Heart Failure (HF) is a key area of research in human medicine, and traditional Chinese medicine (TCM) is an important branch of this field. This study aimed to use bibliometric methods to sort out the trajectory of TCM research on HF in this century (2000-2022) from a high dimension and to analyze its characteristics, hotspots and frontiers., Methods: In this study, the search formula "TS=(("traditional Chinese medicine") OR ("Chinese medicine")) AND TS=("heart failure")" was used to find relevant studies included in the Web of Science Core Collection from 2000 to 2022. Targeted literature records were analyzed and mapped using CiteSpace and VOSviewer., Results: The authors and collaborators of this study were still in the formation process, but several well-known scholars were included: YONG WANG, WEI WANG, etc. The main research institutions in this research area were Beijing Univ Chinese Med, China Acad Chinese Med Sc, etc. The main country of study was China. Current research hotspots and frontiers were Qili Qiangxin capsules, extracts (Tanshinone ⅡA, Panax ginseng, etc.), cardiac hypertrophy, ventricular remodeling, oxidative stress, signaling pathways, network pharmacology, etc. Influential journals that publish papers in this field were the Journal of Ethnopharmacology, Scientific Reports, Biomedicine & Pharmacotherapy, etc. The top 3 co-cited journals were Circulation, J ethnopharmacol, and J am coll cardiol., Conclusions: We analyzed valuable details in TCM research on HF in the 21st century, which may help researchers identify potential collaborators and partner institutions, hotspots, and frontiers in the field., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Developmental sevoflurane exposure leads to neuronal cell death, and subsequent learning and memory cognitive defects. The underlyi\ng mechanism remains to be elucidated. Gasdermin D (GSDMD)-mediated pyroptosis is a form of inflammatory cell death and participates in a variety of neurodegenerative diseases. Several studies illustrated that dysregulation of mTOR activity is involved in pyroptotic cell death. The current study was designed to interrogate the role of GSDMD-mediated pyroptosis and mTOR activity in developmental sevoflurane exposure. We found that inhibition of GSDMD pore formation with Disulfiram (DSF) or Necrosulfonamide (NSA) significantly attenuated sevoflurane neurotoxicity in vitro. In addition, treatment with DSF or NSA also mitigated damage-associated molecular patterns (DAMPs) release and subsequent plasma membrane rupture (PMR) induced by sevoflurane challenge. Further investigation showed that the overactivation of mTOR signaling is involved in sevoflurane induced pyroptosis both in vivo and in vitro. Intriguingly, we found that the DAMPs release and subsequent PMR triggered by developmental sevoflurane priming were compromised by knocking down the expression of mTORC1 component Raptor, but not mTORC2 component Rictor. Moreover, sevoflurane induced pyroptosis could also be restored by suppressing mTOR activity or knocking down the expressions of Ras-related small GTPases RagA or RagC. Finally, administration of DSF or NSA dramatically improved the spatial and emotional cognitive disorders without alternation of locomotor activity. Taken together, these results indicate that mTORC1-dependent and GSDMD-mediated pyroptosis contributes to the developmental sevoflurane neurotoxicity. Characterizing these processes may provide experimental evidence for the possible prevention of developmental sevoflurane neurotoxicity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Elderly patients with coronavirus disease 2019 (COVID-19) who have comorbidities, frailty or profound disabilities experience poor outcomes. We analyzed the clinical characteristics of elderly patients from Wuhan who had COVID-19 during the early stages of the pandemic., Aim: To identify factors affecting the early mortality of elderly patients with COVID-19., Methods: The records of 234 patients who were 65-years-old or more and were hospitalized in Wuhan Huoshenshan Hospital from February 4 to March 4, 2020 were reviewed. All patients had confirmed COVID-19 and the final date of follow-up was April 4, 2020., Results: There were 163 cases of mild disease (69.66%), 39 cases of severe disease (16.67%) and 32 cases of critical disease (13.68%). Twenty-nine patients died within 1 mo (12.40%), all of whom had critical disease. Surviving patients and deceased patients had no significant differences in age or chronic diseases. Overall, the most common symptoms were fever (65.4%), dry cough (57.3%), fatigue (47.4%) and shortness of breath (41%). The deceased patients had higher levels of multiple disease markers (C-reactive protein, D-dimer, lactate dehydrogenase, alanine amino transferase, aspartate aminotransferase, creatinine kinase and creatinine kinase-MB) and higher incidences of lymphocytopenia and hypoproteinemia., Conclusion: This single-center study of elderly patients from Wuhan, China who were hospitalized with COVID-19 indicated that age and chronic diseases were not associated with mortality. Hypertension, diabetes and cardiovascular disease were the most common comorbidities and the most common symptoms were fever, dry cough, fatigue and shortness of breath. Lymphocytopenia, increased levels of D-dimer and other markers indicative of damage to the heart, kidneys or liver were associated with an increased risk of death., Competing Interests: Conflict-of-interest statement: The authors have declared that no competing interest exists., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Activating transcription factor 2 (ATF2) is a tumor driver gene implicated in several human malignancies. This study aimed to determine the roles of ATF2 and its related molecules in the tumorigenesis of hepatocellular carcinoma (HCC). According to the Pan-cancer bioinformatics system, ATF2 is highly expressed in HCC. An increase in the expression of ATF2 was identified in clinically collected tumor tissues and procured HCC cells. The silencing of ATF2 reduced the viability, colony formation, invasion, and death resistance of HepG2 and SNU-398 cells in vitro. ATF2 promoted the transcription of Wolf-Hirschhorn syndrome candidate 1 (WHSC1) by binding to its promoter. WHSC1 further increased the expression of DNA topoisomerase II alpha (TOP2A) in HCC by inducing the dimethylation of histone H3 lysine 36 (H3K36me2) in the TOP2A promoter region. TOP2A activated the oncogenic PI3K/AKT signaling pathway. Further overexpression of WHSC1 activated the TOP2A/PI3K/AKT axis and restored the malignant behaviors of HCC cells suppressed by ATF2 silencing in vitro. In summary, this study demonstrated that, depending on WHSC1, ATF2 can activate the TOP2A/PI3K/AKT signaling cascade to promote the tumorigenesis of HCC. ATF2, WHSC1, and TOP2A may serve as potential targets in managing HCC., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Seven undescribed steroidal alkaloids, including two jervine-type steroidal alkaloids, fritiunibras A-B (1-2), and five cevanine-type steroidal alkaloid glycosides, fritiunibras C-G (3-7), along with six known cevanine-type steroidal alkaloids and their glycosides (8-13) were isolated from the bulbs of Fritillaria unibracteata Hsiao et K. C. Hsia. Their structures were determined by interpretation of comprehensive spectroscopic and single-crystal X-ray diffraction analysis. The absolute configurations of sugar moieties were determined by HPLC analysis and compared with standards after hydrolysis and derivatization. Furthermore, their inhibitory effects on NO production and cytotoxic activities were evaluated., (Copyright © 2022. Published by Elsevier Inc.)

A half-conjugate polydentate Salamo-Salen hybrid ligand, H 5 L , containing two unique N 2 O 2 pockets was first designed so that these metal ions in the complexes appear in different coordination modes. Two heterohexanuclear 3d-s double-helical cluster complexes, [Zn 4 Ca 2 L 2 (μ 1 -OAc) 2 (EtOH) 2 ]·2EtOH ( 1 ; EtOH = ethanol) and [Zn 4 Sr 2 L 2 (μ 2 -OAc) 2 (MeOH) 2 ]·2CH 2 Cl 2 ( 2 ; MeOH = methanol), are reported that are formed through the reaction of H 5 L with zinc(II) and calcium(II) acetate or strontium(II) acetate, respectively. IR spectral analysis of the two complexes showed the existence of monodentate- and bidentate-coordinated acetate ions. The fluorescence properties of the ligand and its two heterohexanuclear complexes were explored in MeOH and water solutions, separately. In addition, theoretical calculations (density functional theory, interaction region indicator, and bond order) were performed to further understand the formation of a single-molecular double helix and the electron distribution characteristics of the two complexes.

A novel bifunctional-group multi-purpose dye probe p-TNS has been designed and synthesized. The probe p-TNS has unique excited-state intramolecular proton transfer (ESIPT) and resonance-assisted hydrogen bonding (RAHB) coupled system, was confirmed to detect cyanide and hydrazine by blocking the ESIPT effect. Cyanide can change the fluorescence of the solution from bright green to orange-red (116 nm Stokes shift), while hydrazine causes the bright green fluorescence to be quenched. The recognition mechanism of the probe p-TNS to CN - and N 2 H 4 was proposed reasonably through spectral characterizations and theoretical calculations. Combined with theoretical calculations, it was speculated that the solvent dependence may be caused by the ICT effect in the molecule. The probe p-TNS could be prepared into test strips for the detection of cyanide and hydrazine. In addition, the probe molecule can also be used to detect trace amounts of cyanide in agricultural products, and respond to gaseous hydrazine by direct contact, indicating that the probe p-TNS has good practical application prospects. Therefore, this molecular framework provides a new way of thinking about detecting multiple target substances., 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 © 2021 Elsevier B.V. All rights reserved.)

Background: To date, no treatment has proven to be absolutely effective for coronavirus disease 2019 (COVID-19) patients, and further research is necessary. As a traditional antiviral drug, arbidol was widely used in Wuhan at the beginning of the COVID-19 epidemic and is of increasing interest for treating COVID-19 based on in vitro data suggesting activity against severe acute respiratory syndrome (SARS). Although arbidol has been widely used in China to treat COVID-19 patients, clinical trials to date have not clearly substantiated this approach., Aim: To evaluate the efficacy of arbidol for COVID-19., Methods: A retrospective study was conducted on 132 moderate and severe COVID-19 patients admitted to Jinyintan Hospital and Huoshenshan Hospital (officially designated for COVID-19 treatment) from February to March 2020 in Wuhan, China. This study mainly evaluated the efficacy of arbidol in patients with COVID-19 in the early stage of the SARS coronavirus 2 epidemic. Arbidol was administered at a dose of 200 mg, three times a day, with a 10-d course to adults not receiving any other drugs. Due to the shortage of beds at the time, not every patient could be admitted immediately. We looked for the early stages of the sudden outbreak, places of limited medical resources, limited ward beds, and delayed admission; thus, some patients naturally fit into the control group who did not receive any antiviral drugs. Out of the 132 patients, 72 received arbidol treatment, and 60 did not. We compared the disease course of the two groups and explored the predictors of extended disease duration., Results: Seventy-two patients commenced arbidol, and 60 patients did not receive arbidol treatment. The disease duration in the former group was shorter (23.42 ± 6.92 vs 29.60 ± 6.49, P < 0.001). Multivariate regression analysis showed that the risk of a prolonged course of disease increased by 7.158 times in the non-arbidol treatment group. Ferritin > 483.0 ng/mL and lactate dehydrogenase (LDH) > 237.5 U/L were found to be independent risk factors for protracted cases, with the risk of an extended disease duration increasing to 2.852 times and 5.946 times, respectively., Conclusion: The duration course of moderate and severe COVID-19 patients is reduced by 6.183 d when arbidol is administered. Ferritin > 486.5 ng/mL and LDH > 239.5 U/L are independent risk factors for delayed recovery from COVID-19. Early oral administration of arbidol 200 mg t.i.d. with a 10-d course of treatment may be an effective management strategy in COVID-19 patients, particularly those with increased serum ferritin or elevated LDH., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Anorexia nervosa (AN) is characterized by a strong fear of weight gain and body image disorders and is classified as a mental illness that can cause direct damage to one's mental health and body. Many individuals with AN tend to commit suicide. Additionally, the disease can lead to chronic undernutrition and low body weight, adversely affecting each body system, exacerbating systemic medical complications, especially acute life-threatening complications. Therefore, AN has the highest mortality and disability rates among all mental diseases. There is a basic clinical need to identify and address the acute and critical complications of this disease as soon as possible. However, the current literature has a poor description of the acute and critical complications of AN and lacks a systematic review. We report a case of a patient with AN and severe hypokalemia, significant Q-T interval prolongation, stomach dilation, and intestinal obstruction who recovered after conservative treatment. The defecation method we used, to our knowledge, has not been previously reported in the literature. We also briefly review the various acute and life-threatening complications of AN., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Sensitization to allergen has long been known to be relate to childhood allergic diseases. Polysensitised children have more severe atopic diseases, whereas allergic rhinitis or asthma children with cosensitized to food and inhalant allergens were under-researched., Objective: To realize the association between sensitization to food allergens and pediatric allergic rhinitis and asthma in Taiwan., Methods: We included 138 participants with sensitized to allergen as assessed by serum-specific IgE. 87 of 138 participants had allergic rhinitis and 51 participants had asthma. All participants underwent a physical examination and measurement of serum total and specific IgE values. Besides, nasal peak expiratory flow rate (nPEFR) that was performed by the participants with allergic rhinitis and were requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQ). Lung function test and asthma control test (ACT)/child asthma control test (C-ACT) were performed by the participants with asthma., Results: 39 of 87 allergic rhinitis participants with sensitized to food and inhalant allergens (AR food group), 48 of 87 allergic rhinitis participants with sensitized to inhalant allergen alone (AR inhalant group). The AR food group had significantly lower nPEFR values and higher total IgE values (p < 0.05) compared with the AR inhalant group. The AR food group had higher PRQLQ scores than the AR inhalant group. 24 of 51 asthma participants with sensitized to food and inhalant allergens (Asthma food group), 27 of 51 asthma participants with sensitized to inhalant allergen alone (Asthma inhalant group). The Asthma food group had significantly higher total IgE values (p < 0.05) compared with the Asthma inhalant group. The Asthma food group had lower lung function test values and asthma control test (ACT) scores than the other group., Conclusions: Children with cosensitized to food and inhalant allergens have more severe clinical symptoms and abnormal laboratory findings. Sensitization to food allergen was more related to pediatric allergic rhinitis than asthma. We may need larger, longer and extended studies to confirm these findings., (Copyright © 2019. Published by Elsevier B.V.)

Background: Novel coronavirus (COVID-19) is highly infectious and requires early detection, isolation, and treatment. We tried to find some useful information by analyzing the covid-19 screening data, so as to provide help for clinical practice., Method: We collected nucleic acid and hematology data from 2510 patients for COVID-19 infection for retrospective analysis., Result: COVID-19 and influenza A and B infection rates were 1.3%, 3%, and 3%, respectively. COVID-19 nucleic acid was detected in stool but not in tear samples from 8 positive patients. Among the 32 patients with COVID-19, 15 (47%) and 16 (50%) patients showed decreased lymphocyte count and lymphocyte ratio, 21(66%) and 24(75%) patients showed decreased eosinophil count and eosinophil ratio, and 18 (56%) patients showed increased C-reactive protein. Ten hematological indicators significantly differed in the blood of patients with COVID-19 and those with influenza A and B (P < 0.05). Eighteen hematological indicators significantly differed between patients with COVID-19 and negative patients (P < 0.05)., Conclusion: The positive rate of influenza A and B infection was higher than that of COVID-19. When pharyngeal swab collection may cause infection, fecal samples can be examined. Evaluation of pharyngeal swab and fecal samples can improve the positive rate of nucleic acid detection. The COVID-19 can cause some hematological indices changes., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Surgical site infection (SSI) after colorectal surgery (CRS) remains a significant problem for its negative clinical outcomes. However, it is poorly understood in China. This study aims to investigate the incidence, risk factors and microbiology of SSI after CRS., Methods: A nationwide prospective multicenter design was applied. Patients in 19 Chinese hospitals from 2015 to 2018 were prospectively monitored for SSI after CRS. Demographic data, hospital characteristics, and potential perioperative risk factors were collected and analyzed, using univariate and multivariate logistic regression models., Results: Among 3,663 study participants, 134(3.66%) episodes of SSI were identified. The incidence rate of SSI decreased from 5.9 infections per 100 procedures in 2015 to 3.1 infections per 100 procedures in 2018 (incidence rate ratio, 0.52; 95% CI, 0.28-0.94). The SSI rates were 1.88, 4.15, 6.27 and 11.58 per 100 operations for the National Nosocomial Infections Surveillance system (NNIS) risk index categories of 0, 1, and 2 or 3, respectively. Escherichia coli (54/134, 40.3%) and Klebsiella pneumoniae (10/134, 7.5%) were the most frequently isolated microorganisms. A high prevalence of antibiotic resistance were observed in our study, with rates of extended spectrum beta-lactamase-producing or carbapenem-resistant Escherichia coli and Klebsiella pneumonia of 50.0%(27/54) and 30.0%(3/10) respectively. Preoperative hospital stay ≥ 48h (OR=2.28, 95% CI: 1.03-5.02, P=0.042) and contaminated or dirty wound (OR=3.38, 95% CI: 1.88-6.06, P=4.50×10 -5 ) were significantly associated with increasing risk of SSI after CRS., Conclusion: A statistically significant but modest decrease in the incidence rate of CRS SSI over the 4-year study period was observed in this study. Noticeably, the relatively high rates of multidrug-resistant pathogens causing SSI after CRS should be alert, while more studies with large population are needed due to the small number of isolates identified in our survey., (Copyright © 2020. Published by Elsevier Ltd.)

Biological modifications of the silk fibroin (silk) material have broad applications in textiles, biomedical materials and other industrial materials. It is economical to incorporate nanoparticles to the biosynthesis of silk fibroin by adding them to silkworm larval diets. This strategy may result in the rapid stable production of modified silk. Glucose-coated silver nanoparticles (AgNPs) were used to improve the AgNPs' biocompatibility, and the AgNPs were efficiently incorporated into silk by feeding. Larvae fed with AgNPs produced silk with significantly improved antibacterial properties and altered silk secondary structures. Both positive and negative effects on the growth and synthesis of silk proteins were observed after different AgNPs doses. Larvae feeding with low concentration of 0.02% and medium 0.20% AgNPs have greater transfer efficiencies of AgNPs to silk compared with feeding high concentration of 2.00% AgNPs. In addition, the elongation and tensile strength of the produced silk fibers were also significantly increased, with greater mammalian cell compatibility. The appropriate AgNPs concentration in the diet of silkworms can promote the synthesis of silk proteins, enhance their mechanical properties, improve their antibacterial property and inhibit the presence of Gram-negative bacteria.

Background: To explore the efficacy of postoperative antifungal treatment for preventing the recurrence of pulmonary cryptococcosis (PC) and occurrence of cryptococcal meningitis (CM), a retrospective study was conducted in 112 hospitalized PC patients with or without antifungal treatment following surgery., Methods: The treatment failure rate, PC recurrence rate, and CM incidence were compared. Additionally, the effectiveness of postoperative antifungal therapy was assessed by gathering and analyzing the published literature., Results: The failure rate ( P =  .054) and recurrence rate ( P =  .178) were similar in the 2 groups, but the incidence of CM was lower in the group that received postoperative antifungal treatment ( P =  .039)., Conclusions: This study did not show any difference in the PC recurrence rate or failure rate in the different treatment duration groups. Thus, a shorter antifungal treatment course of 2 months may be an optional treatment. In addition, upon review of the literature, no case of CM occurrence was reported among the 169 cases given postoperative antifungal treatment., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background and Objectives: Effective management of immunosuppressants is extemely important to improve prognosis of heart transplant recipients. We aim to investigate the effects of cytochrome P450 (CYP) 3A5 (rs776746) single nucleotide polymorphisms (SNPs) on serum tacrolimus concentrations/doses (C/Ds, ng/mL per mg/kg) and long-term prognosis in Chinese heart transplant recipients., Methods: We detected the CYP3A5 SNPs of 203 consecutive Chinese heart transplant recipients between August 2005 and July 2012, and 55 of them who received tacrolimus-based immunosuppressive therapy were enrolled in this study. The tacrolimus C/Ds at 1, 3, 6, 12, 24 and 36 months after transplantation were routinely calculated. X-ray-guided endomyocardial biopsies (EMBs) were performed at 1, 3 and 6 months after heart transplantion to evaluate acute rejection degrees. All participants were then followed up annually until May 2018. The designed primary endpoint was all-cause mortality., Results: In 55 heart transplant recipients (43 males and 12 females), CYP3A5 non-expressors (CYP3A5*3/*3, n = 40) had significantly higher tacrolimus C/Ds than expressors (CYP3A5*1/*3, n = 15) at all time points (P < 0.001). Chi-squared test showed no significant differences in EMB-proven acute rejections between the two groups within 6 months after heart transplantion. The median follow-up period was 94.7 months, and eight patients died. Kaplan-Meier analysis showed CYP3A5 expressors tend to have higher mortality than non-expressors (20% vs 12.5%, log-rank: P = 0.314)., Conclusions: CYP3A5 SNPs affect tacrolimus pharmacokinetics in Chinese heart transplant recipients, and non-expressors have higher tacrolimus C/Ds. In addition, expressors tend to have a worse long-term prognosis than non-expressors.

Objectives: The aim of the study is to identify ceftriaxone resistance-related genes in Neisseria gonorrhoeae., Methods: Differences in gene expression were compared between ceftriaxone-susceptible N. gonorrhoeae isolates [minimum inhibitory concentration (MIC)=0.002-0.004mg/L] and isolates with decreased ceftriaxone susceptibility (MIC=0.125-0.5mg/L) using RNA-Seq (RNA sequencing)., Results: Total RNA of 10 clinical isolates was used to make libraries and generated an average of 24.07Mb reads per sample; these were assembled into 1871 mRNA genes. Moreover, 21 differentially expressed genes (DEGs) were found between the N. gonorrhoeae isolates with susceptibility and decreased susceptibility to ceftriaxone with a fold change of ≥2 (P<0.05), among which 11 were upregulated and 10 were downregulated. Furthermore, all DEGs were verified by quantitative reverse transcription PCR (qRT-PCR), which detected 25 clinical isolates with decreased ceftriaxone susceptibility and 21 ceftriaxone-susceptible isolates. In addition, seven DEGs revealed relative expression levels by 2 -ΔΔ Ct and showed a statistical significance (P≤0.05). Analysis of Gene Ontology (GO) terms and KEGG pathway for functional enrichment showed that six DEGs were related to the cellular component and one DEG was related to the biosynthesis of antibiotics, and these results might be related to ceftriaxone resistance., Conclusions: Examining ceftriaxone resistance-related genes in N. gonorrhoeae is necessary owing to the high morbidity and antimicrobial resistance of N. gonorrhoeae, especially its eventual resistance to third-generation extended-spectrum cephalosporins (cefixime and ceftriaxone). Moreover, this report provides a new direction for the study and control of ceftriaxone-resistant N. gonorrhoeae., (Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Background: Cervical pedicle screw fixation through posterior approach has shown greater cervical stability advantage. The cervical pedicle screw fixation technique through posterior approach is demanding. The key to the technique is the choice of point and angle of screw entrance. The angle of screw placement is variable. Morphometric measurements of the cervical pedicle are a prerequisite for individualized screw. CT imaging has become the most reliable and important means to obtain cervical pedicle's measurement data and morphology in vivo . This study explores the feasibility and application of precise in vivo measurements by multi-slice computed tomography (MSCT) for individualized cervical transpedicular screw placement at C3-C7 in Chinese healthy population., Materials and Methods: 80 adults who underwent cervical examination by enhanced and nonenhanced computed tomography angiography, respectively, were selected and submitted to bone algorithm reconstruction for slice thickness and interval of 0.75 mm to acquire clear images and detailed bone structures. Simulation of individualized screw placement was performed with a 4.0 mm diameter screw with the help of postprocessing workstation. Pedicle transverse angle (PTA) and sagittal angle (PSA) were measured using the single- and double-line methods (analog nailing, 4.0 mm in diameter) in 160 pairs of C3-C7 pedicles, setting positive and negative values for cranial direction and foot side PSAs, respectively. Comparison of the measured change scope in PTA and PSA between the two methods was carried out; the range was defined as the error range., Results: Significantly, different results ( P < 0.05) were obtained between the single- and double-line methods in the error ranges of PTA and PSA in C3-C7 pedicles. Interestingly, the double-line method was better in simulating the actual needs of individualized nailing. The mean values of PTA and PSA were 42.9°, 45.5°, 42.4°, 37.1°, 29.0° and 8.4°, 5.0°, -4.0°, and -7.8°, -8.1°, respectively, with the double-line method., Conclusion: MSCT reconstruction techniques can determine the direction and required parameters for individualized screw placement. In addition, accurate in vivo measurements of PTA and PSA, particularly PSA, provide the orthopedic surgeon with theoretical guidance and reliable basis in screw placement., Competing Interests: There are no conflicts of interest.

Studies have shown that oleuropein has antifungal, anti‑inflammatory, antiviral, antioxidant, anticancer and hypoglycemic functions. TTC solution staining was used to measure myocardial infarction size. A commercial kit was used to measure lactate dehydrogenase (LDH), creatinine kinase‑MB (CK‑MB), tumor necrosis factor‑α (TNF‑α), interleukin‑1β (IL‑1β), IL 6, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and catalase levels. Western blot analysis was used to measure p53, p-MEK p-ERK and p‑IκBα protein expression. The present study reports that the protective effect of oleuropein also prevents against myocardial ischemia/reperfusion (myocardial I/R). The aim of this retrospective study was to evaluate this protective effect of oleuropein and the mechanisms by which myocardial I/R is prevented. Oleuropein inhibited myocardial infarction size, CK‑MB and LDH serum levels in a myocardial I/R rat model. Moreover, oleuropein also attenuated caspase‑3 activity, and p53, phosphorylated (p)‑mitogen‑activated protein kinase kinase (MEK), p‑extracellular signal‑regulated protein kinase (ERK) and p‑IκBα protein expression. TNF‑α, IL‑1β, IL‑6 and MDA were decreased; SOD, GSH and catalase levels inhibited TNF‑α, IL‑1β, IL-6 and MDA levels, and increased SOD, GSH and catalase levels in myocardial I/R rats treated with oleuropein. Rats orally administered the MEK inhibitor PD0325901, in addition to oleuropein, exhibited inhibited myocardial infarction size, CK‑MB and LDH serum levels compared with rats treated with oleuropein only. Rats treated with MEK inhibitor also exhibited suppressed caspase‑3 activity, p53, p‑MEK p‑ERK and p‑IκBα protein expression, TNF‑α, IL‑1β, IL‑6, SOD, GSH, MDA and catalase levels, and induced p‑signal transducer and activator of transcription 3 (STAT3) protein expression compared with rats treated with oleuropein only. Taken together, these results suggest that MEK/ERK/STAT3 signaling regulates the inhibition of myocardial I/R in rats treated with oleuropein.

Pain, especially chronic pain, has always been a heated point in both basic and clinical researches since it puts heavy burdens on both individuals and the whole society. A better understanding of the role of biological molecules and various ionic channels involved in pain can shed light on the mechanism under pain and advocate the development of pain management. Using viral vectors to transfer specific genes at targeted sites is a promising method for both research and clinical applications. Lentiviral vectors and adeno-associated virus (AAV) vectors which allow stable and long-term expression of transgene in non-dividing cells are widely applied in pain research. In this review, we thoroughly outline the structure, category, advantages and disadvantages and the delivery methods of lentiviral and AAV vectors. The methods through which lentiviral and AAV vectors are delivered to targeted sites are closely related with the sites, level and period of transgene expression. Focus is placed on the various delivery methods applied to deliver vectors to spinal cord and dorsal root ganglion both of which play important roles in primary nociception. Our goal is to provide insight into the features of these two viral vectors and which administration approach can be chosen for different pain researches. Anat Rec, 301:825-836, 2018. © 2017 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists., (© 2017 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.)

Objective: To understand the characteristics of imported malaria cases in Qingcheng District, Qingyuan City and explore the strategies and priorities in prevention and control, so as to provide the evidence for improving the diagnosis, treatment and management of imported malaria., Methods: The data of imported malaria as well as the case epidemiological investigations were collected and retrospectively analyzed for the species composition, original countries, population distribution, regional distribution, onset situation, diagnosis, treatment, etc. in Qingcheng District from 2011 to 2016., Results: The number of imported malaria cases was 13 from 2011 to 2016. All the patients were confirmed by laboratory, and of which, 9 patients infected with Plasmodium falciparum , 1 with P. vivax , 1 with P. ovale and 2 with mixed infections ( P. vivax and P. falciparum ). The yearly incidence of imported malaria presented an uptrend. The infection sources of all the patients were from African countries, and the exported labor workers and travelers for business from malaria endemic areas were the high risk population. The reported time was mainly January, February, November and December (11/13, 84.62%). All the patients were male, and the majority of them (12/13, 2.31%) were 21-60 years old. The median time from onset to seeing a doctor was 2.5 days and the median time from seeing a doctor to being diagnosed was 1.9 day. Six patients (46.15%) were diagnosed as other diseases at the first visit to a doctor, and one patient died of falciparum malaria because of delayed diagnosis., Conclusions: The incidence of overseas imported malaria presents an uptrend in Qingcheng District. It is necessary to further strengthen the professional training in medical staff to improve the diagnosis and treatment of malaria cases. It is also necessary to strengthen the multisectoral cooperation, establish the surveillance in the high risk population, etc.

Cavernous sinus thrombosis (CST) is a severe disease which can result from infection of any of the tissues drained by the cavernous sinus. We here review eight cases, including a 12-year-old girl, all secondary to sphenoid sinusitis. The clinical manifestations, laboratory data, imaging findings, pathogens, medications, surgical treatment and clinical outcomes were analyzed. All eight patients had headache and five of them fever. All cases were associated with one or more ophthalmic symptoms. In four cases, computed tomography/magnetic resonance imaging showed isolated sphenoid sinusitis. In three cases, streptococci were isolated from blood culture and two cases showed Staphylococcus aureus in blood and sinus cultures. In seven cases, surgery was undertaken. All eight subjects received antibiotics, and 5 were administered intravenous ceftriaxone and metronidazole. Six subjects received anticoagulation therapy and one received corticosteroids. No mortality was recorded. Three cases showed sequelae, including Lemierre syndrome, ophthalmic complaints, and cranial nerve paralysis. In conclusion, the management of CST should include intravenous antibiotic therapy, combined with endonasal sinus surgery.

Dural defects are a common problem, and inadequate dural closure can lead to complications. Several types of dural substitute materials have recently been discarded or modified owing to poor biocompatibility or mechanical properties and adverse reactions. The small intestinal submucosa (SIS) is a promising material used in a variety of applications. Based on the limitations of previous studies, we conducted an animal study to evaluate the efficacy and safety of the SIS in preclinical trials. Twenty-four male beagle dogs were subjected to surgical resection to produce dural defects. SIS or autologous dural mater was patched on the dural defect. Gross and histological evaluations were carried out to evaluate the efficacy and safety of the therapy. Our findings demonstrated that the SIS, which stimulated connective and epithelial tissue responses for dural regeneration and functional recovery without immunological rejection, could provide prolonged defect repair and prevent complications. The mechanical properties of the SIS could be adjusted by application of multiple layers, and the biocompatibility of the material was appropriate. Thus, our data suggested that this material may represent an alternative option for clinical treatment of dural defects., (Copyright © 2016 Elsevier B.V. All rights reserved.)

An anionic Co II -MOF, (Me 2 NH 2 )[Co 3 (Me 2 NH) 3 (OH)(SDBA) 3 ] (1) (H 2 SDBA=4,4'-sulfonyldibenzoic acid) consisting of highly symmetric Co II 3 (μ 3 -OH) triangles exhibits spin-canting, spin-flop, and easy-plane magnetic anisotropy. Measurement on a single crystal shows that the ab plane of 1 is the easy magnetization plane. After structural modification through simultaneous removal of the coordinated dimethylamine (DMA) molecule at the Co center and the ionic groups DMA + and OH - , the resulting neutral amorphous framework 2 displays an enhanced spin frustration effect. The deionization of 1 does not result in the collapse of the framework, showing the high stability of the backbone structure., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: Investigate the effectiveness of alcohol septal ablation (ASA) and transaortic extended myectomy (TEM) in hypertrophic cardiomyopathy (HCM) with midventricular obstruction (MVO)., Background: MVO is less common than subaortic obstruction. Data on the effectiveness of ASA and TEM in MVO are lacking., Methods: The clinical profiles of 22 patients undergoing ASA and 37 patients undergoing TEM were compared. No patient had apical aneurysm, abnormal chordae, mitral valve replacement or repair., Results: Baseline midventricular pressure gradient and symptoms were comparable between the ASA and TEM groups. During follow-up, both groups demonstrated substantial reduction in pressure gradient (the ASA group: 79.7 ± 21.2 mm Hg to 43.7 ± 28.9 mm Hg, P < 0.001; the TEM group: 69.0 ± 23.9 mm Hg to 15.0 ± 16.9 mm Hg, P < 0.001). The reduction in pressure gradient was greater (78.9 ± 18.6% vs. 46.4 ± 33.4%, P < 0.001) and the residual pressure gradient was lower after TEM versus ASA (P < 0.001). Patients with New York Heart Association class III/IV dyspnea decreased from 59.1 to 18.2% (P = 0.022) in the ASA group and from 56.8 to 5.6% (P < 0.001) in the TEM group. Patients with Canadian Cardiovascular Society class III/IV angina decreased from 40.9 to 9.1% (P = 0.016) in the ASA group and from 32.4 to 0% (P < 0.001) in the TEM group., Conclusions: While ASA and TEM both improve gradients and symptoms, TEM may provide a more reliable reduction in gradients compared to ASA., (© 2016, Wiley Periodicals, Inc.)

Sexual glands are key sites affected by nanotoxicity, but there is no sensitive assay for measuring reproductive toxicity in animals. The aim of this study was to investigate the toxic effects of cadmium telluride quantum dots (CdTe-QDs) on gonads in a model organism, Bombyx mori. After dorsal vein injection of 0.32 nmol of CdTe-QDs per individual, the QDs passed through the outer membranes of gonads via the generation of ROS in the membranes of spermatocysts and ovarioles, as well as internal germ cells, thereby inducing early germ cell death or malformations via complex mechanisms related to apoptosis and autophagy through mitochondrial and lysosomal pathways. Histological observations of the gonads and quantitative analyses of germ cell development showed that the reproductive toxicity was characterized by obvious male sensitivity. Exposure to QDs in the early stage of males had severe adverse effects on the quantity and quality of sperm, which was the main reason for the occurrence of unfertilized eggs. Ala- or Gly-conjugated QDs could reduce the nanotoxicity of CdTe-QDs during germ cell development and fertilization of their offspring. The results demonstrate that males are preferable models for evaluating the reproductive toxicity of QDs in combined in vivo/in vitro investigations.

Mitochondria are organelles responsible for vital cell functions. p53 is a transcription factor that regulates the DNA stability and cell growth normality. Recent studies revealed that p53 can influence mitochondrial function changing from normal condition to abnormal condition under different stress levels. In normal state, p53 can maintain mitochondrial respiration through transactivation of SCO2. When stress stimuli presents, SCO2 overexpresses and leads to ROS generation. ROS promotes p53 inducing MALM (Mieap-induced accumulation of lysosome-like organelles within mitochondria) to repair dysfunctional mitochondria and MIV (Mieap-induced vacuole) to accomplish damaged mitochondria degradation. If stress or damage is irreversible, p53 will translocate to mitochondria, leading into apoptosis or necrosis. Neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease are still lack of clear explanations of mechanisms, but more studies have revealed the functional relationship between mitochondria and p53 towards the pathological development of these diseases. In this review, we discuss that p53 plays the vital role in the function of mitochondria in the aspect of pathological change metabolism. We also analyze these diseases with novel targeted treating molecules which are related to p53 and mitochondria, hoping to present novel therapies in future clinic., Competing Interests: The authors have no conflict of interest.

A new series of isostructural lanthanide-based metal-organic frameworks, [H 3 O][HN(CH 3 ) 3 ] 2 [Ln 3 L 6 ] (Ln=Gd (1), Eu (2), and Tb (3); H 2 L=1,3-benzenedicarboxylic acid), was prepared under solvothermal conditions. Single-crystal XRD studies reveal that these compounds are 3D microporous frameworks with 1D channels distributed in four different directions. The 1D channels contain protonated water molecules and trimethylammonium cations, which can be partially exchanged with different metal ions. Notably, these compounds do not contain any coordinated solvent molecules because the coordination sphere of the Ln 3+ ion is fully occupied by chelating and bridging carboxylate oxygen atoms. Tunable colors and white-light emission can be achieved by encapsulating different molar ratios of Eu 3+ and Tb 3+ ions in the Gd framework through cation exchange. In addition, the Eu framework can act as a sensitive and selective luminescence sensor for both Fe 2+ and Fe 3+ ., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A pair of chiral template induced anionic homochiral frameworks constructed from achiral components has been synthesized. Ion-exchange of counter cations with polar or chiral organic cations enhances the SHG efficiency of the frameworks. The enantioselective sensing of chiral alkamines can be achieved by the SHG response.

The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 siRNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.

Previous research has shown that gold nanoparticles can increase the effectiveness of radiation on cancer cells. Improved radiation effectiveness would allow lower radiation doses given to patients, reducing adverse effects; alternatively, it would provide more cancer killing at current radiation doses. Damage from radiation and gold nanoparticles depends in part on the Auger effect, which is very localized; thus, it is important to place the gold nanoparticles on or in the cancer cells. In this work, we use the pH-sensitive, tumor-targeting agent, pH Low-Insertion Peptide (pHLIP), to tether 1.4-nm gold nanoparticles to cancer cells. We find that the conjugation of pHLIP to gold nanoparticles increases gold uptake in cells compared with gold nanoparticles without pHLIP, with the nanoparticles distributed mostly on the cellular membranes. We further find that gold nanoparticles conjugated to pHLIP produce a statistically significant decrease in cell survival with radiation compared with cells without gold nanoparticles and cells with gold alone. In the context of our previous findings demonstrating efficient pHLIP-mediated delivery of gold nanoparticles to tumors, the obtained results serve as a foundation for further preclinical evaluation of dose enhancement.

Splenomegaly and pancytopenia are common in Wilson's disease (WD) and splenectomy is one of the conventional treatments for splenomegaly and the associated pancytopenia. However, splenectomy remained controversial for hypersplenism in WD as it was reported that splenectomy leaded to serious emotional and neurological deterioration in WD patients with hypersplenism. In the current study, we present our experiences in 70 WD patients with hypersplenism who had undergone splenectomy, outlining the safety and efficacy of splenectomy in WD. The clinical database of 70 WD patients with hypersplenism who had undergone splenectomy in our hospital between 2009 and 2013 were reviewed and followed-up regularly. Before splenectomy, all the patients accepted a short period of anti-copper treatment with intravenous sodium 2, 3-dimercapto-1-propane sulfonate (DMPS). All the patients demonstrated a marked improvement in platelet and leucocyte counts after splenectomy. No severe postoperative complication was observed. In particular, none of the 37 patients with mixed neurologic and hepatic presentations experienced neurological deterioration after splenectomy, and none of the patients with only hepatic presentations newly developed neurological symptoms. During the one year follow-up period, no patient presented hepatic failure or hepatic encephalopathy, no hepatic patient newly developed neurological presentations, and only 3 patients with mixed neurologic and hepatic presentations suffered neurological deterioration and these 3 patients had poor compliance of anti-copper treatment. Quantative analysis of the neurological symptoms in the 37 patients using the Unified Wilson's Disease Rating Scale (UWDRS) showed that the neurological symptoms were not changed in a short-term of one week after splenectomy but significantly improved in a long-term of one year after splenectomy. Additionally, compared to that before splenectomy, the esophageal gastric varices in most patients significantly improved one year after splenectomy. Thus, we may conclude that splenectomy is a safe and effective therapeutic measure for hypersplenism in WD patients who had been preoperatively treated with DMPS for powerful anti-copper therapy.

Four new inorganic-organic hybrid manganese frameworks, formulated as [Mn(Am-Hip)2]·3H2O (1), [Mn2(ip)2(H2O)]·CH3OH (2), [Mn2(OH-ip)2(DMF)]·DMF (3), and (Me2NH2)[Mn4(sdba)4(Hsdba)(H2O)]·3H2O·2DMF (4) (Am-H2ip = 5-aminoisophthalic acid, H2ip = isophthalic acid, OH-H2ip = 5-hydroxyisophthalic acid, and H2sdba = 4,4'-sulfonyldibenzoic acid), have been prepared by solvothermal reactions of Mn(II) ions with different polycarboxylate acids in the presence of LiNO3 or NH4NO3. Single-crystal X-ray diffraction studies reveal that the frameworks of 1-4 contain diverse Mn(II)-oxygen inorganic magnetic chain's sequences, -J1J1J1J1- for 1, -J1J2J1J2- for 2, -J1J1J2J2- for 3, and -J1J2J3J3- for 4. The sequence in 4 has never been seen for the magnetic chain compounds and is a new type of magnetic alternating sequence. Magnetic investigations indicate that these compounds all show weak antiferromagnetic couplings between the adjacent Mn(II) ions. Magnetostructural analyses based on the data of 1-4 and other related Mn(II) chain compounds imply that the magnitude of the magnetic coupling has some relationship with the Mn-O-Mn angle of the μ2-O bridge and the average Mn-O-C-O torsion angle of the carboxylate bridges. Compounds 2 and 4 crystallize in chiral and acentric space groups, and they both exhibit powder second harmonic generation (SHG) efficiencies approximately 0.6 and 0.9 times, respectively, that of the standard potassium dihydrogen phosphate (KDP) powder. In addition, the dielectric properties of 2 and 4 were also investigated.

Objective: To observe the effect of acupuncture at the whole points of Hand Jueyin pericardium meridian on the amplitude of low frequency fluctuations (ALFF) of healthy people in resting state (R1) functional magnetic resonance imaging (fMRI)., Methods: Totally 16 healthy subjects received structure scan of T1 and T2. Then two fMRI scans were conducted for each participant. fMRI included the resting-state scan (R1; the scanning time was 8 min 6 s), the stimulating-acupoint scan (AP; the scanning time was 8 min 6 s). fMRI data acquisition from structure scanning and function scanning were processed with format conversion and statistical analysis., Results: Under R1 state, brain regions with activated ALFF signals included bilateral superior frontal gyrus, medial frontal gyrus, middle occipital gyrus, precuneus, superior temporal gyrus, and cingulate gyrus. Under the AP state, brain regions with activated ALFF signals were bilateral superior frontal gyrus, medial frontal gyrus, middle temporal gyrus, left fusiform gyrus, precuneus, posterior cingulate, and declivis. Compared with R1 state, obvious difference of ALFF signal areas of the brain caused by acupuncture at pericardium were: bilateral cuneus, precuneus, left posterior cingulate gyrus, right middle occipital gyrus, and right occipital lingual gyrus., Conclusion: Acupuncture at the whole points of Hand Jueyin pericardium meridian could significantly change inherent activity states of the cerebral cortex, especially in bilateral superior frontal gyrus, medial frontal gyrus, and precuneus.

A pair of enantiomorphic frameworks featuring rare chiral 3D inorganic connectivity and a {Pb18} wheel, has been obtained via spontaneous resolution. They exhibit rapid and highly selective and sensitive sensing of Co(2+) ions.

Background: Nasal irrigation has been used as adjunctive therapy for sinonasal disease but is under-researched in children. The study aim was to evaluate the effectiveness of nasal irrigation with normal saline in the management of acute sinusitis in atopic children., Methods: We enrolled 60 atopic children with acute sinusitis, of whom 29 received nasal irrigation with normal saline and 31 did not receive nasal irrigation. All participants underwent a nasal peak expiratory flow rate (nPEFR) test, a nasal smear examination, and radiography (Water's projection) and were requested to complete a Pediatric Rhinoconjunctivitis Quality-of-Life Questionnaire (PRQLQ) during the baseline visit. All participants were requested to record symptoms in a daily diary and were followed up at 1-week intervals. A physical examination, nasal smear, and nPEFR were performed at each visit, and all daily diaries were collected. At the final visit (after 3 weeks), the symptom diaries were reviewed and participants were requested to complete the PRQLQ again. nPEFR, radiography, and a nasal smear were also repeated., Results: There were significant improvements in mean PRQLQ and nPEFR values (p < 0.05) for the irrigation compared to the non-irrigation group. There was no significant difference in radiographic findings between the groups (p > 0.05). The irrigation group recorded significant improvements in eye congestion, rhinorrhea, nasal itching, sneezing, and cough symptoms compared with the non-irrigation group., Conclusion: Nasal irrigation is an effective adjunctive treatment for acute sinusitis in atopic children., (Copyright © 2012. Published by Elsevier B.V.)

Objective: To analyze the clinical features, precaution and management of complete heart block (CHB) after transaortic extended septal myectomy operation (extended Morrow procedure) in patients with hypertrophic obstructive cardiomyopathy (HOCM)., Methods: From October 1996 to December 2011, 10[6 men; mean age (45.4 ± 15.8) years, range 13-60 years] out of 160 consecutive HOCM patients underwent extended Morrow procedure developed CHB postoperatively. Their clinical data were retrospectively analyzed. Baseline transthoracic echocardiography showed that the left ventricular outflow tract (LVOT) gradients was from 68 to 149 (105.1 ± 25.9) mm Hg (1 mm Hg = 0.133 kPa), ECG showed right bundle branch block in 5 patients and atrial fibrillation, atrial premature beats or ST-T segment changes in other 5 patients. Besides extended Morrow procedure, concomitant surgical procedures included mitral valve replacement (MVR) in 2 (2/10) and MVR plus coronary artery bypass grafting in another 2 (2/10) patients. Follow-up data were obtained by subsequent clinic visits in outpatient department and telephone interviews., Results: The in-hospital mortality was 20% (these two patients died of low cardiac output syndrome and multiple organs failure). Four patients underwent MVR simultaneously survived the operation. Postoperative echocardiography demonstrated a reduced LVOT gradient[(13.6 ± 9.7) mm Hg, P < 0.001]. Permanent pacemakers were implanted in all 8 survived patients at 6 days to 7 months after operation. No other severe complications were observed. During follow-up [from 4 to 72 (19.4 ± 22.1) months], there was no death, 1 patient readmitted to our center at 71 months post operation to change the pacemaker because of low voltage of previously implanted pacemaker. Physical capacity and quality of life improved significantly post operation in these 8 patients. The NYHA functional class remained at I-II post operation and during follow up., Conclusions: CHB is a severe complication after extended Morrow procedure for patients with HOCM and timely permanent pacemaker implantation is mandatory for patients with post procedure CHB.

Objective: To access the prevalence and risk factors for hypertension after heart transplantation (HT), and the impact of post-transplant hypertension on medium-term survival among HT patients., Methods: Data from 265 consecutive patients underwent HT between June 2004 and May 2012 in Fuwai hospital and survived for at least 6 months were retrospectively analyzed. Hypertension was defined as systolic pressure ≥ 140 mm Hg (1 mm Hg = 0.133 kPa) and/or diastolic pressure ≥ 90 mm Hg or current treatment with antihypertensive drugs. Patients were divided into post-HT hypertension group and non-hypertension group. Logistic regression analysis was used to determine preoperative and postoperative risk factors for hypertension after HT. Kaplan-Meier method and log rank test were used for survival analysis., Results: Hypertension was present in 17.4% (46/265) patients before HT and in 57.4% (152/265) patients post HT. The median follow-up time was 37 months (20 - 57 months). Logistic regression analysis showed that male gender (OR: 2.27, 95%CI: 1.16 - 4.42, P < 0.05), history of pre-HT hypertension (OR: 2.22, 95%CI: 1.05 - 4.71, P < 0.05), and cyclosporine A based immunosuppressive therapy (OR: 2.54, 95%CI: 1.51 - 4.29, P < 0.01) were independent risk factors for the development of post-HT hypertension. At the end of 1, 3, 5 years, the survival rate of heart transplant patients by Kaplan-Meier method estimation were 100%, 97.2%, 86.7% in post-HT hypertension group; 98.1%, 93.8%, 93.8% in non-hypertension group. Log rank test displayed that there was no significant difference between the two survival curves (P > 0.05)., Conclusions: Hypertension is a frequent comorbidity after HT. Male gender, pre-HT hypertension together with cyclosporine A based immunosuppressive therapy are independent predictors for the development of post-HT hypertension. By adjusting the controllable risk factors and active control of blood pressure, the medium-term survival is similar between patients with or without postoperative hypertension in this cohort.

Objective: To assess the clinical outcomes of transaortic extended septal myectomy on early and midterm survival of patients with hypertrophic obstructive cardiomyopathy (HOCM)., Methods: From October 2009 to April 2012, 118 consecutive patients underwent extended Morrow's procedure for HOCM. There were 69 males and 49 females with an average age of (46 ± 13) years. Their clinical data were analyzed retrospectively. Preoperative transthoracic, intraoperative transoesophageal and postoperative transthoracic echocardiography was performed to assess septal thickness, left ventricular outflow tract (LVOT) gradient, mitral valve function and systolic anterior motion (SAM) of anterior mitral valve leaflet, etc. Concomitant surgical procedures were performed if other cardiac diseases required surgical interventions. Follow-up study was carried out during subsequent clinic visits at outpatient department and through telephone interviews with patients and their relatives., Results: The septal thickness was (25 ± 7) mm. SAM was detected in all. The in-hospital mortality was 0.8% (1/118) since one patient died of multiple organs failure one week later. Postoperative echocardiography demonstrated marked reduction in LVOT gradient (92 ± 22 vs 13 ± 10 mm Hg (1 mm Hg = 0.133 kPa), P = 0.000), New York Heart Association (NYHA) class (2.9 ± 0.6 vs 1.2 ± 0.4, P = 0.000) and significant improvement in mitral regurgitation. Concomitant surgical procedures were performed in 45 cases (38.1%, all for preexisting conditions). Complications included complete atrioventricular block (n = 3), first degree atrioventricular block (n = 6), complete left bundle branch block (n = 51), intraventricular conduction delay or left anterior division block (n = 26), transient renal dysfunction (n = 2) and intra-aortic-balloon-pumping (n = 2). No other severe complication was observed. During a follow-up period of 1 - 27 (7 ± 6) months, there was no readmission or death. All patients reported significant increase in physical ability and obvious decrease in limiting symptoms. At the latest follow-up, the NYHA functional class maintained grade I-II in all. And mitral regurgitation remained absent or mild., Conclusion: Surgical procedure for HOCM patients is both safe and efficacious. It provides an excellent relief of LVOT obstruction.

Background and Objective: Our study aimed to elucidate the potential clinical and molecular issues in recurrent atrial fibrillation (AF) following a radiofrequency modified maze procedure in patients with rheumatic valvular disease and persistent AF., Methods and Results: Eighty patients with rheumatic valvular disease and persistent AF (lasting more than 6 months) who had undergone a radiofrequency modified maze procedure and mitral valve replacement were enrolled into this single-center pilot study and were followed up for another 6 months. Their clinical characteristics were analyzed and the expression of matrix metalloproteinase (MMP)-2 including its specific inhibitor and collagen volume fraction (CVF) was also assessed. During the 6-month follow-up, 24 subjects had recurrent AF. Among them, the left atrial diameter was larger compared to that achieved in sinus rhythm (SR). The mRNA and protein expression of MMP-2 was significantly increased in recurrent AF patients, while its specific inhibitor did not show a significant difference (p > 0.05). The CVF of type I collagen increased significantly in the recurrent AF patients compared to SR patients (18.16 ± 3.22 vs. 11.66 ± 3.38, p < 0.001), whereas the CVF of type III collagen showed no significant difference (8.33 ± 3.44 vs. 9.55 ± 3.67, p > 0.05)., Conclusion: This study suggests that the overexpression of MMP-2 is associated with CVF-I in the left atrial appendage which potentially leads to the recurrence of AF following a radiofrequency modified maze procedure in patients with rheumatic valve disease., (Copyright © 2013 S. Karger AG, Basel.)

Unlabelled: OBJECITVE: To explore the block effect of brain-derived neurotrophic factor (BDNF) antibody on the mitogen extracellular kinase (MEK) expression in lung tissues of rats with brain ischemia., Methods: Adult SD rats were divided into sham group, brain ischemia lung injury (BILI) group, and BDNF antibody treated group. Lung tissues were harvested at 3 days after operation. The distribution of MEK in the lung tissue was studied by immunhistochemistry, and the optical density values of MEK immunostaining was used to compare the difference of each group (n=5). RT-PCR was used to determine the block effect of BDNF antibody on the level of MEK mRNA (n=8)., Results: Immunohistochemistry showed that MEK immunoreactive positive products were observed in endothelia cells of airway and blood vessels. The optical density value in rats with brain ischemia significantly increased, compared with sham one (P<0.05). Moreover, BDNF antibody block could reverse this increase of BDNF immunostaining intensity (P<0.05). RT-PCR showed that BDNF antibody block significantly decreased the expressional level of MEK mRNA in the lung tissues with brain ischemia (P<0.05)., Conclusion: BDNF antibody block leads to a significant reduction of MEK expression in endothelia cells of lung tissue in the rats with brain ischemia.