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[This corrects the article DOI: 10.1016/j.apsb.2023.01.022.].
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Tuberculosis (TB) is one of the deadly diseases caused by Mycobacterium tuberculosis (Mtb), which presents a significant public health challenge. Treatment of TB relies on the combination of several anti-TB drugs to create shorter and safer regimens. Therefore, new anti-TB agents working by different mechanisms are urgently needed. FtsZ, a tubulin-like protein with GTPase activity, forms a dynamic Z-ring in cell division. Most of FtsZ inhibitors are designed to inhibit GTPase activity. In Mtb, the function of Z-ring is modulated by SepF, a FtsZ binding protein. The FtsZ/SepF interaction is essential for FtsZ bundling and localization at the site of division. Here, we established a yeast two-hybrid based screening system to identify inhibitors of FtsZ/SepF interaction in M. tuberculosis. Using this system, we found compound T0349 showing strong anti-Mtb activity but with low toxicity to other bacteria strains and mice. Moreover, we have demonstrated that T0349 binds specifically to SepF to block FtsZ/SepF interaction by GST pull-down, fluorescence polarization (FP), surface plasmon resonance (SPR) and CRISPRi knockdown assays. Furthermore, T0349 can inhibit bacterial cell division by inducing filamentation and abnormal septum. Our data demonstrated that FtsZ/SepF interaction is a promising anti-TB drug target for identifying agents with novel mechanisms.
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Objective@#The method of compositional data analysis was used to explore the relationship between 24 hour movement behavior and obesity indicators, and to examine the difference of quantitative effect on obesity indicators when one behavior replaced another behavior, so as to provide specific movement behavior advice for weight control in children and adolescents.@*Methods@#In June 2021, 231 students from eight classes in a primary school and a middle school in Taiyuan City, Shanxi Province were voluntarily recruited by using random cluster sampling. ActiGraph GT3X+ accelerometer was used to measure 24 hour movement behavior and Inbody J20 body composition analyzer was used to measure body composition. The relationship between each component and obesity indicators was analyzed by compositional multivariate linear regression model. In addition, 30 minutes of one behavior was used to replace another behavior to predict the effect difference of the outcomes.@*Results@#After adjusting for covariates such as height, weight, age, and sex, compared with time spent in sedentary behavior(SB), sleep (SLP) and light physical activity (LPA), time spent on moderate to vigorous physical activity (MVPA) was positively correlated with fat free mass index (FFMI) ( β= 0.40, P ＜0.05), negatively correlated with waist circumference (WC) ( β=-2.50, P ＜0.05) and waist hip ratio (WHR) ( β= -0.04 , P ＜0.05). Compared with SB, SLP and MVPA, time spent on LPA was positively correlated with WHR ( β=0.06, P < 0.05 ). If MVPA of 30 min/d replaces SLP, SB, and LPA respectively, WC and WHR decrease 1.10,1.10,1.34 cm and 0.02, 0.02 ,0.02 respectively, and FFMI increases 0.19,0.19,0.15 kg/m 2 respectively.@*Conclusion@#In 24 h movement behavior, with consistent level of sedentary behavior, sleep or low intensity movement behavior, maintaining a high level of MVPA and replacing sedentary with active activities are crucial for optimal abdominal fat and fat free mass in children and adolescents.
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Objective@#To systematically review the associations of physical activity (PA), sedentary behavior (SB) and sleep with obesity, as well as isotemporal substitution effects among behaviors, determined with compositional data analysis methods, to provide a reference for obesity interventions among children and adolescents.@*Methods@#Studies in the CNKI, Wanfang, PubMed, SPORTDiscus, Web of Science and Medline databases were searched from January 1, 2014 to May 1, 2022. Two experienced reviewers independently completed document screening, data extraction and quality assessment.@*Results@#Sixteen articles were included, with a methodological quality score range of 7-12 points. Moderate to vigorous physical activity (MVPA), sleep and obesity were negatively correlated, and substituting other behaviors with MVPA decreased obesity risk. The substitution time ranged from 1.5 min/day to 60 min/day. Light physical activity(LPA) and SB were positively correlated with obesity.@*Conclusion@#MVPA is the primary focus of obesity interventions in children and adolescents, and extra 60 min of MVPA per week on the existing level of physical activity may be the minimum necessary to decrease the risk of obesity.
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Abstract@#As the compositional nature of "constant sum" of physical activity, sedentary behavior and sleep are widely recognized, the methodological and result limitations of previous studies that considered physical activity, sedentary behavior, or sleep as independent influences on physical fitness and health have been highlighted. At present,physical activity guidelines of various countries have shifted from local recommendations based on physical activity amount to global recommendations based on 24 h time frame. From the perspective of time use, the content of daily schedule of children and adolescents also has the attribute of "constant sum" of compositional data, and the reduction of students homework burden and extracurricular discipline training after "double reduction" inevitably means an increase in the time allocated to other activities. From the perspective of time use, the paper focuses on physical fitness and health promotion strategies in the context of "double reduction".
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Objective@#Physical literacy is the breakthrough point and fundamental goal to achieve the integration of sports and education, sports and public health and expand the function of physical education. Studying the children and adolescents physical literacy is a common responsibility for children and adolescents health, sports and health education workers. This article was based on the latest research evidence and expert opinions in China, aiming to develop the core items of physical literacy guidelines for Chinese children and adolescents.@*Methods@#This article systematically combed the dimensions and index system of children and adolescents physical literacy through systematic literature review. After five rounds of Delphi methods, the core items were extracted.@*Results@#The core items included four interrelated dimensions of body, emotion, behavior, and cognition, which were specifically composed of four components: physical ability, emotional experience, physical activity related behaviors, and knowledge understanding and application ability.@*Conclusion@#Children and adolescents are the key periods, sensitive periods, and window periods to cultivate physical literacy. The core items can provide framework recommendations for further refining guidelines. More empirical studies should be carried out in the future, in order to accumulate enough evidences and further to improve Physical Literacy guidelines, better to guide physical literacy promotion.
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Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain-Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.
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Adult , Animals , Humans , Infant, Newborn , Drug Repositioning , Microcephaly , Pharmaceutical Preparations , Zika Virus , Zika Virus Infection/prevention & controlABSTRACT
Purpose The operating skull base meningioma is difficult,and the blood vessel related complications are extremely dangerous.This paper aims to investigate the value of multi-phase CT angiography in preoperative evaluation of skull base meningioma,hoping to improve the operation safety.Materials and Methods The data of a total of 46 patients with pathologically confirmed skull base meningioma in the First Affiliated Hospital of Bengbu Medical College from January 2015 to December 2016 were retrospectively analyzed.Preoperative multi-phase CT angiography was performed on all patients.Post-processing techniques were used to observe the relationship between the supply artery of the tumor,the tumor body and the adjacent vessels,including multi-plane reformation,volume rendering and multi-phase image fusion,the observed results were compared with the intraoperative findings,and the consistency between preoperative angiographic results and intraoperative findings was evaluated.Results Among the CT angiography data of these 46 patients,44 cases could clearly display the supply artery of the tumor,including 15 cases of simple external carotid artery,13 cases of mixed internal and external carotid artery,16 cases of simple internal carotid artery and 2 unclear cases.Compared with the intraoperative findings,the coincident rate was 84.78％,with a favorable consistency (Kappa=0.78).Among the 46 patients,36 cases had no invasion in blood vessels and 10 cases had vascular invasion.The coincident rate between the results of multi-phase CT angiography and intraoperative findings reached 95.65％,and the consistency was favorable (Kappa=0.93);the coincident rate between the results of arterial phase CT angiography and intraoperative findings was 67.39％,and the consistency was ordinary (Kappa=0.45).Conclusion Multi-phase CT angiography can clearly display the feeding artery of skull base meningioma and its relationship with adjacent vessels,and it is of great significance for the preoperative evaluation of surgical risk,the formulation of surgery program and the improvement of surgical safety.
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Objective To investigate the effects of hysteroscopic resection for mild-to-moderate uterine incision diverticulum after cesarean section.Methods From September 2010 to September 2014, hysteroscopic resection was performed under B-ultrasonography in 102 cases of mild-to-moderate uterine incision diverticulum after cesarean section.Results The operation was completed successfully in all the cases, without surgical complications.Outcome evaluation at 1 year after surgery showed cured in 89 cases (87.3%, complete disappearance of symptoms and recovery of normal menstruation), improved in 7 cases (6.9%, menstrual period shortened by 5-7 d, with or without lower abdominal dull pain and menstrual exacerbation), and ineffective in 6 cases (5.9%, no or slight symptom improvement).Conclusion Hysteroscopic resection is a safe, effective, and minimally invasive method for mild-to-moderate uterine incision diverticulum after cesarean section in patients demanding clinical symptom improvement without desire of fertility.
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Background It is determined that the patients with thyroid-associated ophthalmopathy (TAO) often occur dry-eye related symptoms due to increasing tear evaporation caused by exophthalmos.However,more than half of thyroid dysfunction patients without TAO appear ocular surface inflammation.It is very important for us to understand the association of thyroid dysfunction patients without TAO with ocular damage.Objective This study was to observe the ocular surface changes in thyroid dysfunction patients without TAO.Methods A prospective cohort study was performed.Thirty-one patients who were initially diagnosed as thyroid dysfunction without TAO were included in the Second Hospital of Tianjin Medical University from January 2015 to May 2016 as the thyroid dysfunction group,and 16 helthy subjects were simutenniously selected as the control group under the informed consent of all the individuals.The peripheral blood was collected to detect the thyroid function-related indexes.Then the patients with thyroid dysfunction were divided into thyroid stimulating hormone (TSH) reduced group (18 patients) versus TSH elevated group (13 patients) and thyrotrophin receptor antibody (TRAb)+ group (20 patients) versus TRAb-group (11 patients).Exophthalmos degree,Schirmer I test (S I t),tear film break-up time (BUT),fluorescent integral,ocular surface disease index (OSDI) and corneal inflammation index were examined and intergrouply compared.The correlations of thyroid function indexes with ocular surface examination results were analyzed.Results There were no significant differences in exophthalmos degree and S I t values between thyroid dysfunction group and control group (t =0.037,P =0.971;t =0.815,P =0.419).The BUT values were (7.74 ± 1.45) seconds and (10.56± 1.40) seconds,fluorescent integral scores were 5.00 (1.50) and 2.50 (2.38),OSDI scores were 45.58 ± 9.23 and 19.47 ± 6.25,and corneal inflammation index scores were 0.11 (0.22) and 0.00 (0.06) in the thyroid dysfunction group and the control group,respectively,showing significant differences between the two groups (all at P＜0.01).There were not significant differences in exophthalmos degree,S I t,BUT and corneal inflammation index scores between the TSH elevated group and TSH reduced group (t =0.473,P =0.640;t =0.650,P=0.521;t=1.634,P=0.l13;Z=0.270,P=0.787).The fluorescent integral scores were 4.00 (2.00) and 5.00 (1.00),and OSDI scores were 40.08±9.91 and 47.11±9.75 in the TSH elevated group and TSH reduced group,repectively,with statistically significant differences between these two groups (all at P＜0.01).The exophthalmos degrees,S I t,BUT and corneal inflammation index scores were not considerably different between TRAb-group and TRAb+ group (all at P＞0.05);and significant differences were seen in fluorescent integral scores (4.00[1.50] vs.5.50 [1.50]) and OSDI scores ([39.18±6.25] vs.[46.78±8.76]).Corneal inflammation index scores were positive correlated with serum TSH (R2 =0.520,P =0.000),and fluorescent integral scores,OSDI scores and corneal inflammation index scores were positive correlated with serum TRAb (R2 =0.587,P =0.000;R2 =0.329,P =0.024;R2 =0.400,P=0.005).Conclusions Thyroid dysfunction patients without TAO have ocular surface dysfunction,which probably is associated with abnormal serum TSH and TRAb.
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Objective To observe the inhibitory effects of Typhonium Giganteum soft capsules on tumor growth in Hep-2 tumor-bearing nude mice and its effects on the expression of tumor suppressor p53 gene; To discuss its mechanism of action.Methods Human liver cancer Hep-2 cell suspension back subcutaneous vaccination was conducted to prepare tumor models. BALB/c nude mice were randomly divided into model group, cisplatinum group, and TCM high-, medium-, and low-dose groups. Each group was given relevant medicine for gavage, once a day for 21 days. Growth changes of tumor volume were monitored; HE staining was used to observe pathological changes of tumor tissues; RT-PCR was used to detect the expression of p53 gene in tumor tissue of Hep-2 nude mice.Results Compared with the model group, all medication groups could inhibit the tumor growth, and the anti-tumor rates were 55.1%, 42.8%, 30.1%, and 79.5%, respectively; the expression of p53 gene increased; pathological observation results showed that the number and the volume of tumor cells increased, with cytoplasm rarefaction and nucleus anachromasis. All medication groups had karyopyknosis, slight staining, and decreasing blood capillary and focal necrosis in varying degrees.ConclusionTyphonium Giganteum soft capsules can inhibit the growth of human liver cancer, and its mechanism may be associated with the up-regulating expression of p53 gene leading to apoptosis.
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Objective To explore the expression of nemo-like kinase (NLK) in primary hepatic carcino-ma (HCC) and its clinicopathological significance. Methods The expression of NLK was detected in 136 HCC samples by Immunohistochemistry. Results NLK expression was significantly up-regulated in HCC specimens compared to corresponding normal liver tissues. High expression of NLK was significantly associated with Ed-mondson-steiner grade, tumor size and number of tumor nodules (all P < 0.05). There was positive correlation between NLK and proliferation marker Ki-67 (P < 0.01). Kaplan-Meier analysis showed the high expression NLK group was significantly associated with poor overall survival and disease-free survival (all P < 0.001). Univariate analysis showed that the high expression NLK was associated with poor prognosis (P < 0.001). Multivariable Cox regression analysis suggested that the expressions of NLK and Ki-67 , Edmondson-steiner grade , metastasis , tu-mor size and number of tumor nodules were independent prognostic indicators for HCC. Conclusions NLK was markedly upregulated in HCC specimens, and it might be an independent prognostic marker for HCC. NLK might play an important role in tumorigenesis, progression and prognosis of HCC.
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ObjectiveTo explore influence of emergency nursing process reengineering on the satisfac-tion degree of patients, quality of rescue, rescue time and success rate of rescue. MethodsEvidence-based nursing method was used for emergency nursing process reengineering. The first 30 types of acute and sever diseases and the first 6 large emergency events in 2008 were chosen as the rescue objectves, and they received new emergency nursing process. Influence of classic emergency nursing process in 2007 was retrieved and revalued. The satisfaction degree of patients, quality of emergency nursing and success rate of emergency before and after process reengineering were compared and analyzed. ResultsCompared with that before process reengineering, the satisfaction degree of experts, doctors and nurses, and patients was higher, the quality of emergency nursing greatly improved, the rescue time was less, and the success rate of rescue was higher after process reengineering. ConclusionsEmergency nursing process reengineering was more hu-man oriented. It can rescue patients with acute and severe diseases with lest time, reduce disputes between nurses and patients. It is worthy of application in clinic and the process should be reengineered and im-proved constantly in the future.