AIM:To evaluate the reliability of Photo-Hirschberg screening for global strabismus performed by non-specialized personnel.METHODS:Participants at three sites were enrolled.One person at each site was trained in visua...AIM:To evaluate the reliability of Photo-Hirschberg screening for global strabismus performed by non-specialized personnel.METHODS:Participants at three sites were enrolled.One person at each site was trained in visual acuity measurement and use of the computerized system.Visual acuity was measured,and strabismus testing was performed using two flash photographs.All data from the three primary observers were sent to an experienced assistant researcher,who was blinded to the primary results,for re-evaluation.The primary and re-evaluation results of the Photo-Hirschberg screenings using weighted kappa for agreement were compared.RESULTS:The study included 181 participants(88 males and 93 females)and the results for primary and re-evaluation screenings were corresponded.Ten participants with contrasting results presented with unclear corneal light reflex.Sensitivity and specificity were 100%[95%confidence interval(CI):29.0%-100%]and 99.4%(95%CI:96.6%-100%),respectively,based on the Agresti test of the primary evaluation,considering the re-evaluated classification as true.CONCLUSION:The computerized system can be used for primary strabismus screening by non-specialized personnel,with 98.8%agreement with specialists.However,it cannot be used as a substitute for professional examination.展开更多
Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impai...Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impairment(MCl)and evidence of AD's pathology.At this stage,disease-modifying interventions should be used to prevent the progression to dementia.Given the inherent heterogeneity of MCl,more specific biomarkers are needed to elucidate the underlying AD's pathology.Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology,their clinical applications are limited by their high costs and invasiveness,particularly in low-income areas in China.Therefore,to improve the early detection of Alzheimer's disease(AD)pathology through cost-effective screening methods,a panel of 45neurologists,psychiatrists andgerontologistswas invited to establish a formal consensus on the screening of pAD in China.The supportive evidence and grades of recommendations are based on a systematic literature review andfocus group discussion.National meetings were held to allow participants to review,vote and provide their expert opinions to reach a consensus.A majority(two-thirds)decision was used for questions for which consensus could not be reached.Recommended screening methods are presented in this publication,including neuropsychological assessment,peripheral biomarkers and brain imaging.In addition,a general workflow for Screening pAD in China is established,which will help clinicians identify individuals at high risk and determine therapeutic targets.展开更多
To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-bas...To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-based beef analogue diet(PB)for 68 days.Compared with real meat,the plant-based meat analogues increased food and energy intake,body weight,white fat and liver weight and caused adipocyte hypertrophy,hepatic lipid droplet accumulation,and inflammatory responses in mice.Metabolomics revealed that plantbased meat analogues altered the composition of serum metabolites,which regulated lipid metabolism homeostasis.The PB diet upregulated gene expression related to lipid synthesis,lipolysis and adipocyte differentiation while the PP diet upregulated expression of lipolysis-related genes but downregulated expression of adipocyte differentiation-related genes in white adipose tissue.Meanwhile,both PP and PB diets upregulated lipid influx-and synthesis-related genes but downregulated lipid oxidation-related genes in liver.The specific metabolite biomarkers may affect fat accumulation mainly by direct lipid metabolism pathways or indirect amino acid metabolism,protein digestion and absorption,bile secretion,aminoacyl-tRNA biosynthesis,neuroactive ligand-receptor interaction and ABC transporters pathways.These findings provide a new insight into understanding the differences in nutritional functions of meat and plant-based meat analogues.展开更多
As an independent sand control unit or a common protective shell of a high-quality screen,the punching screen is the outermost sand retaining unit of the sand control pipe which is used in geothermal well or oil and g...As an independent sand control unit or a common protective shell of a high-quality screen,the punching screen is the outermost sand retaining unit of the sand control pipe which is used in geothermal well or oil and gas well.However,most screens only consider the influence of the internal sand retaining medium parameters in the sand control performance design while ignoring the influence of the plugging of the punching screen on the overall sand retaining performance of the screen.To explore the clogging mechanism of the punching screen,this paper established the clogging mechanism calculation model of a single punching screen sand control unit by using the computational fluid mechanics-discrete element method(CFD-DEM)combined method.According to the combined motion of particles and fluids,the influence of the internal flow state on particle motion and accumulation was analyzed.The results showed that(1)the clogging process of the punching sand control unit is divided into three stages:initial clogging,aggravation of clogging and stability of clogging.In the initial stage of blockage,coarse particles form a loose bridge structure,and blockage often occurs preferentially at the streamline gathering place below chamfering inside the sand control unit.In the stage of blockage intensification,the particle mass develops into a relatively complete sand bridge,which develops from both ends of the opening to the center of the opening.In the stable plugging stage,the sand deposits show a“fan shape”and form a“V-shaped”gully inside the punching slot element.(2)Under a certain reservoir particle-size distribution,The slit length and opening height have a large influence on the permeability and blockage rate,while the slit width size has little influence on the permeability and blockage rate.The microscopic clogging mechanism and its law of the punching screen prevention unit are proposed in this study,which has some field guidance significance for the design of punching screen and sand prevention selection.展开更多
Photocatalysis,a critical strategy for harvesting sunlight to address energy demand and environmental concerns,is underpinned by the discovery of high-performance photocatalysts,thereby how to design photocatalysts is...Photocatalysis,a critical strategy for harvesting sunlight to address energy demand and environmental concerns,is underpinned by the discovery of high-performance photocatalysts,thereby how to design photocatalysts is now generating widespread interest in boosting the conversion effi-ciency of solar energy.In the past decade,computational technologies and theoretical simulations have led to a major leap in the development of high-throughput computational screening strategies for novel high-efficiency photocatalysts.In this viewpoint,we started with introducing the challenges of photocatalysis from the view of experimental practice,especially the inefficiency of the traditional“trial and error”method.Sub-sequently,a cross-sectional comparison between experimental and high-throughput computational screening for photocatalysis is presented and discussed in detail.On the basis of the current experimental progress in photocatalysis,we also exemplified the various challenges associated with high-throughput computational screening strategies.Finally,we offered a preferred high-throughput computational screening procedure for pho-tocatalysts from an experimental practice perspective(model construction and screening,standardized experiments,assessment and revision),with the aim of a better correlation of high-throughput simulations and experimental practices,motivating to search for better descriptors.展开更多
School-based universal screening for behavioral/emotional risk is a necessary first step to providing services in an educational setting for students with emotional and behavioral disorders (EBDs). Psychometric proper...School-based universal screening for behavioral/emotional risk is a necessary first step to providing services in an educational setting for students with emotional and behavioral disorders (EBDs). Psychometric properties are critical to making decisions about choosing a screening instrument. The purpose of the present study was to examine the psychometric properties of the student risk screening scale for internalizing and externalizing behaviors (SRSS-IE). Participants included 3145 students and their teachers. Item-level analyses of the current sample supported the retention of all items. The internal consistency of the SRSS items ranged from 0.83 to 0.85. Convergent validity between the SRSS-IE and a well-established screening tool, the strength and difficulties questionnaire (SDQ), was found for the total score (r = 0.70). Additionally, the results of this study demonstrate strong social validity, suggesting the SRSS-IE to be a useful and functional screening tool. We conclude that the SRSS-IE is a valid and reliable instrument for assessing the level of emotional and behavioral difficulties among elementary students.展开更多
Objective: To determine the prevalence of diabetes and the level of cardiovascular risk in tuberculosis patients treated in Conakry and surrounding towns. Method: This was a cross-sectional study carried out at tuberc...Objective: To determine the prevalence of diabetes and the level of cardiovascular risk in tuberculosis patients treated in Conakry and surrounding towns. Method: This was a cross-sectional study carried out at tuberculosis treatment centers in Conakry and surrounding towns (Coyah and Dubréka) on World TB Day, November 14, 2022, among 350 tuberculosis patients. We determined the proportion of TB patients with diabetes and high hyperglycemia. We determined the Chi-square to identify the factors associated with the occurrence of diabetes in tuberculosis patients, and a significance threshold with p Results: The average age of participants was 33.5 ± 14.5 years, and they were predominantly male (59.7%). The majority of participants lived in Conakry (96.3%). 5.7% were known diabetics and 4.6% were known hypertensives. We found a prevalence of diabetes of 9.4%. Among diabetics, 39% were diabetes discoveries. 30% were hypertensive or had high blood pressure. Of these hypertensive patients, 26.4% were unrecognized hypertensives. Age and hypertension were statistically significantly associated with the onset of diabetes in tuberculosis patients. Medium, high and very high levels of cardiovascular risk were present in 23.4%, 8.9% and 3.4% respectively. Conclusion: Diabetes is common in tuberculosis patients. Cardiovascular risk factors, notably hypertension and cardiovascular risk level, are frequently associated with tuberculosis. Tuberculosis patients with cardiovascular risk factors should be screened for diabetes.展开更多
Diabetic retinopathy is a leading cause of preventable vision impairment and a common complication of diabetes. Diabetic retinopathy screening can identify early changes in the retina so treatment can be given before ...Diabetic retinopathy is a leading cause of preventable vision impairment and a common complication of diabetes. Diabetic retinopathy screening can identify early changes in the retina so treatment can be given before vision impairment or blindness occurs. The aim of this audit is to evaluate the diabetic eye screening pathway in Malta to reduce the risk of vision impairment among diabetic patients through the identification and effective management of sight-threatening diabetic retinopathy by evaluating adherence to diabetic retinopathy screening guidelines and identifying areas for improvement within the screening pathway at Mater Dei Hospital (MDH). The practical implications of the audit’s findings highlight the importance of more awareness of current guidelines on the recommended time of first eye examination and routine minimum follow up interval at the Endocrinology Department at MDH. 26.7% of the doctors participating in this audit perform fundoscopy on initial assessment only, while 13.3% perform fundoscopy every visit. On the other hand, 60% of the participants never perform fundoscopy.展开更多
Newborn hearing screening(NHS) programs are essential to identify hearing loss early in life and to improve outcomes in children. In Saudi Arabia, the national NHS program has been operational since 2016;however, few ...Newborn hearing screening(NHS) programs are essential to identify hearing loss early in life and to improve outcomes in children. In Saudi Arabia, the national NHS program has been operational since 2016;however, few studies have evaluated its status, and none have covered all provinces across the country. This cross-sectional retrospective study provides an overview of the program's status across all provinces, focusing on screening coverage rates, referral/fail rates, and follow-up procedures. In 2021, 199,034 newborns were screened, with a coverage rate of 92.6% and an overall referral/fail rate of 1.87%. These performance measures provide a foundation for future progress and improvements. This study highlights the importance of ongoing efforts to enhance the program's effectiveness and sustainability.展开更多
Background: Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality in the United States (US) and globally. CHB disproportionately affects Asian Americans and many other immigrant minority ...Background: Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality in the United States (US) and globally. CHB disproportionately affects Asian Americans and many other immigrant minority populations, primarily owing to the high prevalence of CHB in their countries of origin. India is a country with a medium-to-high prevalence of hepatitis B (HB) (>2%) and has over 40 million people infected with hepatitis B virus (HBV), with more than 115,000 deaths annually from HBV-related complications. Indian Americans are one of the largest immigrant populations in the US but remain underdiagnosed and poorly linked to clinical care. We, therefore, assessed the HBV prevalence and evaluated the linkage-to-care (LTC) among Indian Americans to develop strategic plans to reduce the impact of HBV in the US. Methods: Between April 2022 and January 2024, serologic screening and surveys were provided to 328 Indian American adults (age 20 - 80) in New York City. All participants were tested for a triple panel consisting of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core IgG antibody (anti-HBc). A survey was conducted on the subjects chronically infected with HBV regarding their histories of infection. Self-administered questionnaires were employed to evaluate demographic and epidemiologic characteristics. Results: Of 328 screened and evaluated (246 males and 82 females), 10 (3.0%) were HBV-infected, 222 (67.7%) were susceptible to HBV, and 96 (29.3%) were immune. The prevalence of chronic HBV varied between the age groups: 4.6% (age 20 - 40), 3.4% (age 41 - 60), and 1.7% (age 61 - 80). Of 10 chronically infected, only two subjects had been previously diagnosed but were not engaged in care. Conclusion: HBV disproportionately affects Asian Americans, primarily owing to immigration from parts of the world where the disease is endemic. Indian Americans belong to an intermediate-risk group, with an HBV prevalence of >2%, but remain underdiagnosed and poorly linked to care. Our pilot study on Indian American populations, the first of its kind, demonstrates a 3% prevalence of CHB, none of whom are linked to care. In addition, this population has a high percentage of unimmune subjects, creating a large reservoir for future infection. With the growing population of Indian Americans, our findings can be used to develop community-based strategies for HBV screenings and LTC that target high-risk groups.展开更多
Alpha-lactalbumin(α-LA)is a major whey protein found in breast milk and plays a crucial role in the growth and development of infants.In this study,Bacillus subtilis RIK1285 harboring AprE signal peptide(SP)was selec...Alpha-lactalbumin(α-LA)is a major whey protein found in breast milk and plays a crucial role in the growth and development of infants.In this study,Bacillus subtilis RIK1285 harboring AprE signal peptide(SP)was selected as the original strain for the production ofα-LA.It was found thatα-LA was identified in the pellet after ultrasonic disruption and centrifugation instead of in the fermentation supernatant.The original strain most likely only producedα-LA intracellular,but not extracellular.To improve the expression and secretion ofα-LA in RIK1285,a library of 173 homologous SPs from the B.subtilis 168 genome was fused with target LALBA gene in the pBE-S vector and expressed extracellularly in RIK1285.SP YjcN was determined to be the best signal peptide.Bands in supernatant were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and purified by nickel column to calculate the highest yield signal peptide.In addition,different promoters(P_(aprE),P_(43),and P_(glv))were compared and applied.The results indicated that the strain RIK1285-pBE-P_(glv)-YjcN-LALBA had the highestα-LA yield,reaching 122.04μg/mL.This study demonstrates successful expression and secretion of humanα-LA in B.subtilis and establishes a foundation for simulating breast milk for infant formulas and developing bioengineered milk.展开更多
Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally.Despite the progress in scree...Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally.Despite the progress in screening,early diagnosis,and treatment,approximately 20%-25%of CRC patients still present with metastatic disease at the time of their initial diagnosis.Furthermore,the burden of disease is still expected to increase,especially in individuals younger than 50 years old,among whom early-onset CRC incidence has been increasing.Screening and early detection are pivotal to improve CRC-related outcomes.It is well established that CRC screening not only reduces incidence,but also decreases deaths from CRC.Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality,though variations in efficacy have been reported across the literature.However,uncertainties persist regarding the optimal screening method,age intervals and periodicity.Moreover,adherence to CRC screening remains globally low.In recent years,emerging technologies,notably artificial intelligence,and non-invasive biomarkers,have been developed to overcome these barriers.However,controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice.In this review,we aim to cover the current evidence surrounding CRC screening.We will further critically assess novel approaches under investigation,in an effort to differentiate promising inno-vations from mere novelties.展开更多
Background: Breast cancer is the dominant cancer in women in both developed and developing countries. The objective of this study was to assess the knowledge, attitudes, practices and factors associated with early bre...Background: Breast cancer is the dominant cancer in women in both developed and developing countries. The objective of this study was to assess the knowledge, attitudes, practices and factors associated with early breast cancer screening among women in the Municipality of Abomey-Calavi in Benin. Methods: This was a cross-sectional, descriptive, analytical study with prospective data collection from October 1 to 8, 2018, involving 1740 women in the Municipality of Abomey-Calavi, aged 18 years or older and selected by WHO four-stage random cluster sampling. Consenting women who were mentally competent, 18 years of age or older at the time of the survey, and residing continuously in the Municipality of Abomey-Calavi for the last six months prior to the survey were included. On the other hand, women who belonged to a breast cancer prevention service, women in whom secondary screening was noted, or non-consenting women were not included. The initial minimum size was estimated by the Schwartz formula with a cluster effect of k = 2. Information was collected by questionnaire survey, entered with Epidata 3.1. Fr and analyzed with R Studio 3.5.1. software. Results: The mean age of the women surveyed was 32.0 ± 11.5 years with a range of 18 and 71 years. Regarding knowledge, the clinical manifestation known by the majority of women was the presence of a nodule (68.50%). In the series, 1308 (75.17%) declared having heard about breast cancer once before, either on the radio, television or from friends and 726 (55.50%) had heard about breast cancer screening. Five hundred and twelve (70.52%) of the 726 who had heard of breast cancer said they knew that breast cancer could be screened earlier. Breast self-examination was the most cited screening method (67.58%). The disease is of natural origin according to 37.84% of them. Regarding attitudes and practices, the prevalence of early breast cancer screening was 12.93%, of which 11.67% declared that they had checked themselves to know whether they were carriers of the disease or not. The main means of the early screening used was breast self-examination (85.78%). Factors associated with early breast cancer screening found in multivariate analysis were age (≤50 years), education level (increasingly higher), marital status (married/coupled), place of residence (downtown), and socioeconomic level (average/high). Conclusion: The frequency of early breast cancer screening among women is still low in the municipality of Abomey-Calavi, although they have a good knowledge of the disease. This raises the need to strengthen awareness of early breast cancer screening.展开更多
Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no prop...Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no proper guidance is given by the health care provider. This study assessed the roles of community pharmacists in screening and disseminating information about the risks associated with NSAID use in Zambia. Methodology: This was a national cross-sectional study in which a structured self-administered questionnaire was administered to 245 registered community pharmacists in Zambia. Stata/BE, version 15.1 (Stata Corporation, College Station, Texas, USA) and multivariate logistic regression model was used to determine factors associated with information dissemination about ADRs of NS-NSAIDs. Results: 231 of the 245 distributed questionnaires were returned giving a response rate of 94.3%. All (100%) participating community pharmacists claimed to have practiced dispensing NSAIDs. However, only 26 (11.0%) and 71 (30.8%) regularly screened for risk factor of selective COX-2 NSAIDS (SC2-NSAIDS) and non-selective NSAIDS (NS-NSAIDs) respectively. Information dissemination on adverse drug reactions (ADRs) of SC2-NSAIDS was regularly provided by only 22 (9.5%) of pharmacists while that of NS-NSAIDs was regularly provided by 49 (21.2%). In the multivariate logistic regression model, being the owner of a pharmacy (AOR: 5.4, CI: 1.84 - 16.4) was significantly associated with information dissemination about ADRs of NS-NSAIDs while an hour increase in the working hours per day (AOR: 0.9, CI: 0.64 - 0.95) was associated with less likelihood of information dissemination. Conclusion: Pharmacists working in community pharmacies in Zambia did not regularly screen and disseminate information about the risks associated with NSAID use. Therefore, pharmacists should be able to screen and monitor patients at risk and be aware of the majority of risk factors while dispensing NSAIDs to minimize the associated complications.展开更多
BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of...BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.展开更多
BACKGROUND X-ray gastric cancer(GC)screening has been shown to decrease mortality.Population-based X-ray GC screening has been performed in Hiroshima Prefe-cture,Japan,since 1983 but time trends and the efficacy of th...BACKGROUND X-ray gastric cancer(GC)screening has been shown to decrease mortality.Population-based X-ray GC screening has been performed in Hiroshima Prefe-cture,Japan,since 1983 but time trends and the efficacy of the method over 39 years have not been assessed.METHODS This was a population-based retrospective study.The data were derived from aggregated data of the Hiroshima Regional Health Medical Promotion Organization,including the number and rate of participants and those requiring esophagogastroduodenoscopies(EGDs),the number and rate of participants diagnosed as having GC,and the positive predictive value of the abnormal findings detected by X-ray and confirmed by EGDs.The number and rate of esophageal cancers were also collected.Further,the cost of detecting one GC was evaluated.RESULTS The number of participants has decreased during the last four decades,from 39925 in 1983 to 12923 in 2021.The rate of those requiring EGDs decreased significantly in recent years(P<0.001).The number of participants diagnosed as having GC has also declined,from 76 to 10 cases.However,the rate of cases diagnosed as GC among the participants remained around 0.1%.The positive predictive value increased significantly in recent years except during 1983-1991.The number and rate of accidentally detected esophageal cancers have risen recently,from 0%in 2008 to 0.02%in 2021,one-fifth of the diagnosis rate of GC.One GC diagnosis costs approximately 4200000 Japanese Yen(30000 United States Dollars)for the X-ray screenings and EGDs.CONCLUSION X-ray GC screening in Hiroshima has been efficient,but one challenge is the cost.Esophageal cancers may also need to be considered because they have gradually increased in recent years.展开更多
Gastric cancers are caused primarily due to the activation and amplification of the EGFR or HER2 kinases resulting in cell proliferation,adhesion,angiogenesis,and metastasis.Conventional therapies are ineffective due ...Gastric cancers are caused primarily due to the activation and amplification of the EGFR or HER2 kinases resulting in cell proliferation,adhesion,angiogenesis,and metastasis.Conventional therapies are ineffective due to the intra-tumoral heterogeneity and concomitant genetic mutations.Hence,dual inhibition strategies are recommended to increase potency and reduce cytotoxicity.In this study,we have conducted computational high-throughput screening of the ChemBridge library followed by in vitro assays and identified novel selective inhibitors that have a dual impediment of EGFR/HER2 kinase activities.Diversity-based High-throughput Virtual Screening(D-HTVS)was used to screen the whole ChemBridge small molecular library against EGFR and HER2.The atomistic molecular dynamic simulation was conducted to understand the dynamics and stability of the protein-ligand complexes.EGFR/HER2 kinase enzymes,KATOIII,and Snu-5 cells were used for in vitro validations.The atomistic Molecular Dynamics simulations followed by solvent-based Gibbs binding free energy calculation of top molecules,identified compound C3(5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-1H-isoindole-1,3(2H)-dione)to have a good affinity for both EGFR and HER2.The predicted compound,C3,was promising with better binding energy,good binding pose,and optimum interactions with the EGFR and HER2 residues.C3 inhibited EGFR and HER2 kinases with IC50 values of 37.24 and 45.83 nM,respectively.The GI50 values of C3 to inhibit KATOIII and Snu-5 cells were 84.76 and 48.26 nM,respectively.Based on these findings,we conclude that the identified compound C3 showed a conceivable dual inhibitory activity on EGFR/HER2 kinase,and therefore can be considered as a plausible lead-like molecule for treating gastric cancers with minimal side effects,though testing in higher models with pharmacokinetic approach is required.展开更多
Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately ...Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.展开更多
BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still...BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.展开更多
[Objectives]The anti-tumor activity of fractions from Buddleja officinalis Maxim.by petroleum ether,ethyl acetate,n-butanol and water solvent was studied.[Methods]The ethanol extract from B.officinalis Maxim.was extra...[Objectives]The anti-tumor activity of fractions from Buddleja officinalis Maxim.by petroleum ether,ethyl acetate,n-butanol and water solvent was studied.[Methods]The ethanol extract from B.officinalis Maxim.was extracted and then concentrated with petroleum ether,ethyl acetate,n-butanol and water,respectively,and the extracts were obtained.The inhibitory effects of the four different fractions on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the median inhibitory concentration(IC 50 value)was calculated.[Results]The four fractions inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol fraction had the best anti-tumor activity.The IC 50 values of the n-butanol fraction on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.08,1.58 and 0.12 mg/mL,respectively.[Conclusions]Petroleum ether,ethyl acetate,n-butanol and water fractions from the ethanol extract of B.officinalis Maxim.had certain anti-tumor effects,and the n-butanol fraction had the best anti-tumor activity.展开更多
文摘AIM:To evaluate the reliability of Photo-Hirschberg screening for global strabismus performed by non-specialized personnel.METHODS:Participants at three sites were enrolled.One person at each site was trained in visual acuity measurement and use of the computerized system.Visual acuity was measured,and strabismus testing was performed using two flash photographs.All data from the three primary observers were sent to an experienced assistant researcher,who was blinded to the primary results,for re-evaluation.The primary and re-evaluation results of the Photo-Hirschberg screenings using weighted kappa for agreement were compared.RESULTS:The study included 181 participants(88 males and 93 females)and the results for primary and re-evaluation screenings were corresponded.Ten participants with contrasting results presented with unclear corneal light reflex.Sensitivity and specificity were 100%[95%confidence interval(CI):29.0%-100%]and 99.4%(95%CI:96.6%-100%),respectively,based on the Agresti test of the primary evaluation,considering the re-evaluated classification as true.CONCLUSION:The computerized system can be used for primary strabismus screening by non-specialized personnel,with 98.8%agreement with specialists.However,it cannot be used as a substitute for professional examination.
基金the National Natural Science Foundation of China(82171198,U20A20354)the Sci-Tech Innovation 2030 Agenda of China(2022ZD0211603).
文摘Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impairment(MCl)and evidence of AD's pathology.At this stage,disease-modifying interventions should be used to prevent the progression to dementia.Given the inherent heterogeneity of MCl,more specific biomarkers are needed to elucidate the underlying AD's pathology.Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology,their clinical applications are limited by their high costs and invasiveness,particularly in low-income areas in China.Therefore,to improve the early detection of Alzheimer's disease(AD)pathology through cost-effective screening methods,a panel of 45neurologists,psychiatrists andgerontologistswas invited to establish a formal consensus on the screening of pAD in China.The supportive evidence and grades of recommendations are based on a systematic literature review andfocus group discussion.National meetings were held to allow participants to review,vote and provide their expert opinions to reach a consensus.A majority(two-thirds)decision was used for questions for which consensus could not be reached.Recommended screening methods are presented in this publication,including neuropsychological assessment,peripheral biomarkers and brain imaging.In addition,a general workflow for Screening pAD in China is established,which will help clinicians identify individuals at high risk and determine therapeutic targets.
基金supported by Jiangsu Innovative Group of Meat Nutrition,Health and Biotechnologythe Postgraduate Research&Practice Innovation Program of Jiangsu Province(grant number:KYCX21_0575)。
文摘To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-based beef analogue diet(PB)for 68 days.Compared with real meat,the plant-based meat analogues increased food and energy intake,body weight,white fat and liver weight and caused adipocyte hypertrophy,hepatic lipid droplet accumulation,and inflammatory responses in mice.Metabolomics revealed that plantbased meat analogues altered the composition of serum metabolites,which regulated lipid metabolism homeostasis.The PB diet upregulated gene expression related to lipid synthesis,lipolysis and adipocyte differentiation while the PP diet upregulated expression of lipolysis-related genes but downregulated expression of adipocyte differentiation-related genes in white adipose tissue.Meanwhile,both PP and PB diets upregulated lipid influx-and synthesis-related genes but downregulated lipid oxidation-related genes in liver.The specific metabolite biomarkers may affect fat accumulation mainly by direct lipid metabolism pathways or indirect amino acid metabolism,protein digestion and absorption,bile secretion,aminoacyl-tRNA biosynthesis,neuroactive ligand-receptor interaction and ABC transporters pathways.These findings provide a new insight into understanding the differences in nutritional functions of meat and plant-based meat analogues.
文摘As an independent sand control unit or a common protective shell of a high-quality screen,the punching screen is the outermost sand retaining unit of the sand control pipe which is used in geothermal well or oil and gas well.However,most screens only consider the influence of the internal sand retaining medium parameters in the sand control performance design while ignoring the influence of the plugging of the punching screen on the overall sand retaining performance of the screen.To explore the clogging mechanism of the punching screen,this paper established the clogging mechanism calculation model of a single punching screen sand control unit by using the computational fluid mechanics-discrete element method(CFD-DEM)combined method.According to the combined motion of particles and fluids,the influence of the internal flow state on particle motion and accumulation was analyzed.The results showed that(1)the clogging process of the punching sand control unit is divided into three stages:initial clogging,aggravation of clogging and stability of clogging.In the initial stage of blockage,coarse particles form a loose bridge structure,and blockage often occurs preferentially at the streamline gathering place below chamfering inside the sand control unit.In the stage of blockage intensification,the particle mass develops into a relatively complete sand bridge,which develops from both ends of the opening to the center of the opening.In the stable plugging stage,the sand deposits show a“fan shape”and form a“V-shaped”gully inside the punching slot element.(2)Under a certain reservoir particle-size distribution,The slit length and opening height have a large influence on the permeability and blockage rate,while the slit width size has little influence on the permeability and blockage rate.The microscopic clogging mechanism and its law of the punching screen prevention unit are proposed in this study,which has some field guidance significance for the design of punching screen and sand prevention selection.
基金The authors are grateful for financial support from the National Key Projects for Fundamental Research and Development of China(2021YFA1500803)the National Natural Science Foundation of China(51825205,52120105002,22102202,22088102,U22A20391)+1 种基金the DNL Cooperation Fund,CAS(DNL202016)the CAS Project for Young Scientists in Basic Research(YSBR-004).
文摘Photocatalysis,a critical strategy for harvesting sunlight to address energy demand and environmental concerns,is underpinned by the discovery of high-performance photocatalysts,thereby how to design photocatalysts is now generating widespread interest in boosting the conversion effi-ciency of solar energy.In the past decade,computational technologies and theoretical simulations have led to a major leap in the development of high-throughput computational screening strategies for novel high-efficiency photocatalysts.In this viewpoint,we started with introducing the challenges of photocatalysis from the view of experimental practice,especially the inefficiency of the traditional“trial and error”method.Sub-sequently,a cross-sectional comparison between experimental and high-throughput computational screening for photocatalysis is presented and discussed in detail.On the basis of the current experimental progress in photocatalysis,we also exemplified the various challenges associated with high-throughput computational screening strategies.Finally,we offered a preferred high-throughput computational screening procedure for pho-tocatalysts from an experimental practice perspective(model construction and screening,standardized experiments,assessment and revision),with the aim of a better correlation of high-throughput simulations and experimental practices,motivating to search for better descriptors.
文摘School-based universal screening for behavioral/emotional risk is a necessary first step to providing services in an educational setting for students with emotional and behavioral disorders (EBDs). Psychometric properties are critical to making decisions about choosing a screening instrument. The purpose of the present study was to examine the psychometric properties of the student risk screening scale for internalizing and externalizing behaviors (SRSS-IE). Participants included 3145 students and their teachers. Item-level analyses of the current sample supported the retention of all items. The internal consistency of the SRSS items ranged from 0.83 to 0.85. Convergent validity between the SRSS-IE and a well-established screening tool, the strength and difficulties questionnaire (SDQ), was found for the total score (r = 0.70). Additionally, the results of this study demonstrate strong social validity, suggesting the SRSS-IE to be a useful and functional screening tool. We conclude that the SRSS-IE is a valid and reliable instrument for assessing the level of emotional and behavioral difficulties among elementary students.
文摘Objective: To determine the prevalence of diabetes and the level of cardiovascular risk in tuberculosis patients treated in Conakry and surrounding towns. Method: This was a cross-sectional study carried out at tuberculosis treatment centers in Conakry and surrounding towns (Coyah and Dubréka) on World TB Day, November 14, 2022, among 350 tuberculosis patients. We determined the proportion of TB patients with diabetes and high hyperglycemia. We determined the Chi-square to identify the factors associated with the occurrence of diabetes in tuberculosis patients, and a significance threshold with p Results: The average age of participants was 33.5 ± 14.5 years, and they were predominantly male (59.7%). The majority of participants lived in Conakry (96.3%). 5.7% were known diabetics and 4.6% were known hypertensives. We found a prevalence of diabetes of 9.4%. Among diabetics, 39% were diabetes discoveries. 30% were hypertensive or had high blood pressure. Of these hypertensive patients, 26.4% were unrecognized hypertensives. Age and hypertension were statistically significantly associated with the onset of diabetes in tuberculosis patients. Medium, high and very high levels of cardiovascular risk were present in 23.4%, 8.9% and 3.4% respectively. Conclusion: Diabetes is common in tuberculosis patients. Cardiovascular risk factors, notably hypertension and cardiovascular risk level, are frequently associated with tuberculosis. Tuberculosis patients with cardiovascular risk factors should be screened for diabetes.
文摘Diabetic retinopathy is a leading cause of preventable vision impairment and a common complication of diabetes. Diabetic retinopathy screening can identify early changes in the retina so treatment can be given before vision impairment or blindness occurs. The aim of this audit is to evaluate the diabetic eye screening pathway in Malta to reduce the risk of vision impairment among diabetic patients through the identification and effective management of sight-threatening diabetic retinopathy by evaluating adherence to diabetic retinopathy screening guidelines and identifying areas for improvement within the screening pathway at Mater Dei Hospital (MDH). The practical implications of the audit’s findings highlight the importance of more awareness of current guidelines on the recommended time of first eye examination and routine minimum follow up interval at the Endocrinology Department at MDH. 26.7% of the doctors participating in this audit perform fundoscopy on initial assessment only, while 13.3% perform fundoscopy every visit. On the other hand, 60% of the participants never perform fundoscopy.
文摘Newborn hearing screening(NHS) programs are essential to identify hearing loss early in life and to improve outcomes in children. In Saudi Arabia, the national NHS program has been operational since 2016;however, few studies have evaluated its status, and none have covered all provinces across the country. This cross-sectional retrospective study provides an overview of the program's status across all provinces, focusing on screening coverage rates, referral/fail rates, and follow-up procedures. In 2021, 199,034 newborns were screened, with a coverage rate of 92.6% and an overall referral/fail rate of 1.87%. These performance measures provide a foundation for future progress and improvements. This study highlights the importance of ongoing efforts to enhance the program's effectiveness and sustainability.
文摘Background: Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality in the United States (US) and globally. CHB disproportionately affects Asian Americans and many other immigrant minority populations, primarily owing to the high prevalence of CHB in their countries of origin. India is a country with a medium-to-high prevalence of hepatitis B (HB) (>2%) and has over 40 million people infected with hepatitis B virus (HBV), with more than 115,000 deaths annually from HBV-related complications. Indian Americans are one of the largest immigrant populations in the US but remain underdiagnosed and poorly linked to clinical care. We, therefore, assessed the HBV prevalence and evaluated the linkage-to-care (LTC) among Indian Americans to develop strategic plans to reduce the impact of HBV in the US. Methods: Between April 2022 and January 2024, serologic screening and surveys were provided to 328 Indian American adults (age 20 - 80) in New York City. All participants were tested for a triple panel consisting of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core IgG antibody (anti-HBc). A survey was conducted on the subjects chronically infected with HBV regarding their histories of infection. Self-administered questionnaires were employed to evaluate demographic and epidemiologic characteristics. Results: Of 328 screened and evaluated (246 males and 82 females), 10 (3.0%) were HBV-infected, 222 (67.7%) were susceptible to HBV, and 96 (29.3%) were immune. The prevalence of chronic HBV varied between the age groups: 4.6% (age 20 - 40), 3.4% (age 41 - 60), and 1.7% (age 61 - 80). Of 10 chronically infected, only two subjects had been previously diagnosed but were not engaged in care. Conclusion: HBV disproportionately affects Asian Americans, primarily owing to immigration from parts of the world where the disease is endemic. Indian Americans belong to an intermediate-risk group, with an HBV prevalence of >2%, but remain underdiagnosed and poorly linked to care. Our pilot study on Indian American populations, the first of its kind, demonstrates a 3% prevalence of CHB, none of whom are linked to care. In addition, this population has a high percentage of unimmune subjects, creating a large reservoir for future infection. With the growing population of Indian Americans, our findings can be used to develop community-based strategies for HBV screenings and LTC that target high-risk groups.
基金This work was funded by National Natural Science Foundation of China(32272279)the Key R&D project of Qingdao Science and Technology Plan(22-3-3-hygg-29-hy).
文摘Alpha-lactalbumin(α-LA)is a major whey protein found in breast milk and plays a crucial role in the growth and development of infants.In this study,Bacillus subtilis RIK1285 harboring AprE signal peptide(SP)was selected as the original strain for the production ofα-LA.It was found thatα-LA was identified in the pellet after ultrasonic disruption and centrifugation instead of in the fermentation supernatant.The original strain most likely only producedα-LA intracellular,but not extracellular.To improve the expression and secretion ofα-LA in RIK1285,a library of 173 homologous SPs from the B.subtilis 168 genome was fused with target LALBA gene in the pBE-S vector and expressed extracellularly in RIK1285.SP YjcN was determined to be the best signal peptide.Bands in supernatant were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and purified by nickel column to calculate the highest yield signal peptide.In addition,different promoters(P_(aprE),P_(43),and P_(glv))were compared and applied.The results indicated that the strain RIK1285-pBE-P_(glv)-YjcN-LALBA had the highestα-LA yield,reaching 122.04μg/mL.This study demonstrates successful expression and secretion of humanα-LA in B.subtilis and establishes a foundation for simulating breast milk for infant formulas and developing bioengineered milk.
文摘Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally.Despite the progress in screening,early diagnosis,and treatment,approximately 20%-25%of CRC patients still present with metastatic disease at the time of their initial diagnosis.Furthermore,the burden of disease is still expected to increase,especially in individuals younger than 50 years old,among whom early-onset CRC incidence has been increasing.Screening and early detection are pivotal to improve CRC-related outcomes.It is well established that CRC screening not only reduces incidence,but also decreases deaths from CRC.Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality,though variations in efficacy have been reported across the literature.However,uncertainties persist regarding the optimal screening method,age intervals and periodicity.Moreover,adherence to CRC screening remains globally low.In recent years,emerging technologies,notably artificial intelligence,and non-invasive biomarkers,have been developed to overcome these barriers.However,controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice.In this review,we aim to cover the current evidence surrounding CRC screening.We will further critically assess novel approaches under investigation,in an effort to differentiate promising inno-vations from mere novelties.
文摘Background: Breast cancer is the dominant cancer in women in both developed and developing countries. The objective of this study was to assess the knowledge, attitudes, practices and factors associated with early breast cancer screening among women in the Municipality of Abomey-Calavi in Benin. Methods: This was a cross-sectional, descriptive, analytical study with prospective data collection from October 1 to 8, 2018, involving 1740 women in the Municipality of Abomey-Calavi, aged 18 years or older and selected by WHO four-stage random cluster sampling. Consenting women who were mentally competent, 18 years of age or older at the time of the survey, and residing continuously in the Municipality of Abomey-Calavi for the last six months prior to the survey were included. On the other hand, women who belonged to a breast cancer prevention service, women in whom secondary screening was noted, or non-consenting women were not included. The initial minimum size was estimated by the Schwartz formula with a cluster effect of k = 2. Information was collected by questionnaire survey, entered with Epidata 3.1. Fr and analyzed with R Studio 3.5.1. software. Results: The mean age of the women surveyed was 32.0 ± 11.5 years with a range of 18 and 71 years. Regarding knowledge, the clinical manifestation known by the majority of women was the presence of a nodule (68.50%). In the series, 1308 (75.17%) declared having heard about breast cancer once before, either on the radio, television or from friends and 726 (55.50%) had heard about breast cancer screening. Five hundred and twelve (70.52%) of the 726 who had heard of breast cancer said they knew that breast cancer could be screened earlier. Breast self-examination was the most cited screening method (67.58%). The disease is of natural origin according to 37.84% of them. Regarding attitudes and practices, the prevalence of early breast cancer screening was 12.93%, of which 11.67% declared that they had checked themselves to know whether they were carriers of the disease or not. The main means of the early screening used was breast self-examination (85.78%). Factors associated with early breast cancer screening found in multivariate analysis were age (≤50 years), education level (increasingly higher), marital status (married/coupled), place of residence (downtown), and socioeconomic level (average/high). Conclusion: The frequency of early breast cancer screening among women is still low in the municipality of Abomey-Calavi, although they have a good knowledge of the disease. This raises the need to strengthen awareness of early breast cancer screening.
文摘Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no proper guidance is given by the health care provider. This study assessed the roles of community pharmacists in screening and disseminating information about the risks associated with NSAID use in Zambia. Methodology: This was a national cross-sectional study in which a structured self-administered questionnaire was administered to 245 registered community pharmacists in Zambia. Stata/BE, version 15.1 (Stata Corporation, College Station, Texas, USA) and multivariate logistic regression model was used to determine factors associated with information dissemination about ADRs of NS-NSAIDs. Results: 231 of the 245 distributed questionnaires were returned giving a response rate of 94.3%. All (100%) participating community pharmacists claimed to have practiced dispensing NSAIDs. However, only 26 (11.0%) and 71 (30.8%) regularly screened for risk factor of selective COX-2 NSAIDS (SC2-NSAIDS) and non-selective NSAIDS (NS-NSAIDs) respectively. Information dissemination on adverse drug reactions (ADRs) of SC2-NSAIDS was regularly provided by only 22 (9.5%) of pharmacists while that of NS-NSAIDs was regularly provided by 49 (21.2%). In the multivariate logistic regression model, being the owner of a pharmacy (AOR: 5.4, CI: 1.84 - 16.4) was significantly associated with information dissemination about ADRs of NS-NSAIDs while an hour increase in the working hours per day (AOR: 0.9, CI: 0.64 - 0.95) was associated with less likelihood of information dissemination. Conclusion: Pharmacists working in community pharmacies in Zambia did not regularly screen and disseminate information about the risks associated with NSAID use. Therefore, pharmacists should be able to screen and monitor patients at risk and be aware of the majority of risk factors while dispensing NSAIDs to minimize the associated complications.
基金the Foundation for Cancer Research supported by Kyoto Preventive Medical Center and the Japan Society for the Promotion of Science(JSPS)Grants-in-Aid KAKENHI,No.JP 22K21080.
文摘BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.
文摘BACKGROUND X-ray gastric cancer(GC)screening has been shown to decrease mortality.Population-based X-ray GC screening has been performed in Hiroshima Prefe-cture,Japan,since 1983 but time trends and the efficacy of the method over 39 years have not been assessed.METHODS This was a population-based retrospective study.The data were derived from aggregated data of the Hiroshima Regional Health Medical Promotion Organization,including the number and rate of participants and those requiring esophagogastroduodenoscopies(EGDs),the number and rate of participants diagnosed as having GC,and the positive predictive value of the abnormal findings detected by X-ray and confirmed by EGDs.The number and rate of esophageal cancers were also collected.Further,the cost of detecting one GC was evaluated.RESULTS The number of participants has decreased during the last four decades,from 39925 in 1983 to 12923 in 2021.The rate of those requiring EGDs decreased significantly in recent years(P<0.001).The number of participants diagnosed as having GC has also declined,from 76 to 10 cases.However,the rate of cases diagnosed as GC among the participants remained around 0.1%.The positive predictive value increased significantly in recent years except during 1983-1991.The number and rate of accidentally detected esophageal cancers have risen recently,from 0%in 2008 to 0.02%in 2021,one-fifth of the diagnosis rate of GC.One GC diagnosis costs approximately 4200000 Japanese Yen(30000 United States Dollars)for the X-ray screenings and EGDs.CONCLUSION X-ray GC screening in Hiroshima has been efficient,but one challenge is the cost.Esophageal cancers may also need to be considered because they have gradually increased in recent years.
文摘Gastric cancers are caused primarily due to the activation and amplification of the EGFR or HER2 kinases resulting in cell proliferation,adhesion,angiogenesis,and metastasis.Conventional therapies are ineffective due to the intra-tumoral heterogeneity and concomitant genetic mutations.Hence,dual inhibition strategies are recommended to increase potency and reduce cytotoxicity.In this study,we have conducted computational high-throughput screening of the ChemBridge library followed by in vitro assays and identified novel selective inhibitors that have a dual impediment of EGFR/HER2 kinase activities.Diversity-based High-throughput Virtual Screening(D-HTVS)was used to screen the whole ChemBridge small molecular library against EGFR and HER2.The atomistic molecular dynamic simulation was conducted to understand the dynamics and stability of the protein-ligand complexes.EGFR/HER2 kinase enzymes,KATOIII,and Snu-5 cells were used for in vitro validations.The atomistic Molecular Dynamics simulations followed by solvent-based Gibbs binding free energy calculation of top molecules,identified compound C3(5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-1H-isoindole-1,3(2H)-dione)to have a good affinity for both EGFR and HER2.The predicted compound,C3,was promising with better binding energy,good binding pose,and optimum interactions with the EGFR and HER2 residues.C3 inhibited EGFR and HER2 kinases with IC50 values of 37.24 and 45.83 nM,respectively.The GI50 values of C3 to inhibit KATOIII and Snu-5 cells were 84.76 and 48.26 nM,respectively.Based on these findings,we conclude that the identified compound C3 showed a conceivable dual inhibitory activity on EGFR/HER2 kinase,and therefore can be considered as a plausible lead-like molecule for treating gastric cancers with minimal side effects,though testing in higher models with pharmacokinetic approach is required.
基金Supported by Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Clinical Research Funding of Shandong Medical Association-Qilu Specialization,No.YXH2022ZX02031Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06.
文摘Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.
基金Supported by the Project of NINGBO Leading Medical Health Discipline,No.2022-B11Ningbo Natural Science Foundation,No.202003N4206Public Welfare Foundation of Ningbo,No.2021S108.
文摘BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.
基金Supported by Guangxi Key R&D Project(GuiKeAB18221095)Baise Scientific Research and Technology Development Plan of Baise City(BaiKe20211810)+1 种基金Open Project of Scientific Research in Guangxi Key Laboratory of Molecular Pathology of Hepatobiliary Diseases(GXZDSYS-005)Research Project of High-level Talents in Youjiang Medical University for Nationalities(01002018079).
文摘[Objectives]The anti-tumor activity of fractions from Buddleja officinalis Maxim.by petroleum ether,ethyl acetate,n-butanol and water solvent was studied.[Methods]The ethanol extract from B.officinalis Maxim.was extracted and then concentrated with petroleum ether,ethyl acetate,n-butanol and water,respectively,and the extracts were obtained.The inhibitory effects of the four different fractions on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the median inhibitory concentration(IC 50 value)was calculated.[Results]The four fractions inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol fraction had the best anti-tumor activity.The IC 50 values of the n-butanol fraction on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.08,1.58 and 0.12 mg/mL,respectively.[Conclusions]Petroleum ether,ethyl acetate,n-butanol and water fractions from the ethanol extract of B.officinalis Maxim.had certain anti-tumor effects,and the n-butanol fraction had the best anti-tumor activity.
