Aim: To estimate the prevalence of symptoms of depression, anxiety, stress and associated factors in a population of college students. Method: Cross-sectional study of psychological distress measured through the Depression, Anxiety and Stress Scale (DASS-21) in a sample of 1074 college students. Results: We found a moderate prevalence of depression (18.4%), anxiety (23.6%) and stress (34.5%) symptoms in our study population. Being <21, having problematic Internet use behavior, smoking, presenting insomnia and having a low self-esteem were independently associated with symptoms of depression, anxiety and stress. Being a woman, living with their family, having a stable partner, consuming alcohol frequently and having poor nutritional habits were significantly associated with symptoms of stress; lacking a stable partner was significantly associated with depressive symptoms; and frequent consumption of alcohol was significantly associated with symptoms of anxiety. Conclusion: We found a moderate prevalence of depression, anxiety and stress symptoms in our population. Interventions aimed at promoting mental health among college students should be implemented. In its plan for the prevention, treatment and overcoming of mental health disorders, the World Health Organization described mental health as fundamental to human health . Yet, meMost mental health problems appear by early adulthood, yet young adults rarely get any support for their mental health . FurtherGlobally, studies conducted on different samples of undergraduate students have identified a moderate to high prevalence of depression, anxiety and stress in this population ,21,22,23In Spain, mental health problems are highly prevalent in the general population , as wellA cross-sectional study of the prevalence of symptoms of depression, anxiety, stress and associated factors was carried out in a population of college students registered in San Jorge University (SJU) in Zaragoza (Spain).Our participants were undergraduate students registered in one of the bachelor’s degrees offered by SJU’s Faculty of Health Sciences, Faculty of Communication and School of Architecture and Technology during the academic year 2018–2019. Participant recruitment took place from September 2018 to May 2019. The students were informed about the aims of the study and the methods of data collection by a researcher in the classroom; a copy of the participant information leaflet and consent form was given to the students at this time. The students were assured that privacy and confidentiality would be maintained, and that they had a right to refuse to participate in the study or to withdraw consent to participate at any time without reprisal. Of a total population of 1341, 1074 students gave their consent to participate in this study and completed the questionnaire.2). BMI was trichotomized to: (1) low BMI (≤18.5 kg/m2), (2) normal BMI (18.5–24.9 kg/m2) and (3) high BMI/obese (≥25 kg/m2).The questionnaire was divided into two sections, namely sociodemographic characteristics (including anthropometry and habits) and psychological health. Sociodemographic data included a list of variables generally associated with psychological distress in younger populations ,21, namePhysical activity was measured using the short form of the International Physical Activity Questionnaire (IPAQ-SF). This tool measures the intensity, frequency and duration of physical activity over the last seven-day period. Metabolic equivalents (METs), defined as “the ratio of a person’s working metabolic rate relative to their resting metabolic rate” , are theInternet use was measured using Young’s Internet Addiction Test (IAT). This tool comprises 20 items answered on a 5-point Likert scale ranging from 1 to 5, indicating the extent to which they endorse each particular behavior. The IAT total score ranges from 0 to 100, where higher scores represent higher levels of severity of Internet compulsivity and addiction. Specifically, scores <50 suggest a controlled use of the Internet, scores between 50 and 79 suggest excessive Internet use and scores ≥80 imply that the participant is experiencing severe Internet addition, which impacts on his or her personal as well as social life . In thisWe assessed the quality of the participants’ diet through the Healthy Eating Index (HEI) in its Spanish version . The HEIThe presence and severity of insomnia was assessed through the Insomnia Severity Index (ISI). The ISI is a 7-item self-report questionnaire assessing the nature, severity and impact of insomnia experienced in the last month. A 5-point Likert scale is used to rate each item  yielding a total score ranging from 0 to 28. The ISI total score is interpreted as follows: absence of insomnia (0–7); sub-threshold insomnia (8–14); moderate insomnia (15–21); and severe insomnia (22–28) .The participants’ self-esteem was assessed using the Rosenberg Self-Esteem Scale (RSES). This tool consists of 10 items, five of which are expressed in positive statements and the other five in negative statements. Negative items were reverse-scored prior to analysis. The RSES uses a 4-point response scale  with total scores ranging from 10 to 40. Respondents are classified into three levels of self-esteem: high self-esteem (≥30 points), medium self-esteem (26–29 points) and low self-esteem (≤25 points) .Finally, symptoms of anxiety, stress and depression were measured through the Depression Anxiety Stress Scales (DASS-21). The DASS-21 consists of 21 items, 7 items per subscale: DASS-D (depression), DASS-A (anxiety) and DASS-S (stress). Respondents must rate the extent to which each statement applies during the past week on a 4-point Likert scale ranging from 0  to 3 (applied to me very much). Because the DASS-21 is a short-form version of the DASS (42 items), the final score for each sub-scale is multiplied by two and evaluated according to its severity rating index. Depression, anxiety and stress scores are calculated by adding up the scores of the items in each separate subscale. The results are interpreted as follows: DASS-A , DASS-D , DASS-S . This tool has been previously validated in a population of Spanish college students showing high levels of consistency for the three subscales .p = 0.05 and removal of p = 0.10) analysis in order to determine the predictive factors of psychological health in our sample . We performed a collinearity analysis in order to detect variables which showed a condition index ≥30. Subsequently, two analyses were carried out with and without outliers, with minimal differences between them. In this manuscript, we present the results from the analysis including outliers. Data codification, processing and analysis were completed using the statistical software Statistical Package for the Social Science  accepting a level of significance of p < 0.05.The sample characteristics were analyzed using frequency and percentage for qualitative variables and mean and standard deviation for quantitative ones. We used a Kolmogorov–Smirnov test to test for normality of distribution in our data. Bivariant analyses were carried out using Chi-Square, Mann–Whitney or t-test, as applicable. In addition, we carried out a binary logistic regression  prior to the start of this investigation. We confirm that each and every one of the national and international standards for ethical research with human subjects were respected and adhered to.A total of 1074 undergraduate students (71% women and 29% men) took part in this investigation. Age ranged from 18 to 42, with an average of 21.73 ± 5.12 years. The majority of our students were enrolled in a healthcare program (57.3%), had a normal BMI (69.8%), perceived their financial status to be medium (74.7%), did not have a stable partner (53.2%) and lived with their family (66.3%). In addition, 24.9% consumed tobacco habitually, 28% had a low level of physical activity, 23% experienced PIU, 42.9% had some degree of insomnia and 82.6% needed diet improvement see .p < 0.05). The symptoms of depression, on the other hand, were evenly distributed between our male and female participants (19.3% men and 18.1% women)  see .Of our participants, 22.5% presented symptoms of two mental disorders according to the DASS-21 questionnaire, and up to 9.7% of our sample experienced symptoms of anxiety, depression and stress simultaneously see .p < 0.05). In addition, being a woman, living with their family, having a stable partner, consuming alcohol regularly and following an inadequate or unhealthy diet were significantly associated with stress; not having a stable partner was associated with depression; and frequent alcohol consumption was associated with anxiety , anxiety (23.6%) and depression (18.4%) in our population. Previous studies carried out in Spain involving smaller samples have reported an even greater prevalence of psychological distress in our population ,29. SpecWorldwide, there is variation in the reported prevalence of psychological distress among college students. A systematic review of 24 studies estimated an average prevalence of depression of 30.5%, with results ranging between 10.4 and 80.5% . The samOf our participants, 37.4% presented symptoms of two or more psychological disorders. This association has been previously described both in the general population , as wellIn our sample, female students presented a higher prevalence of symptoms of stress and anxiety compared to male students. This is in agreement with previous studies, which also reported a higher prevalence of anxiety, stress and depression among women .The relationship between lifestyle habits and mental health has been studied in detail. Thus, physical activity has often been associated with psychological wellbeing through a range of mechanisms including the secretion of endogen substances such as endorphins, the activity of the regulation of stress responses through the hypothalamic-pituitary-adrenal (HPA) axis, the improvement of sleep quality and the development of self-regulation and other coping mechanisms ,45. HoweVarious possible explanations have been proposed to explain the relationship between tobacco and psychological distress in our population. First, it is likely that tobacco use and mental health problems have a common root; people who experience mental health problems may smoke to regulate feelings of low mood, stress and anxiety; smoking could also cause or exacerbate existing mental health problems . With rePIU has been studied in the past few years, both in the general population and, especially, in the young and adolescent. The negative consequences of PIU include, among others, a possible increase in stress and anxiety, as well as a lack of social communication and interaction ,50. ThisRecent studies ,52 have As has been reported in previous studies involving similar samples, we found an association between certain habits such as tobacco and alcohol consumption , presentIt is also worth highlighting that being enrolled in a healthcare program did not increase the risk of experiencing symptoms of depression, anxiety and stress in our sample. This is contrary to previous studies ,57, whicIt is possible that college students perceive vital events associated with college life as threatening to them, thus negatively affecting their mental health. For example, being under 21 was significantly associated with symptoms of depression, anxiety and stress . This isThis, to our knowledge, is the first attempt to establish an association between the symptoms of anxiety, depression and stress, and a large range of socioeconomic and behavioral variables, in a sample of Spanish college students. Furthermore, we believe that our results are highly representative of, and generalizable to, the population of college students in Spain, owing not only to our sample size but also to the standardized procedures of data collection and plausibility of the associations established. This has allowed us to draw a reliable picture of the psychological health and habits of our population of college students, which may serve as a starting point for the development and implementation of preventative and diagnostic interventions, and treatment services, to promote mental health and well-being.Some authors ,60 have This study has some limitations that need to be acknowledged. Firstly, the DASS-21 questionnaire is a suitable tool to screen for anxious, depressive and stress disorders, and may be useful to identify patients who are at risk of being affected by these conditions. However, additional tools should be used to establish a formal diagnosis. Secondly, the methodology employed in this investigation does allow for the establishment of associations between variables, but not causality. Finally, we would like to highlight that data collection took place over a period of eight months and, consequently, it is likely that academic life conditions were different for some of the students. For example, it is well known that factors such as the proximity of deadlines and exams may become a significant source of stress and anxiety for college students . FurtherFuture investigations in this area should attempt to address these limitations. In any case, we argue that our results bring to light the need to implement strategies to protect and, if applicable, improve the mental health and wellbeing of college students.We found a considerable prevalence of symptoms of depression, anxiety and stress in our population which, in some cases, do not occur in isolation, but coexist. In addition, we identified a number of factors associated with these symptoms. Factors including age, gender, self-esteem, sleep quality and living arrangements of college students, as well as specific behaviors relating to alcohol, tobacco and Internet use seem to be strongly associated with psychological distress in the college student population. We argue that our results can be helpful to design strategies for the early identification of mental health disorders, as well as psychological and other interventions leading to mental health promotion and wellbeing in the population of college students.


Exercise training for the intervention group included various sports games, outdoor activities, martial arts, yoga, and dance. Anthropometry, motor skills (7 tests), and cognitive skills (Raven’s Colored Progressive Matrices and Cognitive Assessment System) were assessed before and after an intervention period in both groups. Data were analyzed using repeated-measures ANOVA. (3) Results: Body weight significantly increased in both groups over time. Compared to the changes observed in the control group, the intervention group significantly increased in chest circumference (p = 0.022). In contrast, the control group demonstrated an increase in waist circumference (p = 0.001), while these measures in the intervention group remained stable. Participants in the intervention group improved running speed (p = 0.016) and standing broad jump (p = 0.000). The flexibility level was maintained in the intervention group, while a significant decrease was observed in the control group (p = 0.010). Children from the intervention group demonstrated progress in the bent-arm hang test (p = 0.001), unlike the control group subjects. Varied improvements in cognitive skills were observed for different variables in both intervention and control groups, with no robust evidence for PA-intervention-related improvements. (4) Conclusions: Preschool children’s participation in a preschool PA intervention improves their motor skills.(1) Background: Regular physical activity (PA) plays an important role during early childhood physical and psychological development. This study investigates the effects of a 9-month PA intervention on physiological characteristics and motor and cognitive skills in preschool children. (2) Methods: Preschool children ( Early childhood represents a crucial period for children’s physical and psychological development . RegularAccording to the current PA guidelines for youth, put together by the American College of Sports Medicine, children should accumulate at least one hour of PA daily as part of commuting, physical education, sport, free play, and structured exercise, whereby moderate- to vigorous-intensity of PA (MVPA) should be emphasized . PA recoRecent studies have shown that participation in PA may modify white matter integrity and enhance cognitive processes in youth ,21,22. MA total of 132 children  participated in this study for a nine-month period. All children attended a standard preschool program during the day at one of the preschool institutions in Novi Sad, Serbia. The intervention group consisted of 66 children who attended the preschool PA program (two 60-min sessions per week) in addition to their participation in a standard preschool institution program. The control group consisted of 66 healthy children from a single preschool institution who did not engage in any additional organized PA outside of the standard preschool program. All participants’ parents gave written consent for their children to participate in the study. This study was approved by the Institutional Review Committee of the University of Novi Sad (Ref. No. 44-01-02/2018-1) and was conducted under the Declaration of Helsinki.All participants were tested before and after the 9-month intervention period. The intervention group attended the preschool PA program  in addition to their participation in a standard preschool institution program. The control group participated in the standard preschool program but did not engage in any additional organized PA outside of that program. Preintervention and postintervention assessments in both groups included measurements of anthropometric characteristics, motor skills, and cognitive function (Raven’s Coloured Progressive Matrices and Cognitive Assessment System (CAS).The intervention group participated in a PA intervention that consisted of two 60-min PA sessions weekly over a period of 9 months (September 2018 to May 2019). PA intervention was carried out by experienced physical education teachers, specialists who work with preschool children. The intervention included the following activities: athletics, sports games , gymnastics, yoga, outdoor activities, aerobic, martial arts, and dance . No signThe skill-related component of the PA intervention included balance, coordination, timing, agility, balance, speed, flexibility, strength, endurance, and agility-based activities. One of the goals of this component of the intervention was to improve the speed of solving complex motor problems, which is a part of cognitive training. Types of exercises included perceptual-motor activities, creative movements, rhythm and dance, stunts, tumbling, running, jumping, throwing, games, and basic elements of team sports. This variety of movement raises the interest of preschool children in skill-related training. The control group was exposed to the standard program for preschool institutions.Anthropometric characteristics were assessed according to the recommendations of the International Biological Program (IBP)  and inclThe assessment of motor skills included seven tests that are described in detail below ,33.20-m dash. Participants stood behind the start line until the command “GO”, after which they had to run for 20 m as fast as possible. Participants were instructed to run in pairs. The score was recorded in tenths of a second using a stopwatch.Obstacle course backward. Participants had to walk backward on all four limbs for the distance of 10 m, climb to the top of a Swedish bench (30 cm), and crawl through the frame. The scores were recorded in tenths of a second using a stopwatch.Standing broad jump. Participants had to jump with both feet from the reverse side of a Reuter bounce board onto a carpet of marked length. The score was the length of the jump recorded in cm.Arm plate tapping. Participants had to alternately tap two plates on a tapping board for 15 sec with their dominant hand while holding the other hand in between the two plates. The number of double hits was recorded.Seated straddle stretch. The subjects sat on the floor in a straddle position, leaning against the wall, and reached forward as far as possible along a straight-angle ruler. The score was the maximal reach measured in cm.Bent-arm hang. Participants were instructed to hang in the pull-up position as long as possible (chin above the bar), holding the bar with an under-grip. The score was the time of the hold recorded in tenths of a second.Crossed-arm sit-ups. Participants had to lie down on their back with knees bent and arms crossed on the opposite shoulders. They were instructed to rise into a seated position and return back to the starting position while the instructor’s assistant held the participants’ feet. The maximal number of correctly performed repetitions within 60 s was recorded.Prior to the assessments, each test was demonstrated by the examiners. Subjects were allowed to perform a trial attempt for each test conducted.Raven’s Colored Progressive Matrices (CPM) represents a nonverbal test of intellectual abilities and discursive thinking, composed of perceptual, figurative material organized in several series, in which the tasks were arranged according to difficulty, from simple to complex . The exaThe children were tested individually by trained psychologists in a quiet room of their schools. The instructions for applying the test were explained to participants in detail to facilitate application. A group of drawings that made up one whole or one principle was presented, with one of the drawings missing. The participant’s task was to discover specific relationships between the figures shown in the picture in a group of six drawings. The participant had to choose one of the six offered figures that fitted, according to a certain relationship. The number of correctly identified drawings was taken for further analysis . A totalThe Cognitive Assessment System (CAS)  was admiA CAS battery test was conducted for each subject individually. Testing, using the basic form with eight CAS battery subtests, took an average of about 40 min. The time for solving the tasks, as well as the number of correct answers, was entered in the results form, where all subtests were later scored, and the subscale and total score on the test were determined.Calculating raw scores differed depending on the subtest and involved the application of a certain method for recording the number of correct answers, incorrect answers, and the reaction time. Due to its complexity, the CAS assessment was completed only in a subset of 62 participants  at the baseline and follow-up.t-test and the chi-square test were used to compare demographic characteristics between the two groups. Furthermore, 2 × 2 repeated-measures ANOVA was used to compare differences in outcome measures after the intervention period between the two study groups, and the paired-samples t-test was used for calculating differences within subsamples. Moreover, p-values of <0.05 were considered statistically significant. No corrections were applied for multiple comparisons. The data are reported as mean ± SD or frequency (percentage). The data were analyzed using the statistical package SPSS version 20.0 .The independent-samples The sample consisted of a total of 132 children aged 5.5 ± 0.7 years, with a mean height of 116.09 ± 6.37 cm and a mean weight of 21.71 ± 4.27 kg. Although no statistically significant differences were observed between the intervention and control groups at baseline, a greater proportion of children in the intervention group were boys and were either in the underweight or normal weight category compared to those in the control group .20-m dash test has been noted in favor of the intervention group (p = 0.016). A significant difference was detected in the standing broad jump test (p = 0.000). This was particularly noticeable among the intervention group, considering that their mean values at baseline and postmeasurement were 108.09 ± 24.70 vs. 121.98 ± 20.44 cm, respectively. Intervention group subjects maintained their flexibility level, whilst the control group reduced their flexibility over time (p = 0.010), which can be noted in the seated straddle stretch test results. Statistically, a significant change was observed in the bent-arm hang test (p = 0.000) due to the improvement of the intervention group and impairment for the control group. Nevertheless, obstacle course backward (agility), arm plate tapping (simple movements), and crossed-arm sit-ups (repetitive core strength) remained stable over time.The results of motor skills tests indicate certain changes among participants. Improvement in the p = 0.03 and p = 0.04, respectively). In verbal–spatial relations, the results demonstrated that significant changes occurred in favor of the control group, while the change in expressive attention was in favor of the intervention group.The results on Raven’s CPM (cognitive skills test) significantly improved from preintervention to postintervention in both groups . The resThis study evaluated the effectiveness of a 9-month PA intervention on anthropometric characteristics, motor skills, and cognitive skills in preschool children. Significant improvements in running speed, jump distance, upper body strength, and flexibility were observed in the intervention group when compared to the control group. Both groups showed improvements in several cognitive test results, although each group demonstrated this improvement in a different subtest of variables, showing no robust evidence of PA-intervention-related improvements. While body weight increased in both groups during the 9-month period, the increase in body weight was greater in the control group versus the intervention group. Taken together, findings from this study suggest that regular PA contributes to the development of motor skills of preschoolers, while its effects on cognitive function remain inconclusive.Only a paucity of studies to date has examined the effects of exercise training on physiological characteristics and motor and cognitive skills in preschool children ,37,38. TGiven that insufficient PA in children is a global health problem, PA intervention studies such as this one can be a useful tool to further emphasize benefits that can be obtained through regular PA. Results from such studies could serve to pinpoint both the problem and potential strategies for informing the future development of curricula for preschool institutions.However, a recent meta-analysis on the effectiveness of PA interventions in children who are 0 to 5 years old showed a small but statistically significant positive effect for interventions targeting increases in children’s moderate-to-vigorous PA, while no evidence of effect was observed for changing their light PA . Even thThe strengths of this study include a 100% completion rate of study assessments (with the exception of the CAS test), a long PA intervention period (9 months), and trained staff involved in the delivery of the intervention and research data collection.This study has several limitations. Small sample size and nonrandom assignment of participants to intervention and control groups represent research design limitations. In addition, the CAS assessment was completed only in a subset of participants. Moreover, although physiological changes observed in the intervention group were significant, it remains uncertain to what degree the PA intervention contributed to those changes and to what degree such changes were a result of normal growth and maturation. Finally, the effects of the PA intervention in this study could have been confounded by contextual variables such as socioeconomic constraints, lifestyle, and other institutional rules and practices that were not measured or controlled in the present study.This study provides evidence that a 9-month PA intervention has beneficial effects on preschool children, demonstrating a positive influence on their motor and cognitive skills. Future studies with a larger sample size and randomized control design should examine whether PA interventions have effects on cognitive function in preschool children.


Patients with amnestic mild cognitive impairment (aMCI) are at high risk of developing dementia. This study used resting-state functional magnetic resonance imaging (rs-fMRI) and an independent component analysis (ICA) approach to explore changes in functional connectivity (FC) in the default mode network (DMN), executive control network (ECN), and salience network (SN). Thirty patients with aMCI and 30 healthy controls (HCs) were enrolled. All the participants underwent an rs-fMRI scan. The brain FC in DMN, ECN, and SN was calculated using the ICA approach. We found that the FC of brain regions in DMN decreased significantly and that of brain regions in ECN increased, which was in accordance with the findings of previous studies on Alzheimer's disease (AD) and aMCI. We also found that the FC of brain regions in SN increased, which was different from the findings of previous studies on AD. The increase in FC in brain regions in SN might result from different pathophysiological states in AD and aMCI, indicating that a decrease in FC in SN does not occur in a person with aMCI. These results are consistent with those of previous studies using the voxel-mirrored homotopic connectivity approach and seed-based correlation analysis. We therefore considered that the decrease in FC in DMN and the increase in FC in ECN and SN might be peculiar patterns observed on the rs-fMRI of a person with aMCI. These findings may contribute to the development of imaging biomarkers for the diagnosis of aMCI. Mild cognitive impairment (MCI) is a pathological state between normal cognition and dementia. MCI is associated with many neurological diseases such as neurodegenerative diseases, cerebral vascular diseases, and metabolic symptoms. MCI has slight impact on activities of daily living (ADL), but patients with MCI have a high risk of developing dementia, for which there is no effective treatment. The annual conversion rate from MCI to dementia is reportedly ~10–15%, which is 10 times that in the normal population . MCI is Great efforts have been made to explore diagnostic and screening tools for aMCI, such as psychological batteries , 4, 5, cHowever, there is insufficient evidence supporting the use of rs-fMRI in the diagnosis of aMCI. Hojjati et al.  reportedIndependent component analysis (ICA) is a new method that separates signals of interest from noise in FC analysis . In contPatients with aMCI seen in our hospital between June 2018 and October 2019 were enrolled in this study. Healthy volunteers [the healthy control (HC) group] were also recruited. The study was conducted in strict compliance with the guidelines of the Declaration of Helsinki of the World Medical Association (2000) and was approved and supervised by the ethics committee of the First Affiliated Hospital of the Heilongjiang University of Chinese Medicine . All participants signed the informed consent form after the study protocol was explained to them in detail.We used the diagnostic criteria of the Chinese Dementia and Cognitive Impairment Diagnosis and Treatment Guidelines (2018) . PatientThe inclusion criteria for the control group were as follows: (1) no complaints of cognitive impairment; (2) no abnormalities detected on neurological examination and no visual or auditory impairment; (3) MMSE ≥ 27 points and multidimensional neuropsychological evaluation results within the corresponding normal range; and (4) no infarction or focal lesions on a conventional MRI scan.The exclusion criteria for all subjects were as follows: (1) a history of nervous system or mental disorder ; (2) incomplete demographic data; (3) inability to complete all neuropsychological tests; (4) inability to undergo image artifact or MRI examination; and (5) scanning head motion parameters of translation > 2 mm, rotation > 2°.The cognitive state of all subjects was graded with a battery of neuropsychological assessments including the MMSE, Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT), Digital Span Test (DST), Verbal Fluency Test (VFT), and Auditory Verbal Learning Test (AVLT); these were performed by an experienced neurologist who was blinded to the allocation of subjects and MRI analysis. The ADL scale, Hamilton Depression Rating Scale (HAMD), HIS, Global Deterioration Scale (GDS), and Clinical Dementia Rating (CDR) were also used for assessment.A Philips 3.0T MR scanner  was used in the present study. All participants were asked to arrive 30 min before their test. They were asked to be fully rested to eliminate psychological factors such as fear, anxiety, and expectation. To reduce possible involuntary head movements caused by respiration and heartbeat, sponge pads were inserted on both sides of the head in the eight-channel parallel acquisition head coil (SENSE-N-8) for fixation.First, all subjects were scanned using the conventional sequence, including T1WI, T2WI, and fluid-attenuated inversion recovery to exclude subjects who did not meet the inclusion criteria. Then, three-dimensional (3D) structural imaging data acquisition (T1W-3D-TFE sequence) was performed; the scanning parameters were as follows: time of repeat (TR) = 8.3 ms, time of echo (TE) = 3.8 ms, field of view (FOV) = 256 × 256 mm, flip angle (FA) = 12°, slices = 188, slice thickness = 1 mm, slice gap = 0 mm, and total scan duration = 4 min 52 s. Finally, functional imaging data (FE-EPI sequence) were collected using the following scanning parameters: TR = 2000 ms, TE = 30 ms, FOV = 220 × 220 mm, FA = 90°, matrix = 64 × 64, slices = 36, slice thickness = 3 mm, slice gap = 1 mm, total scan duration = 8 min 6 s, and a total of 240 time points.http://rfmri.org/DPARSF) software package was run for image preprocessing. This process involved (1) converting data from the Digital Imaging and Communications in Medicine format to the NIfTI format; (2) removing the data of the first 10 time points to avoid the unstable interference of the MRI signal at the beginning of acquisition; (3) slice timing to ensure that all voxel acquisition times in a volume were consistent in theory; (4) realignment, the correction of small head movements between every volume of the subject ; (5) normalization, alignment of the local spatial data of different subjects to the Montreal Neurological Institute standard space and their resampling into 3 × 3 × 3 mm voxels; and (6) spatial smoothing, which is performed to reduce the registration error and increase the normality of the data for statistical analysis. This was done with the Gaussian kernel as the full width at half maximum 8 × 8 × 8 mm.Based on a MATLAB platform , a DPARSF . First, data were imported, the number of components was estimated using the software (30 in this study), and the dimensionality reduction was defined automatically  using principal component analysis. The infomax algorithm was used. We selected the ICASSO method using both the “RandInit” and the “Bootstrap” options. The number of operations was 100. The minimum cluster size was 80, and the maximum cluster size was 100. Then, a spatial–temporal regression was used for the back-reconstruction algorithm, and the spatial components, time series of individuals, and groups were reconstructed. The spatial components were standardized to estimate the Z-scores, and then the average Z-score across the whole cluster was calculated. Based on information from a prior study  was used for statistical analyses. Measurement data were presented as the mean ± standard deviation, and non-normally distributed data were presented as median (quartile). Chi-square test was used for comparing the classified variables between the two groups, and an independent-sample http://www.fil.ion.ucl.ac.uk/spm/) was used for statistical analyses of imaging indicators. In the control and aMCI groups, a single-sample t-test  was used in the three network templates, and a combined template of the two single-sample brain FC areas was made using xjview  software. Then, SPM12 software was used to run the t-test for two groups of the independent samples. The union template was used as the mask. Age, gender, and years of education were used as covariates. The statistical threshold was as follows: voxel level, P = 0.001 (uncorrected); cluster level, P < 0.05 (FWE-corrected); and cluster voxel size, >50. Thus, a t-value map with a significant between-group difference was obtained, and the results were displayed by xjview software.Statistical parametric mapping (SPM)-12 software (P < 0.01). Regarding clinical assessments, no significant between-group differences were observed in ADL and HIS (P > 0.05). However, the aMCI group exhibited higher HAMD, CDR, and GDS scores (indicating a poor performance) than the HC group (P < 0.01). The diagnoses of these patients were confirmed on the basis of the above findings  and 30 healthy subjects  were enrolled in the study. All the subjects were right-handed. findings .r = 0.632; P < 0.001; r = 0.472; P = 0.009; In DMN, the FC of the bilateral anterior precuneus  and righr = −0.409; P = 0.025; In ECN, the FC of the right posterior parietal cortex  was incrr = −0.438; P = 0.015; In SN, the FC of the left anterior insula  was incrThe anatomical model of DMN, ECN, and SN detected using ICA approach in the present study are summarized in In the present study, we investigated changes in the cerebral FC in DMN, ECN, and SN in patients with aMCI using rs-fMRI. First, we found that the significant decrease in FC in brain regions can be attributed to DMN and the increase in FC in brain regions can be attributed to ECN; these findings are in accordance with previous studies on AD and MCI. This confirmed the reliability of our experimental system. Second, the most important finding in this study was that the increase in FC in brain regions can be attributed to SN, which is different from the previous findings in patients with AD. These results might reflect the pathophysiological state of aMCI, which requires further confirmation by setting up an AD group in the future investigation. The results are in agreement with those of previous studies using the SCA  and VMHCOur clinical and neuropsychological examination findings confirmed the diagnosis of the patients with aMCI. The MMSE and MoCA scores; TMT and DST results in both directions; and VFT results, GDS and HAMD scores, and AVLT results  indicated a worse state in the aMCI group. However, there were no between-group differences in ADL and HIS. These findings are consistent with the diagnostic criteria used in the present study  as well We found that the FC of the bilateral anterior precuneus and right medial frontalis gyrus, which belong to DMN, was reduced significantly in the aMCI group than in the HCs group . The subDMN is the most basic resting-state network, and it plays a role in integrated primary perception, advanced cognitive function, situational memory extraction, self-consciousness, and cognitive processes. It is also closely related to social cognition, spatial perception, and other brain functions . AnatomiWe found that the FC of the right posterior parietal cortex in ECN was increased in the aMCI group than in the HC group , which wImportantly, we found that the FC of the left anterior insula in SN was increased significantly in the aMCI group than in the HC group , which wInterestingly, previous studies using the SCA and VMHC approaches have obtained similar results, that is, a decrease in DMN and an increase in ECN and SN in patients with aMCI , 26. We,The relationship among these three networks is complicated and multidimensional and is not fully understood. Normal function with flexible interactions among DMN, ECN, and SN plays a vital role in the maintenance of normal social behavior . These nThere are several limitations to this study. First, our study lacked an AD group; this was the main limitation of our study. We only performed comparisons between patients with aMCI and HCs. From the results of the present study, we cannot obtain direct evidence concerning the difference between AD and aMCI. Moreover, although we found the depression scores in aMCI group were significantly higher than those of HC group, we don't know the depression state in AD patients. Thus, the potential confounding role of the depression in the cognitive impairment is uncertain in the present experimental system. Hence, adding patients with AD to these comparisons would be more meaningful. In the future, we will set up an AD group to perform a direct comparison that will permit a stronger conclusion. Second, we did not perform more neuropsychological assessments for testing the non-memory domains to demonstrate that there was no non-memory impairment in the included patients. Although it has been reported that patients with aMCI may suffer from other impairments as well, such as impairment of executive function , the incTaken together, we found that in the aMCI state, the FC of brain areas in DMN was decreased, whereas that in ECN was increased, which is in agreement with the changes seen in patients with AD. However, FC in SN was also increased in patients with aMCI, which was contrary to the findings in patients with AD, indicating that damage to FC in SN does not occur in the aMCI stage; this could mean that there are differences in the pathophysiological states between AD and aMCI. Compensatory response may occur in the aMCI state but seldom in the AD state . MoreoveThe FC of brain regions was decreased in DMN and increased in ECN and SN, which may be a peculiar pattern observed on rs-fMRI in the aMCI stage. These findings may contribute to developing imaging biomarkers for the diagnosis of aMCI; this would be further beneficial for ameliorating clinical outcomes and improving QOL of patients with dementia.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the ethics committee of the First Affiliated Hospital of the Heilongjiang University of Chinese Medicine . The patients/participants provided their written informed consent to participate in this study.XL, FW, XL, TY, and TA developed the original idea and designed the approach. XL, FW, XL, DC, LC, XJ, XY, and TY contributed to acquisition, analysis, or interpretation of data for the work. XL, FW, XL, and TA wrote the first draft. TY and TA revised the manuscript critically for important intellectual content. TA and TY supervised the study. All authors approval of the final version to be submitted.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Previous data have shown that patients with metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement (BPE) could be refractory to the medical treatment. In this context, the evidence suggests a role for statin use in LUTS/BPE patients. The present systematic review aimed to evaluate the impact of statins on the treatment of men with LUTS/BPE. This review has been registered on PROSPERO (CRD42019120729). A systematic review of English-language literature was performed up to January 2020 in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA statement) criteria. Retrieved studies had to include adults with LUTS connected to BPE treated with statins drugs for metabolic syndrome. After removing duplicates, a total of 381 studies were identified by the literature search and independently screened. Of these articles, 10 fit the inclusion criteria and were further assessed for eligibility. Data from our systematic review suggest that a long-term therapy with statins, at least 6 months, is required to achieve significant impacts on prostate tissue and LUTS. Moreover, besides statins’ direct activity, the risk reduction of LUTS might be connected to the improvement of hypercholesterolemia and MetS. The role of statins for the treatment of LUTS/BPE may be beneficial; however, evidence from robust studies is not enough, and more clinical trial are required.  Lower urinary tract symptoms (LUTS) in men are frequently associated with bladder outlet obstruction (BOO) and benign prostatic enlargement (BPE), often due to benign prostatic hyperplasia (BPH) . LUTS arDifferent classes of drugs are currently available for the treatment of LUTS/BPH: alpha-blockers, 5-alpha-reductase inhibitors (5-ARI), inhibitors of phosphodiesterase-5 (PDE5-i), anti-cholinergic drugs, and beta-3 adrenergic receptor agonists .Recent papers have shown a significant correlation between metabolic syndrome (MetS) and LUTS/BPE ,6. In a Moreover, De Nunzio et al., in a 2012 systematic review, evaluated 11 papers about the relationship between BPH and LUTS. The cumulative evidence summarized in this review suggests an association between MetS and its mediators, and the development of BPH . MetS is a cluster of metabolic components, including obesity, reduced HDL cholesterol, high blood pressure, high triglyceride and insulin resistance . It is aInterestingly, previous data have shown that patients with MetS could be refractory to medical treatments and may exhibit symptoms persistence after surgery ,11. In fIn this context, the evidence suggests a role for statin use in LUTS/BPE patients ,13. StatA systematic review of English-language literature was performed up to January 2020 in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA statement) criteria [The retrieved studies had to include adults with LUTS connected to BPE treated with statins drugs for metabolic syndrome. www.york.ac.uk/crd/guidance). Randomized clinical trials, retrospective, prospective, observational, single-arm studies, and comparative studies on humans, were included, while case reports and reviews, letters to editors, papers on animals and “full text not available in English” were excluded. According to the predefined inclusion and exclusion criteria, titles and abstracts were screened, and articles categorized. After reading the abstract, a more thorough assessment was performed by looking at the full texts of the paper. References from the included studies were manually retrieved to identify additional studies of interest. A new excel table was built including data from the selected articles and including the numbers of participants, interventions, comparators, outcomes, and study design (PICOS), as indicated by the Systematic Review Guidance of the Centre for Reviews and Dissemination of the University of York (UK)  was evaluated according to the Cochrane collaboration risk of bias . For nonAfter removing duplicates, a total of 381 studies were identified by the literature search and independently screened. Of these articles, 10 fit the inclusion criteria and were further assessed for eligibility : 3 retroOverall, the risk of bias of RCTs was deemed to be low , whereasp < 0.001). The strength of this study is the high number of patients enrolled and the long follow-up period (about 17 years), although they have considered only white men  and patients could not use the same dose of statins.St Sauver et al.  conductep < 0.001). In addition, the PSA reduction in group B was statistically significant when compared to group A (p < 0.001). PSA reduction was higher in the C and D groups (dutasteride groups) than in the B group. However, the difference in PSA reduction between groups C and D was not statistically significant (p = 0.682). Interestingly, PV  also showed a reduction in groups B, C and D (p < 0.001), with a statistically significant difference between groups A and B (p < 0.001), but not between groups C and D (p = 0.762). Statin users and nonusers were also compared, excluding dutasteride users. Statin users showed a surprising higher likelihood of PSA reduction  and PV reduction  after 1 year than nonusers. In conclusion, the study demonstrated that serum PSA, PV, and total cholesterol were decreased in BPH patients taking statin medication for 1 year compared with the group taking α-blocker alone. Additionally, the effect of 5ARI on the reduction of PSA and PV was not affected by adding a statin. Statin administration reduced PSA and PV in BPH patients. This infers that statin medication could improve LUTS in addition to preventing cardiovascular disease, which might play a role in the chemoprevention of prostate cancer.In the study from Lee et al., the authors evaluated the effects of statins with alpha-blockers and 5-ARI, investigating changes at the time of initial treatment and after 1 year. Patients were divided into four groups according to medication by Lee et al. : group AThis study had some limitations. First, the effect of alpha-blockers was considered to be the same, and they did not subdivide into categories for statin.Another retrospective study was conducted by Davis et al. , evaluatHowever, in 14,354 patients with no Charlson comorbidities, statin use was significantly associated with an increased risk for BPH , but not for sexual disorder. However, the presence or absence of hyperlipidemia could have affected study results, as hyperlipidemia was likely more common among statin users. Moreover, other drugs that may affect prostate and sexual function, such as phosphodiesterase inhibitors and alpha blockers, were not accounted for.p = 0.012), without any difference between the two statin drugs. Moreover, both atorvastatin and simvastatin treatment significantly reduced PV. However, the mean PV in the simvastatin group was smaller than in the atorvastatin group after 12 months. They also evaluated testosterone levels, without statistical difference between the three groups. The most important limitation of this study is that the patient number in each group is relatively low. Zhang et al.  evaluatep < 0.46); instead, PV was significantly lower in patients taking statin  and combined therapy  at the end of the trial. Maximum urinary flow rate (Qmax), IPSS, postvoid residual urine volume (PVR) and QoL significantly changed in all three groups.Cakir et al.  comparedp < 0.0001 vs. HR alpha blocker −3.16 vs. HR statin −1.55), IPSS  and QoL . The strength of the study is the randomization and the number of patients, evaluating not only statins vs. placebo, but also combined therapy with alpha-blockers. The weakness of this study is the duration of 6 months, and the absence of reporting any side effects of statins therapy.However, combined therapy was found to be superior in improving Qmax . Instead, the risk of having BPE progression in the other statin groups did not significantly differ from the control cohort. Moreover, the trend analysis revealed that the effect of statin use on decreasing BPE progression was related to the length of statin intake (p < 0.001). Shih et al. evaluated statins’ effect on BPE progression in relation to the duration of therapy (31 days minimum to >365 days). Although this study shows beneficial statin effects on BPH progression, a limitation of the study is represented by the lack of a subdivision via different statins. Moreover, the authors have studied the BPH progression without reporting baseline levels of BPH.The risk of having BPE progression  in the cohort with statin use >365 days was significantly lower than in the control cohort , were slightly greater than 1. For moderate of worse LUTS, HR was 1.03, and 95%CI was 0.94–1.13; for severe LUTS, HR was 1.06 and 95%CI was 0.92–1.13. The hazard ratio did not increase with duration of use.Moreover, in their analysis they compared men using a statin with or without hypertension medication with men using only hypertension medication. They observed that men using a statin drug and hypertension medication had essentially the same risk of LUTS as men only using hypertension medication, and men who were not using either medication had a lower risk of LUTS than men taking hypertension medications.In this large prospective cohort of older men, statin drug use did not protect against LUTS incidence or progression. p = 0.00 vs. p = 0.02). After 4 months, there was no difference between the two groups in terms of IPSS (p = 0.69), PV (p = 0.90) and PSA (p = 0.16). Thus, short-term lovastatin treatment does not seem to have any additional effect on IPSS, TPV and PSA in men with BPE treated with finasteride. This 2008 study was one of the first clinical studies developed to understand the effect of statin on LUTS/BPH. Unfortunately, this trial lasted only 4 months and the maximum effect of finasteride is often not seen until after 6 months of therapy.In a clinical study, Stamatiou et al.  divided In a phase 2, double blind, randomized clinical study, Mills et al.  divided At the end, erectile function, with the International Index of Erectile Function Questionnaire (IIEF) questions 3 and 4, which evaluated the strength and durability of the erection, was also assessed at baseline and at the end of the study. This study showed no statistical difference between the atorvastatin and placebo groups. The design of this study was a double-blind, randomized, placebo-controlled clinical study to evaluate the effect of atorvastatin on BPH. They also reported side effects of atorvastatin, and a consideration about statins and erectile function. However, the authors considered only a period of 6 months.Hall et al.  evaluateBeside reducing cholesterol levels, statins also have anti-inflammatory and anti-apoptotic roles , involviIn the present study, we systematically reviewed the literature investigating the association between BPE and the use of statin drugs. A meta-analysis by Yang et al.  was publAll the studies, except those of Mills et al. , StamatiMills et al.  determinp = 0.69), PV (p = 0.90) and PSA (p = 0.16) after 4 months of treatment. However, it could be supposed that statins would have an effect only after the maximum finasteride effect had occurred (minimum of 6 months). In Stamatiou et al.’s study , there wMoreover, it is possible that statins, acting on prostate growth and apoptosis, similarly to 5-alpha reductase inhibitor (5-ARI) drugs, need a longer period time to manifest results in terms of BPE.In fact, Shih et al.  considerIn this regard, only this study assessed this important aspect differently, and although specific recommendations cannot be given with certainty, the data suggest that longer statin prescription (1 year) is more beneficial than shorter duration. It is also important to discuss the potential role of confounding factors, such as diabetes, which may affect or even influence the efficacy of statin. In this context, for example, Shih et al.  evaluateMondul et al.’s study  was a laThe same considerations could be made for Davis et al.’s study . In factRusso et al.  showed tThus, in addition to their direct role in prostate growing, statins, improving MetS parameters and reducing systemic inflammation, might offer a better answer to LUTS therapy. LUTS due to prostate enlargement, and improving with statins, was demonstrated by Hall et al.’s study . In factRegarding statins safety, the American Heart Association have stated that, despite statins’ serious adverse effects, such as myopathy, new diagnoses of diabetes mellitus and hemorrhagic strokes, in the patient population to whom statins are recommended by current guidelines, the cardiovascular benefits far outweigh any safety concerns . Mills eAdditionally, lower levels of testosterone were reported as an adverse effect of statin therapy ,38. In tMills et al.’s prospective study  considerDavis et al.  performeMoreover, there were no statistical differences in testosterone levels between the simvastatin group, the atorvastatin group and the control group in Zhang et al.’s study .There are still many limitations in this systematic review. First, there are few studies on the correlation between BPH and statins, with a need for further evidence. Second, we have considered only English-language studies, so there is a possible language bias. Third, we gained heterogeneous outcomes due to the different kinds of measurements of BPH and LUTS. Fourth, the available studies of this systematic review have used different statins and different doses of statins, so it is difficult to evaluate if statins’ effects on BPH are related to a particular kind of statin, or if they are dose-dependent.However, taking together all these findings and the potential role of statins in BPH/LUTS, we would encourage the performing of an RCT assessing its efficacy when added to low dosage PDE5i or alpha-blockers. Recent evidence, in fact, has demonstrated that statins inhibit inflammation, angiogenesis, cell proliferation, migration/adhesion, and invasion, and promote apoptosis . HarshmaStatins, with their pro-apoptotic and anti-inflammatory proprieties, showed beneficial effects on LUTS in patients with BPE/BPH in most of the trials evaluated. Data from our systematic review suggest that a long-term therapy with statins, for at least 6 months, is required to achieve significant impacts on prostate tissue and LUTS. Moreover, besides statins’ direct activity, the risk reduction of LUTS might be connected to the improvement of hypercholesterolemia and MetS.Despite most of the evidence seeming to support a protective effect of statins on the prostate, improving BPE and LUTS, the results are still controversial, not allowing a definitive indication of the actual effectiveness and clinical meaningfulness. More prospective studies, with multivariate analysis and evaluating wide populations, are needed for a better comprehension of this relation.


Objectives: The present study was undertaken to investigate the relationship between acupuncture therapy and surgery rate.Design: Matched, retrospective cohort study.Materials and Methods: From nationwide health insurance data , patients with new cases of knee osteoarthritis that occurred between January 1, 2004 and December 31, 2010 were analyzed. Patients were divided into an acupuncture group (AG) and a control group (CG), based on records of acupuncture therapy. Propensity scores were calculated by using gender, age, income level, and Charlson comorbidity index (CCI), with the groups matched at a ratio of 1:3 (AG:CG). The final analysis period was 2 years after the first acupuncture therapy for AG and 2 years after initial diagnosis for CG; surgery rates were compared between the two groups. Stratified analyses were performed based on age, gender, and income level; sensitivity analyses were performed based on the frequency and duration of acupuncture therapy.Results: Propensity score-matched AG and CG included 8,605 and 25,815 subjects, respectively. Post-matching surgery rates were 0.26 and 0.93% in AG and CG, respectively. For all age groups, AG showed a lower surgery rate than CG. In the analysis based on gender, the female group showed a significantly lower hazard ratio of 0.225. In analysis based on income level, the results of the entire group were significant, with the lower income group showing the lowest hazard ratio. In sensitivity analyses, AG tended to show a lower surgery rate than CG.Conclusions: The present study demonstrated that acupuncture therapy is associated with a low rate of surgery for knee osteoarthritis. Additional studies are needed to support this conclusion. Osteoarthritis is a degenerative disease associated with degeneration of the ligament and cartilage surrounding the joint; it exhibits gradual infiltration, loss of cartilage, structural change in the bone below the cartilage, and osteosclerosis, accompanied by bony spurs. Patients with knee osteoarthritis present with various symptoms, such as pain, muscle atrophy, stiffness, and limited range of motion . Pain isKey treatment modalities recommended for patients with knee osteoarthritis in most international guidelines include patient education, exercise, and diet . When neNon-surgical treatments are typically administered to patients with early- and mid-stage knee osteoarthritis; among such methods, physical and acupuncture therapies are safe and effective . In partAlthough the effects of acupuncture therapy on functional improvement and pain relief have been identified in cases of knee osteoarthritis, there have been no studies regarding the relationship between acupuncture therapy and knee surgery. Accordingly, the present study aimed to retrospectively review 2002–2013 Korean cohort data to investigate the relationship between acupuncture therapy and surgery rate for knee osteoarthritis.The present study used 2002–2013 cohort data published in 2014 by the National Health Insurance Service of Korea. These data comprise random sampling of 1,025,340 people, representing ~2.2% of the total Korean population, for general research on the health status and health care utilization of all Koreans. The database included all medical claims filed from January 2002 to December 2010. In this study, diseases were classified according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). For traditional Korean medicine (TKM), the Korean Standard Classification of Diseases (TKM), up to the end of 2009, was used. The present study was reviewed and approved by the Institutional Review Board of Jaseng Hospital of Korean Medicine (JASENG 2018-01-007).* was selected as the diagnosis representing knee osteoarthritis, based on review of existing studies and consensus among the researchers . Of the patients with records of acupuncture therapy, patients who were determined to show clinical significance, as agreed upon by the researchers, were considered candidates for the acupuncture group (AG). Subsequently, AG was established for patients who received at least 2 rounds of acupuncture therapy within 6 weeks after the initial diagnosis of knee osteoarthritis , N2072*, N2077*, N2712*, N2717*, N0691*, N0692*, N0694*, N0702* (diagnostic condition), N0707* (diagnostic condition), E7500 (diagnostic condition), N0821*, N0822*, N0826*, and N0827* were selected based on reviews of existing studies and consensus among the researchers ; considering the size of each group, the groups were matched at a ratio of 1:3 (AG:CG) . Data frn = 3,035, 35.20%) in the 70–79 years' age group, while CG had the highest number of subjects  in the 60–69 years' age group. With respect to gender, both groups had a higher percentage of females, with AG  showing a higher percentage than CG   . The num 60.21%) . The medp = 0.307).In the overall analysis, AG and CG showed pre-matching surgery rates of 0.26 and 0.76% and post-matching surgery rates of 0.26 and 0.93%, respectively. AG and CG also showed HRs of 0.301  and 0.273 , respectively . The proStratified analyses were performed based on age, gender, and income level. In the analysis by age, the 70–79 years' age group showed the lowest HR of 0.202 . Among all ages, AG showed a lower surgery rate than CG, with an HR <1. However, the results were statistically significant only in the 60–79 years' age groups. In the 20–39 years' age groups, statistical comparisons could not be made because there were no cases that required surgery. In the 40–59 years' age group, HR was <1, but the results were not statistically significant. In the analysis by gender, males and females showed HRs of 0.5  and 0.225 , respectively; the results were statistically significant only in females. In the analysis by income level, results for all groups were significant, but the lower income group showed the lowest HR, 0.201  .The results of sensitivity analyses based on frequency and duration of acupuncture therapy are also presented. In all analyses, AG tended to show a lower surgery rate than CG, with an HR <1 .The present study examined the association of acupuncture therapy with surgery rate in patients with knee osteoarthritis. In pre- and post-matching cohorts, AG showed a lower surgery rate than CG, with an HR <1. Analysis of surgery rates and HR values between the two groups showed that the results were significant in the age groups of 60–69 and 70–79 years, revealing appreciably lower HRs in older subjects. In the analysis by gender, females showed appreciably lower HRs. In sensitivity analyses based on frequency and duration of acupuncture therapy, the tendency of AG to have a lower surgery rate than CG was maintained, with HR <1.In the pre-matching cohorts, primarily older age groups, females, and upper income level groups showed higher percentages; these patterns were maintained after matching. This may reflect differences in preferences based on age, gender, and income level with respect to TKM, including acupuncture therapy. In a study by Woo et al. that examined TKM preferences in the Korean population , acupuncThe number of subjects in the propensity score-matched groups tended to increase in age groups 50 years or older for both AG and CG, which may be because knee osteoarthritis is generally a degenerative joint disease . In bothThe major finding in the present study is that AG tended to show lower surgery rate than CG in the overall analysis and stratified analyses. However, because of no existing cases or small sample size (n), statistical significance could be found only in some groups.The analysis results showed that pre- and post-matching surgery rates in CG increased from 0.76 to 0.93%, respectively, whereas HRs decreased from 0.301 to 0.273, respectively. This indicated that when the influences of other influencing factors of surgery rate were eliminated by propensity score matching, differences in surgery rate, in comparison with AG, were larger with statistically significant differences.p < 0.0001). This may be due to aforementioned preferences for TKM among the elderly. Moreover, older age groups tend to choose non-surgical treatment over surgery due to concerns regarding possible complications; thus, it is difficult to conclude that the findings in the present study solely reflected the effects of acupuncture therapy. A study by Belmar et al.  and CG showed the highest surgery rate, while its HR was lowest . This may be attributed to a greater number of female patients than male patients, as well as aforementioned gender differences in disease incidence. In the analysis based on income level, the results of the entire group were statistically significant.To test the robustness of the analyses performed in the present study, sensitivity analyses based on frequency and duration of acupuncture therapy were performed. The results based on frequency and duration showed that surgery rate was higher in CG than in AG.The noteworthy result in the analysis based on changes in frequency of acupuncture therapy was the difference between the ≥2 and ≥3 times groups. AG did not show a consistent tendency in surgery rate between the groups, whereas CG showed a noticeably higher surgery rate in the ≥3 times group than in the ≥2 times group; that rate was maintained as the frequency of acupuncture therapy increased. Moreover, the ≥3 times group showed the lowest HR, 0.247 . These results demonstrated that receiving acupuncture therapy ≥3 times within 6 weeks after the initial diagnosis was more closely associated with low surgery rates than receiving acupuncture therapy ≥2 times.With respect to surgery rates based on duration of acupuncture therapy, AG showed a decrease in surgery rate from 0.26 to 0.24% when the duration decreased from 6 weeks to 1 week, while CG showed an increase from 0.93 to 0.95% for the same duration. Moreover, HRs showed a decreasing tendency. These results demonstrated that short-term intensive treatment after the initial diagnosis is associated with a low surgery rate.The findings in the present study demonstrated that acupuncture therapy may be associated with a low surgery rate for knee osteoarthritis. As mentioned above, acupuncture therapy may show functional improvement and relieve pain in patients with knee osteoarthritis, which can reduce the need for surgery. Previous literature –37 mentiThe present study used national cohort data, which had a large sample size that can represent the entire national population. Because the data were based on actual insurance claims, there is the advantage of no follow-up failure or loss, unlike other studies that require additional follow-up observations. While many studies have examined the association between acupuncture therapy and improvement in symptoms of knee osteoarthritis, there have been no studies regarding the correlation between acupuncture therapy and surgery rate for knee osteoarthritis. Moreover, the analyses in the present study were more significant due to additional sensitivity analyses regarding frequency and duration of acupuncture therapy.The present study had some limitations. First, only surgery rate was used as the outcome for determining the association between acupuncture therapy and surgery. In doing so, the actual pre- and postoperative conditions of the patients could not be determined; thus, whether acupuncture therapy or surgery were helpful to patients could not be verified. Moreover, because new cases were defined relative to the date of initial diagnosis, there is a lack of information regarding whether the clinical conditions of the patients at the time required immediate surgery; whether the disease was in early stage; or what disease stage was present, based on radiologic findings. This suggests that the incidence of surgery may be influenced more by existing clinical conditions, compared with acupuncture therapy. Furthermore, the cohort data used in the present study did not consider items not covered under the Korean national health insurance system. Therefore, if the patient had received other treatments not covered by insurance, along with acupuncture therapy, the influence of such treatments could not be assessed. In addition, acupuncture therapy used in the present study was based on the curriculum used in traditional Korean medical colleges in Korea. Therefore, there may be differences with regard to acupuncture therapy used in other countries; differences may exist when applying these findings in other countries. Osteoarthritis is an age-related disease, but patients in their 20s and 30s were included in the analysis because the entire adult was subject to analysis. Although stratified analysis is presented by age, this limitation may weaken the meaning of the present results. Despite efforts to reduce selection bias through propensity matching, the entire health condition of the patient may not have been reflected because only the data in the claim data were checked. There may be concerns about the selection bias. Lastly, the number of patients in AG who underwent surgery was low; as a result, statistical significance could not be measured in some cases.Knee replacement surgery is gradually becoming a more common treatment modality . This poThe findings in the present study demonstrated that intervention by acupuncture therapy is associated with a low surgery rate in Korean patients with knee osteoarthritis. With the growing elderly population, the number of patients with knee osteoarthritis and the associated social burden are expected to increase. Therefore, strategies that can help alleviate the social and economic burdens of surgery, including TKR, are important for public health care policy makers; the findings in the present study may be helpful in that regard.The present study analyzed the NHIS-NSC database, licensed by the Korean NHIS. Data are available from Korean NHIS upon submission of an appropriate study design.Due to the retrospective nature of this study, which utilized data with de-identified personal information, it was granted an exemption by the Institutional Review Board of Jaseng Hospital of Korean Medicine in Seoul, Korea (JASENG 2018-01-007). Informed consents process was waived by Institutional Review Board because the de-identified data was analyzed.B-GG, YJL, M-rK, WK, and I-HH conceptualized and designed the study. J-SS, JL, KK, E-JK, YP, and DN acquired and analyzed the data. B-GG, YJL, KK, WK, and I-HH interpreted the results. B-GG, JL, YJL, M-rK, KK, and WK drafted the original article. J-SS, H-WC, E-JK, YP, DN, and I-HH critically revised the draft. All authors have read and approved of the final version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


SES was positively associated with physical exercise  and community service . Although no direct effect of SES on the health was found, SES mediated the positive effect in their relationship by physical exercise , and community service . This study showed the health disparities of older patients with diabetes were influenced by individual-level  and environmental-level (community service). It suggests that a lack of physical exercise and health-related community service may impair the health of older patients with diabetes with low SES, which recommends individuals' positive actions and environmental supports for promoting health of regarding population.The differences in socioeconomic status (SES) will cause a disparity in the health of the elderly. Taking diabetes as an example, previous studies have focused on risk factors of diabetes, while the relationship and mechanism between SES, multi-faceted factors, and the health of older patients with diabetes are not well-understood. This study aims to investigate the association between SES and health in older patients with diabetes and the interrelated mediators between them. Based on the data of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2018, structural equation modeling (SEM) was used to test whether physical exercise, social interaction, access to care, and community service mediated the effect of SES on the health in older patients with diabetes. We found support for the model in which SES predicted the health in older patients with diabetes . The total indirect effect of SES on the health accounted for 55.52% of the total effect. Results indicated that physical exercise (β = 0.108,  Socioeconomic status (SES) is an overall measure of an individual's position in society relative to others based on a combination of education, occupation and income , 2. As tThese findings were in line with the Anderson's model  , which iFor instance, diabetes is a common chronic and age-related disease in older adults, which has become a leading challenge of global public health due to its high incidence, disability and mortality . As repoThe theoretical framework of this study was adapted from the Anderson's model. Among the four important components in the model, health behavior and environment were taken as mediating domains to investigate the relationship between population characteristics and health outcomes. Health behavior included physical exercise and social interaction, while environment included access to care and community service. Based on the above understanding, we proposed a theoretical framework  of this This study used the data of the cross-sectional survey in 2018 from the Chinese Longitudinal Healthy Longevity Surveys (CLHLS), a nationally representative and public dataset basing on a selected sample of older adults from 22 out of the 31 provinces of mainland China. All these populations represent about 85% of the total population of China  developed by Kaplan and Anderson  was usedSES was the explanatory variable of this study, which was measured by asking three questions: “years of schooling,” “main occupation before age 60,” and “total income of your household last year.” Years of schooling was classified into three categories: 0 years (1), 1~5 years (2), and 6 years or more (3), respectively referred to uneducated, primary school, and middle school or more. The categories of occupation in the questionnaire included professional and technical personnel, governmental, institutional or managerial personnel, commercial, service or industrial worker, self-employed, agriculture, forestry, animal husbandry or fishery worker, house worker, and others. In this study, occupation was recoded into two categories according to occupational characteristics: manual worker (1), including commercial or industrial worker, farmer, self-employed, house worker, and others; and non-manual worker (2), including professional, technical or managerial personnel; Household income was divided into four quartiles with quintile 1 (1) indicating the poorest and quintile 4 (4) indicating the richest.To evaluate the pathways through which SES affected the health of older patients with diabetes, physical exercise and social interaction at the individual level, as well as access to care and community service at the environmental level, were all considered as potential mediators. The question “Do you regularly exercise in the past, such as playing ball, running and Qigong?” was used to collect information on physical exercise, and the responses to this question were dichotomized into no (1) or yes (2). Given the social background and feature of times for the social interaction of Chinese older adults, the measurement of social interaction included three indicators: the frequencies of participation in group leisure activities , informal interaction , and organized social activities. A score was given to each indicator based on five responses: almost every day (5), not daily, but once for a week (4), not weekly, but at least once for a month (3), not monthly, but sometimes (2), and never (1). And the highest frequency of the three kinds of indicators was deemed as the frequency of an individual's social interaction. Access to care was assessed by one question “Can you get medical service in time?” Responses to this question were dichotomized into no (1) or yes (2). Community service was measured with two indicators: the availability of healthcare  and psychological comfort services  in your community. Options for both questions include no (1) and yes (2). The score for community service was recoded after merging options of the two questions as four classes: both (4), the former (3), the latter (2), and neither (1).The respondents' sex and age were the covariates in this study. Females and males were coded as 1 and 2. Ages were classified into three groups: 65~74 years old (3), 75~89 years old (2), 90 years old and above (1).plus 8.0 software.Frequency and percentage were used to describe sample characteristics. Structural equation modeling (SEM) method was applied to test the relationship between SES and health condition of older patients with diabetes as well as the mediating effect of physical exercise, social interaction, access to care, and community service. Following fit indices were used to evaluate the model fit: comparative fit index (CFI), incremental fit index (IFI), the goodness-of-fit index (GFI), the adjusted goodness-of-fit index (AGFI), standardized root mean square residual (SRMR), and the root mean square error of approximation (RMSEA). We aimed at an adequate fit: CFI ≥ 0.90, IFI ≥ 0.90, GFI ≥ 0.90, AGFI ≥ 0.90, SRMR ≤ 0.08, RMSEA ≤ 0.08. The parameters were estimated by the maximum likelihood method. All the analyses were performed with MOf the 15,874 individuals aged 65 and over based on the 2018 CLHLS survey, 1,423 had diabetes. After excluding the sample with missing values in any variables of interest, a total of 1,030 respondents (older patients with diabetes) were included in the final analyses.n = 588) females, 81.9% (n = 844) were under 90 years old, 57.0% (n = 587) were married and lived with their spouse, and 72.5% (n = 747) lived in the urban area. Among the respondents, 45.0% (n = 463) had more than 6 years of schooling, 78.5% (n = 809) mainly engaged in manual labor before 60 years old, and 31.3% (n = 322) were in the highest quartile of household income, i.e., the total household income of more than 100,000 yuan. The prevalence of past exercising was estimated to be 43.8% (n = 451). Of social interaction, 32.8% (n = 338) participated almost daily, whereas 30.9% (n = 318) never participated. Nearly all the respondents  reported that they could get adequate medical service in time. About one third  of the respondents had both healthcare and psychological comfort services available in the community, while another one third  had neither of these two services. The average value of the QWB scores was 0.6.In order to test the proposed framework, we constructed several models. Model fit indices for all models are summarized in p < 0.01). SES positively predicted physical exercise  and community service . Social interaction  had the largest direct effect on the QWB of older patients with diabetes, followed by community service , and physical exercise . Additionally, although the model did not show a direct effect of SES on the QWB for older adults with diabetes (p > 0.05), SES mediated the effect in their relationship through physical exercise  and community service .Model 4, namely the final model, was illustrated in To the best of our knowledge, there was a dearth of studies on the relationship between SES and health among older patients with diabetes. This study not only examined this relationship, but also determined whether SES mediated the health of older patients with diabetes through four latent variables: physical exercise, social interaction, access to care, and community service. Although the direct influence of SES on the health status of older patients with diabetes was not found in the final model, mediation roles of physical exercise and community service in their relationship were observed in this study. Additionally, physical exercise, social interaction, and community service showed significant effects on the health of older patients with diabetes.At the individual level, the findings showed that the SES of older patients with diabetes positively predicted their physical exercise, while its impact on social interaction was not significant. Meanwhile, both physical exercise and social interaction have a positive effect on the health of older patients with diabetes. As a result, SES mediated health through physical exercise rather than social interaction. On the one hand, higher SES tended to have a better sense of control over their life outcomes , which aFrom the environmental perspective, the results indicated that richer community service was predicted by higher SES. Community service significantly affected the health of older patients with diabetes, while access to care did not. SES affected the health with mediation through community service rather than access to care. Benefiting from the health reform initiated in 2009, the coverage of primary care service institutions has been greatly expanded . AccordiIt is also noteworthy that no significant impact of SES was shown on the health of older patients with diabetes in this study, which was inconsistent with the results of Nicklett  and Lee Some limitations of this study should be recognized. First, all of the data in this study were obtained from self-reported, which may result in information bias. Second, considering the limitation of a cross-sectional study in causal inferences, it may be more prudent to investigate the causality by panel session data or so on in future research. Third, since the possibility cannot be ruled out that some potential mediators between SES and the health of older patients with diabetes not included in this study, more comprehensive models should be studied in the future.In this study, we evaluated the relationship between SES and the health of older patients with diabetes, as well as the mediating roles of physical exercise, social interaction, access to care, and community service. The findings showed SES probably enhanced health by increasing regular exercise and providing more community service, which indicated that health-related individual behaviors and environmental supports can mediate the relationship between SES and the health of older patients with diabetes, and relieve the health disadvantages cumulated by SES in old age. To improve the health of older patients with diabetes and create healthier aging, it requires not only the individuals' initiatives and positive actions, such as keeping physical and mental health through exercising and socializing, but also the support of the environment, such as making health-related resources and services available in the community and residence.http://162.105.138.117/dataset.xhtml?persistentId=doi:10.18170/DVN/WBO7LK.Publicly available datasets were analyzed in this study. This data can be found here: The studies involving human participants were reviewed and approved by the Research Ethics Committees of Peking University. The patients/participants provided their written informed consent to participate in this study.WL and QD contributed to the conception and design of the study. QD conducted the data reduction, analyses, and wrote the manuscript. WL guided the whole process and reviewed the manuscript. All authors read and approved the manuscript before submission.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Bronchiectasis and asthma may share some characteristics and some patients may have both conditions. The present study aimed to examine the rationale of prophylactic inhaled corticosteroids (ICS) prescription in children with bronchiectasis. Data of children with radiologically established bronchiectasis were retrospectively reviewed. Episodes of dyspnea and wheezing, spirometric indices, total serum IgE, blood eosinophil counts, sensitization to aeroallergens, and air-trapping on expiratory CT scans, were recorded. The study included 65 children 1.5–16 years old, with non-CF bronchiectasis. Episodes of dyspnea or wheezing were reported by 22 (33.8%) and 23 (35.4%), respectively. Skin prick tests to aeroallergens (SPTs) were positive in 15 (23.0%) patients. Mosaic pattern on CT scans was observed in 37 (56.9%) patients. Dyspnea, presence of mosaic pattern, positive reversibility test, and positive SPTs were significantly correlated with the prescription of ICS. The prescription of ICS in children with bronchiectasis is more likely when there are certain asthma-like characteristics. The difficulty to set the diagnosis of real asthma in cases of bronchiectasis may justify the decision of clinicians to start an empirical trial with ICS in certain cases. Bronchiectasis is a complex and progressive respiratory disorder, characterized by chronic infection, inflammation, and abnormal dilatation of the bronchi. The loss of bronchial wall integrity, the mucus impaction and mucosal oedema may reduce the lumen opening and restrict the airflow especially during expiration when the bronchial walls appose. Bronchiectasis is a syndrome and not a disease per se, and several causative and associated disorders have been described .Children with bronchiectasis, apart from cough, may also develop wheeze and asthma symptoms. with reported rates ranging from 11 to 46% ,3, althoThe treatment of bronchiectasis is based mainly on antibiotics and chest physiotherapy. In cases of bronchiectasis and asthma coexistence, patients must receive treatment for both conditions ,8. NeverThe present study was conducted in the Pediatric Pulmonology Unit of the Attikon University Hospital in Athens, which is one of the main tertiary referral centres for pediatric pulmonary disorders, in Greece. Three consultants and four fellows had been serving in the Unit during the study period. Data of all the children attended in the Unit from 2013 to 2018, up to 16 years old, with chronic wet cough and radiologically established bronchiectasis on chest high-resolution computed tomography (HRCT) scan were retrospectively reviewed. All HRCT scans had been performed in the radiology department of our hospital and were evaluated by the same pediatric radiologist who was aware of the patients’ clinical history. The criteria for the diagnosis of bronchiectasis on HRCT were dilatation of bronchi, as determined by broncho-arterial ratio > 0.80 ; paralle, cypress, house dust mite, fungi, cat and dog dander). Nasal nitric oxide test and high-speed video microscopy analysis were performed only in patients who fit the clinical phenotype of primary ciliary dyskinesia. Spirometry was performed at the initial and the follow-up visits to all patients ≥5 years old who were able to cooperate. TH2-high status was defined as the combination of total serum IgE levels of ≥100 IU/mL and absolute blood eosinophil count of ≥140/mL [Investigations in all patients included a complete blood count, sweat test and/or cystic fibrosis (CF) gene mutation analysis, measurement of serum immunoglobulins, and skin prick tests (SPT) to the most common aeroallergens  or wheezing, and/or their spirometric indices or the shape of the spirometry loop were indicative of airway obstruction, and/or had positive SPT, underwent a bronchodilator response (BDR) test with salbutamol, during their first visit. The BDR test was performed with four actuations of salbutamol metered dose inhaler into a spacer device and interpreted as positive if the change in the forced expiratory volume in one second (FEV1) after bronchodilator administration was ≥ 12%. Spirometric indices were reported as percent predicted (pp) values using the NHANES III reference equations. All patients received antibiotics for 3–6 weeks, started daily chest physiotherapy, and some of them were also prescribed ICS with or without LABA. All were reevaluated in 2–3 months.Patients with CF were excluded from the study.The study protocol was approved by the Attikon University Hospital Ethics Committee.Variables are presented as mean with standard deviation (sd) or as median with interquartile range (IQR). Univariate analysis was performed with paired t-test, chi-square test, and Spearman’s rank correlation test with Bonferroni correction for multiple comparisons. Correlations were expressed as Spearman’s ρ with its corresponding 95% confidence interval (CI). The variables which in univariate analysis were significantly correlated with the decision to start ICS were included as explanatory variables in a multivariate logistic regression model. Results of multivariate analysis are presented as odds ratios (OR) with 95% confidence interval (CI). We further performed three linear regression models where ICS use was the explanatory variable and the differences in FEV1, FEV1/FVC, and the number of positive cultures, between the follow-up and the initial visit, were used as the response variables.Sixty-five children 1.5–16 years old, were diagnosed with non-CF bronchiectasis; 46 (70.7%) of them had been referred as cases of difficult asthma. Thirty-nine (60%) children had been referred by general pediatric practitioners, and 26 (40%) by pediatric departments and clinics. Sixteen (24.6%) patients had underlying disorders directly or possibly related with bronchiectasis: five had tracheoesophageal atresia, five had PCD, one had Crohn disease that was treated with infliximab, one had Job syndrome, one had congenital pulmonary airway malformation (CPAM), one had anhidrotic ectodermal dysplasia with immunodeficiency, and one had IgA deficiency. The remaining 49 (75.4%) patients had no identifiable cause. Apart from the child with the IgA deficiency, all children had normal for age serum concentrations of IgA, IgG, and IgM. Twenty-eight (43.0%) patients commenced daily treatment with ICS with or without LABA. Patients’ clinical characteristics and their correlation with the prescription of ICS are shown in p = 0.036, and OR:10.89; CI:2.21, 53.23; p = 0.003, and OR:12.55; CI:1.21, 121.61; p = 0.034, respectively). BDR test was not included in the model due to its small sample size and the lack of variation that did not allow a reliable estimation of model parameters. The three regression models showed that ICS use was not correlated with the differences in FEV1, FEV1/FVC, and the number of positive cultures, between the follow-up and the initial visit .The multivariate logistic regression model included as explanatory variables the presence dyspnea, positive SPT, and of mosaic pattern, and corroborated the correlations found in univariate analysis between these variables and the decision to prescribe ICS  ,12. HoweDyspnea and wheezing were the only clinical signs/symptoms that were included in our analysis as they represent the two most common characteristics reported by parents, or experienced by children, with asthma ; only dyH2-high status variable. This may have resulted from serum IgE and eosinophil count being less consistent markers of asthma and allergy due to the absence of specific cut off values and the considerable overlap between normal and allergic patients [Atopy, which is a considerable risk factor for asthma development ,18, was patients .Spirometry results were not a significant determinant of ICS prescription in our population. Indeed, spirometric values are usually normal in asthmatic children who are not in exacerbation and so they are not a reliable marker of asthma . On the The mosaic pattern in expiration HRCT scans reflects air trapping and it is a well-known radiological feature of bronchiectasis . HoweverThe present study has certain limitations. The data depict the prescription preferences of physicians from a single centre and so the results are neither free from bias nor can be generalized. Cough, one of the main features of asthma, was not assessed because it is also the cardinal symptom of bronchiectasis and as such it could not offer any discriminative information for asthma diagnosis. HRCT scans were evaluated by a single radiologist and were not blinded. All children received antibiotics and started chest physiotherapy at diagnosis. Because of this, we were unable to determine the net result, if any, of ICS in children with asthma-like features. We tried to examine whether the administration of ICS could result in any measurable clinical changes that would allow us to identify a group of children who could truly benefit from ICS. However, since the study was not designed to investigate this question, included only a few outcome variables, and the sample size was relatively small, the results were inconclusive.In conclusion, it was shown that the prescription of ICS in children with bronchiectasis is more likely when there are certain asthma-like features. The results should be conceptualized as a justification of the clinicians’ decisions in cases where the coexistence of bronchiectasis and asthma seems probable and not as evidence for the need for ICS in certain cases. Indirectly, the study stresses the importance of research data able to illuminate the issue of asthma and bronchiectasis coexistence and define the clinical characteristics of children with bronchiectasis who could benefit from the use of ICS.