In recent years, the incidence of depressive symptoms among Chinese college students has been increasing. Studies have shown that depressive symptoms are related to a variety of psychosocial factors, among which neuroticism, resilience, and attention bias are most notably related, but the correlation among the three is not clear. This study aimed to investigate the influence mechanisms of different degrees of resilience, attentional bias, and neuroticism in the formation of depressive symptoms. The college freshmen of this study were selected through stratified multi-stage cluster sampling. Students provided informed consent and then completed a general situation questionnaire and four scales: the Chinese version of the Connor–Davidson Resilience Scale, the Attention to Positive and Negative Information Scale, the Eysenck Personality Questionnaire, and the Zung Self-Rating Depressive Symptoms Scale. In total, 1,493 freshmen participated in the research group. Our results showed that low resilience, negative attention bias, and high neuroticism jointly increased the risk of depressive symptoms. There is a significant correlation between these three factors and depressive symptoms. Additionally, strength, tenacity, and attention bias all had more significant effects on the occurrence of depressive symptoms. These findings indicate that there may be an important psychological mechanism for the occurrence, development, and poor prognosis of depressive symptoms. Mental health problems among college students in recent years have been a significant concern for society. According to a meta-analysis of 84 studies involving 1,292,811 college students, the detection rate of depressive symptoms among college students in China was 26% . The maiNeuroticism is a pattern of negative emotional responses to setbacks, failures, and dangers . One stuHowever, it is not clear which of the three traits plays a more significant role in depression. Thus, in this study, we aimed to determine the influence of neuroticism, attentional bias, and different degrees of resilience on the occurrence of depressive symptoms, in the hopes that we may understand their different roles and the psychological mechanism of depressive symptoms. We hypothesized that neuroticism, attention bias, and resilience are related to the occurrence of depressive symptoms. We also predicted that neuroticism and negative attention bias may have a greater impact on depressive symptoms under the condition of low resilience. We investigated a large sample of college freshmen to verify our hypothesis and build a foundation for research on the psychological mechanism of the production of depressive symptoms and the prevention and treatment strategy for depression in college students.This study was conducted between February and March 2021. The research data were collected through the Questionnaire Star online system. Participants were selected through stratified multi-stage cluster sampling. First, five universities were randomly selected from a larger group, that is, four from 60 universities in Tianjin and one from 20 universities in Ningxia. In the second stage, we randomly selected a major in each school to recruit students from. A total of 1,698 college freshmen were selected. The school tutor sent the survey link to each student by WeChat. The students read the informed consent form on their cell phones and agreed to participate in the study by completing the form. A total of 1,493 valid questionnaires were collected, representing 87.9% of the total number. There were 568 men and 925 women representing 38 and 62% in the research group, respectively. The average age of the participants was 18.92 ± 0.984 years. The study was approved by the Ethical Committee of the Tianjin Anding Hospital.Participants first completed a demographic information survey form that included age, gender, residence, major, and grade point average.The Chinese version of the Connor–Davidson Resilience Scale (CD-RISC) was revised by Nan Xiao and Jianxin Zhang in 2007. The scale has 25 items covering three factors: tenacity (11–23), strength , and optimism . The scale is scored on a 5-point scale, with 0 meaning “never,” and 4 meaning “always.” The higher a participant’s score, the higher their level of resilience. The sum of the items corresponding to each factor is the factor score. The total scale score is the sum of all items. The original Chinese version of the CD-RISC has a high internal consistency, with Cronbach’s α = 0.91 .The Attention to Positive and Negative Information Scale (APNI) was used to assess positive and negative information attentional biases. The APNI was first developed by Noguchi in 2006 and translated and revised into Chinese by M ± 0.67 SD, or 12.31 + 0.67 * 4 = 14.99. People with scores higher than 14.99 points are considered to experience neuroticism  was compiled by Professor Eysenck and the revision committee was chaired by Professor Yaoxian Gong. Gong conducted the standardization of the Chinese version of the EPQ questionnaire in 1983. The revised EPQ for children measures four factors  across 88 items with yes-or-no answer choices. The Chinese version of the EPQ has good reliability and validity owing to working standardization. The correlation coefficient of EPQ scale ranges from 0.83 to 0.90, with a Cronbach’s alpha ranging from 0.68 to 0.81. According to the formula in the EPQ scale, the division between neuroticism and non-neuroticism is calculated using the formula roticism .The Zung Self-Rating Depressive Symptoms Scale (SDS) was developed by William W. K. Zung in 1965 and translated into Chinese by t-tests, analysis of variance (ANOVA), and non-parametric tests. (r) were conducted to determine the effect size between the two groups . Significant differences were also found between the RLG, RMG, and RHG groups in a two-way comparison: RLG and RMG ; RMG and RHG ; and RLG and RHG . The average scores of resilience were calculated and categorized. Participants who scored higher than the average score plus 1 standard deviation were assigned to the resilience high-score group (RHG); those who scored between the average score plus or minus 1 standard deviation were assigned to the resilience medium-score group (RMG); and those who scored lower than the average score minus 1 standard deviation were assigned to the resilience low-score group (RLG). The average score on resilience and the standard deviation of the research group was 66.02 ± 16.621. The RLG, RMG, and RHG delimitation scores were 49.399 and 82.641. A total of 239 (16%) participants were in the RHG, 1,064 (71.3%) participants were in the RMG, and 190 (12.7%) participants were in the RLG. Non-parametric test showed a statistically significant difference in the resilience score of RLG, RMG, and RHG . Neuroticism accounted for 10.5% in the RHG, 16.3% in the RMG, and 35.8% in the RLG . The detection rates of depressive symptoms and neuroticism in the Chi-square statistical analysis results are shown in A total of 585 participants with depressive symptoms were detected, with a detection rate of 39.2%. Depressive symptoms accounted for only 32.2% in the RHG, 34.9% in the RMG, and 72.1% in the RLG , but no significant difference in the average scores of depressive symptoms and API between gender. The total and factor scores of resilience, ANI, and ANI/API were significantly higher in men than in women (p < 0.01), and the neuroticism score for women was significantly higher than that of men (p < 0.01) as shown in The survey showed that 252 (44.4%) of men had depressive symptoms and 333 (36%) of women had depressive symptoms. There was a significant difference between the men and women , with resilience and its 3 dimensions had a significant negative correlation . Neuroticism had a very significant positive correlation with the ANI/API ratio , and a very significant negative correlation with resilience and its 3 dimensions . Resilience had a very significant positive correlation with its 3 dimensions . Depressive symptoms had a very significant positive correlation with neuroticism and ANI/API ratio (p < 0.01). Depressive symptoms in the RMG had a significant positive correlation with neuroticism, ANI, and ANI/API ratio (p < 0.01), and a significant negative correlation with API, resilience, and its three factors tenacity, strength, and optimism (p < 0.01). The depressive symptoms of the RLG had a very significant positive correlation with neuroticism and ANI/API ratio (p < 0.01) and a very significant negative correlation with API, and resilience across its three factors of tenacity, strength, and optimism (p < 0.01). Male and female depressive symptoms were significantly positively correlated with neuroticism and ANI (p < 0.05), and negatively correlated with resilience, its three dimensions, and API , A NI , tenacity , and strength  entered the equation and these variables had a more significant effect on depressive symptoms in Chinese college students (Depressive symptoms (SDS) scores were used as dependent variables, while neuroticism, attentional bias, and resilience factors were used as independent variables. We included gender, age, ethnicity, neuroticism, attentional bias, and psychological resilience as independent variables in the linear regression analysis and entered the equation by stepwise method. The results showed that gender, age, ethnicity, neuroticism, and optimism did not enter the equation and had no significant effect on depressive symptoms in Chinese college students. API , and low resilience may increase the risk of depressive symptoms. Neuroticism, resilience, and attentional bias seem to be sensitive psychological indicators for predicting the risk of depressive symptoms. Once stress factors are encountered, low resilience, high neuroticism, and negative attentional bias make it more difficult to recover from depressive symptoms. This explains why some people recover from a stressful situation quickly, while others experience lasting depressive symptoms. This study confirmed that low resilience, neuroticism, and negative attentional bias were not only independent influence factors on depressive symptoms, but also significantly correlated with each other to promote the degree of depressive symptoms. These results confirmed our hypothesis. If we can intervene in these factors and improve their function, it may be an effective way to alleviate depressive symptoms. Increasing resilience and reducing the proclivity of neurotic behavior and attentional bias to positive information are some of the most important measures to improve strategies against stress and prevent and treat depressive symptoms. Studies show that focusing on working out solutions and paying more attention to positive aspects after a traumatic incident may alleviate post-traumatic stress disorder symptoms and increase overall mental health . Our regOur results may be of great significance for the prevention and treatment of depressive symptoms in college students; however, during the COVID-19 pandemic, Chinese college students’ resilience, neuroticism, and attentional bias may differ according to their personality, family, ethnicity, and academic performance, thus influencing the onset of depressive symptoms. This has not been discussed in depth in this paper due to space limitation. Our research group was limited to college freshmen in Chinese universities and did not cover all grades. Therefore, the findings do not represent the entire college student population, which future research should address in multiple regions.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.This study was supported by the Okamoto Memorial Foundation for mental health in Japan (Leiwa 2-year research 1).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Prostate cancer (PCa) is the second most diagnosed cancer in men. Most PCa-related deaths result from metastatic disease. Metastases occur most often in the bones (90%). However, the current treatments for bone metastases in PCa are not very effective. Here we present an overview of the current research situation of bone metastases in PCa, focusing on hotspots and trends.We searched the Web of Science Core Collection database for publications related to bone metastases in PCa published between 1999 and 2021. We used VOSviewer, CiteSpace, and a bibliometric online platform to perform a bibliometric analysis of countries, institutions, authors, journals, references, and keywords.Prostate is the journal which published most related articles, and Mundy GR, 2002, Nat Rev Cancer, is the most cited article in this field. Furthermore, the analysis of author keywords can be divided into five clusters: (1) diagnosis of PCa, (2) mechanism of bone metastasis, (3) drug treatments of bone metastases, (4) radiotherapy of bone metastases, and (5) treatments and prognosis of PCa.A total of 4,832 related articles were included in the present study. The USA published the most articles in the field, followed by China and England. The University of Texas MD Anderson Cancer Center is the leading institution in the research field of bone metastases in PCa. Saad F, from Canada, has made great achievements in this area by publishing 91 related articles. mCRPC has been the hottest topic in PCa in recent years. CT is the most common diagnostic method for bone metastases. Enzalutamide and radium-223, as important treatments for bone metastases in PCa, bring about widespread attention. Furthermore, the researchers focus on the tumor microenvironment and biomarkers to explore the mechanism and the therapeutic targets of bone metastases in PCa. Prostate cancer (PCa) is the second most diagnosed cancer type in men . The surAs yet, the exact mechanisms causing BM remain unknown. It is known that the bone marrow has a high blood flow, and PCa cells release adhesive molecules that bind them to marrow stromal cells and bone matrix , 8. AddiThe current treatments of BM are mainly aimed at preventing disease progression and symptom palliation but not cure—for example, bone-targeted agents, such as bisphosphonates and denosumab, have been proved to improve bone structure and quality to minimize the risk of skeletal morbidity –14. The Bibliometric analysis is an information visualization method to identify and summarize the frontiers or hot spots in a certain area. The quantification of literature in this field is based on mathematical and statistical methods through the analysis of literature and metrological characteristics. Moreover, we can compare the research status among various institutions, authors, or journals, evaluate the latest cutting-edge research, understand the scientific articles, and visualize their trends through this method.We aimed to show the developments and trends in the research field of BM in PCa in the past 22 years by bibliometric analysis. Moreover, our study provides an overview of the research of BM in PCa that can serve as a reference for researchers.The data source of our research is the Science Citation Index Expanded (SCI-Expanded) of Clarivate Analytics’ Web of Science Core Collection (WoSCC). The WoSCC is a widely used database for bibliometric studies which contains publications from nearly 9,000 high-impact journals.A search for publications related to PCa and BM was performed on April 25, 2022. The search query was formulated as follows: topic = “(prostate OR prostatic) NEAR/1 (cancer OR tumor OR tumor OR oncology OR neoplasm OR carcinoma)” AND “bone metastasis OR bone metastases” AND “publication date = ”. The search results were downloaded in plain text format and in the tab separator format of “Full Records and cited References”. Furthermore, the publication types were limited to original articles and reviews, and the language was limited to English.To ensure the accuracy of data and the reliability of the research, two researchers independently downloaded and analyzed the data. Co-authorship, co-occurrence, and co-citation analysis are the most significant indicators in bibliometric analysis. Co-authorship analysis is conducted to analyze the relationships among authors, countries, or institutions. Co-occurrence analysis is a quantitative method to analyze the most frequently appearing items in articles. A co-citation analysis was conducted by comparing the ranked results with the co-citation score.Microsoft Excel 2019 was used to analyze the annual publications and generate the line graph and to produce the tables of top-cited or productive countries/regions, publications, journals, and authors.VOSviewer (version 1.6.18), CiteSpace (version 5.8.R3), and a widely used online platform for bibliometric analysis were used to visualize the data. With VOSviewer, one can map network data based on computer programs. It can be used to create a co-authorship, keyword co-occurrence, citation, bibliographic coupling, or co-citation map based on bibliographic data. Furthermore, The VOSviewer shows not only how the subjects are related to each other but also how far away in time they are in different colors. Therefore, we can use this visualization to predict future research hotspots. CiteSpace is mainly used to analyze the potential knowledge contained in the scientific literature and for data visualization. We used CiteSpace to analyze the co-authorship of institution and author, the co-authorship of reference and journal, and the co-citation of authors. We can learn about current and even future research hotspots from the reference’s citation bursts. In addition, we generated a dual map overlay of journals by CiteSpace. The online platform for bibliometric analysis was applied to analyze the country/region’s publications and co-authorship.All data were obtained from the public database. As a result, there was no need to seek ethics approval.We obtained 6,162 related publications from the WoSCC database Figure 1The quantitative analysis of published articles about BM in PCa is shown in In total, 4,832 articles were published by 4,872 organizations in 92 countries Table 1.In total, 4,872 institutions produced related articles. The most productive institutions were from the USA. As shown in In total, 23,495 authors and 64,811 co-cited authors were identified. The top 10 productive authors and the top 10 co-cited authors are shown in Prostate (149), European Journal of Nuclear Medicine and Molecular Imaging (92), Cancer Research (89), Clinical Cancer Research (80), and Anticancer Research (74) were the most contributing journals. Among the top 10 journals, 60% were in JCR Q1, and their impact factors were relatively high, with 70% being higher than 5.0. Besides this, Cancer Research had both the highest number of citations and the highest H-index. A dual map reflecting the relationship between citing and cited journals is shown in A total of 873 journals have published related articles. The top 10 publishing journals are shown in Nat Rev Cancer (464), Parker C, 2013, New Engl J Med (454), Saad F, 2002, Jnci-J Natl Cancer I (430), Roodman GD, 2004, New Engl J Med (406), and Fizazi K, 2011, Lancet (405). Interestingly, these top co-cited references were published relatively long ago, and most of them were published in journals with a high impact factor, which indicates that they are authoritative articles in the research field of BM in PCa. The top 25 references with the strongest citation bursts are shown in We used VOSviewer to analyze the co-cited references. The threshold was set as 100 cited times, and 74 references were included. The co-cited collaboration network is shown in The analysis of the co-occurrences of keywords was performed by VOSviewer. A total of 6,150 author keywords were identified, and 72 keyword co-occurrences were found more than 20 times; their relationship network is shown in J Natl Cancer I , from the Netherlands, is the most influential journal in the field of urology. EU has published 66 related articles in this period, which also indicates that BM in PCa is a hotspot in urology. Besides this, there are also some journals with low impact factors, such as Plos One, having published lots of related articles.Jnci-J Natl Cancer I   . Enzalut 0.0033) . Accordi 0.0033) , 27, enz 0.0033) , 29. A p 0.0033) . Actuall 0.0033) .Bibliometric analysis, because of its function of summarizing research hotspots in a certain research field, can provide directions for future research in this field. Through a bibliometric analysis of prostate cancer bone metastases, we were able to summarize the research in this field over the past few decades. More importantly, we can learn about the research hotspots in this field in recent years, and researchers will benefit from it. Scientific research not only needs to keep moving forward but also needs to summarize the past and gain experience and direction from past research. Therefore, the field of prostate cancer bone metastases research would benefit from the bibliometric analysis of clinical and biomedical exploration—for example, clinical bibliometric analysis can tell us the research hotspots for clinical diagnosis or treatments of prostate cancer bone metastases. In addition, from the bibliometric analysis of biomedicine, we can learn the hotspots in the research on the mechanism of bone metastasis in prostate cancer, and researchers will be guided to pay attention to this aspect. In sum, these could advance the field of prostate cancer bone metastases research.There are still some limitations in our study. First, we cannot ensure that all related articles were included with our search strategy, which may cause a bias of the results. Second, recently published articles have not had enough time to be cited.Based on the present bibliometric analysis of BM in PCa, we conclude that the research field of BM in PCa has been getting hot since 1999. USA leads the way in nearly all aspects of the research field, such as the most productive institutions and authors. Notably, mCRPC has been the hottest topic in PCa research in recent years. CT is the most common diagnostic method for BM. Enzalutamide and radium-223, as important treatment modalities for BM in PCa, have attracted widespread attention. Furthermore, studies focus on the tumor microenvironment and biomarkers to explore the mechanism and the therapeutic targets of BM in PCa. In the future, perhaps mCRPC therapies will be the most critical research field of BM in PCa.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.ZG, HH and YL conceived and designed the study. YC and CT analyzed the data by using Excel and wrote the manuscript. ZS and JZ visualized the data by using VOSviewer and Citespace. ZL and LL searched and downloaded the data from WoSCC. SP and WW revised and reviewed the manuscript. All authors contributed to the article and approved the submitted version.This study was supported by the National Natural Science Foundation of China (nos. 81772733 and 81972384) and Guangdong Scientific Research Projects (no: 2021A1515010223) to ZG, the National Natural Science Foundation for Young Scientists of China (no: 81802527) and Beijing Bethune Charitable Foundation (no: mnzl202026) to YL, Guangdong Provincial Clinical Research Center for Urological Diseases (2020B1111170006), and Guangdong Science and Technology Department (2020B1212060018), National Natural Science Foundation of China , Guangdong Basic and Applied Basic Research Foundation(No: 2019A1515011437), International Science and technology cooperation project plan of Guangdong Province (No: 2021A0505030085), Sun Yat-Sen University Clinical Research 5010 Program (No: 2019005) and Sun Yat-Sen Clinical Research Cultivating Program (No: 201702) to HH.www.letpub.com) for its linguistic assistance during the preparation of this manuscript.We thank LetPub (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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The present study aimed to explore the effect of intermittent theta-burst stimulation (iTBS) on visual working memory for people suffering from methamphetamine use disorder (MUD). Five sessions of iTBS were carried over the left dorsolateral prefrontal cortex (DLPFC) or the vertex as a sham control, with each session in one day. Orientation free-recall tasks were conducted before the iTBS stimulation, after the first and fifth sessions of stimulation. Results showed that when compared with the sham group, a single session of iTBS over the left DLPFC improved participants’ working memory performance. Specifically, iTBS over the left DLPFC increased the working memory capacity and such effects enlarged with multiple sessions. The present finding suggested that iTBS over DLPFC could be a promising intervention method to enhance the cognitive function of addicts with MUD. Drug abuse is a serious, relapsing mental disorder which causes considerable monetary and societal problems. Among the abused drugs, Methamphetamine (MA) is the most prevalent one worldwide. Recently, animal and human studies have revealed the neural mechanisms underlying methamphetamine use disorder (MUD). Chronic MA abuse on the one hand leads to structural and functional deficits of the reward-related dopamine system that influences activity in the orbital frontal cortex (OFC), which then results in an extremely higher reward expectation for MA-related stimuli and reduced interest to other stimuli ,2. On thWorking memory (WM), serving as the short-term storage and manipulation of information, is one crucial component of executive control, which relies on the prefrontal function , and theRecent studies have emphasized the role of repetitive transcranial magnetic stimulation (rTMS) as a safe and convenient way to treat mental disorders ,17,18. TExcitatory rTMS targeting on the DLPFC has been suggested as a promising intervention method to decrease the drug intake, craving, and relapse rates in addicts ,23,24,25Therefore, in the current study, we assessed the excitatory iTBS effects on visual WM in addicts with MUD. We used a free-recall task, which is more sensitive in measuring WM than n-back and change-detection tasks . MultiplEighteen male addicts (mean age 32.35 ± 3.06 years) with a regular use of MA (weekly or daily use for 2–15 years) took part in the experiment. All of them were recruited from Nanchang drug rehabilitation center and met the diagnostic criteria of substance use disorder in the DSM-5. Participants were neurologically healthy, right-handed individuals with normal or corrected-to-normal vision. They participated in the study voluntarily and signed the written informed consent approved by the Institutional Review Board of East China Normal University and Shanghai Mental Health Center before the experiment.t-test, no differences were detected in age, education years, addiction years, current abstinence duration, monthly dosage, and baseline WM performance between the two groups . Thus, there were 9 participants in the iTBS group and 8 in the sham group. After conducting an independent samples o groups .A free-recall WM task was used to measure the cognitive function of addicts. As shown in Stimuli were generated and presented using Psychtoolbox . All of the stimuli were displayed on the black background of an LCD laptop with a resolution of 1024 × 768. The refresh rate of the screen was 60 Hz. To facilitate the detection of orientations, we used elongated high-contrast (75%) and fixed phase Gabor patches . Gabor patches were shown at four fixed positions in each quadrant, distanced by 2.1 eccentricities from the fixation dot.The task procedure is shown in TMS treatments were delivered by the Yiruide CCY-IA TMS machine, with a figure-of-eight coil targeting the left DLPFC and vertex. The stimulation site was defined by a hat based on the international 10–20 system, in which F3 represented the left DLPFC. Before the theta-burst stimulation, we first determined the Resting Motor Threshold (RMT) of the left motor cortex with the minimum strength needed to elicit right-hand finger movement in 5 out of 10 trials. The amplitude of iTBS was applied with 80% RMT. All participants received five sessions of stimulation in one week, each session for one day. As illustrated in Statistical analysis was conducted with SPSS and R. To compare the group differences in demographic and clinical characteristics, independent sample t-tests were conducted. Then, the mean response error and mean reaction time (RT) were calculated for each group separately. The response error was the absolute angular difference between the presented orientation and the reported orientation (ranging from 0 to 90 degrees). We performed a Linear Mixed Model (LMM) analysis to investigate the intervention effect on response error and RT respectively. In this model, the group (with two levels: iTBS and sham) and stimulation  were treated as fixed factors, and the subjects were included as the random factor. We also performed the classic analysis of covariance (ANCOVA) to investigate the intervention effect after one session iTBS and after five sessions iTBS, respectively. The response error or RT before the stimulation (pre-test) was treated as a covariant and the group (iTBS and shame) was included as the fixed factor. In addition, we fitted the response error data with the Standard Mixture Model  to furtAs shown in p < 0.001) and a non-significant main effect of the group  = 0.677, p = 0.424). However, the interaction between the sessions of stimulation and group was significant  = 4.765, p = 0.016), which meant that the differences between groups changed over sessions. Then, we compared the group difference after the first session and the fifth session separately using ANCOVA, with the baseline performance as the covariate. The iTBS group indicated a lower response error than the sham group after the first session  = 8.398, p = 0.012, ηp² = 0.375). The group difference in response error after the fifth session was marginally significant  = 3.750, p = 0.073, ηp² = 0.211). The intervention’s effects on the response error after the first session of stimulation were examined using Linear Mixed Model (LMM). p = 0.035) was significant. However, the main effect of the group  = 0.694, p = 0.418) and the interaction between sessions and group  = 0.211, p = 0.881) were not significant. p = 0.051, Cohen’s d = 0.766), and for about 1.176 items after the fifth session of iTBS , yet the precision did not change over sessions. In contrast, the sham stimulation did not change either the capacity or precision.The results of the standard mixture model are shown in The present study used excitatory iTBS over the left DLPFC on methamphetamine addicts, while measuring their WM performance before the stimulation, after the first session of stimulation, and after five sessions of stimulation. When compared with sham stimulation on the vertex, a significant improvement in the overall WM performance was found following only one session of iTBS on DLPFC. However, such an improvement was not enlarged following five sessions of iTBS on DLPFC. In addition, we fitted response errors with the SMM  to calcuThe prefrontal cortex has been supposed to be highly engaged in WM processing. The first neural evidence of WM-related cells was identified in the DLPFC  and WM fUsing a change-detection task, Wang et al.  have fouWe did not observe changes in WM precision of remembered items after the stimulation. Our previous studies have proven that visual WM precision and high fidelity representations are maintained in visual areas ,41. The The current study was carried out shortly before COVID-19 and the number of participants was not so large, since entering the center became difficult. Although some statistical results were marginal, most of the effect sizes were substantial, and we still found robust and consistent results when compared with previous research. Yet, we did not validly measure subjects’ craving for MA, and thus were unable to correlate increased or decreased WM performance with the changes in craving score. In this case, it is hard to investigate the relationship between WM performance and addiction severity. Future studies could adopt multiple craving measurements to obtain a more accurate craving score, and explore the relationship between changes in craving score and changes in WM precision before and after stimulation. In conclusion, the current study indicated that both a single session and five sessions of iTBS on left DLPFC significantly improved WM performance in MA addicts. Specifically, the stimulation increased visual WM capacity.


Emerging evidence has linked gut microbiota (GM) and its related metabolites to atherosclerosis (AS). This study aimed to analyze the evolution of GM in AS in the past decades, and provide valuable insights in this field.Web of Science Core Collection (WoSCC) was applied to retrieve the publications related to GM in AS from their inception until 2 December 2021, and the data was analyzed in Microsoft Excel, Scimago Graphica, CiteSpace, and VOSviewer.Nutrients, and Nature was the most co-cited journal. Among 3556 related authors, Hazen, Stanley L., Tang, W. H. Wilson, and Wang, Zeneng were the top 3 contributing authors in this field. Aside from “gut microbiota,” “atherosclerosis,” the terms “TMAO,” “metabolite,” “obesity,” and “phosphatidylcholine” were frequently occurred in the abstract and title of articles. Burst detection of keywords indicated that “metabolic syndrome,” “acid,” and “bile acid” were hot topics in recent years. According to the co-citation analysis of references, the research focus in this area has changed over time, and recent researches focus on choline, hypertension, butyrate, and berberine.In total, 560 documents were extracted from the WoSCC databases. The publications have shown rapid growth since 2008. China and Cleveland Clin were the most prolific country and institution, respectively. The journal with the most publications is Our study showed that the researches of GM in AS have been flourishing, and the content themes were constantly deepened. Human GM is critical to atherosclerotic diseases, and this hot topic is still worthy of more focus in the future. Eubacterium and Roseburia, whereas enriched in Collinsella (Enterobacteriaceae and Streptococcus spp. increased significantly in ASCVD (L-carnitine can be converted into trimethylamine oxide (TMAO) under the action of intestinal flora, which finally induces AS and accelerates the pathological process of coronary and cerebrovascular diseases (Atherosclerosis (AS) is a chronic inflammatory disease characterized by accumulation of fatty and fibrous material in the intimal layer of arteries . AS is tlinsella . Jie et in ASCVD . Moreovediseases . Short cdiseases , possessdiseases , and supdiseases . TherefoDifferent from systematic reviews, bibliometric analysis refers to an analysis of using mathematical and statistical methods to analyze publications qualitatively and quantitatively, which is conducive to identify scientific output, research hotspots, and developing trends associated with a particular field –11. AlthA systematic literature search was conducted using Web of Science Core Collection (WoSCC) with no specified start date, but up to 2 December 2021. The literature was limited to the English language. Details of the search strategy were shown in 1 to evaluate the scientific influence of the journal. All data was imported manually into Microsoft Excel 2019 and presented in tables or charts using Excel features.The data to be studied, such as yearly number of publications, and number of articles published by countries/regions, institutions, journals, and authors were downloaded from WoSCC. Additionally, the impact factor (IF) and quartile in category of journals were obtained from the 2020 Journal Citation ReportsVOSviewer software can construct networks of country/region, institutions, journal, researchers, and individual publications based on citation, bibliographic coupling, co-citation, or co-authorship relations . It is eCitespace can visually map highly cited and pivotal documents, areas of specialization within a knowledge domain, and emergence of research topics . In thisApart from the above methods, the Scimago Graphica tool was used to perform collaboration network between countries/regions and institutions.Annual publications can be used to reflect the development profile of a certain field. A total of 560 documents were published by 945 institutions in 59 countries/regions, and the top 10 most productive countries/regions or institutions are shown in The cooperation maps by the country/region and institution were shown in Nutrients , Scientific Reports , Journal of Agricultural and Food Chemistry , Frontiers in Pharmacology , International Journal of Molecular Sciences . And we found that there was an insignificant positive correlation between the total number of journals published and the TCs.The documents included were published in 283 journals. Total citation (TC) represents the total number of citations for a journal. As shown in Nature (IF = 49.9622020) and the other is Plos One (IF = 3.242020). Nature and other journals.Journal co-citation analysis, first introduced by McCain , focusesA total of 3556 authors were included in this field. The top 10 authors who contributed and were cited most are shown in Keywords reflect the topic of an article, which can be identified to analyze research hotspots and frontiers in a field. The keywords co-occurrence visualization map was constructed in VOSviewer software, and 41 high-frequency keywords (more than 20 times) were included . We can Keywords burst detection can find the research hotspots increasing abruptly in a specific field. The strength of the burst and the duration of the burst state are the two attributes of the citation burst . Based oL-carnitine from red meat can be metabolized to a pro-atherosclerotic harmful metabolite, TMAO, under the action of intestinal flora. In addition, it suggested one pro-atherosclerotic mechanism of TMAO was diminishing reverse cholesterol transport (RCT). Additionally, “Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation” and “Symptomatic atherosclerosis is associated with an altered gut metagenome” were two key references in this field with a centrality of 0.1, separately. The former  level by inducing scavenger receptor group B type 1 (SR-BI) expression as well as increases macrophage RCT . In theiLTP gene . FurtherLTP gene . A FXR/ALTP gene . ApolipoLTP gene . FXR alsLTP gene .via increased atherosclerotic burden   family, which was discovered in 2002 . It has c burden . Currentc burden . Disturbc burden . Anotherol (LDL) . Moreoveol (LDL) . Given tThere are some limitations in our study. First, in the study only literature that in WoSCC database were retrieved, and it is possible that related studies to be missed, which may influence the results of this study. Second, we only included articles and reviews in the English language, which may lead to bias. Third, data downloaded was not full text, some important information may be omitted.To our knowledge, this is the first study to use bibliometric analysis to explore the development of GM in AS. A vast amount articles in this field has increased in recent years, meaning the role of GM in AS has received considerable scholarly attention. However, the scientific cooperation network indicated that collaboration between different institutions and academic teams has not been sufficient. With the deepening of the research in this field, there have been several different research topics gradually formed. According to our analysis, bile acids have been the research frontier in this field recently, which may be a potential therapeutic target for AS. All in all, the study of GM is an ongoing research hotspot and contributes to preventing or treating ASCVD.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.YW and QZ conceived the study. DL and ZJ collected the data. QZ and JH re-examined the data. YW, DL and QX analyzed the data. YW wrote the manuscript. QZ, WC, and FX reviewed and revised the manuscript. All authors contributed to the article and approved the submitted 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


PPA stratification (proprioception and lower-limb strength) presented a greater risk of falls in the TG, with proprioception increasing the risk by 2.4 times. Conclusion: Patients undergoing treatment for osteoporosis are influenced by intrinsic factors of falls, many being present in the CG. PPA and ankle strength and flexibility tests are more discriminative for evaluating fall risks in patients in treatment for osteoporosis.Introduction: Elderly women with osteoporosis are at risk of falls and fractures. Objective: To compare the intrinsic factors of falls, including ankle evaluation, in a group of elderly women in treatment for osteoporosis compared with a control group. Methods: A cross-sectional study of elderly women in treatment for osteoporosis (TG) was paired with a control group (CG) not in treatment. All groups completed a questionnaire and underwent a bone mineral density test; the mini-mental state examination (MMSE); physical performance tests; lower-limb strength and power, ankle, and muscle architecture evaluations; and a physiological profile assessment (PPA). Results: A total of 128 women were included ; the mean age was 71.55 ± 3.07 years; TG had a worse performance in the intrinsic factors in the MMSE, plantarflexions range of motion, gait speed, plantarflexions peak isometric strength, and short physical performance battery ( Aging is associated with muscle and bone loss, which reduces sensorimotor skills and physiological capabilities, such as vision, muscle strength, proprioception, and balance, increasing the risk of falls and fractures, especially in women with osteoporosis. The ankle strategy is the first balance attitude to prevent falls and fractures. Little is known about the changes in ankle musculoskeletal functions associated with physiological capabilities in postmenopausal women with osteoporosis. The ankle dorsiflexor and plantiflexors are the first line of defense in postural control while standing; it was shown that during reactive pace, the ankle muscles are activated before the knee and hip muscles . Aging dThis information contributes to the planning of successful intervention strategies. Elderly women have a high prevalence of osteoporosis 30%), which increases with age, and when associated with decreased functional capacity and balance, causes a higher incidence of falls and fractures. Falls cause 87% of all fractures in elderly patients with osteoporosis, usually due to low-impact injuries 0%, which. It is eIn 2010, the prevalence of osteoporosis and low bone mass in non-institutionalized individuals aged 50 years and older was estimated at 10.2 and 43.4 million, respectively. The prevalence is higher in women (15.4%) compared to men (4.3%) and increases with age from 5.1% at the age of 50 years to 26.2% at age ≥ 80 years ,10.A systematic review that aimed to provide evidence for the primary prevention of falls in postmenopausal women concluded that the association of sarcopenia and osteoporosis increases the risk of low-energy fractures . OsteopoAlthough anti-resorptive therapy is effective for elderly women with osteoporosis at low and moderate fracture risks, a systematic review with meta-analysis showed that current screening strategies used for fracture prevention based on bone mineral density (BMD), FRAX, or International Osteoporosis Foundation criteria recommend interventions for only 5 to 25% of the participants, with the need to incorporate a more robust screening method involving the musculoskeletal system to propose a more assertive intervention .Thus, the present study aims to compare the intrinsic factors of falls, including ankle evaluation, in a group of elderly women in treatment for osteoporosis and to compare these with a control group.This is a cross-sectional study using women from the community in treatment for osteoporosis. It was developed based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)  and apprWomen (≥65 years) in treatment for osteoporosis were recruited during their routine visit to the outpatient clinic of the Endocrinology and Metabology Service of the Hospital de Clínicas of the Federal University of Paraná (SEMPR) and composed the treatment group (TG). Women who matched by age and race; who never treated for osteoporosis; and who were recruited among friends, relatives of patients, and from the community composed the control group (CG). The exclusion criteria were chronic renal failure, functional dependence, incapacity to perform the requested tests, patients with chronic diseases under current treatment that could interfere with the assessment of the variables, and medications affecting bone mass other than treatment for osteoporosis.® program . Considering the sample (n = 68) for the treatment (n = 60) and control groups, a size effect of 0.5 (mean effect), and type-I error (5% error rate), the sampling power (1-β) of the study was 0.99.The sample size was calculated using the G*Power 3.1.9The evaluations were divided into two days. On the first day, after signing the informed consent form following the rules of the Declaration of Helsinki of 1975, the included individuals answered a structured questionnaire developed for the study to collect demographics, disease characteristics, treatment, comorbidities, lifestyle habits, amount of dietary calcium intake from dairy foods, self-reported history of falls, and low-energy trauma fractures. Calcium and vitamin D supplementation were evaluated as present or absent, and the daily calcium intake was classified based on dietary recommendations. Missing information was collected from patients’ medical charts. The mini-mental state examination (MMSE) test was applied , followeFall was defined as any event resulting from a body change that caused the individual to inadvertently fall to the ground. This definition did not encompass the result of a violent blow, sudden paralysis, loss of consciousness, or epileptic seizure . The evaTo characterize the sample, the following variables were investigated: age, education, marital status, occupation, income, ethnicity, medication in use, treatment time, comorbidities, fractures, visual acuity, hearing acuity, use of orthotics, metallic prostheses, and history of conservative and/or surgical treatments.®) with a capacity of 150 kg, with the participant barefoot and wearing underwear. Height was measured with a vertical stadiometer (Tonelli Gomes®), with a graduation of 1 mm and a maximum height of 2.20 m. The body mass index (BMI) was calculated by dividing the participant’s weight (in kg) by their height squared (in meters). The BMI results were classified as underweight (BMI < 18.5 kg/m2), normal (>18.5 kg/m2 < BMI < 24.9 kg/m2), pre-obese (25 kg/m2 < BMI < 29.9 kg/m2), and obese (BMI > 30 kg/m2) ). The dynamometer’s grip was individually adjusted according to the size of the participant’s hands. A result less than 16 kg indicated low muscle strength ; small effect [>0.21–<0.39]; medium effect [>0.40 and <0.79]; and high effect [0.80]. Categorical variables were compared using Fisher’s exact or the chi-squared tests. The assumption of homogeneity of variance was evaluated by Levene’s test. The bootstrapping procedures were performed  to obtain a higher reliability of the results and correct possible deviations in the normality, distribution sizes of the groups, and to present a 95% confidence interval. A multivariate Poisson model analysis was performed to identify the main intrinsic factors related to falls. All the analyses were performed using the Statistical Package for the Social Sciences SPSS® v.14.1 .Data normality was assessed using the Kolmogorov–Smirnov and Shapiro–Wilk tests. Data were presented as mean ± standard deviation (SD) or median (minimum and maximum) values, or as absolute and relative frequencies, as appropriate. Categorical variables were described by frequency and percentage. Quantitative variables were compared using the Student’s During the study period, 785 patients were seen in the outpatient clinic, 340 were invited to participate, 192 declined, 39 did not meet the inclusion or exclusion criteria, and 41 did not perform the study tests. Of the remaining patients, 68 were included in TG. Furthermore, 60 women recruited from the community and not in treatment for osteoporosis were included in the CG . Most pap < 0.05 for all  and SPPB tests (p < 0.000). The CG took more time to perform the TUG test compared to the TG (p < 0.008). The HGS and SST were similar between the groups . Both groups had an impairment of ankle musculoskeletal function. The ankle ROM of dorsiflexion and plantarflexion was low in both groups, with a lower range in plantarflexion in the CG compared to the TG; The three parameters of muscle architecture measured by ultrasound were equally reduced in both groups .The physiological risk of falls evaluated by the PPA showed a low or very low risk of falls in both groups, but a greater proportion of moderate/high risk of falls in the treatment group. This difference was mainly observed in the component’s proprioception and strength, which was more affected in the TG .p: 0.010.The multivariate analysis (Poisson regression) considered falls as the dependent variable and all significant intrinsic factors as independent variables  and observed that proprioception increased the chance of falls by 2.4% (95% CI 1.006–1.042); IRR: 1.024, When considering the ample physical–functional evaluation not previously conducted on this type of patients, this study reported a worsened performance of intrinsic factors with a higher risk of falls in patients undergoing treatment for osteoporosis, compared to the control group.Important aspects of fall risks, such as a history of falls and fractures, strength, ankle mobility, and muscle architecture, were similar between patients with osteoporosis under treatment and those not treated. One explanation was the similarity of clinical characteristics between the groups, including race and age, variables related to falls and fractures. The exception was BMI, which was lower in the CG and known to be associated with worse muscle and bone mass . Indeed,Despite the similar number of past fractures between the groups, the TG had worse BMD and bone quality evaluated by TBS, with a higher number of patients classified as having osteoporosis, which could be compatible with a more ill group of individuals already in treatment for osteoporosis, with a higher number of comorbidities and twice the number of medications.The altered intrinsic factors in the TG were related to the physical performance , balance (SPPB), plantarflexion ROM, and PIS. The previous literature has shown a low physical performance in postmenopausal women with osteoporosis as evaluated by SPPB and low physical fitness in the TUG test, with a greater risk of falls compared to healthy elderly women ,28.The low ankle function of TG showed a deficiency in the first approach to overcome the imbalance, confirmed by the poor performance and worse balance in this group. This strategy was not previously investigated in patients with osteoporosis, but it was described in community-dwelling older women . Other sPPA, a method used to evaluate physiological functions , exhibited worse proprioception and lower-limb strength in the TG, which classified the patients as having a high risk of falls. PPA was a critical evaluation used in this study; it showed that proprioception doubled the risk of falling as already presented in another study conducted on elderly women in the community . It coulOther studies presented observations concerning elderly women in the community using a battery of tests, such as PPA or PPA itself . They reThe limitations of this study included the cross-sectional design, the possibility of memory bias when providing the number of medications, fracture and fall history, and a possible bias in the selection of the patients and controls. The positive aspects of the current study were the sample size in both groups, the ample evaluation, screening a high number of risk factors for falls, using low-cost instruments, and the focus on women with osteoporosis. In conclusion, this study showed that patients undergoing treatment for osteoporosis were influenced by the intrinsic factors of falls, many of which were present in the women of the community but not in the treatment. The physiological factors for falls and tests of ankle strength and flexibility were more discriminative in evaluating the fall risks for patients in treatment for osteoporosis, and they should potentially be incorporated into future assessments of these patients to direct more assertive preventive interventions.


The coronavirus disease 2019 (COVID-19) pandemic has posed a profound psychological impact on healthcare workers. However, the role of positive affect in moderating the effect of perceived stress on the psychological states of healthcare workers remains unknown. This study aimed to analyze the moderating effect of positive affect on the association between stress and the mental health of healthcare workers during the COVID-19 pandemic. This cross-sectional study evaluated the relationships between perceived stress , positive affect (the Positive and Negative Affect Schedule), depression , and anxiety  during the COVID-19 pandemic in 644 Chinese healthcare workers who completed online self-reports. The results revealed a significant negative association between positive affect and psychological problems, including stress, depression, and anxiety. At the total group level, multiple regression analysis showed that positive affect alleviated the influence of perceived stress on depression, but no significant moderating effect was found for anxiety. In the subgroups divided by perceived stress, the moderating effect of positive affect on depression was only significant in healthcare workers with a high level of perceived stress. These results suggested that positive affect played a moderative role in alleviating the effect of stress on depression among healthcare workers, particularly those with a high level of stress, thus emphasizing the importance of positive affect as an intervention strategy for promoting the mental health of healthcare workers in the context of the ongoing COVID-19 pandemic. The coronavirus disease 2019 (COVID-19) poses a serious challenge to the global public health system. As of 27 June 2022, more than 500 million confirmed COVID-19 cases and 6 million related deaths had been reported to the World Health Organization , exertinThe uncertainty and hazards associated with public health emergencies represent substantial stressors that may lead to a series of psychological pressure reactions. Stress is a feeling experienced in situations where external demands exceed the resources available . Stress Positive affect is defined as an individual’s pleasant interpretation of and reaction to their surroundings, including positive emotional states such as confidence and enthusiasm . A formeTo date, most studies have focused on the negative impacts of negative affect on physical and mental health status or the simple relationships between positive affect and anxiety and depression ,26,27. SGiven the relationship between positive affect and perceived stress, depression, and anxiety, the purpose of this research was to evaluate the characteristics of positive affect and its moderating effect on the relationship between perceived stress and anxiety, and depression. Moreover, in order to further explore the differences in the moderating role of positive affect under different stress statuses, we divided the participants into high and low levels of stress subgroups. Two hypotheses were defined, and we expected:At the total group level, positive affect could alleviate the impacts of perceived stress on psychological problems, including depression and anxiety.At the subgroup level, the moderating role of positive affect was different according to the level of perceived stress. Particularly, compared with the subgroup with a low level of stress, the moderating effect of positive affect on the relationship between stress and psychological problems was more significant in the high-stress subgroup.www.wjx.cn, accessed on 6 December 2021) to collect all data.Recruitment information for this cross-sectional study was delivered at all levels of medical institutions, including general hospitals, specialized hospitals, traditional Chinese medicine hospitals, Centers for Disease Control and Prevention, community health service centers, and maternal and child health care hospitals in all municipal districts of Guangzhou, Guangdong province, China. The study assistants sent the online questionnaire using the Questionnaire Star survey tool  at least 18 years old; (2) currently employed as a healthcare worker ; (3) able to independently complete the online questionnaire; and (4) having a mobile phone or tablet connected to the Internet. Potential participants were excluded if they reported a serious mental disorder or suicidal ideation. This study was approved by the Public Health Ethics Committee of Sun Yat-sen University [2021-120].Participants provided background characteristics, including age, gender, education level, income, marital status, residence status, seniority, and professional title.The Positive and Negative Affect Schedule was developed by Watson and Clark based on a two-dimensional model of emotions: positive affect  and negative affect  . Each itThe perceived stress scale was used to measure the extent of self-perceived stress over the past month . The scaThe Generalized Anxiety Disorder 7-item Scale was used to assess the severity of anxiety symptoms reported by participants during the past 2 weeks. The scale has seven items, which are rated on a 4-point Likert scale from 0 = “not at all” to 3 = “nearly every day.” The total scores range from 0 to 21. The details of the items on the scale are shown in The Patient Health Questionnaire-9 is a self-rating scale widely used in primary health care to evaluate depression in the past 2 weeks . The PatDescriptive analysis was performed by means of reporting frequencies and percentages for categorical variables and means and standard deviations (SD) for continuous variables. An Analysis of Variance and Chi-square tests were used to assess differences in perceived stress, positive affect, anxiety, and depression according to the general sociodemographic characteristics. The Bonferroni adjustment was used to account for multiple comparisons. Pearson’s correlation coefficient was used to assess the relationships between variables. R2 and F in the final model. Significant positive affect × perceived stress interactions were also explored using the simple slope post hoc analyses. According to Jaccard et al. [Multiple regression analysis was performed to determine whether positive affect moderates the influence of stress on the two psychological problems (depression and anxiety). To increase the interpretability of the moderation model and control for multicollinearity, stress and positive affect were centered , and thed et al. , the simThe descriptive statistics and differences in stress, positive affect, anxiety, and depression according to sociodemographic characteristics are shown in F = 4.717, p = 0.009) and marital status . Specifically, the level of positive affect was higher in participants with incomes >10,000 yuan and those who were married. Depression levels significantly differed among participants grouped by marital status  and residential status ; the level of depression was higher in participants who were unmarried or living alone. The difference in anxiety levels among participants grouped by education level was significant, but the pairwise comparisons did not reach significance. No statistically significant differences in stress were detected among participants grouped by sociodemographic characteristics.The average age and seniority of the 644 participants were 30.93 ± 6.95 and 8.11 ± 7.77 years. As shown in r = −0.47, p < 0.001) and positively correlated with anxiety and depression . Positive affect was negatively correlated with anxiety and depression . The means, SDs, and correlation coefficient for the studied mental health status are presented in b = −0.075, p = 0.004, Model 3), and perceived stress was positively associated with depression . The interaction term stress × positive affect was significantly negatively associated with depression in Model4 . The simple slope analysis revealed that compared with participants with a low level of positive affect , participants with a high level of positive affect  had a weaker association between perceived stress and depression , and perceived stress was positively associated with anxiety . However, the interaction term stress × positive affect showed there was no moderating effect of positive affect between perceived stress and anxiety in the total group . In conclusion, this suggested that positive affect had a moderating effect on the relationship between stress and depression rather than anxiety in the total group.Similar analyses were conducted for anxiety. As shown in n = 433, average score of perceived stress: 20.96 ± 4.26). After controlling for the sociodemographic variables, positive affect was negatively associated with depression , and perceived stress was positively associated with depression . The interaction term stress × positive affect was significantly negatively associated with depression in Model4 , suggesting that positive affect had a moderating effect on depression in the high-stress group. As shown in B = 0.610, p < 0.001, 1 SD above mean, b = 0.425, p < 0.001). This suggested that positive affect could moderate the impact of stress on depression in the high-stress subgroup.n = 231, average score of perceived stress: 9.82 ± 3.21). Positive affect had no significant association with depression . There was also no moderating effect of positive affect was observed .b = −0.004, p = 0.525, Model4 in b = −0.008, p = 0.829, Model3 in b = 0.006, p = 0.591, Model4 in The results of moderating effect of positive affect on the relationship between stress and anxiety in the high- and low-stress subgroups were presented in To the best of our knowledge, this is the first study to analyze the relationship between positive affect and perceived stress and psychological problems among healthcare workers in the context of the COVID-19 pandemic. We found that positive affect was an important moderator, alleviating the impact of perceived stress on depression, especially among healthcare workers with a high level of stress.According to the present study, healthcare workers in marital relationships had higher levels of positive affect and lower levels of depression than unmarried one. According to the social support theories, the marriage relationship is the most potent source of social support and a significant form of social relationship, which could have a positive impact on health and emotional well-being ,40. NumeThis study found that positive affect was a protective factor for both anxiety and depression in healthcare workers during the COVID-19 pandemic. Such finding was consistent with literature which reported that positive affect was negatively associated with mental health problems and recovery time from stressful events ,50. FurtHowever, positive affect did not have a moderating effect on perceived stress and anxiety in the present study. Such a finding suggests that anxiety is, to some extent, more difficult to alleviate through positive affect than depression. It is possible that according to the influential tripartite  and quadBecause of the nature of healthcare work, healthcare workers were more likely to encounter epidemic-related stressors and develop psychological problems such as depression after the outbreak of COVID-19 than the general population ,64. ThisThe present results indicate that positive affect could alleviate the influence of perceived stress on depression in healthcare workers. This finding suggests that positive affect plays a crucial role in promoting mental health and preventing psychological problems related to COVID-19-induced stress in healthcare workers. Similarly, a meta-analysis of 51 studies highlighted the importance of positive emotional intervention strategies for mental health. Interventions that foster positive affect was shown to significantly enhance well-being and reduce depression severity . FurtherThis study has several limitations. First, because the study design involved online non-probability sampling and the participants were from a single region (Guangzhou), the representativeness and extrapolation of the results may be limited to some extent. Second, the average age of healthcare workers in our research was relatively low and may not correctly represent the population of healthcare workers. Thirdly, our study was cross-sectional and thus could not determine the causal relationship between variables. Consequently, longitudinal research is warranted to determine the dynamics of the relationships between positive affect, stress, depression, and anxiety.The mental health of healthcare workers in the context of COVID-19 deserves immediate attention. The findings of the present study showed that positive affect played a significant role in alleviating the effect of stress on depression among healthcare workers, particularly those with high levels of stress. As a result, our findings suggest that positive affect may be a significant perspective for health managers to design targeted interventions such as expressive writing and adaptive emotion regulation activities to mitigate the effects of perceived stress on psychological problems in healthcare workers during COVID-19.


It is only by knowing the most common causes of falls in the hospital that appropriate and targeted fall prevention measures can be implemented. This study aimed to assess the frequency of falls in a hospital geriatrics ward and the circumstances in which they occurred and evaluate the parameters of the comprehensive geriatric assessment (CGA) correlating with falls. We considered medical, functional, and nutritional factors associated with falls and built multivariable logistic regression analysis models. A total of 416 (median age 82 (IQR 77–86) years, 77.4% women) hospitalizations in the geriatrics ward were analyzed within 8 months. We compared the results of a CGA  in patients who fell and did not fall. Fourteen falls (3.3% of patients) were registered; the rate was 4.4 falls per 1000 patient days. They most often occurred in the patient’s room while changing position. Falls happened more frequently among people who were more disabled, had multimorbidity, were taking more medications (certain classes of drugs in particular), had Parkinson’s disease and diabetes, reported falls in the last year, and were diagnosed with orthostatic hypotension. Logistic regression determined the significant independent association between in-hospital falls and a history of falls in the previous 12 months, orthostatic hypotension, Parkinson’s disease, and taking statins, benzodiazepines, and insulin. Analysis of the registered falls that occurred in the hospital ward allowed for an analysis of the circumstances in which they occurred and helped to identify people at high risk of falling in a hospital, which can guide appropriate intervention and act as an indicator of good hospital care. Fall prevention in a hospital ward is one of the most critical components of in-patient care for older patients. One overarching goal of a skilled interdisciplinary team is to ensure patient safety and avoid adverse events . Falls cEconomic and social repercussions for frail patients and their families are severe . An oldeFrom a formal and legal point of view, one may perceive a hospital fall as a failure to provide the patient with the so-called safety of stay, which may determine the organizational guilt of the medical facility. Increasingly more often, patients in Poland claim compensation for damages resulting from such events . We can Although falls occur in all wards of Polish hospitals , there aFalls are multifactorial and can result from intrinsic and extrinsic factors. The former include diseases, medications, and physical and mental disabilities. The latter include environmental factors, home hazards, or unfriendly hospital routines. Therefore, fall prevention is all about the management of internal risk factors  and optimization of the ward routine, and the design of hospital environment ,12.Because the problem of falls in Polish hospitals seems to be underestimated and not thoroughly researched, our study aimed to identify the frequency of falls in a geriatric hospital ward. Furthermore, we attempted to assess the circumstances in which they occurred  and evaluate the comprehensive geriatric assessment parameters correlated with falls. The secondary aim was to propose changes in the fall prevention procedure in the ward based on these findings to make it more precise and effective.We analyzed the medical records of all patients participating in a prospective cross-sectional study on the functional health status of geriatric in-patients . FurtherThe focus of this study was on in-hospital falls. Therefore, we adopted the World Health Organization’s definition of a fall: “inadvertently coming to rest on the ground, floor or other lower level, excluding intentional change in position to rest in furniture, wall or other objects” , which oAt our department, we follow the national fall prevention standards, as detailed in the study by Mazur et al. . Based oAll falls in the ward are registered, and nurses on medical duty collect patients’ vital signs shortly after the fall . They note pre-fall behavior, time and place of the fall, injuries, taken drugs that could be a cause, and hospitalization day. In addition, each patient receives fall prevention recommendations for use in the hospital and subsequent recovery at home regarding risk factors that increase the unfortunate event, and anti-fall prevention regarding movement, medications, safe home space preparation, bathroom adaptation, footwear, and orthopedic equipment for their individual needs.2DS2-VASc scale.We collected data on patients’ sociodemographic characteristics  and medical information. The latter included data on 15 chronic diseases  or stroke, diabetes or prediabetes, chronic renal disease, chronic obstructive pulmonary disease, dementia, parkinsonism, neoplasm, chronic osteoarthritis, and osteoporosis). We also gathered information on the length of hospital stay, number of chronic diseases (we defined multimorbidity as 5 or more diseases of the 15 listed above), falls and hospitalizations in the last 12 months, blood pressure at admittance, and selected laboratory values , and assessed the thromboembolic risk with the CHAWe checked for medications that could influence the risk of falls . We collected data on the number of medications taken at admittance and defined polypharmacy as five or more drugs taken .We gathered data on the physical and mental abilities of an older person assessed within a routine comprehensive geriatric assessment. It included the Barthel index score  , the DukData on the risk of recurrent fall assessment included the Performance Oriented Mobility Assessment (POMA) score  , Timed U2 tests or Fisher’s exact test as appropriate while the Mann–Whitney U test and Kruskal–Wallis test by ranks were used to compare the distribution of continuous variables. We regarded a two-tailed p value of less than 0.05 as significant in all analyses. We omitted missing values and calculated the statistics for the adequately reduced groups. We included fatal cases in the analysis, as they did not exceed 1% of cases.We used STATISTICA 13.3 software package  and the IBM SPSS Version 18 Software suit  to analyze the collected data. First, we assessed the distribution of variables with the Shapiro–Wilk test. We presented data as the medium (M) and standard deviation for normally distributed variables and as the median (Md) and interquartile range (IQR) for non-normally distributed ones. We presented the number of cases and percentage for categorical variables. We compared proportions using χp-value less than 0.1 and excluding those highly correlated with avoiding multicollinearity. In the first step, we aimed to evaluate the possibility of using some simple tests associated with fall risk assessment and easily identifiable in clinical practice (making the model possible to be implemented straightforwardly) to predict falls in the hospital. We used a backward stepwise regression (Model 1 with a block of four predictors). Next, we controlled the influence of other variables that were significantly correlated with in-patient falls . In the final Model 3, we retained only variables that were statistically significant at p-value < 0.05 (enter method). We reported ORs with 95% CIs and p values for each model parameter. Finally, we evaluated the statistical significance of the model with the Hosmer–Lemeshow goodness-of-fit C-statistics .We performed a multivariable logistic regression analysis to determine the possibility of the prediction of falls, including predictors with a During the study period, 14 (3.3%) of 416 hospitalized patients experienced a fall during their hospital stay. The calculated rate was 4.4 falls per 1000 patient days. Four (<1%) patients deceased within the duration of this study, and none of the deaths were due to a hospital fall.Most falls occurred in patients’ rooms  and lessp ≤ 0.001), percentage reporting falls in the previous year , number of chronic diseases  vs. non-fallers: Md 5.0 (IQR 3.0–6.0), p = 0.001), and prevalence of multimorbidity . Additionally, the prevalence of some medical problems was significantly higher in the fallers group: orthostatic hypotension , Parkinson’s disease , and diabetes . In the in-patient fallers group, the total cholesterol level was significantly lower (133.5 (112.0–165.0) mg/dL vs. 179 (147.0–213.0) mg/dL in non-fallers, p ≤ 0.001) in addition to LDL and HDL cholesterol levels, and the serum creatinine level was significantly higher. However, the percentage of chronic kidney disease and the prevalence of other chronic diseases were not substantially different in both groups. Patients who experienced a hospital fall had a significantly higher risk of thromboembolic complications as assessed using the CHA2DS2-VASc scale.The in-patient fallers’ and non-fallers’ sociodemographic and chosen medical characteristics are presented in p = 0.01), the prevalence of polypharmacy was similar. The percentage of patients taking some medications was significantly higher in the in-hospital fallers group: insulin , metformin , statins , and benzodiazepines . This difference was on the verge of statistical significance in the case of neuroleptics .The in-patient fallers’ and non-fallers’ pharmacotherapy characteristics are presented in p = 0.03). The handgrip strength did not differ significantly between in-hospital fallers and non-fallers. Additionally, we did not observe any difference between fallers and non-fallers in the percentage of patients with dynapenia. Most patients who experienced a fall in the hospital were significantly frailer according to the Clinical Frailty Scale; the level of frailty status classified with the CFS was significantly higher in fallers (Md = 5.5 (5.0–6.0) vs. 5.0 (4.0–5.0) in non-fallers, p = 0.01). The mean BMI and percentages of patients with BMI below 24.0 kg/m2 and BMI above 30 kg/m2 were not significantly different between the study groups. Additionally, the MNA-SF score did not differ significantly.The Barthel index and the Duke OARS scale median scores were lower in the fallers group, although the differences were not statistically significant. 2 = 0.208). In the next step, we added to this model a block of another 16 patient characteristics that were significantly correlated with in-patient falls in the univariable analyses: Barthel index, IADL, sex, diabetes mellitus, Parkinson’s disease, number of conditions, taking statins, insulin, sulfonylurea, metformin, quetiapine, neuroleptics, benzodiazepines, SSRI, serum level of cholesterol, and creatinine. The backward stepwise regression in Model 2 confirmed the significance of four of these variables: Parkinson’s disease, statin, benzodiazepine, and insulin use, and it was found that the CFS variable was statistically insignificant. The overall success rate for the model was 98.2%, with the same specificity (100%) as Model 1 and better (44.4%) sensitivity (Nagelkerk’s R2 = 0.579). The Hosmer–Lemeshow goodness-of-fit p-values for Model 1 and Model 2 were above 0.05, leading to rejection of the null hypothesis of a lack of fit.We performed a multivariable logistic regression analysis on falls in the hospital as a dependent variable. In the first step, we included in the regression Model 1 a block of four predictors: history of falls in the last 12 months, a positive test for orthostatic hypotension, result in the Clinical Frailty Scale, and result in POMA test, as shown in p-value confirmed it fitted well, and Nagelkerk’s R2 was 0.541, similar to that of Model 2.Based on Models 1 and 2, we created the final multivariable logistic regression model of the determinants of in-hospital falls, using the enter method, which included only six relevant, statistically significant variables , even though it is a group with a high frequency of characteristics that are considered important fall risk factors ,28. It mFalls in older adults are considered one of the geriatric syndromes because of their high prevalence, multiple causes, reoccurrence, and serious consequences. The majority of hospital falls observed in our study occurred while getting up (43%) or walking (22%) in a patient’s room (71%) or bathroom (21%). Half of them resulted in an injury requiring medical intervention, and the hospital length of stay of patients that experienced in-hospital falls was significantly longer. Struble-Fitzsimmons described the location and activity of patients related to falls in the department of geriatric psychiatry. Most of the 61 falls, 67.8%, occurred in the patient’s room (44.1%), the bathroom (23.7%), and the corridor (18.6%). The most common activities of the patients during the fall were walking (49.1%) and shifting . More than half (57.1%) of all transfer-related falls occurred while getting out of bed . Draper In our study, in-hospital falls were significantly more frequent among people dependent on others during basic and instrumental activities of daily living, with multimorbidity and taking more medications  and reporting falls in the last year. They were more often diagnosed with Parkinson’s disease, diabetes, orthostatic hypotension, lower cholesterol , and higher serum creatinine. The characteristics of gait and balance measured by the POMA score were significantly worse in the in-patient fallers group. They were also frailer according to the CFS scale.The fact that 1/4 of the falls occurred in the bathroom and 3/4 of those who experienced a fall were dependent on others for bladder control and using the toilet or bathroom demonstrates the importance of properly securing the use of the bathroom by elderly patients in the geriatric ward. It is worth mentioning that the housing conditions were not optimal. All patients shared toilets and showers, which could also have influenced these results. Most of the falls in our ward occurred while the patient was standing up, which could be directly related to orthostatic hypotension ,35. This2) and increased risk of hospital falls [2) appeared to be an in-hospital fall risk factor [No significant association with being a faller was observed in our study for many other recognized risk factors for falls. However, this may be due to the geriatric ward patients’ specificity , as we observed in our previous analyses . So, foral falls , and in k factor . Decreask factor ,39. Howek factor .Many researchers are still looking for the best tool for in-patient fall risk screening . We alsoAs revealed by multivariable logistic regression, the most important independent predictors of falls in our group of geriatric patients were a positive history of falls within the previous 12 months, orthostatic hypotension diagnosed at the beginning of hospitalization, diagnosis of Parkinson’s disease, and taking benzodiazepines, statins, and insulin. However, the model built on these variables allowed for identification of people with no risk of falling in hospital rather than those who suffered a fall. Nevertheless, it points to patient characteristics that should be paid close attention during hospitalization. Indeed, an indispensable element of assessment of a geriatric patient should be the question about falling in the last 12 months, performing an orthostatic test, and paying attention to the medications taken . Our stuThe registration of falls conducted in the hospital ward allowed us to analyze the circumstances of their occurrence and potential risk factors that may guide the appropriate intervention. Diagnosis of the causes of falls and targeted interventions can reduce the risk and frequency of occurrence to prevent morbidity and mortality associated with falls. This is an element of the appropriate quality of care in a medical facility, which may also translate into economic results of its functioning.The main limitation of this study is that it was a cross-sectional study based on retrospective data, and the study sample consisted of patients from only one geriatric ward, followed over a relatively short period of eight months. Hence, they cannot be generalized to the entire population of patients hospitalized in geriatric wards in Poland. Furthermore, the relatively small group of patients who fell in the hospital may also have affected the results. As our study was not a prospective clinical trial but a “usual practice” study, we included final patient clinical assessment results as part of the comprehensive geriatric assessment rather than scores for individual questions on different scales. Therefore, the data collected during this study did not allow evaluation of the Cronbach alpha or other psychometric properties of most scales (except for the Barthel index scores and Duke OARS IADL).Our study confirmed that falls affect a relatively low percentage of people hospitalized in the geriatric ward. Still, half of the cases were associated with severe injuries and extended hospital stays, so they should be treated as ‘never events’ for patients in a hospital. Therefore, we need to pursue fall prevention much more aggressively. It is crucial to document falls and their circumstances in a given medical facility and analyze them from the perspective of risk factors typical of hospitalized patients. Our study showed that in the case of the geriatric ward, special attention and preventive measures should be directed at patients with a positive history of falls in the last year, diagnosed with orthostatic hypotension and Parkinson’s disease, and treated with statins, benzodiazepines, or insulin. It is worth extending these studies to other geriatric wards and assessing the results obtained in prospective analyses from the perspective of the effectiveness of preventive interventions.


IL18), as an important regulator of both innate and acquired immune responses, was selected as candidate gene and subjected to the expression profile analysis, single nucleotide polymorphism (SNP) scanning and association analysis by using quantitative real-time PCR (qRT-PCR), PCR amplification, Sanger sequencing, and KASP genotyping. The results of qRT-PCR indicated that IL18 is predominantly expressed in lymph and lung compared with that in the other tested tissues. In addition, three novel polymorphisms  were identified in IL18, and the three SNPs were in a strong linkage state. Therefore, only a SNP was genotyped and performed association analysis in the enlarged experimental population, the result of association analysis demonstrated that the polymorphism g. 24991651 A > G was significantly associated with RBC, MCV, MCHC, and RDW_CV. These results will provide the reference values and the novel genetic markers of hematological parameters in sheep.Hematological traits are important indexes to evaluate health status and immunological conditions in human and livestock. In this study, we measured the hematologic indexes of 819 male Hu lambs and performed the descriptive statistical analysis. The results showed the coefficients of variation of partial indexes were >10%, and the heritability for mean erythrocyte volume (MCV), white blood cell count (WBC), hemoglobin concentration (HGB), hematocrit (HCT), and red blood cell (RBC) distribution-standard deviation (RDW_SD) were medium to high, ranging from 0.17 to 0.43. In addition, Interleukin 18 ( Ovis aries) are important economic animals, which provide people with valuable agricultural commodities  is a member of IL-1 family of cytokines, and first discovered for its interferon-γ-inducing properties, which play crucial roles in the regulation of innate and acquired immune response , and erythrocytes , which are important indexes for evaluating the immune capacity of animal . To dateresponse , 18, anddiseases , while hon human , there aIL18 gene was considered as candidate gene, the expression features of IL18 gene were analyzed, and the polymorphisms for IL18 gene were identified to perform an association analysis of hematologic indexes and different genotypes. These results will provide the reference information and the potential genetic markers of hematological parameters in sheep.Hence, in this study, we measured the hematologic indexes of 819 male Hu lambs and estimated their genetic parameters. Simultaneously, All animal studies were performed in strict accordance with the guidelines proposed by the Regulation of the Standing Committee of Gansu People's Congress. The collection of blood and tissue samples as well as the experimental procedures involved in this study was approved by the Ethics Committee of the College of Pastoral Agriculture Science and Technology of Lanzhou University.n = 819) used in this study were obtained from four Hu sheep farms as follows: Zhongsheng Huamei Sheep Industry Development Co. Ltd.; Shandong Runlin Sheep Industry Co. Ltd.; Changxing Yongsheng Husbandry Co. Ltd.; and Hangzhou Pangda Agricultural Development Co. Ltd. All lambs were transferred to Minqin Defu Agriculture Co. Ltd., 56 days after weaning, and reared indoor in a single pen with free access to clean water and pellet feed, of which the pellet feed is commodity material from Gansu Sanyangjinyuan Husbandry Co. Ltd. Throughout the period, all lambs used the same immunization procedures, feeding regime and management methods according to our previous report . The instrument was installed and operated in the veterinary clinic at the Minqin Defu Agriculture Co. Ltd; the samples collected were measured within 10 min of collection according to sheep standard. After slaughtered, a small portion tissue sample from the same section of the heart, liver, spleen, lung, kidney, rumen, duodenum, lymph, tail fat, and longissimus dorsi were collected from each sheep, briefly washed with PBS and placed in freeze tube (2 ml), and immediately preserved in liquid nitrogen. At the end of the slaughter experimental procedure, the tissue samples placed in liquid nitrogen were transferred to the laboratory, then stored at −80°C until further use.The male Hu lambs with healthy and detailed pedigrees (s report . At 180 n = 819) for collecting the tissue sample; total RNA was extracted from 10 tissues  using the TRIzol reagent  in accordance with the manufacturer's instruction. First-strand cDNA was synthesized from 2-μg total RNA using an Evo M-MLV RT Kit with gDNA Clean for qPCR  following the manufacturer's protocols.Genomic DNA was extracted from the above blood samples using an EasyPure Blood Genomic DNA Kit  following the manufacturer's instructions, and the extracted DNA were used as a template for subsequent PCR amplification and KASP genotyping studies. Four male Hu sheep were randomly selected at 6 months of age from the experimental population . Specific primers (IL18-expression-F and IL18-expression-R) for IL18 gene (Accession No. NM_001009784.3) as listed in −ΔΔCT method was used to calculate the expression level (The expression levels of on level .IL18-SNP-F and IL18-SNP-R) was designed for IL18 gene (Accession No. NC_040266.1) using Oligo 7.0 , with a final extension 72°C for 5 min. The 1.5% agarose gel electrophoresis was used to check the amplified products, then, the PCR product was sequenced using Sanger sequencing by Tsingke . The sequencing results were blast to by DNAstar software to identify the candidate SNPs. Finally, the competitive allele-specific fluorescence resonance energy transfer (FRET)-based PCR were used to genotype the SNPs identified within IL18 gene according to a previously studied method  to estimate variance components and heritability. The pedigree was used for constructing the matrix of relationships between the individuals. The linkage disequilibrium analysis and construction of haplotypes were performed using Haploview 4.2, the allele and genotypic frequency and Hardy-Weinberg equilibrium (HWE) testing p-value were calculated using SNPassoc package of R language (version 4.1.0). The heterozygosity (He), homozygosity (Ho), polymorphic information content (PIC), and effective allele number (Ne) were directly calculated by using online software  based on the allele frequency, genotypic frequency and number. The association of the different genotype with hematological parameter indexes, including RBC (red blood cell count), HGB (hemoglobin concentration), HCT (hematocrit), MCV (mean erythrocyte volume), MCH (mean erythrocyte hemoglobin content), MCHC (mean erythrocyte hemoglobin concentration), RDW_SD (red blood cell distribution-standard deviation), RDW_CV (red blood cell distribution–coefficient of variation), and WBC (white blood cell count) was performed by using SPSS 17.0 software. The following general liner model was adopted: Yijkl = μ + Genotypei + Batchj + Fatherk + Motherl + εijkl, where Yijkl represents the traits observation value, μ is the population mean, Genotypei represents the effect of genotype, Batchj is the effect of the jth batch , Fatherk and Motherl are the family effects within breed, εijkl is the random error. One-way ANOVA was performed to estimate the difference of different genotypes, the result was expressed as “mean ± standard error (SE).” A p < 0.05 was considered as the statistically significant criterion. The bar graph and violin plot were drawn using the ggplot packages of R software (version 4.1.0).The multiple traits model was constructed based on average information (AI) restricted maximum likelihood method (REML) using Hiblup software  were calculated, and shown in p > 0.05).First, in the experimental population of 96 Hu sheep, these three SNPs were genotyped by the KASP assay, and all three genotypes were generated: GG, GA, AA/GG, GA, AA/TT, TA, AA, respectively . Then, tIL18 on selected traits. The association analysis between different genotype and traits was performed by using SPSS 17.0 software. The results demonstrated that the polymorphism g. 24991651 A > G was significantly associated with RBC, MCV, MCHC, and RDW_CV, and the individuals with AA genotype had higher RBC and MCHC than the individuals with GA and GG genotypes (p < 0.05), while the MCV in the animals with AA genotype was lower than those of the animals carrying the GA and GG genotypes (p < 0.05)  .In livestock breeding, health-related traits are becoming a priority, while hematologic parameters are important to evaluate the health condition, feeding management and nutrition level of animal, and the variation hematologic traits are caused by genetic and non-genetic  . At presIL18 gene was used as a candidate gene to detect the expression level and identify the polymorphisms. First, we detect the expression feature of IL8 in different tissues of Hu sheep aged 6 months, the result showed that the broad expression pattern of IL18 gene in Hu sheep, with expression detected in all 10 of the tissues tested , and the expression level of IL18 was evidently higher in lymph and lung tissues compared with the others tested tissues (p < 0.05). Fournout et al. reported IL18 expression levels in different organs of piglets, the results demonstrated that the expression level of IL18 was higher in the lymph, while IL18 is weakly expressed in the lung , and all the phenotype measured values of RBC, MCHC, and RDW_CV in the experimental population with the AA genotype were evidently higher than those with the GA and GG genotypes (p < 0.05), there was no evident difference between the GA and GG genotypes. The phenotype values of MCV in the animals with the AA genotype were significantly lower than those with the population with the GA and GG genotypes (p < 0.05), whereas the difference between GG and GA were not significant.Genetic variability of hematological indexes will directly or indirectly affect the profitability of the sheep breeding industry. Screening genetic variations of the key candidate genes related to the hematological indexes will contribute to design the breeding strategies for evaluating the animal health condition. Single nucleotide polymorphisms are served as the most effective and extensive DNA marker in the modern genetic breeding. Interleukin 18, as a immune regulator, plays a vital role in immune responses . In thisthe lung . The lymthe lung . Furthertructure , 33. TheIL18 may be regarded as candidate genetic markers for evaluating the health state and the feeding management of sheep. In spite of this, the functions of IL18 gene need to be further explored at the cell and protein levels.The changes observed in MCHC, MCV, and RDW are probably directly associated with the reticulocytosis . In addiIL18 expression features were detected in different tissues, the results indicated IL18 expressed predominantly in lung and lymph compared with the others tested tissues. Additionally, a novel polymorphism detected in IL18 was significantly association with RBC, MCV, MCHC, and RDW_CV. These results provide the reference information of sheep hematological parameters and identified the potential of the ovine IL18 gene as a candidate for improving immune traits in the sheep breeding program.In this study, the descriptive statistics and heritability of hematologic traits were estimated in male Hu lambs, revealing that the partial hematologic indexes have great potential for selection and show medium-to-high heritability. Simultaneously, the The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/All animal studies were performed in strict accordance with the guidelines proposed by the Regulation of the Standing Committee of Gansu People's Congress. Collection of blood and tissue samples as well as experiments procedures involved in the present study were approved by the Ethics Committee of the College of Pastoral Agriculture Science and Technology of Lanzhou University.WW and DZ designed and conceived the experiments. DZ, XZ, FL, YuaZ, XL, JW, LZ, YukZ, JC, WL, CL, and BZ contributed to the sample and data collection. DZ, XY, LZ, and JW involved in RNA and DNA extraction. DZ wrote the manuscript. WW, XZ, and DZ reviewed and edited the manuscript. All authors have read and approved the final manuscript.This work was supported by the National Key R&D Program of China (2021YFD1300901), the National Joint Research on improved breeds of Livestock and Poultry (grant no. 19210365), and the Key R&D Program of Gansu Province (grant no. 20YF3NA012).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.