Then, we validated the upregulation of zfp281 in adipose regeneration via immunofluorescence. Following that, we found that ZNF281 (the human homolog of Zfp281) was upregulated in most types of cancer and related to worse prognosis in 10 tumors. We further investigated the role of ZNF281 in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), pancreatic adenocarcinoma (PAAD), and stomach adenocarcinoma (STAD) and confirmed the high accuracy in the clinical diagnostic feature. Beyond that, based on these three types of cancers, we analyzed the ZNF281-related tumor immune infiltration and DNA methylation sites and finally built risk prediction models for future disease diagnosis. Taken together, our findings provide new insights into the dual role of ZNF281, and we found that it was a potential biomarker for regeneration and tumor prognosis.Regeneration and tumorigenesis are indicated as related processes, while regeneration leads to life and the outcome of tumorigenesis is death. Here, we show the upregulation of  Regeneration is characterized by the process of restoring homeostasis when organs sense the signals of damage, and this renewal process is orchestrated by a complex network of gene regulation and cellular processes . Like wozfp281, the human homolog of which is ZNF281, upregulated in a mice adipose regeneration model through RNA-seq. However, the role of ZNF281 in the regeneration program and tumorigenesis is largely unveiled.ZNF281 (zinc finger protein 281) plays a role in the regulation of embryonic stem cell (ESC) differentiation and is very important in maintaining cellular stemness . Knock-ovia controlled release of decellularized cells to induce adipocyte regeneration in C57BL/6N mice, and this model has been proven efficient in inducing adipogenesis ; however, in kidney renal papillary cell carcinoma (KIRP), higher ZNF281 expression was related to a better prognosis, and this may due to the complexity and heterogeneity in cancer. Then, in three types of cancer, cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), pancreatic adenocarcinoma (PAAD), and stomach adenocarcinoma (STAD), ZNF281 was confirmed as a good prognostic molecular marker considering the high accuracy in the clinical diagnostic feature. After that, we applied single-sample Gene Set Enrichment Analysis (ssGSEA) and found a positive relation between ZNF281 and T-cell activation in these three tumors. Then, we screened DNA methylation sites. The least absolute shrinkage and selection operator (LASS)) builds on linear regression by increasing the penalty term  to reduce the overfitting of the model and improve the generalization ability of the model  ogenesis . In addihe model . Statisthe model . FinallyThe procedure of decellularizing adipose tissues was accomplished following our previous protocols . All proin situ regeneration . The animals were sacrificed at 1, 2, 3, and 12 weeks, and the samples were obtained for RNA-seq and histological analysis.All animal model studies were approved in advance by the Animal Ethics Committee at the Chinese Academy of Medical Sciences & Peking Union Medical College and performed following the Animal Ethics Committee’s guidelines. Female eight-week-old C57BL/6 N mice were used for injecting the bFGF-loaded DAM mixture. As a control group, heparinized DAM mixed with PBS was used. The volume of suspension was 200 μL per site of injection  according to the manufacturer’s instructions, and RNA integrity was checked with the RNA integrity number (RIN) by using a bioanalyzer . RNA purification was performed by using the RNAClean XP kit  and RNase-Free DNase Set . After the quality control of RNA, the sequencing libraries were constructed. After library inspection using the Qubit fluorometer and Agilent 4200, the libraries were sequenced with the Illumina NovaSeq 6,000 sequencing platform, and the PE150 mode was selected. All the data were analyzed in R 3.6.4, and the R package DESeq2 was used for differential expression significance analysis. For filtrating differential expressed genes, the absolute value of log2(fold change) was selected above 2, and the κ ZNF281 antibody , rabbit polyclonal perilipin-1 antibody , CoraLite 488-conjugated goat anti-rabbit IgG (H + L) , and CoraLite 594-conjugated goat anti-mouse IgG (H + L) . The nuclei were stained with DAPI (Invitrogen). Single-channel and merge images were generated in Photoshop.After 24–48 h fixation , the samples retrieved from the animals were dehydrated and embedded in paraffin (Leica) for routine sectioning. The sections underwent deparaffinization and rehydration, and then, antigen retrieval was processed in a microwave in citric acid (Solarbio). After washing with PBS, slides were blocked with 5% goat serum for half an hour at 37°C, and overnight incubation with the primary antibody at 4°C was performed. Secondary immunofluorescent-tagged antibodies were used to incubate slides for 1 hour at 37°C for signal amplification. The following antibodies were used for immunofluorescence: mouse monoclonal IgG2a ZNF281 in normal tissues was analyzed in the Human Protein Atlas (HPA) online platform (https://www.proteinatlas.org/)  and the Genotype-Tissue Expression (GTEx) database using USCS Xena (http://xena.ucsc.edu/) on 16 August 2022  . Based oust 2022 . The datZNF281 or model risk scores, patients could be subdivided into the high-expression group and the low-expression group. The survminer R package was used for visualization, and the survival R package was used for the statistical analysis of survival data. OS was set as the survival outcome.The survival curve  can describe the survival of each group of patients. Based on the median expression of ZNF281 was used as the input in ROC analysis in 30 types of cancer. To proceed with further analysis, we selected tumors for which ZNF281 might be recognized as a risk factor based on differential analysis, OS, ROC, and AUC; then, CESC, PAAD, and STAD were selected.The receiver operating characteristic (ROC) curve is a comprehensive index reflecting the sensitivity and specificity of continuous variables, and the composition method reflects the correlation between sensitivity and specificity. When the expression of a molecule is a trend to promote the occurrence of events, the area under the curve (AUC) of this molecule will be >0.5, and the closer the AUC approaches 1, the better the prediction performance. When the expression of a molecule is contrary to the trend of event occurrence, the molecule will be <0.5, and the closer the AUC is to 0, the more accurate the prediction performs. In brief, the point closest to the top left of the curve is the critical value with the highest sensitivity and specificity on the ROC curve. The larger the area under the curve, the higher the diagnostic accuracy. The R package pROC was used in the ROC analysis, and the ggplot2 R package was applied to visualize results . The expZNF281 expression in CESC, PAAD, and STAD was calculated by Spearman correlation analysis.As an extension of Gene Set Enrichment Analysis (GSEA), single-sample Gene Set Enrichment Analysis calculates separate enrichment scores for each pairing of a sample and gene set. Gene markers for 24 immune cells were obtained from an article, and the classification and description of specific cells are shown in ZNF281 was calculated. Spearman correlation analysis was included. The stat R package was used. DNA methylation sites with p value less than 0.05 and Spearman correlation coefficient greater than 0.3 were selected.The correlation between the beta value of methylation sites within 5000bp upstream and downstream of the transcription start site (TSS) and the expression level of ZNF281 expression via Spearman and Pearson correlation analyses. To find genes with statistical significance, P (Spearman) and p (Pearson) less than 0.05 were selected as the basic screening rule. Genes with correlation coefficient (Cor) more than 0.55 or less than −0.55 for both Spearman and Pearson analyses in CESC and STAD were screened. For PAAD, the absolute value of Cor (Spearman) was filtered over 0.7 and the absolute value of Cor (Pearson) was filtered over 0.6. This procedure was achieved via the stat R package.In CESC, PAAD, and STAD, we investigated the correlation between other genes and ZNF281-related genes was selected as the input in LASSO. In the process of ten-fold cross validation, the seed number was set as 2021. The screening threshold of the model coefficients was selected as lambda. min. According to the selected genes by LASSO, we built the risk models in CESC, PAAD, and STAD. Also, the LASSO coefficients were used to calculate the risk scores with the expression of genes in models. The glmnet and survival R packages were used.The expression of ZNF281 at 1, 3, and 5 years were calculated.Time-dependent receiver operating characteristic (tdROC) curve analysis was mainly used to analyze the predictive efficacy of one continuous variable in predicting outcomes related to time. The tdROC was used to complete the analysis, and ggplot2 was used to visualize the results. Also, the tdROC results of the expression of zfp281 is shown between the two groups. Compared to the control group  showed a significant adipose regeneration phenomenon. Moreover, zfp281 expression in the early stage (1 week) was validated higher in the bFGF-loaded DAM group , CESC , KIRP , LUSC , MESO , PAAD , SKCM , STAD , THCA , and UCEC . However, patients with lower ZNF281 expression levels based on the median value showed the worst prognosis in KIRC . However, in the other types of cancer, ZNF281 was not related to prognosis, and the results are shown in According to the results of survival analyses , patientZNF281 showed a good diagnostic ability in differentiating tumors from benign tissues in CESC  might be related to the transcription of ZNF281 in PAAD , PAAD , and STAD . Furthermore, these three lncRNA prognostic models for CESC, PAAD, and STAD exhibited good predictive ability for PFI at 1, 3, and 5 years  would be a potential biomarker in some forms of regeneration and tumorigenesis, which share similar molecular pathways. We first detected the upregulation of zfp281 in de novo adipogenesis through RNA-seq and then validated the histological expression in the early stage of the adipose regeneration model. Through literature review, we found that ZNF281 was related to the tumor development and progression mechanism, such as EMT (ZNF281 expression in pan-cancer and related normal tissues using RNA-seq data from TCGA and GTEx and found the upregulation of ZNF281 in most types of cancer. Moreover, the ZNF281 expression level was related to worse prognosis in 10 types of cancer. However, in KIRC, higher expression of ZNF281 was expected to have survival benefits given the OS analysis. Further investigation indicated ZNF281 had good prognostic value in CESC, PAAD, and STAD. Also, certain types of T-cell activation were positively correlated to the ZNF281 expression. In addition, we explored two DNA methylation sites in the TSS region of ZNF281 that may regulate its transcription activity in PAAD and could be targeted when treating PAAD. Finally, we established clinical prognostic models based on ZNF281-related lncRNA in CESC, PAAD, and STAD.We hypothesized that ZNF281 (zfp281 in h as EMT . ConsideZNF281 has also shown its role in regeneration regulation. ZNF281 inhibits the differentiation of neurons, and higher expression was proven related to a worse prognosis in neuroblastoma . MoreoveSharing common molecular pathways, more and more evidence indicates that regeneration and carcinogenesis are related processes, although accompanying diverse outcomes are life and death . In this


To compare treatment within 12 months of diagnosis, and survival by country of birth for people diagnosed with invasive non-small cell lung cancer (NSCLC) in New South Wales (NSW), Australia.A population-based cohort study of NSW residents diagnosed with NSCLC in 2003–2016 using de-identified linked data from the NSW Cancer Registry, NSW Admitted Patient Data collection, Emergency Departments, Medicare Benefits and Pharmaceutical Benefits Scheme, and National Death Index.Odds of receiving any treatment, surgery, systemic therapy, or radiotherapy respectively, in the 12 months following diagnosis were calculated using multivariable logistic regression. The hazard of death  at one- and five-years following diagnosis was calculated using multivariable proportional hazards regression.27,114 People were recorded with NSCLC in the 14-year study period. Higher percentages of older males from European countries applied in the earlier years, with a shift to younger people from South East Asia, New Zealand, and the Middle East. Adjusted analyses indicated that, compared with the Australian born, people from European countries were more likely to receive treatment, and, specifically surgery. Also, people from Asian countries were more likely to receive systemic therapy but less likely to receive radiotherapy. Survival at one- and five-years following diagnosis was higher for people born in countries other than Australia, New Zealand the United Kingdom and Germany.Variations exist in treatment and survival by country of birth in NSW. This may be affected by differences in factors not recorded in the NSW Registry, including use of general health services, family histories, underlying health conditions, other intrinsic factors, and cultural, social, and behavioural influences.The online version contains supplementary material available at 10.1186/s12890-022-02163-z. Lung cancer is the leading cause of cancer death for males and females in NSW, with similar age-standardised incidence, mortality and survival outcomes to corresponding national figures , 2. For Australia’s diverse, multicultural population is reflected in NSW where the percentage of people born outside of Australia increased to 28% in 2016, with 25% of that population mainly speaking a language other than English at home . During Previous studies in NSW and other Australian jurisdictions have indicated migrants to generally have lower overall cancer incidence and mortality rates than the Australian-born, although differences applied by cancer type and country of birth –7.We aim in this study to determine whether differences exist in NSW between people diagnosed with invasive non-small cell lung cancer (NSCLC) during 2003–2016, in treatment and survival by country of birth. We used analyses adjusted for the baseline characteristics including age at diagnosis, sex, year of diagnosis, comorbidity prevalence, and socioeconomic status.This is a population-based cohort study using linked cancer registry, treatment and death data. The analysis used linked diagnostic data for invasive NSCLC from the NSW Cancer Registry (NSWCR) , hospitaProbabilistic, privacy-preserving, person-level linkages of NSW datasets were performed by the Centre for Health Record Linkage (CHeReL), and of Commonwealth datasets, by the Australian Institute of Health and Welfare (AIHW) .Ethics approval was provided by the NSW Population and Health Services Research Ethics Committee (HREC/15/CIPHS/15) and the AIHW Ethics Committee (EO2016/1/224).The study population comprised all NSW residents aged 18+ years diagnosed with primary invasive NSCLC of the lung, bronchus, or trachea  with histopathological confirmation, during 2003–2016 .Multiple primary cancers, NSCLC recorded from death certificate only, and cancer cases of unknown country of birth were excluded from the cohort. Residents of local health districts adjacent to NSW borders were also excluded as they may have travelled to other jurisdictions for treatments that were not recorded in NSW Fig.  9].Fig..Fig.9].FData on types of treatment received  during the 12 months from diagnosis (including neoadjuvant therapies), included fact of surgery identified using APDC data; fact of radiotherapy using a combination of APDC and MBS data; and fact of systemic therapy from a combination of APDC, MBS and PBS data  was categorised as Australia, China , Germany, Greece, Italy, Lebanon, New Zealand, the Philippines, United Kingdom, and Vietnam, based on the country of birth recorded on the NSWCR . These countries represent the ten countries of birth with the highest lung cancer incidence during the study period. All other countries were grouped into “other English-speaking” or “other non-English speaking” categories .Age was analysed as either a continuous or categorical  variable. Socioeconomic status of residential address at time of diagnosis was classified using the Index of Relative Socioeconomic Advantage and Disadvantage developed by the Australian Bureau of Statistics . The yeaCross tabulations and the Pearson chi-square test; comparisons  were used to describe cohort characteristics for each covariate, with people born in Australia as the reference group , 13. MulMultivariable logistic regression was also used to determine odds ratios for treatment  , 13. AllMultivariable proportional hazards regression models were created to obtain hazard ratios for death  in the first- and five-year period following diagnosis , 13–15. Data preparation and analyses were undertaken using SAS 9.4  , and R 3There were 37,560 invasive lung cancers diagnosed in NSW residents during 2003–2016. After applying the study inclusion criteria, 27,114 people with NSCLC were included in the cohort , Italy (79%), and Lebanon (79%). Compared with the Australian-born, people born in China, Greece, Italy, and the United Kingdom tended to be older (median age > 70 years) while people born in the Philippines, New Zealand, and Vietnam tended to be younger (median age < 70 years).other English-speaking countries category. The prevalence of comorbidities in the year leading to cancer diagnosis varied across countries, ranging from 14% for China to 26% for Italy. More cases were diagnosed in the later time periods, particularly for China (9% of cases diagnosed in 2003–2004 increasing to 20% in 2015–2016), the Philippines (6% of cases diagnosed in 2003–2004 increasing to 22% in 2015–2016), and Vietnam (9% of cases diagnosed in 2003–2004 increasing to 21% in 2015–2016). Table Number of cases increased as level of disadvantage increased, except for the The percentage of people lost to follow up at one year following diagnosis varied across countries, from 0.1% for Australia to 5.3% for New Zealand. A similar pattern was seen for loss to follow up at five years following diagnosis, varying from 0.2% for Australia to 6.9% for New Zealand.After adjusting for age at diagnosis, sex, year of diagnosis, comorbidity score, and socioeconomic status, the percentage of people recorded as having any treatment in the 12 months from diagnosis varied across country of birth categories from 68% for Australia to 76% for Greece  and from 69% for China to 77% for Italy .Corresponding percentages receiving any treatment within 12 months from diagnosis for more advanced disease varied from: 68% for Vietnam to 93% for other English-speaking countries , and from 61% for New Zealand to 71% for the Philippines (distant disease). Compared with the Australian-born, and apart from those born in Germany, those born in most European or other English-speaking countries had higher odds of receiving any treatment. Odds of receiving any treatment was also elevated for people born in Lebanon. While this pattern generally applied for each extent of disease, “statistical significance” was inconsistent. In addition, for distant disease, receipt of any treatment had higher odds for those born in the Philippines and other non-English speaking countries than for the Australian-born. , 40% for Vietnam to 53% for other English-speaking countries , and 27% for Lebanon to 48% for other English-speaking countries . Compared with the Australian-born, those born in Greece, Italy, other English-speaking, and other non-English speaking countries had higher odds of surgery, whereas lower odds applied for those born in Vietnam. While this generally applied for each extent of disease, “statistical significance” was less consistent. In addition, people born in Vietnam had lower odds of surgery for localised disease. ; 9% for Lebanon to 24% for Greece ; 39% for Vietnam to 58% for the Philippines ; and 37% for New Zealand to 55% for the Philippines (distant disease). Compared with those born in Australia, people from the United Kingdom, China, the Philippines, Greece, and Italy were more likely to receive systemic therapy for all NSCLC, people from Greece were more likely to receive systemic therapy for regional disease, and people from the United Kingdom, China, the Philippines, Greece, Italy, Lebanon, and other non-English speaking countries were more likely to receive systemic therapy for distant disease ; 16% for China to 29% for Vietnam ; 38% for Vietnam to 54% for Lebanon ; and 38% for China to 53% for Lebanon (distant disease). Compared with those from Australia, people from Asian countries were less likely to receive radiotherapy , and distant disease , other English-speaking countries, and other non-English speaking countries had a reduced hazard of death at one year following diagnosis. This pattern was seen across all extents of disease , other English-speaking countries, and other non-English speaking countries had a lower hazard ratio for death in the five years following diagnosis. This pattern was seen across all extents of disease  and older age, male sex, and comorbidities tended to be associated with an increased risk of death (a higher HR), which was not explained by the extent of disease at diagnosis. Further research is needed into the underlying causes of these differences.During the 2003–2016 study period, NSCLC treatment options and guidelines have changed markedly . The incStudy limitations included lack of access to data on systemic therapies and treatments given under a clinical trial protocol that were not yet included in the PBS. Also, we did not have access to data on public hospital treatments performed outside of NSW or treatments performed in other countries. We consider it possible that some people may have returned to their birth countries for a second opinion and treatment. A similar limitation exists with the survival results, as people may have returned to their home country prior to dying there, such that these people would be misclassified as alive in our data.It is also possible that the comparatively higher survival seen in people born outside Australian may be partly due to the health requirements and screening of migrants at entry to Australia, which may have led to migrant groups being younger, fitter, and healthier than the Australian-born  .The use of country of birth to infer cultural differences has limitations, as it may not accurately reflect a person’s culture or ethnicity. The analyses did not account for heterogeneity between people within each country of birth group . Also peAlthough the need for complete and accurate data on country of birth or cultural background has been acknowledged, few data elements are currently available in routinely collected administrative datasets that would allow more in-depth analyses by ethnicity , 19. FurThe present data indicate that variations exist in NSW in extent of disease at diagnosis, treatment, and survival from NSCLC for people born in different countries. These variations may be influenced by differences in the underlying health of migrants from different countries, cultural and social factors, differences in health behaviours (including tobacco use), and other factors. Further research is needed to investigate these and other possible explanations for variations in survival. Attempts should be made where possible to improve access to health services and better outcomes for all people diagnosed NSCLC in NSW.Variations exist in treatment and survival by country of birth in NSW. This may be affected by differences in factors not recorded in the NSW Registry, including use of health services, family histories, underlying health conditions, other intrinsic factors, and cultural, social, and behavioural influences. Means of complementing existing prognostic data with TNM and other prognostic indicators are needed, including new and emerging biomarkers. Major challenges include improving patient follow-up, as when they return to their birth countries in the terminal stages of their cancer treatment.Additional file 1. Logistic and proportional hazards regression and APDC, MBS, and PBS item code lists.


Escherichia coli, Bifidobacterium, and Fusobacterium nucleatum), and gut bacteria metabolites , which have the potential to improve the diagnosis, treatment, and prognosis of diseases. We found that therapeutic strategies targeting the miRNA–microbiome axis focus on miRNA drugs produced in vitro; however, some studies suggest that in vivo fermentation can greatly increase the stability and reduce the degradation of miRNA. Therefore, this method is worthy of further research.An increasing number of research suggests that the microRNA (miRNA)–microbiome interaction plays an essential role in host health and diseases. This bibliometric analysis aimed to identify the status of global scientific output, research hotspots, and frontiers regarding the study of miRNA–microbiome interaction over the past decade. We retrieved miRNA–microbiome-related studies published from 2011 to 2021 from the Web of Science Core Collection database; the R package bibliometrix was used to analyze bibliometric indicators, and VOSviewer was used to visualize the field status, hotspots, and research trends of miRNA–microbiome interplay. In total, 590 articles and reviews were collected. A visual analysis of the results showed that significant increase in the number of publications over time. China produced the most papers, and the United States contributed the highest number of citations. Shanghai Jiaotong University and the University of California Davis were the most active institutions in the field. Most publications were published in the areas of biochemistry and molecular biology. Yu Aiming was the most prolific writer, as indicated by the h-index and m-index, and Liu Shirong was the most commonly co-cited author. A paper published in the International Journal of Molecular Sciences in 2017 had the highest number of citations. The keywords “expression” and “gut microbiota” appeared most frequently, and the top three groups of diseases that appeared among keywords were cancer , inflammatory bowel disease (Crohn’s disease and ulcerative colitis), and neurological disorders . This bibliometric study revealed that most studies have focused on miRNAs , gut microbes (e.g.,  Approximately 100 trillion microbes inhabit the human body , and neamiRNAs are small non-coding RNAs about 22 nucleotides in length that regulate target gene expression . First dIn 2011, Bibliometric analysis is a statistical method that can be used for both qualitative and quantitative analysis and the evaluation of emerging trends in scientific research . DespiteSaccharomyces,” “Lactobacillus,”, “Bifidobacterium,” and “E. coli”. The present analysis was concerned with articles and reviews from 2011 to 2021. Publications irrelevant to the search subject were omitted. After the removal of duplicates, a text file containing the remaining 590 analyzed records was downloaded.All of the data were obtained from the WoSCC database, which includes high-quality scholarly peer-reviewed literature published worldwide and commonly used in bibliometrics . ConsideIn our study, the distribution of countries/regions, years of publication, and authors were analyzed by using the bibliometrix package in R (version 4.1.2). The fitting polynomial model was employed to better demonstrate the variations in the yearly document quantity. Meanwhile, we used the following indicators to assess publication quality by authors: Publications, citations, h-index (H), and m-index (M) are used to assess a researcher’s academic contribution and forecast future scientific breakthroughs . To evalThe VOSviewer Version 1.6.18  was utilized to map bibliometrics, such as co-authorship analysis of authors/institutions/countries, citation analysis of documents, co-citation analysis of journals/references, and co-occurrence analysis of keywords. The following are the VOSviewer parameters: counting method is full counting; the minimum number of citations per source is 100; visualization weights is citations; normalization is association strength; resolution for clustering is 1.00; the minimum cluster size is one; minimum line strength is 200; and the maximum number of lines is 500. Moreover, keywords plus that occurred more than five times were shown in two visualizations  of the co-occurrence analysis in order to discover hot topics in the interplay of microRNA and microbiome.R2 = 0.9813) (WoSCC was searched for 590 articles relating to the relationship between microRNA and microbiome published between 2011 and 2021. From nine publications (1.53%) in 2011 to 142 publications (24.07%) in 2021, the field’s global publications indicated a robust growth tendency. . The log 0.9813) .The contributions of countries to microRNA and microbiome research were assessed and illustrated by Bibliometric in a globe map . 49 counThere were a total of 1,009 institutions engaged in this area. Shanghai Jiaotong University and University calif Davis contributed the greatest number of publications , followed by Huazhong agriculture University , Tongji University, Sun yat-sen University, Zhejiang University, and Louisiana state University all followed with eight publications. We examined the co-authorship of 60 institutions with over four publications. The exclusion of fifteen items that were not connected revealed the collaborations of 45 institutions . Tongji International Journal of Molecular Sciences  had the most publications, followed by Frontiers in Microbiology , Scientific Reports , Plos One , and Frontiers in Immunology . We investigated 71 journals for all papers co-cited in more than 100 publications , followed by Nature , Proceedings of the National Academy of Sciences (PNAS) (902 citations), Cell (894 citations), and Science (699 citations). In all, 54 research areas were used to classify publications. Biochemistry and Molecular Biology was the field with the highest representation , followed by Microbiology , Pharmacology and Pharmacy , Gastroenterology and Hepatology , Immunology  and Multidisciplinary Sciences   .According to the number of publications, Yu AM. was the most prolific author with 10 publications , followed by Tu M. J. , Lukiw W. J. , Guan L. L.  and Dalmasso G.  . AccordiE. coli Endotoxin-Induced Acute Lung Injury in Mice” , Bartel D. P., , and Dalmasso G., .According to the analysis of citation, 70 documents contained more than 50 citations . The topin Mice” , with 40in Mice” . And theE. coli (68), gene expression (65), and microRNAs (61). A total of 195 keywords that were discovered to have appeared more than five times were analyzed . The fivThis study used bibliometric analysis and network visualization to conduct a comprehensive review of research progress on the interaction between miRNA and the microbiome, identifying hot topics within this field and predicting potential directions for future research.590 articles and reviews spanning 2011–2021 were retrieved. The polynomial-fitting curve showed an overall upward trend for the number of annual publications; 79% of all identified contributions were published in the latter half of the study period. Furthermore, 142 studies were published in 2021, and the curve predicted that more than 200 studies will be published in 2023; this indicates strong growth in the annual publication output in the field.in vivo fermentation and identifying the mechanism of miRNA–microbiome interaction .Keywords can be used to present and summarize the central argument and core content of the literature. This study used keyword co-occurrence analysis to explore the distribution and development of research hotspots in the field . The keyIn vitro indicated that the downregulation of one of these miRNAs, mmu-miR-665, upregulated the expression of the target gene Abcc3 during colonization, suggesting that miRNA may be implicated in gut microbiota-regulated changes in host gene expression -α and interleukin (IL)-6 and regulate suppressor of cytokine signaling 1 (SOCS1) on dendritic cells, thus playing a role in adaptive immune responses  miRNA-deficient (Dicer1ΔIEC) mice, which exhibit dysfunctional gut microbiota (F. nucleatum and E. coli) and affect their growth, supporting the above research results. Conversely, host miRNA may also regulate gut microbiota colonization and gene expression. In 2016, crobiota . Interescrobiota . TherefoF. nucleatum, Bacteroides fragilis, E. coli, and Enterococcus faecalis, accompanied by increased levels of inflammatory factors and macrophage inflammatory protein 3A (MIP3A) in the serum  ranks as the third-leading cause of cancer-related death worldwide and represents approximately 10% of all tumors every year . Multiplhe serum . Additiohe serum . Recentlferation . In addiferation . Thus, mF. nucleatum-related CRC by provoking tumor-specific proteins, such as c-Myc and cyclin D1  and ulcerative colitis (UC). Recently, a growing body of evidence has suggested that inflammation is connected to the overexpression of miRNA-21, which is positively correlated with histologically assessed disease severity . Moreoveroidetes . This suroidetes .via a MyD88-dependent pathway, promoting intestinal homeostasis (E. coli (AIEC) has been linked to IBD pathology as a cause or contributing factor  in a colitis mouse model and reverse the disruption of the intestinal immune barrier  have been widely used to treat diseases such as cancer, neurological disorders, and IBD , researchers have begun to produce miRNA drugs using in vivo fermentation.Because of the role of miRNA–microbiome interplay in modulating physiological and pathological conditions, therapeutic strategies such as dietary change, probiotic supplementation, fecal transplantation, and miRNA drug administration are promising . In phar and IBD . However and IBD . The strpression , whereaspression . Becausein vivo and then form recombinant RNA molecules in bacteria to regulate the expression of target genes  with wider coverage are strongly encouraged. Second, although the study period of 2011–2021 reflects the major research breakthroughs and hotspots, some original papers that made groundbreaking contributions to this field, along with newly published papers, may have been overlooked. Third, all information was extracted by the R package bibliometrix and VOSviewer, which may be biased by the results of other bibliometric tools.E. coli, Bifidobacterium, F. nucleatum, and butyric acid have the potential to improve disease diagnosis, treatment, and prognosis. Our results indicate that future research may explore miRNA drugs produced by in vivo fermentation, a technology that can greatly increase the stability and reduce the degradation of miRNA.This bibliometric study revealed that the number of publications in the field of miRNA–microbiome research in the past decade has increased continuously and rapidly. China was a major producer of studies, and the USA had a great influence in this field. The interaction between the microbiome and miRNA regulates host gene expression and is implicated in the pathogenesis of many groups of diseases, such as cancer , IBD (CD and UC), and neurological disorders , and this interaction has thus become a research hotspot. The literature suggests that miR-21, miR-155, miR-146a,


Exercise programs have shown anxiolytic effects in psychiatric patients. Adherence to exercise programs and subsequent long-term lifestyle change is influenced by acute affective responses of the exercise programs. This research aimed to assess acute affective responses of two different exercise modalities compared to a non-exercise control program and its effects on persisting physical activity behavior change.n = 26), nordic walking (n = 19), social contact control (n = 21). Affective responses were assessed pre, during, and post activity. General physical activity behavior was recorded prior to participation in the program, post program, and at follow-ups three and six months after the program.Sixty-six outpatients diagnosed with an anxiety disorder or posttraumatic stress disorder were randomly allocated to one of three groups in a randomized longitudinal controlled clinical pilot trial: climbing (Multilevel modeling analyzes of 1,066 individual data points revealed increases in affective valence in the exercise sessions compared to the social contact sessions. State anxiety decreased in the climbing group compared to the social contact group. Physical activity behavior was increased immediately following the program as well as at six months follow-up in both exercise groups. A larger increase in affective valence during and after the sessions was associated with higher physical activity post program.Climbing and conventional nordic walking exercise sessions revealed positive affective changes in outpatients indicating therapeutic potential of both modalities for acute emotion regulation. In accordance with theoretical models of human behavior change, it was judged that the experience of a more pleasant affective state following the exercise sessions induced more persisting effects on physical activity behavior after the exercise programs.https://www.clinicaltrials.gov/ct2/show/NCT03758599, identifier: NCT03758599. Physical activity is valued for its positive effects on physical and psychological health , 2. The Studies on exercise programs in the treatment of psychiatric disorders focus predominantly on the effects on symptom severity: For individuals with anxiety disorders, anxiolytic effects can be achieved through exercise programs . IndividWhile the positive short-term and long-term effects of exercise on mental health are widely researched and discussed, one of the major challenges is to design interventions which induce persistent behavior change with longer lasting effects within an evidence-based comprehensive framework . AffectiRecently, a controlled, randomized study comparing occupational therapy, swimming, and climbing was carried out in children and adolescents with mental and behavioral disorders: Results showed that climbing has a positive effect on immediate affective responses during the exercise bout compared to both swimming and occupational therapy . In a noHowever, study designs in which different exercise program effects are compared are rare, although the importance of this comparison is increasingly recognized , 24, 25.Therefore, the primary aim of the present project was to compare affective responses between different exercise programs based on multiple sessions of the programs. For this purpose, an already established program  was compared to a relatively new exercise program (climbing exercise) in groups of individuals with anxiety disorder or PTSD. Exercise programs were controlled for effects of social contact by implementing a social contact control program with the same amount of social contact, but without exercise. The secondary aim was to compare the effects of the two exercise programs on future physical activity behavior and to analyze the role of affective valence during the sessions of the programs on future physical activity behavior.The overarching aim of the research project was to analyze the effects of two exercise programs  in comparison to a social contact control group on various health-related outcomes, including symptom severity, in patients with anxiety disorder or posttraumatic stress disorder. In the present study, we focus on the affective responses and their role in future physical activity behavior as one of the health-related outcomes. Participation in the groups was offered as an add-on to the regular clinical outpatient care program in a low-threshold, interdisciplinary network in the area of Innsbruck, Tyrol.Participants were screened and enrolled by clinical professionals  in the Department of Psychiatry, Psychotherapy and Psychosomatics at the Medical University of Innsbruck. When assessed as eligible for the study, outpatients were invited to an informative meeting and randomly allocated to one of three groups by use of a computer-generated, blockwise cluster-randomization scheme with an allocation ratio of 1:1:1. Block sizes were a minimum of three and a maximum of eight. Whether participants had a diagnosis of AD vs. PTSD was not considered in randomization. This procedure was of an organizational nature, so that the participants were offered the earliest possible start of the study program to reduce drop out.Participants received study information and timetables for their group attendances by administrative staff of the Department. The program started within the following two weeks and the period ended after eight group sessions within four weeks. Follow-up measures were conducted immediately after, three, and six months after the program ended .In the first session, focus was set on the practical implementation. Participants were introduced to the program to be able to familiarize with the situation. The intervention was performed and personal assistance was provided as required.Starting with session two, affective responses  were assessed with standardized questionnaires at three points in time at each session: pre (beginning of the session), during (after 45 minutes), and post (immediately after) session . In sessThe participants were recruited by local treatment staff.Inclusion criteria were: (a) outpatients with a primary ICD-10 diagnosis of any anxiety disorder or posttraumatic stress disorder (PTSD) , (b) aged between 18 and 65 years, and (c) giving written informed consent.Exclusion criteria were: (a) patients with acute psychosis or suicidal behavior, (b) medical contraindication to exercise (assessed by a clinician), (c) somatic comorbidity with contraindication to moderate physical activity  (judged by patients primary care physician), (d) cognitive deficits , and (e) problems with German language .No a priori power analysis is available for the primary outcome affective responses. Since the present study is part of a research project to assess different health-related outcome variables, only one power analysis based on symptom severity was conducted for the research project, an outcome not considered in this study. However, the sample size of the present study is in the range of previously published studies, e.g., , 26, 27.All programs were led by two professionals, including clinical health psychologists, sport and exercise psychologists, sport scientists, training therapists, and physicians. All programs consisted of eight 90-minutes sessions spread over four weeks (two sessions per week). Both exercise programs were performed with comparable intensity. Participants in both exercise programs were instructed to perform the sessions with moderate intensity .At the beginning of each session, a standardized body-centered warm-up of ten minutes identical with the nordic walking group took place. The group sessions were held in an outdoor climbing gym when weather and temperature conditions allowed. In bad weather conditions, the indoor climbing gym was used. The general warm-up was followed by a climbing specific warm-up, which consisted of bouldering  for around 25 minutes. After warm-ups, the actual rope climbing sessions lasted around 45 minutes. During the first five sessions of rope climbing, only the therapist provided rope security. Safety and belaying of partners were trained throughout those sessions. Depending on participants' knowledge and skills, they were allowed to belay each other; however, always guided by a therapist. As in Gallotta et al. , climbinThe nordic walking group started with a ten-minute body-centered warm-up identical to the climbing group, followed by a five-minute nordic walking specific warm-up. Afterwards, the group walked with a moderate pace outdoors on varying paths for 70 minutes using the nordic walking technique. Specially designed poles were used in this technique to push against the ground with each stride, activating the upper body while walking. The session ended with a five-minute cool-down session identical to the climbing group.Social interaction is discussed as one of the anxiolytic mechanisms of exercise programs in group settings . The socThe dimension of affective valence was assesse by the Feeling Scale . This sThe dimension of perceived activation was assessed by the Felt Arousal Scale . This sThe State-Trait-Anxiety Inventory  is a 20Physical activity was assessed in a practitioner interview that took place four times during study participation. During a pilot phase prior to the present study, patients provided feedback and were observed to have difficulty completing the International Physical Activity Questionnaire . Therefhours of light intense physical activity/walking” x 0.75 + hours of “moderate intense physical activity” + hours of “vigorous intense physical activity” x 2.“The data on affective responses were collected across several sessions and were nested within patients. Since there is no data on comparing several program sessions available, the project included all compiled data. Ordinary methods of analyses of variances might produce biased inferential statistics since the inter-correlation of repeated observations in the same patients over time cannot be accounted for . TherefoCohens d  was calcFor the secondary research question, the differences in physical activity between groups were analyzed using SPSS version 26  on a per protocol basis. In a series of analyses of covariance with physical activity at t1 (pre program) as a covariate, group differences in physical activity at t2 (post program), at t3 (follow-up three months post program), and at t4 (follow-up six months post program) were analyzed. Pre-planned simple contrasts with “climbing group” as the reference category were conducted. Following the analyses on group differences, generalized estimating equations (GEE) were calculated to assess the role of affective valence in future physical activity. A linear relationship was chosen in accordance to previous literature  and a woP-values < 0.05 were considered as significant. Unless otherwise stated, data are presented as mean ± SD.n = 15) or lack of interest (n = 8). Seventy-three patients were randomized, and seven patients dropped out after the first session . The total sample for the analysis of affective responses consisted of 66 patients (mean age 44.2 ± 13.2 years). Twenty-six patients participated in the climbing group, 19 in the nordic walking group, and 21 in the social contact group . For perceived activation, 1,065 observations from 66 different patients were available . The intercepts for affective valence varied significantly across patients, variance = 2.4, F = 14.83, p < 0.001  = 81.30, p < 0.001, and group, F = 6.28, p = 0.003.A significant time-by-group interaction emerged for affective valence,  < 0.001 . Simple F = 2.53, p < 0.001  = 18.64, p < 0.001, but not for the factor group, F = 0.49, p = 0.617.Perceived activation showed a significant time-by-group interaction,  < 0.001 . No signp < 0.001, but not between sessions, variance < 0.01, p < 1.000.For state anxiety, 188 observations from 60 different participants were available . The intercepts for state anxiety varied significantly across participants, variance 108.6, F = 4.14, p < 0.018  = 44.10, p < 0.001, but not for factor group, F = 2.17, p = 0.123.A significant time-by-group interaction emerged for state anxiety,  < 0.018 . Simple F = 18.98, p < 0.001, and at t4, F = 3.89, p = 0.028  = 1.97, p = 0.151, d < 0.51.When adjusted by physical activity at t1, significant group differences in physical activity were found at t2,  = 0.028 . Simple B = 0.41, and post sessions, B = 0.37, was associated with higher physical activity at t2. No significant associations between changes in affect and physical activity were found for t3 and t4, p > 0.280. The models using the change in affective valence from pre-during session and pre-post session were widely similar.Generalized estimating equations showed the best model for the prediction of physical activity post program at t2 . PhysicaThe main findings of the present study are(1) Both types of exercise sessions resulted in more pleasurable and higher activated affective states as well as a short-term anxiolytic effect in individuals with anxiety or posttraumatic stress disorder, compared to social contact sessions without exercise.(2) Higher positive affective states during and after the exercise sessions were associated with intermediate term increases in physical activity.(3) The modality of exercise appears to be secondary for affective states, although small-sized beneficial effects were found in affective valence for climbing sessions compared to nordic walking sessions.(4) The increase in physical activity persisted six months following completion of the clinical pilot trial.The finding of a more pleasant, higher activated state after exercise sessions is consistent with findings in existing literature on single exercise bouts in psychiatric patients, e.g., , 25, 33.In the present study, a more pleasant, higher activated state during and after exercise was found in comparison to social contact sessions. Currently, the effect of social contact may be underestimated and only few studies control for these effects, e.g., , 25.However, when the exercise sessions are not compared to a physically inactive control condition, but the two exercise modalities are compared, similar beneficial changes in affect were observed , 25. TheThere is a further influence from indoor and outdoor effects. While in this study climbing was practiced indoors or outdoors, depending on the weather conditions, nordic walking took place outdoors all the time. The social contact group took place indoors under all weather conditions. In studies with depressive in-patients it could be shown that the same physical activity in the outdoors produced better results on the affective state , 50, 51.When looking at perceived activation, this dimension increased pre-post programs in climbing exercise compared to nordic walking exercise and non-exercise control. From previous studies it is known that even a few minutes of exercise increase perceived activation . An incrState anxiety showed a larger decrease with moderate effect size in climbing exercise compared to non-exercise control, but not compared to nordic walking exercise. This finding points out the potential of exercise and confirms earlier research results .It is remarkable that climbing showed a decrease in state anxiety although some components in climbing are associated with increased anxiety . These findings are in line with previous findings in depressive patients .Interrupting social withdrawal and increasing social interaction is one of the mechanisms seen responsible for the anxiolytic effect of exercise . This stGiven the low rate of physical activity and the health benefits connected with physical activity , 56, it Findings of the present study showed higher physical activity with a large effect size in the climbing group after the program ended and six months after the program ended in the follow-up, compared to the non-exercise control group. In the social contact control group, the weekly amount of physical activity decreased slightly over the seven-month observation period. We therefore conclude that exercise might trigger consciousness for physical activity in general; a desirable finding from a health behavior perspective , 56. SimExploring the role of affective valence in longer term physical activity behavior, the present study showed that a more positive affective state during and post sessions was associated with higher physical activity in the post program period. A change of one unit on the Feeling Scale used to measure affective valence was associated with an increase of 25/22 minutes per week for climbing/nordic walking. This result is similar to an augmentation of 38 minutes that has been reported in the study of Williams et al. . HoweverRegarding the timing of affective assessment, the present results do not suggest a stronger association of physical activity to affective valence during the exercise compared to affective valence post sessions. For the time points three and six months after program, however, no significant association of physical activity to affective valence was found. The regression coefficients of affective valence during and post exercise were similar suggesting that affective valence post sessions should not be neglected at least for the present population. This finding contradicts Rhodes and Kates  who concTo the best of our knowledge, this is the first study comparing two exercise modalities and further control for social contact group effects in people with anxiety disorder or PTSD. Another strength of the project was to analyze several sessions instead of a single bout of exercise as well as the long-term follow-up. However, in order to attract participants, it was necessary to make the program suitable for everyday use. This was accompanied by some limitations that have to be considered when interpreting the findings. Firstly, a program period of only eight sessions was limited in scope. Secondly, the project investigators had no control about who agreed or refused to participate in the program. Therefore, the randomization process was weakened because patients may have dropped out because their randomized group did not match their interest . Thirdly, the project included outpatients with a psychiatric diagnosis of PTSD or any anxiety disorder. Ideally, the results would be interpreted in a diagnosis-homogeneous manner. Due to the sample size, a differential diagnosis was not considered. Fourthly, the assessment of physical activity was methodically relatively weak. Since reported and actual PA are known to differ, accelerometers would have ideally been used.The present findings provide new insights in immediate affective responses to exercise compared to non-exercise programs based on multiple sessions. The more pleasant and higher activated affective state during and after exercise sessions as well as the anxiolytic effect suggest a benefit of exercise beyond social effects of the exercise group settings. Both nordic walking and climbing are considered appropriate exercise modalities for acute emotion regulation in outpatients with anxiety disorder or PTSD. The equipment expenditure for climbing should be critically weighted against small affective advantages of climbing compared to nordic walking when selecting an appropriate exercise modality for patients with anxiety disorder or PTSD. While the affective responses during and following exercise were associated with intermediate term increases in physical activity, the increase in exercise at six months post intervention indicates longer-lasting behavioral changes induced by the exercise programs. The difficulty of achieving sustainable behavioral changes is one of the major challenges in medicine, and this study shows promising results in a hard to reach group with anxiety disorder or PTSD.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the Medical University of Innsbruck. The patients/participants provided their written informed consent to participate in this study.CB and MK were responsible for the investigation, concept, and design of the study. MG, KH, and BS-U provided the acquisition of data. MN and CB were given visualizations and charge of the methodology. The project administration was given by MG, BS-U, KH, and CB while resources were provided by MK and BS-U. MN sub served data curation and formal analysis that was validated by CB and MK. MK and BS-U supervised the project. CB, MN, and MK wrote the first draft of the manuscript which was reviewed and edited by KH, MG, and BS-U. All authors contributed to manuscript revision, read, and approved the submitted version.This research was supported by the Department of Sport Science, University of Innsbruck and the Department of Psychiatry, Psychotherapy, Psychosomatics and Medical Psychology, University Hospital for Psychiatry II, Innsbruck.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.


In psoriatic arthritis (PsA), low disease activity as defined by the Minimal Disease Activity (MDA) index is considered a good treatment target. However, as MDA is based only on clinical findings, it might not capture pauci-symptomatic inflammation. Sensitive imaging such as ultrasound (US) might disclose residual inflammatory signs in PsA patients in MDA.In this cross-sectional multicentre study, adult PsA patients on biologic treatment in MDA for at least 6 months were consecutively enrolled for a thorough clinical and US examination. Data collection included demographics, personal history, main patient's reported outcomes, clinical and US findings of joints, tendon sheaths, tendons, bursae, and entheses involvement. All centers performed the US investigation in B-mode and Power Doppler (PD)-mode using a similar US machine equipped with a 18–6 and 13–5 MHz multifrequency linear probe. Statistical analysis included comparisons between groups and correlation tests.The 72 PsA patients enrolled in the study had a median duration of MDA of 12 (6–65) months. Overall, US examination revealed a low number of acute lesions. However, 54% of patients had at least one PD signal in the examined tissues. A joint or enthesis positive PD signal was found in about 19 and 24% of patients, respectively. Synovial hypertrophy, at least one acute entheseal lesions, and bursitis were the most common changes, detected in 41.7, 41.7 and 26% of patients, respectively.PsA patients in a stable state of MDA may still have residual inflammation in peripheral articular structures detectable by US examination. According to the most recent recommendations, remission, or alternatively, minimal/low disease activity is the target to be achieved and maintained in patients with psoriatic arthritis (PsA) –3. A numIn this study, we evaluated the presence of residual inflammation as detected by US in joints, entheses, tendon sheaths, and bursae of PsA patients with persistent good disease control.This was s a cross-sectional multicentre study conducted in the rheumatologic centers of seven Italian cities  with a specific expertise in spondyloarthritis (SpA) and US imaging. The study was approved by the local ethical committees of all participating centers according to the Italian current legislation on epidemiological studies.Adult patients (age 18–65 years) were consecutively enrolled by the participant centers if they had PsA according to the CASPAR classification criteria , if theyFor each enrolled patients the following personal data were collected: demographics, anthropometry (including body mass index), life-style habits , social profile, concomitant diseases and previous and ongoing medications. The rheumatologic interview encompassed family history of arthritis, any inflammatory rheumatic condition, inflammatory bowel disease, uveitis, date of PsA onset and diagnosis, history of arthritis (pain and swelling in one or more joints), peripheral enthesitis , and dactylitis (history of a sausage digit), presence of inflammatory back pain according to the Assessment of SpondyloArthritis international Society (ASAS) criteria , of buttUS examination was performed in B-mode and PD mode using two US machines  equipped with a 18–6 and 13–5 MHz multifrequency linear probe. The sonographers participating in this study had previously attended a training meeting that was preliminary to a US study in patients with PsA, psoriasis and fibromyalgia whose results have been recently published  and GlasWrists, metacarpo-phalangeal joints, knees and ankles were evaluated according to standardized methods: synovial hypertrophy, effusion and articular bone erosions were recorded as present or absent. The presence of intra-articular PD and synovial hypertrophy were recorded using a 4 grade scale according to Outcome Measures in Rheumatoid Arthritis Clinical Trial (OMERACT) criteria  . Tendon As this was an observational descriptive study, the sample size was not calculated. All patients meeting the inclusion criteria in the pre-defined time-frame of 1 year entered the study.t-test or Mann-Whitney test when the distributions were skewed. Comparison of categorical variables was performed by using chi square or Fischer's exact test as appropriate. Correlations between variables were evaluated by Spearman's rho. Bonferroni correction was applied to the correlation results to counteract the multiple testing problem.Continuous data were described as mean and standard deviation (mean + SD) or median and range, and categorical variables as absolute frequencies and percentages. Continuous variables were compared by using The comparison between patients with higher and lower clinical disease activity was performed using as cut-offs the DAPSA and BASDAI median values.The level of significance was set at 0.05. Data were analyzed using the SPSS v.23 .Seventy-two patients with PsA in a state of MDA for at least 6 months were enrolled in this study; 40 of them with MDA for a 6–12 month period and 32 for more than 12 months. Their demographics, personal, and clinical data are reported in The results of the US evaluation are shown in The comparisons between patients with a DAPSA score greater or lower than 1.6 and a BASDAI values greater or lower than 1.5 are shown in p = 0.003), with BASDAI , with VAS global  (not significant after Bonferroni correction), and with BASFI  (not significant after Bonferroni correction). A negative correlation was found between months of MDA duration and number of joints with effusion , number of articular or periarticular structures with PD signal , and number of enthesis with hypoecogenicity  but none of these correlations remained significant after Bonferroni correction.The correlation tests revealed the following weak but significant associations: number of joints with effusion at US with HAQ-DI  and the comparison according to the duration of MDA revealed a significantly higher number of patients with at least one US-PD lesions in the ≤ 12- than in the >12-month group, 22 (55%) and 13 (41%), respectively (p = 0.024).Finally, only 2 (8.2%) of the 24 patients taking csDMARDs had positive joint PD signal, as opposed to 12 patients (25%) not taking them (The results of this study suggest that patients with PsA with a persistent good clinical control of disease may still have joint and/or entheseal inflammation as revealed by US imaging. A positive PD signal in at least one joint and/or enthesis was found in about 19 and 24% of patients, respectively. As the mean number of joints and entheses with US signs of acute inflammation was very low, in most patients this involvement was limited to one or few sites. US findings of “active inflammation” in joints and entheses can also be found in healthy subjects. In a recent study, US acute lesions in the entheses were seen in up to almost 35% of healthy subjects but a positive PD signal was detected in < 10% of them . In anotThe definition of MDA  allows fWhether the presence of smoldering joint and entheseal inflammation by US may be of clinical relevance should be investigated by longitudinal prospective studies. One study on PsA patients in MDA, showed that US-detected synovitis was a strong predictor of disease flare . SimilarAnother interesting result yielded by this study was that the patients with a longer period of MDA had less US acute lesions than those with a shorter time of MDA. This finding might suggests that a long-lasting disease control may lead to a deeper state of remission. This possibility was also corroborate by the negative correlation between duration of MDA and number of joint and enthesis US acute changes.The study has some limitations. First, as the sample size was not pre-calculated, the number of evaluated patients might not have been adequate for a fully powered statistical analysis. Second, all patients were in stable good disease control and the number of findings revealed by the US examination was relatively low. As a result, some differences might not have achieved the level of significance. Finally, the cross-sectional design of the study, did not allow to understand the prospective usefulness of the US findings. The main results of our study, however, should not be impaired by these limitations.In conclusion, this study showed that in a group of PsA patients in a state of long-standing MDA, US examination revealed the presence of residual inflammation in joints, entheses, tendon sheaths and bursae. Therefore, sonography might help to better define the state of disease activity in the individual PsA patient in persistent clinical MDA.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the Santa Maria Nuova Hospital, Reggio Emilia, Italy. The patients/participants provided their written informed consent to participate in this study.PM: study design, patient enrollement, and data analysis. AM: data interpretations and drafting of the manuscript. GC, GS, AZ, GV, LM, MF, MG, AS, NM, FZ, MB, and FM: patient enrollment. CS: work conception and coordination. All authors contributed to the article and approved the submitted version.


This study aims to clarify the profiles of the psychological antecedents of vaccine hesitancy among Shanghai nurses with a person-centered approach.N = 1,928). In the online survey, participants were asked to report their sociodemographic, the 5C vaccine hesitancy components, their knowledge level of COVID-19 vaccine and vaccination, and the COVID-19 vaccination uptake intention and attention to vaccine news. Latent profile analysis was used to reveal distinct profiles of vaccine hesitancy.A population-based cross-sectional online survey was conducted on Shanghai nurses from July to August 2021 , “free riders” , “middlemen” , and “contradictors” . Compared to believers, middlemen were younger, more likely to be female, childless, less educated, held lower professional titles, had fewer years of nursing service, sometimes or never complied with recommended vaccinations, had satisfactory or poor self-assessed health status, had no work experience during the COVID-19 epidemic, and possessed greater levels of knowledge. Free riders were more likely to work in community health centers and have a lower degree than believers. Contradictors were more likely to work in community health centers, had junior college degrees or lower, and had no work experience during the COVID-19 epidemic than believers. From the highest to the lowest on vaccination intention and attention to vaccine news were believers, then free riders, contradictors, and finally middlemen.This study could aid in the development of personalized vaccination strategies based on nurses' vaccine hesitancy profiles and predictors. In addition to vaccine believers, we identified other three profiles based on their 5C psychological antecedents, emphasizing the significance of establishing tailored vaccination campaigns. Further research into the prevalence of profile structure in other groups of healthcare workers is required. The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a significant threat to global public health. Since 2019, over 7.6% (576 million) of the global population has been infected with SARS-CoV-2, resulting in over 6 million deaths  during tVaccine hesitancy, according to the Strategic Advisory Group of Experts (SAGE) Working Group, is defined as a delay in accepting or refusing vaccination despite the availability of vaccination services . More thAlthough the reasons for vaccine hesitancy differ by country and population, healthcare workers play a critical role in restoring public trust in vaccines  and are As a complicated and dynamically shifting term, vaccine hesitancy challenges the traditional perspective of a simple dichotomization of an individual's immunization behavior into acceptance or refusal . PreviouThe local COVID-19 epidemic in Shanghai has been rapidly spreading since March 2022 , and nurAn exploratory, cross-sectional latent profile analysis (LPA) on vaccine hesitancy was conducted among nurses in Shanghai, China. Ethics approval was granted by the Institutional Review Board of the School of Public Health and Nursing at Shanghai Jiao Tong University (Reference number: SJUPN-202018).via the Wenjuanxing website, and all participants were required to scan a QR code and provide informed consent on the survey platform before completing the questionnaire. Simplified Chinese is the language used in the questionnaire. A total of 2017 nurses completed the survey, and a final sample of 1928 was included for analysis, after deleting invalid responses. Inclusion criteria were that participants were (1) working nurses and (2) not nursing trainees or practical nurses.Nurses from Shanghai's tertiary hospitals and community health centers (CHCs) participated in this study before the beginning of the COVID-19 booster vaccination program in China. Researchers contacted several hospitals and partnering community health centers affiliated with Shanghai Jiao Tong University School of Medicine, and nurses who volunteered to provide data for the study were recruited through advertisements. The pilot survey was first conducted in May 2021, before the formal conduct of the study. A purposive sample of 10 nurses from Shanghai was selected for the pre-survey of the study instrument. By recording the respondents' level of understanding of the content and format of the questionnaire and suggestions for modifications, we adjusted for specific situations to improve the accuracy and clarity of the questionnaire. From July to August 2021, nurses who were interested in participating in the study completed an online survey. No financial incentives are offered, and participation is entirely voluntary. We collected data Participants were requested to give sociodemographic information in the first section of our study, including age , sex , marital status , no. of children , workplace , education level , professional title , years of nursing service , previous compliance with recommended vaccination , chronic diseases , self-assessment of health status , and working experience during COVID-19 epidemic .A questionnaire based on the 5C scale was used to assess the psychological antecedents of vaccine hesitancy. The 5C scale consists of 15 items, including five subscales consisting of three items each, with subscales addressing each of the five psychological antecedents: confidence, complacency, constraint, calculation, and collective responsibility. For these items, the allowable response values range from 1 to 7 . For each subscale, average scores were generated; the higher the mean value, the more consistent the associated region is in that construct. The higher mean value of the construct indicates stronger consistency of that construct. While the original 5C scale was designed to assess vaccinations in general, we added prompts before participants completed the section to make it vaccine-specific and to focus on the COVID-19 vaccine specifically.2 = 7729.676, P < 0.001) further confirmed the decomposability and sufficiency of the data sample, according to EFA results. Except for the backward scoring item that was part of the collective responsibility subscale of the original scale entered into the constraint subscale, all items conformed to the original factor structure using the Oblimin rotation, with factor loadings ranging from 0.577 to 0.912. As a result, the lone reverse item was put into the constraint subscale, and the original scoring was used to create the modified Chinese 5C scale, which gave a 5-factor structure that explained 77.908 % of the total variance. The redesigned scale's CFA (X2)/df ration indicates good agreement with 2.73, while TLI (0.929), CFI (0.946), and RMSEA (0.081) goodness-of-fit indices demonstrated good fit. Since the original scale was developed in English, the Chinese version of the 5C scale was developed through cross-cultural adaptation and psychometric testing after gaining allowed approval from the original authors. The 5C scale was translated from English to Chinese using Brislin's translation approach . A furthA questionnaire was developed based on the COVID-19 vaccination knowledge on the technical guidelines and expert consensus. A focus group discussion was held to choose and revise the questionnaire's items after the first draft was finished. The discussion convened two chief physicians from the Department of Infection, one chief physician from the Department of Respiratory Medicine, and two professors from the School of Public Health. After that, a pilot study revisited the updated questionnaire. A random sample of 30 nurses was pre-surveyed before the survey's official launch to ensure the questionnaire's internal consistency. The Cronbach's coefficient was 0.732. In all, the final questionnaire had 30 closed-ended items  that could be answered with a simple “yes” or “no.” The accurate response rate (a possible range of = 0.0–100.0%) was used to measure participants' knowledge of the COVID-19 vaccination. The correct response rates were divided into two categories: pass (≥60%) and fail (<60%).Vaccine-related outcomes include two indicators of vaccination intention and attention to the news. The intention to take the COVID-19 vaccine was measured by a single item that asked participants on a Likert scale  how likely they would be to have the COVID-19 vaccine when it is recommended for the current vaccination schedule. One question was utilized to evaluate the participants' attention to news reports about the COVID-19 vaccination. The item was assessed on a five-point Likert scale ranging from 1  to 5 , with higher scores indicating greater interest in vaccine information.Person-centered analysis approach, in contrast to “variable-centered” statistical methods that treat individuals as homogeneous or essentially homogeneous, focuses on studying combinations or developmental patterns of behavioral variables to produce more individually meaningful statistical results. It has been used in health and psychological behavioral research, for example, in examining the profiles of emotional labor , vulneraP < 0.05)   and the  < 0.05) . Among t < 0.05) . The ent < 0.05) . In addi < 0.05) .rho. Multiple group differences were evaluated using the Kruskal–Wallis test and reported p-values were adjusted to account for multiple comparisons using the Bonferroni post-hoc test. SPSS (version 26.0) and Mplus (version 8.3) were used to analyze the data. There were no missing values discovered.Sociodemographic characteristics  and COVID-19 vaccination knowledge level were used as predictor variables, the COVID-19 vaccination intention and attention to COVID-19 vaccine news were used as outcome variables, and we utilized the R3STEP and DCON commands in Mplus to model the predictors and outcomes of the latent categorical variable , 46. Scon = 10), or the response time was too short (n = 55). Unlike prior research, this study included a certain number of community nurses (n = 718), more representative of the nurse population, and some of the participants (n = 343) worked as frontline nurses during the COVID-19 epidemic. Because the 5C scales vary in their theoretical predictive aspects of vaccination intention, we checked questionnaires with repeated responses in 15 entries in extreme cases, including responses with repeated 1 (n = 5), 2 (n = 2), 6 (n = 3), or 7 (n = 11). We finally retained 1,928 cases for subsequent analysis. The characteristics of the study sample are shown in In this online survey, a total of 2,017 questionnaires were completed; 65 were eliminated for the following reasons: The questionnaire was unfinished , contradicting the original authors' hypothesis , workplace , educational level , professional title , previous compliance with recommended vaccination , self-assessment of health status , working experience during COVID-19 epidemic , and vaccine-rated knowledge level . However, there was no significant difference in the three subtypes for gender, marital status, no. of children, and chronic disease. When compared with those in the other profiles, nurses in the “believers” subtype tended to be those who were >30 years, those who worked in tertiary hospitals, those who had more than undergraduate degrees, supervisor or professor nurse professional titles, better previous compliance with recommended vaccination, and better self-assessment of health status, and those who worked during COVID-19 epidemic, and better vaccine-related knowledge level.Chi-square tests  showed tN = 1,382, 68.9%), which was the profile of the largest portion. Believers are most likely to be vaccinated, and they will actively seek out vaccination issues, believing that vaccines are efficacious and provide optimum protection to the public. Beyond that, they have few restrictions on vaccination.N = 282, 14.6%), with all indicators around the sample median . They have mixed feelings about the efficacy of vaccines and the hazards of preventable diseases. They are apprehensive about the risks linked with vaccination, even though they can seek information and certify the herd immunity impact of vaccines to some level.There was also a profile marked as middlemen  as free riders . They could search for information in response to vaccination questions, and they believed that vaccines are effective and had low limitations on vaccination. However, if others supply adequate protection, they could enjoy indirect protection as beneficiaries without contributing to herd immunization.We marked high confidence (Median = 6.00) and calculation (Median = 5.33) and low other indicators . They are high in all 5C indicators . Contradictors will conduct considerable research on vaccine-related topics, and while they recognize that vaccinations are helpful, they do not believe they need vaccines to stay healthy, or they may have too many barriers to vaccination. Furthermore, they consider that immunizations do protect the population.The profiles with the smallest part are contradictors , we obtained the following results . We founThe COVID-19 vaccine-related outcomes showed the following results see . The higBefore the implementation of the booster vaccination program in China, this study focused on nursing staff to understand the heterogeneity of vaccine hesitators and to provide specific evidence for targeted interventions to address vaccine hesitancy. We found a profile that was high in both confidence and collective responsibility (believers), as expected, and another profile that was high in confidence but low in collective responsibility (free riders). There were two quantitatively distinct profiles, with individuals having all 5C constructs around the median (middlemen) and all at high levels (contradictors). The study also observed differences between profiles in terms of predictors, and the profiles revealed disparities in their intention to COVID-19 vaccination and attention to COVID-19 vaccine news.In this study, nurses had higher median score in confidence (Median = 6.33), calculation (Median = 6.00), and collective responsibility (Median = 6.50) and lower median score in complacency (Median = 2.67) and constraints (M = 1.25). The overall distribution of the five dimensions is similar to prior research on nurses in Hong Kong . HoweverOur study found that there are four types of nurses based on the 5C structure of vaccine hesitancy. Among them, the largest proportion was believers (68.9%), a group with the highest intention to vaccinate and the highest frequency of attention to vaccine-related information, which is very helpful for the smooth progress of vaccination. Therefore, it is necessary to find the differences between the other three profiles and believers and adopt targeted interventions.Participants with all indicators around the sample median made up 14.6% of the population, who were categorized as middlemen. They had the lowest intention of taking the COVID-19 vaccine and frequency of paying attention to vaccine news than the other three profiles. The rapid spread of the COVID-19 pandemic forced people to rapidly acquire and implement health knowledge and change their behavior , and theParticipants with high confidence but low collective responsibility accounted for 12.7% of the population, which were named free riders. It is clear from the results that free riders had a higher intention of taking the COVID-19 vaccine and frequency of paying attention to vaccine news than middlemen but were lower than the other two profiles. Collective responsibility appears to be a more fundamental factor in free riders' decisions to get the COVID-19 vaccine than in believers. People who believe in collective responsibility advocate for individual subordination to society and feel that the collective's interests trump the individuals, which implies they will participate in more pro-social conduct . Our stuThe survey results demonstrate that, despite making up the smallest fraction of these four groups, the contradictors (3.7%) are not the least likely to be vaccinated and the least likely to follow vaccine news. This group possesses the same high levels of confidence, calculation, and collective responsibility as believers, but in contrast to believers, they also demonstrate a very high level of complacency and constraints. As a result, their perspectives on the advantages and hazards of vaccination are equivocal. This could indicate a lack of concern about the COVID-19 vaccine's function in curbing the spread of the epidemic, an undue complacency about their health status, or an unwillingness to confront the limits imposed on them by vaccination barriers. As a result, making health information more available and explaining the risk of developing the disease are extremely critical in persuading these healthcare providers to be vaccinated. Furthermore, workload and shift work are barriers to vaccination and particularly affect nurses' vaccination rates , and it For nurses themselves, vaccination is very important for their protection in high-risk settings. Even though the vaccination rate among Chinese nurses is high, their reluctance to uptake the COVID-19 vaccine is commonly disregarded, which may impede the advancement of continuous immunization programs. Nurses are not vaccinologists and do not know everything about vaccine development, clinical trials, etc. . They maFor patients and the public, our study is also relevant. Nursing staff are at the front line of safeguarding public health and are a reliable source of vaccine-related information , and manIn addition, this study has other public health implications in promoting vaccination efforts. First, we found some association between the 5C model and vaccination intention among nurses in mainland China. In future, tailored immunization promotion interventions can also be developed based on testing the psychological antecedents of vaccination in other groups of healthcare workers or even the public. Second, this study was conducted before the third dose (booster) of the COVID-19 vaccine in Chinese adults. Since the COVID-19 pandemic is likely to be widespread over a long period, a person-centered approach to vaccine hesitancy at different time points in the pandemic could help control the social and economic impact of the pandemic . Third, Despite the practical implications of the results of this study, there are some limitations to its generalizability. First, we used convenience sampling, which inhibits generalizability. Future studies should investigate samples from a variety of other settings to further analyze the characteristics of nurses' hesitancy to work with vaccines in the Shanghai region vs. other provinces and cities. Second, we implemented a cross-sectional design, and vaccine hesitancy is susceptible to pandemic severity. Therefore, longitudinal studies are needed to explore the long-term changes in vaccine hesitancy and the factors influencing it. Third, since participants may answer these items in a manner consistent with social expectations, the results may be biased. Fourth, our choice of the 5C model as a theoretical framework to understand participants' vaccine hesitancy issues for COVID-19 was not completed adequately, so some others such as vaccine literacy and altruistic beliefs , 63 can Overall, Shanghai nurses demonstrated a high level of confidence, calculation, collective responsibility, low complacency, and constraints with COVID-19 vaccination. By profiling the psychological antecedents of COVID-19 vaccination among nurses in Shanghai, this study identified four distinct profiles of vaccine hesitancy related to COVID-19 . We further explored the differences in sociodemographic, vaccine knowledge, vaccination intention, and attention to vaccine news among individuals between each profile. The characteristics of the latent profiles can help provide more targeted guidance for nursing managers to develop interventions that complement vaccine knowledge gained through continuing education, provide some peer or supervisory support, and thus aid nurses in reducing vaccine hesitancy and facilitating smooth vaccination and immunization planning.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Institutional Review Board of the School of Public Health and Nursing at Shanghai Jiao Tong University (Reference number: SJUPN-202018). Participants provided informed consent to participate in the study by using an electronic informed consent form.EZ: conceptualization, data curation, formal analysis, and writing—original draft. ZD: conceptualization, data curation, investigation, and writing—reviewing and editing. CW: conceptualization and writing—reviewing and editing. JH: writing—reviewing and editing. SW: conceptualization, data curation, and investigation. LZ: writing—reviewing and editing. QF: writing—reviewing and editing, project administration, and resources. All authors contributed to the article and approved the submitted version.This study was supported by grants from the three-year action plan for the construction of Shanghai's public health system (2020–2022), academic leaders cultivating project (Grant No. GWV-10.2-XD33), an Innovative research team of high-level local universities in Shanghai (Grant No. SHSMU-ZDCX20212801), and Shanghai Jiao Tong University School of Nursing Student Innovation Training Program (Grant No. HLDC21-05).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.


Clinical practice guidelines emphasize the importance of the prevention and treatment of non-specific back pain through exercise therapy and health education. However, it has not yet been confirmed that the combination of exercise plus education is more effective than usual medical care.The aim of this study was to determine if the combination of exercise plus education is more effective for the prevention of non-specific back pain than usual medical care.A systematic search in PubMed, Scopus, Web of Science and Medline was conducted with the terms Back Pain, Neck Pain, Musculoskeletal Pain, Exercise, Exercise Therapy, Health Education, Cognitive Behavioral Therapy, Primary Prevention, Secondary Prevention and Clinical Trial. The inclusion criteria were: articles published from 2016 to 2021, the intervention included exercise and education, and the sample consisted of non-specific back pain patients.p = 0.03); and in disability, standardized mean differences was found to be −0.24 .A total of 4 randomized controlled trials were selected (average PEDro score 6.5 points). The meta-analysis showed statistically significant differences in the pain intensity, standardized mean differences was found to be −0.75 (95% CI = −1.41 to −0.08; Exercise therapy and health education combination prevent better non-specific back pain than usual care.Combining exercise with educational interventions has a higher improvement on disability and kinesophobia than usual care.Interventions combining exercise and education seem to have a greater preventive effect on non-specific back pain than usual medical care. Back pain is a global problem and is a leading contributor to the increasing prevalence of disability over the past 30 years . The mosTo avoid these serious socioeconomic problems, it is essential to prevent its progression and limiting consequences, such as loss of functionality or work capacity ,7.It is essential to know the risk factors associated with NBP in order to prevent it, with the aim of reducing the serious socioeconomic repercussions caused by NBP . This coThis complicates an accurate diagnosis, the definition of a prognosis and the design of effective interventions that reduce the use of invasive methods  . ClinicaSeveral systematic reviews have examined the benefits of ET in preventing pain, disability, loss of quality of life and kinesophobia related to non-specific low back  and cervThis study was prospectively registered on PROSPERO (ID: CRD42022311026) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)  reportinA systematic search of publications was conducted in December 2021 in the following databases: PubMed, Scopus, Web of Science and Medline. The search strategy included different combinations with the following Medical Subject Headings (MeSH) terms: Back Pain, Neck Pain, Musculoskeletal Pain, Exercise, Exercise Therapy, Health Education, Cognitive Behavioral Therapy, Primary Prevention, Secondary Prevention and Clinical Trial. The following word was used as a free term: Prevention. The search strategy according to the focused PICOS question is presented in After removing duplicates, two reviewers (P.H.-L) and (J. L.-B.) independently screened articles for eligibility. In case of disagreement, both reviewers debated until an agreement was reached. The following inclusion criteria were applied for the selection of studies: (i) published in the last five years; (ii) ET plus HE was administered to the study sample; (iii) the sample consisted of participants with NBP; (iii) the research included a group that received UC, with neither exercise nor education. On the other hand, studies with the following characteristics were excluded from this review: (i) no quasi-experimental and observational studies; (ii) participants with specific causes of back pain; (iii) pregnant women; (iv) full text not available.After screening the data, extracting, obtaining, and screening the titles and abstracts for inclusion criteria, the selected articles were obtained in full texts. Articles with titles and abstracts lacking sufficient information regarding the inclusion criteria were also obtained in full text. Full text articles were selected in case of compliance with inclusion criteria by the two reviewers using a data extraction form.The two reviewers independently extracted data from the included studies using a customized data extraction table developed in Microsoft Excel. In case of disagreement, both reviewers debated until an agreement was reached.The following data from the included articles were selected for further analysis: demographic information , characteristics of the sample , study-specific parameters  and results obtained . Tables were used to describe both the studies’ characteristics and the extracted data.The Jadad scale and PEDRO scale were used to assess the quality of the studies.Tables were used to describe both the studies’ characteristics and the extracted data. When possible, the results were gathered based on type of intervention applied.p < 0.05. The I2 statistic was used to determine the degree of heterogeneity, where the percentages quantified the magnitude of heterogeneity: 25% = low; 50% = medium; and 75% = high heterogeneity [Standardized mean differences (SMD) and their 95% confidence interval (CI) were calculated as the between-group difference in means divided by the pooled standard deviation (SD) . SMDs weogeneity . The anaOut of 8414 search results, 1832 studies were considered eligible for inclusion after removing duplicates. Among the 1860 papers screened, 1531 were excluded after abstract and title screening. After the first reading of all candidate full texts, the Kappa score of reviewers 1 and 2 was 0.85  . All fouThe methodological quality of the studies was five or more points on the PEDRO scale and the average score was 6.5 points . AccordiA total of 1,235 patients took part in the included studies  . SMD effect size was found to be −0.75 (p = 0.03), with a variance of 0.115 (95% CI = −1.41 to −0.08). The forest plot is shown in Four studies included in this systematic review analyzed the pain variable, with a total sample size of 1,235 participants . Three sp = 0.001, I2 = 85.3%). SMD effect size was found to be −0.24 (p = 0.001), with a variance of 0.005 (95% CI = −0.38 to −0.1).Three articles  with a tp < 0.01), with a mean difference between groups of −3.3 and (95% CI −5.11 to −1.5).Turner et al.  researchThe aim of this study was to determine whether the combination of ET and HE is more effective for the prevention of NBP than UC. The results suggest that there is a positive effect of combining ET and HE in the prevention of NBP. In addition, improvements were observed in other variables, such as disability and kinesophobia.In the studies analyzed , the comIn addition, Miyamoto et al.  concludeThe disability variable also showed a positive result in the meta-analysis . These rCurrently, there are reviews that analyse the effects of exercise applied in isolation in which a larger number of articles are analysed ,33. HoweAmong the limitations of the present investigation, the authors must acknowledge that they have not taken into account differentiated analyses by gender and age subgroups, nor have they included studies comparing the combination of ET and HE with UC in pregnant women. It is worth mentioning that, due to the high heterogeneity in the analyzed studies, it was not possible to establish which ET and HE interventions are the most effective, as well as the most appropriate frequency and duration of sessions. However, this is the first meta-analysis that analyzes the effects of the combination of exercise therapy, and HE compared to usual medical care in the prevention of LBP. In view of the above, further research is needed to compare the effects of different interventions with the aim of developing specific protocols for NBP prevention.Interventions combining ET and HE seem to have a greater preventive effect on NBP than UC. In addition, combining exercise with educational interventions has a higher improvement on disability and kinesophobia than UC.The obtained results may help healthcare professionals to increase the effectiveness of their clinical interventions and thus reduce the severe socioeconomic impact caused by NBP worldwide.P. H.-L., R. L.-R., J. L.-B., J. L. G.-S. conceptualized and designed the study, drafted the initial manuscript, designed the data collection instruments, collected data, carried out the initial analyses, and critically reviewed the manuscript for important intellectual content. All authors have read and agreed to the published version of the manuscript.