Thus, aerobic exercise could effectively improve the physical fitness, emotional state and mental health of drug addicts, and reduce their drug addiction. For clinical practitioners and researchers, this study could provide more reliable evidence for addiction treatment.This study aims to discuss evidence for the efficacy of aerobic exercise in reducing drug addiction and improving the physical and mental health of drug addicts. We systematically searched several online databases as of the end of September 2022, including PubMed, EMBASE, the Cochrane Library, Web of Science, Scopus, Science Direct, CNKI, VIP, CBM, and Wanfang. All articles were identified, screened and included according to the inclusion or exclusion criteria. The Cochrane Handbook for Systematic Reviews of Interventions was used as a criterion for assessing the methodological quality of included studies. Random and fixed effects models were used for the analysis of standard mean differences (SMD) or mean differences (MD) with their 95% confidence intervals (CI). A total of 27 studies involving 2022 drug addicts were finally included in the analysis. The results of the meta-analysis showed that aerobic exercise could improve the physical fitness , regulate the systolic blood pressure: MD = −4.38, 95%CI , diastolic blood pressure: MD = −2.66, 95% CI , beats per minute: MD =−1.92, 95%CI ; emotional state , and promote the mental health , with statistically significant differences( One of the most serious problems in the world is drug addiction, which has been classified as a world public health hazard. Drugs refer to heroin, methamphetamine, marijuana, cocaine and other illegal substances that can cause addiction under the control of the state. Drugs can trigger abnormal excitatory or inhibitory effects in the human central nervous system, with a range of neurological and psychiatric symptoms ,2. They Non-pharmacological intervention has become a priority in the treatment of drug addicts, and exercise interventions have been suggested as an important measure of physical therapies. The American College of Sports Medicine has repeatedly and strongly recommended exercise interventions as an effective way to promote health and treat disease. Animal studies and human trials have shown that exercise can effectively prevent addiction, inhibit drug-seeking behaviors, help drug addiction and prevent relapse ,8. AmongThis study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Cochrane Handbook of Systematic Reviews.A comprehensive search was conducted as of the end of September 2022, through the following databases: PubMed/MEDLINE, Scopus, EMBASE, Science Direct, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), WanFang, Weipu Database (VIP). Randomized controlled trials (RCTs) of aerobic exercise interventions for drug addicts were identified. Any research that may qualify was considered for review regardless of the publishing language, population, or main results. The databases were searched using a combination of subject terms and keywords. The literature was identified after repeated pre-screening, supplemented by hand searching and tracing references of included literature when necessary. Database searches were limited to studies assessing humans and adults, and conducted using the following keywords: aerobic exercise, physical training, drugs, detoxification, heroin, cannabis, methamphetamine, rehabilitation, drug addiction, randomized controlled traits.To be included in the systematic review and meta-analysis, studies had to fulfill the following inclusion criteria. Inclusion criteria included study participants aged 18 years or above who were drug dependent and met the diagnostic criteria for illicit drug abusers; the intervention duration and the sample size were unlimited, and all the participants were involved in aerobic exercise. The outcome indicators of this study involved physical fitness , cardiorespiratory function , muscle force (grip strength), flexibility (sit-and-reach), balance (one-leg stand with eye closed)), emotional state , depression , drug craving ), mental health . Exclusion criteria included duplicate published studies, studies with unqualified results, and those without appropriate outcome indicators.Two reviewers independently screened the title and abstract of the studies and then performed full-text reading and study selection based on eligibility criteria. The extracts included basic information , intervention aspects , and outcome indicators. Disagreements between the two reviewers were resolved in discussions with the senior author. Authors of original publications were contacted for additional information if necessary.The methodological quality of the included studies was assessed by using the Cochrane risk of bias tool, with assessment form entries containing random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases.2 statistic. Fixed-effect  and random-effect models  were used as analysis models based on the heterogeneity results. Effect values were counted using the standardized mean of difference (SMD), mean difference (MD) and 95% confidence interval (CI). In addition, a p value less than 0.05 in the Egger test for publication bias indicated publication bias sensitivity analysis tests for the stability of the results by excluding each study consecutively.All the data extracted from each study were analyzed by Stata 16.0 software and Review Manager 5.4 software. The heterogeneity of included studies was assessed using the IAccording to the search strategy mentioned above, 1568 records were retrieved from the databases. After deleting duplicate records, there were 956 records left. The titles and abstracts were reviewed, and 863 studies that did not meet the standards were excluded. We reviewed the full text of the remaining 93 studies, and further excluded 66 studies. Finally, we included 27 studies for systematic review and meta-analysis .Twenty-seven RCTs were included in this review, involving 2022 drug addicts. The sample size included in the studies ranged from 22 to 200, and the duration of aerobic exercise intervention ranged from 2 weeks to 32 weeks, with a frequency of 3~7 and 15~120 min each week. The basic information of the included studies is shown in We evaluated the bias risk of all included studies according to the Cochrane collaboration tool. The risk of bias in the included studies is shown in 2 = 80%, p < 0.00001) and studies on body fat percentage  and mass  should use a fixed effects model. The results of the meta-analysis showed that there was a statistical significance between aerobic exercise and the control group in terms of body fat percentage in drug addicts  , p = 0.09], as shown in In this meta-analysis, there were eighteen studies  involving aerobic exercise interventions for body composition in drug users, with the main indicators including BMI, body fat percentage and mass. The results of heterogeneity analysis suggested that BMI studies should use a random effects model  and systolic blood pressure  should use a random effect model; and the studies of diastolic blood pressure  and beats per minute  should use a fixed effects model. The pooled effect of these studies showed that in vital capacity , systolic blood pressure , diastolic blood pressure , and beats per minute , the aerobic exercise intervention groups had better rehabilitation results than the control groups, as shown in Nineteen studies  reported the results of cardiopulmonary function evaluation, including vital capacity, systolic blood pressure, diastolic blood pressure and beats per minute. The results of heterogeneity analysis showed that the studies of vital capacity . The pooled effect size showed significant effects of aerobic exercise intervention on muscle force , as shown in Eleven studies  measured the effects of aerobic exercise on grip strength. The results of heterogeneity analysis suggested that grip strength studies should use a fixed effects model . The pooled effect size showed significant effects of aerobic exercise on flexibility , as shown in Twelve studies  measured the effects of aerobic exercise on flexibility for sit-and-reach. The results of the heterogeneity analysis suggested that sit-and-reach studies should use a random effects model . The results showed that after the aerobic exercise intervention, the experimental group had a longer standing time on one leg with eyes closed than the control group , as shown in Sixteen studies  used a one-leg stand with eyes closed as an index to evaluate balance ability. The results of the heterogeneity analysis suggested that one-leg stand with eye closed studies used a random effects model . The results show that aerobic exercise interventions could significantly reduce the anxiety of drug addicts , as shown in Ten studies  reported the effect of aerobic exercise on the SAS of drug addicts, and the combined analysis adopted a fixed effects model . The results showed that aerobic exercise interventions could effectively alleviate the depression of drug addicts , as shown in Ten studies  reported the effect of aerobic exercise on SDS of drug addicts, and the combined analysis adopted a random effect model  showed evidence of significant differences between the exercise group  and the control group, as shown in Nine studies  used three scales as indicators to evaluate drug cravings. The pooled analysis using a random effects model  and obsessive-compulsiveness  should use a random effect model; the studies of somatization , depression , psychoticism , phobic anxiety, paranoid ideation , interpersonal sensitivity , and hostility  should use a fixed effects model. Meta-analysis showed that the therapeutic effect of aerobic exercise on mental health (SCL-90) of drug addicts was significantly superior to that of the control group. The specific manifestations were as follows: anxiety , obsessive-compulsiveness , somatization , depression , psychoticism , phobic anxiety , paranoid ideation , interpersonal sensitivity , and hostility , as shown in The SCL-90 study included nine items and explored the therapeutic effects of aerobic exercise on the mental health of drug addicts . In SCL-90, nine indicators of mental health symptoms of drug users were included, including anxiety, psychoticism, phobic anxiety, paranoid ideation, obsessive-compulsiveness, somatization, interpersonal sensitivity, depression, and hostility. The results of heterogeneity analysis showed that the studies of anxiety , SAS (p = 0.760), and interpersonal relationships (p = 0.096) were tested to be greater than 0.05, indicating that there was no publication bias.In this study, the Egger test was used to analyze the vital capacity index, SAS index of emotional state, and interpersonal index of mental health of drug addicts during aerobic exercise interventions. Compared with the funnel plot method, the Egger test overcomes the drawbacks of subjective judgments of funnel plots and the results were more objective. The This meta-analysis was conducted to estimate the effects of an aerobic exercise intervention on the physical fitness, emotional state and mental health of drug addicts, and provide an overview of the latest evidence through 27 randomized controlled studies. Our pooled analysis showed that aerobic exercise had a significant beneficial effect on the emotional state and psychological well-being of drug addicts, with improvements in aspects of the evaluation indexes of physical fitness.Firstly, our study showed that aerobic exercise was significantly better than the control group in enhancing cardiorespiratory fitness, muscle force and balance and flexibility in drug addicts. Previous studies have shown a significant cardioprotective effect of aerobic exercise. Aerobic exercise couldimprove oxygen utilization and blood supply to the heart, increases lung vital capacity, and contributes to cardiopulmonary function and physical fitness in drug addicts . Wei 4040 found Next, the results of this study showed that aerobic exercise was effective in alleviating anxiety and depressive symptoms and reducing the craving for drugs in drug-addicted individuals. Drug craving is a core symptom of drug addiction and an important indicator of clinical diagnosis. Anxiety and depression drive addicts to become more dependent on drugs and are the most common negative emotions associated with drug addiction. The phenomenon of depression and anxiety in drug addicts concerns ambivalence . They clFinally, the results of this study showed that aerobic exercise was effective in promoting significant improvements in the mental health of drug addicts, and the differences in SCL-90 scores were statistically significant. Drug addicts may be emotionally depressed due to their families, living environment, etc., and their mental health outlook may not be optimistic. In many studies on the mental health of drug addicts, the SCL-90 has become an important research tool that can effectively screen for common psychological problems through investigations, usually adopting standardized measurement tools such as the SCL-90, and taking samples by random or convenient sampling to carry out the test. Although this avoids the subjectivity of the results, it is difficult to guarantee the representativeness of the samples, which leads to the poor ecological validity of the research and the difficulty in popularizing the conclusions . Given tThere are limitations to our study. Due to the limitations of existing studies, only published RCTs from the libraries to date were included, and unpublished papers were not obtained and included; the lack of clear study information in the interpretation of some of the included literature affects the quality of the studies and reduces the validity of the assessment of clinically relevant data; as the frequency and intensity of exercise interventions taken in the 27 papers included in this study varied between studies, as well as the duration of the experiments conducted, these differences may affect the accuracy of the meta-analysis results; finally, this review was not registered for systematic evaluation, and it is recommended to use this in future reviews to better avoid certain scientific biases.Thus, taken together, the results of this study demonstrated that aerobic exercise could be an effective adjunct to drug addiction treatment, and be beneficial in improving health during and after detoxification. This systematic review and meta-analysis assessed the effectiveness of aerobic exercise intervention in drug addicts, including physical fitness, emotional state and mental health. Some of the studies included in this study have varying degrees of heterogeneity and there is still insufficient evidence to suggest a clinical advantage in improving mass and BMI in drug addicts. Therefore, a multicenter, large-sample RCT and more high-quality, homogeneous studies to further validate the results of this study are recommended for future studies, thus providing a more reliable evidence-based basis for clinical practice.


The COVID-19 pandemic and its aftermath have increased pre-existing inequalities and risk factors for mental disorders in general, but perinatal mental disorders are of particular concern. They are already underdiagnosed and undertreated, and this has been magnified by the pandemic. Access to services (both psychiatric and obstetric) has been reduced, and in-person contact has been restricted because of the increased risks. Rates of perinatal anxiety and depressive symptoms have increased. In the face of these challenges, clear guidance in perinatal mental health is needed for patients and clinicians. However, a systematic search of the available resources showed only a small amount of guidance from a few countries, with a focus on the acute phase of the pandemic rather than the challenges of new variants and variable rates of infection. Telepsychiatry offers advantages during times of restricted social contact and also as an additional route for accessing a wide range of digital technologies. While there is a strong evidence base for general telepsychiatry, the particular issues in perinatal mental health need further examination. Clinicians will need expertise and training to navigate a hybrid model, flexibly combining in person and remote assessments according to risk, clinical need and individual patient preferences. There are also wider issues of care planning in the context of varying infection rates, restrictions and vaccination access in different countries. Clinicians will need to focus on prevention, treatment, risk assessment and symptom monitoring, but there will also need to be an urgent and coordinated focus on guidance and planning across all organisations involved in perinatal mental health care. The COVID-19 pandemic has evolved rapidly and had global impacts on all areas of our lives. Although restrictions have been lifted in many countries, case rates have continued to fluctuate with significant surges in many countries such as Australia and New Zealand recently .The pandemic has exacerbated known risk factors for mental disorders in general, but perinatal mental health during and in the aftermath of COVID-19 is of particular concern . PerinatThe perinatal period is already one of significant biological, psychological and social change, and before COVID-19, perinatal mental health conditions of different types and severity were estimated to affect around 10–20% of pregnancies . A numbehttps://oxfordhealthbrc.nihr.ac.uk/our-work/oxppl/pregnancy-and-the-perinatal-period/).There have also been significant disruptions to mental health services. Shortages of staff existed before the pandemic and have continued. Mother and baby units (MBUs) and specialist mental health beds have faced particular challenges: length of stay has been shorter with greater use of compulsory admissions, a higher proportion of psychotic illness and overall acuity , and adaEven when available, women and clinicians may have been hesitant to access mental health emergency services and inpatient stays when needed. This has meant that more severe illness has been managed as an outpatient and often remotely . Mental In addition to altered services, pregnant women have been asked to, or chosen to, practice more extreme social distancing during the pandemic . This isThe impact of the pandemic also needs to be evaluated not only in terms of the mental health of the mother but also in potential effects on the neurodevelopment of babies, and the relationship between mother and baby. There is a lack of definitive evidence to support direct vertical transmission of SARS-CoV-2 or direct effects of in utero viral exposure which might directly affect neurodevelopment, but there is some early evidence that maternal psychological experiences and increased stress during pregnancy in the context of the pandemic could influence foetal development and functioning . For womClinicians and patients in perinatal mental health have been faced, therefore, with particular challenges in addressing these multifactorial risks to mother and child in the perinatal period, during and in the aftermath of the COVID-19 pandemic. Areas of uncertainty such as how to organise specialist services, when and how to use virtual or in-person consultation and the assessment of risk particularly in women with multiple mental, physical and social risk factors are key issues in this area.The Washington Post, These extra challenges have been on the background of significant variations in perinatal mental health services both between and within countries and regions, which existed even pre-pandemic . GeneralAs the pandemic has evolved from an acute crisis and beyond, clinicians, patients, and health care organisations have needed access to reliable and pragmatic clinical guidance and evidence . In the https://oxfordhealthbrc.nihr.ac.uk/our-work/oxppl/pregnancy-and-the-perinatal-period/ and show that, in general, the COVID-19 guidance available for perinatal mental health services is relatively sparse, focused mainly on obstetric care and almost entirely from a small number of sources and countries. Much of the guidance is UK focussed  and therefore not always applicable to other settings.As mental health clinicians, we assessed available guidance on the management of perinatal mental disorders during the COVID-19 pandemic using a validated evidence-based approach : a team In particular, the use of telepsychiatry in perinatal mental health, particularly after the acute phase of the pandemic, is not specifically addressed in the current guidance. This is an area where clinicians may need to navigate a hybrid approach, and formal guidance would be helpful. Prior to the pandemic, there was already a strong evidence base for general telepsychiatry , with exTelepsychiatry had already been investigated pre-pandemic as a possible route for increasing access and cost effectiveness in perinatal services . It offeThe pandemic accelerated the adoption of telepsychiatry in perinatal care and increased patients’ and clinicians’ confidence in using the various platforms and media available, but treatment still needs to be adapted to the needs of the individual and not all interventions are the same. Small differences in design, delivery and frequency of contact can affect acceptability, adherence and outcome. For example, adherence to a web-based psychological treatment was higher with telephone-based coaching than with low-intensity online support . In addiNot only do patients vary in their skills and confidence in accessing digital health, so do clinicians. The pandemic has accelerated the use of telepsychiatry in general, but pre-COVID concerns from mental health clinicians including lacking detailed knowledge of the wider range of telepsychiatry techniques, experience in establishing rapport and therapeutic alliance , and keyhttps://oxfordhealthbrc.nihr.ac.uk/our-work/oxppl/domestic-violence-and-abuse/ for summary). In addition, some new emergency support routes which were developed and used during the pandemic, such as using existing public places and increases in pre-existing support (helplines and shelters), can be used in addition to remote assessments. Techniques such as the use of code words or signals during a consultation may also be helpful. However, for some patients who are at higher risk of DVA or self-harm, or relapse of severe mental illness, in-person meetings will be essential to assess these risks. For others, a hybrid model of telemedicine and in-person meetings may be the optimal solution  fell during the pandemic , and thisolution .In summary, perinatal services, consistent with all health care services, rapidly shifted during the pandemic to the use of telepsychiatry. Given the clear advantages, we should not lose the impetus to integrate telepsychiatry into practice in the post-COVID-19 world. Mental health services should explore ways to use technology to improve integration of services and facilitate access to perinatal mental health treatment. Mobile applications are particularly accessible and provide low-cost opportunities. With the increasing access to smartphones, there is the potential to address some of the urgent challenges in ensuring prompt and equitable access and uptake for perinatal health services globally. Rigorously designed trials are needed to address some of the unanswered questions in this specialist setting  and apprAside from the use of telepsychiatry, there are wider issues in perinatal care highlighted by the pandemic which clinicians and managers will need to consider and where formal guidance would be helpful . The panWomen with a history of depression or anxiety disorders should continue to use preventive psychotherapies. These may be in person or via virtual health platforms according to clinical need and patient preference . Psychothttps://oxfordhealthbrc.nihr.ac.uk/our-work/oxppl/pregnancy-and-the-perinatal-period/ for examples), and voluntary and community organisations provide vital maternal mental health support as a key addition to formal mental health services. However, strategies are required on all levels, and there need to be system-level changes to address not only the pre-existing deficiencies in care provision in perinatal mental health, but also the extra pressures resulting from the pandemic. While clinicians can make a significant impact by focussing on prevention, treatment, risk assessment, and symptom monitoring, the task of organising perinatal mental health services for the current ongoing crisis and preparing for the next needs guidance and planning across organisations including government departments, health care providers, and the voluntary sector.Many professional organisations and treatment providers have developed psychoeducational materials for patients and carers (see


Renal cell carcinoma (RCC) is a highly vascularized and immunogenic tumor, and its treatment has been revolutionized by the development of immune-checkpoint inhibitors. However, the clinical benefit of these agents is limited in patients with metastatic disease. The microbiome has emerged a novel therapeutic target in recent years and has shown promising values. Understanding the microbiome of the tumor microenvironment is essential for the treatment of RCC.Microbes play different roles in metabolism, local or systemic inflammation, and immunity, and the human microbiome in tumor microenvironment (TME) is important for modulating the response to immunotherapy in cancer patients. Renal cell carcinoma (RCC) is an immunogenic tumor, and immunotherapy is the backbone of its treatment. Correlations between the microbiome and responsiveness to immune checkpoint inhibitors have been reported. This review summarizes the recent therapeutic strategies for RCC and the effects of TME on the systemic therapy of RCC. The current understanding and advances in microbiome research and the relationship between the microbiome and the response to immunotherapy for RCC are also discussed. Improving our understanding of the role of the microbiome in RCC treatment will facilitate the development of microbiome targeting therapies to modify the tumor microbiome and improve treatment outcomes. Renal cell carcinoma (RCC) originates within the renal cortex and accounts for approximately 90% of primary malignant renal tumors. The incidence of RCC varies widely from region to region, with the highest incidence reported in Western countries . The AmeRCC comprises different subtypes with specific histopathological and genetic characteristics. The 2016 World Health Organization (WHO) classification categorized RCCs into three main histological types ; however, RCCs comprise a broad spectrum of histological entities [–5%]; how%, and chComplete surgical tumor resection is the standard of care for patients presenting with localized RCC ,7. HowevAlthough advances in systemic therapies have improved the life expectancy of patients with advanced metastatic disease, there is still an unmet need to identify novel targeted therapies for mRCC patients . The hetThe tumor microenvironment (TME) is the ecosystem that surrounds a tumor, and it is composed of immune cells, the extracellular matrix, blood vessels, and fibroblasts; it provides the factors necessary for cancer growth, invasion, and angiogenesis ,15. BecaAngiogenesis is one of the hallmarks of cancer, and malignant tumors secrete multiple angiogenic growth factors simultaneously. These factors, which are involved in tumor growth and survival, are targeted by anti-angiogenesis treatments, mainly TKI therapies, including the anti-VEGF, anti-mTOR, and the recently introduced anti-MET [also tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR)], anti-RET, anti-platelet derived growth factor receptor (PDGFR), and anti-fibroblast growth factor receptors (FGFRs); these therapies have become a weapon of fundamental importance . In addiccRCC is extensively infiltrated with leukocytes such as CD8+ T cells, CD4+ T cells, and natural killer (NK) cells, as well as myeloid cells including macrophages and neutrophils . The immRecently, unexpected guests, the microbiota have emerged as an important part of the TME in many types of cancer and are shown to affect tumorigenesis and tumor progression . The TMESince 2007, the Human Microbiome Project (HMP) has been charged with the mission of facilitating the comprehensive characterization of the human microbiome and analyzing its role in the human health and disease . The creThe human microbiome is the collective genomes and by-products of all microorganisms such as bacteria, viruses, and fungi that inhabit the human body . These mThe link between the tumor microbiome and cancer is mediated by four main mechanisms, as follows: (1) tumor microbiome-induced gene mutations directly promote tumorigenesis; (2) the tumor microbiome regulates oncogenes or oncogenic pathways; (3) the tumor microbiome modulates the host immune system; and (4) the tumor microbiome produces small molecules or metabolites that influence cancer development, progression, and response to therapeutic agents ,28. The Blautia, Streptococcus, [Ruminococcus]_torques_group, Romboutsia, and [Eubacterium]_hallii_group are dominant and positively associated with ccRCC [Streptococcus lutetiensis promotes ccRCC proliferation, migration, and invasion in-vitro via the TGF-signaling pathway, which could be a target for RCC treatment. The main limitation of this study was the 16S rRNA sequencing method used, which can only identify the microbiota composition at the genus level. Thus, to identify the exact strains, a more precise detection method such as metagenomic sequencing can be applied in future evaluation. The same genus, Streptococcus, , was more abundant in primary ccRCC tumors than in the thrombus or normal adjacent tissues in another study [The microbiome of RCC is the least studied among genitourinary cancers ,40. In 2th ccRCC . In parter study . In conter study . The stuer study . The stuEarlier detection of small renal masses is associated with a significant stage migration of RCC at presentation, and the development of novel therapies increases the life expectancy of RCC patients. Except for the potential contribution of the microbiome to the etiology of RCC, studies have provided information on the responsiveness of RCC to certain drugs such as ICIs and TKIs. Resistance to ICIs is associated with impaired immune modulation caused by intrinsic or extrinsic factors including complex components of TME and their associations in the TME. Tumor cell-intrinsic factors that contribute to immunotherapy resistance include the expression or repression of certain genes and pathways in tumor cells, such as constitutive PD-L1 expression, loss of tumor antigen expression, and alterations in the antigen-presenting and processing machinery that prevent immune cell infiltration or function within the TME. These mechanisms may exist at the time of initial presentation, which constitutes primary resistance, or evolves later after an initial response, thus forming part of adaptive resistance mechanisms. The tumor cell-extrinsic factors include inhibitory immune checkpoints , T cell exhaustion and phenotype change, immune suppressive cell populations , and the release of cytokines and metabolites in the TME .Akkermansia muciniphila, that was associated with the response to ICIs [A. muciniphila, resulting in an increase in CXCR3+CCR9+CD4+ T cells and the upregulation of IL-12 and the function of dendritic cells (DCs) to improve the effect of PD-1 inhibitors [A. muciniphila. SCFAs regulate tumorigenesis either by suppressing the activity of histone deacetylase to inhibit transcription factors involved in tumorigenesis or indirectly by modulating inflammation [Alistipes putredinis, also discovered by Routy et al., modulates the host immune system by recruiting unique memory CD8+ T cells and NK cells to the periphery to enhance the PD-1 blockade effect [Bacteroides, Bifidobacterium, Firmicutes, and Faecalibacterium sp. are also associated with the response to ICIs in RCC patients [Bifidobacterium also induces immune responses by increasing tumor-infiltrating lymphocytes, promoting the maturation of DCs, up-regulating the expression of IFN-γ and pro-inflammatory cytokines, and priming tumor-specific CD8+ T cells [+ T cells is associated with longer survival in melanoma patients [Bifidobacterium are more sensitive to ICIs. Faecalibacterium sp. induces the proliferation of CD4+ or CD8+ T cells, increases the production and differentiation of Treg cells, and upregulates the expression of inducible T cell costimulatory, thereby decreasing the risk of ICI-related colitis and improving the response to ICIs in melanoma patients [Firmicutes, these microbiome components improve the clinical outcome of patients treated with ICIs by producing SCFAs and regulating the immune response. In patients with mRCC, Stenotrophomonas maltophilia and Corynebacterium sp. are increased in ICI responders [Clostridium butyricum MIYAIRI 588 (CBM 588) in combination with first-line ICIs (ipilimumab and nivolumab combo) in patients with intermediate or poor-risk mRCC, and to evaluate whether this could modulate the gut microbiome of these patients [Bifidobacterium sp. in the microbiome. The initial results of this clinical trial showed that patients who received ICIs plus CBM-588 had better progression-free survival (PFS) and overall survival (OS) than those treated with ICIs alone. Analysis of the microbiome identified several increased  and decreased (Desulfovibrio sp.) microorganisms in responders receiving CBM-588 [Recent studies identified a specific microbiome in patients who are sensitive to ICIs. Of five studies that used different sequencing methods, four identified the same bacterium,  to ICIs ,48,49,50hibitors ,51. Thisammation . Alistipe effect . Bacteropatients . Bifidob T cells ,55. A hipatients , suggestpatients . Along wsponders . These dpatients . CBM588  CBM-588 . No diff CBM-588 . The ideBacteroides species was evaluated by Hahn et al., and the results showed that PFS was increased in RCC patients receiving first-line VEGF-TKIs with antibiotics [Several factors that alter the composition of the gut microbiome affect the interaction of the microbiome with the immune system, thus determining the hosts’ response to treatment. Environmental factors such as the administration of antibiotics or proton pump inhibitors (PPIs) are the most important factors affecting the response to ICIs. A study that included 603 RCC patients treated with ICIs from ten study groups showed that antibiotics decrease PFS and OS rates ,68,69,70ibiotics . HoweverA summary of microbiome studies on RCC presented in A. muciniphila is commonly present in abundance in both healthy donors and patients with improved outcomes [Maintenance of gut homeostasis is essential for human health due to the bidirectional feedback loop that exists between the host-associated microbiota and human health . Many huoutcomes . Currentoutcomes . Howeveroutcomes .Other kidney cancer subtypes, such as pRCC and chRCC, differ from ccRCC in the prognosis and treatment strategies. These RCCs are included in the non-clear cell RCC (nccRCC) group, and each type has unique molecular drivers that differ from those of ccRCC . For nccThe clinical use of ICIs in mccRCC has limited benefits on the survival outcomes of patients, and many patients experience resistance to ICIs. The response rates to ICIs are even lower in other types of RCC. Predicting the response to ICIs and designing strategies to overcome ICI resistance are unmet needs to improve the survival of RCC patients. The dynamic interplay between the TME and treatment response has been a subject of interest in recent years. The microbiome was identified as a novel component of the TME, and the association of the microbiome with the response to anticancer therapy, as well as with the incidence of adverse events, has been reported by several studies. This review discusses the systemic therapies used to treat mRCC and the intimate relationship between the microbiome and the response to immunotherapy for RCC. The microbiome participates in host immune responses and regulates antigen presentation and T-cell initiation and activation. Elucidating the immune mechanism of the microbiome and the dynamic interactions between the microbiome and other factors in the TME is not only essential to predict the prognosis of patients but also for the development of microbiota-based anticancer immunotherapies for the treatment of different RCC histological types. Ultimately, the objective of prospective studies is to validate novel biomarkers that can be used and integrated into clinical practice. Furthermore, innovative biotechnological strategies are needed for the clinical application of the microbiome as an anti-cancer treatment target. Over the past few decades, the successful application of nanotechnology in cancer diagnosis and treatment has made it possible to target specific oncogenic microbes by intervening with the microbiome. This is an instant hit and brings the nascent field of microbiome intervention in cancer, however, it still has many aspects that need to be improved.


The governing equations of momentum, energy and concentration are transformed into partial differential equations by using similarity transformations. These transformed equations are grasped numerically at MATLAB by using the boundary value problem technique. The influence of different parameters are presented through graphs. The numerical outcomes for rotation, Nusselt, Prandtl, and Schmidt numbers are obtained in the form of tables. The heat transfer rate increases by augmentation in the thermophoresis parameter, while it decays by increasing the Reynolds number. Oxide nanoparticles hybrid nanofluid proved more efficient as compared to mixed nanoparticles hybrid nanofluid. This research suggests using oxide nanoparticles for good heat transfer.This research investigates the two different hybrid nanofluid flows between two parallel plates placed at two different heights,  A crucial component of numerous industrial and technological processes is the fluid flow above a stretched surface with mass and heat transfer. Applications include the chilling of sheets, melt-spinning operations, fiber spinning, casting, etc. Additionally, fluids flow is used in geophysics, industrial engineering, petroleum engineering, groundwater hydrology, ceramic engineering, and chemical engineering. The final finishing of products depends upon the amount of heat transfer. Therefore, it is crucial to check the velocity and heat transfer inside a fluid to obtain a basic understanding of these processes.Crane  gave theNon-Newtonian nanofluids do not obey the Newton law of viscosity, while Newtonian nanofluids obey this law because they have direct relations between shear stress and shear rate when subjected to applied stress. Such fluid plays an essential part in different industrial applications such as polymer extrusion, cosmetics, coolants, in the food industry and the final finishing of the products. The nanofluids are prepared by suspending nanometer-sized particles in a host fluid, and these fluids have improved heat transfer rates as compared to the host fluid. Similarly, hybrid nanofluids are the mixture of one or more nanoparticles in nanofluids that perform extraordinary heat transmission. Sarada et al.  considerRout and Mishra  gave a cMany industrial uses involve different types of heat flow like in plastic industries, molding, blowing, and extrusion of plastic. Similarly, converting industries involve presses, rolls, laminating, and printing. Nuclear power plants involve radiations that play an important role. Zeeshan et al.  exploredThe thermophoresis phenomenon is defined as the particle’s migration from a higher temperature to a lower temperature. This technique is very useful for the accumulation of particles like the movement of holes of electrical charge in semiconductors. Tsai et al.  presenteThe temperature gradient is a physical quantity, which describes at which rate and in which direction temperature is being transferred around a particular region. Similarly, the concentration gradient is defined as the mass transfer rate. These types of flow have a crucial impact on various applications. Makinde et al.  presenteThe main objective of this research is to examine the flow of a viscous, incompressible, hybrid nanofluid above a stretchy, rotating, permeable plate with a heat source and chemical reaction under the influence of a magnetic field. The fluid and plates are rotating simultaneously with constant speed about the axis of rotation. The governing equations of momentum, energy and concentration are transformed into ODEs by a similarity transformation and tackled at MATLAB using the boundary value problem technique. The influence of different constraints is discussed in the form of graphs and tables.y-axis is perpendicular to the x-axis and the z-axis is perpendicular to both axes. The lower level is placed at a height y-axis in which fluid is rotating. Two different namely Suppose a rotating three-dimensional, steady, incompressible, and electrically conducting hybrid nanofluid flow between two permeable parallel plates. The cartesian coordinate system is considered to understand the problem as the Continuity Equation:Momentum Equations:Energy Equation:Concentration Equation:z-axis The Rosseland thermal radiation approximation relation is defined as Here, The corresponding boundary conditions are:Similarity Transformation:The following similarity transformation is utilized to convert leading equations into a set of ordinary differential equations.The differentiation is with respect toTransformed Governing Equations:The flow governing equalities of continuity, momentum, energy and concentration takes the following form after employing the similarity transformation. The continuity equation is identically satisfied, and the remaining are:By removing the pressure gradient term from above mentioned Equations (10) and (11) reduced toHere, So, the leading equations of momentum/velocity of the current problem take the following form:The Roseland approximation in the energy equation for radiative heat flux  is definHere, Energy equality takes the form by utilizing the definition of heat fluxSimilarly, the following form (dimensionless) takes the concentration Equation (6):The transformed boundary conditions are:The The dimensionless quantities magnetic field, porosity, mixed convection, Prandtl number, Schmidt number, Reynolds number, radiation, Brownian motion, thermophoresis, radiation, heat source/sink, chemical reaction and constants for hybrid nanofluid are defined below as:Quantities of Physical Interest:The skin resistance coefficient Here, The dimensionless form is:Here The temperature field can be used to compute the Nusselt number (dimensionless) for the temperature transference constant at the surface:The concentration field can be used to compute the non-dimensional form of the mass transfer coefficient at the sheet in terms of the Sherwood number:Obtain the highly non-linear system of PDEs using the boundary layer approximation (BLA) and stress tensor.Converting the achieved PDEs into ODEs with the help of suitable similarity transforms.Transforming a set of ODEs and associated boundaries into first-order ordinary differential equations so that we can easily call @ex8ode and @ex8bc to compute the problem in MATLAB.Achieving the dimensionless form of shear skin relation, Nusselt and Sherwood relations and using them to obtain numeric results.Finally, coding the whole problem in MATLAB and obtaining graphical and numeric outcomes and providing analysis of results.These equalities are converted to first-order linear equalities with the help of the following newly defined variables. Asymptotic behavior is gained by setting the solution tolerance rate up to The Equations The boundary condition is in the following form:The skin frictions, Nusselt and Sherwood numbers take the formThe obtained results show the impact on different profiles. The solution is compared with the literature in Q, chemical reaction Kc, etc. The reduced skin friction coefficient, Nusselt number coefficient and Sherwood number coefficient are noted for different values of constraints and presented through graphs and tables in the following.The results are obtained for different constraints like magnetic field The impact of magnetic field The influence on the temperature profile of Prandtl number The results obtained for Schmidt number z-axis. Similar behavior is noted for magnetic field parameter The numerical outcomes for various study parameters are presented in the form of the tables given below. −6. Graphs and tables are used to present the obtained outcomes. The major outcomes of this comparative research are listed below for velocity, concentration, temperature, Nusselt number and Sherwood number.This research article investigates the 3D mixed convection oxide nanoparticles hybrid nanofluid and mixed nanoparticles hybrid nanofluid flow in a permeable rotating system under the influence of a magnetic field and heat source/sink. The governing equationsare transformed into ordinary differential equations by using similarity transformations. The boundary value problem technique is used to tackle the transformed governing equations at MATLAB by setting the solution tolerance rate 10The increase in the magnetic field parameter increases the resistance to flow so the velocity profile decays with an increase in the magnetic parameter.The porosity and rotation parameter increases the velocity profile while the Reynolds number and mixed convection parameter decay.Thermophoresis parameters have a direct relation with the temperature profile, whereas heat source/sink, Prandtl number and Reynolds number have an inverse relation with the temperature profile.Heat source/sink does not have a prominent effect on the concentration profile.Schmidt number and chemical reaction parameter decay the concentration while the heat source/sink parameter increases.x-axis decreases and the z-axis increases by increasing the Reynolds number for both hybrid nanofluids.Skin friction along the Reduced skin friction and high Nusselt number are being observed for oxide nanoparticles hybrid nanofluid.


Diffuse idiopathic skeletal hyperostosis (DISH) is a systemic condition characterized by new bone formation and enthesopathies of the axial and peripheral skeleton. The pathogenesis of DISH is not well understood, and it is currently considered a non-inflammatory condition with an underlying metabolic derangement. Currently, DISH diagnosis relies on the Resnick and Niwayama criteria, which encompass end-stage disease with an already ankylotic spine. Imaging characterization of the axial and peripheral skeleton in DISH subjects may potentially help identify earlier diagnostic criteria and provide further data for deciphering the general pathogenesis of DISH and new bone formation. In the current review, we aim to summarize and characterize axial and peripheral imaging findings of the skeleton related to DISH, along with their clinical and pathogenetic relevance. Diffuse idiopathic skeletal hyperostosis (DISH) is a bone-forming disease characterized by excessive new bone formation in the axial and peripheral skeleton. In the axial skeleton, DISH usually affects the thoracic spine, and in the peripheral skeleton, new bone formation affects entheseal sites, mainly in the pelvis ,2,3.DISH is primarily observed in adults older than 45 years, with a male preponderance .DISH may be asymptomatic or may manifest as back and cervical pain, dysphagia, pain at peripheral entheseal sites, and limitation of motion of the spine, often mimicking ankylosing spondylitis (AS) . In addiA diagnosis of DISH relies on the radiographic criteria of Resnick and Niwayama, which require flowing osteophytes over at least four contiguous vertebrae of the thoracic spine, preservation of the intervertebral disc space without extensive degenerative intervertebral disease, and the absence of apophyseal and costovertebral joint ankylosis and sacroiliac joints (SIJs) erosion, sclerosis, or bony fusion . These cThe pathogenesis of DISH is not well understood. It is hypothesized that there is, on one hand, excess of growth factors  inducing the transformation of mesenchymal cells into fibroblasts and osteoblasts, and on the other hand, there is reduced inhibition of bone-promoting peptides  .DISH is considered a non-inflammatory condition with an underlying metabolic derangement that results in new bone formation ,15. HoweTherefore, imaging characterization of the axial and peripheral skeleton in DISH subjects may help to develop earlier diagnostic criteria and provide further data for deciphering the pathogenesis of DISH and new bone formation.The body of knowledge regarding imaging characteristics of DISH has grown over the last decade, leading to a change in perception regarding DISH, and from a merely radiological entity of doubtful significance, it is now commonly accepted that diagnosis of DISH is of important clinical significance.In the current review, we aim to summarize the most up-to-date reports characterizing axial and peripheral imaging findings of the skeleton related to DISH, along with their clinical and pathogenetic relevance.A characteristic feature of DISH is the presence of paraspinal flowing osteophytes resulting from the ossification of soft-tissue structures surrounding the vertebrae . A lucenThe differences in soft-tissue calcification result in two types of osteophytes: vertically oriented syndesmophytes, which are typical of AS, and horizontally oriented osteophytes, which are characteristic of DISH . HoweverAnterior ossification of the spine in DISH may involve the cervical spine, primarily along the lower half of the anterior border of the vertebral body, forming a “candle flame” or “parrot-beak” image  32]. Th. Th32]. In DISH subjects, bridging osteophytes in the cervical spine primarily occur anteriorly and are symmetrically distributed relative to the midline of the vertebral bodies . In contThe chunky anterior cervical osteophytes in DISH are known to impinge upon the anteriorly located airways and esophagus and cause airway obstruction and dysphagia  33], so, so33], Another phenomenon known to coexist with DISH is an elongation of the styloid process, which results from entheseal calcification and ossification of the stylohyoid ligament A 38,39,,39,40,41Ossified posterior longitudinal ligament (OPLL) is a hyperostotic condition that may lead to spinal canal stenosis and, potentially, neurological manifestations of varying degrees . OPLL isThe thoracic spine is the main segment of the spine affected by DISH and to which the Resnick and Niwayama classifications apply ,34,49. OBridging osteophytes in DISH are located along the anterolateral aspect of the vertebral bodies, most commonly involving the seventh through eleventh thoracic vertebrae ,51,52. TIn two studies that evaluated CT examinations for thoracic spinal DISH evolution, the amount of newly formed bone increased consistently over time ,55. BothAn ankylosed spine, such as that observed in DISH, is rigid and, as a result, is susceptible to injury, even from low-energy trauma. DISH is associated with a prevalence of thoracolumbar vertebral fractures of 4–18%, of which multilevel fractures are reported in about 8% ,57. ThesThe lumbar spine is the least affected and most likely the last affected segment of the spine in DISH . When DIThere is clinical significance to the involvement of the lumbar spine in DISH. In patients that undergo surgical treatment due to lumbar spinal stenosis, the coexistence of DISH increases the re-decompression rate and expansion of the decompression range ,64. In aTo distinguish between SpA and DISH, the SIJs appear as an exclusion criterion in the Resnick and Niwayama criteria, so that findings compatible with sacroiliitis, such as erosions, sclerosis, and ankylosis of the SIJ on pelvic radiographs, preclude the diagnosis of DISH . In subsPelvic and appendicular enthesopathy is common, characteristic extra-spinal manifestation of DISH ; consequEnthesopathy of the sacrotuberous and iliolumbar pelvic ligaments and insertional enthesopathy of tendons such as the iliopsoas, as seen on pelvic AP radiographs , have beEnthesopathy of the appendicular skeleton is a characteristic feature of DISH and has been found to be more prevalent in DISH subjects versus subjects without DISH . AppendiAppendicular DISH is characterized by the involvement of joints that are not commonly affected by primary osteoarthritis  ,78 as weA clinical radiographic study divided subjects with DISH and/or pelvic enthesopathy into three distinct phenotypes: (1) spinal DISH as per the Resnick and Niwayama criteria and <3 peripheral enthesopathies, (2) extensive spinal DISH as per the Resnick and Niwayama criteria and extensive peripheral enthesopathy, and (3) ≥3 peripheral enthesopathies but no spinal DISH, as per the Resnick and Niwayama criteria . In theiDISH and SpA are both bone-producing ankylosing diseases involving the axial and appendicular skeletons, in which enthesopathy is a major feature. However, while SpA is considered an inflammation-based disease, DISH is regarded as mechanical or degenerative in nature, although it has been suggested that local inflammation may also play a role in its development . The difGenerally speaking, new bone formation and enthesophytes in the spine and the appendicular skeleton are thick and prominent in DISH but thin in SpA. In addition, DISH-related osteophytes in the spine are primarily located on the right and are horizontal in nature, while in SpA, they are vertically oriented with no predilection to any side ,66. HoweThis coexistence may result from the fact that both bridging osteophytes and syndesmophytes have been reported to appear in both diseases, although with different ratios, e.g., a majority of syndesmophytes in AS and a majority of right-sided bridging osteophytes in DISH . AnotherPartial or complete ankylosis of the apophyseal joints has been described in advanced AS , whereasMany studies describing the co-occurrence of DISH and SpA have based their diagnosis of SpA on abnormalities seen at the SIJ, whereas their presence is an exclusion criterion in the Resnick and Niwayama classification for DISH ,80. HoweOne clear difference between DISH and SpA is the presence of SIJ erosions. These are common features of SpA but are seldom seen in DISH . TherefoPelvic enthesopathy on radiographs in DISH has a distinct appearance, with hypertrophic whiskering of entheseal attachments, whereas in SpA, bone proliferation is milder and is associated with bony erosion and sclerosis . MoreoveSeveral studies have described the MRI appearance of the spine and SIJs in DISH. Here, bone marrow edema and fat in the vertebral corners comparable to those characteristic of SpA have been described. However, their prevalence is much lower compared with SpA, and has been attributed to a degenerative process rather than an inflammatory process ,31,88. BDISH is not solely an imaging entity, but can manifest with significant clinical consequences, including spinal fractures even from low-energy trauma, neurologic deficits resulting from spinal stenosis, and dysphagia or airway obstruction due to abutting anterior cervical bridging osteophytes. In addition, diagnosing DISH and differentiating it from SpA is important for facilitating correct and targeted treatment. It is therefore important for clinicians to recognize the imaging characteristics of DISH in the axial and peripheral skeleton and understand DISH’s clinical consequences, evaluation, and management.The body of knowledge regarding imaging characteristics has grown over the last decade. The current Resnick and Niwayama criteria for DISH correspond to an end-stage diagnosis of the disease, in which the spine is already ankylosed. A newer set of classification criteria is warranted for diagnosis in an earlier, pre-ankylotic stage of the disease.The pathogenesis underlying this disease is still unclear, and although it is thought to be a degenerative disease, it has been suggested that similarities to SpA may imply an inflammatory basis. Imaging studies further characterizing the disease may potentially aid in deciphering the currently obscure pathogenesis of DISH.


Lack of archaeological and whole-genome diversity data has restricted current knowledge of the evolutionary history of donkeys. With the advancement of science and technology, the discovery of archaeological evidence, the development of molecular genetics, and the improvement of whole-genome sequencing technology, the in-depth understanding of the origin and domestication of donkeys has been enhanced, however. Given the lack of systematic research, the present study carefully screened and collected multiple academic papers and books, journals, and literature on donkeys over the past 15 years. The origin and domestication of donkeys are reviewed in this paper from the aspects of basic information, cultural origin, bioarcheology, mitochondrial and chromosomal microsatellite sequences, and whole-genome sequence comparison. It also highlights and reviews genome assembly technology, by assembling the genome of an individual organism and comparing it with related sample genomes, which can be used to produce more accurate results through big data statistics, analysis, and computational correlation models. Background: The donkey industry in the world and especially in China is developing rapidly, and donkey farming is transforming gradually from the family farming model to large-scale, intensive, and integrated industrial operations, which could ensure the stability of product quality and quantity. However, theoretical research on donkey breeding and its technical development lags far behind that of other livestock, thereby limiting its industrial development. This review provides holistic information for the donkey industry and researchers, that could promote theoretical research, genomic selection (GS), and reproductive management of the donkey population. The donkey is an equine animal of the order Odd-toed ungulates. Among common livestock animals, it occupies an important place in the history of human transportation. It is often used as a pack animal for long-distance transportation due to its good packability, durability, and traction, thereby greatly facilitating commerce among regions. With the advancement of modern technology, mechanization of agriculture, and rapid development of transportation, the service value of donkeys has decreased. In economically developed regions , donkeys are more often bred as ornamental pets. However, in fast-growing developing countries (such as China), donkeys are more often used as a source of meat for mass breeding because of their rich intra-muscular fat and superior taste . In recehttps://www.fao.org/agroecology/database/detail/en/c/1473377/ (accessed on 1 January 2019)), the total number of donkeys worldwide is approximately 50 million. The highest number of donkeys in China was about 12 million, but by 2019, donkeys faced a gradual decline in breeding stock to 2.6 million . The number of donkeys in Ethiopia has risen from 5 million to over 8 million, making it the country with the largest number of donkeys in the world (Food and Agriculture Organization of the United Nations). Sub-Saharan Africa, Northern India, and the tropical highlands in Latin America have been the main areas of increased donkey populations over the past three decades, while the Mediterranean region has experienced a decline, and the overall trend has been moderate growth [According to incomplete statistics .The early history of the African donkey is arduous to explore due to the lack of direct archaeological data. The wild relatives of the donkey have been hunted to extinction. Therefore, gathering detailed data to track the genetic information of their ancestors is difficult. Another strategy for filling this historical gap is the use of linguistics. Donkey and donkey terminologies have been recorded in various African and Near Eastern languages. Compiling these terms and tracing the connections could suggest some hypotheses about the domestication process and its pathways of transmission. These connections could be combined with modern ethnographic data to reconstruct the prehistory of the African donkey ,7.Linguistic evidence suggested that various branches of West Asian-African languages appear to have fairly distinctive wild-ass vocabularies. The main distributions are as follows: #kuur, which is widely distributed in Africa; #harre Ethiopian; #d-q-r Cushitic; #aɣyul Berber; and #aʒḍ Berber. In most cases, people were sufficiently familiar with the wild ass to name the creature in pre-domestication times. A comprehensive analysis revealed that the root #k-r is common in Central Africa, and it appears to have been transmitted to the Lake Chad region from the Cushitic region of the Horn of Africa (thus subsumed under the Nilo-Saharan languages). These findings prove that donkeys have been described in various languages of different tribes at different times, leading to the hypothesis that donkeys may have been domesticated many times on the Sahara periphery ,9.In the early years of human society, small city states proliferated, and the political, economic, social, and ritual natures of cities experienced an extensive change. Production specialization, large-scale long-distance transportation, and the extensive increase in the scale of warfare led to an increasingly important role of donkeys in the exchange between regions. Goods, such as copper and other products, were increasingly transported. Development that transformed the scale of the economic system benefited the domestic asset owners, creating a new class of merchants, and donkeys became progressively valuable. As donkeys began to be widely used in the Near East, “donkey caravans” were formed to specialize in the transportation of goods. Donkeys spread as a totem associated with worship among merchants and herders, who occupied specialized positions in the growing complexity of the social structure of urban societies, to secure their social status. An intact fossilized donkey bone was found at a site in Israel. The results of the burial excavation and analysis were used to integrate zooarchaeological, architectural, stratigraphic, and typological analyses of this bioarcheological deposit and identified donkey burial as a ritual deposit, clarifying the importance of this taxon to the religious and economic spheres of the Near East Early Bronze Age (EBA). If the results are confirmed, these findings will open a new gateway to understanding donkey burials scattered throughout the region ,11.The domestication process in donkeys may be slower and not as linear as previously supposed. Species–specific indicators of the early stages of domestication need to be identified to characterize the length and course of this complex process. Unfortunately, the earliest stages of donkey domestication are when they most resemble their wild ancestors, making them difficult to distinguish. The recently discovered skeleton and concurrent studies of modern African wild ass and donkey metacarpals were intended to elaborate the analysis of the original skeleton and develop markers for the domestication process of the donkey. Skeletal fragments show a tendency for Egyptian donkeys to decrease in size over time; thus, skeletologically, large donkeys are usually considered wild and small donkeys are usually considered domestic . MorpholEquus hemionus hemionus), water buffalo  and Przewalski’s gazelle . They prioritized the exploitation and use of nutrients from these large- and medium-sized herbivores  over domestication and load-carrying [Equus hemionus) is not the ancestor of the Chinese domestic donkey and they are related as two different species from the same genus [In 2011, a complete donkey skeleton was found at the Xinjie site in Lantian, Shaanxi Province, China . It was buried in a foundation pit at the house base, and archaeologists extracted the complete skeleton. Archaeologists further analyzed the bones and confirmed that the donkey had been domesticated, making it the earliest domesticated donkey found in China. This finding illustrated that donkeys have been raised in China for about 4000 years . Comparacarrying . Mongolicarrying . Althougme genus ,18. ThesEquus, which was formed approximately 4–4.5 million years ago. Although the equine fossil record represents a textbook example of evolution, the sequence of events that led to the existence of species diversity to date remains unclear. The entire genome and the genomes of surviving equine species were sequenced, the genetic material composition of specific genealogies were deciphering, and the complex history of the formation of equine species was revealed. Surprisingly, multiple examples of hybridization have been found throughout the genus Equus despite extremely different chromosomal structures, in contrast to theories that promoted chromosomal incompatibilities as a driving factor in the origin of the equine species [Horses, donkeys, and zebras belong to the genus  species ,20.Six indexed DNA libraries from the Somali wild ass (SOM), Onager (ONA), Tibetan kiang (KIA), Grevy’s (GRE), mountain (HAR), and plains (BOE) zebras were prepared successfully. The genome sets of all extant zebras and donkeys of the genus are currently completely represented. In addition, museum specimens were used to characterize the genome of extinct quagga zebra (which became extinct in the early 1900s) . CombineEquus caballus) and domestic donkeys (Equus asinus) by using primed in-situ DNA synthesis (PRINS) and FISH. The findings did not reveal any additional sites in horses and donkeys but confirmed the differences in signal intensity and frequency between the individual chromosome pairs in the two species. As in horses, no interstitial telomeric sites (ITSs) were detected in the donkey genome through PRINS analysis, possibly due to the multiple chromosomal rearrangements or the gradual loss of repetitive sequences that occurred during evolution after divergence from a common ancestor. On the contrary, another hypothesis indicated that these sequences are present in a very low copy number, hence not detected [Chromosome banding and new molecular cytogenetic techniques, particularly FISH, using chromosome painting probes, were used early on to understand the phylogenetic and systemic relationships of species and provide insights into the possible mechanisms of species formation . Comparadetected ,26.E. asinus) and stallion  spermatozoa was investigated using DNA breakage detection–FISH and comet assay. ALSs in the sperm of donkey was 1.3 times greater than in stallion and the length of the comet tail obtained in donkey sperm was 1.6 times longer than that observed in horse (p < 0.05). The difference is significant between these two species. The results suggested that ALS represents a species-specific issue in mammalian species related to chromatin organization in sperm and somatic cells, and it may diverge even at short phylogenetic distances [The presence of constitutive alkaline disruption sites (ALSs) in donkey , Somali wild ass , and ancient donkeys. The results indicated that the donkeys of clade 1 have a long history in the Sahara, and their ancestors were Nubian wild asses that were crossed with domestic donkeys over a long period of time by introducing several maternal haplotypes from the wild asses; the gene flow of this clade is continuous. A relative of the Somali wild ass is the ancestor of clade 2 (probably extinct). The Somali wild ass, on the other hand, belongs to clade 3, which is highly separated from clades 1 and 2, indicating that the Somali wild ass is not the ancestor of these two clades. The low variation and large sample size of the Somali wild ass made it unlikely that other lineages could be identified [The available genetic data from donkeys revealed two distinct mitochondrial DNA (mtDNA) haplotypes, indicating two distinct domestication events that occurred in Northeastern Africa approximately 5000–7000 years ago. The absence of a clear phylogeographic structure in domestic donkey haplotypes and the paucity of information on the genetic composition of African wild ass ancestors resulted in difficulty determining the feral ancestry and geographic origin of domestic mitochondrial branches. The analysis of ancient archaeological and historical museum samples provided genetic information on the historical Nubian wild ass . Microsatellite markers are simple sequence repeats, usually consisting of 1–6 nucleotide repeats, which are abundant and distributed throughout the genome. Microsatellite markers are highly polymorphic, species-specific, and co-dominant compared with other molecular markers, and thus have become increasingly important genetic markers for genetic diversity, population genetics, and disease diagnosis. These advantages validate the continued use of microsatellite markers in different studies to quantify genetic variation within and between species for the conservation management of animal populations ,34.Studies on the genetic characteristics of donkey breeds is scarce, and they are mainly concentrated on Mediterranean and Asian breeds. In 2006, 24 pairs of microsatellites from the horse genome were used to amplify the genomes of eight local donkey breeds in China. The results indicated that the microsatellites of similar species are conserved and could be used to analyze the genetic diversity of donkeys. Researchers also needed to have a deeper understanding of the genetic information and genetic relationships within and among breeds to obtain more accurate and generalized conclusions, which could be more effectively applied to the conservation and further utilization of donkey breeds ,36,37. IEquus kiang) in China, and the Pantesco, Ragusano , and Grigio Siciliano in Italy [In the past decade, researchers in various countries around the world, such as the United States , India , South Kin Italy , and Banin Italy  are protMitochondrial DNA (MtDNA) is maternally inherited so that any maternally related individual could have the same mtDNA sequence. In contrast to the more traditional nuclear DNA markers typically used, mtDNA provides a valuable locus for forensic DNA typing in some cases. With technological advances, researchers in molecular laboratories have developed new assays. Long-term dead or missing individuals or any living maternal relatives could provide a reference sample that is extremely useful in determining the identity of an individual. Furthermore, a large number of nucleotide polymorphisms or sequence variants in two highly variable portions of the non-coding control region could be effective in distinguishing between individuals and/or biological samples. Muscle, bone, hair, skin, blood, and other body fluids may provide sufficient material to type the mtDNA locus despite degradation due to environmental stress or time. MtDNA is inherited only from the mother: thus, any maternally related individual could provide a reference sample in cases where direct comparison with biological samples is not possible. However, the maternal inheritance pattern of mtDNA may also be considered problematic. As all individuals in a maternal lineage have the same mtDNA sequence, mtDNA could not be considered a unique identifier. Indeed, apparently unrelated individuals may have shared an unknown maternal relative at some distant point in the past. E. hemones and E. kiang) and two extant wild African ass subspecies, the Somali wild ass  and the Nubian wild ass (E. africanus africanus). The findings ruled out the possibility of Asian wild half-asses as an ancestor of the Chinese donkey. The African wild ass is anticipated to be an ancestor of the Chinese donkey. Research showed that the practice of animal domestication first emerged in the Near East but re-emerged in Northeastern Africa, a region that may have been particularly instrumental in the expansion of population and trade in the Old World. The domestication of donkeys may have originated as a response to Saharan desertification (5000–7000 years ago) by pastoralists and other social elements in Northeastern Africa, and it supplies clues for archaeological studies looking for evidence of the original domestication of the donkey.The donkey is the only individually domesticated hoofed animal in Africa. Its origin was assessed by sampling donkeys from 52 countries in the Eastern hemisphere and sequencing 479 base pairs (bp) of the mtDNA control region . Two higEquus asinus L.) in Serbia are diverse, with populations that are highly genetically diverse at the nuclear and mtDNA levels, but with severely declining populations. The two groups of individuals were found to have similar phenotypic characteristics, different nuclear backgrounds and different proportions of mtDNA haplotypes belonging to maternal Clades 1 and 2. Clade 2 may have appeared in Greece before Clade 1, while the expansion and diversification of Clade 1 in the Balkans preceded that of Clade 2.In 2017, Stanisic et al. assessed the current genetic status of the three largest populations of E. asinus in the central Balkans (Serbia) by analyzing the variability of the nuclear microsatellite and mitochondrial (mtDNA) control regions of 77 and 49 individuals, respectively [MtDNA D-loop and cytochrome b gene fragments were amplified and sequenced from 21 suspected donkey remains from four archaeological sites in China to explore the matrilineal origin and transmission routes of the Chinese donkey . PhylogeA total of 367 mtDNA D-loop sequences of Chinese donkeys were analyzed by scholars, and 96 haplotypes and 57 polymorphic loci were found to have a rich genetic diversity by analyzing the experimental results . ConsideBy using mtDNA Cyt b gene sequences and Y chromosome microsatellite methods, the genetic diversity and origin of 273 male donkeys from 13 domestic donkey breeds in China were studied . The resThe genetic diversity, origin, and domestication of donkeys have been extensively studied using autosomal microsatellites and mitochondrial genomes. However, the male-specific regions of the Y chromosome of modern donkeys are largely uncharacterized. Fourteen published Y-chromosome-specific microsatellite (Y-STR) studies were performed on 395 male donkey samples from China, Egypt, Spain, and Peru by fluorescently labeling microsatellite markers . The resWGS is a comprehensive method for analyzing entire genomes. It could detect single nucleotide variants, insertions/deletions, copy number changes, and large structural variants. Due to the recent technological innovations, the latest genome sequencers can perform WGS more efficiently than ever. Unlike focused approaches, such as exome sequencing or targeted resequencing, which both analyze a limited portion of the genome, WGS delivers a high-resolution, base-by-base view of the genome. Firstly, it could capture large and small variants that may be missed with targeted approaches. Then, it could identify potential causative variants for further follow-up studies of gene expression and regulation mechanisms. Lastly, it could deliver large volumes of data in a short amount of time to support the assembly of novel genomes. Although WGS has many advantages, it also has several disadvantages that should be mentioned. First, the role of most genes in the genome is still unknown or incompletely understood, indicating that some “information” found in the genome sequence is unusable at present. Second, an individual’s genome may contain information that the individual does not want to be known. Third, the volume of information contained in a genome sequence is vast, and analyzing these data is difficult. The scalable, flexible nature of next-generation sequencing technology makes it equally useful for sequencing any species, such as livestock, plants, or disease-related microbes. The rapidly dropping sequencing costs and ability to produce large volumes of data with today’s sequencers make WGS a powerful tool for genomics research.Equus have a more pronounced karyotypic diversity, and they are high-quality models for exploring karyotypic instability. The high frequency of mitogenic repositioning events in this genus is a puzzling phenomenon, and analysis of whole-genome sequences is a sophisticated and powerful method to study chromosome evolution. The findings of whole-genome assembly from donkeys and Asian wild asses could reflect the donkey’s unique characteristics, that is, more efficient energy metabolism and better immunity than horses [Equus, and comparative analyses based on these genome sequences provided important insights into the demographic history and adaptive evolution of the donkey. Furthermore, these results enhanced the understanding of chromosomal rearrangements and characteristic sequence dynamics associated with filament repositioning; the data could contribute to future studies of genomics and mammalian chromosome evolution in the genus Equus.Compared with other mammals, the species of genus n horses . ResearcLong-range and highly accurate de-novo assembly from short-read data is one of the most pressing challenges in genomics. Read pairs generated by proximity ligation of DNA in living tissue chromatin could solve this problem, thus extensively improving the scaffolding continuity of the assembly. In 2016, Putnam et al. reported an in-vitro method for generating long-distance ligation data that improves the scaffolding of de-novo assembled genomes . Their mDonkeys and horses share a common ancestor of the genus that lived 4.0–4.5 million years ago. While high-quality genome assembly for horses at the chromosomal level is available, the current genome assembly for donkeys is limited to moderate scaffold size. The novel high-quality donkey genome assembly obtained using HiRise assembly technology, which provides scaffolds of higher quality and length  than the existing donkey genome assemblies, further expanded the studies of selective breeding, equine evolution (including species formation and domestication), and conservation. The new assembly could identify runs of homozygosity (ROHs) caused by low effective population size and ancestral affinities, thus exploring their impact on the existing distance patterns between donkeys and horses . This neEPAS1 and EGLN1, respectively) to adapt to low oxygen conditions associated with living at high altitude. Both genes, EPAS1 and EGLN1, are the two most important genes for high altitude adaptation in Tibetan and other highland animals, indicating that the number of potential biological pathways involved in high altitude adaptation in mammals may be limited. The results of the comparative analysis revealed that the Tibetan donkeys did not acquire the ability to withstand high altitude through adaptive evolution with the Kiang, and gene introgression between the two is rare. On one hand, it may be because Kiang and Tibetan donkeys’ hybrids cannot reproduce offspring. On the other hand, it may also be because donkeys live on the Tibetan plateau for a short period of time and have limited encounters, making it difficult to generate gene flow. Given their biological similarities, EGLN1 and EPAS1 could provide markers for donkeys bred at other high altitudes in the world.Recently, researchers assembled a new draft genome of the Kiang and performed a large-scale resequencing of the Kiang and domestic donkey genomes . The finHi-C sequencing is based on chromosome conformation capture technology (3C), which applies high-throughput sequencing to capture spatially contiguous fragments across the entire genome and reveals three chromatin conformations in the nucleus. In descending order, the three-dimensional (3D) hierarchical structural units of the mammalian genome are chromosome territory, chromatin compartment A/B, topological associated domain, and chromatin loop. The advancement of high-throughput technologies has led to faster and more efficient ways of obtaining transcriptome data. RNA-seq (a sequence-based approach) has been the dominant technique in transcriptomics since the 2010s, and a recent study reported the transcriptome atlas of 16 Dezhou donkey tissues . The uniTBX3 gene was responsible for the pigmentation of the brown phenotype in both species, whereas the mutation in the non-brown phenotype in donkeys was caused by a 1 bp deletion, which may have a regulatory role.Previous studies have suggested that the Nubian wild ass and the Somali wild ass may be the ancestors of domestic donkeys. However, these findings only relied on the analysis of mtDNA variability, which only represents matrilineal inheritance. The genetic basis of the non-Dun phenotype, a pigmentation pattern that may have been selected during domestication or early post-domestication, was investigated by elucidating the history of donkey domestication through a population genomic approach that was based on whole-genome sequence data . The curHi-C technology has more advantages than the de-novo assembly from short-read data. First, Hi-C works through the spatial distance on the chromosome and the linear distance of the different resulting interaction frequencies to complete the chromosome localization. Thus, building a population is not needed because a single individual could be able to achieve chromosome localization. Second, greater marker density and more complete sequence localization could be achieved through Hi-C technology. It could generally be 90% of the above genomic sequences localized to chromosomes. Third, correcting the errors in the assembled genomic sequences is possible through the magnitude of the interaction frequency between scaffolds. Equus. Comparative analyses of sequences based on these genomes could provide important insights into the population history and adaptive evolution of horses. Furthermore, these results may strengthen the understanding of chromosomal rearrangement mechanisms (using Oxford Nanopore and Pacific Biosciences technologies) and these data may contribute to studies of equine genomics and mammalian chromosome evolution. Donkey genome assembly was first performed by Huang et al. at Inner Mongolia University, China, in 2015 . SequencIn 2018, Renaud et al. used emerging technologies to perform genome assembly in donkeys . The difIn 2020, Wang et al. constructed a de-novo assembly of the donkey genome by using cutting-edge methods . This apWith the advancement of science and technology, the discovery of archaeological evidence, the development of molecular genetics, and the perfection of genome sequencing, people have increased systematic and in-depth understanding of the origin and domestication of the donkey. In this paper, the development of research on the origin and evolution of the donkey was analyzed in detail in terms of archaeology, molecular cell studies, genetic material studies, genome sequencing, and assembly, and the advanced techniques were summarized. The domestic donkey originated in Africa and has two main clades, with a single domestication in Africa about 7000 years ago, followed by further expansion in that continent and Eurasia and eventual return to Africa. Undoubtedly, assembling an individual organism by its genome and comparing it with related samples could lead to more accurate results through big data statistics, analysis, and calculation of relevant models. In the era of bioinformatics, many biological experiments could be performed by genome sequencing under the existing conditions, but large-scale and high-quality research in the field of genome assembly is still urgently needed to achieve perfect whole-genome translation, application, and editing.


Acute respiratory failure (ARF) is a common life-threatening medical condition, with multiple underlying etiologies. In these cases, many factors related to systemic inflammation, prolonged use of steroids, and lung mechanical abnormalities (such as hyperinflation or increased elastic recoil due to pulmonary oedema or fibrosis) may act as synergic mechanisms leading to diaphragm dysfunction. The assessment of diaphragm function with ultrasound has been increasingly investigated in the emergency department and during hospital stay as a valuable tool for providing additional anatomical and functional information in many acute respiratory diseases. The diaphragmatic ultrasound is a noninvasive and repeatable bedside tool, has no contraindications, and allows the physician to rapidly assess the presence of diaphragmatic dysfunction; this evaluation may help in estimating the need for mechanical ventilation (and the risk of weaning failure), as well as the risk of longer hospital stay and higher mortality rate. This study presents an overview of the recent evidence regarding the evaluation of diaphragmatic function with bedside ultrasound and its clinical applications, including a discussion of real-life clinical cases. Acute respiratory failure (ARF) is a common life-threatening medical condition, with multiple underlying etiologies. Diaphragm muscle dysfunction is increasingly recognized as an important element that can present in patients with ARF or who are critically ill ,2. As ofAs compared with standard diagnostic approaches, chest ultrasound has been proven to improve the overall diagnostic accuracy in critical care settings, as well as in the emergency department . In thisThe diaphragmatic ultrasound is a noninvasive and repeatable bedside tool, has no contraindications , and allAn overview of the recent evidence regarding the evaluation of diaphragmatic function with bedside ultrasound and its clinical applications is hereby presented, including a discussion of real-life clinical cases.The diaphragm is an ample dome-shaped muscle which separates the thoracic cavity from the abdomen. It is comprised of three different portions: the central tendon, which is a non-contractile, fibrous structure; the costal portion, which inserts to the rib cage and thoracic vertebrae; and the crural portion, which inserts to the upper three lumbar vertebrae . The areThe diaphragm is the main respiratory muscle. During inspiration, its contraction lowers and widens the inferior part of the thorax, thus lowering the intrathoracic pressure  and allowing the insufflation of the lungs. During exhalation, the relaxation of the diaphragm allows the elastic recoil of the lungs to increase pleural pressure, thus removing air from the lungs . In healAssessing the anatomy and function of the diaphragm can be an auxiliary or, in many conditions, an invaluable tool to diagnose, characterize, and monitor both acute and chronic respiratory diseases. Ultrasonography is particularly promising for this purpose, due to its availability, fast execution, repeatability, low costs, and safety; moreover, it can be easily deployed bedside, which is very helpful in the acute or critical care setting ,19,20,21Ultrasonography of the diaphragm was first described at the end of the 1960s, but the true cornerstone of its implementation in the clinical practice was the seminal study by Wait and collaborators in 1989 . Wait inThe technique to perform diaphragmatic ultrasonography has been currently revised in an Expert Consensus statement, relatively to its adoption in the Critical Care setting . The diaThe diaphragm can be visualized as a three-layered band, which includes (from the outer to the inner layer) the hyperechogenic diaphragmatic pleura, the relatively hypoechogenic muscle, and the hyperechogenic peritoneal pleura .The distance between the inner margins of the diaphragmatic and peritoneal sheets is defined as the thickness of the diaphragm, the normal median (interquartile range) value of which is highly variable, with the majority of measurements ranging 3.3 (1.3–7.6) mm. Thickness is lower in female than in male patients, and is positively correlated to height and body weight, but independent of age ,25. MoreVariations of the thickness of the diaphragm during the respiratory cycle are inversely proportional to variations of its transverse surface, which results from its contractile activity. Since the volume of the muscle is constant, the shortening and flattening of the diaphragm during contraction is associated by a proportional increase in its thickness  22]. Th. Th22]. Assessment of the diaphragmatic thickening fraction shows good intra- and inter-observer repeatability also in mechanically ventilated patients ,29,30.It has been demonstrated that, in sedated and mechanically ventilated patients, passive inflation of the lungs causes an increase in the diaphragmatic thickness only when a volume of air superior to 50% of the total lung capacity is insufflated; therefore, at lower lung volumes, the thickening fraction reflects the diaphragmatic activity rather than passive alterations of the diaphragm induced by chest inflation, hence the utility of this assessment even in ventilated patients ,27.The thickening fraction has been widely studied as an indicator of the contractile efficiency of the diaphragm , and conIn fact, despite the fact that some studies have found a positive correlation between the thickening fraction and the pressure output of the diaphragm ,38, the Ultrasonography also allows the measurement of the diaphragmatic cranio–caudal excursion during the respiratory cycle. This requires employing curvilinear, low-frequency probes (2–6 MHz), which can be positioned just below the right costal arch, on the right midclavicular line, and directed upwards and laterally, so that the liver acts as an acoustic window and the ultrasound beam reaches the dome of the diaphragm perpendicularly. The diaphragm will be visualized as a bright, hyperechogenic line which lays over the profile of the liver. After having obtained a good visualization of the diaphragm in 2D brightness (B) mode, ultrasonography will be switched to movement (M) mode, in order to visualize the diaphragmatic respiratory excursions over time  Figure . The samDiaphragmatic ultrasonography can be limited by a poor acoustic window, for example in obese patients, in the presence of marked abdominal meteorism, or in patients with massive contraction of abdominal muscles during exhalation. Moreover, complete visualization of the diaphragm over the entire respiratory cycle may be impaired in patients with ribcage anomalies. As a result, diaphragmatic excursion may be hardly measurable in up to 28% of patients . InterprDue to the challenges of the ultrasound assessment of the diaphragm, the learning curve of this procedure is likely to require significant practice before being reliably implemented in the clinical setting. A randomized controlled educational study performed in eight Italian University hospitals in 2019 showed that integrating theoretical formation with practical training was able to achieve much better results in educating medical students or residents to perform diaphragmatic ultrasound ; the autBoth the thickening fraction and the excursion can be used as indexes of diaphragmatic contractility, and thus should be included in the functional evaluation of the diaphragm both in acute and chronic conditions. These parameters, and particularly the thickening fraction, have been explored as non-invasive predictors of ventilation or weaning failure in mechanically ventilated patients in the ICU setting, as discussed above ,46,47,48The gold standard procedure to assess inspiratory efforts is measuring the diaphragmatic pressure–time product (PTPdi) by means of gastric and esophageal balloons; experimental studies have demonstrated that the diaphragmatic thickening fraction has a significant, but often-underwhelming, correlation with PTPdi ,39,55,562) 75-year-old female with no smoking history, was admitted to the emergency department in October 2021 for progressive dyspnea and constrictive chest pain worsened in the last days. Her past medical history included moderate aortic–stenosis and mitral insufficiency, permanent atrial fibrillation, and arterial hypertension. Her chronic pharmacological therapy consisted of a beta-blocker, DOACs, and statin.B.M., an obese  septicemia, treated with daptomycin. Her weaning from tracheostomy was complicated by fever and a further increase in bronchial secretions, which occurred a week after starting antibiotic therapy. A chest HRCT was performed, revealing a mild right pleural effusion, associated with atelectasis of the lower lobe and elevation of the right hemidiaphragm. Given the recent heart surgery, which might have been complicated by phrenic nerve injury, and the presence of right hemidiaphragm elevation, diaphragm ultrasound was performed. Right hemidiaphragm dysfunction was confirmed by the absence of diaphragmatic excursion, in association with reduced muscle thickness and absence of diaphragmatic thickening (She was then transferred to the intensive care unit (ICU), where she was mechanical ventilated. After 3 days, a first trial of extubation was performed, but reintubation was necessary after 6 h. After a week, she underwent percutaneous tracheostomy. Her clinical course in the ICU was complicated by ventilator-associated pneumonia (VAP), with isolation of P. mirabilis on broncho-alveolar lavage treated with ceftazidime, and by methicillin-resistant ickening . PhrenicD.G., a 76-year-old former smoker (25 PKY), with a past medical history of arterial hypertension and a recent diagnosis of pheochromocytoma, was admitted to the intensive care unit (ICU) for acute respiratory failure which occurred after a right adrenalectomy to remove the pheochromocytoma in June 2022. Due to the high risk of cardiocirculatory arrest, he was intubated and mechanically ventilated for 3 days. After extubation, the patient was transferred to our high-dependency respiratory unit, where he was treated with non-invasive ventilation (NIV) and high-flow nasal oxygen for a relapse of respiratory distress and hypoxic respiratory failure. The chest X-ray showed the presence of bilateral inflammatory infiltrates and right hemidiaphragm elevation . ConsidePatients admitted to the emergency department or to the intensive care unit because of acute respiratory failure have considerably high in-hospital and one-year mortality rates . DiaphraDiaphragm ultrasound has been already successfully used in patients admitted to the emergency department with ARF, and particularly in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) ,13.Marchioni and colleagues evaluated the usefulness of early and noninvasive US diaphragm evaluation in patients admitted for acute exacerbation of COPD. They reported that the presence of diaphragm dysfunction on admission, defined as a change in diaphragm thickness less than 20%, was associated with a sixfold increased risk of NIV failure within the first 48 h and a fivefold higher risk of dying during the follow up .Moreover, Bobbia and colleagues proved that diaphragmatic excursion is feasible and reproducible (at both intra and inter observer level) . They alDiaphragm dysfunction can present also as a complication of thoracic surgery, particularly after coronary artery bypass graft (CABG) . In thesTo prevent the occurrence of post-surgery diaphragmatic impairment, it has been speculated that diaphragm ultrasound might also help the assessment of pre-operative risk, in addition to the EuroSCORE II , in patients undergoing cardiac surgery .More recently, Chen and colleagues analyzed the use of bedside diaphragm ultrasound in septic patients and acute respiratory failure in ICU . They obSeveral risk factors for diaphragmatic dysfunction during ARF have been identified  60,64].,64.60,64Formenti and colleagues demonstrated how ultrasound characteristics of the diaphragm and skeletal muscles such as rectus femoris and intercostals are strongly associated with ICU unfavorable outcomes in intubated patients with COVID-19 and ARDS . More spThe diaphragm is the main muscle involved in ventilation and whole-body homeostasis. In patients with respiratory impairment or acute respiratory distress due to different etiologies , many factors related to systemic inflammation, prolonged use of steroids, and lung mechanical abnormalities (such as hyperinflation or increased elastic recoil due to pulmonary oedema or fibrosis) may act as synergic mechanisms leading to diaphragm dysfunction . This exIn conclusion, assessment of diaphragmatic anatomy and function by bedside ultrasonography should be encouraged as an integral part of clinical practice in respiratory care.