The diversity and community assembly mechanisms of eukaryotic plankton in coastal waters is so far not clear. In this study, we selected the coastal waters of Guangdong-Hong Kong-Macao Greater Bay Area, which is a highly developed region in China, as the research area. By use of high-throughput sequencing technologies, the diversity and community assembly mechanisms of eukaryotic marine plankton were studied in which a total of 7,295 OTUs were obtained, and 2,307 species were annotated by doing environmental DNA survey of 17 sites consist of surface and bottom layer. Ultimately, the analysis reveals that the species abundance of bottom layer is, by and large, higher than that in the surface layer. In the bottom, Arthropoda is the first largest group, accounting for more than 20% while Arthropoda and Bacillariophyta are dominant groups in surface waters accounting for more than 40%. It is significant of the variance in alpha-diversity between sampling sites, and the difference of alpha-diversity between bottom sites is greater than that of surface sites. The result suggests that the environmental factors that have significant influence on alpha-diversity are total alkalinity and offshore distance for surface sites, and water depth and turbidity for bottom sites. Likewise, the plankton communities obey the typical distance-decay pattern. Analysis about community assembly mechanisms reveals that, overall, dispersal limitation is the major pattern of community formation, which accounts for more than 83% of the community formation processes, suggesting that stochastic processes are the crucial assembly mechanism of the eukaryotic plankton community in the study area. Recently, the progressed high throughput genome sequencing technology has been one of powerful tools to obtain biological big data, laying a good foundation for the study of biodiversity and related mechanisms . By eDNA2.2.1.in situ water quality parameters were determined using CTD, such as ORP, EC, T, salinity, depth, DO, pH, chlorophyll a, turbidity, and irradiance (E). For each sample, two liters of water were collected and divided into two subsamples, one for eukaryotic plankton community analyses and the other for water chemistry determination. According to the Specification for Marine Monitoring, Part 4: Seawater Analysis (GB17378.4-2007), nitrate, nitrite, DOC, TC, NH4+, DIC, and PO43-were assessed. In addition, total alkalinity (TALK) was determined according to the industry standard SL 83-1994. For the community analyses, 1,000 ml of water was filtered through 0.22 μm Millipore polycarbonate filters  method combined with the Zymo DNA Clean & Concentrator kit  has no correlation with other parameters except for PO43-in the surface samples, while in the bottom samples, the other three salts are correlated with some parameters except for NH4+ . The surface site with the highest diversity is GB-7S , and the surface site with the lowest diversity is GB-12S . The difference of Shannon index between the two sites varies nearly 5 times. The sites with the highest and lowest diversity in the bottom layer are GB-13B (Shannon index = 5.02) and GB-9B (Shannon index = 0.34), respectively, with a difference of more than 10 times, denoting that the alpha-diversity difference among bottom sites is more pronounced than that among surface sites.Both the alpha-diversity portrayed by Shannon index and its correlation analysis with environmental factors are presented in p = 0.0011) and offshore distance (p = 0.017) are significantly correlated with Shannon index of the surface layer. On the contrary, for the bottom layer, the depth (p = 0.032) and turbidity (p = 0.014) are significantly correlated with Shannon index. Meanwhile, more than 10 other environmental factors have no significant correlation with Shannon index of surface or bottom layer  include NH4+, PO43−, and TALK. It is particularly worth mentioning that because mollusks (larvae) are found so sensitive to ammonia that the original freshwater criteria of ammonia are not enough to protect shellfish, the United States Environmental Protection Agency (USEPA) revised the national ammonia criteria in 2013  among different sites in bottom layer is 10 times higher than that in surface layer. Ulteriorly, the environmental factors affecting alpha-diversity in surface and bottom layers are different, too. More precisely, biodiversity of communities in surface are mainly affected by TALK and offshore distance, while in the bottom, are the depth and turbidity. Seawater depth and terrestrial input may contribute much on beta-diversity of coastal communities. Additionally, the biomes investigated in this study also show a typical distance-decay pattern, and the distance decay effect of surface layer is stronger than that of bottom layer. The assembly mechanisms of surface and bottom biological communities are likely to each other and are both dominated by stochastic processes. As for the whole region, dispersal limitation, accounting for more than 83%, is the major way of assembly mechanisms of eukaryotic plankton communities, followed by heterogeneous selection and homogenizing dispersal, which account for 6.45 and 1.96%, respectively.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Z-GY contributed to the experimental design, data analysis, and the manuscript draft. X-MZ contributed to the experimental design and data analysis. S-WZ carried out the chemical analysis and data analysis. HJ contributed to the sampling and manuscript writing. S-PW contributed to data analysis. CW, JW, YS, and CL contributed to the sampling. HW contributed to the final proofreading. All authors contributed to the article and approved the submitted version.This study was financially supported by the National Key Research and Development Program of China (nos. 2021YFC3201005 and 2021YFC3101700), and the project of Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai) (no. SML2020SP008).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Cerebral microbleeds (CMBs) are common in the hypertensive population and can only be detected with magnetic resonance imaging (MRI). The anticoagulation and thrombolytic regimens for patients with >5 CMBs are different from those for patients with ≤ 5 CMBs. However, MRI is not suitable for evaluating CMBs in patients with MRI contraindications or acute ischemic stroke urgently requiring thrombolysis. We aimed to develop and validate a nomogram combining clinical and brain computed tomography (CT) characteristics for predicting >5 CMBs in a hypertensive population.In total, 160 hypertensive patients from 2016 to 2020 who were confirmed by MRI to have >5 (77 patients) and ≤ 5 CMBs (83) were retrospectively analyzed as the training cohort. Sixty-four hypertensive patients from January 2021 to February 2022 were included in the validation cohort. Multivariate logistic regression was used to evaluate >5 CMBs. A combined nomogram was constructed based on the results, while clinical and CT models were established according to the corresponding characteristics. Receiver operating characteristic (ROC) and calibration curves and decision curve analysis (DCA) were used to verify the models.In the multivariable analysis, the duration of hypertension, level of homocysteine, the number of lacunar infarcts (LIs), and leukoaraiosis (LA) score were included as factors associated with >5 CMBs. The clinical model consisted of the duration of hypertension and level of homocysteine, while the CT model consisted of the number of LIs and LA. The combined model consisted of the duration of hypertension, level of homocysteine, LI, and LA. The combined model achieved an area under the curve (AUC) of 0.915  with the training cohort and 0.887 (95% CI: 0.783–0.953) with the validation cohort, which were higher than those of the clinical model  and CT model . DCA showed that the clinical value of the combined model was superior to that of the clinical model and CT model.A combined model based on clinical and CT characteristics showed good diagnostic performance for predicting >5 CMBs in hypertensive patients. Cerebral microbleeds (CMBs) are subclinical brain lesions primarily characterized by minor hemorrhage in microvessels . CMBs of*-weighted imaging gradient-recalled echo (GRE-T2*WI) or susceptibility-weighted imaging (SWI) sequences ; (2) a history of cerebral surgery (n = 20); (3) a high suspicion of CAA according to the Boston criteria (n = 8) (n = 5); and (5) Alzheimer's disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, or multiple sclerosis (n = 0). A total of 160 patients whose medical records were obtained from February 2016 to December 2020 constituted the training cohort, and the remaining 64 patients, whose medical records were obtained from January 2021 to February 2022, were included in the validation cohort  SWI examination; (2) brain CT performed within 2 weeks of the SWI examination; (3) a history of hypertension; and (4) complete medical data records. The exclusion criteria were as follows: (1) a history of brain parenchymal contusion, lacerations, or subarachnoid hemorrhage ( (n = 8) –16; (4) n cohort .9/L), and homocysteine .The clinical and laboratory data were collected by screening the institutional medical reports. The clinical data included age, sex, duration of hypertension, grade of hypertension, history of diabetes, coronary heart disease, cerebral infarction, anticoagulant drug use, smoking, and drinking. The laboratory data included high-sensitivity C-reactive protein , triglycerides , total cholesterol , high-density lipoprotein , low-density lipoprotein , platelets . SWI was obtained with the following parameters: repetition time (TR): 40 ms, time to echo (TE): 25 ms, slice thickness: 1.8 mm, slice interval: 0 mm, flip angle: 30°, matrix: 320 × 320, and field of view: 230 × 230 mm. SWI images were obtained by transferring the original data into the MRI workstation for postprocessing. Brain CT examinations were performed with a multidetector CT device . The scanning parameters for CT were 120 kV tube voltage, 250 mA tube current, field of view: 250 × 250 mm, matrix: 512 × 512, slice thickness 5 mm, and 5-mm slice interval.Susceptibility-weighted imagings were evaluated by two radiologists (with 8 and 12 years of experience in neuroradiology) with the help of artificial intelligence (AI) software , who were unaware of the CT results. CT images were evaluated independently by two board-certified neuroradiologists (with 30 and 32 years of experience in neuroradiology) who were blinded to the SWI results. CMBs were defined as circular and uniform signal loss areas with a diameter of 2–5 mm and a clear edge on SWI images . Lacunart-test and the Mann–Whitney U test were used for comparing continuous variables when applicable. Interobserver variability was obtained by using an intraclass correlation coefficient (ICC) model, and differences in data were agreed upon negotiation. Multivariate analysis was conducted for statistically significant variables from the univariate analysis and demonstrated the absence of multicollinearity. A combined nomogram was constructed and expressed based on the results, while a clinical model and a CT model were established based on the clinical and CT characteristics, respectively. The receiver operating characteristic (ROC) and calibration curves and decision curve analysis (DCA) were used to verify the model internally and externally. Comparisons between the ROC curves of different models were performed using the Delong nonparametric method. The statistical analyses were performed by using software packages, including SPSS 23.0 , R , and MedCalc v. 19.0 . p < 0.05 indicated statistical significance.The chi-squared test or Fisher's exact test was used for comparing categorical variables when applicable. The independent-sample The interobserver ICCs for number of LIs, LA, brain atrophy, and >5 CMBs were 0.873 , 0.927 , 0.865 , and 0.955 , respectively. All ICCs indicated good agreement.p < 0.05; p < 0.05). However, there were no significant differences in other characteristics between the two groups.Differences in clinical and CT characteristics between patients with >5 CMBs and ≤ 5 CMBs are presented in p = 0.005), homocysteine level , number of LIs , and Blennow score of LA  were identified as independent factors predicting >5 CMBs . In the validation cohort, the combined model yielded the greatest AUC , which confirmed that the model achieved better predictive efficacy than the clinical model  and CT model . The Delong test showed that there were no significant differences among the three models in the validation cohort . Details of the performance of the three models are shown in All ROC curves are shown in p-value of 0.401, suggesting that the nomogram had a perfect fit. The calibration of the nomogram was further confirmed with the validation cohort  was above that of the CT model (blue) and the clinical model (green) both in the training cohort and validation cohort over a large range of threshold probabilities, suggesting that the combined model had a higher overall net benefit in identifying patients with ≤ 5 and <5 CMBs than both the CT model and the clinical model ,B. The nThis study retrospectively analyzed the clinical and CT characteristics of hypertensive patients to predict the probability that they had >5 CMBs to assist physicians in clinical decision-making. Four predictors were screened to build the model in this study, namely, duration of hypertension, homocysteine level, number of LIs, and LA score. The combined model had good predictive performance in both the training cohort and the validation cohort, and the areas under the ROC curve were 0.915 and 0.887, respectively, which were higher than those of the clinical model  and CT model . The Hosmer-Lemeshow test showed that the combined model had a good fit in both the training cohort and the validation cohort. DCA confirmed that the combined model was beneficial for making clinical decisions and provided superior benefit to the clinical model and CT model.In a previous study, Henskens et al.  found a We developed a combined model including two clinical characteristics (duration of hypertension and homocysteine level) and two CT characteristics (the number of LIs and the LA score) for predicting >5 CMBs in the hypertensive population. To the best of our knowledge, relevant reports about similar models have not been found, indicating the uniqueness of our findings. In our study, the AUCs of the combined model in the training cohort and the validation cohort were 0.915 and 0.887, respectively, indicating that this model has high diagnostic performance. Furthermore, the AUC of the combined model was higher than that of the CT model and the clinical model for both the training and validation cohort, which showed that the combined model had the best prediction effect. However, the Delong test showed that the differences in the ROC curves for the validation cohort were not significantly different among the three models. We speculated that the reason might be related to the small amount of data and the low sensitivity of the combined model in the validation cohort. In addition, when compared with MRI, CT is widely used in primary hospitals because it is less expensive, has a faster image acquisition speed, and could be applied to patients with MRI contraindications; it is also a necessary examination for patients with acute cerebral infarction for excluding ICH. In our study, the number of LIs and the LA score, both evaluated by CT, were associated with CMBs, similar to the conclusions of previous multisequence MRI studies, which all describe a mechanism of endothelial injury of intracranial small vessels caused by long-term hypertension –33. AddiOur study had several limitations. First, selection bias might be present because of the retrospective design of our study. We hope to conduct prospective studies in the future. Second, this was a single-center study without an external validation cohort. Thus, we should focus on multicenter studies to validate the results with external datasets in the future. Third, only recent antihypertensive control was recorded in the medical system, and there was a lack of follow-up records for long-term antihypertensive control. We hope to collaborate with cardiologists and further search the literature to explore indicators of long-term antihypertensive control and apply them to our study. Fourth, our inclusion criteria did not allow populations requiring anticoagulation or thrombolysis because of the small sample size. We would like to expand this study by only including the hypertensive population with ischemic stroke, TIA, or atrial fibrillation in order to better approximate clinical settings in which the sample size is sufficient. Fifth, hemoglobin A1C (HbgaA1C) level may be a more accurate factor as a measure of diabetes control rather than the presence/absence of diabetes. However, it was excluded because the data on HbgaA1C level of some patients are missing. We will include the HbgaA1C level when the sample size is large enough in the future study.In conclusion, we established a combined model for predicting >5 CMBs in a hypertensive population by incorporating four critical characteristics. This model demonstrated good discriminability and thus could provide substantial assistance for clinical practice, especially for the formulation of antithrombotic regimens for patients with contraindications to MRI or those in primary hospitals not equipped with MRI and for the formulation of thrombolytic regimens for patients with acute ischemic stroke who do not have enough time to undergo MRI.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Institutional Review Boards of Xiaoshan District First People's Hospital. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.X-BW contributed to data analysis and manuscript editing. HD, Y-GQ, C-CL, D-HC, and HF helped in images analysis. D-YH and JZ helped in collecting clinical data. XF helped critically revise the manuscript for important intellectual content. All authors contributed to the article and approved the submitted version.This research was supported by the Major Science and Technology Project of Xiaoshan District (Grant No. 2019214), the Medical and Health Science and Technology Project of Hangzhou (Grant No. B20210068), and 234 Platform Discipline Consolidation Foundation Project (2020YPT001).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Endometriosis affects approximately 6 to 10% of reproductive-age women globally. Despite much effort invested, the pathogenesis that promotes the development, as well as the progression of this chronic inflammatory disease, is poorly understood. The imbalance in the microbiome or dysbiosis has been implicated in a variety of human diseases, especially the gut microbiome. In the case of endometriosis, emerging evidence suggests that there may be urogenital-gastrointestinal crosstalk that leads to the development of endometriosis. Researchers may now exploit important information from microbiome studies to design endometriosis treatment strategies and disease biomarkers with the use of advanced molecular technologies and increased computational capacity. Future studies into the functional profile of the microbiome would greatly assist in the development of microbiome-based therapies to alleviate endometriosis symptoms and improve the quality of life of women suffering from endometriosis. According to a recent study, 196 million women between the ages of 12 and 52 have endometriosis, an uncomfortable condition that is estrogen-dependent and causes chronic pelvic and lower abdominal pain ,4. MeanwThe quantity of bacteria in the human body was once thought to be ten times greater than that of human cells ,24. HoweBefore discussing possible important risk factors that could potentiate the development of endometriosis, it is important to understand the prevalence of the disease across the globe, which further enhances our knowledge of the disease burden among different countries. While it is accepted that endometriosis could affect women of any age, a cross-sectional online survey conducted in Canada estimated the prevalence of endometriosis in Canada to be 7.0% , with nearly half of the respondents (47.5%) aged 18–29 years old when they were diagnosed with endometriosis . Interesp < 0.01) [p = 0.0003), whereas Hispanic women and other races/ethnicities did not differ significantly from Caucasians. A systematic review published by Bougie et al. in 2019 found that Asian women were more likely to have the diagnosis of endometriosis  [Fuldeore and Soliman  surveyed < 0.01) . Asian wn women) .Spanning over to Africa continent, a 10-year retrospective cohort study (from June 2003 to November 2014) at Nordica Fertility Center Lagos, Nigeria explained that 2.69% of participants (61/2265) were diagnosis with endometriosis via laparoscopy, with the highest proportion 43/61) of endometriosis patient in the age group of 31–40 years old . Several/61 of enn = 1025) had a self-reported history of endometriosis. Subsequent analysis of the data collected from 862 participants showed that the mean age of endometriosis diagnosis was 32 years old with the highest proportion observed among those aged 32 to 44 years . Conversely, a study by Feng and the team estimated the trends in endometriosis incidence from 1990 to 2019 were estimated using join point regression [How prevalent is endometriosis in the Asia Pacific region? Back in 1976, Miyazawa observed an interesting phenomenon in Hawaii whereby clinicians reported a high incidence of endometriosis among Oriental women. The study by Miyazawa analyzed the data of gynecologic admission and endometriosis diagnosis from three hospitals (two in Hawaii and one in Japan) which led to the conclusion that indeed there is a higher incidence among the Japanese population . Approxigression . When cogression . This stgression . The teap < 0.001). According to a study from Thailand, 30.5% (101/331) of the women who underwent surgery for the benign gynecological disease were found to have endometriosis (mean age: 39.4 ± 17.4 years old) [In 1992, a study in Southeast Asia that was completed by Yamamoto et al. in the United States reported findings that were in line with their findings ,49. Arumars old) . One wouars old) . Nonethears old) ,53. WhilDespite the fact that endometriosis can manifest itself in various ways, there are suggested diagnostic procedures that clinicians, including gynecologists and general practitioners, should follow ,55. One Endometriosis management calls for an individualized, multimodal, and interdisciplinary strategy . This maPrevotella, Streptococcus, Veillonella, Rothia, and Haemophilus genus [Lactobacillus, Akkermansia, Enterobacter, Lachnospiraceae, Prevotella, and several more [The term “microbiome” refers to a collective group of microorganisms that live in a habitat or specific site. Therefore, it is understandable that the microbiome across the human body may demonstrate differences in the microbial population . The claus genus ,95. In cral more . It is iral more . The gasral more .Lactobacillus spp. and these microbes protect the host against pathogens by creating a low pH environment and production of bacteriocins as well as hydrogen peroxide. The vaginal community state type (CST) classification system describes a total of five CSTs, whereby CST I, II, III, and V are dominated by Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii, respectively [Prevotella, Dialister, Atopobium, Gardnerella, Megasphaera, Peptoniphilus, Sneathia, Eggerthella, Aerococcus, Finegoldia, and Mobiluncus), is suggested to be linked with inflammation or dysbiosis in the vagina. Additionally, it is important to note that vaginal CSTs can change throughout women’s lifetimes. Given that some microbes can stimulate the immune system to trigger inflammation while a portion of them helps to maintain homeostasis in the host by the production of antimicrobial compounds or even immunomodulatory compounds, researchers are now exploring the possibility of microbiome involvement in the development and progression of endometriosis.The role of the gut microbiome in the etiology and pathogenesis of the human disease remains one of the top research areas for the past few decades ,100. Nevectively ,107. TheLactobacillus spp. dominated the cervical microbiome of endometriosis patients, they still presented a higher abundance of Corynebacterium, Enterobactericaea, Flavobacterium, Pseudomonas, and Streptococcus as compared to control (without endometriosis) [Enterobacteriaceae and Streptococcus abundance were statistically different between endometriosis and non-endometriosis control (p > 0.05). Similarly, another team in Taiwan described that not only the cervical microbiome of endometriosis patients was different from healthy women, but there were also some differences between endometriosis patients in Stage I and II as compared to those in Stage III and IV [L. jensenii or members in Corynbacteriales, Porphyromonadaceae, and Ruminococcaceae, (b) Stage III–IV: Bifidobacterium breve and Streptococcaceae members .The majority of the clinical studies investigating endometriosis and microbiome changes were derived from Asia including Japan, China, Taiwan, Korea, and Turkey  21,108,,117,118.I and IV . The teaLactobacillus in the endometriosis group as compared to the control [Gemella and Atopobium spp. was absent in the vaginal samples obtained from the endometriosis group. A similar approach was taken by Perrotta et al., but the team took a broader approach to look at the vaginal CST rather than looking at just a specific group of microbes [Anaerococcus (phylum Firmicutes).Given the challenges in obtaining cervical specimens without cervicovaginal contamination and the nature of biomass in the upper FRT, several teams have attempted to study the differences in the microbiome of the lower FRT. For instance, three studies in Brazil and China studied the vaginal swab or fluid obtained from patients and observed a lower abundance of  control ,118,119. control . At the microbes . These dClostridia Clostridiales, Lachnospiraceae Ruminococcus, Clostridiales Lachnospiraceae, and Ruminococcaceae Ruminococcus, along with an increased abundance of Eggerthella lenta and Eubacterium dolicum in endometriosis patients as compared to women without endometriosis. Likewise, another report by Shan et al. increased Firmicutes/Bacteriodetes ratio in endometriosis group, with enrichment of Actinobacteria, Cynaobacteria, Saccharibacteria, Fusobacteria, and Acidobacteria (p < 0.05) as compared to the control [On the contrary, Chen et al. were unable to identify microbial signatures from FRT microbiome for use as a biomarker but a prediction of metagenome functions using bioinformatic tools indicated a higher proportion of microbes involved in general metabolism, lipid metabolism as well as synthesis and degradation of ketone bodies . Further control . In esseAcidovorax (p = 0.01), Devosia (p = 0.03), Methylobacterium (p = 0.03), Phascolarctobacterium (p = 0.03), and Streptococcoccus (p = 0.04) in endometriosis group than the control group. In order to investigate potential crosstalk between different microbiomes, a research group in Korea decided to study the extracellular vesicles in the peritoneal fluid of endometriosis patients in comparison to those without endometriosis [Actinobacteria at the phylum level among endometriosis patients.Apart from the FRT and gut microbiome, there is another special microbiome that has been investigated to understand the development of the progression of endometriosis—the peritoneal microbiome. Once thought to be “sterile”, the peritoneal microbiome is found to be associated with the etiology of diseases such as end-stage kidney disease and cancer ,126,127.etriosis . The teaOver the past few years, researchers have developed animal models for endometriosis to study the changes in the microbiome, specifically to understand how microbes are involved in the pathogenesis of endometriosis as well as the influence on disease progression. Based on the published literature, the majority of studies reporting microbiome changes established the endometriosis model via three main ways: (a) homologous (syngeneic) transplantation, (b) autologous transplantation, or (c) heterologous transplantation of uterine or endometrial tissue . HomologBifidobactericeae and Alcaligenceae [Clostridium_sensu_stricto_1, Bifidobacterium, and Candidatus_Saccharimonas, on top of elevated Lactobacillus abundance in the gut microbiome of endometriosis mice [Similar to the findings from clinical studies, animal models of endometriosis reflected potential impact on different microbiomes. Most of the studies which attempted to search for microbial signatures in endometriosis were focusing on a specific locality—the gut microbiome which harbors the most microbes in the human body. Interestingly, an earlier study by Yuan and the team in 2018 reported enrichment of Firmicutes and Actinobacteria phylum in mice with endometriosis induced via intraperitoneal injection of endometrial segments, along with an elevated level of igenceae . Consistsis mice . Their tFirmicutes/Bacteroidetes has been used as a general indicator of a healthy gut microbiome, given that these two populations constitute a large proportion of microbes in the gut. Results from endometriosis studies involving the use of mice reported heterogeneity in results. While most of the studies reported an increase in Firmicutes and a reduction in Bacteroidetes abundance, there were two studies reporting the opposite effect, observing a drop in Firmicutes abundance and an elevated abundance of Bacteroidetes [Furthermore, the ratio of roidetes ,134. Everoidetes .Ruminococcaceae. Decreased Ruminoccoccaceae abundance has been proposed to have a negative impact, given that these strictly anaerobic bacteria can produce anti-inflammatory short-chain fatty acids such as butyrate and contributes substantially to maintaining the general health of the gut [Ruminococcaceae abundance in the gut microbiome in autoimmune diseases such as inflammatory bowel disease, several reports emphasized significant inverse correlations of Ruminococcaceae and its member, Ruminococcus with the inflammatory cytokine IL-6 [Additionally, the interest in identifying the key microbiome changes that contribute to the pathogenesis and progression of endometriosis continues to encourage scientists to explore animal models other than mice. In fact, a study in China adopted the autologous transplantation methods used in mice to create endometriotic lesions in six-to-eight weeks-old female Sprague Dawley (SD) rats . The res the gut ,139,140.ine IL-6 ,142.Papio Anubis) in reproductive age also indicated the involvement of T regulatory cells as they investigated changes in the gastrointestinal and urogenital microbiome [Succinivibrio, Prevotella, Megasphaera, Lactobacillus, and CF231 was decreased in fecal samples at three months post-induction of endometriosis; out of these genera, three of them—Succinivibrio, Prevotella, and CF231 abundance increased throughout the disease progression from six to nine months post-induction. Among the literature retrieved from databases reporting endometriosis in animal studies, this is the only study that implies the relationship between gastrointestinal, urogenital, and peritoneal microbiome. In the peritoneal cavity, it was reported that a group of unclassified bacteria dominated the peritoneal microbiome followed by Proteobacteria. The team reported that both the peritoneal and vaginal microbiome were diminished upon disease induction and failed to be restored throughout the progression of the disease. An in-depth correlation study on microbial species and peripheral immune cells after induction of endometriosis identified that certain microbial populations in the GI tract displayed a positive correlation with immune cell populations  at different study time points, but not the peritoneal and vaginal microbiome. Altogether, the authors concurred that additional analysis needed to be conducted to elucidate the exact mechanisms of these bacterial species in modulating host immune response. These exciting findings further strengthen the rationale to exploit microbiomes as treatment targets, especially their potential in modulating the host immune system and potentially alleviating pelvic inflammation which is commonly seen in endometriosis patients.Another recent study on non-human primates, olive baboons  and dysmenorrhea on the verbal rating scales (VRS) in the active group, recording at −3.28 ± 0.36 and −1.44 ± 0.17, respectively, as compared to the −2.00 ± 0.29 and −1.03 ± 0.16 recorded in the placebo group [L. gasseri OLL2809 in the treatment of the condition. In this study, endometriosis volume was significantly different between the active group of rats and the control and dienogest-treated groups, with a significant difference in log value of p < 0.05 recorded after four weeks of treatment [® capsule  among Stage III-IV endometriosis patients. The team noted a significant drop in dysmenorrhea scores after 8 weeks of treatment in the probiotic group—from 6.53 ± 2.88 to 3.07 ± 2.49 as compared to 5.60 ± 2.06 to 4.47 ± 2.13 (p = 0.018). Then again, more studies should be conducted to evaluate the actual changes in different microbiomes post-administration of probiotics to monitor the microbial dynamics throughout the period as well as test different administration routes to ensure optimal results from microbiome-based therapeutics. Given that the methods of probiotics preparation differ between administration routes, considerations should also be given to its stability to ensure optimal delivery to the targeted site [While pharmacotherapy remains critical in the symptomatic management of endometriosis patients, microbiome-based therapeutics may potentially be used in the nearest future to restore the balance in microbiomes and to alleviate chronic inflammation that is commonly observed among endometriosis patients ,144,145.bo group . Correspreatment . Anotherted site ,149. AloIn the past few decades, the scientific community witnessed the advancements in molecular techniques that allow in-depth investigations on host biology as well as the involvement of microbes in human diseases. As a matter of fact, understanding a complex disease such as endometriosis requires more than just perseverance and collective efforts from experts in different fields. Based on the gathered literature, there were some levels of changes in microbial signatures present among endometriosis patients; interestingly, these changes were not only restricted to the FRT but also at other sites including the gut as well as the peritoneal region. Yet, it is evident that the search for microbial-derived disease biomarkers for endometriosis is still in the infancy stage, especially for its implementation in clinical applications. Further studies would need to be conducted to resolve the heterogeneity issue observed in different clinical studies, given that these differences in data may arise from several factors including ethnicity, diet, or specimen quality ,151,152.Another essential point to consider in the crosstalk of microbiome and host processes is the estrogen-microbiome axis ,154,155.


Conflicting findings of the association between serum uric acid (SUA) and atrial fibrillation (AF) have been reported in both men and women. The sex-specific associations between SUA and the risk of AF are unclear, although hyperuricemia is independently associated with the risk of AF. We performed this meta-analysis to assess the sex-specific effect of SUA on the risk of AF.The PubMed, EMBASE, and Cochrane Library databases were searched up to October 3, 2021, for studies that reported sex-specific associations of SUA levels with AF. Linear relationships were assessed by the generalized least squares trend estimation. This study was registered with PROSPERO (42020193013).2 = 34%) and women . In the dose-response analysis, for each 60 μmol/L (1 mg/dL) increase in the SUA level, the risk of AF increased by 15%  in men and 35%  in women. There was a borderline difference in the impact of SUA on the risk of AF between men and women (P for interaction = 0.05). A significant linear relationship between SUA and the risk of AF was observed in men (P for non-linearity = 0.91) and women (P for non-linearity = 0.92).Ten eligible studies with 814,804 participants  were identified. In the category analysis, high SUA was associated with an increased risk of AF in both men (OR: 1.42; 95% CI, 1.18–1.71, IThis study suggested that there was a significant linear relationship between SUA and the risk of AF among men and women, with a higher risk estimate for women. Additional trials are required to assess the effect of reduced SUA therapy on AF incidence.https:www.crd.york.ac.uk/PROSPERO/, identifier: CRD 42020193013. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and it is associated with an increased risk of stroke, thromboembolic events, heart failure and other comorbidities. Due to its high rate of disability and mortality, AF has become a worldwide health problem . It is win vivo . This meta-analysis was performed in accordance with the PRISMA statement    40)..https:wwuric acid” OR “urate” OR “hyperuricemia” OR “gout”) AND .Database search, literature selection, quality assessment, and data extraction were carried out independently by two authors (J-H. X and W. S). Any disagreements were settled through discussions. The PubMed, EMBASE, and Cochrane Library databases were searched up to October 3, 2021 for all related studies. No restrictions were imposed on the language of the publications. The following MeSH words were used in our search strategies: (“The inclusion criteria were as follows: (1) reported sex-specific association of SUA levels with AF or reported for a specific sex; (2) risk estimates  and corresponding 95% CIs of the association between SUA and AF were reported. In addition, studies were excluded if they met the following conditions: (1) reviews, meta-analyses, congress abstracts, practice guidelines, patents, cases, editorials, replies, or comments; (2) the required data were not extractable even after contacting the corresponding authors for further information.The data were collected into a predesigned standard spreadsheet. The following data were abstracted from each included study: study characteristics , patient characteristics , and outcomes .We used the Joanna Briggs Institute critical appraisal checklist to evaluate the quality of the cross-sectional studies . The NewTo examine the relationships between SUA level and the risk of AF among men and women, we pooled the ORs and the corresponding 95% CIs by using the inverse-variance method. The RRs and HRs were considered equivalent to ORs. For the category analysis, both patients with highest vs. lowest and hyperuricemia vs. normal was analyzed. Hyperuricemia was defined as a SUA level > 7 mg/dl in three studies , 25, 31 2 test  and I2 test   by using the method proposed by Greenland and Longnecker . Additioctively) . ORs andp-value < 0.05 was considered significant.Subgroup and meta-regression analyses were used to identify potential sources of heterogeneity among the analyses. Studies were stratified by the mean age of the participants; region; NOS scores; study design; sample size; population; and adjustments for important risk factors, including age, body mass index (BMI), smoking, history of hypertension, and diabetes. We performed a sensitivity analysis by omitting 1 study at a time to assess the robustness of the conclusions. The possibility of publication bias was assessed by funnel plots, Egger's test , and Begn = 5); (2) the studies did not report sex-specific outcomes (n = 10); (3) editorials or review articles (n = 5); and (4) univariate analysis (n = 1). The reasons for exclusion are listed in The literature screening process is shown in The basic characteristics of all included studies are summarized in 2 = 34%, 2 = 0%).Six studies –36, 38 w2 = 70%, 2 = 0%) when excluding the above studies , with high heterogeneity  but not in women   .2 = 74%; P for non-linearity = 0.91; A total of 10 articles –38 with 2 = 73%; P for non-linearity = 0.92; Nine studies –37 with P for interaction = 0.05).There was a borderline significant difference in the impact of SUA [per 60 μmol/L (1 mg/dL) increase] on the risk of AF between men and women (As shown in P heterogeneity <0.001) or women (P heterogeneity = 0.001). Sensitivity analyses performed by omitting each study did not change the conclusion, which supported the robustness of our results (Data not shown). Further sensitivity analysis performed by removing the only study , we further investigated the sex-specific association and found a positive linear dose-response relationship between SUA and AF in both men and women. For each 60 μmol/L (1 mg/dL) increase in SUA levels, the risk of AF increased by 15% in men and 35% in women. There was a borderline significant sex difference in the impact of SUA on the risk of AF, with the risk estimates being higher in women.Two studies , 32 withSUA predicts the development of hypertension , which iP = 0.14, Interestingly, the category analysis of hyperuricemia vs. normal SUA showed patients with hyperuricemia were associated with increased risk of AF in men but not in women. No statistically significant difference among women . Therefore, our results do not seem to support the hypothesis that increasing age accounts for the sex-based difference in the context of SUA and AF.The occurrence of AF increases with age. SUA levels in postmenopausal women are increased due to metabolic changes caused by menopause , which mConsidering the proven association between high SUA and an increased risk of AF, SUA-lowering therapy may be a therapeutic target for reducing the risk of AF in the future. A retrospective, single-center study of 603 patients with heart failure showed that the use of allopurinol reduced the risk of AF by 13% . In a reAs we know, SUA level was regulated by kidney function. Evidence from recent studies showed renal dysfunction could impair the excretion of uric acid and contribute to a higher prevalence of hyperuricemia in the elderly. We performed a subgroup analysis stratified by adjustment for renal function. A positive association between SUA and the risk of AF among men and women persisted and there was little evidence of heterogeneity. Therefore, the association between SUA and risk of AF might be independent of kidney function.Our results appear to agree with previous meta-analyses –28, whicHowever, there are several limitations to the present systematic review and meta-analysis that need to be discussed. First, all of the included studies were observational studies. Hence, additional randomized, controlled trials are warranted to properly validate the associations of the SUA levels with the risk of AF in both men and women. Second, a high degree of heterogeneity was observed in our results. This was not surprising because of variations in the characteristics of the study populations and study designs. Third, although the trim-and-fill method was applied to address the problem of publication bias, such a test could have limited power in the setting of relatively few studies . Thus, tThe findings of this study suggest that there is a significant linear relationship between SUA and the risk of AF among men and women, with a higher risk estimate in women. Additional trials are required to assess the effect of lowering SUA therapy on the AF incidence.The original contributions presented in the study are included in the article/XL and KM were responsible for the entire project and revised the draft. JX and WS performed the study selection, data extraction, statistical analysis, and interpreting the data. WS drafted the first version of the manuscript. All authors participated in the interpretation of the results and prepared the final version of the manuscript.This work was supported by the National Natural Science Foundation of China , China Postdoctoral Science Foundation , the Jiangxi Provincial Natural Science Foundation for Youth Scientific Research , and the Jiangxi Provincial Key Laboratory of Cardiovascular Diseases of Traditional Chinese Medicine (20212BCD42010).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The relationship between diet and psychological disorders in older adults has attracted considerable attention as the global trend of aging. This study examines the relationship between Dietary inflammatory index (DII) and the risk of depression and suicide in older adults using the National Health and Nutrition Examination Survey (NHANES) as a large cross-sectional study.The data were extracted from NHANES from 2005 to 2018, and cross-sectional studies were conducted on older adults (age ≥ 60 years). According to their median DII, participants were classified into High-DII (DII ≥ 1.23) and Low-DII (DII < 1.23) groups. Depression was the primary outcome, and suicidal ideation was a secondary outcome. Utilizing multi-factor logistic regression to correlate DII with outcomes.P < 0.001) and higher ideation to commit suicide . Moreover, in terms of gender ratio, men accounted for 44% of the High-DII group, which was significantly lower than 56.2% of the Low-DII group (P < 0.001). Furthermore, logistic regression revealed that High-DII group had a higher risk of depression in the previous 2 weeks  and a higher risk of suicidal ideation . Additionally, after adjusting for demographic covariates such as age, gender and race, High-DII group still had a higher risk of depression  and suicidal ideation . Furthermore, after adjusting for various covariates like demographic, social factors, and comorbidities, the High-DII group remained at higher risk for depression , and the risk of comorbid suicidal ideation remained high , but the difference was not significant (P = 0.243).There were 10,956 elderly participants included in the analysis. In comparison to Low-DII group, High-DII group exhibited a higher rate of depression (8.9% vs. 6.7%; In older adults, high levels of DII are associated with depression and suicidal ideation. Multiple factors affect the mental health of older adults, and it is unknown to what extent a pro-inflammatory diet contributes to depression and suicidal thoughts in older adults. Nonetheless, daily dietary management in older adults should be emphasized. The mental health of the elderly is gradually becoming a critical global public health issue as the global aging trend develops. As of 2013, nearly 10% of the world’s population (approximately 615 million) suffers from a psychiatric disorder, with more than 20% of the older population over the age of 60 suffering from a psychiatric disorder, of which depression is one of the most common . ResearcP = 0.009), and each unit increase in DII score was associated with a 62% increase in the odds of developing schizophrenia  (There is research evidence that depression is significantly associated with chronic systemic inflammation . Chronic17–2.26) . Chronic17–2.26) . Several17–2.26) , 17 have17–2.26) . FurtherThere is a scarcity of direct and robust evidence between DII to an increased risk of depression and suicide in the elderly population. Data from large-scale demographic surveys are still required, given the potential economic burden and adverse effects of psychological disorders in older adults on an individual and societal level and the guiding significance of a rational daily dietary pattern. It is essential to investigate the relationship between psychological disorders and nutritional habits in the elderly, emphasizing daily dietary interventions.The National Health and Nutrition Examination Survey (NHANES) is a cross-sectional survey conducted by the National Center for Health Statistics and the Centers for Disease Control and Prevention, utilizing data from a nationally representative sample of the U.S. civilian population. This study’s dataset was constructed using NHANES public data files from 2005 to 2018, and the study population comprised all NHANES respondents.The key exposure variable in this study was DII, and the types and amounts of food and beverages consumed by the participants in 24 h were extracted. As documented in the literature , DII wasThis study’s primary outcome was depression. NHANES questionnaire yielded Patient Health Questionnaire-9 (PHQ-9) data. They consisted of nine clinical depression symptom items for the past 2 weeks, with scores ranging from zero to three for each item, with zero indicating no symptoms during the period, one suggesting a few days of symptoms, two showing more than half of the days with symptoms, and three describing symptoms almost every day. The cumulative PHQ-9 score was used to determine the presence and severity of clinical depressive symptoms in the previous 2 weeks. According to prior studies , when thEven though the proportion of elderly suicides is relatively low compared to depressive symptoms, it is important to focus on the study of suicidal ideation in the elderly, considering that suicide is mainly secondary to severe depressive symptoms and the heavy burden on society. Consequently, suicidal ideations were chosen as the secondary outcome in this study, and item nine of the PHQ-9 , diabetes, and cancer were collected.t-test or Analysis of Variance, and data for categorical variables were analyzed using the χ2 test for differences in cohort characteristics between exposure groups. The preliminary analysis employed multi-factor logistic regression to determine the relationship between the exposure group and the outcome variable. All descriptive studies were assessed for significance using two-sided tests at the P < 0.05 level of energy. Eventually, a Generalized additive model was employed to test for non-linear relationships between the outcome variables and exposure factors. All data analyses were performed utilizing Empower Stats software1  and R.3.5.2.2Quantitative data were examined using the First, initial survey data were obtained from 70,190 participants. After eliminating individuals who lacked outcome, exposure, or covariate data (with the exceptions noted above), the analysis included 10,956 older participants .P > 0.05). Furthermore, regarding gender ratio, males accounted for 44% of the High-DII group, significantly lower than 56.2% of the Low-DII group (P < 0.001), indicating that men tend to have a lower DII. Similarly, in terms of social factors, the High-DII group had a higher proportion ratio of family income to poverty ≤ 2.9,” “Married or living with a partner,” and “Never married” compared to the Low-DII group (P < 0.05). Furthermore, the differences in BMI, hypertension, diabetes and tumor history were statistically significant (P < 0.05).All elderly subjects’ median DII was calculated to be 1.23. As a result, the subjects were classified into the High-DII group (DII ≥ 1.23) and Low-DII group (DII < 1.23), with 5,478 participants in each group. P < 0.05).The High-DII group had 487 (8.9%) participants with comorbid depression and 205 (3.7%) with comorbid suicidal ideation, while the Low-DII group had 367 (6.7%) participants with comorbid depression and 166 (3.0%) with comorbid suicidal ideation. Therefore, depression and suicidal ideation were higher in the High-DII group than in the Low-DII group, and the differences were statistically significant (P < 0.001) and suicidal ideation  in the previous 2 weeks. After adjusting for demographic covariates like age, sex, and race, high DII was still associated with a higher risk of depression  and suicidal ideation . In addition, after adjusting for various covariates like demographic, social factors, and comorbidities, high DII remained an independent risk factor for depression . However, it was not a risk factor for suicidal ideation .As indicated in P = 0.047), while men were not . Another study (P = 0.003) and anxiety symptoms . The relationship between dietary patterns and depression remains significant, and strong epidemiological evidence proposes that poor diet may hurt mental health disorders (These outcomes are consistent with earlier studies  on the rer study  of residisorders . Howeverisorders , 25.Furthermore, our gender stratification results indicate that both men and women in the High-DII group are at higher risk of developing depression than those in the Low-DII group. Women with high DII are more likely to experience suicidal ideation. The differential results for suicidal ideation may be driven primarily by the female population. Although women generally have lower rates of committing suicide than men, they have higher suicidal ideation and attempt rates, especially in women over the age of 75 . This coIn short, the relationship between diet and mental health is complicated. Even though our observational studies reveal that high levels of DII may be related to depressive mood and suicidal ideation, there are many biological, psychological and social factors involved. As the global trend of population aging develops, numerous aspects of demographic changes increase socioeconomic pressures, and declining somatic functionality further complicates the discussion linked to mental health in the elderly population. The previous study has focused on the association between social factors and mental health in older adults.However, there are some limitations of the present work. First, it is difficult to elaborate on the causal relationship between an inflammatory diet and depression/suicide in the present cross-sectional study. Because the NHANES study collected data at a single time point, nutritional data were recorded only once for all participants, and PHQ-9 scores, as well as suicidal ideation questionnaires, were measured only once, which resulted in some possible bias in DII scores and PHQ-9 scores. In addition, this study may also have overlooked some relevant factors that influence depression/suicidal ideation in older adults, such as the presence of major life changes, chronic pain, family atmosphere, etc. Therefore, in the future, we need to conduct a multicenter longitudinal clinical trial to confirm our findings, dynamically assess changes in each of the factors that may influence depression/suicidal ideation in older adults, and conduct a long follow-up to investigate how inflammatory diet specifically affects the onset and progression of depression in older adults.Nonetheless, studies of dietary patterns and cognitive problems in older adults are scarce and primarily single-centered with small sample sizes. As our understanding of the factors influencing mental health in the elderly population improves, we should carefully evaluate dietary patterns’ long-term benefits and harms to mental disease in future studies and develop appropriate nutritional patterns for the elderly.By analyzing a nationally representative sample, we discovered that high levels of DII were related to moderate to severe clinical depression and suicidal ideation in older adults. This relationship is complicated, and further studies are required to understand it fully. However, the extent to which a pro-inflammatory diet leads to significant depressive symptoms and suicidal ideation is complicated and requires further research to demonstrate this relationship.https://www.cdc.gov/nchs/nhanes/index.htm.Publicly available datasets were analyzed in this study. This data can be found here: Before being interviewed or examined, all survey participants provided informed consent, and the NCHS Ethics Review Board approved the data collection protocol.YX and WH carried out the acquisition and interpretation of data and was the major contributor to drafting the manuscript and participated in drawing tables and diagrams. YX carried out the clinical data collection and analysis. WH contributed to the ideas of the article and reviewed the manuscript. Both authors provided final approval for publishing the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Capsaicin is a specific agonist of TRPV1 , which improves oropharyngeal dysphagia by increasing sensory input from the oropharynx and hypopharynx and by increasing repetitive stimulation of the cerebral cortex. The aim of this systematic review was to evaluate the therapeutic effect of capsaicin on swallowing disorders in stroke patients and the elderly.We searched Medline, Embase, PubMed, and Cochrane Library databases. We used the Mesh terms search database to screen all clinical trials that complied with the inclusion criteria. Studies were subjected to literature screening, quality assessment, and data extraction to remove studies that did not meet the inclusion criteria. After literature screening, quality assessment, and data extraction, a systematic review and meta-analysis of the included study were performed.P = 0.01] and on the Water swallowing test the improvement was significantly higher in the capsaicin group .This systematic review and meta-analysis were prospectively registered on PROSPERO under registration number CRD42022313958. Five high-quality randomized controlled trials were ultimately included. The results of our meta-analysis showed a more significant reduction in swallowing function score change in the capsaicin group compared to the control group [SMD = −1.30, 95% CI: , Although the results of our meta-analysis showed that capsaicin improved swallowing function, most studies had an unclear bias and included few studies. More studies are needed to support this in the future.www.crd.york.ac.uk/prospero/display_record.php?RecordID=304061, identifier: 304061. Oropharyngeal dysphagia (OD) is caused by a variety of diseases, the most common causes being stroke and aging  and the registration number was CRD42022313958 .The databases searched for this systematic review and meta-analysis included Medline, Embase, PubMed, and the Cochrane Library. The search keywords used MeSH terms which were “swallowing” OR “swallowing disorders” OR “deglutition disorders” OR “dysphagia” AND “capsaicin” OR “TRP” OR “vanilloid receptor agonist” . Randomized controlled trials (RCTs) published up to July 2022 were included based on inclusion and exclusion criteria. Two researchers with medical specialties independently assessed the title and abstract of each item using predetermined inclusion and exclusion criteria. When judgment could not be made on the basis of titles and abstracts, the full text of the articles was obtained. There was no potential bias between the two researchers and agreement was reached through discussion.Inclusion criteria: (1) patients with dysphagia associated with aging and stroke [Elderly or stroke patients were evaluated for Oropharyngeal dysphagia by Standardized Swallowing Assessment (SSA) scales or Volume-Viscosity Swallowing Test (V-VST) or Video Fluoroscopic Swallowing (VFS)]; (2) age > 18 years old; (3) patients were willing to participant the study and signed the informed consent.Exclusion criteria: (1) patients with lung disease and heart disease who cannot receive stimulation; (2) patient suffers from other diseases that may affect swallowing function; (3) patients who were allergic to capsaicin.Inclusion criteria: (1) patients received oral or topical capsaicin stimulation; (2) may be combined with other treatments .Patients in the control group were treated with placebo or combined with other drugs same as in the experimental group. No control group was set and studies comparing capsaicin with other treatments were excluded.The inclusion criteria were (1) only published RCTs were included; (2) studies with a follow-up of at least 80% and at least one primary outcome and (3) those with complete treatment outcomes.Exclusion criteria: review articles, animal studies, a case study, not relevant to the question and data was not extractable.The primary outcomes included: swallowing function score and water swallowing test. Secondary outcomes: efficacy of capsaicin, substance P (SP) concentrations, individual latency time, the standardized low-resolution brain electromagnetic tomography software (sLORETA), and safety of the treatment.Two researchers individually extracted and tabulated data on authors, date of publication, study site, sample size, sample characteristics, gender, age, experimental design, interventions, mode of administration, and outcomes. For incomplete data, the authors were contacted and any missing data were obtained. Controversial data were discussed or a third investigator was consulted to resolve any disagreements.The PRISMA guidelines  was used to perform the meta-analyses. For heterogeneity analysis, a fixed-effects model was used when I1- x̄2; S= Some studies reported the median, first and third quartiles, and maximum and minimum values. To perform a valid meta-analysis of continuous variables, these data were then transformed into means and standard deviations using the Box-Cox transformation method Langan, . Change Qualitative assessment of the funnel plot to determine publication bias, and visual inspection to determine whether there are any asymmetries , The funnel plot  is symme2 = 0%, p = 0.35). There is no heterogeneity therefore a fixed-effects model is used. Relative risks (RR) with 95% confidence intervals (CI) were used to assess the results of the dichotomous method. This meta-analysis results showed a significant difference between the capsaicin and control groups [RR = 2.46, 95% CI: , P < 0.0001; A meta-analysis of the treatment efficacy of the water swallowing test after administration of capsaicin or placebo. Treatment is considered effective when the experimental grade is raised to level I or II. The heterogeneity was observed in forest plots (Ip < 0.001) in Nakato's study  in the capsaicin group than those who took the placebo     . Therefore, both meta-analyses demonstrated that capsaicin can improve swallowing function. The Swallowing Function Test describes basic aspects of dysphagia, but it is not the gold standard for evaluating dysphagia, and clinical outcomes may be influenced by other important parameters, such as consciousness, cognitive ability, and language impairment, which can have an impact on swallowing scores. Therefore, caution is needed when using swallowing function tests to describe swallowing function.The results of this meta showed that swallowing scores improved more in the capsaicin group compared to the control group in stroke patients and elderly patients. In our meta-analysis of the water swallowing experiment, the increased grade of the patients was considered an improvement in swallowing function. The grade was significantly higher in the capsaicin group compared to the control group . Two studies reported the concentration of substance p in patients' serum and saliva, respectively. The SP of the capsaicin group was significantly higher than that of the control group in both studies.Stimulation of transient receptor potentials has been reported as a target for the treatment of swallowing disorders, and activation of transient receptor potentials may improve swallowing function   time (p < 0.539). In Nakato's study, only patients who responded to capsaicin were found to have a cervical esophageal wall opening time duration was significantly shorter (p = 0.0003).Esophageal manometry studies confirm that capsaicin exerts a prokinetic effect on esophageal motility by increasing the amplitude, duration, and speed of contraction of esophageal body peristalsis  Our meta-analysis included only 6 studies; our analysis would have been more credible if we had included more RCTs. (2) The Water Swallow Test and Swallowing Score are reliable but subjective methods for evaluating dysphagia. (3) Only English-language publications were included in our meta-analysis. (4) Heterogeneity is inevitable due to differences in gender, age, mode of administration, differences in experimental design and different disease conditions of the patients included in the studies.In summary, capsaicin may be a new perspective in treatment of oropharyngeal disorders in the elderly and stroke patients. There is still a lack of evidence for capsaicin in swallowing function, and more studies are needed to support this in the future.The original contributions presented in the study are included in the article/CY proposed the study idea, searched the database, screened and evaluated the evidence, and wrote the manuscript. RC extracted the data and analyzed the data. MF revised the manuscript. MZ revised the English. DW, XL, and WL suggested revisions to the article. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This study aims to create an all-around insight into the evolutions, status, and global trends of rhythmic auditory stimulation (RAS) research via enhanced bibliometric methods for the 2001–2020 time period. Articles concerning RAS were extracted from the Web of Science database. CiteSpace, Bibliometrix, VOSviewer, and Graphpad Prism were employed to analyze publication patterns and research trends. A total of 586 publications related to RAS between 2001 and 2020 were retrieved from the Web of Science database. The researcher Goswami U. made the greatest contribution to this field. The University of Toronto was the institution that published the most articles. Motor dysfunction, sensory perception, and cognition are the three major domains of RAS research. Neural tracking, working memory, and neural basis may be the latest research frontiers. This study reveals the publication patterns and topic trends of RAS based on the records published between 2001 and 2020. The insights obtained provided useful references for the future research and applications of RAS. Rhythmic auditory stimulation (RAS) is a therapeutic technique that uses predictable time cues to improve different outcomes related to movement ,2. RAS iA large number of clinical research and systematic reviews have examined the effectiveness of RAS in the rehabilitation of Parkinson’s disease (PD) ,7, strokBibliometric analysis is used for analyzing literature characteristics, research impact, and trends over time . In compThis study conducts a bibliometric analysis of RAS based on articles published between 2001 and 2020 to provide an all-around insight into the evolutions, status, and global trends of RAS research. The results can also be used to facilitate further experimental designs, study submissions, and clinical applications.Published papers were retrieved via a topic search of the Science Citation Index Expanded (SCI-Expanded) from the Web of Science Core Collection database (WoSCC) in September 2021. The searching strategy was based on free-terms: TS = (rhythmic + auditory + cue* OR rhythmic + auditory + stimulation* OR rhythmic + auditory + training* OR rhythmic + auditory + therapy* + rhythmic + acoustic + stimulation*), index = SCI-Expanded, and time span = 2001–2020.Only studies designated as “article” were included, covering all types of studies. Other document types such as meeting abstracts and letters, were excluded. The critical information  were comprehensively collected. Only studies that were published in English were considered. Finally, a total of 586 records published during the period 2001–2020 met the inclusion criteria.The data were analyzed by three bibliometric analysis tools: Bibliometrix R Package , VOSviewA total of 586 articles were identified. As PLoS One published the most RAS-relevant studies, with 32 articles , European Journal of Neuroscience (n = 14), and Gait & Posture (n = 14) ranked from eighth to tenth. Amongst the ten journals, there were six neuroscience journals, one multidisciplinary journal, one psychological journal, one neuroimaging journal, and a rehabilitation journal.Research relating to RAS has been published in 234 journals. articles . The Fron = 176) of the total. The United Kingdom (n = 60), Germany (n = 54), Canada (n = 53), Italy (n = 33), France (n = 30), The Netherlands (n = 25), Australia (n = 24), South Korea (n = 23), and China (n = 22) ranked from second to tenth and were all far behind on article totals. Authors from 40 countries have contributed to research on RAS. As shown in n = 25), Northwestern University (n = 22), Washington University (n = 22), McMaster University (n = 21), University of Maryland (n = 21), University of California Irvine (n = 20), and Max Planck Institute for Human Cognitive and Brain Sciences (n = 18). Half of the institutions were American colleges. The other five included two Canadian institutions, and The Netherlands, Germany, and the UK each had one.Aligned with the contribution of countries, n = 10), Rochester L (n = 10), Kotz S. (n = 9), Trainor L. (n = 9), Grahn J. (n = 8), Kwakkel G. (n = 8), and Earhart G. (n = 7).A total of 2263 authors contributed to the total output of RAS research. The top 10 authors published a total of 101 papers , which aThe keywords co-occurrence analysis produced a network map to reflect high-frequency keywords and topics within RAS research. As Journal of Cognitive Neuroscience in 2007 and received a total of 501 citations. Most of the articles  were published in journals in the field of neuroscience, and the other three appeared in medical and multidisciplinary journals. The top ten cited RAS articles in the past five years (2016–2020) were shown in Proceedings of the National Academy of Sciences of the United States of America in 2017. Among these ten articles, four were published in neuroscience journals, four in multidisciplinary journals, one in a biological journal, and one in a psychological journal.The frequency of citations could reflect the research topics within the field. The top ten cited articles in the field of RAS were shown in Burst detection was applied to investigate the research hotspots further. Burst keywords can be identified as indicators of emerging trends . Figure Clinically, RAS has been widely applied as a rehabilitation strategy. According to the analysis of high-frequency keywords, PD was the most focused disease within RAS research . A totalThe bibliometric analysis aimed to investigate the developmental trends and hotspots of research on 586 RAS articles during 2001–2020 by using VOSviewer, Bibliometrix, and Citespace. This work summarized research trends, topics, sources, and contributions for RAS.An exponential growth has been observed in the output of RAS research. If the overall growth rate that was observed also applies to the future, we can expect the publication volume in the RAS research field to double about every five years. This strong growth of research output may be partially attributed to the increased prevalence of neurologic and psychiatric diseases (those were major types of disease applying RAS treatment). Given this, researchers and practitioners worked on exploiting RAS to facilitate rehabilitation. Intervention methods and analysis strategies are being developed ,43,44. TAmong the top-performing journals, more than half were neuroscience journals. It seems that RAS researchers preferred to submit studies to the neuroscience area. An explanation is that for promoting research in the relevant field, some of the neuroscience journals have set auditory cognition and/or brain stimulation research sections or special columns. Most RAS studies were published in multidisciplinary journals also reflected a trend. This could be attributed to how the multidisciplinary journals tended to have a larger number of articles published than subject-specific journals. In addition, RAS has always been considered a transdisciplinary subject . PublishOf the top productive countries, the U.S. ranked first in the number of RAS publications. Five American affiliations came in the top 10 institutions in the research of RAS, symbolizing that the U.S. possessed the most elite institutions around the world. However, there is only one American author in the top ten authors, indicating the contributions of US researchers were more even. This may be because the concept of integrating RAS into rehabilitation was initially proposed by an American researcher  thus theKeyword analyses can be used for detecting research topics, analyzing research hotspots, as well as monitoring the research frontier transitions . ThroughFacilitating walking rehabilitation is a major use of RAS ,32. RAS Early studies regarding the beneficial effects of auditory stimuli on cognition  had been inconsistent . HoweverThe broad application of electrophysiological technologies  allowed researchers to explore the associations between RAS and sensory perception. Most early studies attempted to explain how neural sensory, and motor contributed to behavioral beat synchronization ,63. OverWe tried to provide information for future research and clinical uses based on quantitative bibliometrics, but a few limitations should be noticed. One is the findings of the study may be limited by the scope of the analytic tools. We only retrieved data from the WoS database, some vital information might have been missed. Another one is that the bibliometric data might not be adequate to assess the actual contribution of the research/researchers. Even though the quantitative metrics  can reflect the popularity, the results should be explained carefully.This study may help practitioners and researchers discover the publication patterns and emerging trends of RAS and present reference values for future research and applications. The most influential author, institutions, journals, and countries were Goswami U., University of Toronto, PLoS ONE, and the U.S., respectively. Motor dysfunction, sensory perception, and cognition are the three major clinical domains of RAS research. Neural tracking, working memory, and neural basis may be the latest research frontiers.


Background: Juvenile idiopathic arthritis (JIA) is childhood’s most frequent chronic rheumatic disease. JIA is a broad term that includes all arthritides starting before 16 years, lasting at least six weeks, and of unknown cause. The temporomandibular joint (TMJ) could be involved in JIA both at onset and during the disease course. The presence of TMJ synovitis might severely impair dentofacial maturation in pediatric patients. The ultrasound (US) application to detect early signs of TMJ synovitis in children with JIA has provided contradictory results. We sought to assess the current role of TMJ US in JIA through a systematic literature review. Methods: The systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Results: The literature search found 345 records. After duplicates removal, 253 records were screened, 20 full-text articles were reviewed to assess their eligibility, and 7 of them were included in the qualitative analysis. Joint effusion was the most recorded parameter, followed by bony condylar abnormalities. Compared to contrast enhancement MRI, the capability to detect signs of active synovitis of TMJ by US is low, especially at the early stages. Conclusion: Understanding how US may help diagnose and manage children with JIA is advisable for several reasons. MRI cannot be frequently repeated, may need sedation, and is expensive. The constant technical improvement of US will undoubtedly allow for better evaluation of what, in the past, was not clear or not even captured by sonography. So far, the role of US in the assessment of TMJ involvement in JIA is indubitably secondary to the MRI. Even so, we think that a baseline MRI of TMJ and the repetition of the sonography over time might both help the interpretation of US images and intercept significative changes. Juvenile idiopathic arthritis (JIA) is childhood’s most frequent chronic rheumatic disease, with a prevalence estimated between 16 and 150 per 100,000. JIA is a broad term that includes all arthritides starting before 16 years, lasting at least six weeks, and of unknown cause . AccordiThe temporomandibular joint (TMJ) could be involved in JIA both at onset and during the disease course; TMJ arthritis may affect a substantial number of JIA patients up to 87%) ,6,7. The% ,6,7. TIn the general population, the causes of temporomandibular disorders (TMD) are various; indeed, several factors may influence the development of this alteration: traumatic or post-traumatic abnormalities, intrinsic anatomic factors, and systemic conditions .In JIA patients, the term dentofacial deformity refers to the alteration in facial bone growth, development, and structure due to TMJ arthritis . MicrognTherefore, the early recognition and adequate treatment of TMJ arthritis are advocated. Unfortunately, the assessment of TMJ involvement in JIA is still challenging. Indeed, signs of TMJ synovitis can be absent at onset, and patients might develop symptoms afterward when the damage is already present. Therefore, clinical examination is not enough to exclude active arthritis, nor to rule out other diagnoses ,18. In tNevertheless, the high cost, the exam length, and the frequent need for sedation are considered significant disadvantages of this imaging modality, limiting its application in daily clinical practice. Furthermore, doubts have been raised regarding the sensitivity of an abnormal TMJ-MRI exam. Indeed, a slight effusion (<1 mm of diameter) and/or contrast enhancement, in the absence of chronic changes, has been reported in healthy children as well ; therefoA systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) . This reA literature search was developed first for a MEDLINE search and then adapted, if needed, to comply with the syntaxes of the following databases: EMBASE, WEB OF SCIENCE, and SCOPUS. The following keywords were used for the search: “juvenile idiopathic arthritis” OR “juvenile rheumatoid arthritis” OR “juvenile chronic arthritis” OR “juvenile idiopathic arthritides” OR “juvenile chronic arthritis” OR “Still disease” OR “still disease” OR JIA OR JCA OR JRA AND “temporomandibular joint” OR “temporomandibular joints” OR TMJ AND “Ultrasound” OR “Ultrasonography” OR “Sonography” OR “US”. The literature search was conducted through March 2022. The inclusion criteria were randomized clinical trials, cohort studies, observational studies, and case series using ultrasound for TMJ involvement assessment in JIA patients. The exclusion criteria were the following: insufficient data regarding US use; lack of comparison indicators ; non-peer-reviewed studies ; articles mainly reporting on JIA patients older than 20 years of age; case series reporting fewer than five JIA patients; and non-English-written studies. Two reviewers (AM and ODL) reviewed the results independently. Duplicates were removed. The first evaluation relied on titles only, and then abstracts of the included titles were screened. Results considered relevant were reviewed in full text and evaluated if they met selection criteria. Two authors (AM and ODL) manually evaluated the references of each full paper assessed. In case of disagreement, a third reviewer (RC) helped to make the final decision. A discussion of the original article was conducted, and if no accord could be reached, RC was then involved. Bias criteria were adapted according to the low level of evidence within this field using Cochrane guidelines as reference ,32. TablThe literature search found 345 records: 183 from Medline, 28 from Embase, 86 from Web of Science, and 48 from Scopus. Nine articles were added from the reference list of records considered interesting. After duplicate removal, 253 records were screened, and 20 full-text articles were reviewed to assess their eligibility ,42,43,44Joint effusion was clearly defined in three out of the six studies in which this parameter was evaluated: capsular width was used in three studies, but with different cut-offs ,27.Weiss et al. defined acute arthritis as the presence of joint effusion, but they did not observe any joint effusion among the 24/32 patients of their cohort who showed acute TMJ arthritis at MRI .Muller et al., using a capsular cut-off of 2 mm, detected the presence of joint effusion in 8/29 (28%) patients and 10/58 (17%) joints. At the same time, signs of active TMJ synovitis were documented in 19/30 patients (63%) and 32/60 joints (53%) at MRI . MelchioIn the study by Weiss et al., chronic TMJ arthritis, defined as the presence of condylar changes and/or erosions, was found in 9 patients (28%) by US and in 22 (69%) by MRI . Deformities of the mandibular condyle  were detected in 7/29 24%) patients by US and in 9/30 (30%) in the study by Muller et al. % patient. In the Assaf et al. assessed the synovial thickening using a cut-off value of 1.56 mm. They found 55/160 abnormal images that documented a concurrent narrowing of the joint space .p = 0.000); furthermore, the coronal closed-mouth position resulted in the most appropriate acquisition mode, given the narrowest confidence interval (0.022). However, the authors stated that LPAS does not help differentiate acute from chronic synovitis [Tonni et al. used the lateral periarticular joint space (LPAS) measured from the condyle’s cortical contour to the capsule’s contour as indirect parameters of the synovial joint space . The meaynovitis . Ultrasound can document synovial vascularization and hyperemia through a power Doppler signal; this amplifies the US sensitivity for acute inflammation in several joints . Only thp 0.047 for patients). Nevertheless, the level of the contrast enhancement at MRI influenced the correspondence between US and MRI: an 88% agreement in severe enhancement compared to 33% in moderate enhancement (chi-square p 0.003 for the difference) [p = 0.001 and 0.347; p = 0.001 at condylar level) [p of 0.623 and a p < 0.05) [In all except one study , TMJ-MRIference) . Kirkhusr level) . In compr level) . The val < 0.05) .In comparison with the healthy controls, low values of TMJ capsule width (<1.4 mm) were found in the 40 controls by Melchiorre et al. . In the The technological improvements and accessibility, the low cost, the time-consumption advantages, and the lack of ionizing radiations all represent the main reasons for the spread of daily US usage in rheumatology. With regard to pediatric rheumatology, interpreting US images of JIA patients is particularly challenging given the changes in children’s growth. Nevertheless, the role of US as a diagnostic tool in JIA has not been exhaustively established yet . SonograThe peculiarity of the TMJ makes it hard to evaluate by US, since only the lateral aspect of this joint can be seen with this imaging modality . This juIt is appropriate to highlight how a standardized image acquisition protocol for TMJ in children with JIA is necessary. Indeed, the difficulty in comparing the studies lies principally in the different parameters analyzed and their respective definitions. Even so, several considerations can be abstracted. No study demonstrated the superiority or the equivalence of US to MRI, which remains by far the best imaging modality to detect early signs of TMJ arthritis. Furthermore, a baseline MRI might be helpful for the US image interpretations. Indeed, US accuracy may be improved in light of the MRI result, as documented by a non-JIA study .By analyzing the studies collected herein, the weakest point of US seems to be the capability to detect signs of active synovitis, especially at the early stages. This can partially be explained by the peculiarity of TMJ, both anatomically and functionally: a little joint set among the temporal bone and the mandible, the presence of the articular disc separating the superior from the inferior part, and the possibility of both sliding and hinge movements . The need for synchronism with the contralateral TMJ represents a singularity that further complicates its evaluation. By the current evidence reported in this study, joint effusion does not appear to be a suitable parameter of active TMJ arthritis; nor does the analysis of the power Doppler signal. Synovial thickening seems more sensible than the abovementioned parameters. However, it is interesting to note that no study evaluated joint effusion, synovial thickness, and power Doppler signal altogether, despite these parameters being normally assessed in a routine US for evaluating the other joints. Furthermore, other specific parameters could help to characterize TMJ involvement in JIA. Disc dislocation detected by US has been found to play a role in the diagnosis of TMJ disorders; whether this is also true in JIA should be investigated . Understanding how US may help diagnose and manage children with JIA is advisable for several reasons. MRI cannot be frequently repeated, may need sedation, and is expensive. Furthermore, knowledge about the gadolinium-based contrast medium effects is growing and, besides the nonallergic and allergy-like reactions, additional complications such as brain deposition are nowadays a matter of concern ,53,54,55To date, few studies have analyzed the diagnostic value of US in TMJ synovitis of JIA patients. The parameters used in these studies were heterogeneous and needed clear definitions. The presence of joint effusion alone, the most frequently analyzed measure, has shown a modest correlation with MRI findings.The constant technical improvement of US will undoubtedly allow for a better evaluation of what, in the past, was not clear or not even captured by sonography. As yet, the role of US in the assessment of TMJ involvement in JIA is indubitably secondary to the MRI. Even so, we think that a baseline MRI of TMJ and the repetition of the sonography over time might both help the interpretation of US images and intercept significative changes. Whether the US sensitivity for active synovitis shall be improved in the future, this paradigm could be inverted as US would become an exam of the first level for TMJ arthritis to select those patients who need an MRI.The current efforts made for the standardized evaluation of TMJ-MRI could be essential to developing a US acquisition protocol. Indeed, using a shared MRI protocol as a reference may serve as a guide to understanding the more suitable parameters of normality and active synovitis by US.


Today, the situation of Syrian refugees is one of the world’s worst humanitarian crises. To estimate the prevalence of malnutrition among pediatric populations of Syrian refugees, 176 Syrian refugee children, with stays of more than two years at three refugee camps  or from the town of Yohmor, Lebanon were authorized by their parents to participate in this study. The children were anthropometrically evaluated and height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and weight-for-height (WHZ) Z-scores were obtained and compared with WHO standards. Furthermore, mid-upper arm circumference (MUAC) was analyzed for screening children 6–59 months old. According to the anthropometric measures, no child met the criteria for chronic, global, acute malnutrition (CGAM), severe acute malnutrition (SAM), or moderate acute malnutrition (MAM). In the total sample, 49.4% of participants were moderately thin, with girls presenting a higher prevalence of thinness than that of boys. Thus, the absence of high rates of malnutrition was verified despite the magnitude of the Syrian refugee’s problem. The data provided by this study identify the need to carry out further research to assess anthropometric growth and nutritional status among long-staying refugee children in order to prevent any health issues that may arise in the future. The Syrian civil war has resulted in citizens and permanent residents of Syria who have now become new refugees, with this type of situation increasing in other parts of the world due to other wars. Data have suggested that the pre-war population of the Syrian Arab Republic was approximately 22 million, including permanent residents. The United Nations (UN) identified 13.5 million displaced persons who required humanitarian assistance. Often described as one of the largest refugee crises in history, and since early 2011, growing political instability and escalating violence in the region have caused Syrian citizens to seek asylum by fleeing to neighboring countries .The World Health Organization (WHO)  has estiGrammatikopoulou et al.  observedTaking into consideration the especially vulnerable nature of refugee children as reflected in the literature ,17,18,19https://flourish.studio (accessed on 9 January 2023)) software, as a library to create visualizations, was used to map the distribution of places selected in ©OpenStreetMap contributors (https://www.openstreetmap.org (accessed on 9 January 2023)). The sample size was calculated with the sample size calculator website: http://www.raosoft (accessed on 9 January 2023), based on an error margin of 5% and a 90% confidence level, resulting in approximately 177 children in the four places. Children, from 1.2 to 16.4 years old, were selected through convenience sampling  of families from a comprehensive resident list provided by the refugee camp authorities (United Nations High Commissioner for Refugees (UNHCR)). All parents who had children under the age of sixteen and who had resided in the camps for at least one year were offered participation. The selected family had the option of choosing which of their children, if any or all, would participate in the study.This cross-sectional study was carried out during March and April 2017, in three camps: Zalhé (eastern Lebanon), Deddeh (northern Lebanon), and Kfar Jouz (southern Lebanon), and in the town of Yohmor (southern Lebanon) . The ©FlThis study was accepted by the authorities of these locations, approved by the Ethics Committee of the Universitat de Valencia (Spain) (EH-1-2017), and followed the fundamental principles established in the World Medical Association Declaration of Helsinki . FurtherAnthropometric assessments were conducted during morning hours after a short physical examination; the psychology and developmental stage of the children were considered. For children over 2 years old, body weight was recorded to the nearest 0.1 kg using a digital scale , while wearing lightweight clothing and standing erect with head straight and facing forward. For children <2 years old, the mother was weighed alone, and then the mother and child, wearing lightweight clothing, were weighed together. Subsequently, the child’s weight was calculated by the difference between the previous measured values .For children who were unable to stand using an infantometer, height was measured to the nearest 0.1 cm using a wall-mounted stadiometer that was calibrated daily.Height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and weight-for-height (WHZ) Z-score were calculated using the WHO AnthroPlus software , using the WHO child growth standard 2005 version for children aged 0–5 years  and the Furthermore, the BMI-for-age Z-score (BAZ) was used to classify the population according to their nutritional status into the following categories: severe thinness, moderate thinness, normal, overweight, and obese with cut-points of <−3 SD, from ≥−3 SD to <−2 SD, from ≥−2 SD to ≤+1 SD, from >+1 SD to ≤+2 SD, and >+2 SD, respectively .Mid-upper arm circumference (MUAC)  was meas2) test with Yates correction and type III analysis of variance , respectively, taking into account that the independent variable was the “location” . Significance was set at p < 0.05, and two-sided tests were performed. The prevalence of malnutrition in each location, according to gender and age group, was assessed with the chi-square (χ2) test or Fisher’s exact test. The statistical analysis was performed using the “R” statistical software  version 2.5.1 (2007).Variables were categorized and described using frequency distributions or percentage, mean, and SD. The normality of distribution was assessed through the Kolmogorov–Smirnov test. A statistical analysis for categorical and continuous variables was conducted through a chi-square . It is important to separate the results by gender because this malnutrition is hidden if we consider the value of the total number of children. Furthermore, the results reflected that, although no children had CGAM, SAM, or MAM, around half of the children were malnourished. This is because they were in the moderately thinness nutritional status category, which can have an effect on their health status. Several studies have shown that there is an increased risk of malnutrition and malnutrition of infants and children during migrations and war ,30. HoweHossain et al.  demonstrIn hospital admissions located in Tal-Abyad’s pediatric in-patient care/department, among children <1 year old, 13.0% exhibited severe acute malnutrition . Acute mMeanwhile, Syrian refugees in Jordan and Lebanon, according to the WHZ values from 0.23 to 0.39, were slightly overweight as compared with the WHO’s standard . SimilarThe prevalence of stunting 17.0%) was significantly higher among children living in the Zaatari refugee camp from Jordan as compared with children outside the camp (9.0%) . Grammat.0% was sBilukha et al.  demonstrIn fact, Rizkalla et al.  conducteAl Masri et al.  conducteKhuri et al.  indicateIn addition, several nutrition-related pathologies have been associated with Syrian refugees, such as (i) anemia due to inadequate iron intake by women during pregnancy and (ii) suboptimal maternal and child nutrition due to increased nutrient requirements , diabeteThe use of a prediction model of this pandemic in Syrian refugees could be useful. McCall et al.  conducteAll this implies that adequate assistance is required to overcome financial barriers and allow equitable access to medicines and medical care to guarantee the health and quality of life of Syrian refugees.The importance and implications of our study demonstrated that the continuous analysis of anthropometric measurements in this population must be carried out, in addition to other measurements, to ensure the health and successful growth of children.The limitations of this study are that we had a small sample and low female participation, which could impact the interpretation of the results and underestimate the presence of malnutrition. From our point of view, we believe that the reasons for the low female participation rate could be due to protective family attitudes towards girls and not allowing them to participate in the study, together with the fact that participating women preferred doctors of the same gender, geographic location, and cultural background, which has been demonstrated in several studies ,59,60. IIn conclusion, the present data demonstrate that the prevalence of malnutrition appears low among long-staying refugee children. However, when interpreting the data, one must consider that their stay in the camps for more than two years has not protected them against malnutrition, which was not expected to be found. Given that a significant number of refugees are children, more research is needed on the health status of this population. There is also a need to evaluate the actual objective strategies for assessing the health of children refugees. The main objective for this population should be to apply safety nets, interventions, and programs to address this issue.