Hashimoto thyroiditis (HT) is an autoimmune disease which may result in extensive damage of the thyroid gland. Chronic atrophic gastritis (CAG), is the most frequent HT-associated disorder, with anti-parietal cell autoantibodies (APCA) being a screening test for autoimmune CAG. The aim of this study was to investigate, in a cohort of HT patients: a) the prevalence of APCA in an attempt to define their clinical phenotype and b) any possible associations of APCA with other autoimmune diseases and malignancies.This is a single-center, case-control study, conducted at a University Hospital. The study included patients with HT diagnosed between November 2017 and November 2020. Excluded were patients <18 years old, with sonographic features of HT but negative thyroid peroxidase (TPOAbs) or thyroglobulin autoantibodies (TgAbs), Graves’ disease, Down or Turner’s syndrome.A total of 840 patients with HT were included in the study, from whom 180 (21.4%) had positive APCA. A total of 79 patients (9.4%) had one or more organ-specific autoimmune diseases and 61 (7.3%) had a systemic autoimmune disease. Autoimmune diseases were more frequent in female than in male patients . APCA-positive patients were older than APCA-negative  and had more often positive TPOAbs . Gastric neoplasms were documented only in APCA-positive patients (p <0.001). A higher frequency of organ-specific autoimmune diseases was observed in the APCA-positive group . In the subgroup of patients with additional autoimmune diseases (n = 140), younger age and positive APCA were independently associated with the presence of organ-specific autoimmunity . Papillary thyroid cancer (PTC) occurred in 3.5% of patients (26/29 women). Positive family history for thyroid autoimmunity and negative TPOAbs were the only independent risk factors for PTC among women .This study reveals for the first time an association of APCA with organ-specific autoimmunity in HT patients. APCA together with patient age were independently associated with the presence of organ-specific autoimmunity. Finally, this study showed an association between APCA and gastric neoplasms in these patients. Hashimoto thyroiditis (HT) is an organ-specific autoimmune disease, characterized by the immune-mediated destruction of the thyroid gland and together with Graves’ disease, constitutes the functional ends of autoimmune thyroid disease (AITD) spectrum. HT is the most common autoimmune disease with a prevalence in the general population ranging between 10 and 12% .+/K+ ATP-ase, is a screening test for autoimmune chronic atrophic gastritis and gastric enterochromaffin-like (ECL) cell hyperplasia, and can be detected in 85–90% of patients with pernicious anemia . All APCA-positive patients underwent gastroscopy and gastric biopsy to confirm histologically atrophy of parietal cells and to document the presence of pre-malignant or malignant lesions . TgAbs were assessed with an electrochemiluminescence immunoassay. The Roche E170 TgAbs is a competitive assay in which patient TgAbs competes for binding to solid-phase Tg with ruthenylated human monoclonal TgAbs. Interassay precision was 5.4% at 80.8 kU/L and 5.9% at 238.6 kU/L . APCA were assessed with an immunofluorescence assay (IFA) using mouse stomach substrate. Specific immunofluorescence pattern at serum dilutions >1/80 defined the positive values.A comparison between the APCA-positive vs APCA-negative subgroups was carried out using 2-sided Chi-squared test corrected by Fisher’s exact test when appropriate for categorical variables, while the continuous variables were analyzed by Student’s t-test for parametric and Mann–Whitney U test for non-parametric continuous variables. Among patients with additional autoimmune diseases, a bivariate logistic regression analysis was performed to identify factors associated with organ-specific autoimmunity and the unadjusted ORs and their 95% Confidence Intervals are presented. The independent variables of the model comprise of age, gender, presence of APCA, TPOAbs and TgAbs, family history for thyroid autoimmunity, and presence of malignancy. Moreover, a bivariate logistic analysis was performed to identify factors associated with PTC and overall malignancies (dependent variables). In these models, independent variables were age, gender, presence of APCA, TPOAbs and TgAbs, family history for thyroid autoimmunity and coexistence of other autoimmune diseases. A p-value <0.05 was considered statistically significant. SPSS software  was used for the statistical analysis.Overall, 840 of the total 1,126 patients with HT, agreed and were included in the study, from whom 180 (21.4%) had positive APCA. No HT included patient had laboratory findings of anemia. The APCA-positive patients were older than the APCA-negative patients  and had more often positive TPOAbs . No differences were observed regarding gender, presence of TgAbs, family history for thyroid autoimmunity or presence of other autoimmune diseases or malignancies between the two groups Table 1.We subsequently analyzed patients with coexistence of other autoimmune diseases (n = 140). Distribution of gender, TPOAbs, TgAbs, presence of family history for thyroid autoimmunity and malignancies did not differ significantly between patients with organ-specific and those with systemic autoimmunity Table 2.In our cohort, 29 (3.5%) patients of whom 26 (89.7%) were women, were diagnosed with PTC at a mean age of 47.9 ± 17.0 years old. Nine of them had positive APCA (31%). There was no statistically significant superiority of APCA in patients with PTC compared to those without . The presence of malignancy was not associated with gender, TPOAbs, TgAbs, APCA, family history for thyroid autoimmunity or coexistence of other autoimmune diseases, but individuals with a malignant disease were older than those without . In multivariate analysis, only age was significantly associated with the presence of malignant disease . Because of the small number of gastric malignancies in our cohort, we could not perform a multivariate analysis, and we were not able to assess the severity of gastric atrophy by histology. Studies regarding the risk of gastric neoplasms in patients with CAG do not discriminate between CAG due to chronic  lacking , 23.PTC occurring in 3.5% of the patients with negative TPOAbs was the only independent risk factor for PTC among women  , 25. TheIn our cohort, thirty-one (3.7%) patients had overall 3 or more organs affected. The association of autoimmune thyroiditis with other autoimmune disorders is well established, and the most frequent associations are autoimmune thyroiditis with CAG and non-segmental vitiligo, and autoimmune thyroiditis with CAG and polymyalgia rheumatica, respectively . AutoimmA limitation of our study is that APCA were measured by IFA, which is a semi-quantitative and qualitative method and not by ELISA, which would have eventually allowed quantitative assessments and correlations. Nevertheless, the two methods are comparable and monitoring of APCA levels was not a purpose of our study , 29.A strength of our study is the large number of HT patients included and the exclusion of patients with Grave’s disease, which may have a different pathogenetic basis.In conclusion, our study reveals for the first time an association of APCA with organ-specific autoimmunity in HT patients. APCA together with patient age were independently associated with the presence of organ-specific autoimmunity. Moreover, our study showed an association between APCA and gastric neoplasms in these patients.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Laiko General Hospital and School of Medicine National and Kapodistrian University of Athens. The patients/participants provided their written informed consent to participate in this study.GB conceived the idea of the study, designed the study and wrote the manuscript. EK participated in the design of the study, wrote the manuscript and performed the statistical analysis. AG reviewed and edited of the manuscript. IK and IG were responsible for data collection. PV reviewed and edited the manuscript. HM provided revisions to the scientific content of the manuscript. AT reviewed, edited and provided revisions to scientific content of the manuscript. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.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 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. 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To determine the association between chronic kidney disease (CKD) and mortality in persons with a confirmed coronavirus disease 2019 (COVID-19) diagnosis.Cross-sectional secondary baseline study. The study population consisted of 243,065 patients confirmed to have COVID-19 during May–December 2020. Stata 16.0 was used for statistical analysis, Chi-square test was used for bivariate analysis, and Poisson regression with robust variances was used for multiple analysis.The prevalence of patients with a confirmed COVID-19 diagnosis who had CKD and died was 1.42 times the prevalence of mortality in those without CKD. The comorbidities combined with CKD that presented the highest probability of mortality were diabetes mellitus and hypertension.CKD is associated with a high mortality rate in patients with a confirmed COVID-19 diagnosis. Patients with CKD, diabetes mellitus, and arterial hypertension have a higher prevalence of mortality than those without comorbidities. The physiopathology of coronavirus disease 2019 (COVID-19) involves inflammatory processes that initially occur as a local immune response triggered by the destruction of lung cells . HoweverPatients with chronic kidney disease (CKD) experience alterations, such as chronic inflammation, enhanced oxidative stress , and epiThe systematic reviews and meta-analysis by According to the above findings, CKD is related to COVID-19 severity and mortality risk . HoweverA cross-sectional study of secondary analysis of the Mexican open COVID-19 database was performed. The information in this database is collected by the Epidemiological Surveillance System for Viral Respiratory Diseases (SISVER) .th most populous country in the world and the third most populous in the Americas , the ruling committee , presence of a laboratory sample or antigenic test positive for SARS-CoV-2. The entire sampling frame was used.Inclusion criteria included patients with a confirmed diagnosis of COVID-19, patients aged 18 years or older and who had been hospitalized. Cases with invalid laboratory result, cases suspected of SARS-CoV-2, Cases tested negative and outpatients were excluded See .The statistical software Stata® 16.0 was used to calculate the statistical power for the two proportions. The patient populations with and without CKD were compared. According to the study by 2 without other signs of kidney disease  database. The covariates were age, sex, and smoking as well as diagnoses of pneumonia, chronic obstructive pulmonary disease (COPD), obesity, diabetes mellitus (DM), arterial hypertension (HT), cardiovascular disease, and immunosuppression.For collecting information, the database was provided by SISVER, a system executed by 475 monitoring units of the entire viral respiratory disease health sector (USMER) in Mexico (datos.gob.mx). Health personnel used the epidemiological study file of a suspected case of viral respiratory disease that contains the record of personal and clinical data, treatment, epidemiological history, laboratory results, and case evolution. The data were set up and updated on a regular basis, being able to freely access their registry through the open data catalog of the Government of the Mexican Republic. The updated database through 05 December 2020, was downloaded and imported in a “comma-separated values” (.csv) format to the statistical software Stata 16.0. Dates-associated variables were imported as a string (.str). Data cleaning was performed, and the confirmed COVID-19 cases were selected. Data of patients without confirmed COVID-19 were removed from the database. It was verified that there were no duplicate or lost data in the database.p < 0.05 was considered statistically significant, in the case of multiple comparisons, the Bonferroni correction was considered. A crude and adjusted analysis of the presence of CKD with another comorbidity was performed to know the effect on the prevalence of mortality. PR was used to assess the effects of CKD, DM, HT, COPD, and their combinations compared with no comorbidity, generated as individual models. Crude and adjusted PRs were estimated for age, sex, COPD, obesity, diabetes mellitus, hypertension and immunosuppression as well as for their 95% CI.Stata® version 16.0  was used for the statistical analysis. The categorical variables were expressed using absolute and relative frequencies. The Chi-square test was used for the bivariate analysis comparing the proportions. The multiple analysis considered mortality and ICU admission as the outcome variables. This analysis used a generalized linear model with Poisson family, logarithmic link, and robust variances to estimate the prevalence ratio (PR). The CI was 95%, and https://datos.gob.mx/) according to the decree published on 20 February 2015 in the Official Gazette of the Federation, which concluded that the general population is able to access it . The confirmed COVID-19 diagnosis was more frequent in men than in women, with an approximate ratio of 3:2 (60.35% and 39.65% respectively).Hypertension, DM, and obesity were the comorbidities with the highest frequency , occurring in more than 90% of the population with a confirmed COVID-19 diagnosis. Approximately two thirds of the cases presented pneumonia as a complication, and 8.46% of the patients were admitted to the ICU. Regarding CKD, it was found that 5.37% of the population had this disease See .vs 38.37%, p < 0.001). Considering the Bonferroni correction, this comparison remains statistically significant. Patients with CKD and COVID-19 experienced higher mortality than those without CKD (55.29% vs 38.95%). CKD was the comorbidity with a higher frequency of mortality than other diseases . Considering the Bonferroni correction, this comparison remains statistically significant. Men with a confirmed COVID-19 diagnosis presented a higher number of admissions to the ICU than women , as seen in the mortality frequency. Furthermore, 11.43% patients with pneumonia were admitted to the ICU vs 3.02% without pneumonia. Patients with CKD and COVID-19 were admitted to the ICU less frequently than those without CKD , while patients with obesity and COVID-19 were admitted to the emergency room more often than those without obesity . . See .p < 0.001). The prevalence of mortality in women was 22% , which was lower than that in men. CKD and hypertension were found to be the most prevalent comorbidities in people who faced mortality . The prevalence of confirmed COVID-19 cases that had CKD and died was 1.42  times that of cases with no kidney disease as a comorbidity. This number decreased to 1.29  in the multiple analysis when adjusting for the variables of age, sex, COPD, obesity, diabetes, hypertension, and immunosuppression. In the multiple analysis, it was found that the PR of death for the cases with obesity vs no obesity as a comorbidity was 1.10 times  higher than that observed in bivariate analysis . It stands out that the death prevalence with CKD as a comorbidity was 1.42  times than that without kidney disease. However, this prevalence was reduced to 1.29  times in the multiple analysis . Multiple analysis adjusted for the variables of age, sex, COPD, obesity, diabetes, hypertension, and immunosuppression showed that the prevalence of being >65 years of age and admitted to the ICU was 1.10 times than that of being >45 years of age and admitted to the ICU . The prevalence of admission to the ICU with CKD was 26%  lower than that of admission to the ICU with no CKD  times than that in patients without any comorbidity. The prevalence of mortality in patients with CKD and hypertension was 1.65  times than that in patients without any comorbidity .CKD is an important risk factor for mortality in COVID-19. Previous reports in Mexican patients with confirmed COVID-19 showed frequencies of CKD presentation ranging from 2.4% to 4.78%, while in this study the frequency of presentation rose to 5.37% . This diWe decided to include hospitalized patients to control bias, considering moderate-to-severe patients with a clinical severity associated with high mortality .vs no CKD in the Mexican population was 1.42, while vs no CKD as 6.86 until April (The results showed that the prevalence of mortality among patients having CKD as comorbidity il April . This diAge is significantly associated with mortality in COVID-19. In the present study, it was determined that the population hospitalized with confirmed COVID-19 and aged >65 years had a higher frequency of mortality compared to other age groups. This high mortality is similar to that reported in other studies, where the population >65 years of age has a high frequency of mortality, reaching values of up to 87.1% . AccordiWe expected to find that patients with CKD had a risk factor for admission to the ICU; however, we found that this comorbidity was a protective factor for admission to the ICU. It is considered that this finding corresponds to a possible methodological error related to the decision to admit patients with CKD to the ICU. According to previous studies, it is known that having CKD is a high predictor of mortality , therefoIn the present study, an association was found between chronic conditions and mortality in confirmed COVID-19 cases. According to the results obtained by analyzing the occurrence of CKD with another comorbidity, the death prevalence in those patients with CKD and DM was 1.64 times the probability of dying compared to patients who did not have any other comorbidity. This finding is based on the fact that one of the most common complications of DM is CKD, and patients frequently have both conditions; therefore, their prognoses are closely related . FurtherLimitations of the present study: The database used is secondary in nature and we were unable to evaluate other variables such as difference in treatments, severity of COVID-19, laboratory data, and control of chronic diseases. Hence, we should be cautious while interpreting the findings. In addition, we acknowledge Berkson’s bias, in generalizing these data to Mexican hospitalized patients with CKD and COVID-19. Finally, in relation to the result obtained where CKD would be a protective factor for ICU, it can be pointed out that there could possibly be a survival bias with respect to the ICU outcome.The study concludes that there is an association between CKD and mortality in patients with a confirmed COVID-19 diagnosis. The results show a high frequency and prevalence of mortality in patients with CKD, a finding supported by other studies conducted in Mexico with results similar to those obtained in the present research. Likewise, an association was found between chronic conditions and mortality in confirmed COVID-19 cases.10.7717/peerj.13437/supp-1Supplemental Information 1ckd, Chronic kidney disease; ckd_dm, Chronic Kidney Disease and Diabetes Mellitus; ckd_dm_hta, Chronic Kidney Disease; Diabetes Mellitus and Hypertesion; ckd_hta, Chronic Kidney Disease and Hypertension; copd, Chronic Obstructive Pulmonary Disease; dm, Diabetes Mellitus; hta, Hypertension; icu, Intensive Care Unit; id, Record ID.Click here for additional data file.10.7717/peerj.13437/supp-2Supplemental Information 2ckd, Chronic kidney disease; ckd_dm, Chronic Kidney Disease and Diabetes Mellitus; ckd_dm_hta, Chronic Kidney Disease; Diabetes Mellitus and Hypertesion; ckd_hta, Chronic Kidney Disease and Hypertension; copd, Chronic Obstructive Pulmonary Disease; dm, Diabetes Mellitus; hta, Hypertension; icu, Intensive Care Unit; id, Record ID.Click here for additional data file.


Background: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a clinical syndrome associated with mitochondria and lacks effective preventive and therapeutic measures. This bibliometric study aims to gain insight into the scientific findings regarding mitochondria in ALI/ARDS. Methods: We retrieved the Science Citation Index Expanded (SCIE) of the Web of Science Core Collection (WoSCC) for mitochondria in ALI/ARDS publications from 2012–2021. VOSviewer, CiteSpace (5.8. R3) and Bibliometrix (3.1.4) R package were used for further analysis and visualization. Result: A total of 756 English-language articles and reviews were identified. The annual number of publications presented a rapidly developing trend. China was the most productive and cited country, and the USA had the greatest impact. In the keyword co-occurring network, the terms “acute lung injury”, “oxidative stress”, “inflammation”, “mitochondria” and “apoptosis” occurred most frequently. The co-citation network revealed that #1 mesenchymal stromal cell and #3 endothelial cell had the most bursts of citations. In addition, research hotspots have shifted from “potential therapeutic treatments” and “mitochondrial DNA (mtDNA)” to “endothelial cell” and “mesenchymal stromal cell (MSC)”. Conclusion: This bibliometric analysis reveals the research directions and frontier hotspots of mitochondria in ALI/ARDS, which has shown a rapid growth trend in annual publication numbers. mtDNA, mitophagy, and apoptosis have been the most active research areas, while studies on mitochondrial transfer in stem cells have become a hot topic in recent years. Acute lung injury (ALI) is a clinical syndrome caused by a variety of direct or indirect pathogenic factors and accompanied by extensive lung inflammation, which is characterized by acute diffuse alveolar injury, congestion, increased alveolar capillary permeability, inflammatory cell infiltration and an impaired blood–gas barrier. The clinical manifestation is hypoxic respiratory failure, which can further develop into acute respiratory distress syndrome (ARDS), and 80% of ALI/ARDS cases are caused by severe sepsis ,2. AccorBibliometrics is a field of study in library and information science. As a new method of statistical analysis, it plays an important role in analyzing impacts and trends . TherefoOur raw data were retrieved and downloaded from the Web of Science Core Collection (WoSCC) Expanded Science Citation Index (SCIE), developed by Thomson Scientific. Web of Science consists of a large number of high-quality and high-impact scientific studies, making it the most comprehensive and inclusive collection of information available worldwide. Due to the differences in citation data in each database, no database used for bibliometric studies is considered to be the most superior ,26. We cIn this study, both objective and evaluative bibliometrics were used to visualize and analyze mitochondrial research findings in the field of ALI/ARDS. Objective bibliometrics measures the amount of literature, the number of citations and the analysis of citations . The proVOSviewer, CiteSpace and R (version 4.1.3) were used for statistical calculations and graphical visualization. VOSviewer is a free Java-based software. The software’s clustering algorithm is related strength-based and provides a comprehensive and detailed bibliometric map based on collaborative data . CiteSpaA total of 756 articles (580) and review articles (176) published within the last decade were retrieved. The total Nc of the retrieved publications was 20,762, the mean Nc per paper was 28.1 and the total H-index was 63. Overall, for mitochondrial-related research in the ALI/ARDS field, 4574 authors affiliated with 1217 institutions have been published in 346 journals worldwide, with authors from 61 countries or regions.2 of 0.9727 indicated a high correlation between the number of publications per year and the year of publication. The annual growth rate calculated using bibliometric methods was 35.7%, and the growth rate increased with time. At the level of the top three countries in terms of Np, the annual Np of China has increased rapidly since 2017, while the growth trends tend to be stable in the USA and Germany, indicating that China has been productive in this field of research in recent years.In A total of 61 countries/regions have published academic articles in the field of mitochondria in ALI/ARDS, but more than 75% of the publications were contributed by researchers from the top two most-active countries (China and the USA). We listed the top 10 countries with the highest publication output of articles . China iA total of 346 journals published papers in the area of mitochondria and ALI/ARDS. The dual-map overlay obtained using CiteSpace is a useful tool to show the disciplines to which they belong. The left and right sides of the dual-map overlay represent citing and cited journals, respectively, and are interconnected by citation waves. The citing side can be considered the research frontier, and the cited side can be considered the basis of their research ,45. The The LCS significantly represents the impact of an article in the local field. Keyword co-occurrence analysis easily summarizes the themes of various studies in a field and suggests research hotspots and directions. We visualized the hot themes in this field using VOSviewer A. The 26Co-citation networks can help scholars understand the important publications, research bases, and research hotspots and frontiers of a field. Therefore, we used the CiteSpace tool to classify these references into nine clusters: #0 suggested model, #1 mesenchymal stromal cell, #2 potential therapeutic benefit, #3 endothelial cell, #4 targeting mitochondria, #5 mitochondrial DNA, #6 melatonin-mitochondria treatment, #7 lung disorder, and #8 reinforcing autophagy. The silhouette value of each cluster was greater than 0.8, and the numbers 0 to 8 represented the clusters from large to small. A citation burst is a sudden increase in the number of citations during a short period, and burst detection reveals the most active areas and emerging trends in the network. In this study, we collected data from 756 papers on mitochondria in ALI/ARDS during the last decade from the SCIE database. We performed a series of bibliometric analyses and data visualization through the Biblimetrix (3.1.4) R package, CiteSpace (5.8. R3) and VOS viewer, revealing that the number of publications in this field per year shows a rapid growth trend, especially after 2015.Among the top-ranked countries/regions, China ranked first in production , followed by the USA , indicating that China and the USA led in this field. In recent years, China’s scientific development has grown by leaps and bounds. China’s position as the largest publishing country was closely related to its substantial support for scientific research and the vigorous training of scientific talent. However, compared to China, the USA had higher Nc, Na and H indices, representing a more solid research foundation and results in this field. More importantly, six of the top 10 affiliates were from the USA, which may be one of the reasons why the USA was more influential in mitochondrial research in ALI/ARDS. Except for China and the USA, the publication volume was low, but Canada, England, Italy, France and Korea were at a high level of Na index, representing the relatively high quality of publications in these countries. In this regard, scholars and affiliates in China, Germany, Japan and India should make further efforts to improve the quality of papers in this area. As seen from the co-occurrence network, China and the USA take a central position with the thickest line between them, which represents a very close collaborative relationship. In addition, the connecting lines between countries are intertwined, indicating that scholars and institutions in each country contribute their respective strengths to remove academic barriers and promote academic cooperation and exchange.Of the top 10 journals with the highest Np, seven had an IF above 5, indicating a high demand for research exploration of mitochondria in ALI/ARDS and that most of the research in this field was of high quality. It is noteworthy that almost all of the top 10 articles of LCS were published in very high IF journals, including three articles on the mitochondrial transfer of stem cells, which created a great impact by establishing the basis of research in this direction. In addition, based on the burst detection findings, it was suggested that stem cells and endothelial cells were a recent research hotspot in this field; therefore, scholars in this field can actively focus on these topics. As seen from the double map overlay, the main disciplines at the forefront of research have undergone a general shift from “Medicine, Medical, Clinical” to “Molecular, Biology, Immunology” over the past decade, meaning that the direction of research in this field has gradually shifted from clinical research to basic research. “Molecular, Biology, Immunology” is still the most important research discipline in general. In addition, the two cited disciplines of “Molecular, Biology, Genetics” and “Health, Nursing, Medicine” have been closely related for many years. The results suggest that research on mitochondria in ALI/ARDS is currently focused on molecular, biological, immunological and genetic science; thus, scholars in this field should consider delving deeper into these disciplines to discover more exhaustive mechanisms.We found that the years from 2012 to 2015 were the nascent phase of the field, and the research in this phase was mainly focused on establishing the theoretical foundations for later studies. For example, Islam MN et al.  discoverIn the next phase of rapid publication growth, scholars in the field focused on the specific mechanisms and signaling pathways of mitochondria in ALI/ARDS and considered the role of mitochondria in various lung diseases and cellular interactions. Mitophagy, mitochondrial biogenesis, mitochondrial energy metabolism, cellular autophagy and apoptosis are gradually being unveiled by researchers in this field. Signaling molecules and pathways, such as ROS, NLRP3, Nrf2, HO-1, and NF-κB, have also been tightly linked to mitochondrial functions. For instance, Yu J et al.  found thWith the outbreak of the COVID-19 epidemic, researchers began to explore the relationship between mitochondria and COVID-19. It has been shown that COVID-19 viruses can manipulate the host cytoplasm to release mtDNA and activate the mtDNA-induced inflammasome, thereby suppressing innate and adaptive immunity . MitochoThe VOS Viewer, CiteSpace and R (Version 4.1.3) allow a visual analysis of the papers, thus revealing research trends and hotspots in the field. Meanwhile, through LCS and burst detection, we found some essential classical papers that have been the basis of research in the field, leading the development direction, exercising great influence and providing further research ideas. Compared to traditional reviews, bibliometric studies provide more visual analysis and better tracking of changing research hotspots. Moreover, this study utilizes more visualization tools than some past bibliometric studies to present the results of research in a field from multiple perspectives. However, there are still some limitations. First, the data in this study only included articles in English and reviews from SCI-Expanded. Second, we only included papers from 2012–2021. Ten years, as a common time span for bibliometric analysis, provides a great overview of the developmental history of the field but may overlook earlier classical research. In addition, we excluded influential low-NC papers published in 2022, making this study unavoidably delayed. Therefore, a bibliometric analysis of newly published articles should be continued at specific times to enrich the findings in this area continuously.This bibliometric analysis reveals the research directions and frontier hotspots of mitochondria in ALI/ARDS, which has shown a rapid growth trend in annual publication numbers. China and the USA have led the field, with China producing the largest number of papers and the USA producing higher-quality research. Similarly, many of the classical theories came from the research of USA institutions. The major disciplines at the forefront of research have shifted from clinical research to basic research. mtDNA, mitophagy and apoptosis have been the most active research areas, while studies on mitochondrial transfer in stem cells have become a hot topic in recent years. In addition, studies on the mechanisms of mitochondria in COVID-19-associated ALI/ARDS are still of great potential value.


The association between mental health problems and crime in immigrants has attracted recent academic interest, with results suggesting that there were possible interactions between immigration, schizophrenia, and criminal behavior. However, very few studies have examined these interactions, especially in developing countries that have mass internal immigration. Therefore, this study sought to identify the associations between the sociodemographic, clinical, and criminal factors in migrants and non-migrants with schizophrenia who had been involved in criminal activities in China.Forensic archives of suspects who had been referred for criminal responsibility assessments in the Sichuan West China Forensic Center from January 2015 to December 2019 were reviewed. The sociodemographic, and criminal activity information of the suspects were extracted, while the clinical and social function were measured by the Brief Psychiatric Rating Scale (BPRS) and Social Disability Screening Schedule (SDSS) based on the archives. A Chi-squared test, a T-test, a Mann-Whitney U test, and Multinomial logistic regression were employed for the statistical analysis.n = 95) of which were migrants. The migrant patient group was younger than the non-migrant patient group. The BPRS and SDSS scores for the migrant patient group were lower than for the non-migrant patient group. The migrant patient group had more work experience and more had been employed at the time of the crime than the non-migrant patient group. The unemployed migrant patients were more likely to commit a property-related crime.A total of 552 patients were reviewed and evaluated, 17.2% (Compared to the non-migrant schizophrenia patient group, the migrant patient group had less severe psychiatric symptoms and less social function impairments. Employment was an important factor in preventing criminality in patients with schizophrenia, especially for migrant patients. Vocational rehabilitation focuses on developing appropriate employment that can significantly assist in schizophrenia patient recovery, which in turn could reduce their chances of committing crime. Besides, reducing other obstacles to stigma, housing and health insurance would also be beneficial to crime reduction. The association between mental health problems and crime in immigrants has attracted recent academic interest, with the results suggesting that there were possible interactions between immigration, schizophrenia, and criminal behavior. While people generally migrate for social, economic, or political reasons, many studies have found that migration increases the risk of developing schizophrenia –4. FurthThe associations between mental disorders and criminal violence have been extensively studied, especially for people with schizophrenia –11. A reGiven these associations between immigration and schizophrenia, and the association between immigration and crime, it is plausible to assume that there could be some interactions between immigration, schizophrenia, and criminality. However, very few studies have focused on this possibility, especially in developing countries that experience mass internal immigration (migration across cities or provinces within China). With a population exceeding 1.4 billion, China is the largest developing country in the world. The 2020 Chinese population census showed that there was a floating population of 375.82 million people, of which 124.84 million people had moved to other provinces, and 250.98 million had moved within their provinces . The intThis study analyzed a sample of internal immigrant forensic psychiatric patients and compared their demographic, clinical, and criminal characteristics with non-immigrant forensic patients. The migrants were divided into two subgroups; those that had moved between provinces  and those that had moved within one province ; and the demographic, clinical, and criminal characteristics again were compared. Rural-to-urban and city-to-urban migration groups were also compared.The archives of criminal suspects who had been referred for criminal responsibility assessments and diagnosed with schizophrenia in the Sichuan West China Forensic Center from January 2015 to December 2019 were retrospectively reviewed. The archives included comprehensive demographic, criminal, mental status, and medical history information. Demographic information; gender, ethnicity, year of birth, education level, marital status, place of residence, domicile place, employment history, living situation; clinical information; mental status, drug use, and medical history; and crime information; crime location, crime type, relationship with the victims, injury outcomes, tools used, and criminal history; were collected for the analysis. Schizophrenia was diagnosed based on the criteria in the third edition of the Chinese Classification of Mental Disorders (CCMD-3), which was modeled on the tenth edition of the International Classification of Diseases (China's household registration (Hukou) system registers each citizen at a specific place  and defines household status by residence location  and type  . A persoThe BPRS is an 18-item scale, which has been widely used to measure several symptoms . The BPRThe Social Disability Screening Schedule (SDSS) used in this study was a simplified Chinese version of the 1988 World Health Organization's Disability Assessment Schedule, which subjectively measures adult social, occupational, and psychological functioning. The SDSS has 10 items, each of which has a score ranging from zero to two. An epidemiological survey on people with mental disorders in China concluded that a total score of ≥2 points indicated obvious social functioning impairments . The relP < 0.05 (two-sided). A chi-squared test was used to compare the categorical variables between the groups, the two independent groups were compared using a T-test or a Mann-Whitney U test, Multinomial logistic regression was used to examine the effects of employment on criminal type in the migrant and non-migrant groups, and odds ratios revealed the probability of membership in each class compared to the reference class.All analyses were performed using IBM SPSS Statistics (version 20.0), with the significance level set at As shown in p = 0.827), ethnicity (p = 1.00), education (p = 0.770), or marital status (p = 0.758). The migrant group patients had a higher proportion of males than the non-migrant group , and the mean age of the migrant group (35.58 ± 9.893) was significantly lower than the mean age of the non-migrant group (40.18 ± 12.103) (p = 0.001). The migrant group patients were less likely to live with relatives (62.1%) than non-migrant group patients (74.6%) (p = 0.003). Significantly more migrant group patients had a history of employment (90.5%) than the non-migrant group (75.7%)(p = 0.001); in the meanwhile, there were much more (around 44.2%) migrant patients employed at the time of their crime than the non-migrant patients (17.1%)(p <0.001).The migrant and non-migrant patient variables were compared using a chi-squared test see . No statp = 0.028) more non-migrant group patients (69.5%) had had schizophrenia for more than 5 years than the migrant group (57.9%). However, there were no significant differences between the migrant and non-migrant patients in terms of antipsychotic treatment histories, hospitalizations, or medication at the time of the crime. The BPRS indicated that there were no significant differences in the affect, activation, or resistance between the groups (p > 0.05); however, statistically significant differences were observed in the negative symptoms , positive symptoms , and the total scores , with the median of negative symptoms (5.00 vs. 6.00), positive symptoms (9.00 vs. 12.00), and total BPRS scores (39.00 vs. 42.00) being significantly higher in the non-migrant group. Moreover, the median of SDSS in the non-migrant group patients was 8.00, which was also significantly higher than the score among migrant patients (6.00)  (see As shown in 001) see .p < 0.001). No significant differences were observed between the groups for criminal offense history. When the sample was restricted to only include violent crimes against a person, there was a significant difference between the patient victim relationships(p < 0.001) between the two groups, with most victims in the migrant group being strangers (60.0%) and most victims in the non-migrant group being acquaintances (51.7%). There was a significant difference (p = 0.031) between the two groups in the crime location, with the migrant group committing more crimes in a public space (66.7%) than the non-migrant group (49.2%). There were no statistically significant differences in the number of victims between the two groups; however, much more cases  in the non-migrant group have at least one victim death relative to that in the migrant group . The non-migrant group (79.5%) also tended to use more tools in their crimes than the migrant group (66.7%); however, this difference was not statistically significant (p = 0.052) (see As shown in 052) see .p = 0.001) and other crimes   than the employed migrant group patients; however, this difference was not statistically significant in the non-migrant group(p > 0.05).As shown in p = 0.049) and more likely to offend in urban areas(p = 0.005). No statistical differences were found between the two subgroups for any other features (p > 0.05). Moreover, no significant difference in sociodemographic, clinical, and criminal features was found between the rural-to-urban migrants and the city-to-urban migrants; however, a significantly higher proportion of the city-to-urban migrants had higher education levels (>9 years) than the rural-to-urban migrants .As shown in Previous studies have widely documented the association between violence and schizophrenia , 28, 29.While the non-migrant patients mostly committed offenses against people, the migrant patients were more likely to commit property offenses, such as theft, fraud, and robbery. In line with this, some studies have also found that migration increases the level of property crime , 30 and Most migrant patients in this study came from rural areas, which is to some extent related to the trend of rural residents migrating to urban to seek more employment opportunities after the reform and opening policy implemented in China in 1978 . InteresThe association between unemployment and crime has been widely examined in literature , 42, witThe SDSS and BPRS scores  for the migrant patients were lower than for the non-migrant patients, which suggested that the migrant patients may have had less severe psychiatric symptoms and less social function impairments than the non-migrant patients. The migrant patients were also younger and had suffered for a shorter time with their illnesses than the non-migrant patients, which could also explain why more migrant patients were employed than non-migrant patients . In ChinHowever, regardless of the degree of illness, all patients with schizophrenia need to feel useful. Therefore, vocational rehabilitation needs to be provided for both migrant and non-migrant sufferers to ensure that they can gain and keep employment. Currently, vocational rehabilitation services in China are only at the preliminary stage , and morThis study had several limitations. First, the sample was taken from only one medical forensic assessment center in Sichuan province. As regional development impacts migration, the results cannot be generalized to forensic patients throughout China. Second, data on previous migration experiences was missing, which may have had some effect on their involvement in crime; therefore, these connections need to be examined in future studies. Third, the sample size in subgroups was relatively small, especially in the inter-provinces migrant group, which may have limited the statistical ability to detect slight differences between the groups. Future studies with larger subgroup sample size are needed to verify the results of the present study. Fourth, this study was a retrospective study based on archival research, which limited the potential for checking data accuracy and thorough comprehensiveness of the extracted data. Fifth, since the data was based on a sample of suspects rather than convicts, the findings on associations with criminal conduct may not be conclusive since those who are charged with some crimes may not eventually be convicted for them. This could potentially alter the descriptive patterns and attendant associations. Sixth, the application of the SDSS and BPRS to archival contents could potentially under- or over-rate the presence of items on both scales since not all items may be fully captured in the archival content.In spite of the aforementioned limitations, the data presented here suggests that the migrant patients with schizophrenia, are younger, and have less severity of psychiatric symptoms with better social function, than non-migrant patients. The higher rate of property crimes in the migrant patients may result from the failure in employment and the subsequent economic difficulties. These results indicate that some patients with schizophrenia still preserved the motivation and willingness of social and vocational participation by migration. Employment is beneficial to improve not only economic situation, but also social function. However, many social obstacles may preclude them from participating in social activities and getting employed. Thus, policies focusing on vocational rehabilitation and developing more appropriate employment for patients with schizophrenia, especially for migrant patients are crucial for reducing their chances of committing a crime. Moreover, efforts to reduce stigma and residential segregation, and promote welfare in health insurance and housing could also aid in the recovery of the patients and the reduction of criminality. Future studies with larger sample size to further investigate the interaction between schizophrenia, migration and criminality are warranted.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Medical Ethical Committee of Sichuan University. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.ZH, GL, and YH conceived and designed the study. ZH and GL provided oversight and direction. YH, YL, and SW contributed to data extracting. YH and YG contributed to data analysis and interpretation. YH drafted the manuscript. YH, ZH, GL, YG, SW, and YL contributed to the revision of the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by China Postdoctoral Science Foundation [grant number 2018M643488] and the National Natural Science Foundation of China [grant number 81901928].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.


Although publications have been increasing rapidly, the research quality has yet to improve in the field of critical care medicine (CCM) in China. This study aimed at investigating the current status of and the influential factors for impactful publications in CCM research by Chinese authors.Publications by authors with the affiliation of critical care medicine department or intensive care unit (CCM/ICU) in Chinese as well as American hospitals from 2001 to 2020 were retrieved from the Web of Science Core Collection (WoSCC) database for this bibliometric analysis. Moreover, statistical analyses to test factors affecting impactful publications by Chinese authors were performed.M (IQR): 1.85 (9.592) vs. 27.77 (7.3), p < 0.001]. In addition, impactful articles were significantly less published by Chinese than by American authors, including articles either in journals with a high impact factor (p < 0.001) or in the top 10 journals in the field of CCM , and articles with high citation frequency as well (p < 0.001). Moreover, the percentage of impactful publications by Chinese authors was likely associated with academic background and regions of the author's affiliations, funds support, public health events of COVID-19, and collaboration between authors.Of 13,487 articles retrieved by this search strategy, 6,622 were published by Chinese authors as first or corresponding authors. The annual publications by Chinese authors have been rapidly increasing from 2001 to 2020, and so did the citations to these articles. However, the proportion in the world of publications by Chinese authors was much less than that by American authors each year [Our results demonstrated that CCM research in China grew rapidly in the recent 20 years. However, the impactful publications remained limited, largely owing to the shortage of comprehensive research training, inactive collaboration, and underfunded CCM research. Critical care medicine (CCM) in China was seen to make great progress in the past two decades . It playTo promote the scientific research in CCM, experts from the Chinese Society of Critical Care Medicine established the China Critical Care Clinical Trials Group (CCCCTG), comprising intensivists from 24 ICUs from 21 provinces in China, which joined the Global Sepsis Alliance (GSA) in 2010. In addition, there were more and more activities specific to scientific research training, for example, the Conference of Critical Care Research Forum (CCCRF), Salon for Young Critical Care Investigators, and Critical Care Research Campaign, etc –8. MeanwWeb of Science Core Collection (WoSCC) database is one of the most comprehensive, systematic, and authoritative databases, which has been successfully used for bibliometric analysis , 12. PubData regarding publications retrieved from WoSCC included title, keywords, authors, affiliations and regions, journal, date of publication, funding, citations, etc. Data were extracted by two authors (QW and ZL) independently and the agreement of the results was 98%, showing significant consistency. All data were saved in a text or excel format for further analysis.https://incites.clarivate.com/), VOSviewer (version 1.6.15), and Microsoft Excel 2019. WoS-Incites were used to analyze the number of publications, impact factors of the journals, citation frequency, characteristics of the authors, and their affiliations. VOS viewer 1.6.15  was used to analyze and visualize co-authorship of authors, institutes, countries, and co-occurrence analysis of keywords ] depending on whether they followed a normal distribution. Differences between groups were compared by Student's t-test or the Wilcoxon rank sum test based on data distribution. Categorical variables were described using cases and percentages or proportions. And differences between groups were compared by the chi-square test or Fisher's exact probability method. Two-sided p-values < 0.05 were considered statistically significant.Continuous variables were expressed as mean ± standard deviation (mean ± SD) or median  or the individual citation frequency in WOSCC  was significantly lower in Chinese authors publications  out of 1,724 publications focused on COVID-19 research in 2020. Compared with non–COVID-19 publications in 2020 and in 2019 as well, the percentages of COVID-19-related publications in impactful journals  were significantly increased  articles were reported with funds support. In comparison with the percentage of publications without fund, the percentage of those with funds supporting was significantly increased in journals with either IF ≥ 5 (36.41 vs. 25.77%) or IF ≥ 10 , followed by the China Medical University  and Shanghai Jiao Tong University . Hopefully, the researches of Chinese intensivists will be conducted with the impetus to study questions arising through intensive caring. In this way, the production of Chinese intensivists' research will be not only rich but more impactful in future.Previous studies suggested that several factors facilitate Chinese CCM research, including rapid economic growth, expansion of ICUs and intensive care practitioners , and resA comprehensive training in scientific research is the base for highly impactful publications. Our findings suggested that authors who got better research training probably, for instance, who served in hospitals with academic backgrounds and in cities with more medical colleges/universities/research institutes, be more likely to publish impactful articles . To our Collaboration can enhance the power, efficiency, generalizability, and rapid completion of clinical research , and henhttps://fund.sciencenet.cn/) for grants from catalog of H15 (“acute and intensive care medicine/trauma/burns/plastic surgery”) of NSFC  and successfully applied by the Chinese intensivists from 1 January 2016 to 31 December 2020. Of a total of 1,073 (517.85 million RMB Yuan) funded projects, as shown in https://clinicaltrials.gov/) and ChiCTR  registered by Chinese intensivists from 1 January 2016 to 31 December 2020  out of 19,257 grants funded by the National Institutes of Health were definitely related to critical care and a maximum of 1,212 (6.3%) grants were possibly related to critical care . Fourth, there may be differences in data recognition by different software, resulting in possible errors in results. Finally, when calculating clinical registration research items, we cannot completely exclude a very small number of projects led by respiratory and critical illness experts, anesthesiologists, or other emergency department experts from being included in this study.This bibliometric analysis demonstrated that CCM research in China grew rapidly in recent 20 years. However, the impactful publications remained limited. The results of this study suggested that the lack of universality, as well as a comprehensive training in scientific researches, inactive collaboration, and underfunded, be the important barriers to the promotion of the quality and quantity of Chinese CCM research.The original contributions presented in the study are included in the article/WQ, CX, and ZL contributed to the acquisition, analysis, interpretation of data, statistical analysis, data arrangement, and draft of the manuscript. LY contributed to interpret the results. FS contributed to supervision manuscript. LZ completed all statistical analyses of this study. PM contributed to study concept, supervision, organize the final manuscript, identified as the guarantor of the article, taking responsibility for the integrity of the work, and from inception to published article. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background: Several dietary patterns are reported as risk factors for several chronic diseases including oral diseases. However, thus far, there has been no comprehensive quantitative analysis of nutrition and periodontal diseases. Methods: This systematic review was conducted according to the PRISMA guidelines. Cohort, case–control, and cross-sectional studies were eligible for inclusion in this study. The Newcastle–Ottawa scale was used to qualitatively assess the risk of bias in the included studies. The number of samples was used for odds ratio calculation, followed by the unadjusted value and 95% confidence interval. Results: Nine papers were included for the systematic review and meta-analysis. The results of screening for database search records showed that four diet patterns  have enough data for meta-analysis. The risk of periodontal disease in the western-diet group and the lowest dairy product intake group was 1.05 (0.51–2.13) and 1.28 (0.89–1.84), respectively. The risk of periodontal disease in the highest sugar intake group and the lowest vitamin C intake group was 1.52 (0.79–2.91) and 1.15 (1.08–1.23), respectively. Conclusions: With aging of the population globally, the prevalence of periodontal disease increases, and the associated cost also increases. Though this study, we found foods related to the risk of periodontal disease, and we are confident that it will contribute to lowering the incidence of the disease. Periodontal disease is an oral, chronic infectious, and inflammatory disease that can damage the supportive tissues surrounding the teeth and consequently cause tooth loss ,2. The pNutritional intake and dietary patterns have been studied as risk factors for several chronic diseases including oral diseases ,8,9. AccAs mentioned above, several review papers and systematic literature reviews have been reported on the association between various dietary habits and periodontitis, but a meta-analysis performed by quantifying the related papers has not been published. Therefore, the aim of this paper is to conduct a systematic literature review and meta-analysis on the association between specific dietary habits and periodontitis.PRISMA guidelines were followed in conducting this systematic review . A protoThe search was performed on 29 January 2021, using Embase and Medline. The search words were discussed by all authors. The detailed search terms are as follows:  AND  AND . We did not have restrictions by language or year of publication.We defined the PICO question as follows: Does the group with a particular dietary pattern increase the risk of periodontitis compared to the group without it? In this study, a term that includes various diets and nutritional intake such as western diet, sugar and vitamin C intake, and dairy product was defined as the term ‘dietary pattern’. The results of screening for database search records showed that these four diet patterns have enough data for meta-analysis. We included studies that presented the number of samples or effect measures. The western diet is defined as a diet that contains a large amount of saturated fat, refined carbohydrates, and salt and has a low proportion of fruits and vegetables . Dairy pThe titles and abstracts of each study were reviewed independently by two authors (JJ and KK). For inclusion, the same authors reviewed full-text articles. Disagreements were resolved through discussion.The following variables were extracted during the screening phase: title, abstract, journal, author name, publication year, and publication type. We extracted additional information from the full-text assessment, such as the study design, WHO region, number of samples, type of diet, diagnostic criteria, race, and age.Qualitative risk of bias assessments were conducted for the cohorts and case-control studies based on the Newcastle-Ottawa scale . We used2 statistics [Odds ratio and 95% confidence interval was extracted by a 2 × 2 contingency table of exposures and outcomes. We performed subgroup analysis by classifying the diet patterns into 4 categories; western diet, dairy product, sugar, and Vitamin C. Forest plots were drawn to clearly visualise the synthesised risk. Evaluation of the effect measures’ heterogeneity was conducted using the classification of Iatistics . In caseWe identified and screened 682 potentially relevant articles (including overlapping publications across the two databases); 495 articles were excluded on the basis of the title and abstract and 187 articles were further searched for a more detailed assessment. After further evaluation of the full articles, 168 were excluded because they had study designs other than the pertinent one, or no results on the association between diet pattern and periodontal disease were presented. Finally, 9 studies were included in the systematic review and meta-analysis . The chaTwo studies provided two data sets were included to derive the result. The risk of periodontal disease in the western-diet group was 1.05 (0.51–2.13) compared to that in the non-western diet group . The hetFour studies provided four data sets were included to derive the result. The risk of periodontal disease in the lowest dairy product intake group was 1.28 (0.89–1.84) compared with that in the highest dairy product intake group . The hetTwo studies provided two data sets were included to derive the result. The risk of periodontal disease in the highest sugar intake group was 1.52 (0.79–2.91) compared with that in the lowest sugar intake group . The hetTwo studies provided two data sets were included to derive the result. The risk of periodontal disease in the lowest vitamin C intake group was 1.15 (1.08–1.23) compared with that in the highest vitamin C intake group . The hetOne cohort study was rated good. One case-control study was rated Fair. Out of 13 cross-sectional studies, 8 were evaluated as very good, 3 as good, and 2 as satisfactory. Detailed evaluation results are presented in In this systematic review and meta-analysis of observational studies, we found that certain nutritional and dietary patterns significantly affected the prevalence of periodontal disease. Western diet, dairy products, and high sugar intake were not statistically significant with periodontitis, and vitamin C low intake was positively associated with risk of periodontitis. Because poor periodontal health may cause systemic diseases such as cardiovascular diseases, cancers, and diabetes, oral hygiene-related factors should be studied in detail.Western diet, which includes processed foods, red meat, snacks, and soft drinks, is a well-studied risk factor for inflammatory diseases and many types of malignancies ,34. LongDairy products  are one of the most studied foods for their association with several diseases. Although there is no association with the risk of all-cause mortality, many epidemiological studies have reported that dairy products have protective effects against periodontal diseases, cancers, and chronic inflammatory diseases, especially cardiometabolic diseases ,40,41,42A high-sugar diet contributes to the formation of dental biofilms and, consequently, caries and reduction of pH ,45. HypeWe found that vitamin C intake slightly reduced the prevalence of periodontal disease. According to two recently published systematic reviews of the literature, it was reported that low vitamin C intake and low vitamin blood levels increase the risk and progression of periodontitis ,12. Our Our meta-analysis had several limitations that could have affected the results. First, it was difficult to clearly identify the causal relationship because the majority of the included studies in the meta-analysis had a cross-sectional design. Second, errors in reporting, such as food frequency questionnaires, or uncertainties about the source and composition of food, during the course of the investigation may have affected drawing conclusions. Third, it was impossible to calculate the total number of patients with periodontal disease included in the study because the articles did not present information on the sample size. Finally, three (rather than 2) data sets are often considered the minimum for meta-analysis, but in this study, the number of included studies for each diet pattern was very small.In this study, we analysed the relationship between various food patterns and the prevalence of periodontal diseases through a comprehensive analysis of dietary habits. Overall, there were no deviations from the conventional common sense. The diet suggested in our study was considered to be similar to various diets used for the prevention of metabolic disease. With aging of the population globally, the prevalence of periodontal disease increases, and the associated cost also increases. Therefore, by studying this issue further and controlling the intake of foods that appear to be a risk factor, the risk of periodontitis could be reduced.


The past few decades have seen ongoing development of continuous glucose monitoring (CGM) systems that are noninvasive and accurately measure blood glucose levels. The conventional finger-prick method, though accurate, is not feasible for use multiple times a day, as it is painful and test strips are expensive. Although minimally invasive and noninvasive CGM systems have been introduced into the market, they are expensive and require finger-prick calibrations. As the diabetes trend is high in low- and middle-income countries, a cost-effective and easy-to-use noninvasive glucose monitoring device is the need of the hour. This review paper briefly discusses the noninvasive glucose measuring technologies and their related research work. The technologies discussed are optical, transdermal, and enzymatic. The paper focuses on Near Infrared (NIR) technology and NIR Photoplethysmography (PPG) for blood glucose prediction. Feature extraction from PPG signals and glucose prediction with machine learning methods are discussed. The review concludes with key points and insights for future development of PPG NIR-based blood glucose monitoring systems. Diabetes mellitus is one of the most chronic diseases in the world with an annual death rate of 1.5 million. . ApproxiInsulin is a hormone made by the pancreas, which regulates blood glucose levels (BGL) in the human body. In diabetic patients, either the pancreas are unable to produce enough insulin hormone or the cells in the body are not responding to insulin (insulin resistance). Insufficient insulin production is classified as Type 1 diabetes and is mostly diagnosed in children. Insulin resistance is classified as Type 2 diabetes. Diabetes developed during pregnancy is gestational diabetes . The mosThe conventional method for checking BGL is the finger-prick method. As it can be done by the patient, it is called a self-monitoring blood glucose (SMBG) monitoring device. It is an electrochemical-based method in which the finger is pricked to draw small drops of blood on a test strip, and a discrete glucose value is displayed within a few seconds . This meIn summary, minimally invasive and non-invasive glucose monitoring technologies have become an interesting and emerging research field. The researchers aim to offer a solution for continuous glucose monitoring with minimal pain or painless methods, with the integration of smart monitoring. This review paper will be discussing noninvasive BGL monitoring technologies with a particular focus on research work in NIR technology. Noninvasive methods studied in recent years for glucose estimation can be grouped according to their technologies. Mainly, they fall into the category of electromagnetic (EM) wave sensing, transdermal, and enzymatic ,12,13,14Infrared spectroscopy, or vibrational spectroscopy, is the measurement of how infrared radiations interact with matter. The absorption, emission, and reflection of IR waves are measured and studied to identify functional groups or chemical substances present in matter. The infrared region of the electromagnetic spectrum is usually divided into three sub-regions, the near-, mid-, and far-infrared, which are named by their relation to the visible spectrum. Mid-Infrared waves lie in the region of 2500–25 µm of electromagnetic waves. They use the reflection principle to detect glucose concentration in interstitial fluid (ISF) . MIR hasNear-Infrared spectroscopy is an optical method in which scattered, transmitted, or reflected light from the illuminated surface is studied. NIR waves lie in the EM bandwidth of 700–2500 nm. NIR spectroscopy finds its application in numerous fields like medicine, pharmaceutics, food analysis, quality control of chemical products, material sciences, astronomy, and agriculture ,21,22,23Raman spectroscopy is based on measuring the scattering of incident monochromatic (laser) light due to the vibrational and rotational motion of particles under study. The change in light wavelength due to scattering (Raman shift) is measured to identify glucose molecules in which vibration modes are linked with carbon, hydrogen, and oxygen bonds ,52. RamaThermal Emission Spectroscopy uses the heat radiation principle of the human body in the far-infrared region (8 µm–14 µm). When the body radiates heat, some of it is absorbed by different tissue and molecules, including glucose. The wavelength absorbing most is around 9.4 µm. Buchert  suggesteMicrowaves range from 1 mm to 1 m in the EM wave spectrum. They are widely used in the fields of detection, communication, and medicine. As they can easily penetrate media with a millimeter of thickness, they can penetrate deep in skin tissue, reaching blood vessels in the dermis layer. The reflection, absorption, and transmission theory of microwaves through skin tissues can correlate to the changes in dielectric property, relative permittivity, and conductivity with fluctuating glucose concentrations ,55,56. HMetabolic Heat Conformation technology estimates blood glucose by measuring various physiological parameters using multi-wavelength spectroscopy methods along with humidity and temperature sensors ,58. The Photoacoustic Spectroscopy exploits the photoacoustic method for glucose estimation. The theory states that if an energy source radiates on the skin surface, it causes thermal expansion at the illuminated site. Due to thermal expansion, acoustic or ultrasound waves are generated and can be detected by pressure sensors. The peak-to-peak variation of the detected signal can be correlated to the glucose level in the blood ,60,61. TOcclusion spectroscopy is a technique in which scattered light is measured from the pressurized tissue site. The blood flow is restricted for a few seconds at the site by applying pressure. The dynamic changes in blood flow increase the intensity of scattered light. The scattered light is measured to estimate blood glucose concentration . Like otOptical Polarimetry uses the concept of chiral molecules of glucose to estimate its concentration. Chiral molecules can rotate the polarization plane of the incident light beam at a particular angle. The amount of rotation is dependent upon the optical path length, temperature, wavelength of the incident beam, and concentration of an analyte. OP is unsuitable for skin measurements due to the high scattering of light and other physiological parameters. An aqueous humor of the eye is a suitable analyte for glucose estimation using OP ,64. ThisOptical Coherence Tomography is an optical imagining technique that can give high-quality 2D images. The signal acquisition method is based on detecting interferometric signals. A low coherence light source is illuminated on the sample placed in an interferometer. The backscattered light from sample tissue and a reference mirror (inside the interferometer) forms an interferometric signal and is detected by a photodetector. With an increase in glucose concentration present in interstitial fluids, the refractive index also increases. The increase in refractive index decreases the scattering coefficient of illuminated light. Hence, measuring the scattering coefficient indirectly gives the glucose concentration present in the sample ,66. ThisBio-impedance measures the changes in permittivity and conductivity (impedance) through human tissue. The resistance to the flow of electric current through plasma fluid can be correlated to glucose molecules ,68. ThisElectromagnetic sensing exploits the dielectric properties of blood to estimate glucose concentration. The fluctuation of voltage or current produced due to electromagnetic coupling of inductors indicates the varying concentration of blood glucose molecules ,70. ElecNoninvasive enzymatic technology includes a technique that involves blood glucose using human fluids such as tears, saliva, and sweat. Ocular technology also falls in this category. It utilizes specially designed contact lenses that determine the glucose present in tears ,72,73,74NIR spectrometry applicability has evolved in recent decades owing to significant improvements in spectral analysis and instrumentation. NIR spectrometry finds its application in various fields. In food analysis, the NIR technique is utilized to determine the chemical compositions and physical properties of bioactive compounds, commonly protein, fat, dry matter, and moisture content . In agriNIR spectroscopic imaging is employed to study the atmosphere, plants, and soil. NIR spectroscopy in material sciences is used in measuring the film thickness of microscopic samples and analyzing optical characteristics of nanoparticles and optical coatings. In the medical field, NIR spectrometry is used in medical imaging and physiological diagnostics . It is nNear-Infrared spectroscopy is a vibrational spectroscopy technique like Infrared and Raman spectroscopy. The interaction of molecules in the sample with electromagnetic waves stimulates the internal degree of freedom (DOFs) of molecules, i.e., bonds of the interacted molecules vibrate at different frequencies depending on the type and energy of the bonds. This determines the shape of the spectra of the sample. NIR can be divided into three regions according to its bandwidths: the first overtone band (1400–2000 nm), the second overtone band (750–1400 nm), and the combinational band (2000–2500 nm). NIR has a maximum penetration depth in the skin, compared to other infrared waves. Also, NIR is minimally absorbed by water and hemoglobin; hence, spectral measurements can be easily collected from skin or body surface.The NIR waves are partially scattered or absorbed as they penetrate through skin tissue. As previously mentioned, the scattering and absorption are related to the molecular vibrations of chemical bonds of molecules present in the medium. This phenomenon can be utilized in measuring the concentration of biological functional groups such as C–H, N–H, C–O, and O–H present in the blood. Glucose molecules contain C–H and C–O bonds, so the absorption and reflectance of NIR waves passing through the skin can be developed to detect the concentration of glucose in the blood. The NIR absorption for isomers of glucose, such as fructose, lactose, and galactose, has absorption peaks at different wavelengths, ranging in first overtones and combinational bands of NIR spectra ,22,23. TMany works in the literature show a detailed study of variations in NIR bandwidths and characteristic spectra due to changes in the concentration of glucose solution ,30,31,32Recent works in the literature show high accuracy in blood glucose prediction using NIR-based systems. They have been designed in reflectance and transmission modes. NIR spectroscopy, here, has been divided into two main subcategories: NIR spectrometry analysis and NIR PPG signal analysis. In NIR spectrometry analysis, logged voltage values after absorption and reflectance are measured, while in NIR PPG signal analysis, PPG signals are acquired using NIR LEDs. The following subsections will discuss them in detail.Many experiments and studies verify the proof of concept to relate varying NIR intensities with BGL. They are briefly discussed. Yadav et al.  developeThese works on NIR-based systems confirmed the proof of the concept of a strong correlation between NIR absorption/attenuation with varying glucose concentrations. The work carried out consisted of mostly two phases. In first phase, simple in vitro lab experiments were performed to determine effect of different concentrated glucose solutions on NIR transmission. In the second phase, human subjects were involved and NIR voltage measurements were recorded for different times of day or before or after meal intake. The voltage variations were correlated linearly with glucose concentration.2) value obtained is 0.9084; mARD is 5.18%. MAD is 6.25 mg/dL and RMSE is calculated to be 9.24 mg/dL. The model developed in this study has a limited number of training datasets. The study can be improved if the training dataset included more subjects with a wider range of blood glucose values.Studies carried out by Haxha , as showDai et al.  studied Joshi et al. in  propose PPG signals are unique, as they contain important information. The fingertip PPG waveform reflects the blood flow in blood vessels pumping from the heart to the fingertip. Its well-defined peaks represent the systole and diastole of heart rate . The PPGMonte-Moreno’s study  is one o2 of 0.88. The overall system performance has an R2 of 0.9.Performance factors of different machine algorithms compared are Linear Regression (LR), neural network (NN), Support Vector Machines (SVM), and Random Forest (RF). In the simulation, Random Forest performs better than the rest, and, hence, is selected for the testing dataset. The coefficient of determination of test subjects, with the Random Forest trained model, has an RRachim  proposedRamashyamam et al.  designedThe study in ,40 needsChu et al.  studied Habbu et al.  presenteIn Single Pulse Analysis, the pulses are separated within a given window, and features such as pulse energy, pulse transit time, pulse interval, pulse amplitude, pulse onset, and end time, etc., are calculated. After that, their statistical parameters such as mean, variance, IQR, and skewness (similar to work ) are als2 = 0.84, while for SPA, it is R2 = 0.91, showing a better performance comparatively. The Clarke error grid analysis for BGL estimation for both cases was completed. Using the time and frequency domain feature set, the data distribution was 80.6% in class A and 17.4% in class B. For SPA, the data distribution was 83% in class A and 17% in class B, showing a better estimation.This feature vector is input into the NN model for training. The performance of both models is seen in the test dataset. The value of the coefficient of determination for time and frequency domain features (FV) is Rn, are given in Equation (4).Yadav et al.  develope2, calculated was 0.612. Using ANN, the correlation coefficient of test data significantly improved to 0.96.Blood glucose levels were estimated using multiple linear regression (MLR) and ANN. For ANN, a Multilayer Perceptron (MLP) network was trained using the Levenberg–Marquardt (LM) algorithm. Using the MLR technique, the correlation coefficient, RSimilar features sets are used in work ,42,43. T2. The designed SoC consumes 1.62 mW of power. The PPG readout architecture comprises a transimpedance amplifier of 1 MΩ gain and a switched capacitor low pass filter of 10 Hz. The input-referred current noise of the analog front-end is 7.3 pA/√Hz, and it allows a DC bias current rejection up to 20 µA. The implemented digital processor removes baseline drifts from the recorded PPG signal, extracts six features, and predicts BGL using Support Vector Regression (SVR) with a Fine Gaussian kernel (FGSVR). A piece-wise linear (PWL) approach is used for the exponential function FGSVR implementation on-chip. Using the proposed SoC, 200 healthy and diabetic subjects are tested. The system performance is evaluated with mARD and R square. It achieves an mARD of 7.62 and an R2 of 0.937. The authors [F) is given by:Hina et al.  presente authors ,45,46 al authors  for glucIn this work, the authors also determine the optimal number of features needed for the best glucose estimation. Using the Wrapper method, different combinations of features are studied to see how many features and which combination set performs better than others. The performance of different machine learning algorithms is also studied for the set of combinations. PD), Detrended Fluctuation Analysis (SF(W)), and wavelet entropy (WPPG). Three statistical features are extracted from PPI, which are the standard deviation of peak-to-peak amplitudes, the standard deviation of peak-to-peak intervals (kurtosis), and the Mean Absolute Deviation (MAD) of peak-to-peak amplitudes (PPA). The input vector formed is given by:Hina A. et al.  use a neThese features show a better performance with ensemble boosted trees, as seen in This section briefly describes the mathematics of the features extracted from PPG signals in thework ,45,46,47(1)Kaiser Teager Energy feature (KTE)Kaiser Teager Energy helps in determining the instant energy profiles of signals ,78,79. Tframe − 1. The value of Lframe is 128 for the work in [For PPG signal analysis, KTE features are calculated for a whole signal window and frame level signal as well. KTE for window level is given by Equation (8), while for frame level, it is given by Equation (9): work in ,42,45,46skewness  (KTEskew(2)Logarithmic Energy feature (LogE)Logarithmic Energy is a time-domain feature which measures energy of the signal. It is commonly computed from a full-band spectrum of the signal . The Log(3)Autoregressive model of PPG signalPPG, ARKTE, and ARLogE. These are vector quantities where the dimension is one, plus the order of the AR model selected. The authors in [AR coefficients are commonly used for extraction of respiratory rate from PPG signals . AR coefthors in  uses the(4)Spectral entropy feature (SE)Spectral entropy approximates the spectral power distribution of a given signal. It determines the damping of pulses, spectral shape, and the harmonic components of a signal. Using spectral entropy, a signal can be examined to be noisy or missing some information. Spectral entropy has also been used in speech signal detection in previous literature work ,84,85. Tf Peak-to-peak interval (PPI)N is the total number of samples in the signal, A is peak-to-peak amplitude, and Np is the number of peak-to-peak intervals in 1 min of recorded PPG signals.Peak-to-peak interval (PPI), as understood by the name itself, is the distance between two peaks of a signal. In PPG signal analysis, it reflects the cardiac cycle of the human body. It is a time-domain analysis of the signal and is used to determine heart rate. The three statistical features that are derived from PPI are the standard deviation of peak-to-peak intervals (kurtosis) in Equation (17), the Mean Absolute Deviation (MAD) of peak-to-peak amplitudes (PPA) in Equation (18), and the standard deviation of peak-to-peak amplitudes given in Equation (19).(6)Detrended Fluctuation Analysis (DFA)S(i) is the length of the signal. The signal is divided into segments of width, w. Any integer value is selected for width after computational analysis. In the work of [w = 10 is chosen. The average fluctuation of the signal, Detrended Fluctuation Analysis is a time-domain analysis of a signal. DFA is a statistical method to compute correlations that have a long range in a time series . An inte work of , the len(7)Power Spectral Density (PSD)S(i).The Power Spectral Density is a frequency domain feature. The distribution of power signal over frequency is revealed by PSD analysis. It is defined as:(8)Wavelet entropy (WE)Using wavelet entropy , three s2 for the test datasets.The PPG signals from three different subjects are shown in The Clarke grid error analysis (EGA) is the golden standard for analyzing the estimation performances of proposed blood glucose monitoring systems . The ClaSo far, the experiments and research conducted using NIR technology focus more on data collection from adult volunteers. Adult volunteers include healthy subjects and diabetes patients having Type II diabetes. The studies need to expand the dataset to include a greater number of diabetic subjects suffering with hypoglycemia. These includes patients of type I diabetes. Apart from adding more subjects, diversity needs to be added in subjects too. The data collection should be expanded to different cities. Volunteers from different regions should be encouraged to participate. This will help in developing a generalized training models for machine learning methods. The reproducibility of a sensor is of equal importance. For checking the reproducibility of the sensor in work , the datAs diabetic patients are increasing day by day, there is a need to develop a noninvasive continuous glucose monitoring system for better diabetic management. Researchers are working to develop a device that is painless, cost-effective, and accurate. NIR spectrometry has great potential in noninvasive glucose monitoring. This review paper summarizes the recent works in noninvasive blood glucose monitoring with a focus on NIR technologies using PPG signals with machine learning. The mathematical details of the features extracted are discussed briefly. Work with similar features is compared. Although the works show promising results, most of them only show simulation results for the test data. More extensive research is required to develop an NIR-based noninvasive BGL system.For acquiring PPG data, different NIR wavelengths or pulse oximeters are used in the literature. To have a more precise comparison, PPG data should be acquired using similar wavelengths. The number of features used for the training model also varies among the previous works. A deeper feature analysis is needed to determine and optimize the number of features that will be sufficient for glucose estimation. A much larger dataset acquisition is required for better training of ML models. Most of the literature’s work on NIR technologies is software-based. There is a need to develop and design cost-effective and low-power hardware that can process incoming, real-time data for glucose estimation. Only then can the noninvasive system performance be truly evaluated. Later, this system can be further developed into a wearable device for continuous glucose monitoring.


Nutrition is an important part of the care of patients with chronic kidney disease (CKD). However, there is limited clinical research on the skeletal muscle nutrition of patients with CKD. We carried out this study to find out whether a low-protein diet supplemented with ketoacids (LPD + KA) could improve muscle wasting in patients with CKD.Patients were enrolled in this non-blind, parallel-group, randomized trial assessing the nutritional status of CKD, randomly assigned to either the LPD + KA group or conventional LPD group. Blood samples such as Hemoglobin, Cystatin C, Creatinine, BUN, Albumin, Pre- Albumin, Glycerin Trilaurate, and Cholesterol were measured at baseline and every 3 months. The parameters of skeletal muscle and other body composition were assessed before and after dietary intervention for 12 months.A total of 58 patients with CKD completed the study and were available for further analysis. The hemoglobin and albumin were observed to be markedly improved in the LPD + KA group during the follow-up as compared to baseline. Body mass index and total body water index of both groups were increased upon follow-up but the increase in the LPD + KA group was comparatively higher. Moreover, an increase in body fat%, skeletal muscle mass index, and appendicular skeletal muscle mass index was observed in both groups between baseline and follow-up, but it was statistically insignificant.This study did not find a significant improvement of KAs on muscle wasting, and a long time or more indices study may need to find the effects of the LPD + KA diets.www.ClinicalTrials.gov], identifier [NCT02568020].[ Chronic kidney disease (CKD) makes complex metabolic processes alter and affect muscular homeostasis, leading to a loss of muscle mass and, ultimately leading to muscle atrophy , 2. TherNutrition is an important part of the care of patients with CKD. For decades, protein restriction has been used to improve complications such as abnormal glucose metabolism and hypertension in patients with CKD and protect remnant kidneys’ function. As in long-term protein restriction, decreased amino-acid supply may lead to decreased protein synthesis and malnutrition, we often prescribed a low-protein diet (LPD) together with ketoacids (KAs), a nitrogen-free substitution for the essential amino acids, to patients with advanced CKD , 9.Ketoacids supplementation may be protective against muscle atrophic in animal models –13. In 5Although the reviewed evidence seems to suggest that KAs supplementation can be expected to bring positive results, there is limited clinical research on the skeletal muscle nutrition of patients with CKD. We, therefore, carried out this study, and divided subjects into the LPD group or LPD + KAs group, following up and testing their blood assay and body composition analysis.www.ClinicalTrials.gov as NCT02568020). All individuals came from the outpatient clinics of Shanghai General Hospital. Once identified, they continued routine medical care in their clinics and had an investigative follow-up. Only those who finished the follow-up were further analyzed. Demographics of the patients were obtained from medical records or patient interviews.Between 26 October 2016 and 13 May 2020, subjects were enrolled from the Nephrology department of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, as part of this non-blind, parallel-group, randomized trial assessing the nutritional status of CKD ; long-term immobilization; chronic respiratory failure; cancer; any pharmacological treatment that could modify muscle structure or function such as glucocorticoids or insulin; contraindications of Ketosteril, such as hypersensitivity to the active substances or to any of the excipients, hypercalcemia, disturbed amino acid metabolism to the study protocol. Furthermore, patients who were ≥ 150 kg body weight, had a physical disability, or have metal implants were excluded to make sure the prerequisites of body composition were monitored.All protocols were approved by the Institutional Review Board of Shanghai Jiao Tong University Affiliated Shanghai General Hospital. Written informed consent was obtained from all patients or their closest family members. This research was conducted in adherence to the principles of the Helsinki Declaration of 1975 as revised in October 2013.®, Fresenius Kabi) at a dosage of one tablet/5 kg ideal body weight/day, divided into three doses taken during meals.Patients were randomly assigned to either conventional LPD  or LPD + KAs . All patients were treated with an LPD containing 0.6 g protein/kg body weight per day and 120–125 kJ/kg body weight per day. Besides, the LPD + KAs group will be supplemented with keto-amino acids  (2 (meters2), and TBWI was calculated as the total body water (kilograms)/height2 (meters2).The parameters of body composition were assessed at baseline and at the end of follow-up. Body composition was determined through the Donghuayuan body composition monitor (DBA-550). It works on the principle of bioelectrical impedance. Variables such as sex, age, and height were input into the monitor. Patients were asked to stand barefoot on the foot electrodes of the measurement platform, with knees and back upright and straight without moving, then hold the grip electrodes firmly with their hands and extend their arms straight at a 45° angle to their body. As the measurement was completed, body mass index (BMI), percent body fat (BF%), skeletal muscle mass, in intracellular water (ICW), extracellular water (ECW), and total body water (TBW) appeared on the report. Appendicular skeletal muscle mass index (ASMI), Skeletal Muscle Mass Index (SMMI), and total body water index (TBWI) were calculated. ASMI was calculated as the sum of lean mass for the arms and legs (kilograms)/heightmeters2) . AccordiThe endpoint is the arrival point or the patient is converted to dialysis. The initiation of chronic dialysis was obtained through participant self-reporting during the follow-up period and was verified by the clinical and hospital records at the local site.The primary efficacy variable will be ASMI. Secondary efficacy variables will be BMI, BF%, and SMMI.Safety variables will be serum creatinine.SD), the comparison between two groups was performed by t-test, and the comparison among multiple groups was performed by analysis of variance. The differences between the same periods comparing the two groups were analyzed using an independent Student’s t-test. The same group between baseline and 12 months was compared by Paired Student’s t-test. The sample size calculation assumes that the primary variable is the percentage change from baseline ASMI. With 30 patients per group, a one-sided t-test at a significance level of 2.5% has a power of 80% to detect an improvement of 7.36% in the LPD + KA group vs. the LPD group. P < 0.05 was considered statistically significant, and SPSS 20.0 statistical software was used for analysis.The normally distributed measurement data were expressed as mean ± standard deviation . It could be seen that, in LPD group, pre-Albumin was markedly improved (p < 0.05), hemoglobin, albumin, and cholesterol was improved statistically insignificant (p > 0.05), while glycerin trilaurate progressed but statistically insignificant (p > 0.05). In LPD + KA group, the hemoglobin and albumin were observed to be markedly improved at the end of 1-year followed up as compared to the baseline (p < 0.05). Although an improvement was beheld in pre-Albumin, glycerin trilaurate, cholesterol of LPD + KA group this change was statistically insignificant (p > 0.05).It could be seen from p < 0.05). Moreover, an increase in BF%, SMMI, and ASMI were observed in both groups between baseline and follow-up, but it was statistically insignificant (p > 0.05).Body composition analysis at baseline and the end of 1-year follow-up is shown in 2 , a VLPD with 0.28 to 0.43 g protein/kg plus KAs added to meet protein requirements were recommended.Nutrition is a key component of care during CKD. There were findings suggesting that patients with CKD inhibiting protein intake can obtain the adaptation of muscle protein metabolism through the combined response to protein degradation and the recycling efficiency of protein breakdown amino acids. KAs supplementation has been proposed to reduce the risk of nutritional disorders of a very low-protein diet (VLPD), and VLPD + KAs were included as part of the clinical recommendations for patients with CKD in KDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update : for CKDpost hoc analysis of the MDRD Study  between baseline and 1-year follow-up in both groups but it was statistically insignificant. This may be because reducing protein intake can delay hyalinosis, and reduce proteinuria and glomerular hyperfiltration . In the RD Study , the autRD Study .As to body composition in this study, BMI and TBWI in the LPD + KA group were significantly increased, but the increase of BF%, SMMI, and ASMI was not statistically significant, indicating that the increase in BMI may be related to the change in TBWI. According to analysis in the MDRD study , body weThere were other short-term studies that did not show a significant effect of LPDs and VLPDs + KAs on nutritional parameters. And there are also some studies that observed the small anthropometric measurement declines which may be for the prolonged use of LPDs and VLPDs + KAs in routine practice and the adverse effect of end-stage kidney disease. That is why physicians who prescribe LPDs must regularly monitor patients for their protein and energy intake, body weight, and nutritional status. Although this diet is not associated with wasting in carefully monitored studies, attention should focus on energy intake, which may decrease over time and lead to weight loss and consumption.There were many limitations in this study, although there was a significant change in serum hemoglobin and albumin, neither of them was a direct indicator of muscle wasting. As for the completeness of the low-protein diet or the daily protein intake, it is not guaranteed. But it was documented that medication adherence is strongly associated with patient medication knowledge , 20, andThe original contributions presented in this 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 Board of Shanghai Jiao Tong University Affiliated Shanghai General Hospital. The patients/participants provided their written informed consent to participate in this study.YYZ explored the data and wrote the manuscript. LJG and LW collected the data. SR reviewed this manuscript. WJY designed this study and reviewed this manuscript. All authors contributed to the article and approved the submitted version.