Background: The treatment of hypertensive nephropathy has remained unchanged for many years. Salvianolate is the main active component extracted from Salvia Miltiorrhiza. The current studies seem to suggest that salvianolate has a certain therapeutic effect on hypertensive nephropathy.Objective: The purpose of this meta-analysis is to evaluate the effect and safety of salvianolate on hypertensive nephropathy under the condition of standardized use of valsartan.Methods: We conducted a systematic search  in PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Data knowledge service platform, China Science and Technology Journal Database, China Biomedical Literature Service System. Searching for the study of salvianolate on hypertensive nephropathy. Two reviewers independently included the study that met the inclusion criteria, and extracted data, evaluated the quality of the study. We use RevMan5.4 and stata15 software for this meta-analysis. We use GRADEprofiler 3.2.2 software for evidence quality assessment.Results: This meta-analysis included seven studies (525 patients). Compared with the use of valsartan combined with conventional treatment, salvianolate combined with valsartan and conventional treatment can further improve the efficacy , reduce blood pressure , serum creatinine , blood urea nitrogen , urine microalbumin , and urinary protein to creatinine ratio , cystatin C  and increase calcitonin gene-related peptide  without increasing adverse reactions . But it has no additional effect on endothelin-1 and malondialdehyde. The quality of evidence ranged from moderate to very low.Conclusion: This meta-analysis shows that the salvianolate can further improve renal function of hypertensive nephropathy patients based on valsartan was used. Therefore, salvianolate can be used as a clinical supplement for hypertensive nephropathy. However, the quality of the evidence is not high due to the uneven quality of the included studies and the insufficient sample size, we still need a lot of large sample size studies with more perfect design to confirm these results.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373256, identifier CRD42022373256 It is estimated that about 30% of the general population worldwide suffers from hypertension, and hypertensive nephropathy (HN) is considered one of the consequences of uncontrolled hypertension over a long period . Blood pShennong Herbal Classic, and was listed as the top grade (in vivo and in vitro. This effect mainly by suppressing the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and the expression of cyclooxygenase-2 and inducible nitric oxide synthase  is a commonly used traditional Chinese herbal medicine. It has been first recorded in op grade . Salvia op grade . Animal synthase . In addisynthase , dose-desynthase . It can synthase , can alssynthase . In clinsynthase , signifisynthase .As previously mentioned, valsartan, as an ARBs, is currently recognized as a first-line medication for the HN . SalvianWe have registered this system review and published the protocol on International Prospective Register of Systematic Reviews (PROSPERO) before we started retrieval studies, and we have completed this systematic review in accordance with this protocol. The registration number is CRD42022373256.We performed a systematic search  in the following databases: PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data knowledge service platform (Wanfang Data), China Science and Technology Journal Database (VIP), and China Biomedical Literature Service System (SinoMed). The search strategy we used in the English database was Salvia* AND hypertens* AND , and in the Chinese database was danshenduofen AND gaoxueya AND (shenbing OR shensunhai OR shenzangbing OR shenzangsunhai) . The retTwo authors (QX and YS) independently included or excluded the retrieved literature according to the following criteria.Included studies must met each of the following inclusion criteria: 1) The patients included in the study met the accepted diagnostic criteria for HN, such as those specified in clinical guidelines, World Health Organization criteria, authoritative works, and clinical medical textbooks; 2) The study was a published clinical randomized controlled study; 3) The intervention factors of treatment group included salvianolate and valsartan with combined with conventional treatment which refers to other treatment for NH and treatment for patients’ original diseases in accordance with medical principles; 4) The intervention factors of control group included valsartan combined with conventional treatment; 5) The duration of treatment did not exceed 2 weeks according to the drug instructions of salvianolate injection; 6) The outcomes of the study reported included one or more of BP, renal function , inflammatory factors , oxidative stress indicators , factors affecting vasodilatory state , clinical efficacy, and adverse reactions. BP, renal function and clinical efficacy were the primary outcomes. The other outcomes were the secondary outcomes. Clinical efficacy refers to whether the patient’s condition is improved judged by researcher according to the clinical performance. It is effective if the condition is improved, otherwise it is invalid.Studies that meet any of the following criteria will be excluded: 1) The design of the study was seriously flawed; 2) Sufficient valid data could not be secured; 3) All data was published repeatedly.Two authors (QX and JZ) independently assessed the degree of bias risk of methodological of included studies with the RavMan5.4 software from the Cochrane Collaboration. A consultation was conducted when there was a disagreement between the two assessments. If there was still a disagreement, the third author (JS) will make the final decision.Two authors (QX and YS) independently extracted data from each study according to excel spreadsheet designed in advance based on our research proposal. The data extracted included name of authors, publication year, condition of grouping, basic information about the sample , course of disease, intervention methods, and outcome indicators. A third reviewer (JS) was included for arbitration purposes. We contacted the corresponding author for confirmation when the data in the study was unclear, not detailed, or some studies were duplicated.p <0.05  independently evaluated the quality of each result from five aspects of risk of bias, inconsistency, indirectness, imprecision, and publication bias by GRADEprofiler 3.2.2 software according to GRADE Handbook . Four divia email, but there was no response. The characteristics of included studies were summarized in We retrieved 518 studies from both Chinese and English databases, and finally included seven randomized controlled trials  for systAmong all the studies, six studies  explicit2 = 0.00%, p = 0.955), fixed effect model analysis showed that compared with valsartan-included conventional treatment group, the clinical efficacy of the group of salvianolate with valsartan-included conventional treatment was better   (Five studies  (445 pat0.00001) . The sub = 0.73) .2 = 63%, p = 0.04), the random effects model was chosen, and the forest plots showed that compared with control group, SBP of the treatment group decreased more significantly  . Fixed effect model analysis showed that salvianolate combined with the valsartan-included western medicine group had a more obvious DBP reduction  (p = 0.623) , heterogeneity within subgroups (CKD III-IV) disappeared , and DBP reduction between subgroups did not differ  (There were four studies  (336 pat0.00001) . No sign0.00001) . No publ= 0.623) . In subg = 0.16) .2 = 35%, p = 0.18). Fixed effects model analysis showed that salvianolate combined with the valsartan group had a better effect on reducing Scr  , but differences mainly occurred in the unclear CKD stage group, and the heterogeneity increased in this group, while the heterogeneity of CKD III-IV group disappeared   . Differe = 0.90) .2 = 92%, p = 0.0004), and a random effect model analysis showed that compared with the valsartan group, salvianolate combined with valsartan could better reduce BUN   .2 = 0%, p = 0.93), then a data synthesis by a fixed effect model showed that the decrease of UMAlb was more obvious in the salvia miltiorrhiza polyphenol acid group  (There were two studies  (183 pat0.00001) .2 = 0%, p = 0.99). Data synthesis and subgroup analysis by fixed effect models showed that patients who used salvianolate had a more significant reduction in UPCR than those who did not use salvianolate , and there was no difference among subgroups based on the stage of CKD  (Four of the included studies  (352 pat = 0.95) .2 = 96%, p <0.00001), so a random effect model was selected for processing the data. The analysis showed that salvianolate combined with the valsartan group had a better effect on reducing Cys-C  (p = 0.623) , but the heterogeneity of CKD III-IV group disappeared , while the heterogeneity increased in unclear CKD stage group , and the MD value of this subgroup becomes no longer statistically significant   . Egger’s= 0.623) . The sub = 0.29) .In the seven included studies, endothelin-1 and calcitonin gene-related peptide has been reported two or more times, and data can be synthesized.2 = 99%, p <0.00001). The egger’s test suggested that there was no publication bias  (p = 0.07) (There was significant heterogeneity among three studies  (273 pat= 0.407) . Random  = 0.07) .2 = 0%, p = 0.90). The fixed effect model analysis showed that CGRP increased more significantly in patients used salvianolate   .p = 0.24) , nicotinamide adenine dinucleotide phosphate oxidase, and reactive oxygen species, among which MDA was reported in two studies  and othe = 0.24) .One study  out of s2 = 0%, p = 0.82). Fixed effects model analysis showed that the difference between the two groups on adverse reactions was no statistical significance  (Only 2 of 7 the included studies  reported = 0.29) .We conducted egger’s test for the studies that reported SBP, Cys-C, and ET-1 to analyze publication bias. Meta-analysis of these indicators showed significant heterogeneity among studies, and each meta-analysis included more than two studies. No publication bias was found in all three egger’s tests .Sensitivity analysis was conducted by eliminating the included methods one by one to observe whether there were significant changes in the results to evaluate whether the results of our meta-analysis were robust . As showWe used the GRADE evidence quality rating to evaluate the evidence quality of the results of this meta-analysis. Among them, the quality of evidence of the effect of salvianolate on Scr in patients with hypertensive nephropathy is moderate; The clinical efficacy, adverse reactions, DBP, UMAlb, Cys-C, UPCR, and CGRP were low quality evidence; The quality of evidence on the impact of SBP, BUN, ET-1, and MDA was very low .This systematic review included a total of 7 randomized controlled studies with 535 participants and is the first to specifically and comprehensively analyze the effect of salvianolate on the treatment of HN on the basis of standardized use of ARB drugs. This meta-analysis suggests that compared with valsartan alone combined with conventional western medicine, the addition of salvianolate can further improve the overall clinical efficacy, more effective in reducing BP, decrease Scr, BUN, UMAlb, UPCR, Cys-C, further increase of CGRP, no additional effect on ET-1, and MDA, no additional adverse reactions.Controlling BP by various means is still an effective strategy to delay the progression of HN . LowerinDuring the diagnosis and treatment of HN, various indicators of renal function are the top priority of the monitored items. Glomerular filtration rate (GFR), Scr, BUN, UP, Cys-C, etc., are all such indicators. Albuminuria is an early manifestation of CKD, and the presence of elevated creatinine or decreased glomerular filtration rate indicates that nephron loss has occurred . So contOxidative stress and inflammatory reaction are the key factors in the process of renal damage caused by hypertension, and they can promote each other . TherefoHypertension can lead to the increase of vasoconstrictors (such as ET-1) and the decrease of vasodilators (such as nitric oxide), further leading to the increase of renal vascular resistance and promoting renal vascular remodeling, which is also one of the mechanisms of hypertension leading to kidney disease . The effAccording to our meta-analysis, the effect of salvianolate on HN is definite, especially in improving renal function. Even if valsartan has been used, it can still further improve renal function without increasing adverse reactions. We graded the quality of evidence of our results using the GRADE approach. In the evaluation of evidence quality, only Scr is moderate, and others are in low and very low quality, which indicates that the overall quality of evidence of this meta-analysis is not high. The main reasons for the degradation of the quality of evidence are inadequate allocation concealment, missing of blinding of participants and personnel and insufficient sample size . At the Some limitations remain with this meta-analysis. First, although we developed a detailed search strategy, due to language limitations, we only searched in English and Chinese, and all included studies are in Chinese. As a result, we cannot guarantee an absence of language bias. Secondly, the overall quality of the included studies is not very high. All the studies did not accurately describe whether to use blinding, which undoubtedly increased the risk of performance bias. Some of the included studies do not clearly define the renal function stage of patients, so our subgroup analysis can only be conducted for the CKD III-IV stage. Fourth, the meta-analysis of CGRP and MDA showed significant heterogeneity, and the subgroup results of Cys-C were inconsistent. But we have not found convincing concrete reasons. It may be related to the sample size, course of the disease, CKD stage, etc., but the number of studies is insufficient, and the data provided by the study is limited, so we failed to conduct further analysis to find out the reason. Fifth, HN is a chronic disease, but all the studies we include do not carry out long-term follow-up and do not evaluate the long-term effect. Sixth, the results of this meta-analysis, as evidence, are generally of low quality. Finally, although several studies have been included, the overall sample size is still insufficient in this meta-analysis, and there are no relevant clinical studies after 2018 after the retrieval. Therefore, more new and large sample clinical studies are needed to provide data support.As discussed in this meta-analysis, patients with HN can still benefit from salvianolate even if they have been treated regularly with valsartan. Salvianolate can still further improve efficacy, reduce BP and improve renal function, but the effectiveness of this treatment in further reducing oxidative stress and improving endothelial function needs to be confirmed. At the same time, we need to see that the quality of evidence of other results is very low except for Scr. In general, salvianolate can be used as an auxiliary treatment drug for HN, but further randomized controlled trials with large sample sizes, multi-centers, and double-blinding are needed to provide more reliable and accurate data to assess the efficacy of salvianolate for HN.


Shame and guilt in polysubstance abusers are still understudied despite their significance in substance use disorders (SUD). The goal of the current study is to develop a better understanding of how shame and guilt interact among polysubstance abusers who are receiving residential treatment.The sample of two hundred four males with SUD admitted to five rehabilitation centers from two cities in Pakistan participated in this study. For comparison, 215 age-matched healthy individuals were recruited (control). All participants reported their scores on the state shame and guilt scale (SSGS) and demographic form. A cross-sectional study design was adopted.r = 0.79, p < 0.001) as compared to healthy (control) individuals . Further, multivariate analysis indicated that people with SUD who were of older age, unemployed, living in a nuclear family system, with a higher level of education, and low income, experienced higher levels of shame and guilt. Multinomial logistic regression analysis revealed that people with SUD in the age group 41–60 years , unemployed , nuclear family system  and low monthly income group  had a significantly high risk of shame and guilt than the control group.The group with SUD reported greater activations on SGSS (Findings of the current study indicate an association between shame and guilt activation and SUD. These results suggest that polysubstance users may benefit from therapeutic interventions to avoid a generalization of shame and guilt toward their substance use. Reducing shame and guilt should be considered a priority in treating adults with multiple SUD. There is evidence that individuals with a history of addictive behaviors experience excessive self-conscious emotions, and shame and guilt can be especially challenging –3. ShameToxic shame and chronic guilt are major reasons for all addictive behaviors . A studyResearch conducted on alcoholics presented that shame and guilt activation were positively associated . HoweverBased on the researchers' initial review of related literature, it was found that limited studies have been conducted on this topic in Pakistan among inpatient poly-substance abusers. Some researchers have claimed shame and guilt are detrimental to treatment-seeking behaviors , 8, 13, Thus, the current research was designed (a) to explore the relationship between shame and guilt activations among inpatient polysubstance abusers and (b) to investigate the difference between shame and guilt activations concerning sociodemographic factors. It was hypothesized that there would be a strong positive correlation between shame and guilt activations in polysubstance abusers. Further, it was expected that there might be significant differences in shame and guilt activations in sociodemographic variables.Mean = 31, SD = 4.6) were recruited in five rehabilitation centers in two cities of Pakistan (Lahore and Mirpur Azad Kashmir). To receive services at the hospital participants had to meet the criteria  of SUD according to the diagnostic and statistical manual of mental disorders (DSM-V). It has already been defined by Flanagan , who were not using treatment services for alcohol and drug problems and were free of any psychiatric disorder, were recruited for the study. The demographic characteristics of the control group were matched, as much as possible, with the group of SUD. Divisions of the sample are given in The current study adopted cross-sectional research design. A sample of 204 males, polysubstance abusers with ages ranging from 18- 65 years  variables  between the addiction and control group were examined, a Chi-square test was performed, Additionally, the association of sociodemographic factors with different levels/degrees of shame and guilt was tested using Multinomial logistic regression analysis. Dummy variables 1 to 5 were assigned to shame/guilt levels, and four models were estimated by keeping the level-1 as the reference group. All models were estimated separately for the group with SUD and control. Results were interpreted using the Odds ratio (OR) with a 95% confidence interval (CI) for each independent variable.p-value <0.05 was considered statistical significance for all analyses. All analyses were performed using SPSS version 26 IBM.Effect sizes were calculated using partial eta squared and interpreted using  guidelinM = 31, SD = 4.6) and the control . The overall mean shame and guilt level for the group with SUD was about 2 times higher than the control, followed by the mean level of shame  and mean guilt level  for the people with SUD. The detailed descriptive statistics for the level of education, employment status, family system, and sample group characteristics can be seen in The study was conducted on age-matched participants between the group with SUD and the control, with the mean age of the group with SUD  as compared to control  and had a linear correlation in the control group . Further, the correlation of sociodemographic factors with shame and guilt scores of people with SUD and control individuals was computed, which revealed that education level was moderately correlated with guilt activation in the group with SUD (F (2.414) = 283.22, p-value < 0.001, For mean comparison by sociodemographic factors between the group with SUD and control was performed using multivariate two-way MANOVA. Results show significant mean differences in shame and guilt across age groups between the group with SUD and control. Participants from the group with SUD scored higher on shame and guilt levels in all age groups compared to the control group. By education level comparison, results revealed significant mean differences between groups. Participants in SUD group reported high mean scores compared to the control. Furthermore, findings revealed a significant multivariate main effect for occupation between the group with SUD and the control group. This partial eta square value indicates a large effect size. Comparison over occupation categories revealed that unemployed participants got high scores than other occupation ranks on shame and guilt in the group with SUD. Moreover, findings showed significant mean differences in both groups concerning the family system. The group with SUD scored higher on shame and guilt, than control group  were significantly associated with a high risk of shame in model-2 to model-4 compared to the reference group , i.e. ORs 95% Cis), 2.5 (1.8–3.6) for model-2, 4.3 (2.7–5.4) for model-3 and 5.2 (2.4–6.8) for model-4. As for other demographic variables, the participants belonging to unemployed, nuclear family system, and low monthly income groups had a significantly high risk of shame and guilt in the last three models as compared to the reference group among both groups with SUD and control individuals see , 5.% Cis, 2.This research has addressed an identified gap in the literature whereby little has been written about shame, guilt, and their relationship to inpatient polysubstance abusers. This study aimed to determine the correlation between shame and guilt-activation among polysubstance abusers hospitalized in a rehabilitation center. The study also explored whether the people with SUD reported higher shame and guilt scores than the control group. We were also interested in how sociodemographic characteristics might be associated with shame and guilt scores among people with SUD and control groups.The study was restricted to male participants, given the fact that SUD is significantly more prevalent in men where the study was conducted, and whether the findings of this study are generalizable to female populations needs further exploration , anxiety, and depression) on shame and guilt-activation. Finally, our whole sample consisted primarily of men. Future research should examine whether shame and guilt affect men and women differently.From the study results, one possible implication for clinicians is the importance of evaluating people with SUD for their shame and guilt levels. Clinicians may help patients differentiate between shame and guilt, particularly by noting the motivating potential of guilt and the more extreme negative significance of shame. The present study's findings provide more credence to Dearing et al.  contentiWe found a strong relationship exists between shame and guilt activations among inpatient polysubstance abusers. The findings of this study confirm that polysubstance abusers experience a higher degree of state shame and guilt than healthy individuals. Further, polysubstance abusers with older age, higher education, unemployment status, nuclear family system, and low income, experience higher levels of shame and guilt.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 the Ethics Board Committee of the Department of Psychology, Wuhan University, China. The patients/participants provided their written informed consent to participate in this study.NA, MI, and SM: conceptualization and methodology. NA, MI, YY, SM, MT, and RY: validation and visualization. NA, MI, MN, and RY: software. NA, MI, SM, and MT: writing—review and editing. MI, SM, and MN: formal analysis. YY, SM, MN, and RY: investigation. NA: funding acquisition. MI: roles/writing—original draft. YY: project administration, resources, and supervision. MN: data curation. All authors contributed to the article and approved the submitted version.This research was conducted under the Mianyang Normal University's scientific research promotion project The effect of Praise and Academic Motivation on Social Identity on college adaptation among College Students: A Cross Cultural Comparison between China and Pakistan (QD2020B04).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 there are clear moral components to traffic violations and risky and aggressive driving behavior, few studies have examined the relationship between moral values and risky driving. This study aimed to examine the relationship between moral views of driving behavior and brain activity. Twenty healthy drivers participated in this study. A questionnaire regarding their moral values concerning driving behavior was administered to the participants. Brain activity was measured using near-infrared spectroscopy while eliciting moral emotions. Based on the results of the questionnaire, the participants were divided into two groups: one with high moral values and the other with low moral values. Brain activity was statistically compared between the two groups. Both groups had significantly lower activity in the prefrontal cortex during the self-risky driving task. The low moral group had significantly lower activity in the left dorsolateral prefrontal cortex than the high moral group, while it had lower activity in the right dorsolateral prefrontal cortex in the self-risky driving task than in the safe driving task. Regardless of their moral values, the participants were less susceptible to moral emotions during risky driving. Furthermore, our findings suggest that drivers with lower moral values may be even less susceptible to moral emotions. Road traffic injuries are a major global health and development problem . AccordiMoral emotions play an important role in maintaining social norms and promoting prosocial behavior ,14. WeinMany studies have long shown that driver personality-related factors  influence risky driving behavior ,20,21,22Extensive research has been conducted to elucidate the neural basis of moral emotions, as they have a significant impact on daily life and social norms . In partConsidering the hypothesis that drivers with low morality may be less likely to generate moral emotions during hazardous driving than drivers with high morality, the research question for this study was set as follows: “Do different moral values of drivers lead to different activity in brain areas involved in moral emotions during risky driving”? Accordingly, the aim of this study was to examine the relationship between moral values for driving behavior and brain activity using NIRS. In this study, moral values were defined as “the idea of making judgments of right and wrong based on personal values and moral emotions”.The novelty of this study is that it focused on individual differences in drivers’ moral values and examined brain activity during a moral judgment task simulating driving behavior. The findings will increase the understanding of neurological aspects of the relationship between drivers’ moral values and driving behavior. Furthermore, because inappropriate, immoral behavior is more likely to occur after brain injury ,39, we bThe study protocol was approved by the Ethics Review Committee of Nittazuka Medical Welfare Center (NE: 2022-13).The participants were recruited between April and July 2022 in an automobile-dependent area of Japan. The inclusion criteria were (1) driving on a daily basis and (2) at least one year after obtaining a regular automobile license; the exclusion criteria were (1) cognitive decline or (2) a history of central nervous system disease. The participants were informed of the experiment in writing and orally, and informed consent was obtained from all participants. The participants were informed that the purpose of the study was to investigate the relationship between driving behavior and brain activity, and they were not told that the study would investigate their moral views regarding driving behavior in order to avoid socially desirable responses. There were 20 participants  with a mean age of 25.3 years (SD = 6.8) and a mean driving experience of 6.9 years (SD = 7.0).First, a questionnaire was administered to all participants regarding their moral values for driving behavior. The questionnaire consisted of 15 items, which were translated into Japanese and partially modified based on aggressive driving behavior reported by Houston  Table 1Table 1. The median and mean scores for the 15 items were calculated. The median score for the self-version was 48.5, and that for the others-version was 48. Those participants with a score above the median of the self-version were defined as the group with high moral values , while those below the median score were defined as the group with low moral values . Two participants scoring within the median score range were excluded from the analysis. As a result, there were nine participants . The basic attributes of the participants in each group are presented in The testing room was a quiet, private room where NIRS measurements were performed in the absence of sunlight. Brain activity was measured using NIRS  while presenting sentences concerning driving behavior to elicit moral emotions. Activity in the frontal lobe, which is associated with the generation of moral emotions, was measured ,26,27. TThree tasks were performed: (i) safe driving, (ii) self-risky driving, and (iii) others-risky driving. (i) The safe driving task used sentences that complied with traffic rules. (ii) The self-risky driving and (iii) others-risky driving tasks used sentences described in the questionnaire on moral values for driving behavior. The protocol was measured in five consecutive sections, with 20 s of pre-task rest, 30 s of task, and 20 s of post-task rest as one block. At 30 s of the task, three sentences were presented for 10 s each. The three tasks were randomly ordered. The experimental design is shown in Location estimation was performed using Fusion imaging software (Shimadzu Corporation) based on the probe location information obtained with FASTRAK. Then, the cortex localization of the channels was obtained using Statistical Parametric Mapping for Near Infrared Spectroscopy (NIRS-SPM), which was programmed with MATLAB R2014a . The dorsolateral prefrontal cortex (DLPFC) and prefrontal cortex (PFC) are regions of interest that are particularly involved in moral emotions ,31. A toNoise in the NIRS signal was corrected using a 0.01–0.2 Hz band-pass filter and independent component analysis . Among op-value < 5%.Statistical comparisons were made for age, driving history, moral values for driving behavior, and Oxy-Hb changes between the two groups. Age and driving history were analyzed using the Mann–Whitney U test. The self-version and others-version scores of moral values for risky driving between the groups were analyzed using repeated-measures analysis of variance . The amount of change in Oxy-Hb in the three tasks between the groups was analyzed by repeated-measures analysis of variance . Multiple comparison tests (Bonferroni) were performed as post-tests. All statistical analyses were performed using EZR  , and theThe mean age and mean driving history of the high moral group/low moral group were 23.9 years (SD = 5.7) and 5.4 years (SD = 6.0)/25.9 years (SD = 7.0) and 7.4 years (SD = 7.2), with no significant differences between the two groups .p < 0.001), but no significant main effect of VERSION or interaction between GROUP and VERSION  for the high moral group/low moral group were 62.6 (SD = 6.9) and 55.1 (SD = 11.2)/41.4 (SD = 3.0) and 41.2 (SD = 8.0). There was a significant main effect of GROUP  = 39.130,  VERSION .p = 0.029, F = 4.966, p = 0.013, respectively). Post-test results showed no significant difference for Ch14 but for Ch27, the low moral group showed significantly less brain activity in the self-risky driving task than in the safe driving task (p = 0.040). In Ch12, there was a significant main effect of GROUP  = 4.765, p = 0.044), indicating that brain activity was significantly lower in the low moral group than in the high moral group. In Ch15 and Ch30, there was a significant difference in the main effect of the task  = 4.185, p = 0.024 and F = 4.581, p = 0.017, respectively), with brain activity being significantly lower in the self-risky driving task than in the safe driving task .The changes in Oxy-Hb levels in the three tasks in both groups are shown in That is, the low moral group had less activity in the area corresponding to the left DLPFC than the high moral group, and the low moral group had less activity in the area corresponding to the right DLPFC in the self-risky driving task than in the safe driving task. In addition, the left and right PFC were less active in the self-risky driving task than in the safe driving task, regardless of the moral value.In this study, we investigated the moral view of driving behavior in healthy drivers and measured their brain activity using NIRS while eliciting moral emotions. Two groups, one with high moral values and the other with low moral values, were created based on a questionnaire, and differences in brain activity were compared between these groups. Based on the characteristics of the traffic society, the present study focused on not only self-directed emotions such as shame and guilt but also other-oriented emotions such as anger and disgust as moral emotions toward risky driving. In the NIRS measurement task, the safe driving task was set as a control condition, in addition to the self-risky and others-risky driving tasks. Self-directed emotions were targeted in the self-risky driving task, and other-directed emotions were targeted in the others-risky driving task. The safe driving task targeted moral emotions during compliance with the traffic norms. In this case, positive emotions such as conscience and a sense of responsibility were considered to be affected, rather than negative emotions such as shame, guilt, anger, and disgust.First, no significant differences were found in the main effects and interactions of the conditions on moral attitudes toward driving behavior, suggesting that the low moral group was less likely than the high-moral group to have negative feelings of shame, guilt, anger, and disgust toward risky driving, whether by themselves or with others. This is consistent with previous reports  that driNext, brain activity was measured while eliciting moral emotions, and the results showed significant differences in the interaction and group main effects in the DLPFC. The DLPFC is generally considered to act in an inhibitory manner on emotional expression , and PaqNext, with regard to the PFC, we found significant differences in the main effects of the tasks. The PFC, including the medial PFC, was associated with emotional responses . AndersoIn addition, drivers with low moral values may be even less susceptible to moral emotions when driving, which may be more pronounced when they are driving riskily. In other words, they may be more likely to drive risky and may be a potential problem for others.The present analysis of the relationship between moral values and brain activity with respect to driving behavior suggests that the amount of specific brain activity differs depending on differences in moral values and driving conditions, although it is difficult to say that there are marked differences in brain activity. van den Berg et al.  noted thThe first limitation of this study was the small number of participants. Furthermore, the drivers who participated in this study were able-bodied individuals living in one automobile-dependent area of Japan. Moral values are influenced by acquired aspects such as environment and experience, which may lead to different results depending on the country and region in which one lives. For the generalization of the study findings, it is imperative to increase the number of participants and expand the areas covered by the survey. Furthermore, we believe that a comparison of healthy individuals and individuals with brain injury is necessary in order to develop supportive measures for the resumption of driving after brain injury. Finally, instead of presenting sentences that simulate driving behavior and induce moral emotions, researchers will need to clarify the relationship between actual driving behavior and brain activity.We investigated the relationship between moral values and brain activity for driving behavior in healthy drivers using NIRS. Brain activity in two groups, one with high moral values and the other with low moral values, was compared. The results suggest that regardless of the difference in moral values, it is difficult to induce moral feelings during risky driving. In addition, drivers with low moral values may be less susceptible to moral emotions when driving, which may be more pronounced during risky driving.


The diet of schoolchildren can be improved by reducing the intake of grain and edible oils. Physical fitness of schoolchildren can be improved by increasing exercise time and selecting exercises with higher metabolic equivalents. Rope skipping appears to be the best option because it can ameliorate obesity by increasing muscle strength. The results of this study can provide a reference for the development of obesity intervention methods for children in China and worldwide.Childhood obesity is observed not only in developed countries but also in some developing countries in Asia, where low physical activity and poor physical fitness have been reported. The primary goal of weight loss is to reduce body fat mass, thereby reducing the risk of metabolic syndrome. Unfortunately, a concomitant decrease in lean mass, including muscle mass, is often observed when weight is lost. This study aimed to clarify the nutritional status and physical fitness of local elementary school children and to investigate the factors associated with nutritional status. This study evaluated measures that can reduce the tendency toward obesity and recommends exercise that can reduce weight while maintaining or increasing muscle strength. A total of 911 elementary school children were recruited for this study. All the participants completed anthropometric measurements, dietary surveys, and physical fitness tests. Compared with the Chinese obesity criteria, the proportions of obese and overweight subjects were generally high [22  to 47% (urban boys)], and urban children had a higher obesity rate than rural children. Overall, rural children had better physical fitness test results than urban children did. Skipping rope was correlated with muscle mass. Exercise time (β = −0.31,  Global childhood obesity rates have considerably increased . From 19Poor physical fitness in children deserves further attention. According to a review of 137 studies conducted in 19 countries, cardiorespiratory fitness in children aged 9–17 decreased significantly in most countries between 1981 and 2014, as measured by the 20-m shuttle run test –7. The 2Previous studies have found that poor physical fitness and obesity are important factors for high blood pressure, coronary heart disease, and stroke , 10. AltExercise is an important means to ameliorate obesity. Several studies have confirmed the effectiveness of exercise in ameliorating obesity –14. HoweThe purpose of this study was to explore the factors associated with nutritional status and provide a theoretical basis for the formulation of obesity intervention programs for primary school students.This cross-sectional study selected one of eight urban elementary schools and two of three rural elementary schools with the largest number of students in one district of Benxi City, Liaoning Province, in Northeast China. Two of the four classes from each grade were chosen randomly from the urban elementary schools. All the classes were chosen from the two rural elementary schools. As the population of students aged 5 and 12 years was minimal, these students were excluded from the study. A total of 911 students  aged 6–11 years were included in the study conducted from May to July 2021.Height was measured at 0.1 cm precision using a portable stadiometer . Weight was measured at 0.1 kg precision using a digital scale . Upper arm circumference (AC) was measured at 0.1 cm precision a using fiberglass tape measure. Triceps skinfold thickness (TFS) was measured at 0.5 mm precision using a skinfold adipometer  . All mea2) was calculated using height and weight measurements. BMI-for-age z-scores (BMI-AZ) were calculated using World Health Organization (WHO) reference data for sex and age  = [AC (cm) – π × TSF (mm) × 10]2/4π. BMI-AZ was quantified using Cole's Box-Cox transformation, calculated as follows: BMI-AZ = [(BMI/M) L – 1]/S*L, where M is the median of the parameters, S is the generalized coefficient of variation, and L is the power in the Box-Cox transformation.The arm muscle area (AMA) was calculated using the AC and TFS as follows: AMA , screen time (min/day), and sleep time (min/day) in the last week. Exercise time was defined as the sum of the time spent exercising or playing sports. Adolescent students were asked to separately report the time spent in physical activities at school  and sports clubs and during their free time. To estimate screen time, adolescent students were asked to separately report the time spent watching TV, playing video games, playing mobile games, and using a computer. Sleep time included sleeping overnight and during naps.Information regarding education level and family monthly income was collected from the parents using a questionnaire.t-test was used to verify differences in the participants' mean body composition and physical fitness test results by area  and sex. Pearson's correlation coefficients were calculated to assess the relationship between AMA and physical fitness test scores. Multiple regression analysis was performed using BMI-AZ as the dependent variable. The 50-m run time (seconds), long-seat body anteflexion (cm), skipping rope (times/min), exercise time (min/day), screen time (min/day), sleeping time (min/day), intake values for nine food groups (g/day), three major nutrients (g/day), energy , education level of the father and mother, family income (yuan/month), area, and sex were used as predictor variables. Variables were selected using the stepwise increase-and-decrease method, and a threshold p-value of 0.20, calculated using the likelihood ratio test. JMP Pro 16.0.0 (SAS Institute Inc.) was used to perform statistical analyses, with a significance of p < 0.05.An independent The prevalence of underweight among children in both rural and urban areas was <10% . Both urThe means and standard deviations for the physical fitness test results by area are shown in r = 0.17–0.25, p < 0.05; To clarify the relationship between muscle mass and physical fitness, we examined the correlations between AMA and individual physical fitness test scores. There was a significant positive correlation between skipping rope and AMA in all groups .The reported means and standard deviations (min/day) for daily exercise time, screen time, and sleep time by area and sex are shown in p < 0.01), skipping rope , screen time , sit-ups , 400-m run , area , oil intake , family income (yuan/month) , and sex  were significant predictive factors ( factors .The results of this study showed that the overweight and obesity rates of children in northern China are relatively high. Compared to the other groups, rural girls had the lowest proportion of overweight and obesity . HoweverThe physical fitness of children in local areas was poor  comparedThe energy intake of urban children was higher than that of rural children, which was confirmed by the fact that the intake of nine food groups of urban children was higher than that of rural children , 3. ThisBoys and children from high-income families were more likely to be obese . SocioecThe one-child policy has been considered one of the causes of the increasing childhood obesity problem in China . This stShort exercise and long screen times were risk factors for obesity , 5. PhysExercise is effective in reducing fat and enhancing lean body mass in children, resulting in positive effects on ameliorating obesity . Our resFurthermore, this study indicated that skipping rope can increase muscle mass, which is expected to increase with the amount of exercise performed . SkeletaWe selected only one city, Benxi, as the study area. Therefore, it is difficult to generalize the results to other cities in Liaoning Province and northeastern China. Because this was a cross-sectional study, it was not possible to determine the causal relationships between nutritional status, diet, lifestyle, exercise performance, and the factors affecting them in elementary school children.Rural children had a better nutritional status and physical fitness than urban children. However, both urban and rural children showed high rates of obesity and poor physical fitness. Diet can be improved by reducing the intake of grains and edible oils. Physical fitness can be improved by increasing exercise time and selecting exercises with higher metabolic equivalents. Rope skipping appears to be the best option because it can ameliorate obesity by increasing muscle strength.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by Ethical approval for the study was granted by the Gannan Medical University, China. The patients/participants provided their written informed consent to participate in this study.BL and XL: data collection, data analysis, and manuscript writing. QW: study design and data analysis. WY: study design, data collection, data analysis, and manuscript writing. MH: study design, data collection, data analysis, manuscript writing, and funding acquisition. All authors contributed to the article and approved the submitted version.This study was supported by the Starting Research Fund of Gannan Medical University.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts 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.


Conclusions: Harm-avoidance seems to be the most important dimension in personality patients with chronic pain, as previously found. We found no differences between OA groups and between sensitized groups, but there are differences between FM and OA-noCS, so harm-avoidance might be the key to describe personality in patients with CS rather than the presence of prolonged pain, as found in the literature before.Background: Personality traits are relevant for pain perception in persistent pain disorders, although they have not been studied in depth in sensitized and nonsensitized patients with knee osteoarthritis (OA). Objective: To explain and compare the personality profile of patients with OA, with and without central sensitization (CS), and fibromyalgia (FM). Setting: Participants were selected at the Rheumatology Department in two major hospitals in Spain. Participants: Case-control study where the sample consists of 15 patients with OA and CS (OA-CS), 31 OA without CS (OA-noCS), 47 FM, and 22 controls. We used a rigorous and systematic process that ensured the sample strictly fulfilled all the inclusion/exclusion criteria, so the sample is very well delimited. Primary outcome measures: Personality was assessed by the Temperament and Character Inventory of Cloninger. Results: The percentile in harm-avoidance dimension for the FM group is higher compared to OA groups and controls. The most frequent temperamental profiles in patients are cautious, methodical, and explosive. Patients with FM are more likely to report larger scores in harm-avoidance, with an increase in logistic regression adjusted odds ratio (OR It is known that personality, a person’s predispositions and patterns of thinking, feeling, and acting , plays aWe would like to focus on two pathologies where chronic pain (CP) is the main feature. The first is osteoarthritis (OA), which is already one of the ten most disabling diseases in developed countries. The worldwide estimates are that 9.6% of men and 18% of women aged over 60 years have symptomatic osteoarthritis . Even ifPsychological and personality factors should be considered an important contributor in the processing of CP, as we know that they play a role in modulating therapeutic responses and pain perception ,16. PersLittle is known in the field of personality in OA, although it is the most prevalent musculoskeletal disease; presumably, plenty of OA patients suffer CP, and there are studies that show that the patient’s personality predicts recovery after total knee arthroplasty . Çidem, The initial sample was composed of 90 patients with knee OA diagnosis and 150 with FM diagnosis at the Rheumatology Department in two major hospitals in Spain , selected by a senior rheumatologist and a senior clinical psychologist during an 18 month period. There was a control group with 35 participants.Patients with OA were divided into 2 groups: (1) presence of clinical central sensitization, defined by the presence of both spreading sensitization and temporal summation to repeated pressure pain stimulation ,31,32,33Radiological and clinical diagnosis of knee OA based on the American College of Rheumatology (ACR) criteria, affecting at least one knee with a minimum of 3 months of symptom duration prior to screening.Male or female  at least 45 years old.A minimum of 4 out of 10 on the numerical rating scale (item 5 of Brief Pain Inventory) at screening and/or a requirement for the use of an analgesic for the knee pain.The principal inclusion criteria for the OA patients were:Clinical evidence of pain or altered sensations spread beyond the knee joint by manual palpation in the baseline rheumatologist assessment.2 [At least 3 tender points in the extended version of the Arendt–Nielsen peripatellar map . A tender point is defined as a point showing a pressure pain threshold below 4 kg/cm2 .2 pressure stimulation on the anterior surface of the tibial bone.A pain score of 4 points or more in an 11-point verbal scale during a 2 s, 4 kg/cmPresence of temporal summation  on the most sensitive site of the peripatellar region [The specific inclusion criteria for the OA-CS group were:Diagnosis of FM following the ACR criteria .History of widespread nonarticular pain with insidious onset primary over 3 months.One year minimum of disease evolution.Absence of comorbid chronic fatigue syndrome.The principal inclusion criteria for FM patients were:No history of rheumatic disorder, no history of functional pain or physical widespread pain.No history of Axis I or II psychiatric illness and no history of neurological disease.Inclusion criteria for control group were:Additionally, control participants underwent a brief semistructured clinical psychopathological interview according to DSM-5 diagnostic criteria carried out by a senior member of the research team (JD) to rule out any personality disorder. A convenience sampling was carried out where the researcher selects the patients who are easily accessible in a waiting room, through a satisfaction survey of the health system.In all groups, patients with a history of psychotic disorder or substance abuse, patients with a history or diagnosis of personality disorders, and patients with a history of neuropathic pain were not included. A flow chart of the sample selected is shown in The participants signed informed consent to accept the conditions of the study. We used a methodical and strict process that allowed us to ensure the sample strictly fulfilled all the inclusion/exclusion standards; therefore, the sample was very well delimited. The final sample  was madeFirst, patients attended rheumatologic visits where they were selected, and after verifying the inclusion/exclusion criteria as well as the will to participate, they were enrolled. During the next few days, patients attended psychological assessment, performed by the same clinical psychologist, which lasted about 90 min. Patients were visited twice in case of causing too much fatigue that may have influenced answers. The research only analyzes some aspects of this broad protocol.Novelty-seeking (NS), defined as the inclination to respond impulsively to novel stimuli with active avoidance of frustration.Harm-avoidance (HA) as the tendency to inhibit responses to aversive stimuli leading to avoidance of punishment.Reward dependence (RD) as the predisposition to answer to signals of reward.Persistence (PS) as the tendency to perseverance despite frustration and fatigue.Revised Temperament and Character Inventory (TCI-R) : We admiSelf-directedness (SD), which refers to the ability to control, regulate, and adapt behavior to fit the situation.Cooperativeness (CO), which is related to acceptance of other people.Self-transcendence (ST), which is viewed as the identification with everything conceived as essential and consequential parts of a unified whole.The 3 character scales are:Exploratory excitability (NS1), impulsiveness (NS2), extravagance (NS3), and disorderliness (NS4).HA: Anticipatory worry (HA1), fear of uncertainty (HA2), shyness with strangers (HA3), and fatigability (HA4).RD: Sentimentality (RD1), openness to warm (RD2), attachment (RD3), and dependence (RD4).PS: Eagerness of effort (PS1), work-hardened (PS2), ambitious (PS3), and perfectionist (PS4).The temperament facets in NS are:Responsibility (SD1), purposefulness (SD2), resourcefulness (SD3), self-acceptance (SD4), and enlightened second nature (SD5).CO: Social acceptance (C1), empathy (C2), helpfulness (C3), compassion (C4), pure-hearted conscience (C5).ST: Self-forgetful (ST1), transpersonal identification (ST2), and spiritual acceptance (ST3).The character facets for SD are:Specifically, this inventory allows us to assess the possibility of the psychometric presence of some symptomatic personality disorders  if the scores of SD and CO are low or very low (17–33%). The lower cut-off point is situated in 35 points and the upper in 75. This questionnaire has proved to be reliable in its original version, with internal consistency alpha coefficients ranging from 0.65 for persistence to 0.89 for cooperativeness. The Spanish version also shows good estimates of internal consistency alpha coefficients, such as in our study except in the novelty-seeking scale .We performed nonparametric Kruskal–Wallis and chi-square statistical tests to analyze the differences between the four groups  in TCI-R mean percentile scores and in the distributions of the temperamental profiles and personality disorders of TCI-R, respectively. Logistic regression models were adjusted to identify the most characteristic personality pattern of these groups. For the statistical analysis we used the statistics Package SPSS 20 .Descriptive features of the final sample are shown in p < 0.001). p < 0.001) but not in the distribution of personality disorders . There are also no differences between groups in the frequency of absence/presence of personality disorder  and personality disorder  obtained depending on the temperamental profile. The contingency coefficient scored 0.589 (p < 0.05), which is high (according to the formula: Max (C) = √χ2/(χ2 + n)) and is directly proportional. After the contingency table and the chi-square test, we found a relation statistically significant between group  and temperamental profile. To obtain a descriptive profile of personality for each group, a logistic regression analysis was completed. The initial model included the following confounding factors: gender, age, academic level, and cognitive screening.The outcomes of the logistic regression between OA-CS and OA-noCS and between FM and OA-CS show no statistical significance in their profiles. We also performed logistic regression in every subdimension of each temperament, and character dimensions where we found no significant differences.The aim of this research was to describe the most frequent temperamental profile for different groups of patients, including the control group, to study whether the participants show a potential personality disorder or not, and of what type, and finally to describe the pattern of personality for different groups, focusing on the presence of CS. Many researchers found higher scores in HA and lower in SD, with some variations with the role of the other dimensions of temperament and character, for example, lower scores in NS ,20. GencRegarding the temperamental profile results of combining temperamental dimensions NS, HA, and RD, for OA-noCS patients, the most frequent profiles are cautious (19.4%) and explosive (19.4%), for OA-CS it is methodical (26.7%), for FM patients it is cautious (36.2%), and for controls it is independent (36.4%). Explosive (high scores in NS), methodical, and cautious (both low scores in NS) show high scores in the HA dimension, while independent shows high scores in RD. When SD and CO are low, the possibility of having a personality disorder exists. In our sample, most of the patients do not show a potential disorder. However, patients who do show obsessive, avoidant, and borderline disorders correspond to methodical, cautious, and explosive temperamental profile. Thus, patients with a potential personality disorder of cluster C show high scores in HA. Thus, both patients with and without personality disorder show inhibition, passive avoidance, pessimism, fear of uncertainty, cautiousness, shyness, anticipation of problems, and fatigue after stress. When the disorder is present, these traits are more exaggerated, meaning that the person is not able to control his or herself driven by the situation.After the regression analysis, we found that patients with and without CS are more likely to show RD traits, a fact that has not been found in research before. These dimensions assess the tendency to be influenced by others, be very sensitive to social signs, sentimental, and be able to understand the feelings of others. Garcia-Fontanals et al.  and GencThere are authors who state that central sensitization syndrome has been produced by the existing duration of chronic pain that begins in the early stages of life or due to innate personality traits (temperament), learned personality traits (character), or a combination of both. Our study covers an older population and, therefore, innate temperament traits are what determine the presence of SSC .The sample size is small, especially for the OA-CS group. Given the size of the sample, we were not able to carry out an analysis that differentiates between gender and age.External validity is limited by the sample size, even though the sample is very specific and restrictive, with the inclusion/exclusion criteria. For example, FM patients showed no chronic fatigue, which is a very common characteristic.The FM group was not divided into potential subgroups of patients according to severity; for example, there are few studies that show evidence in this field. Thus, it is complicated to find previous studies to compare our results with others.The effects of other symptoms of central sensitization that may be present in these patients, such as migraine, irritable bowel syndrome, or low back pain, have not been studied in OA groups due to the small sample size.This research has some limitations:Therefore, our results show that patients with CP show a diverse personality pattern compared to control subjects ,37, and Multiple differences between groups with CS and without CS have been reported in previous research; Clark et al.  found a Personality assessment with TCI-R gives us the opportunity to evaluate treatment responses. Many studies found that the pretreatment level in the SD dimension predicts the scope of improvement. When the therapy is successful, levels of SD increase, giving control across the situations ,21. TherWe changed the focus from CP to CS; however, more investigations are needed in CS syndromes to find out if this phenomenon is an important factor in the role of the HA dimension, and not the presence of CP, as is normally reported. Further research is recommended to include the controlled pain parameter that differs in personality traits.In conclusion, harm-avoidance seems to be the most important dimension in personality patients with chronic pain, as previously found. We found no differences between OA groups and between sensitized groups, but there are differences between FM and OA-noCS, so harm-avoidance might be the key to describe personality in patients with CS rather than the presence of prolonged pain, as found in the literature before.


Inflammation in overweight/obesity may condition the development of insulin resistance (IR). New markers of inflammation and systemic inflammation, such as leukocyte and platelet counts, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), could be used as indicators of IR. The aim of the present study was to investigate the relationship between these markers and IR in overweight/obese children.p75 for each sex. IR was defined as HOMA-IR >3.16.A total of 1,035 schoolchildren were studied (398 overweight/obese). Anthropometric, hematological and biochemical measurements were collected. Inflammation was considered to be present when the values of leukocytes, platelets, NLR, PLR and MLR were ≥p75) and IR was found in the entire population  and in boys .In overweight/obese schoolchildren, leukocytes were higher in both boys and girls, and platelets and NLR were higher in boys with IR than in boys with insulin sensitivity. An association between leucocytes and NLR values (≥Elevated white blood cell values and elevated NLR in overweight/obese children, and particularly in boys, could be indicators of the presence of IR in these subjects and should be considered when predicting possible complications, such as type II diabetes mellitus. Obesity is becoming a global epidemic, increasing the health burden of associated complications of insulin resistance and diseases such as cardiovascular disease  or type Among the main and most studied inflammatory mediators released by adipose tissue are interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), angiotensinogen and the growth factor TGF-beta, and hormones secreted by adipocytes, such as leptin and resistin. Along with adipose tissue, acute-phase proteins of hepatic origin, C-reactive protein (CRP), amyloid A, fibrinogen and plasminogen activation inhibitor have also been linked to the development of inflammatory processes . In partComplete blood count is an inexpensive and simple laboratory examination, and in recent years, leukocyte and platelet counts, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) have been studied as inflammatory markers in various chronic subclinical diseases –17. ThesHowever, there are few studies, especially in school children, using these indicators of inflammation. Therefore, based on the findings of previous studies, the aim of the present study was to investigate the relationship between these novel indicators of systemic inflammation and IR in overweight/obese (OW/OB) children.A convenience sample of 1,035 schoolchildren between 8 and 13 years of age were studied. To select them, the head teachers of different primary schools in 5 Spanish provinces  were contacted by telephone, and the characteristics and importance of the intended study were explained to them. Once the acceptance of the head teacher and the parents' association had been obtained, a meeting was held with the families of the schoolchildren in which the details of the study were explained to them, their questions were answered, and their signed authorization was requested. All participants took part in the study on a voluntary basis.Inclusion criteria were:th grade of primary school and between 8 and 13 years of age.- They were in 4, 5, and 6- Written informed consent signed by the child's parents and/or guardians.- Absence of diseases related to the metabolism or intake of nutrients, such as metabolic or endocrine diseases.- Not having a pharmacological treatment that interferes with intake, bioavailability or implies changes in nutritional needs.Exclusion criteria were:- Lack of signed authorization to take part in the study.- Failure to accept some of the conditions required to take part in the study.- Not attending school on the days on which the tests and interviews were carried out.- Having any pathology  which, due to its characteristics or severity, could contribute to modifying eating habits (and nutrient intake).The acceptance rate was roughly calculated. Having in mind the line of each school  and that the ratio of each class is usually 25, the number of potential students to be studied were 3,850. Therefore, since 1,035 students finally participated, the approximate participation rate was 27%.This study was conducted in accordance with the guidelines established in the Declaration of Helsinki, and all procedures involving human subjects were approved by the Human Research Review Committee of the Faculty of Pharmacy of the Complutense University of Madrid.All measurements  were taken in the morning in the schools themselves and according to the standards established by the World Health Organization .2).Weight and height were measured using a digital electronic scale   and a Harpenden digital stadiometer  , respectively. Measurements were taken with the schoolchildren in their underwear. Body mass index (BMI) was calculated by dividing weight (kg) by height squared (mOverweight and obesity were defined in terms of body mass index (BMI) using the reference tables of Hernández et al. , i.e., oThe plane of the waist was taken as the point midway between the inferior margin of the last rib and the crest of the ilium. Waist measurements were determined in triplicate using Holtain flexible metallic tape  held snugly around the body  and with the subject standing relaxed. An assistant helped to hold the tape on the side of the subject's body opposite to the measurer. The mean of the three measurements was used for analysis.The waist-to-height ratio (WH ratio) was calculated as an indicator of the presence of central obesity .Triceps and biceps skinfold thickness was measured on the right side in triplicate to the nearest millimeter using a Holtain skinfold caliper . All calipers were calibrated each day prior to taking measurements.The percentage body fat (%BF) was determined using the equation of Parizkova :girls: %BF = 39.032Y - 30.084boys: %BF = 32.914Y - 21.973where Y= log (sum of skin fold thickness of the biceps + triceps)An adapted physical activity daily questionnaire  which haBlood samples were taken by venipuncture after 12 h of fasting, between 8 and 9 a.m.p75 for each sex, i.e., for platelets, 335.25 × 103/μL in boys and 334 × 103/μL in girls and for leukocytes, 7.685 × 103/μL in boys and 7.3 × 103/μL in girls.The complete blood cell counts and differential counts of white blood cells in anticoagulated whole blood were determined by a Model S Coulter Counter . Inflammation was considered to be present when platelet and leukocyte values were ≥p75 according to sex .Neutrophil-to-lymphocyte ratio (NLR) dividing absolute neutrophil count by absolute lymphocyte count, monocyte-to-lymphocyte ratio (MLR) dividing the absolute monocyte count by the absolute lymphocyte count, and platelet-to-lymphocyte ratio (PLR) dividing the platelet count by the lymphocytes were calculated. Inflammation was considered to exist for these ratios ≥® hsCRP assay; Dade Behring, Milan, Italy) (CV = 3.1%). Inflammation was considered to be present when the hs-CRP value was ≥p75 according to sex (girls: 0.09 mg/dL and boys: 0.1 mg/dL).Serum high-sensitivity C-reactive protein (hs-CRP) was tested by immunonephelometry . Glucose levels were assessed by colorimetric techniques using the glucose oxidase-peroxidase method .The HOMA index was calculated from glucose and insulin values to determine the degree of existing insulin resistance in schoolchildren , 32 usinHOMA = fasting plasma glucose (mmol/L) × fasting serum insulin (mU/L)/22.5.The cutoff point for HOMA to identify individuals with insulin resistance was 3.16, which has been used in other studies for obese pediatric populations , 34.From the total population, we obtained insulin values of 895 schoolchildren, glucose of 962 , hs-CRP of 555 and complete blood count of 996.p25–p75) were calculated for all variables. Differences between means were established using the Mann–Whitney test, as the variables did not follow a normal distribution. Pearson's logistic and Spearman's monotonic correlation coefficients between data were also calculated. A univariate analysis was first performed to identify any potential predictor variables. Variables with a p-value < 0.2 according to a univariate analysis and those considered to be clinically relevant were included in the multivariate analysis to determine any independent predictors of the primary outcome variables. Also, those variables known or likely to be associated with insulin resistance were included in the logistic regression models as potential independent variables were examined in the multivariate model using logistic regression. To avoid multicollinearity, only one variable was retained in a set of variables with a significative correlation. SPSS version 25 for Mac was used to process and analyze all data.Data was tested for normality distribution according to the sex using Kolmogorov Smirnov Test. All continuous variables were not normally distributed. The median and interquartile range , we observed that within the OW/OB group, girls had higher, z-BMI, insulin and HOMA-IR values than boys. Insulin and HOMA-IR parameters were also different between sexes in the underweight/normal weight group .p = 0.005 and Rho = 0.179, p = 0.011, respectively). This relationship was not seen in girls with OW/OB or in either sex in the underweight/normal weight group. Platelet concentration correlated with BMI  and waist-to-height ratio  in boys and only with waist-to-height ratio  in girls.Leucocyte levels correlated with body fat percentage and waist-to-height ratio in boys with OW/OB  were found to be risk factors for insulin resistance (HOMA >3.16)   .Obesity represents the major risk factor for the development of insulin resistance during childhood and adolescence. The relationship between obesity and the existence of insulin resistance (and diabetes mellitus type II) has been well-described and studied previously in the literature . It has Focusing on OW/OB, previous studies have shown that increased adiposity appears to increase leukocytes within the circulation and that OW children have higher levels of circulating leukocytes than normal weight children . In our In our work, consistent with this, platelet and CRP values were higher in schoolchildren (both boys and girls) with OW/OB than in those with low/normal weight.p75) were found to be risk factors for IR, suggesting the existence of an inflammatory response in these population and boys. In this regard, meta-analysis studies have shown that an increased count of circulating leukocytes is associated with a higher risk of type II diabetes mellitus   . It is w< 0.001) . Finallyp75) did not constitute a risk factor for the appearance of IR in these children, nor was any relationship observed between the existence of IR and PLR. Relatedly, it has been reported that the NLR seems to predict inflammation better than the PLR because neutrophils play a dominant role in inflammation, as neutrophils may lead to increased endothelial permeability by releasing vasoactive and cytotoxic agents such as reactive oxygen species and digestive proteases during inflammation .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.