This study aimed to investigate the relationships between regional neural activity and multiple related indicators in patients with major depressive disorder (MDD).Forty-two patients and 42 healthy controls (HCs) were enrolled. Pearson/Spearman correlation analyses were applied to examine the associations between abnormal regional homogeneity (ReHo) and different indicators in the patients.Compared with HCs, patients with MDD had increased ReHo in the left inferior temporal gyrus (ITG) and decreased ReHo values in the left putamen, anterior cingulate cortex (ACC), and precentral gyrus. The ReHo of the left putamen was positively correlated with the PR interval, Repeatable Battery for the Assessment of Neuropsychological Status 4A, and Discriminant analysis (D), and negatively correlated with Ae (block) and Ae  in the patients. The ReHo value of the left ACC was positively correlated with the severity of depression, Stroop Color Word Test of C − 2B + 100 in reaction time, and negatively correlated with Ce (Missay) and Perseverative Responses in the patients. The ReHo of the left ITG was positively correlated with the Neuroticism scores and negatively correlated with the Lie scores in the patients.These results suggested that the decreased ReHo of the salience network might be the underpinning of cognitive impairments in patients with MDD. Major depressive disorder (MDD) is a highly prevailing and disabling mental disorder associated with high morbidity and mortality . About 2MDD is a psychological abnormality concerning mood dysregulation, including neuroendocrine changes, autonomic nervous system (ANS) disorder, immune system activation rhythm disturbances, and oxidative stress . The HamA systematic review and meta-analysis by Rock and Roiser et al. suggested that cognitive impairment was a central feature of MDD . About tNotably, There is a good deal of tools widely used in measuring cognitive function in MDD, including the Wisconsin Card sorting test WCST; , Stroop Most of the research theories on the causes of MDD comprise of psychological, biological, and social factors , but fewRegional Homogeneity (ReHo) is a voxel-based analysis, which is according to the synchronicity between the time sequences of a given voxel and its neighboring voxels. ReHo is computed by the Kendall consistency coefficient (KCC) of blood oxygen level-dependent (BOLD) time series. ReHo has a good test–retest reliability , and it Previous studies separately report that patients with MDD have a diversity of brain structural and functional connectivity abnormalities, which are associated with manifold abnormal indicators. Nonetheless, there is an inconsistency with the results on abnormal functional synchronization of brain regions at rest in patients with MDD, and the interconnection with multifarious indicators remains unclear. Therefore, we collected fasting blood samples, HAMA, HAMD, SDSS, SSRS, SCSQ, EPQ, WCST, SCWT, RBANS, eye-tracking test, ERP and resting state MRI data of MDD patients and healthy subjects for comparison, and conducted correlation analysis with abnormal ReHo value of depression. This study aims to examine the alterations of brain functional synchronization in patients with MDD and their correlations with various indicators including biological, clinical, psychological, and cognitive indicators. We hypothesized that patients with MDD would exhibit abnormal ReHo in multiple brain regions, which were associated with clinical and cognitive parameters.Diagnostic and Statistical Manual of Mental Disorders, fifth edition  data were collected by a 12-lead ECG machine. HAMA and HAMD were used to evaluate emotional states. EPQ, SDSS, SSRS, and SCSQ were applied to evaluate the psychological status of the subjects. The RBANS, SCWT, and WCST were utilized to assess cognitive function. Eye movement analysis was performed using an eye movement analyzer, and event-related brain potentials were analyzed using an evoked potentiometer.Resting-state functional magnetic resonance imaging was performed using a 3.0 T GE scanner (GE 3.0 T Signa Pioneer). During image collection, subjects were required to keep quiet and still and stay awake with closing their eyes. Foam pads were used to reduce the head movement of the subjects, and soft earplugs were used to reduce the noise of the scanner. The parameter setting of repetition time (TR)/echo time (TE) in this study is 2000/30 ms, the number of layers is 36, the number of rows and columns in the MR image layer is 64*64 matrix, the flip Angle is 90°, the field of view (FOV) is 24 cm, the thickness of the exciting layer is 4 mm, no gap, and a total of 250 volumes (500 s).3 resolution. The acquired images were bandpass filtered (0.01~0.08 Hz) and linearly detrended.Data Processing Assistant for Resting-State fMRI (DPARSF) software package  was usedWe performed ReHo analysis using the DPARSF toolbox to investigate the functional synchronization of spontaneous neural activity. ReHo describes the synchronization between a voxel and its neighboring voxel time series. The calculation formula of KCC has been stated in a previous study . In the t-tests were used to analyze the blood biochemical, ECG, psychological status, and cognitive indicators of the two groups. The significance level was set at p < 0.05.A Chi-square test was used to analyze the difference in gender of patients with MDD and HCs. Two-sample t-tests with education level, gender, age and mean framewise displacement (FD) as covariates. The significance level was corrected for multiple comparisons based on Gaussian Random Field (GRF) theory .For the voxel-based ReHo map, the differences between patients with MDD and HCs were compared by two-sample p < 0.05 was considered as the significant threshold. The Bonferroni correction was performed for several dependent or independent statistical tests that were performed simultaneously.Pearson/Spearman correlation analyses were performed to clarify the correlation between ReHo values and various indicators in the patients. p = 0.001). There were significant differences in HAMD and HAMA (p < 0.001).There was no significant difference in years of education and gender between patients with MDD and HCs . But thep = 0.006), and no statistical difference was detected in the rest parameters (p = 0.006), PR interval (p = 0.001), and QTc (p < 0.001), except for QRS width , Neuroticism , and Lie , except for Psychoticism (P) in the EPQ. There were significant statistical differences in the total scores of SDSS between patients with MDD and HCs (p < 0.001). In terms of SSS, there were significant differences in total scores (p < 0.001), objective support scores (p < 0.001), subjective support scores (p < 0.001), and utilization of support (p < 0.001) between the two groups. In terms of SCSQ, except for the total scores, there was a statistical difference between active coping (p < 0.001) and negative coping (p = 0.001).As shown in p = 0.008) in the WCST examination, whereas Categories Completed (CC), Correct Responses (RC), Errors Responses (RE), Perseverative Responses (RP), and Perseverative Responses Errors (RPE) showed no significant differences. In the RBANS test, there was no significant difference between the two groups. In eye movement examination, there were statistical differences in the Number of Eye Fixation , Responsive Search Score , and Discriminant analysis  between the two groups. In the ERP examination, there was no statistical difference between the two groups in N100 and P200, but there was a statistical difference in N200 (p = 0.038) and P300 (p = 0.012). To the reaction time of SCWT, there were significant differences in At, Bt, Ct, and C − 2B + 100 between patients with MDD and HCs , and precentral gyrus .p = 0.021), RBANS 4A , and D of eye movement examination , and negatively correlated with Ae  and Ae  of Stroop word color test  in the patients. The ReHo value of left ACC was positively correlated with HAMD score , C − 2B + 100 of Stroop word color test ; and negatively correlated with Ce (Missay) of Stroop word color test  and RP of WCST  in the patients. The ReHo value of the left precentral gyrus was positively correlated with the N of EPQ  and negatively correlated with the L of EPQ  in the patients. However, no correlation could survive the Bonferroni correction. In addition, ReHo values of the left putamen, ACC, ITG, and precentral gyrus were not correlated with scores of HAMA, blood biochemistry, SSS, SDSS, and SCSQ in the patients.As shown in This study was designed to detect the alterations of ReHo of patients with MDD and its relationship with a lot of clinical indicators. We observed notable differences between patients with MDD and HCs, with ReHo values increased in the left ITG; and decreased in the left putamen, ACC, and precentral gyrus. In the meanwhile, the ReHo values of left PG, putamen, and ACC are interconnected with multitudinous indicators in patients with MDD.The results showed that abnormal ReHo values in patients with MDD were concentrated to the left side of the brain. Previous studies on the dominant cerebral hemisphere had shown that the left hemisphere had a dominant role in coordinating the hands to carry out complex movements and processing tools, as well as using language to communicate . TherefoBrain network dysfunction is thought to underlie the cognitive and emotional abnormalities in MDD . CurrentConsistent with previous studies , the ReHAs for the correlation between ReHo values and clinical indicators in patients with MDD, abnormal ReHo values of the left putamen were positively correlated with the PR interval. Valenza G et al. demonstrated that brain regions, such as the frontal gyrus, insula, paracingulate and cingulate cortex, lateral occipital cortex, and precuneus cortex, as well as subcortical structures  were involved in the regulation of ANS and mediated cardiovascular control . PatientIn line with a previous study , the ReHDecreased ReHo values were observed in the left precentral gyrus and were positively correlated with EPQ-N scores and negatively correlated with EPQ-L scores in the patients. Reduced ReHo values of the left precentral gyrus in patients with MDD have been found in the published literature . PreviouThe ITG plays an important role in visual object recognition, decision-making, and attentional impulse . Some stAlthough there are valuable findings, there are still some limitations in this study. First, the sample size is relatively small. Second, the age of the two groups was mismatched, and mismatched age might have effects on our results although it was applied as a covariate in the analyses. Third, all correlations could not survive the Bonferroni correction although there were several correlations between abnormal ReHo and clinical and cognitive parameters in the patients. Thus, these results should be interpreted with caution. Finally, changes in ReHo values in patients with MDD after treatment were not tracked. Future studies with a view of the dynamic changes in ReHo values in patients with clinically cured MDD are needed to clarify whether the changes in ReHo values in patients with MDD are a trait phenomenon or a state marker.Overall, this study is the first to evaluate the correlations between ReHo values and numerous indicators of MDD, including biological, clinical, psychological, and cognitive indicators. We found that the ReHo values were mainly significantly correlated with the cognitive indicators of patients with MDD, suggesting that the reduced ReHo values in brain regions of the salience network might be the underpinning of cognitive impairments in patients with MDD.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 Committee of Foshan Third People’s Hospital. The patients/participants provided their written informed consent to participate in this study.YW, XL, and HY: methodology, data curation, formal analysis, and writing and editing. YO, WeW, WS, WC, YY, JL, WaW, HL, ZL, and XM: conceptualization and data curation. GX and WG: methodology, data curation, writing—review and editing, and funding acquisition. All authors contributed to the article and approved the submitted version.This study was supported by grants from the “The 14th Five-Year” Medical High-level Key Medical Specialty Development Project of Foshan (grant no. FSGSP145069), the project of Foshan Science and Technology Bureau (grant no. 2020001005608), and National Natural Science Foundation of China (grant no. 82171508).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.https://www.frontiersin.org/articles/10.3389/fpsyg.2022.1090181/full#supplementary-materialThe Supplementary material for this article can be found online at: Click here for additional data file.Click here for additional data file.


Catastrophic incidents would necessitate the intervention of multiple specializations with plastic surgery (PS) as an indispensable area of expertise. In view of PS, prognostic assessment of trauma patients should be focused on the qualitative value rather than mortality because plastic surgeons rarely handled patients’ vital signs in actual. Thus, we explored the association between the involvement of the PS department and qualitative prognoses for severe trauma patients. From November 2014 to December 2019, we enrolled total 529 trauma patients with an injury severity score (ISS) over 15 points. We set the prognostic factors that the rate of admission in intensive care unit (ICU), total or ICU duration of hospitalization, post-discharge progress and disability diagnosis which were regarded as qualitative prognoses. The analysis was performed with logistic regression analysis or regression analysis adjusted for age, sex, past medical history, cause of trauma, and frequency of operation. Among total of 529 patients, 290 patients in PS group and 239 patients in non-PS group were analyzed. In both groups, the under-65-year ages and male patients were significantly predominant. The rate of going home showed 2.082 times higher in PS group than non-PS group after adjusting for covariates, while there was no significant difference in diagnosis of disability. Meanwhile, overall prognoses were highly correlated with either higher ISS or lower Glasgow Coma Scale (GCS). In conclusion, higher severity generally affected to the severe trauma patient’s prognoses, and the PS treatment only contributes to discharge disposition to home. Given the variety of injuries found in victims of such disasters, many patients require plastic surgery (PS); a case in point is the 1999 Turkey earthquake, where more than 13% of the hospitalized needed care from plastic surgeons. In general, patients who are treated for acute trauma should subsequently be examined and managed by plastic surgeons, who will close their wounds with grafts, flaps, or by transferring adjacent tissue.In the recent decades, disasters of massive scale, such as the 1995 Oklahoma City bombing, the attack on the World Trade Center in 2001, and the 2005 London Underground bombing, have raised disaster awareness not only across health professions but also among the public in general. Such experiences have thrown light on the crucial role of surgical specialists, most particularly that of plastic surgeons.Even an isolated case of trauma calls for the collaboration of a team led by trauma surgeons and emergency medicine physicians, who work with specialists from the disciplines of neurosurgery, orthopedists, critical care, PS, and many others. As general trauma requires a multidisciplinary response, catastrophic incidents with large numbers of casualties would also necessitate the intervention of a team of medical professionals from multiple specializations, with PS as an indispensable area of expertise. This underscores the role of plastic surgeons in improving the qualitative prognoses for trauma patients.Plastic surgeons are experienced and knowledgeable in burns and trauma of soft tissue, face and extremities, the most common injuries encountered in natural disasters. Though not always life-threatening, these wounds, when not properly managed, may leave lasting functional complications.We note that existing literature on trauma mostly deals with initial assessments, with few studies discussing qualitative prognoses. This study aims to explore the association between the involvement of the PS department and qualitative prognoses for severe trauma patients, and will establish the contribution of plastic surgeons in treatment of major trauma.We designed a retrospective study to review the data for severe trauma patients (Injury Severity Score [ISS] > 15 points) in the Trauma Registry System of our hospital from November 2014 to December 2019. Following institutional guidelines, this study was approved by the Institutional Review Board of Dankook University Hospital (IRB No. 2021-04-021). Of the 2551 total patients during study period, 332 were treated by specialists from the PS department. To match the number of samples in each group, we extracted 332 patients among the 2219 patients who were not treated by the PS department (non-PS) using a simple randomized sampling method. Forty-two patients in the PS group and 93 in the non-PS group were excluded because they died or were transferred during hospitalization. After exclusion, a total of 290 patients in the PS group and 239 patients in the non-PS group were enrolled in the study  as a physiological indicator. ISS is calculated by adding the squares of the top 3 categories of the Abbreviated Injury Scale (AIS), and the score ranges from 0 to 75. Generally, the score is divided into 6 groups , with higher scores indicating a higher risk of mortality. Patients with a score over 15 points are usually classified as having severe trauma. In contrast, for the GCS, a lower score indicates a worse prognosis, with a score of 13 to 15 points indicating a mild condition, 9 to 12 points indicating a moderate condition, and a score of 3 to 8 points indicating a severe condition. In our study, in which we analyzed a group of patients with an ISS over 15 points, the patients were divided into 2 ISS groups (based on a score of 25 points) and 2 GCS groups (based on a score of 13 points). In addition, of the 6 AIS categories , we further analyzed those with facial injuries.We set the prognostic factors such as the rate of admission in the intensive care unit (ICU), total length of stay (LOS), ICU LOS, post-discharge disposition , and disability diagnosis. Among them, post-discharge disposition and disability diagnosis were regarded as qualitative prognostic indicators. Disability diagnosis was determined based on the disability certificate that was prepared either during admission or after discharge, from any department.Additional data on all trauma patients were retrieved from the Trauma Registry System of the study institution, which included age, sex, past medical history, cause of trauma, and frequency of operations. Age was divided into 2 groups according to the age of 65 years. Past medical history included hypertension, diabetes mellitus, tuberculosis, and hepatitis. The causes of trauma included traffic accidents, falls, occupational accidents, and assaults. The group classified as “etc.” included events such as slip down, suicide attempts, loss of consciousness, and unknown. The frequency of operations was divided into 3 groups .t tests, and ANOVAs were performed to establish whether covariates were associated with prognosis and severity factors. Logistic regression was conducted to compare the prognosis for PS participation and severity factors , after adjusting for age, sex, past medical history, cause of trauma, and frequency of operations. All statistical analyses were performed using IBM SPSS software version 23 . Statistical significance was set at P < .05.A chi-square test was performed to establish whether PS was associated with the covariates and severity factors. Chi-square tests, P < .005). Most of the patients in both groups had no past medical history . The causes of trauma were also similar in both groups, with traffic accidents being the most common cause (64.9% vs 54.4%), followed by falls (17.2% vs 17.6%). However, the frequency of operations was not significantly associated with PS involvement (P = .299).Of the 529 patients analyzed, 290 and 239 patients were included in the PS and Non-PS groups, respectively. The under-65-year ages (77.6% vs 66.1%) and male (82.4% vs 72.0%) were significantly predominant in both groups, and a significant difference was found between the groups (P = .391), ISS categories were significantly different between the groups. In particular, the subgroup of patients with an ISS < 25 was dominant in the PS group compared with the non-PS group . In addition, the patients in the PS group were more likely to have face involvement on the AIS than those in the non-PS group .Regarding the severity indicators between the 2 groups, while the GCS category showed no significant differences  or sex . In contrast, the involvement of the face on the AIS was significantly associated with sex (P = .037). In the analysis according to the cause of trauma, both the ISS and facial injury on the AIS were significantly different .Neither the ISS nor GCS scores were significantly different according to age (P = .004) and ICU LOS (P = .001) according to sex.The mean duration of hospitalization  was 34.2 ± 32.2 days for all 529 patients, 431 of which (81.5%) entered the ICU, with an average ICU LOS of 7.8 ± 13.2 days. These quantitative outcomes were generally not significantly associated with the covariates ; however, there were significant differences in the rate of ICU admission (P = .005) and the group with no past medical history (P = .003). However, disability diagnosis was only significantly correlated with the frequency of operation (P < .001).In the qualitative analysis of prognosis, which included discharge disposition (home) and disability diagnosis, the rate of discharge to home was significantly correlated with the under-65-year age group , an ICU LOS that was 7.872 days longer (P < .001), and a rate of ICU admission that was 11.848 times (95% CI = 4.658–30.137) that of the group with an ISS < 25. However, for the qualitative prognostic indicators, the rate of discharge to home in the PS group was 2.082 times that in the non-PS group (95% CI = 1.421–3.050), and the rate in the ISS ≥ 25 group was 0.602 times that in the ISS < 25 group (95% CI = 0.404–0.895). However, there were no significant differences according to disability diagnosis.The first model was performed to assess the relationship between the participation of the PS department and the ISS. For the quantitative prognostic indicators , a significant correlation was found according to the ISS but not between the PS and non-PS groups. The group with an ISS ≥ 25 had a total LOS that was 10.827 days longer .P = .039 for the PS group and β = 9.910, P = .002 for the GCS < 13 group) and the rate of discharge to home . In contrast, only the group with a GCS score < 13 was significantly correlated with a disability diagnosis .The last model was performed to assess whether the participation of the PS department and the GCS score were correlated. Both were significantly correlated with the total LOS , and the ICU LOS was 7.292 days shorter than that of the reference group . Additionally, PS involvement also affected the rate of discharge to home in the same subgroup .For the first model, the effect that the ISS subgroup and the involvement of the PS department had on prognosis was assessed. The LOS of the ISS < 25 subgroup was 13.510 days shorter than that of the reference group .P = .014 in the PS and GCS ≥ 13 group and β = −4.146, P = .368 in the Non-PS and GCS ≥ 13 group). In addition, the synergic effect of the combination of a higher GCS score and PS involvement was found only for the analysis of the rate of discharge to home. The patients with a GCS score ≥ 13 in the PS group were discharged to home 2.20 times more than those in the non-PS and ≥ 13 GCS group . There was no significant difference among the subgroups for any of the 3 models for the disability diagnosis analysis.For the final model, the effect that the GCS score and PS involvement had on prognosis was assessed. For the analysis of the total LOS, the group with a GCS score ≥ 13 was correlated with the duration of hospitalization only when the PS department was involved . The PTDR of countries with advanced medicine, such as the United States, the United Kingdom, and Germany, was about 15%, while it was close to 35% in Korea in 2010. However, in 2017, 5 years after the establishment of the Korea Regional Trauma Center, the PTDR was 19.9%, a significant improvement in a short period of time.According to the 2019 annual report on the Cause of Death Statistics in Korea, 53.1 subjects per 100,000 died due to trauma. Specifically, 21.2% of the working-age population (aged 15–64 years) died due to trauma; Due to their approach to reconstruction and rehabilitation, plastic surgeons are uniquely positioned to play a vital role in a subspecialty for trauma reconstruction. The improvement in outcomes when coordinated care is provided from the resuscitation to rehabilitation stage is exemplified in open lower limb fractures. A combined effort from orthopedic and plastic surgeons for early soft tissue reconstruction in such fractures is established as the gold standard of care in the United Kingdom, as described in the national guidelines set out in February 2016 by the National Institute for Health and Care Excellence. This underscores the importance of clinicians and multidisciplinary health care professionals collaborating for the patient’s journey extending beyond immediate treatment of injury. Plastic surgeons also play a crucial role in such cases, in addition to dealing with nonfatal disease.As plastic surgeons are involved in both elective and emergency surgery, they figure significantly in treating major trauma patients, who often suffer from fractured facial bones, injuries of bodily soft tissue, and injuries to the hand or neurovascular injuries. Our previous study statistically explored the contribution of plastic surgeons to trauma patient management. The study found that approximately 5% of all emergency room patients were treated by plastic surgeons, while the proportion rose to roughly 15% for trauma patients. Historically, many trauma severity scoring systems have been proposed since the 1970s, when trauma center systems began to be developed in the United States. Such systems are usually divided into anatomical, physiological, and combined systems. The ISS, which was created by Baker et al in 1974, has been considered the “gold standard” among the available anatomic injury severity indicators. Additionally, since the GCS was introduced in 1974, it has been widely used to assess patients’ physiological condition, as head and face trauma is a common cause of mortality and morbidity in patients with severe trauma. The Trauma Injury Severity Score and A Severity Characterization of Trauma are examples of combined indicators.Trauma severity scoring systems can help to improve communication among medical staff through the quantification of various and complex injuries, as well as preparing guidelines such as prioritizing severe trauma treatment. These scoring systems are also used for assessing risk adjustment, which is a fundamental premise of therapeutic performance research. Since the PS department does not handle patients’ vital signs directly and evaluating the quality of life of trauma patients is more meaningful, we focused on qualitative indicators of prognosis, such as discharge disposition and disability diagnosis. In addition, common quantitative indicators of prognosis, such as LOS and ICU admission rates, were simultaneously evaluated.Such indicators focusing on the mortality rate, however, are not able to gauge the effect of trauma care over longer periods of time, complicating the evaluation of the lasting impact of trauma among survivors. While Trauma Quality-of-Life is the only measure of long-term outcomes of trauma that incorporates a biopsychosocial perspective on patient care, it is not applied due to its inconveniently lengthy duration of measurement, lack of composite scores, and uncertain validity. Other more specific yet generalizable methods with more reliability and tested validity for all trauma populations are currently being studied.,13 The reason for the high rate of discharge to home in the PS group was that while this population usually suffered facial injuries, they could often ambulate. Therefore, it was difficult to conclude whether the patients’ satisfaction with PS was significantly high, as the rate of disability diagnosis was similar in both groups.Among the qualitative prognoses assessed, only discharge disposition had significant correlations based on the participation of the PS department. Similarly, previous studies have argued that discharge disposition is affected by age, ISS, ICU LOS, and facial injuries.,14 Nevertheless, a major strength of this study was the analysis of the characteristics and qualitative indicators of prognosis in patients with PS involvement among severe trauma patients, and these differences were recognized through a comparison with controls.One of the limitations of this study was its design as a retrospective study in a single center. A second limitation is that while we were able evaluate trauma patients’ severity indicators with the ISS and GCS, there was limited information regarding the patients’ overall condition. In addition, since the severity evaluation index for Korea has not yet been established, it is expected that more accurate data will be available only when the severity evaluation tool for those who treated in Korea is developed. A third limitation is the variation in the triage of trauma patients depending on the hospital or region. For instance, while our hospital mainly treats patients with facial bone fractures, in England, lower extremity trauma is dominant.In conclusion, this study was conducted to better understand the effect of PS on the qualitative prognoses of severe trauma patients. We found that higher trauma severity generally affected the prognoses of severe trauma patients, and that PS involvement only significantly contributes to discharge disposition to home.Conceptualization: Nam Kyu Lim.Data curation: Sungyeon Kim, Jae Hee Yoon.Formal analysis: Nam Kyu Lim, Jae Hee Yoon.Investigation: Nam Kyu Lim, Sungyeon Kim, Jae Hee Yoon, Kyung-Hwa Choi.Methodology: Nam Kyu Lim, Kyung-Hwa Choi.Project administration: Nam Kyu Lim.Resources: Nam Kyu Lim.Software: Kyung-Hwa Choi.Supervision: Nam Kyu Lim, Kyung-Hwa Choi.Validation: Nam Kyu Lim, Kyung-Hwa Choi.Visualization: Nam Kyu Lim, Kyung-Hwa Choi.Writing – original draft: Nam Kyu Lim, Jae Hee Yoon.Writing – review & editing: Nam Kyu Lim.


The COVID-19 pandemic provided an opportunity for office workers to experience work from home (WFH). The aims of this study are to investigate the prevalence rate of musculoskeletal discomfort (MSD) and the work conditions of homeworkers during WFH as well as to evaluate the association and predicted risk of ergonomic factors and MSD. A total of 232 homeworkers completed questionnaires. Chi-square test and logistic regression were used to analyze the association and prediction of work arrangements and home workstation setups and musculoskeletal outcomes. The result showed that 61.2% of homeworkers reported MSD while WFH. Because of the small living spaces in Hong Kong, 51% and 24.6% of homeworkers worked in living/dining areas and bedrooms, respectively, potentially affecting their work and personal life. Additionally, homeworkers adopted a flexible work style, but prolonged computer use while WFH. Homeworkers who used a chair without a backrest or a sofa could predict a significantly higher risk of MSD. The use of a laptop monitor posed about a 2 to 3 times higher risk of suffering from neck, upper back, and lower back discomfort than the use of a desktop monitor. These results provide valuable information to help regulators, employers, homeworkers, and designers create better WFH guidelines, work arrangements, and home settings. Remote work is not a new concept that emerged from the pandemic the novel coronavirus disease COVID-19) caused. Dyer and Shepherd 9 caused. coined tTraditionally, employees work from an office, which is the main place to perform their work duties. The home, meanwhile, is a place where one carries out personal and family activities. The images of the workplace and the home are those of two separate environments: that of the employers and that of the employees. Suitable furniture and sufficient equipment are necessary to carry out work activities at home. Many employees were not ready for a home office setting prior to the COVID-19 pandemic. Employees found it difficult to separate work activities from home activities and balance their work, and family lives during the forced WFH arrangements the pandemic necessitated ,12,13. ESome discussions have been held on the implementation of telework in the countries of the European Union. Some of these countries have developed hard laws and collective agreements, such as Poland, Germany, and Belgium. Hard laws refer to regulations, directives, and decisions that regulate employees’ right to remuneration and fair working conditions, as well as employers’ obligations to teleworkers, whereas soft laws refer to guidelines and opinions on telework arrangements. Collective bargaining between trade unions and employer organizations on telework has been implemented at the national, cross-industry, or company level ,14. Recent studies reported positive and negative outcomes of WFH in different home working arrangements and home conditions ,16,17,18The current study was conducted in Hong Kong during the fifth wave of the COVID-19 pandemic in 2022. Hong Kong has more than seven million people and is densely populated. After the rollback of social contact measures, the Hong Kong government published WFH guidelines for government employees and sent advisory notices to encourage private employers to follow WFH arrangements ,27. TherThe WFH environment in Hong Kong was generally found to be inadequate during the COVID-19 pandemic. The shortage of housing in Hong Kong has forced most families to live in tiny flats or rooms . These iA study concluded that, currently, WFH is not one of the preferred solutions for most Hong Kong employees. The study highlighted the issues with WFH in Hong Kong, such as the lack of adequate workspaces, information, and communication technology resources, and access to business documents during remote work . StudiesThe Occupational Safety and Health (Display Screen Equipment) (DSE) Regulation (Cap. 509B) was enacted in 2003 in Hong Kong. The regulation has six provisions: (1) workstation risk assessment, (2) risk assessment record, (3) reduction in risks, (4) workstation requirements, (5) health and safety training, and (6) users’ compliance with a safe system of work. It aims to protect the health and safety of employees who use DSE at work for a prolonged period . In prinThe neck, lower back, and shoulders are the three most commonly reported body regions that suffer from musculoskeletal symptoms among computer users ,33,34,35Other studies also highlighted the relationship between computer use and musculoskeletal disorders. Many studies reported high prevalence rates of MSD among office workers. Risk factors for musculoskeletal disorders were identified, including psychosocial, organizational, and physical elements in the workplace setting, such as computer usage time, working posture and movement, workplace conditions, repetitiveness, rest breaks, demographic characteristics, and computer user characteristics ,34,37,38Ardahan and Simsek  confirmeA study covering the 2015 to 2019 period concluded that more than 96% of 1701 office employees in Hong Kong spent at least six hours a day on computing operations. Meanwhile, a 2002 study found that 48% of 368 office employees spent at least four hours a day on a computer ,40. ThesSuitable furniture is essential to create a conducive work environment. Additionally, working postures should be adapted according to the design and condition of the workstation. These factors area ultimately associated with the physical well-being and musculoskeletal health of the employee ,42. ErgoA workstation should be ergonomically designed to allow users to adopt a safe and healthy working posture. In a workstation setup, the following are important: screen quality and position, keyboard and mouse design, support for forearms, work surface size, desk height, and foot support, chair back support and adjustability, body size of the user, illumination, noise management, ventilation, and air quality ,47,48. Home office ergonomics should be promoted so that homeworkers know how to set up workstations. Government bodies have published guidelines and reference information on WFH setups for creating a healthy home office environment  and haveThe purposes of the study were (1) to investigate the prevalence rate of musculoskeletal problems in computer-based homeworkers during WFH in Hong Kong, (2) to identify work arrangements and conditions of computer-based homeworkers during WFH, and (3) to evaluate the association between work arrangements and home workstation setups and the predicted risk of MSD of computer-based homeworkers during WFH. A cross-sectional study was conducted measuring the outcomes and exposures of study participants at one point in time. The target population was office workers who were required to use computers for work almost every day and who were required to WFH during the COVID-19 outbreak in Hong Kong. The study was conducted using a structured online questionnaire on an online survey platform. Data were collected using the random sampling method. The first page of the questionnaire highlighted the confidentiality statement, which aimed to protect the privacy of all participants. The collected data were anonymized. Participants were presumed to have completed the questionnaire voluntarily and to have given informed consent. The bilingual (English and Chinese) questionnaire was divided into four parts with questions on the type of home workstation, musculoskeletal health, work arrangements during WFH, and demographic information. Convenience sampling was used to access members of the population at a low cost during the COVID-19 pandemic. Emails, messages, and posts were sent to 10 Hong Kong companies and five academic societies inviting participants. Three corporations and three academic societies agreed to distribute the invitations to their members. Additionally, invitation messages and posts with links to the questionnaire were released on social networks. Participants completed the online questionnaire voluntarily. The completed questionnaires were collected between 16 May 2022 and 15 June 2022 during the fifth wave of the COVID-19 pandemic in Hong Kong. Respondents were offered the opportunity to receive supermarket vouchers in a draw if they completed the questionnaires and provided their contact details.In this study, (a) demographic characteristics, (b) work arrangements, (c) home workstation setups, and (d) MSD during WFH data were collected. (a)Demographic CharacteristicsDemographic data included gender, age, employment status, and employment position in the company. (b)Work ArrangementsWork arrangements data included the average number of days of WFH in a week, work hour changes, total hours of work on a computer on a workday, regular meal breaks, and rest break arrangements.(c)Home Workstation SetupsSurvey participants selected the workspace, furniture, and equipment type that was most representative of their WFH period during the fifth wave of the COVID-19 pandemic. Measures of home workstation setups covered five areas: workspace, desk, chair, display screen, and input devices. Based on the guidelines and the literature on the most ergonomic to the least ergonomic designs and arrangements, during the data analysis, each area was classified into two to three groups ,47,48,51(d)MSDMSD was assessed by adopting the improved version of the MSD assessment tool, which Marley and Kumar  developeStatistical analysis includes descriptive statistics and inferential statistics. Demographic characteristics were used to understand the individual profiles of the surveyed homeworkers. Homeworkers’ work arrangements, including the number of WFH months, the number of WFH days per week, working hours during WFH, hours of computing work, and meal and rest break patterns, were presented as descriptive statistics.The home workstation setups in five areas, workspace, work desk, chair, display screen, and input devices, were summarized. Further, the prevalence of work-related MSD with discomfort level details in 14 body regions per homeworker was reported in the descriptive statistics sections. In order to evaluate the association between work arrangements, home workstations, and MSD of computer-based homeworkers during WFH, inferential statistical analysis was conducted. p < 0.05 in the chi-square test were retained for the multivariate regression model. In the logistic regression analysis, the reference group was carefully selected after considering the past literature. The first group was the reference category in the analysis [p-value < 0.05 was considered statistically significant for the prediction of MSD. All data were analyzed using IBM SPSS Statistics (version 29).First, univariate analysis was conducted using the chi-square test for each independent variable in demographic characteristics, work arrangements, and home workstation setup factors. The aim was to compare the differences between no discomfort and discomfort in any body region, neck/lower back/right shoulder region, and individual body regions . Second, to reduce the number of variables in the logistic regression analysis, variables that reached the significance level of analysis . FinallyData were collected from 16 May 2022 to 15 June 2022. A total of 237 surveys were submitted online. Out of them, 232 surveys were considered valid. The criteria for validity were that the respondents were office workers, had experience with WFH during COVID-19, and had completed the entire questionnaire. Respondents who reported using a mobile phone for working at home and who were not required to work with a computer almost every day were excluded. Because of the significant decrease in COVID-19 reported cases in the fifth wave since early May 2022, the WFH arrangement also gradually changes. Thus, the research team decided to complete the data collection in a month after considering the acceptable response rate.A total of 61.2% of homeworkers self-reported discomfort for at least one body region, and 38.8% reported no discomfort. The results of the level of self-reported discomfort for 14 body regions showed that, except for the neck, the percentage of respondents with no discomfort was higher than that with discomfort . For theBody regions with MSD on the right side were reported more frequently than those on the left side. For example, participants reported 9% higher MSD for the wrist and 4.8% higher MSD for the shoulder on the right side. The right shoulder was also the third-highest reported body region for MSD. These results showed the dominant musculoskeletal issue on the right side of the body.At the time of the study, during the fifth COVID-19 wave in Hong Kong, more than 30% of the surveyed homeworkers had already worked from home for two to three months since 1 January 2022. About 40% of them were asked to work from home five days or more per week. Regarding working hours at home, 41.4% of homeworkers reported that working hours in the office and at home were almost the same, whereas 17.2% reported increased working hours at home. Most of the respondents (44.8%) reported working eight hours or more on their computers at home. The second highest group (34.5%) reported working six to eight hours. Regarding rest break arrangements, more than 50% of respondents ‘often’ or ‘always’ scheduled regular meal breaks during WFH, whereas most respondents (38.4%) did not schedule rest breaks .Regarding the setup of the workstation, most homeworkers worked in the living area (32.8%) and at the dining table (40.9%) and used the dining chair (34.1%) during WFH. The bedroom (24.6%) and the dining area (22.4%) were the second and third-highest reported workspaces. About 20% of homeworkers did not use a proper chair for WFH. They used a bench without back support, a folding chair without back support, a sofa/armchair, or a lower chair/kid-sized chair/bar tool. A total of 4.3% of participants worked on the floor/on the bed. More than 60% of homeworkers only used a laptop screen as a display screen. Comparatively, only 12.9% (9.9% and 3.0%) of homeworkers used desktop monitors as display screens. A total of 50% used laptop keyboards and an external mouse as input devices. The second highest number of participants used an external keyboard and mouse (28%) during WFH .p-value of 0.05 was used for statistical comparisons. Gender was significantly associated with MSD. Gender and body height were significantly associated with discomfort reported at the neck/lower back/right shoulder region(s). The chi-square test was used to find significant differences in self-reported MSD between groups in the bivariate analysis. A For work arrangements with six factors, including the number of WFH months, the number of WFH days per week, working hours during WFH, hours with computing work, regular meal breaks, and rest break patterns, only the arrangement of regular meal breaks was associated with MSD and neck/lower back/right shoulder discomfort .For home workstation setups with five ergonomic factors, the type of work desk, chair, and display screen used was associated with MSD . In the p-value < 0.05 was set to determine the statistical significance of the variable in the logistic regression model. The odds ratio (OR) shows the strength of the association between two variables. An OR greater than one represents the risk of exposure to MSD associated with an increased likelihood of MSD occurring [The ccurring . p-value, OR, and 95% confidence interval (CI) (lower to upper bounds). Logistic regression was performed to determine the effects of gender and body height on the probability that participants had MSD and neck/lower back/right shoulder discomfort. p = 0.015, OR = 2.330, 95% CI = 1.181–4.597) and neck/lower back/right shoulder discomfort . Female homeworkers showed a higher risk of developing MSD and neck/lower back/shoulder MSD than male homeworkers. The OR for gender was greater than one, which means that the risk of females suffering from MSD and neck/lower back/right shoulder discomfort was 2.330 times and 2.280 times higher than for males, respectively. Body height was a statistically insignificant predictor of MSD and neck/lower back/right shoulder discomfort. Logistic regression models were statistically significant for MSD (χ2(2) = 9.679, p < 0.05) and neck/lower back/right shoulder (χ2(2) = 10.73, p < 0.05) models.Gender was a statistically significant predictor of MSD . Logistic regression was performed to determine the effects of work arrangements on taking breaks and on the probability that participants had MSD and neck/lower back/right shoulder discomfort. p = 0.024, OR = 2.165, 95% CI = 1.109–4.223) but not of neck/lower back/right shoulder discomfort (p = 0.054), whereas rest breaks were a statistically insignificant predictor of both models. The arrangement of ‘sometimes/often’ with regular meal breaks compared to that of ‘never/rarely’ with regular meal breaks was significantly associated with a high risk of MSD and an OR greater than one. Homeworkers who ‘always’ arranged regular meal breaks showed an insignificant association with reduced MSD or neck/lower back/right shoulder discomfort. The arrangement of regular rest breaks was statistically insignificant to the risk of developing MSD (p = 0.157) and neck/lower/right shoulder (p = 0.172) discomfort.Regular meal breaks were a statistically significant predictor of MSD . Furthermore, the type of display screen—that is, desktop monitor(s) and laptop monitor only or desktop monitor only, was a statistically significant predictor of MSD . Logistic regression models were statistically significant for MSD (χ2(3) = 15.394, p < 0.001). The OR for both chair and display screen factors was greater than one, so homeworkers who used a laptop monitor as a display screen and a chair without a backrest/the sofa or a high/low chair were 2.635 and 2.828 times more likely to suffer from MSD, respectively.The type of chair homeworkers used—that is, chair with a backrest and chair without a backrest or sofa, lower chair, and bar stool—was a statistically significant predictor of MSD (p = 0.012), lower back (p = 0.031), and upper back (p = 0.013) discomfort, but not of right shoulder (p = 0.124) discomfort. Homeworkers using a laptop monitor as a display screen were associated with an increased likelihood of suffering from the neck (OR = 3.033), lower back (OR = 2.689), and upper back (OR = 3.105) discomfort.Logistic regression was performed to determine the effects of the chair and display screen on the probability that participants would develop neck, lower back, upper back, and right shoulder discomfort . The typGender in demographic characteristics and regular meal breaks in work arrangements were two predictors of MSD and neck/lower back/shoulder discomfort. However, the body height of homeworkers was not able to predict the risk of MSD. Females anticipated a higher risk of MSD than males. Furthermore, rest break arrangements were not able to predict the risk of MSD. The arrangement of ‘sometimes/often’ regular meal breaks could increase the risk of MSD .For home workstation setups, the display screen was a significant predictor of the risk of MSD and neck, lower back, and upper back discomfort; however, it was an insignificant predictor of right shoulder discomfort. For chair type in the home workstation setups, the only significant result was found for MSD prediction. A suitable display screen  and chair design  significantly predicted the risk of MSD .The findings indicated that there are gender differences in the risk of suffering from MSD. Female homeworkers reported a higher risk of MSD and neck/lower back/right shoulder discomfort than male homeworkers. Published scientific studies have found that women have a higher risk of musculoskeletal symptoms than men. The same results were obtained for office employees with prolonged computer use ,56,57. SAge was not a predictor of MSD in this study. A previous study found that the age of office workers was significantly associated with the intensity of shoulder pain . AnotherThe current study found an association between body height and neck/lower back/right shoulder in the chi-square test. Body height and musculoskeletal condition may have an association with the use of a fixed-height desk  or a lowThe number of months of experience with WFH and the number of days of WFH per week had no significant association with self-reported MSD. Changes in total working hours during WFH and daily hours of computing work were also insignificant in this regard. These findings contradict those of previous studies on office work, and WFH homeworkers reported a higher risk of musculoskeletal risk for prolonged computer users ,64,65,66Previous studies have shown that homeworkers have greater control over their work tasks, work schedules, office hours, and work-life balance because of the autonomous nature of working from home ,67,68,69This study also showed that regular meal breaks are a predictor of MSD. However, there was no prediction effect of rest breaks on MSD for homeworkers. Surprisingly, ‘sometimes/often’ regular meal breaks compared to ‘never/rare’ regular meal breaks predicted a higher risk of MSD. When working in the office, a fixed lunch hour is usually provided, and office workers are expected to take advantage of it. In this study, 22.9% of homeworkers never or rarely arranged a ‘regular’ meal break, indicating that when workers work from home, they adopt a flexible work style. The study results revealed that homeworkers have the benefit of scheduling meal breaks on their own instead of having a fixed meal schedule or a fixed meal time. Thus, companies should consider allowing homeworkers to set their own times for meal breaks.Approximately 40% of homeworkers did not schedule a rest break at all. Because of the nature of flexible work arrangements and of autonomy in work control for homeworkers, mini breaks can be arranged according to their wishes rather than scheduled intentionally. Furthermore, a comparison of the arrangement of rest breaks between office employees and homeworkers showed that, unlike office employees, homeworkers did not take regular rest breaks. However, the WFH study showed that increased risk of physical and psychological fatigue for those who failed to take rest breaks. Homeworkers who put in prolonged hours without taking breaks often disregarded the need for their internal recovery .Although total work hours during WFH and prolonged hours with computers did not show an association with MSD, frequent breaks are still needed to prevent physical fatigue. These findings will be helpful to human resources managers and management when considering WFH arrangements. Health education of homeworkers on taking regular breaks and on techniques to maintain a good work-life balance are of significant value in regularising WFH employees’ behaviors. Adopting a flexible work style and allowing more control are the most suitable methods to achieve this for homeworkers . Many factors have been linked to ergonomic practices and the effects of telework arrangements . OptimalWorkspace: Only 19% of homeworkers had a study room/reading room for WFH. About 25% of homeworkers worked in the bedroom. People in Hong Kong live in tiny spaces. The space per person is approximately 25% smaller than in Tokyo ,30, and Desk and chair: Among the survey participants, most conducted their work on a dining table (40.9%) and a dining chair (34.1%). In a study carried out in Japan (N = 4112), the dining table (18.6%) and dining chair (21.1%) were the second most used types of furniture for WFH. A work desk/PC desk (63.2%) and a backrest work chair (55.7%) were the most used. Homeworkers in Japan seem to have better workspaces and furniture arrangements than in Hong Kong. When comparing the prevalence rate of MSD, our study found that 50.4% of participants reported neck symptoms and 44% of lower back symptoms during WFH. Meanwhile, in a study in Japan, 72% of participants reported neck/shoulder pain, and 52% of the participants reported back pain. Both studies revealed the high rate of musculoskeletal problems among homeworkers using home furniture for work. The type of chair used was a predictor of MSD. Homeworkers who used a chair with a backrest compared to homeworkers who used a chair without a backrest, a sofa, a lower chair, or a bar stool faced a significantly lower risk of MSD. In the Code of Practice for Working with Display Screen Equipment published by the Hong Kong Labour Department , the cheRisk assessment is the first step to identifying and assessing risks to the occupational safety and health of homeworkers according to the workstation condition. The employer shall, so far as is reasonably practicable, ensure that home furniture and equipment are suitable for homeworkers. Employers are advised to develop internal reimbursement policies on home working setups and related expenses . When coDisplay screen and use of laptop computer: The findings provided useful information to compare desktop and laptop screen use. The position of the laptop and poor working posture, such as slouching and looking downwards, are correlated with reported musculoskeletal disorders . GerdingInput devices: Half of the survey participants used a laptop keyboard and external mouse (50%) as input devices, and less than 30% of workers used an external keyboard and mouse during WFH. The laptop is convenient to use in a mobile environment because it comes with a keyboard and mouse, and about 20% of homeworkers did not use an external keyboard and mouse. A study on home office equipment reported that the laptop keyboard and external mouse are ‘always’ equipped. Although an external keyboard and mouse would be the most ergonomically preferred settings, respondents ‘never’ used them at home during COVID-19 . The curIn summary, the use of different types of furniture, display screens, and input devices is relevant for computer users to adopt different working postures. A workstation is an assembly comprising the computer screen, chair, desk, printer, accessories, or other peripheral items . Office This study provides scientific evidence for reviewing occupational health regulations in Hong Kong for protecting computer users during WFH. This review will protect office workers as WFH becomes a new norm. The government can refer to the laws and collective agreements of some countries in the European Union as a reference ,14. WhenA less-than-ideal environment was found for most homeworkers in this study. Management should now understand the unfavorable conditions under which homeworkers work. The study sends a clear message to employers about providing the necessary support, such as providing suitable furniture, assessing the home workstation setups, and offering ergonomic training to workers. Regular communication between homeworkers and businesses on the WFH topic and staff surveys should be encouraged. Homeworkers working in a noisy home or homeworkers living with dependent family members require mutual understanding and schedule modification by the human resources manager ,76.Although the ergonomics program at the workstation was not evaluated to assess its usefulness for reducing the risk of MSD in homeworkers, the program is widely promoted for protecting employee health and well-being . CompaniThe study also gave clear results that inappropriate furniture and workstations pose the risk of developing musculoskeletal disorders. If their home condition is not suitable for WFH, employees should raise their concerns with their employers.Finally, interior designers and product designers can play an important role in creating a suitable home environment, suitable furniture, and suitable computing equipment. A user-oriented design of furniture and equipment that considers living and working purposes would be of great help for homeworkers.The current study focuses on the work arrangements and factors of home workstations associated with MSD. Further investigation of the practicality and cost-effectiveness of implementing the WFH ergonomics program will generate valuable findings for companies and homeworkers. For example, a cost-benefit study can be conducted on the correlation between the availability of suitable furniture and equipment, training and education of homeworkers and advice on work arrangements and breaks, and outcomes for homeworkers’ musculoskeletal health and their physical well-being. When a future study is conducted in more in-depth human research, the inclusion of an ethics committee will be considered.The study offered useful information on home workstation setups, work arrangements, and musculoskeletal conditions of homeworkers during WFH in Hong Kong. Employers are suggested to arrange flexible work styles with suitable workspaces and breaks for homeworkers and to provide health education on WFH arrangements. Most homeworkers do not have a suitable workspace or furniture according to the assessment checklist in the code of practice. This study found significant factors for predicting higher risks of MSD when using unsuitable chairs and laptop screens. It also painted a clear picture of the deficiency of workspaces and the unergonomic setup of workstations. Employers should arrange home workstation risk assessments and provide the right furniture and equipment where applicable.The limitations of the present study were identified. First, the self-reported MSD levels may not reflect pre-existing MSD conditions. Second, the possibility of aggravation of discomfort due to inappropriate workstation setups or equipment is unknown and difficult to measure objectively.


Coronary heart disease (CHD) is characterized by forming of arterial plaques composed mainly of lipids, calcium, and inflammatory cells. These plaques narrow the lumen of the coronary artery, leading to episodic or persistent angina. Atherosclerosis is not just a lipid deposition disease but an inflammatory process with a high-specificity cellular and molecular response. Anti-inflammatory treatment for CHD is a promising therapy; several recent clinical studies  provide therapeutic directions. However, bibliometric analysis data on anti-inflammatory conditions in CHD are lacking. This study aims to provide a comprehensive visual perspective on the anti-inflammatory research in CHD and will contribute to further research.All the data were collected from the Web of Science Core Collection (WoSCC) database. We used the Web of Science’s systematic tool to analyze the year of countries/regions, organizations, publications, authors, and citations. CiteSpace and VOSviewer were used to construct visual bibliometric networks to reveal the current status and emerging hotspot trends for anti-inflammatory intervention in CHD.5,818 papers published from 1990 to 2022 were included. The number of publications has been on the rise since 2003. Libby Peter is the most prolific author in the field. “Circulation” was ranked first in the number of journals. The United States has contributed the most to the number of publications. The Harvard University System is the most published organization. The top 5 clusters of keywords co-occurrence are inflammation, C-reactive protein, coronary heart disease, nonsteroidal anti-inflammatory, and myocardial infarction. The top 5 literature citation topics are chronic inflammatory diseases, cardiovascular risk; systematic review, statin therapy; high-density lipoprotein. In the past 2 years, the strongest keyword reference burst is “Nlrp3 inflammasome,” and the strongest citation burst is “Ridker PM, 2017 (95.12).”This study analyzes the research hotspots, frontiers, and development trends of anti-inflammatory applications in CHD, which is of great significance for future studies. In recent decades, inflammation has been a growing concern in atherosclerotic coronary artery disease. Meanwhile, the basic and clinical anti-inflammation studies in coronary artery disease have been widely explored . In 1986Bibliometry is the cross-science of quantitatively analyzing all knowledge carriers using mathematical and statistical methods . BibliomThe literature data was collected from the Web of Science Core Collection (WoSCC) database through the Science Citation Index Expanded (SCI-E) on August 9, 2022. Our search strategy was: TS = (antiinflammatory or anti-inflammatory or anti-inflammation) AND TS =  AND PY = (1990–2022) AND LA = (English). Only articles and reviews met the requirement and were included. The literature search was conducted by two authors independently (JL Z and CY J). After data normalization, all documents, including the complete records and cited references, were exported in pure text format. All valid data were imported to VOSviewer and CiteSpace for visual analysis. We analyze the essential characteristics of the literature. Microsoft Excel 2019 was used to predict the growth trend of publications in 2022. VOSviewer is a procedure for building and viewing bibliometric maps . It can A total of 5,818 articles focus on anti-inflammatory studies in CHD. Among the most prolific authors, Libby Peter (USA) was ranked first with 28 articles, followed by Aukrust, Pal (Norway), and Ridker, Paul M (USA), with 27 and 26 articles, respectively. Anker, Stefan D (Germany) and Tousoulis, Dimitris (Greece) were ranked fourth and fifth with 22 and 20 articles, respectively. For the details of all literature, see In terms of publications, they have now been published in over 1,458 journals. Circulation has published 98 articles on the application of anti-inflammatory in CHD. This was followed by PloS One (84 papers), Atherosclerosis (79 papers), International Journal of Cardiology (68 papers), and Current Pharmaceutical Design (65 papers). Impact Factor (IF) is a quantitative index representing a journal’s impact and general evaluation of international journals’ academic level and publication quality . AccordiThe literature on anti-inflammatory intervention in CHD has been published in 103 countries and regions. The United States leads the way, with 1,708 publications, followed by China (929 publications), Italy (496 publications), Germany (397 publications), And England (394 publications).Among the research institutions, 4,959 institutions were involved in the research field. According to the statistical analysis, Harvard University ranked first with 213 articles, followed by the University of California System (149 publications), Brigham and Women’s Hospital (144 publications), University of London (124 publications), and Institut National De La Sante Et De La Recherche Medicale Inserm (111 publications). In conclusion, the top three institutions are all research institutions in the US, where Brigham and Women’s Hospital are affiliated hospitals under Harvard Medical School. The US remains a leader in anti-inflammatory intervention for coronary heart disease, and Harvard University’s system ranks first in various organizations’ publications.The top 20 most cited references besides the clinical guidelines are shown in Big data reveals that cooperation between high-level academics or research institutions can produce more effective results . The anaIn the national cooperation analysis, there are three main trends. First, the United States and China as the central core cluster. Second, it has three obvious geographical advantages, the American continent research cluster, the research cluster of European countries, and the East Asian research cluster, and third, there are spatio-temporal change trends. Before 2014, mainly in Europe and America and other developed countries, after 2014, China and developing countries in Asia began to emerge .In the analysis of institutional cooperation, from the perspective of the frequency of institutional collaboration, the Harvard University system was dominated in the early stage. Harvard Medical School, Brigham & Women’s Hosp participated; after 2010, the University of Amsterdam, Wuhan University, and Nanjing Medical University participated in the research. China followed closely in the study, with a small-scale but systematic cluster of research institutions .In the author’s cooperation analysis, there are two apparent characteristics; Developed countries such as Europe and the United States have presented a research pattern of the cooperative cluster formed by a group of Harvard University experts led by Peter Libby and Paul M. Ridker. Developing countries, represented by Chinese experts’ concentrated research, including Qizhu Tang’s –33 and WAcademic journals serve as a vehicle for disseminating disciplinary knowledge, and the relationship between the journals cited in each discipline can reflect the flow of knowledge between journals. Journal coupling analysis refers to the reference situation where two pieces of literature are cited together , i.e., iAll journals had a total of 346,140 citations. From the total citations of the journals, Circulation ranked first with 21,817 citations, followed by NEJM. NEJM published only nine publications, but these nine references’ total citations reached 14,256 times. Lancet published 12 related articles with a total frequency of 6,285 citations. Among the latest journal impact factor, the Circulation score was 39.918, ranking second in Cardiology and Cardiovascular Medicine. The lancet score was 202.731, and the NEJM impact factor was indexed third in the Medicine disciplines, at 176.079. Although the number of publications is low, internationally renowned academic journals greatly influence co-citation .The journal coupling method can be used to analyze the relationship between journals, help journal classification and explore the internal knowledge structure of the disciplines. The larger node also shows the more significant influence of the journals. We screened journals with a minimum citation count of five times, yielding 294 publications. In the journal coupling analysis, we can find that; Early years focus on the association of traditional publishing journals. Moving on to open access journals after 2015. With an apparent trend, early years as Circulation, American Journal of Cardiology, Atherosclerosis, International Journal of Cardiology, Current Pharmaceutical Design’s multiple non-open access journals, as the leading core group. Journal coupling density maps formed at later stages, including coupled clusters with open access journals .Keywords are the values used to identify specific data items in the literature, mainly to briefly and accurately describe the article’s topic, and are primarily used for indexing or cataloging . TherefoA keyword merged coexistence network with 459 nodes and 5,024 links were constructed using CiteSpace. The parameters of the software are set as follows. Time slicing: from 1990 to 2022, 1 year per slice. Node types: reference. Selection criteria: select the top 50 levels of most occurred items from each slice. Cluster analysis was performed based on these keywordsand the results are shown in . The smathe larger the cluster size. According to the cluster results analysisthe critical clusters are coronary heart diseasec-reactive proteincardiovascular diseasemyocardial infarctionrheumatoid arthritisand gastrointestinal toxicity. According to the VOSviewer analysis of the keyword cooperative network and keyword densitythe top five core keywords are inflammationC-reactive proteincoronary heart diseasenonsteroidal antiinflammatoryand myocardial infarction CiteSpace provides burst detection that can perceive significant changes in references and keywords over a certain period . We screThe strongest keywords were “coronary heart disease (20.73),” and most recently “heart failure (18.28), nonsteroidal anti-inflammatory drug (NSAIDs) (17.51), oxidative stress (16.62), c reactive protein (12.18), and tumor necrosis factor (10.36). In addition, the Nlrp3 inflammasome in the last 2 years is a strong reference to the sudden hot spot, reflecting the current hot spot trend.Moreover, the most cited citation burst is “Ridker PM, 2017 (95.12),” ranked by citation time; the top five are Tardif JC, 2019 (52.59), Ridker PM, 2019 (37.9), Ridker PM, 2018 (22.82), Prabhu SD, 2016 (23.51) and Ridker PM, 2017 (95.12).According to the analysis of study topics, reference co-citation clustering is a superior function of CiteSpace, enabling us to study issues and hotspot trends comprehensively. Each cluster is considered to represent a hot frontier of research. Therefore, we used CiteSpace to describe the cluster view  and the The clustering results jointly cited by references give us some hints: early attention focus on the anti-inflammatory effects of statins –46, receCoronary heart disease has become the highest mortality disease in the world. The number of cardiovascular diseases in China is 290 million, containing 11 million coronary heart diseases, and morbidity trends are increasing yearly , 55. WitThe number of anti-inflammatory interventions in CHD-related studies has generally increased over the past 30 years. It shows that inflammation, as a critical pathological change during atherosclerosis progression, is attracting increasing attention from researchers . Early sIn addition, there is a class of clusters focused on rheumatoid arthritis, which is not exploring the comorbid mechanisms of RA and CHD, but instead uses anti-inflammatory drugs to treat rheumatoid arthritis. Recent studies have focused on mechanistic intervention in cardiovascular disease with the anti-inflammatory drugs allopurinol , 69 and According to the time trend analysis of the keyword strongest burst, from the late 1990s, the anti-inflammatory application of traditional indicators  was concerned. Around 2010, research focused on NSAIDs’ use in CHD, including the gastrointestinal toxicity of NSAIDs , 83. In The NLRP3 inflammasome/IL-1β signaling pathway plays an important role in the development of AS. Caspase-1, IL-1β, and IL-18, related components of the NLRP3 inflammasome signaling pathway, were highly expressed in atherosclerotic plaques, and the expression levels were higher in vulnerable plaques than in stable plaques , indicatSimilar results were shown according to the timeline of the research topic. The early 90s focused on traditional mechanisms such as tumor necrosis factor , 98 and Around 2000, attention was paid to the anti-inflammatory effects of statins in patients by regulating CRP in CHD –108. DesThe references with the strongest citation bursts revealed that recent attention has focused on the anti-inflammatory clinical studies of Canakinumab and colchicine in cardiovascular diseases , 123–126Allopurinol is commonly used as a first-line agent to lower serum uric acid and prevent acute attacks in patients with gout, and cardiovascular benefits have also been reported , 69. A pp < 0.001). The COLCOT (p = 0.02) reduction in the risk of the primary endpoint event . The results of a CT coronary angiography study  are the main population for anti-inflammatory therapy . It showNatural products as anti-inflammatory supplements. Recently, anti-inflammatory nutritional supplements, including fish oil, have attracted widespread attention. Inflammation-induced by dietary components is usually chronic and often caused by alterations in the intestinal flora . TherefoTo the best of our knowledge, this is the first study summarizing the research progress on anti-inflammatory in CHD studies by bibliometric analysis, intuitively presenting contributors, collaboration networks, research hotspots, and development prospects through visualization. This paper analyzes the research trends and hot spots of anti-inflammation in CHD. Researchers can refer to the research trends and grasp the current research hotspots. Meanwhile, researchers can adjust the study design according to the research hotspots to make the study more innovative and feasible. The future can focus on three main points to concentrate on exploration.However, it is important to consider that our study still has these limitations. First, this study only contains literature written in English and no literature in other languages, which may bias the study results. Second, we only retrieved data from the WoSCC database, which may lead to incomplete literature collection. Still, it is noteworthy that the academic community recognizes WoSCC as one of the most authoritative literature data platforms covering most studies. Third, the parameter setting and analysis methods of CiteSpace software lack systematic standards, which may lead to discrepancies in the results, so we used CiteSpace combined VOSviewer to achieve a complete visual presentation. Furthermore, articles published in the past 2 years with high impact factor publications were less cited. Therefore, some recently published papers with high quality should have been included in the analysis of highly cited articles.This study systematically analyzes the global research results of anti-inflammatory intervention for CHD over the past 30 years. It explores the already published papers’ hotspots, frontiers, and trends. Overall, the literature on anti-inflammatory intervention in coronary heart disease has increased yearly. It is expected that nearly 500 articles will be published in the whole year 2022. Further investigation into the interaction between inflammatory mechanisms may be a future research direction, and the treatment’s screening and efficacy evaluation of anti-inflammatory drugs is the focus. Our results summarize the current status of the study and are of great significance for future clinicians and researchers to condense their research directions.The original contributions presented in the study are included in the article/JH and HT designed this study. JZ and CJ collected all the articles and wrote the manuscript. CJ carried out software operation and figure drawing. XZ contributed to the final version. All authors contributed to the article and approved the submitted version.The work is supported by the National Key R&D Program of China (2019YFC1708501), the National Natural Science Foundation of China (82074316), and the scientific and technological innovation project of Foshan City in the field of traditional Chinese medicine (2020001005585) and the Fundamental Research Funds for the Central Public Welfare Research Institutes (YZ-202142 and YZ-202218).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.


Coronary artery disease (CAD) is an ischemic condition that occurs as a result of partial or complete interruption of blood flow by narrowing or complete blockage of the vessels supplying the heart, which are called coronary arteries. Our objective in this study is to investigate the RhoA/Rho-associated kinase (ROCK)-1 signaling pathway and oxidative stress in CAD patients.A total of 81 individuals aged between 40-70 years - including 45 patients  who were admitted to the Artvin State Hospital Cardiovascular Surgery Clinic and were diagnosed with CAD and 36 healthy volunteers  - participated in this study. Serum samples were tested for total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, malondialdehyde (MDA), superoxide dismutase (SOD), RhoA, and ROCK-1 values.P<0.001). Concordantly, serum SOD activity was found to be statistically significantly lower in the CAD group than in the control group (P<0.001).Serum RhoA, MDA levels, and ROCK-1 activity in the CAD group were found to be statistically significantly higher than in the control group (Inhibition of the activity of RhoA/ROCK-1 pathway would be beneficial in treating cardiovascular diseases since this pathway plays an important role in the development of these diseases. As the leading cause of deaths, CAD is responsible for approximately 48% of deaths in the world population. About 17.3 million people died due to heart attack in 2008, and the World Health Organization predicted that around 23.6 million people will die from cardiovascular disease by 2030. Although atherosclerosis is the primary factor causing CAD, many other reasons such as coronary vasospasm, coronary artery embolism, coronary artery anomalies, vasculitis, rheumatic diseases, and trauma can also lead to CAD. Atherosclerosis is a chronic inflammatory disease characterized by the formation of fibrous-fatty plaques called “atheroma” in the intimal layers of the medium and large arteries.Coronary artery disease (CAD) is an ischemic condition that occurs as a result of partial or complete interruption of blood flow by narrowing or complete blockage of the vessels supplying the heart, which are called coronary arteries.Epidemiological studies have clearly determined today the relationship between the risk of developing CAD and total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels. HDL level was shown to be inversely associated with the risk of developing CAD, because cholesterol is carried mostly by HDL. Therefore, an increase in HDL level is correlated with a decrease in CAD risk. Thus, a close relationship was determined between HDL metabolism, reverse cholesterol transport, and atherogenesis, and the course of CAD can change according to how these three different processes function. The inverse relationship between HDL and the formation of atherosclerosis is partially due to factors other than cholesterol transport+2 sensitivity of vascular smooth muscle cells (VSMCs) by inhibiting myosin phosphatase activity. The enzyme called Rho-associated kinase (ROCK) is one of the key targets of Rho proteins in the regulation of cytoskeletal changes. ROCKs are the principal mediators of RhoA activity. ROCK is a serine/threonine protein kinase with a molecular weight of about 160 kDa. There are two isoforms of the Rho-kinase enzyme, ROCK-1 and ROCK-2. Both enzymes are expressed in all cells. The RhoA/ROCK signaling pathway is shown to have important functions on vascular physiology and cardiovascular disorders. Although it is recognized as the major regulator of cell contraction, the ROCK enzyme is also known to control migration, proliferation, cell apoptosis, and gene transcription and differentiation. Therefore, ROCK activation appears to be a key factor in initiating the angiogenic process through increased endothelial permeability and migration,9. The RhoA/ROCK-1 signaling pathway is known to be associated with several pathological conditions including hypertension, atherosclerosis, stroke ischemia-reperfusion injury, and heart failure,11.RhoA is a small, guanosine-5’-triphosphate binding protein, bound to the plasma membrane. It is known that Rho regulates the Ca. Oxidative and antioxidative parameters play an important role in the pathophysiology of atherosclerosis and atherosclerosis-induced CAD. Malondialdehyde (MDA) is one of the important parameters of lipid peroxidation. Oxidative stress increases in correlation with the increase in MDA levels in the development of CAD. Oxidative stress can increase reactive oxygen species (ROS) reducing the formation of antioxidant defenses. The reduction of activity of antioxidant enzymes such as superoxide dismutase (SOD) facilitates the oxidative aggression to the cells, especially in subjects with CAD. Some authors have demonstrated that in the early stages of CAD, SOD level increased to protect and prevent lipid peroxidation whereas they decreased significantly with the worsening of the disease.Oxidative stress has an important role in the initiation and progression of CAD. And oxidative stress occurs as a result of excessive free oxygen radical production and inadequate antioxidant defense against oxidant radicalsThe RhoA/ROCK-1 pathway plays an important role in various cellular events involved in the pathogenesis of cardiovascular diseases as well as in the development of the effects of many vasoactive substances. Our objective in this study is to investigate the RhoA/ROCK-1 signaling pathway and oxidative stress in CAD patients.Ethical approval for the study was obtained from the Ethics Committee of Non-Invasive Clinical Research, Faculty of Medicine of Uşak University, in the session with date 12.12.2018 and number 2018/16, and written consent was obtained from the provincial health directorate of Artvin. The study was conducted in accordance with the guidelines proposed in the Declaration of Helsinki and was approved by the local ethics committee. Written informed consent was obtained from all patients. A total of 81 individuals aged between 40-70 years - including 45 patients  who were admitted to the Artvin State Hospital Cardiovascular Surgery Clinic and were diagnosed with CAD and 36 healthy volunteers  - participated in this study. The volunteers were questioned about atherosclerosis risk factors such as hypertension, diabetes, heart disease, family history of early myocardial infarction, and smoking, and those who meet these criteria were eliminated; ultimately, 36 individuals were included. However, chronic renal failure, chronic liver disease, thyroid diseases, an active infection, cancer history, and chronic inflammatory disease history were determined as exclusion criteria for both groups. All the participants were non-smokers and non-drinkers.Venous blood samples were taken after 10-12 hours of fasting into tubes with no anticoagulants for biochemical tests. These samples were centrifuged at 4000 rpm for 10 minutes after coagulation was completed to obtain serum samples. After centrifugation, serum samples were tested for TC, TG, LDL, and HDL values. After the required immediate routine tests, the remaining serum samples were stored at -80 ºC until testing for MDA, SOD, RhoA, and ROCK-1.RhoA and ROCK levels of the study groups were measured by the ELISA method, using ELISA test kits . The ELISA method is based on investigating activity of the enzyme linked to the antibody, on the basis of antigen-antibody relationship. The principle is based on showing the antigen-antibody complex formed as a result of the reaction between the antigen or antibody labeled and the enzyme and free antigen or antibody, in the presence of an enzyme-specific substrate. RhoA results are presented in pg/ml. ROCK-1 results are presented in ng/ml. In the measurement of serum SOD activity, a color is formed when the superoxide radical produced by the xanthine-xanthine oxidase system reduces the nitroblue tetrazolium (NBT). The resulting color change, that is the reduction of NBT by superoxide radical, ends with the formation of blue colored formazan, giving the maximal absorbance, and the change is determined by spectrophotometer at 560 nm. The results are presented in U/ml.SOD enzyme activity was measured using the method developed by Sun et al.Measurement of Malondialdehyde Levels The principle of the test is based on measuring the intensity of the pink-red color spectrophotometrically at 532 nm wavelength; where the color was displayed by the compound formed by MDA with thiobarbituric acid in hot environment, and MDA is one of the end products produced in the peroxidation of polyunsaturated fatty acids (PUFAs). The results are presented in nmol/ml.MDA levels were measured using the method developed by Ohkawa et al.t-test were used for comparing more than two variables. For intragroup significance, Tukey’s least significance difference test was used for variables with homogenous variances, and Mann-Whitney U test for non-homogeneous variables. For the correlation analysis of the data, Pearson’s correlation analysis was performed for the data with normal distribution, and Spearman’s correlation analysis for the data with non-normal distribution. P<0.05 was determined as the threshold for statistical significance.Statistical analyses were performed using the IBM Corp. Released 2013, IBM SPSS Statistics for Windows, Version 22.0, Armonk, NY: IBM Corp. Numerical data were given as mean ± standard deviation. Kolmogorov-Smirnov test was used for normal distribution of data. One-way analysis of variance and independent sample Forty-five patients with CAD were included in our study . Thirty-six healthy volunteers were included in the control group .P>0.05). TC, TG, and LDL levels were found to be statistically significantly higher in the CAD group than in the control group (P<0.001). However, serum HDL levels were statistically significantly lower in the CAD group than in the control group (P<0.001). In our study, serum RhoA levels in the CAD group were found to be statistically significantly higher than in the control group (P<0.001) (P<0.001) (P<0.001). Serum activity of SOD, one of the antioxidant enzymes, is shown in P<0.001).The demographic and clinical characteristics of the CAD group and the healthy control group are shown in P<0.001) . ConcordP<0.001) . Serum MP<0.001) and between RhoA and MDA , and a significant negative correlation between RhoA and SOD . A significant positive correlation was observed between ROCK-1 and MDA  and between ROCK-1 and LDL ; and a significant negative correlation  was observed between ROCK-1 and SOD.Correlation analysis results of our study data are presented in P<0.001) and between MDA and LDL . A significant negative correlation was observed between MDA and SOD  and between MDA and HDL .A significant positive correlation was found between MDA and TG . And finally, a significant negative correlation was determined between SOD and TG  and between SOD and LDL .SOD and HDL displayed a significant positive correlation  reductase inhibitors, were also reported to have inhibitory effects on the RhoA/ROCK signaling pathway. MDA, a carbonyl group produced during lipid peroxidation, is widely used in determining oxidative stress. Increased MDA levels in CAD were demonstrated in several clinical studies,25. It was reported in the literature that serum MDA level was a diagnostic parameter in patients with CAD and that there was a strong relation between MDA levels, LDL oxidation, and the development of coronary lesions.Free radicals are molecules containing unpaired electrons generated through biochemical redox reactions that occur during cell metabolism. It is well known that oxidative stress and free radicals have important roles in the process of developing cardiovascular diseases,28. The accumulation of damaged DNA can trigger cell apoptosis or cause permanent cell cycle arrest leading to vascular cell senescence. Vascular cell senescence promotes impaired VSMC proliferation.In our study, significantly increased MDA and LDL levels and decreased SOD levels were also observed in the CAD group. Our findings are compatible with the results in the literature. A strong positive correlation was found between MDA and LDL whereas a negative correlation was found between MDA and SOD. In addition, an increase in MDA levels showed a positive correlation with RhoA and ROCK levels. It was reported in the literature that excessive ROS production can cause deoxyribonucleic acid (DNA) damage and DNA strand breaks. However, studies indicated that the progression of atherosclerotic plaques were induced by oxidative stress, increasing DNA breaks. In their study on CAD patients, Gupta et al. reported decreased SOD activities. In our study, SOD levels were also decreased in CAD patients compared to the healthy control group.Increased production of free radicals is counterbalanced by endogenous antioxidants. SOD is one of the most potent enzymatic antioxidants inhibiting free radical formation. Increased SOD levels play a protective role against acute or chronic oxidative damage, including atherosclerosis. But, this increase in SOD levels is provided by foods containing exogenous antioxidants.When our study groups were examined in terms of dyslipidemia, there was a significant increase in serum TG, TC, and LDL levels in the CAD group, and a decrease in HDL levels was also found. HDL is involved in the reverse cholesterol transport from tissues. It also has antioxidant, anti-inflammatory, and antiapoptotic effects. By virtue of these properties, HDL contributes to the prevention of atherosclerosis by reducing the adverse effects of oxidative stress involved in the initiation and development of this disease. Increased levels of excessive free radical activity in this region due to decreased antioxidant levels or impaired endothelial function will make PUFAs vulnerable for free radical attacks and initiate a peroxidation chain reaction on LDL. In this case, LDL is changed by modification mechanisms such as glycosylation, oxidation, and acetylation, acquiring atherogenic properties,35. Dyslipidemia in our CAD group may have triggered the formation of oxidative stress by causing an increase in MDA levels and a decrease in SOD levels.LDL accounts for approximately 70% of plasma cholesterol, providing cholesterol to peripheral tissues. The PUFAs contained in LDL are vulnerable to free radical attacks. Against this oxidative attack, LDL tries to prevent the oxidation of PUFAs by means of vitamin E, which is a powerful antioxidant that LDL containsOxidative stress is an important factor in the initiation and progression of CAD, and increased free radicals due to oxidative stress may cause the activation of the RhoA/ROCK signaling pathway.Our findings suggest that the RhoA/ROCK signaling pathway is important in the pathogenesis of CAD, so the inhibition of the activity of RhoA/ROCK-1 pathway would be beneficial in treating cardiovascular diseases.