Sleep duration, sleep quality and circadian rhythm disruption indicated by sleep chronotype are associated with type 2 diabetes. Sleep involves multiple dimensions that are closely interrelated. However, the sleep patterns of the population, and whether these sleep patterns are significantly associated with type 2 diabetes, are unknown when considering more sleep dimensions. Our objective was to explore the latent classes of sleep patterns in the population and identify sleep patterns associated with type 2 diabetes. Latent class analysis was used to explore the best latent classes of sleep patterns based on eleven sleep dimensions of the study population. Logistic regression was used to identify sleep patterns associated with type 2 diabetes. A total of 1200 participants were included in the study. There were three classes of sleep patterns in the study population: “circadian disruption with daytime dysfunction” (class 1), “poor sleep status with daytime sleepiness” (class 2), and “favorable sleep status” (class 3). After controlling for all confounding factors, people in class 2 have significantly higher prevalence of type 2 diabetes than those in class 3 . Sleep problems have aggregated characteristics. People with sleep patterns involving more or worse sleep problems have higher significantly prevalence of T2DM. Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia. There were 537 million adults aged 20–79 years with diabetes worldwide in 2021, of which type 2 diabetes mellitus (T2DM) accounted for more than 90% . AlthougMultiple behavioral and lifestyle factors, such as sleep, physical activity and eating behavior, have been confirmed to be associated with T2DM ,7,8,9, aSleep is a vital physiological process involved in regulating many physiological functions of the human body . Most exLatent class analysis (LCA) is a statistical method used to identify populations with similar characteristics based on the selection propensity of individuals in different manifest variables. An advantage of this approach is that the grouping originates from data; therefore, the categories are not predefined and are not limited by current conceptual frameworks . The claWe hypothesized that through a comprehensive analysis of people’s sleep dimensions, accurate classification of their sleep patterns could be made, and the prevalence of T2DM is closely associated with sleep patterns involving more or worse sleep problems and poor sleep behaviors. This study aims to (1) comprehensively consider various aspects of sleep, including subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, daytime dysfunction, daytime sleepiness, bedtime procrastination, sleep chronotype, SJL, and use of sleep medication, and explore the latent classes of sleep patterns based on LCA; and (2) identify the sleep patterns associated with T2DM.This was a cross-sectional study conducted between March and July 2022 in Xuzhou, Jiangsu Province, China. The participants were recruited while receiving a conventional physical at the community hospital, and a face-to-face questionnaire survey was administered. The inclusion criteria were as follows: aged 18 years or older and volunteered to participate in the study. Meanwhile, participants who were diagnosed with type 1 diabetes, gestational diabetes, or other specific types of diabetes, who were in a state of secondary hyperglycemia due to diseases (except diabetes) or medications, or who were unable to cooperate in completing the questionnaire, were excluded from the study.Participants were selected using a multistage random sampling method. Stage 1: first, all administrative districts of Xuzhou City were numbered, and three administrative districts were randomly selected from them by drawing lots. Stage 2: two communities were randomly selected by drawing lots from the communities under the jurisdiction of each district, yielding a total of six communities as the basic sampling unit. Stage 3: a convenience sampling method was used to recruit more than 200 participants from each community who met the inclusion criteria.The Chinese version of the Pittsburgh Sleep Quality Index (PSQI) was used to measure seven domains of sleep, namely, subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, use of sleep medication and daytime dysfunction, with a Cronbach’s alpha coefficient of 0.84 . There aThe Chinese version of the Epworth sleepiness scale (ESS) was used to measure daytime sleepiness, with a Cronbach’s alpha coefficient of 0.81 . The queThe Chinese version of the Bedtime Procrastination Scale (BPS) was used to measure the propensity of individuals to delay bedtime when they can freely choose, that is, bedtime procrastination, and the Cronbach’s alpha coefficient was 0.91 . The scawww.thewep.org (accessed on 5 October 2022). According to a previous study, participants were divided into morning and night sleep chronotypes using the 75th percentile of MSFsc as the cutoff point [The Chinese version of the Munich Chronotype Questionnaire (MCTQ), performed in collaboration with the original authors of the MCTQ, measures sleep chronotype and SJL . The intff point .Participants who had a fasting blood glucose ≥ 7.0 mmol/L, or 2 h postprandial blood glucose ≥ 11.1 mmol/L, or HbA1c ≥ 6.5%, or self-reported previous diagnosis of diabetes by a healthcare professional were defined as having diabetes . PatientSelf-designed questions and questionnaires with good reliability and validity were used to collect information, namely, sociodemographic characteristics , behavioral lifestyle , personal medical history , mental psychological state , and family history of diabetes. Because all the respondents had established electronic medical records at community hospitals, information on personal medical history and diabetes was obtained from the community hospital database.The Chinese version of the International Physical Activity Questionnaire—Short Form (IPAQ-SF) has good reliability and validity for measuring physical activity levels . The scaThe Chinese version of the Dutch Eating Behavior Questionnaire (DEBQ) is a 33-item questionnaire measuring eating behavior, with each item rated on a 5-point Likert scale . The queThe Chinese version of the Depression, Anxiety and Stress Scale-21 (DASS-21) consists of 21 items with three subscales consisting of 7 items in each subscale to measure depression, anxiety, and stress separately . The CroThe neuroticism subscale from the brief version of the Chinese Big Five Personality Inventory (CBF-PI-B) developed by Wang et al. was used to measure the level of neuroticism . The Crot tests, chi-square tests, or nonparametric tests were used for comparisons between groups, followed by post hoc tests.SPSS  was used for all statistical tests except the LCA. Continuous and categorical variables were expressed as the means ± standard deviations (SDs) and numbers (percentages), respectively. The p value of LMR and BLRT indicated a better fit of the model compared with a model with one less class [Mplus  was used to conduct LCA. We examined the model fit indices: Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), sample-size-adjusted BIC (aBIC), entropy, mean class assignment probabilities, the Vuong-Lo-Mendell-Rubin (LMR) test, and the bootstrap likelihood ratio test (BLRT). Lower AIC, BIC, and aBIC values, higher entropy values, and mean class assignment probabilities indicated a better fit . A signiss class . All indp values of <0.05 were considered statistically significant.We used binary logistic regression to estimate the relationship between latent classes of sleep patterns and T2DM and calculated the odds ratios (ORs) and 95% confidence intervals (95% CIs). Potential confounding factors were selected based on the results of the univariate analyses. The missing data were processed by SPSS missing value analysis. All statistical tests were two-sided, and A total of 1253 participants were recruited, among which 21 individuals failed to meet the inclusion criteria and 32 individuals failed to complete the questionnaire. A total of 1200 participants were included. The time required for participants to complete the face-to-face questionnaire survey ranged from 40 to 60 min. Of the 1200 participants included, aged 18 to 85 years, the mean (SD) age was 45.2 (14.8) years, 49.7% of the participants were female, and all participants were ethnic Han Chinese. There were 198 participants with T2DM, accounting for 16.5% of the total.Compared with people without diabetes, those with diabetes were more likely to be older and to have a higher BMI and waist circumference, lower levels of education, lower annual household income, lower levels of physical activity, higher levels of stress and anxiety, and higher likelihood of restrained and emotional eating; more likely to suffer from hypertension, dyslipidemia, coronary heart disease, stroke, thyroid disease and osteoporosis; and more likely to be men, smokers, married and have a family history of diabetes. No significant differences were found between the two groups in the proportion of drinkers, external eating behaviors, levels of depression and neuroticism, or the prevalence of arthritis and cancer .p value of LMR and BLRT was not significant in the 4-class model, and the entropy value was highest in the 3-class model. Considering these indicators holistically, we finally chose a 3-class model. The mean class assignment probability of each class was 0.89, 0.95, and 0.93 .Our study considered multiple aspects of sleep and constructed three latent classes of sleep patterns using LCA, namely, “circadian disruption with daytime dysfunction”, “poor sleep status with daytime sleepiness”, and “favorable sleep status”. In addition, we found that “poor sleep status with daytime sleepiness” was significantly associated with T2DM.We found that there were aggregated characteristics of sleep problems. For example, poor sleep quality, low sleep efficiency, insufficient sleep duration, difficulty falling asleep and daytime sleepiness often coexisted, and this was highly similar to the findings of Chen et al. . HoweverThe sleep pattern of “poor sleep status with daytime sleepiness” is predominantly distributed in older adults, and the involved sleep problems are highly consistent with a series of physiological sleep changes in the normal aging process . In addiThe sleep pattern of “circadian disruption with daytime dysfunction” was mainly found in the younger population. Young adults tend to delay bedtime due to work stress and excessive use of smartphones, causing circadian disruption and daytime dysfunction , followeIn this study, we used LCA to analyze the complex associations between sleep dimensions, and we categorized participants into three classes of sleep patterns according to these associations. In addition, we considered confounding factors, such as sociodemographic, behavioral lifestyle, chronic diseases and mental psychological state, and found that “poor sleep status with daytime sleepiness” was significantly associated with T2DM. This explained the real-world relationship between sleep and T2DM accurately and comprehensively and may serve as a practical guide. Nevertheless, there were several limitations in our study. First, the study was unable to determine a causal relationship between sleep patterns and T2DM due to its cross-sectional design; however, the significant correlation found in our study provides a basis for future prospective analyses of this relationship. Second, since this was a large sample survey, all sleep dimensions were measured by subjective self-reports. Hence, although the measurement tools had good reliability and validity, bias may exist. Finally, because the survey was conducted in Xuzhou city, Jiangsu Province, China, and all participants were ethnic Han Chinese, extrapolation of the findings to other regions and ethnic groups is potentially limited.In the future, objective sleep measures can be used to investigate latent classes of sleep patterns in multicenter populations based on LCA, and the causal relationship between each sleep pattern and T2DM can be prospectively analyzed. Future research may be used to inform intervention programs and validate the effects of unhealthy sleep patterns on T2DM. The findings of our study suggest that health care institutions, especially those involved in primary care, should pay attention to the impact of sleep on health and routinely assess the characteristics of sleep patterns of residents. Particular attention should be given to the population exhibiting “poor sleep status with daytime sleepiness”, and early intervention strategies should be formulated. Healthy sleep patterns should be promoted and publicized to improve the overall sleep health of all populations.Aggregated features exist between multiple sleep problems. Sleep patterns with sleep problems such as poor subjective sleep quality and sleep efficiency, long sleep latency, short sleep duration, severe sleep disturbance and daytime sleepiness, and moderate daytime dysfunction were significantly associated with T2DM. The causal relationship should be further verified by longitudinal studies in the future.


To track the clinical outcomes in patients who initially presented with tumefactive demyelinating lesions (TDLs), we summarized the clinical characteristics of various etiologies, and identified possible relapse risk factors for TDLs.Between 2001 and 2021, 116 patients initially presented with TDLs in our hospital were retrospectively evaluated. Patients were followed for relapse and clinical outcomes, and grouped according to various etiologies. Demographic information, clinical data, imaging data, and laboratory results of patients were obtained and analyzed. The risk factors of relapse were analyzed by the Log-Rank test and the Cox proportional hazard model in multivariate analysis.P<0.05). And diffuse infiltrative lesions , multiple lesions  and infratentorial involvement  may be independent risk factors for recurrence. Relapse free survival was assessed to be 36 months.During a median follow-up period of 72 months, 33 patients were diagnosed with multiple sclerosis (MS), 6 patients with Balo, 6 patients with neuromyelitis optica spectrum disorders (NMOSD), 10 patients with myelin oligodendrocyte glycoprotein antibody-associated demyelination (MOGAD), 1 patient with acute disseminated encephalomyelitis (ADEM), and the remaining 60 patients still have no clear etiology. These individuals with an unknown etiology were categorized independently and placed to the other etiology group. In the other etiology group, 13 patients had recurrent demyelinating phases, while 47 patients did not suffer any more clinical events. Approximately 46.6% of TDLs had relapses which were associated with multiple functional system involvement, first-phase Expanded Disability Status Scale score, lesions morphology, number of lesions, and lesions location (In clinical practice, around 46.6% of TDLs relapsed, with the MS group showing the highest recurrence rate, and lesions location, diffuse infiltrative lesions, and multiple lesions might be independent risk factors for relapse. Nevertheless, despite extensive diagnostic work and long-term follow-up, the etiology of TDLs in some patients was still unclear. And these patients tend to have monophase course and a low rate of relapse. Tumefactive demyelinating lesions (TDLs) are rare consequences of central nervous system idiopathic inflammatory demyelinating diseases (CNS-IIDD), which can be the initial presentation in various pathological entities with overlapping clinical and radiographic features . Most paRelapse is a crucial and controversial clinical aspect of demyelinating diseases, and it not only accelerates the course of the patient’s condition but also places a significant psychological load on them . IdentifTherefore, the primary purpose of our study was to assess the long-term outcomes of TDLs with varied etiologies by clinical follow-up and to identify possible relapse risk factors.The study collected and analyzed the clinical follow-up data of patients with TDLs diagnosed in the Sixth Medical Center of PLA General Hospital from January 2001 to December 2021. Inclusion criteria were (1): pathological confirmation or clinical confirmation according to the Chinese TDLs diagnostic criteria . (2) WitHistopathology was available in 72 cases. All biopsies were conducted between January 2001 and December 2021 and at least one board-certified neuropathologist assessed the material in each case. In most cases, it was impossible to pinpoint the precise indication for a brain biopsy because the majority of biopsy specimens were obtained retroactively, several years after the date of the biopsy, and clinical follow-up was not carried out by the clinician who was initially involved in the patient’s consultation at the time of the biopsy.Two neurologists with more than 12 years of experience categorized the TDLs patients jointly and reached a consensus to divide into six etiology-based categories: MS, NMOSD, MOGAD, Balo, ADEM, and the other etiology . PatientPatients were followed up by outpatient, telephone, or hospitalization. Recurrence was the end point of follow-up. Relapse free survival (RFS) was the time from onset to recurrence, and the time of death from other diseases or no recurrence at the end of follow-up was the end value.p < 0.05 as the threshold of statistical significance.The measurement data that conformed to normal distribution were expressed as mean ± standard deviation (X ± S), whereas those that skewed distribution were expressed as median (quartile). And the counting data was expressed by percentage. The association between each variable and the outcome was evaluated using the Kaplan Meier method and the log rank test for survival analysis. The statistically significant log rank test factors were then used as variables in the Cox proportional hazards model for multivariate analysis to figure out the final influencing factors. We used a The average age at presentation was 37.3 ± 14.1 years (range 5–73 years), and there was no significant difference in gender . The median course of disease and median EDSS score at presentation were 2 months (range 1–72 months) and 3 points, respectively. Fewer patients were current or previous smokers (13.8%) or alcoholics (7.8%).Initial symptoms and clinical symptoms of patients were summarized, with headache , limb numbness  and hemiplegia  being most common, followed by dysarthria , visual impairment , epilepsy , mental symptoms , cognitive impairment , aphasia , dizziness , and dysuria . According to the EDSS score, the function of the nervous system was classified as pyramidal, cerebellar, brainstem, sensory, bowel & bladder, visual, cerebral, and others, and 80 patients (69.0%) had multisystem functional impairment in our study.2O, which rose in 23 participants; the median white blood cell (WBC) count in CSF was 2×106/L, which increased in 13 cases; and the median CSF protein concentration was 368mg/L, which increased in 23 cases. The median glucose level was 3.5 mmol/L, and 9 patients were abnormal; the median chloride level was (122.2 ± 4.5) mmol/L, and 23 cases were abnormal. 19 out of 70 patients were OCB positive. On the basis of clinical suspicion of NMOSD, AQP4 antibody serology was done on 78 participants and 5 of them were positive. 10 of the 30 participants who underwent MOG antibody serology obtained a positive result and were subsequently diagnosed with MOGAD.The median lumbar puncture pressure of cerebrospinal fluid (CSF) in 70 patients was 165mmHOf the 72 biopsied patients, 47 were in the other etiology group, 16 in the MS group, 5 in the MOGAD group, 2 in the Balo group, 1 in the ADEM group, and 1 in the NMOSD group. The histopathological examination of the patient’s brain biopsy tissue revealed that MS, NMOSD, MOGAD, and ADEM all exhibit demyelination with inflammatory cell infiltration, and some patients with sever CNS inflammation could demonstrate acute axonal injury. Specific antibodies like AQP4-IgG and MOG-IgG are necessary for the distinction of these illnesses. Among the brain tissues of the 2 Balo patients we collected, a typical laminar pattern between demyelination and myelin preservation area was seen in one patient, and the other patient had a histopathological presentation similar to that of MS Figure 1The MRI of the brain revealed that 54 patients (46.5%) had a single lesion, while the remaining 62 patients (53.4%) had multiple lesions. And our cohort had 73 patients with infiltrative lesions, 28 ring-shaped, 4 megacystic, and 11 Balo-like lesions. Localization: cortex/subcortical in 88 cases, periventricular white matter in 72 cases, deep gray matter in 46 cases, and infratentorial in 41 cases. And the spinal cord MRI was available in 111/116 patients, and 15/111 patients had spinal cord lesions . On T2WI, the median size of cerebral lesions was 4 cm (range: 2cm-11.4cm).During the 72-month (range: 6–228months) follow-up period, six patients were diagnosed with NMOSD Figure 2P > 0.05). But there were significantly more male patients in the MS group compared to other etiological categories (P = 0.033). In addition, we classified the lesions as cortical/subcortical, paraventricular, deep gray matter, infratentorial, and spinal cord, and compared the number of lesions. Multiple lesions were more prevalent in MS, NMOSD, and Balo groups than in the other etiology group (P < 0.001). And patients with MS, NMOSD, and MOGAD were more likely to have spinal cord involvement compared to other etiological groups (P = 0.016).We compared the clinical characteristics of MS, NMOSD, MOGAD, Balo, and other etiology groups. There was no statistically significant difference in age, course of disease, or EDSS score at initial onset across the various etiology groups (P < 0.001).54 (46.6%) of the 116 patients suffered a second attack, with a median interval of 36 months between the first and second attacks (range: 1–108 months). MS group had the highest recurrence rate (84.8%), followed by NMOSD (83.3%) and MOGAD (80.0%). The median recurrence period was 7 months (range: 3-108 months) in the idiopathic group, where 13 patients (21.7%) experienced relapse. The recurrence of the other etiology group did not match the diagnostic criteria for 2017 McDonald’s MS and other demyelinating etiologies and was defined by recurrence solely at the initial lesion, solitary lesion, and absence of additional intracranial lesions. In comparison to the MS, MOGAD, and NMOSD groups, the other etiology group and the Balo group had lower rates of relapse, and there was a statistically significant difference between these groups (P > 0.05). But the clinical symptoms of multiple system function involvement, a higher EDSS score (EDSS ≥ 4), multiple lesions, diffuse infiltrative lesions, infratentorial involvement, and spinal cord involvement were associated with an increased risk of recurrence, according to the log-rank test (P < 0.05) , size, laboratory examination, and biopsy between recurrent patients and non-recurrent patients , multiple lesions , and infratentorial involvement  may be independent risk factors for TDLs recurrence , and the consent of patients was obtained by the treating physician.JL, CS and QW designed the original research and revised the paper. XL, XM analyzed the data and wrote the manuscript. All authors contributed to the article and approved the submitted version.This work is supported by the PLA General Hospital Big Data Project (2019MBD-047).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.


Vitiligo is a common depigmentation disorder of an unknown origin characterized by the selective loss of melanocytes, resulting in typical white macules and patches. However, vitiligo is now recognized as more than just a skin disease, what a dermatologist observes as a white spot of skin is just the “tip of the iceberg” of the condition. We attempt to clarify the classification of comorbidities associated with vitiligo from various reviews and reports, and describe their possible pathogenesis. In conclusion, the literature provides evidence of an association between vitiligo and ocular and auditory abnormalities, autoimmune disorders, other dermatological diseases, metabolic syndrome and related disorders, and psychological diseases. These associations highlight the importance of a multidisciplinary approach in managing vitiligo patients. GlobWe searched the electronic database PubMed, Web of Science, Embase and Cochrane Library from inception to April 30, 2022 and analyzed the relevant literature related to vitiligo and associated comorbidities, including case–control, cross-sectional, and cohort studies, as well as systematic reviews and meta-analyses. A combination of medical subject headings (MeSH) and free terms were used in the search. The MeSH terms included “vitiligo,” “eye diseases,” “ear diseases,” “autoimmune diseases,” “metabolic syndrome” and “mental disorders.”2.Epidermal melanocyte damage is one of the causes of vitiligo. However, in addition to the skin, melanin and melanocytes are also present in the eyes, cochlea, leptomeninges, heart, and even inhospitable environments, such as adipose tissue . Therefo2.1.Melanocytes are found in both the retinal pigment epithelium (RPE) and the choroid of the eye, with the RPE originating from the neural ectoderm and the latter from the neural crest . MelanocPrabha et al.  found vaAccording to one study by Ma et al. , patient2.2.In the auditory system, melanocytes are distributed in the stria vascularis and spiral ligament of the cochlea, which are required for maintaining the endocochlear electrical potentials that play an essential role in normal hearing . MelaninAccordingly, numerous studies have examined the relationship between vitiligo and hearing impairment but with varying results –28. A reBased on the findings of the above studies, we recommend regular evaluation of patients with vitiligo to detect ocular and auditory abnormalities and to treat these conditions in the early stage. Melanocyte destruction in patients with vitiligo can affect melanocytes that share a common embryological origin, ultimately affecting the function of the organs in which they reside. However, small sample sizes and heterogeneous definitions have led to conflicting results between these studies. Further large-scale studies are required to clarify the disease burden and the associated pathogenesis of ocular and auditory abnormalities in patients with vitiligo.2.3.Vogt–Koyanagi–Harada syndrome (VKH) is an autoimmune disease that mainly affects melanocyte-containing systems, such as the eyes, ears, meninges, skin, and hair follicles . It is cMelanocytes are also located in the brain and leptomeninges, possibly with neuroendocrine and detoxification functions . Melanoc3.There is an extensive correlation between vitiligo and other organ-specific or generalized autoimmune disorders. A 10-year retrospective study involving 3,280 patients showed that comorbid autoimmune conditions occur in approximately 23% of vitiligo patients, including thyroid disease (TD), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and type 1 diabetes mellitus . Of notein situ and provide efficient protection. They also respond to autoantigens in other barrier tissues, including the lungs, gastrointestinal tract, and reproductive tract, as well as in non-barrier tissues, including the brain, pancreas, and joints, which may be involved in the pathogenesis of organ-specific autoimmune disorders, such as IBD, multiple sclerosis, and type 1 diabetes mellitus , and thyroglobulin antibodies (TGAbs) was 15.7, 1.9, 16.8, and 11.4%, respectively, which was significantly higher than that in healthy controls . AnotherAn increasing number of studies focusing on the type and onset of vitiligo or gender and race of patients aim to identify the confounding factors based on subgroup analyses. Many studies have confirmed that NSV patients are more susceptible to TD than SV patients, possibly because SV is more associated with neural mechanisms . Some st3.1.2.A significant correlation was found between vitiligo and Addison’s disease. Alkhateeb et al.  reportedAutoimmune polyglandular syndrome (APS) occurs when two or more endocrine glands in the same individual become hypofunctional because of autoimmune inflammation, either sequentially or simultaneously . It can 3.2.3.2.1.IBD is an immune-mediated chronic intestinal inflammatory disease and includes Crohn’s disease (CD) and ulcerative colitis (UC). Some large-scale studies found a higher frequency of IBD among vitiligo patients, but the prevalence varies according to country and ethnicity. Hadi et al.  reported3.2.2.Autoimmune atrophic gastritis (AAG), characterized by the development of antibodies against parietal cells and intrinsic factor, leads to mucosal destruction that primarily affects the corpus and fundus of the stomach . Vitilig3.3.Several observational studies have found an increased prevalence of pernicious anemia (PA) in the vitiligo population. A 10-year cross-sectional retrospective study of 1,487 vitiligo patients in urban USA showed that an estimated 0.4% of patients have combined PA . AnotherPA occurs in the later stage of AAG with severe gastric intrinsic factor deficiency and consequent vitamin B12 deficiency . PA is l3.4.The most commonly reported comorbid connective tissue diseases (CTD) in vitiligo patients are SLE and RA. Other associated CTDs include Sjögren’s syndrome (SS), systemic sclerosis (SSc), and dermatomyositis/polymyositis (DM/PM).Choi et al.  performe3.5.Recent studies have suggested an observational link between vitiligo and neuroimmune disorders involving the peripheral and central nervous systems. According to a cross-sectional analysis of 1,098 patients with vitiligo, three had Guillain-Barré syndrome (0.2%), two had multiple sclerosis (0.2%), and two had myasthenia gravis (0.2%) . ConsideAutoimmune encephalitis is a group of disorders characterized by antibodies reacting with the extracellular epitopes of neuronal cell membranes or synaptic proteins . Of the Based on the above, we speculate that vitiligo may be a clue to understanding the diagnosis or autoimmune etiology of other autoimmune disorders. Patients with vitiligo are prone to disruption of autoimmune tolerance and autoimmune attack, thereby increasing their risk of concomitant autoimmune diseases. Similarly, if vitiligo lesions are observed in patients with diseases of other tissues, autoimmunity may be responsible for the pathogenesis. A diagnosis based on this information may be more accurate. Several large cross-sectional or retrospective studies have also noted that these diseases often occur alongside one another, which implies that their pathologies are inextricably linked. As a result, vigilance should be exercised when searching for possible concomitant diseases, and patients should be referred to specialists where necessary. Nevertheless, further studies are required to determine whether therapies for vitiligo can slow the progression of concomitant autoimmune disorders.4.4.1.Vitiligo and alopecia areata (AA) are common autoimmune conditions characterized by white spots on the skin (vitiligo) and bald spots on the scalp (AA) . A retroOxidative stress and autoimmunity with genetic susceptibility are associated with the pathogenesis of AA and vitiligo . Both co4.2.Psoriasis is a relatively common disease with an estimated prevalence ranging from 0.51 to 11.43% in adults . A recenAIS1, PSOR7 . A meta-analysis of 16 studies showed that patients with vitiligo had a 7.82-fold increase in AD compared with control patients without these disorders. Intriguingly, the odds of having AD were higher in those with early-onset vitiligo than in those with adult-onset vitiligo . SimilarThere are a few possible explanations for the pathomechanism linking AD and vitiligo. Campione et al.  suggesteVitiligo and other associated dermatological diseases are characterized by a complex combination of factors, including genetic predisposition and the immune response triggered by exogenous stimulation. Vitiligo can precede or co-occur with other skin comorbidities, or emerge at different stages of the development of other skin comorbidities. Despite these obvious clinical differences, skin diseases share much in common, and understanding their similarities may help us to better determine their pathogenesis and develop common therapeutic approaches to treat them in a more efficient way, such as biological agents or Janus kinase inhibitors.5.MetS is described as the clustering of obesity, hypertension, hyperglycemia, and dyslipidemia in an individual, ultimately leading to diabetes mellitus, cardiovascular diseases, or other chronic diseases . SeveralRecently, Chuang et al.  conducteMetS and its components are important risk factors for cardiovascular disease. Carotid ultrasound measurements, including carotid intima media thickness (CIMT), are used for the assessment of subclinical atherosclerosis and can be independent predictors of cardiovascular events . A hospiIFIH1, BACH2, BTNL2, IL2RA, SH2B3, and ZMIZ1  indicators. Morrison et al.  conducteDepression and anxiety are the most commonly reported psychosocial comorbidities. Wang et al.  showed tEzzedine et al.  also invIn summary, vitiligo can increase the psychological burden of patients and cause several psychological problems. Simultaneously, mental and psychological stress can further aggravate the progression of vitiligo, thus creating a positive feedback effect. Moreover, the degree of inflammation may be enhanced under emotional stress, which in turn contributes to the development of other comorbidities associated with vitiligo . Therefo7.There is evidence in the literature that vitiligo is associated with several comorbid disorders , 2. HoweZH performed the literature search and drafted the first version of the manuscript. TW provided expert guidance and critically revised the work. All authors contributed to the article and approved the submitted version.This work was supported by National High Level Hospital Clinical Research Funding (2022-PUMCH-B-092), National High Level Hospital Clinical Research Funding (2022-PUMCH-A-164), Beijing Municipal Natural Science Foundation (Z210017), and Peking Union Medical College Hospital (ZC201911051).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This study aimed to evaluate the association between methionine intake and diabetes prevalence in Chinese adults and explore whether the association was source-specific. Data from 12,849 adults aged ≥20 years old were used from the China Health and Nutrition Survey during 1997–2011. Diabetes was diagnosed as self-reported and/or when blood tests results met the diagnostic criteria. A 3-day, 24-h recall was used to assess different sources of methionine. Multivariable mixed linear regression was used to examine the associations. Across the quartiles of total methionine intake, the odds ratio  of diabetes were 1.00, 1.49 (1.21 to 1.82), 1.72 (1.37 to 2.15), and 2.53 (1.97 to 3.23). In the subgroup analysis, similar trends were observed in both animal and plant methionine. There was a significant interaction between urbanization and diabetes. The positive association was only significant in those who lived in low or medium urbanization areas. The ORs (95% CI) were 1.00, 1.27 (0.85 to 1.88), 1.56 (1.01 to 2.39), and 1.79 (1.09 to 2.95) for medium urbanization, respectively. No interaction was identified when stratified by different methionine sources. In conclusion, methionine intake was positively associated with diabetes independent of food source, and it was modified by urbanization levels. Non-communicable chronic diseases (NCDs) have become the leading cause of mortality and disease burden worldwide, while diabetes is one of the most common NCDs globally . EstimatLong-term dietary patterns and compositional interventions have beneficial effects on the prevention and treatment of diabetes . MethionDespite the clear benefits of methionine in laboratory animal models, evidence from the human population focused on the association between methionine intake and diabetes, was rare. One 16-week dietary intervention with MR (>80% relative to controls) in subjects with obesity and a metabolic syndrome reported that MR did not alter insulin or glucose directly, but enhanced the shift from carbohydrate to fat oxidation, which was closely involved in glucose metabolism . On the Compared with plant-based sources, animal food sources generally have higher amounts of methionine, although the proportion varies substantially . Along wUsing the longitudinal survey data collected in the China Health and Nutrition Survey (CHNS) during 1997–2011, our aim was to assess the long-term association between total methionine intake and diabetes among adults and determine whether the association was source-specific.This study is an association analysis based on repeated measurements of data on dietary intake and diabetes using the CHNS data. The CHNS is an ongoing open-cohort study and profound cooperation project between the China Centers for Disease Control and Prevention (CCDC) and the Carolina Population Center at the University of North Carolina at Chapel Hill. Since its establishment in 1989, CHNS has been used to collect 11 panels of data in 1989, 1991, 1993, 1997, 2000, 2004, 2006, 2009, 2011, 2015, and 2018 using a multistage random-cluster sampling method. The composition of the CHNS includes more than 30,000 participants from 15 provinces in China [Individuals with extreme values of energy intake  were excluded . The anaThe primary outcome was diabetes. Self-reported diabetes was identified based on the questionnaire if an individual answered “yes” to the question “Have you ever been told by a doctor that you have diabetes?” Additionally, a fasting blood sample was obtained in 2009 with diabetes defined as a fasting glucose of ≥7.0 mmol/L or the hemoglobin A1c (HbA1c) of ≥48 mmol/mol  . Thus, tIndividual dietary intake data were collected by trained investigators who conducted a 24-h dietary recall on each of 3 consecutive days at each wave using a standardized questionnaire. Food purchased from markets, harvested from gardens, and foods and condiments in the home inventory were weighed and recorded by interviewers at the beginning and end of the 3-day survey period. The types and amounts of foods, the types of meals, and the places of consumption for each participant were tracked from both dietary recall and the records kept by the individual. Cooking oil and condiment consumption for everyone in the household was estimated using an individual energy-weighted intake. A detailed description of dietary measurements has been published previously . In addiFor this study, the food intake data from 1997–2011 were recorded and converted to nutrient intake. We used the 3-day average food intake data to calculate the intake of nutrients, including total, animal, and plant methionine, according to the Chinese Food Composition Table . The cumSocioeconomic and lifestyle factors were evaluated using a structured questionnaire. The socioeconomic status (SES) included: annual family income , education , and urbanization levels . The lifestyle factors included: (1) the level of physical activity , which was calculated based on self-reported activities and duration using a Compendium of Physical Activities; (2) smoking status, which was categorized as non-smokers, ex-smokers, and current smokers; and (3) alcohol consumption, which was recorded as yes or no.2). According to the Chinese standard, being overweight and obesity were defined as having a BMI of ≥24.0 kg/m2 [The BMI (body mass index) was calculated as weight (kg) divided by height square (m.0 kg/m2 . Hyperten (%) for categorical variables. The characteristics at baseline according to the quartiles of total methionine intake were compared using a one-way analysis of variance (ANOVA) for continuous variables and chi-squared tests for categorical variables.The mean intake of cumulative methionine was recorded as quartiles. Descriptive statistics were calculated using the mean ± standard deviation (SD) for continuous variables and The association between methionine intake and diabetes was assessed using mixed effect logistic regression models. Unadjusted and adjusted odds ratios ) of the fixed part of the models were reported. Adjusted models were built by including age, gender, and energy intake initially in Model 1; adding education, income, urbanization, smoking, alcohol drinking, and physical activity in Model 2; and then adjusting for dietary patterns, BMI, and hypertension in Model 3. In the subgroup analyses, the multiplicative interaction between the different sources  of methionine intake and the covariates  was tested by adding a product term into the regression model. In the fully adjusted model, we also conducted a restricted cubic spline with three knots at 10, 50, and 90th to assess the non-linear association between methionine intake and diabetes. We found no evidence of a non-linear association.p < 0.05 was considered statistically significant (two-sided).The analyses were performed using STATA 17.0 . A Mixed-effect models showed the associations between total, animal, and plant-based methionine intake and diabetes in adults aged ≥ 20 years . Across p < 0.001) and hypertension status (p = 0.011) in relation to diabetes (Interestingly, there was a significant interaction between urbanization (diabetes . Across diabetes .Among the 12,849 participants who completed at least two nutrition surveys in the CHNS, across the quartiles of methionine intake, the intake derived from an animal source increased by 4.7 times, while plant-based intakes only rose by 52.7% from Q1 to Q4, respectively. Meanwhile, those with a higher methionine intake were more likely to have diabetes independent of the food source. In addition, the positive associations between total methionine intake and diabetes were stronger in adults with lower urbanization levels or who did not have hypertension. To our knowledge, this is the first longitudinal study that has reported such associations in Chinese adults.Since the opening up of China, the economy of the country has constantly and rapidly increased, which may greatly affect the Chinese diet and related malnutrition issues. Data from the nationally representative study showed that the dietary structure of Chinese adults has changed significantly, characterized as a reduced intake of cereals and vegetables and increased intake of meat, eggs, fish, and dairy . This shCompelling evidence from animal models shows that a lower methionine intake could reduce the incidence of diabetes ,12,13,14On the other hand, we failed to observe a significant interaction between methionine intake and education and income levels in relation to diabetes. Generally, individuals with higher education or income levels were more likely to have healthier food habits and meet nutritional recommendations , which mThis study also found that the same nutrients from different food sources may show different effects on health. A recent review documented that a higher intake of plant protein was associated with a lower risk of diabetes, while the association was divergent for animal protein . AnotherOur study has several strengths. First, we used the CHNS database to select a prospective, large sample of a nationally representative cohort, to make repeated measurements of dietary intake and diabetes. Second, the data were originally obtained through a 3-day 24-h diet record recall, which increased the reliability and validity of long-term methionine intake. Third, in addition to the large sample size, the data were drawn from different cities and rural areas in different provinces in the country, which make our results highly promotable. Fourth, several known and potentially confounding factors were adjusted in our analyses. Our study expanded on previous evidence and is the first to support the positive link between different methionine intakes and diabetes in the Chinese population.This study has several limitations.. First, the ascertainment of diabetes was self-reported except for 2009, which might pose a misclassification of the outcome. However, the associations between food and nutrient intake with diabetes were validated by other studies using data from the CHNS ,36. AlthIn conclusion, methionine intake was positively associated with risk of diabetes among Chinese adults independent of different methionine sources. There was a significant interaction between methionine intake and urbanization levels, showing the increased risk of diabetes in those with higher total methionine and lower urbanization levels. Further research is needed to elucidate the association between methionine and diabetes at the population level.


Due to the high clinical and genetic heterogeneity of MELAS, it is still a major challenge for clinicians to accurately diagnose the disease at an early stage. Herein, we evaluated the neuroimaging findings of MELAS with an m.3243A>G  associated with MELAS were reviewed in our case series. The anatomic location, morphological features, signal/intensity characteristics and temporal evolution of lesions were analyzed on magnetic resonance imaging (MRI), and computed tomography (CT) images. The supplying vessels and metabolite content of the lesions were also evaluated by using MR angiography (MRA)/CT angiography (CTA), and MR spectroscopy (MRS), respectively.Fifty-nine imaging studies in 24 patients who had a confirmed genetic diagnosis of The lesions were most commonly located in the posterior brain, with 37  in the occipital lobe, 32  in the parietal lobe, and 30  in the temporal lobe. The signal characteristics of the lesions varied and evolved over time. Bilateral basal ganglia calcifications were found in 6 of 9 (67%) patients who underwent CT. Cerebral and cerebellar atrophy were found in 38/59 (64%) and 40/59 (68%) patients, respectively. Lesion polymorphism was found in 37/59 (63%) studies. MRS showed elevated lactate doublet peaks in 9/10 (90%) cases. MRA or CTA revealed that the lesion-related arteries were slightly dilated compared with those of the contralateral side in 4 of 6 (67%) cases.The imaging features of MELAS vary depending on the disease stage. Polymorphic lesions in a single imaging examination should be considered a diagnostic clue for MELAS. Stroke-like episodes may be involved in a complex pathogenetic process, including mitochondrial angiopathy, mitochondrial cytopathy, and neuronal excitotoxicity. Mitochomutation . Approxi(MT-TL1) .MT-TL1 mtDNA gene (m.3243A>G), the pathogenesis of stroke-like episodes (SLEs) remains controversial. Recently, with the technological development of magnetic resonance imaging (MRI) and computed tomography (CT), neuroimaging has played an increasingly important role in the accurate diagnosis of MELAS and speculation on the pathogenesis of SLEs.Due to the high heterogeneity of mitochondrial genes , the same clinical phenotypes might be caused by different mutations, and the same mutation in mitochondria can cause different clinical phenotypes. Thus, MELAS is highly variable and non-specific in its clinical presentation, characterized by multisystem involvement, particularly with organs highly dependent on aerobic metabolism, including the central nervous, musculoskeletal, endocrine, and gastrointestinal systems. The main clinical manifestations of MELAS include headache, vomiting, impaired consciousness, seizures, muscle weakness, visual field defects, deafness, growth retardation, endocrinopathies, dementia, diabetes mellitus, gastrointestinal dysmotility, etc. . Generalm.3243A>G mutation in MT−TL1, emphasizing the distribution, signal characteristics and temporal evolution of lesions, and proposing that the significance of polymorphic lesions in the diagnosis of MELAS in a single examination for the first time. Our aims were to discover imaging features for the accurate diagnosis of MELAS, explore the possible underlying pathogenesis of SLEs, and place the pathogenetic process in the context of clinical practice.In this study, we retrospectively analyzed the clinical manifestations and neuroimaging findings of MELAS syndrome with an The study protocol was approved by the Human Ethics Committee of Children’s Hospital of Chongqing Medical University and was conducted in accordance with the tenets of the Declaration of Helsinki. The need for informed consent from the patients was waived.Between May 2015 and Jan 2022, a total of 29 pediatric patients with MELAS underwent MR or CT examinations in the Department of Radiology at Children’s Hospital of Chongqing Medical University. The diagnosis was in line with the diagnostic criteria of MELAS in 2002 : (1) Them.3243A>G mutation in MT-TL1, five patients with other genetic mutations were excluded from the 29 patients. Hence, data from 24 pediatric patients with MELAS of the m.3243A>G mutation in MT−TL1  with 48 cerebral MR imaging studies in 22 patients (the frequency of follow-up ranged from 1 to 5 times) and 11 cerebral CT imaging studies  were included in our case series study  administered orally 20 min before MRI examination.TR) 2,000 ms, echo time (TE) = 20 ms, inversion time (TI) = 800 ms, for axial T1-weighted imaging (T1WI); TR = 3,500 ms, TE = 80 ms for axial T2-weighted imaging (T2WI); TR = 3,000 ms, TE = 80 ms for sagittal T2WI; TR = 8,000 ms, TE = 125 ms, TI = 2,500 ms for axial T2 fluid-attenuated inversion recovery (FLAIR); TR = 2,298 ms, TE = 87 ms, b factors = 0 and 1,000 or 800 mm2/s for diffusion-weighted imaging (DWI). Apparent diffusion coefficient (ADC) maps were automatically calculated from the original DWI data on a workstation . Three of 22 patients underwent contrast-enhanced MR examination. Gadopentetate dimeglumine  was intravenously manually injected at a dose of 0.1 mmol/kg and flushed with the same volume of saline, at the same flow rate when possible. Then, contrast-enhanced and fat-suppressed T1WI of the axial, sagittal and coronal planes was immediately and successively performed with the same parameters as the abovementioned T1WI. Single-voxel 1H MR spectroscopy (1H-MRS) was performed to separate lactate from lipids by confirming peak inversion using different TEs . Brain MR angiography (MRA) was performed using three-dimensional time of flight (TOF), and the intracerebral artery images were obtained using maximum intensity projection (MIP) reconstruction. The parameters were as follows: TR = 25 ms, TE = 3.5 ms, 200 slices with a slice thickness of 1.6 mm and FOV of 20 cm.Brain MRI scans were performed on a 3.0-T MRI scanner  with an eight-channel head coil (SENSE-Head-8). A supine, head-first position was used for all patients. Images were obtained in the axial, sagittal, and coronal planes. The scanning sequences and parameters were as follows: Slice thickness 5 mm, slice gap 1 mm; the field of view (FOV) ranged from 22 to 24 cm covering the whole brain; repetition time =  administered orally 20 min before CT examination.Computed tomography images were obtained on a 256-slice CT scanner . The scanning parameters were as follows: Tube voltage, 100 kilovolts (kV); automatic tube current, from 100 mA to 150 mA; screw pitch, 0.39; and the idose iterative reconstruction algorithm was used for data processing. The scanning range extended from the auditory canthus line up to the top of the skull.via an antecubital fossa cannula using a double barrel high-pressure syringe  using 1.5–2 ml/kg contrast at 1.5 ml/s followed by 10–15 ml of saline at the same rate. A fluoroscopy trigger was used for the scanning. The trigger zone was set at the center of the common carotid artery at the horizontal level of the third cervical vertebra, with a circular region of interest (ROI). The size of the ROI was 10 mm2. The scanning range was from the base of the skull to the superior extent of the calvaria, the scanning direction was from inferior to superior, and the slice thickness was 5 mm.Intravenous contrast non-ionic iohexol  was injected m.3243A>G in MT-TL1 were reviewed. Lesion location, cerebral and/or cerebellar atrophy, signal characteristics, morphological features, and temporal evolution of lesions were analyzed on MR and CT images. Calcification, especially in the basal ganglia, was assessed mainly on CT images. In addition, metabolism of the lesions was evaluated via MRS in 12 patients, and the supplying vessels of lesions were also analyzed by using MRA/CT angiography (CTA) in six patients.Fifty-nine imaging studies in 24 MELAS patients with In this study, we propose the concept of lesion polymorphism. In a single imaging examination, whether CT or MR, the lesion can be considered polymorphic if it meets more than three of the following conditions: (1) Swelling in the cerebral cortex and subcortical with an increased DWI signal and an increased ADC; (2) swelling in the cerebral cortex and subcortical with an increased DWI signal and a decreased ADC; (3) cortical laminar necrosis with high linear T1 signal intensity; (4) black toenail sign : Focal lAll studies were reviewed in consensus by two pediatric neuroradiologists with 10–20 years of experience. Although the diagnosis was known, the readers were blinded to the imaging report and clinical data during the review. In the event of disagreement, the two neuroradiologists repeated the double-blind reading along with a third senior neuroradiologist until a consensus was reached.Statistical analyses were performed using IBM SPSS software . Demographic, clinical, and CT/MRI data were summarized using the mean ± standard deviation for continuous variables and counts or proportions for categorical variables.MT-TL1 m.3243A>G. The mothers of six patients  had mutations at the same site, and the rest were uncertain. Nine cases  had a family history, 12 cases  had no family history, and the remaining three cases were uncertain. Two patients  died, one 9 years after onset and the other 3 years after onset. All patients had had at least one SLE; headache occurred in 17 cases ; hirsutism was diagnosed in 16 cases ; episodic visual impairment and hearing impairment occurred in 13 cases  and 7 cases , respectively; and cognitive impairment was found in 7 cases . Blood lactic acid testing was performed in all 24 cases, of which 20 cases  showed elevated levels of blood lactic acid, and the remaining 4 cases showed normal levels.As summarized in The signal characteristics of the lesions varied, mainly depending on the different stages of the disease. During the acute stage, the main finding was swelling of the cortex, which showed signal features similar to those of acute cerebral infarction but not restricted to arterial territories and migrated over time. Six of the 18 patients (33%) with lesions demonstrating acute diffusion restriction on MR images were followed up 1–5 times, and the lesion location, extent and signal changed to various degrees . During For all 59 imaging studies, cerebral atrophy occurred in 38 (64%), and cerebellar atrophy occurred in 40 (68%). Some patients with MELAS showed no abnormal findings on routine MR except cerebral and/or cerebellar atrophy. Five of 12 (42%) cases without abnormal signals showed brain atrophy.In this study, we propose the concept of lesion polymorphism, which refers to the spatial diversity of lesions in a single neuroimaging examination. Forty of 59 (68%) studies showed polymorphisms of lesions in our cohort, which might show cortex swelling, cortex atrophy with gliosis in different regions and calcification of the bilateral basal ganglia .MR spectroscopy assessment was performed in 10 patients, in which 9 (90%) cases demonstrated elevated lactate doublet peaks in both acutely affected and unaffected regions of subcortical white matter accompanied by a decrease in N-acetyl-L-aspartic acid (NAA) .Brain MRA and CTA were performed in 5 and 1 patients, respectively. The relevant arteries of the lesion were slightly dilated compared with those of the contralateral side in 4/6 (67%) cases .In this study, we reviewed a group of MELAS case series in children and identified several imaging characteristics, including predominant involvement of the posterior brain cortical region, varying signal characteristics over time, calcification of the bilateral basal ganglia, cerebral and/or cerebellar atrophy, elevated lactate doublet peaks in both acutely affected and unaffected regions, and slight dilation of the relevant arteries. These findings have implications for the early and accurate diagnosis of MELAS. In addition, we propose the novel concept of lesion polymorphism, which features a diversity of lesion morphology and signals and reflects the progression of the disease. If polymorphic lesions are detected in a single imaging examination, the possibility of MELAS should be considered.Since MELAS is a progressive disease, it often shows various MRI features in different disease stages. In the acute stage, cerebral edema is commonly observed, often involving the occipital or posterior parietal cortex. Cerebral edema can be cytotoxic or vasogenic. In this group of cases, some cortical edema developed into laminar necrosis and brain atrophy, while the other cortical edema disappeared without remaining lesions in a short time. We speculated that it was related to the type of edema (cytotoxic or vasogenic). However, due to the retrospective nature of the analysis, we did not regularly follow up all the children. This required us to better design research routes in the future to find biological markers for predicting lesion evolution in the short term.With disease progression, the lesions are characterized by laminar necrosis, which often indicates that the lesion is irreversible. Laminar necrosis often showed linear T1 hyperintensity along the gyri. The black toenail sign is specific for indicating gyrus necrosis, which was detected in 35% of subacute cases. When the disease enters the chronic stage, brain atrophy and calcification of the bilateral basal ganglia are common features of MELAS. Lesions at different stages can be presented on a single image, which we call polymorphic lesions. This sign occurred in 40/59 (68%) cases and was relatively specific to MELAS. The previous MELAS-related literature  emphasizMR spectroscopy is a useful technique for diagnosing MELAS because it can assess brain metabolites . The lacComputed tomography has limited value in the diagnosis of MELAS, apart from revealing calcifications in the bilateral basal ganglia. According to To date, although the precise pathophysiology of SLEs with MELAS has not been completely elucidated, three possible hypotheses for these episodes are as follows: (1) mitochondrial angiopathy (vascular hypothesis) ; (2) mitThe theory of mitochondrial angiopathy is the concept of vascular caliber alterations and extravasation caused by mitochondrial abnormalities inside vascular smooth muscle cells and vascular endothelial cells on the cerebral surface arterioles and soft membrane arterioles, which result in angioedema. The angioedema on MRI showed an increased DWI signal and an increased ADC value. Twelve cases in our cohort did so. Recently, some studies detected local vasodilation on MRA and hyperperfusion on ASL in some lesions of SLEs , which wOur study is limited by its retrospective nature. The imaging modality, parameters, interval time and frequency of follow-up were not uniform, which could lead to a bias in imaging analysis. MRS and MRA were performed only in some cases. Meanwhile, some of the images in our study may not be of high quality, which may affect the diagnosis of the disease. In this case, it is possible to improve image quality by applying the image processor mentioned in the literatures . In futuThe imaging manifestations of MELAS depend on the stage of the disease. Cerebral vasogenic or cytotoxic edema is commonly observed in the acute stage. With disease progression, laminar necrosis might be observed. Brain atrophy and calcification of the bilateral basal ganglia are features of MELAS in the chronic stage. In this article, we proposed that polymorphic lesions on a single radiologic examination can serve as an important clue for the early and accurate diagnosis of MELAS. The mechanism of SLEs in MELAS may involve a wide range of factors, comprising mitochondrial angiopathy, mitochondrial cytopathy, neuronal hyperexcitability, and others.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by the Human Ethics Committee of Children’s Hospital of Chongqing Medical University. Written informed consent from the participants or their legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.HZ, XZ, YG, and JC designed the study. HZ and JC wrote the manuscript. XZ, LT, and SD analyzed the data. BL, XH, and LW performed the experiments. All authors contributed to the article and approved the submitted version.


Currently, there are increasing surgical treatments for neck pain. However, whether to use cervical brace after operation remains poorly defined. We aim to clear the clinical efficacy of the use of cervical brace after cervical surgery.We searched for relevant studies in 8 electronic databases up to March 2021. The mean difference and 95% confidence intervals were used for continuous data. Cochrane Collaboration’s tool was used to assess the risk of bias. The data were collected and input into the Review Manager 5.3 software .Four randomized controlled trials were finally included in our study. For pain, the pooled analysis showed that postoperative neck brace compared with no brace can relieve neck pain at all follow-up periods except 6 months. For neck disability index, the result showed that postoperative neck brace compared with no brace can improve neck disability index during the 3 to 12 month follow-up period. However, no significant difference was identified between 2 groups within the follow-up of 6 weeks after surgery. In addition, the result tends to get the opposite at follow-up of 24 months. For 36-Short form health survey Physical Component Summary, there was no significant difference between 2 groups in the early 3 weeks after surgery, but the results were changed after 3 weeks. For 36-short form health survey Mental Component Summary, there appears to be no significant change between 2 groups at all time intervals.Wearing a cervical brace after cervical surgery is conducive to improving symptoms after cervical surgery at different stages. However, there is no relevant evidence indicating it can improve the mental health of postoperative patients. Higher quality, large prospective randomized studies are needed to verify the current conclusions. As ranked 19th overall in the global cause of disability-adjusted life years, it has brought a great economic burden to society.,2 According to the Global Burden of Disease 2010 Study, neck pain is the fourth greatest contributor to global disability, ranking behind back pain, depression, and arthralgias. Treatment options for neck pain include conservative and surgical measures. In addition, conservative treatment is a reasonable treatment choice for nonneuropathic neck pain. While surgical management can be beneficial to patients with cervical radiculopathy or myelopathy that had failed a course of nonoperative methods. Numerous studies–9 have shown that cervical surgery can effectively alleviate the pain and symptoms of patients and improve functional activities. However, about 22% of patients will have postoperative complications such as loss of height of the intervertebral space, displacement of the implant, and decreased fusion rate.–12 Hence, the cervical brace is often used after cervical surgery to improve the above complications.,13,14Neck pain, causing pain and disability, is a common condition in the present climate.–18 However, there is still no consensus regarding the use of cervical brace after cervical spine surgery. Several studies,19 reported that cervical brace treatment was recommended for postoperative patients of cervical spine because of better relief of symptoms. Nevertheless, some studies,21 suggested the postoperative treatment with brace immobilization was not inferior to those without brace immobilization. In addition, to the best of our knowledge, no clinical guidelines concerning the use of cervical brace after cervical spine surgery have been found.The use of cervical brace during postoperative period is commonly based on the belief that it may include the restriction of neck movement, providing spinal stability, reducing pain, and even increasing sense of security for patients.The controversy surrounding the efficacy of cervical brace after surgery demonstrates the need for further exploration of the effects of cervical brace use following surgery. There are no published quantitative meta-analyses, which are often used to provide scientific guidance for clinical practice, investigating if the use of cervical brace actually improves postoperative clinical outcomes. Therefore, this meta-analysis was to evaluate the existing literature about the use of postoperative cervical brace to determine the strength of evidence. Besides, it was based on previously conducted studies. Thus, no ethical approval and patient consent are required. The review protocol was registered with the International Prospective Register of Systematic Reviews registration, available online: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019121778.This article was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. An independent review of the Pubmed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure Database, Wanfang database, China Biology Medicine, and VIP database was performed from inception to March 2021. There were no limits on study dates or any language, publication type, and status restrictions. The search was conducted with the following keywords: cervical surgery  and cervical orthoses . Different search strategies were used for Chinese and English language databases. To identify trials that may not have been published in full or were missed through the electronic search, we manually searched all references from the included studies and relevant previous systematic reviews.As with the original review, we used the search strategies recommended by the Cochrane Back Review Group for the identification of randomized controlled trials (RCTs).The retrieved literature was screened by 2 independent investigators to evaluate eligibility, and any discrepancies were settled by discussion and consensus. Studies that met the following criteria were included in the analysis: Patients: suffering from cervical surgeries, including anterior cervical discectomy and fusion, cervical laminoplasty, cervical disc replacement, cervical decompression, cervical endoscope, etc.; Intervention: external cervical immobilization; Control: without external cervical immobilization; Primary outcome: neck pain; and Study style: prospective RCTs. The excluded studies were excluded due to the following reasons: studies do not conform to the above criteria; studies were in the form of letters, abstracts, reviews, or comments; and studies were impossible to extract relevant data.Two reviewers independently extracted several data using a predesigned data extraction form, and the results were compared to avoid bias from the data extraction process. The following characteristic information was extracted from each study: design , participants , interventions , and outcomes . When relevant data had not been reported, we contacted the authors by email or in other ways to attempt to obtain the missing information. We assessed the following items: the generation for random sequence, concealment for allocation sequence, blinding of participants, incomplete outcome data, selective outcome reporting, and other sources of bias. For each included study, each type of bias was rated as high, low, or unclear and entered into the risk of bias table. The risk of bias was examined by 2 reviewers concurrently, and discrepancies were resolved by consensus.We assessed the study quality of each included trial according to the Cochrane risk of bias tool for randomized trials.The 3 most recommended outcome indicators, which are Visual Analog Scale; NDI, 36-Short form health survey (SF-36), or 12-Short form health survey, in the guidelines on cervical radiculopathy issued by the North American Spine Society were selected as outcome indicators. In addition, the pain was the main outcome, and the secondary outcomes were NDI, SF-36, or 12-Short form health survey. We took into account the following items: risk of bias, inconsistency, indirectness, imprecision, and publication bias, and we operated on this web page: https://gradepro.org/.We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)  method to assess the quality of the evidence for each outcome of meta-analysis. Levels of quality of evidence were defined as high(++++), moderate(+++), low(++), and very low(+).P < 0.05. The forest plot for each parameter was constructed to illustrate the weight ratio of each incorporated study to evaluate potential publication bias if enough studies are included. We also used the GRADE approach to rate the quality of evidence and generate absolute estimates of effect for the outcome. Furthermore, the within-subject change standard deviation, which was calculated based on means and standard deviations at baseline and follow-up provided in articles, was required for the meta analysis. Thus, weighted by the sample size of each trial:We used DerSimonian and Laird random effects models in RevMan 5.3  to conduct the meta-analyses. The outcomes of interest only include continuous variables. We used mean difference (MD) to assess the difference in the continuous outcomes between the groups. Study weights were generated using the inverse of the variance. We present results as MD and associated 95% confidence intervals (CIs). In order to evaluate the sensibility of the meta-analysis, we excluded trials at high risk of bias. The significance threshold was a 2-sided ,20,21,27 Among the excluded articles, 28 trials were excluded because these are clinical trials lack a control group, 3 studies were excluded because of RCTs or cohort studies that do not meet the purpose of this study, 8 case reports were excluded, and 30 studies were excluded because these belong to the field of basic researches. Table ,27 1 for semi-rigid brace, and 1 did not describe the brace used. The intervention period is reported between 2 and 6 weeks, of which 2 articles reported 6 weeks with brace after cervical surgery,,27 1 reported 3 weeks, and 1 reported 2 weeks. Two studies used brace for cervical myelopathy undergoing open-door laminoplasty,,27 and 2 other studies used brace after anterior cervical discectomy and fusion. Baseline imbalance was not found in the demographic characteristics or the outcomes between the study groups. Three trials,21,27 reported details of sample size calculations.The search results are displayed in Figure ,20,27 And Overley et al’s study did not report it clearly. All studies,20,21,27 either did not use blind methods or did not report it clearly. Only the study by Cheung et al described using blinding outcome assessment. Three trials,20,27 reported participant losses during follow up period. In addition, the study by Cheung et al reported all the participants took part in the follow-up. Selective reporting was difficult to assess in 2 articles,21 because trial protocols were unavailable. All judgments concluded low risk of bias , suggesting future studies might influence the results in this meta-analysis and require revising the conclusion.Figure ,20,27 reported the result of cervical pain. We performed a subgroup analysis according to different follow-up periods. Pooled analysis showed that postoperative neck brace compared with no brace can relieve neck pain at 1 week, 2 weeks, 3 weeks, 6 weeks, 3 months, 12 months, and 24 months after surgery. The results of the meta-analysis are that −3.00 (−4.96 to −1.04) at the follow-up of 1 week after surgery, −2.70 (−4.90 to −0.50) at the follow-up of 2 weeks after surgery, −2.30 (−3.69 to −0.91) at the follow-up of 3 weeks after surgery, −0.98 (−1.59 to −0.37) at the follow-up of 6 weeks after surgery, −0.87 (−1.44 to −0.30) at the follow-up of 3 months after surgery −1.30 (−1.81 to −0.80) at the follow-up of 12 months after surgery, and −1.26 (−1.81 to −0.71) at the follow-up of 24 months after surgery. However, there was no significant difference between the 2 groups at the follow-up of 6 months .The cervical pain is shown in Figure ,21,27 involving a total of 118 patients reported NDI as an outcome in the groups, as shown in Figure  only including 33 patients, reported the result of follow-up of 24 months, suggesting tend to get the opposite (1.99 [0.60–3.38]).Three trials,20,27 involving a total of 158 patients showed the SF-36 Physical Component Summary scale (PCS) with cervical brace and nonbrace after cervical surgery  result involving a total of 158 patients. According to different follow-up times, the results are that (MD and 95% CI) 4.90 (−2.01 to 11.81) at 1 week, 6.20 (−0.89 to 13.29) at 2 weeks, 6.00 (−1.09 to 13.09) at 3 weeks, 0.45 (−0.40 to 1.30) at 6 weeks, −0.25 (−5.36 to 4.85) at 3 months, 0.25(−0.81 to 1.30) at 6 months, 1.78 (−1.58 to 35.14) at 12 months, and 1.75 (−2.76 to 6.26) at 24 months. Therefore, SF-36 (MCS) does not change significantly in the brace group or the nonbrace group at any time after surgery.As shown in Figure The GRADE level of evidence is moderate for all of the results. Table For the same outcome, the number of included trials (<10) was too small to conduct any sufficient additional analysis of publication bias.To the best of our knowledge, this is the first meta-analysis that provides comprehensive and quantitative evidence for postoperative cervical spine with and without cervical brace. In addition, the purpose of this study was to examine the pain, functional outcome, and quality of life with the 2 methods of postoperative management. In this meta-analysis of 4 trials, 208 patients were included. Overall, we found that postoperative use of the cervical brace can relieve cervical pain slightly and partially improve NDI and SF-36 (PCS) and intermittently showed statistically significant improvements. However, for SF-36 (MCS), there was no significant difference between the braced group and the nonbraced group.–30 Although the exact cause of axial neck pain has not been detected, intraoperative invasion to the cervical muscles is presumed to be involved in this complication.–32 External cervical brace can limit cervical activity. The use of rigid cervical neck collars has been shown to reduce the usual cervical range of motion by 62.9%, which may promote the repair of neck tissue, so it is a possible cause of pain relief. In the present research, postoperative use of the cervical brace can relieve cervical pain compared with no neck brace during the 24-month follow-up period. Only in the 6 months after surgery, the braced group shows no advantage in relieving cervical pain. At the same time, the advantage of wearing a neck brace to relieve neck pain tends to decline over time. Furthermore, to evaluate treatment effectiveness, Carreon et al have reported the minimal clinical important difference (MCID) for pain to be 2.5. Therefore, the pain relief in only 2 weeks with and without neck brackets has clinical significance. The research by Ebata et al showed that the postoperative neck pain of patients wearing cervical brace scores significantly reduced at 2 weeks following cervical laminoplasty surgery, which is similar to our results. In addition, according to a questionnaire study sampling spine surgeons, 63% of spine surgeons employed routine postoperative cervical bracing following surgery may be due to improving pain relief.Postoperative cervical pain typified by persistent pain around the neck and shoulders is a common problem associated with cervical laminoplasty and anterior cervical decompression and fusion. in all the literature included in this meta-analysis showed that nonbraced group was slightly better in NDI than braced group at 24 months. In addition, the author reported more than 50% loss to follow-up in NDI outcome measures at 24 months. Therefore, this study outcome should be interpreted with caution. According to the study by Carreon et al, MCID for NDI is 7.5, so for the outcome of NDI in this study, although there are statistical differences in the improvement of cervical brace wearing after cervical surgery, there is no clinical significance.We used NDI to evaluate cervical function. Braced group for 3, 6, and 12 months could reduce the NDI, but there was reversed result for 24 months. Actually, only the study by Abbott et al and MCID for SF-36 (PCS) is 4.1. However, no association between postoperative cervical brace and SF-36 (MCS) was seen in our study. This study was able to identify that the use of cervical brace can be associated with the improvement of SF-36 (PCS) at 6 weeks after operation and may be related to the early cervical vertebral movement restriction, which is beneficial to the healing of the incision and the fusion of vertebral, so as to relieve the preoperative symptoms better. Similarly, in the study by Campbell et al, significant improvements in SF-36 (PCS) were seen at the follow-up period of 6 to 24 months for cervical braced group. SF-36 (MCS) is related to mental health, and there appears to be no significant change at all time intervals. However, the patients wearing neck brace in the first 3 weeks after operation have a tendency to improve SF-36 (MCS), which may be concerned with additional treatment of neck brace. The patients get some psychological comfort. From 6 weeks after the surgery, the neck brace was released during this time, and psychological factors were eliminated. Therefore, the improvement in the trend of SF-36 (MCS) has also disappeared.With regard to the quality of life, both procedures were found to be associated with significant improvement in SF-36 (PCS) compared with baseline. Additional, we found a statistically significant difference of 5.04 points, 4.83 points, 5.18 points, 5.1 points, and 1.83 points for SF-36 (PCS) in favor of the braced group from 6 weeks to 24 months, clinical significance exists except for 24 months in line with the study by Carreon et al,There were some potential limitations. First, the test power was limited by sample size. Only 4 studies were included in this meta-analysis, and all of them had a relatively small sample size (n < 100) although all the literature from 8 databases is RCTs, which are considered as highly reliable and evidence-based study designs. Therefore, the GRADE shows a moderate level of evidence in all results, and the main reason for the downgrade is the small sample size. Second, the included studies in this meta-analysis were performed in different patient groups, different cervical surgical procedures, different braces, and various clinical settings. Therefore, the risk of introducing potential heterogeneity is present. Finally, publication bias will have influenced results to some degree, but the number of included trials (<10) for the same outcome was too small to conduct any sufficient additional analysis of publication bias. However, we strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to improve the quality of this systematic review and meta-analysis.The limited existing literature does seem to suggest that wearing cervical brace helps relieve pain. In addition, the improvement of cervical function by brace is mainly from 3 to 12 months after surgery. As for the quality of life, cervical brace is recommended to improve the state of physical health from 6 weeks to 24 months. However, there is no relevant evidence indicating whether cervical brace is an option for mental health of patients. Besides, the evidence of all results is moderate. More higher quality randomized studies are needed to verify the current conclusions.The study was conceptualized by ZHF, and MY, MY, and JDZ searched and selected the trials, and extracted, analyzed, and interpreted the data. MY drafted the article. ZHF and JDZ helped with the study design and critically reviewed the article. All authors read and approved the final version of the article.


Psoriasis is a chronic systemic inflammatory disease associated with a higher incidence of cardiovascular disease, especially in patients with moderate to severe psoriasis. It has been estimated that severe psoriasis confers a 25% increase in relative risk of cardiovascular disease, regardless of traditional risk factors. Although the underlying pathogenic mechanisms relating psoriasis to increased cardiovascular risk are not clear, atherosclerosis is emerging as a possible link between skin and vascular affection. The hypothesis that the inflammatory cascade activated in psoriasis contributes to the atherosclerotic process provides the underlying basis to suggest that an anti-inflammatory therapy that improved atherosclerosis would also reduce the risk of MACEs. In this sense, the introduction of biological drugs which specifically target cytokines implicated in the inflammatory cascade have increased the expectations of control over the cardiovascular comorbidity present in psoriasis patients, however, their role in vascular damage processes remains controversial. The aim of this paper is to review the mechanistic link between psoriasis and cardiovascular disease development, as well as analyzing which of the biological treatments could also reduce the cardiovascular risk in these patients, fueling a growing debate on the modification of the general algorithm of treatment. Psoriasis is a chronic inflammatory disease whose characteristic manifestation is hyperplasia of the epidermis in the form of erythematous and scaling lesions on the skin as the ultimate consequence of hyperproliferation of epidermal keratinocytes . CurrentMany studies over the last decade have warned that psoriasis is not an exclusive skin disease, but rather that it should be viewed as a systemic disease . There iThe association between psoriasis and a higher incidence of cardiovascular disease (CVD) has been known for decades ,20,21,22In recent years, studies have been carried out with the aim of finding the pathways and/or cells responsible for the connection between psoriasis, cardiovascular risk factors and CVD. Although the underlying pathogenic mechanisms are not clear, the high prevalence of atherosclerosis  and the The aim of this review is to present a thorough analysis of the data available to date regarding the mechanistic link between psoriasis and cardiovascular disease development, as well as analyzing which of the biological treatments available to date for psoriasis could also provide increased prevention of the development of these cardiovascular disorders.psoriatic march. It suggests that the sum of environmental factors that trigger psoriasis , together with chronic systemic inflammation and the presence of concomitant diseases results in the development of insulin resistance. This insulin resistance subsequently induces endothelial dysfunction of the blood vessels, which leads to their hardening and the formation of atherosclerosis, that could ultimately lead to a cardiovascular event [Atherosclerosis is a phenomenon driven by inflammation ,44, whicar event ,47. In tar event . This coTogether with the classic markers of inflammation, multiple studies have shown the clinical presence of insulin resistance in psoriasis patients ,49, withTogether with insulin resistance, these patients also present lipid abnormalities, both quantitative and functional ,63. The A third direct mechanism proposed linking psoriasis and the development of atherosclerosis is the generation of epicardial adipose tissue, since it has been demonstrated that its presence is significantly increased in patients with psoriasis, being an additional source of visceral fat deposition and inflammatory cytokines, that are associated with coronary artery disease .Once the atherosclerotic layer is established, there are several factors that can promote the transition from its stable phenotype to an unstable one ,65,66 anConsequently, the inflammatory condition that surrounds moderate–severe psoriasis is a primary factor both in the development of atherosclerotic plaques and in their subsequent destabilization, increasing the risk of rupture and formation of thrombotic processes, which can ultimately lead to cardiovascular events such as myocardial infarction and stroke.The molecular mechanisms and proinflammatory cytokine profile of psoriatic lesions are remarkably similar to those of atherosclerotic vascular lesions, with a comparable inflammatory infiltrate of T cells, macrophages, and monocytes ,46,69,70More recent studies have revealed the importance of the activation of the Th17 pathway and of IL-17 itself, specifically the IL-17A subtype, in the context of psoriatic and atherosclerotic inflammation, relating the overexpression of this cytokine in skin lesions to the existence of a proatherogenic state in the psoriatic patient . ElevateThe relevant role of the different blood cells is another of the characteristics shared by psoriasis and atherosclerosis. In plaque psoriasis, intraepidermal accumulations of neutrophils are formed ,78. ThesAs to monocytes and macrophages, their participation has been demonstrated in both diseases: they are frequently detected in psoriatic lesions ,86 activFinally, platelets also seem to actively contribute to both pathologies. Their involvement in immune and inflammatory processes is increasingly being recognized. In fact, patients with psoriasis have elevated levels of platelet activation markers  ,91. MoreThe identification of the similarities and shared mechanisms between the formation of the psoriatic plaque and the atherosclerotic plaque shows why both conditions feed off each other and frequently coexist in the same individual; but whether vascular involvement is a consequence of the skin process or an accompanying manifestation of the disease is a matter of debate.The hypothesis that the inflammatory cascade activated in psoriasis contributes to the atherosclerotic process has laid the groundwork to expect that anti-inflammatory therapy could also improve atherosclerosis and reduce the risk of MACEs. Both phototherapy and topical treatments used in psoriasis improve localized cutaneous symptoms, but barely affect the underlying causes of the disease . As for With the introduction of biological therapies, expectations of control over cardiovascular comorbidity have increased markedly : data frThe biological drugs used for psoriasis are mostly monoclonal antibodies that act on specific inflammatory pathways and are administered subcutaneously  on different weekly schedules. Currently, the biological drugs included in the therapeutic regimen for psoriasis target two key pathways in the development and chronicity of the disease: TNFα signaling and the IL-23/Th17 axis ,111,112.TNFα inhibitors have been on the market the longest and are therefore considered first-generation biological drugs. Currently, there are four drugs in this group for the treatment of psoriasis: adalimumab (ADA), etanercept (ETA), infliximab (INF) and certolizumab (CER) .p = 0.005) [p < 0.001; I2 = 66.2%; RR, 0.67; 95% CI, 0.52 to 0.88; p = 0.003; I2 = 9.3%; overall: RR, 0.60; 95% CI, 0.48 to 0.74; p < 0.001; I2 = 57.3%) [p = 0.003; I2 = 56.2%; compared with methotrexate: RR, 0.65; 95% CI, 0.48 to 0.89; p = 0.007; I2 = 0.0%) and a trend of lower incidence of mortality compared with control group topical/photo therapy or MTX group . A retrospective study published later found that, although the rate of myocardial infarction was significantly lower in patients treated with TNFα inhibitors or methotrexate than in those treated with topical treatments, there was no statistical difference when comparing patients using TNFα inhibitors with those treated with methotrexate. Interestingly, when categorizing anti-TNFα patients according to the PASI score response, there were striking differences between PASI 75 (which were considered responders) and PASI 50 (non-responders): the standardized myocardial infarction rate in the group of patients showing PASI 75 improvement after one year of TNF-α inhibitors treatment was much lower than in PASI 50 patients [The cardioprotective benefits of anti-TNFα drugs were first documented in patients with rheumatoid arthritis, where they were associated with improved endothelial function  and a re= 0.005) ,107. The= 0.005) . Blockad= 0.005) . Althoug= 0.005) , in pati= 0.005) , and red= 0.005) ,118. In = 57.3%) . In partpatients ,120, othpatients . Therefopatients .Regarding vascular inflammation, several studies did not report a significant reduction in patients treated with adalimumab ,124. OneThus, although the literature remains heterogeneous, in part due to methodological differences, anti-TNFα agents have been shown to exert beneficial effects at the cardiovascular level and are beginning to be considered as the preferred systemic agents for the treatment of psoriasis in patients with coexisting cardiovascular risk factors , althougAs has already been described, the cytokine IL-23 is key in the pathogenesis of psoriasis for the differentiation and proliferation of Th17 and Th22. IL-17 released by Th17 lymphocytes is highly relevant in the development of lesions. Currently, three monoclonal antibodies directed against IL-17 are available: secukinumab and ixekizumab, which block IL-17A; and brodalumab, which targets the IL-17A receptor ,113.The IL-23 cytokine is a dimer composed of two subunits: p40 and p19, both of which are key to its inhibition. In addition, p40 is not exclusive to IL-23, but rather is shared with IL-12, a cytokine involved in the differentiation of naïve T cells into Th1, therefore drugs directed against this subunit will block both Th17 activation and Th22, as well as Th1. The currently available IL-23 inhibitors are: ustekinumab, whose target is the p40 subunit and which inhibits both IL-23 and IL-12, and three monoclonal antibodies directed against the p19 subunit: guselkumab, tildrakizumab, and risankizumab, that neutralize the activity of IL-23 without affecting IL-12 ,113.Positive cardiovascular effects are being increasingly documented with anti-IL17A therapy, results which were less expected and more surprising than those obtained with the inhibition of TNFα . It has On the other hand, experimental data suggest that this cytokine could play a central role in the relationship between psoriasis and cardiovascular disease , but thep = 0.12). However, a second meta-analysis including nine RCTs  which used a different statistical technique (the Peto one-step method), yielded opposite results and concluded a higher risk of MACEs in patients treated with anti-IL-12/IL-23 drugs  [Anti-IL12/23 agents are the ones that raise the more doubts in terms of cardiovascular impact: although IL-12 and IL-23 have been suggested as potential proatherogenic factors ,143,144  = 0.04) .In this same line, a recent case-control study also identified a significant association between the onset of ustekinumab treatment and early occurrence of severe cardiovascular events , mainly among patients with high cardiovascular risk . HoweverRegarding the monoclonal antibodies directed against the p19 subunit, phase 3 reSURFACE 1 and reSURFACE 2 trials analyzing the efficacy and safety of tildrakizumab in adult patients with moderate to severe chronic plaque psoriasis showed limited changes in cardiometabolic risk factors with no increased short-term risk of CV events ,157,158.In general, most data in the literature suggest that anti-IL12/23 have a neutral profile on the development of events and parameters but do not draw definitive conclusions.A summary of the main studies on the rates of MACEs in psoriatic patients treated with biological agents can be found in There is an association between psoriasis and a higher incidence of CVD, especially in patients with moderate to severe psoriasis, whose relative risk of suffering CVD is increased in 25%, and that of suffering a MACE in 6.2% within 10 years of diagnosis, regardless of traditional risk factors ,34,35,36Psoriasis seems to coexist with a state of vascular inflammation in which circulating neutrophils could be the main cell type involved, and which could explain, at least in part, this increased CV risk. The main biological therapies—which are effective against the skin manifestations of the disease—are not equally effective in controlling this vascular inflammatory environment. In this sense, the anti-TNFα and anti-IL17 drugs appear to be the most advantageous, since many of the studies with adalimumab and secukinumab speak of a general reduction in all CVDs and suggest that their effects go back to the earliest stages of vascular inflammation. In addition, anti-TNFα and anti-IL17 have widely shown better tolerability and fewer side effects than conventional treatments. This should be a compelling reason to rethink the position of these drugs in the general algorithm of treatment of moderate to severe psoriasis, who are at high risk of developing CVDs.