Detection of genes responsible for cetuximab sensitization in colorectal cancer cells using CRISPR-Cas9.

Colorectal cancer (CRC) is a common malignant tumor in digestive tract with highly invasive and metastatic capacity. Drug sensitivity remains a significant obstacle to successful chemotherapy in CRC patients. The present study aimed to explore genes related to cetuximab (CTX) sensitivity in CRC by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9. Celigo image cytometer was used to detect suitable cells and optimal dosage of CTX. Inhibition rate of CTX on Caco-2 cells was evaluated by cell counting kit-8 (CCK-8) method before and after transfection. 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) was performed to explore suitable concentration of puromycin and multiplicity of infection (MOI). CRISPR-Cas9, sequencing data quality analysis and cell viability test were used for the selection of genes related to CTX sensitivity in CRC cells. Finally, the selected genes associated with CTX sensitivity in CRC cells were further validated by colony formation and CCK-8 assays. In the present study, Caco-2 cells had a better prolificacy, and CTX 100 µg/ml exhibited a good inhibition trend on the 7th and 14th days of infection. MTT assay indicated that the minimum lethal concentration of puromycin was 2.5 µg/ml. Forty-six candidate genes were preliminarily screened via sequencing data quality analysis. Subsequently, we found that knockout of any of the four genes (MMP15, MRPL48, CALN1 and HADHB) could enhance CTX sensitivity in Caco-2 cells, which was further confirmed by colony formation assay. In summary, MMP15, MRPL48, CALN1 and HADHB genes are related to the mediation of CTX sensitivity in CRC.

Rotigotine transdermal patch in Chinese patients with advanced Parkinson's disease: A randomized, double-blind, placebo-controlled pivotal study.

INTRODUCTION: Rotigotine was demonstrated to be efficacious and well-tolerated in three placebo-controlled studies (CLEOPATRA-PD/PREFER/SP921) of patients with advanced-stage Parkinson's disease (PD), most of whom were Caucasian. This multicenter phase 3 study (SP1037; NCT01646255) was the first to investigate the efficacy and safety of rotigotine in Chinese patients with advanced-stage PD. METHODS: Chinese patients with PD, inadequately controlled on levodopa (stable dose ≥200 mg/day), with ≥2.5 h/day "off" time, and Hoehn & Yahr stage 2-4, were randomized 1:1 to receive transdermal rotigotine or placebo, titrated over ≤7 weeks, maintained at optimal/maximum dose (4-16 mg/24 h) for 12 weeks. Primary efficacy variable: mean change in absolute "off" time (according to patient diaries) from baseline to end of maintenance. Safety variables included adverse events (AEs) and discontinuations due to AEs. RESULTS: 346 patients were randomized and 89.9% completed the study (87.8% placebo; 92.0% rotigotine). All were Chinese (58.7% male; mean ± SD age: 62.2 ± 8.9 years; mean ± SD time since PD diagnosis: 6.62 ± 3.70 years). Rotigotine significantly reduced "off" time vs placebo (LS mean [95% CI] treatment difference: -1.20 h/day [-1.83, -0.57]; p = 0.0002), and resulted in more responders (≥30% decrease in "off" time: 36.9% placebo; 48.8% rotigotine; p = 0.0269). AEs were reported for 86 (50.0%) placebo- and 103 (59.2%) rotigotine-treated patients; 15 discontinued due to AEs (placebo 7; rotigotine 8). The most common AEs (≥5%) were dizziness, nausea, pruritus, and dyskinesia. CONCLUSIONS: Rotigotine was efficacious in Chinese patients with advanced-stage PD as add-on therapy to levodopa, significantly reducing "off" time vs placebo; the treatment difference was similar to that observed in previous studies of mainly Caucasian patients. Rotigotine was generally well-tolerated and had a similar AE profile to those observed in previous studies.

REG3A promotes the proliferation, migration, and invasion of gastric cancer cells.

The mechanism underlying the metastasis of gastric cancer (GC) cells remains elusive. REG3A is considered an oncogene in various cancers, but in GC its role is unclear. Here, we report that the expression of REG3A was significantly increased in the tumor tissues of patients with GC compared with the matched normal tissues. Knockdown of REG3A induced by specific small interfering RNA (siRNA) significantly repressed the proliferation of GC cells for 24 h or 48 h. Moreover, knockdown of REG3A significantly suppressed the migration, invasion, and adhesion of GC cells in vitro. Furthermore, knockdown of REG3A reduced the phosphorylation of JAK2 and STAT3, and altered the messenger RNA (mRNA) and protein expression levels of E-cadherin, Snail, RhoC, MTA1, MMP-2, and MMP-9. Taken together, REG3A is overexpressed in GC and promotes the proliferation, migration, invasion, and adhesion of GC cells by regulating the JAK2/STAT3 signal pathway. REG3A may be a potential therapeutic target for GC.

[Outcome and cognitive changes of mild cognitive impairment in the elderly: a follow-up study of 47 cases].

OBJECTIVE: To examine the cognitive changes and outcome of mild cognitive impairment (MCI) in the elderly and to explore the predictive factors of development from MCI into dementia. METHOD: A cross-sectional and longitudinal parallel cohort study design was conducted among 47 patients with MCI (MCI group), aged 72.4 +/- 7.1, and 50 sex, marital status, and professional structure-matched normal controls (NC group), aged 67.9 +/- 5.3, using the Neuropsychological Battery of Cognitive Assessment Instruments developed by World Health Organization (WHO-BCAI) and the Wechsler Memory Scale (WMS) to assess the cognitive function. Follow-up was conducted for 34.0 +/- 1.8 months. The diagnosis of dementia was based on the criteria in the Diagnostic and Statistical Manual-IV. RESULTS: Dementia was diagnosed in 13 of the 47 MCI patients with a prevalence rate of 27.7%, significantly higher than that in the NC group (2.0%, 1/50, P < 0.01). The mean total score of mini-mental status examination (MMSE) of the MCI group decreased by 2.2 +/- 3.7, significantly more than that of the NC group (1.0 +/- 1.9, P < 0.01). The mean total mental quotient (MQ) of the MCI group decreased by 12.6 +/- 17.3, significantly more than that of the NC group (3.9 +/- 8.4, P < 0.01). The values of MMSE and MQ of the 13 cases in the MCI group who developed into dementia patients decreased by 5.5 +/- 2.8 and 30.0 +/- 18.0 respectively. The WHO-BCAI assessment demonstrated that the scores of performance of verbal learning, verbal fluency, visual reasoning, trail making, sorting and spatial construct tests of the cases in the MCI group who developed into dementia patients were significantly poorer than those of the NC group (P < 0.01). Logistic analysis based on the baseline assessment suggested that the total score of MMSE and its subtest of orientation, score of orientation memory of WMS, and the scores of performance of trail making, attention, and delayed recall tested by WHO-BCAI were all statistically significant predictive factors for MCI converting into dementia (P < 0.01 or 0.05). The predictive accuracy rates of MMSE, WMS, and WHO-BCAI were 70.3%, 78.4% and 90.7% respectively. CONCLUSION: MCI diagnosed based on the criteria of pure MCI modified by the authors is indeed a transitional state from normal aging to dementia, especially Alzheimer's type of dementia. The cognitive change for MCI converting into dementia is characterized in the areas of orientation, attention, speech and executive function. These predictive factors for MCI to develop dementia are valuable in early detection and prevention of dementia in the elderly.

Efficacy and safety of olanzapine for treatment of patients with bipolar depression: Chinese subpopulation analysis of a double-blind, randomized, placebo-controlled study.

BACKGROUND: Depression in bipolar I disorder responds to the atypical antipsychotic olanzapine. This subpopulation analysis assessed whether olanzapine is superior to placebo specifically in the treatment of Chinese patients with bipolar I depression. METHODS: This was a subpopulation analysis of a 6-week, multicenter, double-blind, parallel, randomized, placebo-controlled trial among 12 Chinese study centers. Eligible inpatients and outpatients were randomized to olanzapine (5 to 20 mg/day) or placebo. Patients were primarily assessed by the Montgomery-Åsberg Depression Rating Scale total score. Secondary assessments used a range of other efficacy and safety measures. This subpopulation analysis was underpowered to show statistically significant differences between treatment groups. RESULTS: In total, 210 patients (mean age 32.9 years at baseline, 54.3% females) were random-ized. Similar proportions of patients treated with olanzapine (75.0%) and placebo (72.9%) completed the double-blind phase. Baseline-to-endpoint least-squares mean ± standard error decrease in the Montgomery-Åsberg Depression Rating Scale total score in the olanzapine group (-13.55±0.80) was similar to that noted in the parent trial (-13.82±0.65). However, the difference between olanzapine and placebo groups was not statistically significant (P=0.44); this finding was also true for the secondary efficacy measures. A post hoc analysis showed a greater emergence of mania in the placebo group, which likely reduced the treatment difference between olanzapine and placebo in the primary efficacy measure. Safety data were consistent with the known safety profile of olanzapine, including a higher incidence of weight gain (≥7%) in the olanzapine group (24.1% vs 1.4%, P<0.001). CONCLUSION: Olanzapine provides similar improvement in depression among Chinese and non-Chinese bipolar I patients. The lack of a statistically significant difference between the olanzapine and placebo groups in this Chinese subpopulation analysis may relate to an a priori lack of study power, and underestimation of the effect of olanzapine because of a greater emergence of mania in placebo-treated patients and missing data associated with a high early discontinuation rate.

[The neuropsychological test battery for elderly people].

OBJECTIVE: To establish a Chinese T-score norm of neuropsychological test battery for the elderly (NTBE). METHODS: 903 normal elderly people over 60 years old from Shanghai, Beijing, Hebei, Jiangsu, Hubei, Hunan, Zhejiang, Shandong and Liaoning were evaluated by using NTBE which includes tests of auditory verbal learning, sorting, cancellation, language, motor, visual function, construction, trail making 1 and 2, etc. RESULTS: Age and education greatly affected the score of NTBE, but gender did not. Based on these facts, the 903 normal subjects were divided into 12 subgroups, according to the age and the years of education they had received. The raw scores of NTBE were transformed to standard score and normalized standard score, and then these scores were transformed to a total T score (Mean = 100, SD = 10). Using another normal elderly sample (n = 474) to analysis, the correlation between the raw scores and the total T score was significant. Using NTBE to diagnose 110 mild cognitive impairment (MCI) and 63 Alzheimer's disease (AD) patients, the sensitivity and specificity were 66% and 91% for MCI, and 79% and 96% for AD. CONCLUSION: The T norm of the NTBE is suitable for Chinese elderly, and can be a useful instrument for diagnosing mild cognitive impairment and Alzheimer's disease.

[Measurement of regional cerebral metabolism rate of glucose in patients with Alzheimer's disease in different levels of severity].

OBJECTIVE: To measure the changes of regional cerebral metabolism rate of glucose (rCMRglc) in patients with Alzheimer's disease (AD) and explore their value to diagnosis of AD. METHODS: 10 patients with AD who met the diagnostic criteria of DSM-IV and 10 normal controls (NC) were assessed with (18)F-2-fluoro-deoxy-D-glucose positron emission tomography (PET). RESULTS: The two groups were matched in age, gender and education. The mean total scores of the mini-mental status examination (MMSE) were 16.5 +/- 6.1 for AD and 28.7 +/- 1.6 for NC. The mean total memory quotient of Wechsler Memory Scales (MQ) were 32.3 +/- 19.6 for AD and 93.1 +/- 9.0 for NC. Comparing to NC, the AD groups showed statistically significant decline of rCMRglc in frontal lobe, temporal lobe and the hippocampal formation with decreased rates ranged from 3.3% to 28.4% (P < 0.05, P < 0.01). The hypo-metabolism was more salient in the regions of upper and middle frontal gyri, middle temporal gyrus, orbital gyrus and anterior cingulate gyrus, in which areas the metabolism decreased over 20% compared to NC. The hypo-metabolism was correlated to the severity of dementia. Discriminant analysis demonstrated that the variables of right inferior temporal gyrus, left upper temporal gyrus, left hippocampus and right insular lobe were entered into the discriminant functions and the total discriminant accuracy reached 100%. CONCLUSIONS: (18)F-FDG PET is a very sensitive tool in measurement of the changes of rCMRglc in patients with AD. The findings show a frontal-temporal type of metabolism in AD patients and suggest that hypo-metabolism in hippocampal formation and temporal lobe is helpful in early detection of AD.

Correlation between changes in quality of life and symptomatic improvement in Chinese patients switched from typical antipsychotics to olanzapine.

PURPOSE: The aim of this study was to investigate the correlation between changes in symptoms and changes in self-reported quality of life among Chinese patients with schizophrenia who were switched from a typical antipsychotic to olanzapine during usual outpatient care. PATIENTS AND METHODS: This post hoc analysis was conducted using data from the Chinese subgroup (n=475) of a multicountry, 12-month, prospective, noninterventional, observational study. The primary publication previously reported the efficacy, safety, and quality of life among patients who switched from a typical antipsychotic to olanzapine. Patients with schizophrenia were included if their symptoms were inadequately controlled with a typical antipsychotic and they were switched to olanzapine. Symptom severity was measured using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity scale (CGI-S). Health-Related Quality of Life (HRQOL) was assessed using the World Health Organization Quality of Life-Abbreviated (WHOQOL-BREF). Paired t-tests were performed to assess changes from baseline to endpoint. Pearson's correlation coefficients (r) were used to assess the correlations between change in symptoms (BPRS and CGI-S scores) and change in HRQOL (WHOQOL-BREF scores). RESULTS: Symptoms and HRQOL both improved significantly over the 12 months of treatment (P<0.001). Significant correlations were observed between changes from baseline to end of study on the BPRS and the CGI-S and each of the WHOQOL-BREF four domain scores and two overall quality-of-life questions. The correlation coefficients ranged from r=-0.45 to r=-0.53 for the BPRS and WHOQOL-BREF. The correlation coefficients were slightly smaller between the CGI-S and WHOQOL-BREF, ranging from r=-0.33 to r=-0.40. CONCLUSION: For patients with schizophrenia, assessing quality of life has the potential to add valuable information to the clinical assessment that takes into account the patient's own perspective of well-being.

Olanzapine in Chinese patients with schizophrenia or bipolar disorder: a systematic literature review.

BACKGROUND: Despite the burden of schizophrenia and bipolar disorder in the Chinese population, country-specific data to guide practitioners regarding antipsychotic therapy are lacking. The primary aim of this systematic review was to examine evidence of the efficacy, effectiveness, and safety of olanzapine in Chinese populations. METHODS: A systematic literature search was conducted using databases covering international and Chinese core journals using search terms related to schizophrenia and bipolar disorder, specified countries (People's Republic of China, Hong Kong, Taiwan), and olanzapine treatment. Following initial screening, inclusion and exclusion criteria were applied to the search results to identify relevant studies from which data were extracted. RESULTS: A total of 489 publications were retrieved and 61 studies were identified for inclusion. Most studies were related to schizophrenia (n=54), with six studies related to bipolar disorder and one study related to both conditions. The quality of study methods and reporting in international journals was noticeably better than in Chinese language journals. Most studies included relatively small patient populations and were of short duration. The efficacy of olanzapine in Chinese populations was confirmed by multiple comparative and noncomparative studies that found statistically significant reductions in symptom measures in studies conducted for ≥6 weeks (schizophrenia) or ≥3 weeks (bipolar disorder). Findings related to effectiveness (treatment discontinuation, quality of life, and neurocognitive improvements) were generally consistent with those observed in non-Chinese populations. No new safety signals specific for Chinese populations were raised for olanzapine. CONCLUSION: Chinese and non-Chinese populations with schizophrenia or bipolar disorder treated with olanzapine display broadly similar responses. Differences between these populations, especially in relation to the relative efficacy of olanzapine versus other antipsychotics, may warrant further investigation via studies incorporating both populations. Use of local data to provide evidence for practice guidelines should be encouraged, and may promote ongoing improvements in the quality of research and study reporting.

Does participation in a weight control program also improve clinical and functional outcomes for Chinese patients with schizophrenia treated with olanzapine?

OBJECTIVES: This study examined whether participation in a weight control program (WCP) by patients with schizophrenia treated with olanzapine was also associated with improvements in clinical and functional outcomes. METHODS: A post-hoc analysis was conducted using data from the Chinese subgroup (n=330) of a multi-country, 6-month, prospective, observational study of outpatients with schizophrenia who initiated or switched to oral olanzapine. At study entry and monthly visits, participants were assessed with the Clinical Global Impression of Severity, and measures of patient insight, social activities, and work impairment. The primary comparison was between the 153 patients who participated in a WCP at study entry (n=93) or during the study (n=60) and the 177 patients who did not participate in a weight control program (non-WCP). Mixed Models for Repeated Measures with baseline covariates were used to compare outcomes over time. Kaplan-Meier survival analysis was used to assess time to response. RESULTS: Participants had a mean age of 29.0 years and 29.3 years, and 51.0% and 57.6% were female for WCP and non-WCP groups, respectively. Average initiated daily dose for olanzapine was 9.5±5.4 mg. WCP participants gained less weight than non-participants (3.9 kg vs 4.9 kg, P=0.03) and showed statistically significant better clinical and functional outcomes: greater improvement in illness severity (-2.8 vs -2.1, P<0.001), higher treatment response rates (94.1% vs 80.9%, P<0.001), shorter time to response (P<0.001), and greater improvement in patients' insight (P<0.001). Patients who enrolled in a WCP during the study had greater initial weight gain than those who enrolled at baseline (P<0.05), but similar total weight gain. CONCLUSION: Participation in a WCP may not only lower the risk of clinically significant weight gain in olanzapine-treated patients, but may also be associated with additional clinical and functional benefits.

The personal, societal, and economic burden of schizophrenia in the People's Republic of China: implications for antipsychotic therapy.

BACKGROUND: This article describes the personal, societal, and economic burden attributable to schizophrenia in the People's Republic of China and highlights the potential for effective outpatient treatment to reduce this burden given recent changes in the Chinese health care system. The importance of effective antipsychotic therapy in reducing the burden of schizophrenia is also examined. METHODS: Published research on the burden, disability, management, and economic costs of schizophrenia in the People's Republic of China was examined in the context of the larger body of global research. Research written in English or Chinese and published before June 2012 was identified using PubMed, CNKI, and Wanfang Med database searches. The contribution of effective antipsychotic therapy in reducing the risk for relapse and hospitalization and improving patients' functioning is described. RESULTS: Schizophrenia imposes a substantial burden on Chinese society, with indirect costs accounting for the majority of the total cost. Functional impairment is high, leading to lost wages and work impairment. In the People's Republic of China, schizophrenia is the most common diagnosis among hospitalized psychiatric patients. Ongoing changes in the Chinese health care system may reduce some barriers to effective relapse prevention in schizophrenia and potentially reduce hospitalizations. The use of antipsychotics for acute episodes and maintenance treatment has been shown to decrease symptom severity and reduce the risk for relapse and hospitalization. However, discontinuing antipsychotic medication appears common and is a strong predictor of relapse. Cost-effectiveness research in the People's Republic of China is needed to examine the potential gains from improved outpatient antipsychotic treatment. CONCLUSION: Schizophrenia is a very costly mental illness in terms of personal, economic, and societal burden, both in the People's Republic of China and globally. When treated effectively, patients tend to persist longer with antipsychotic treatment, have fewer costly relapses, and have improved functioning. Further research examining the long-term effects of reducing barriers to effective treatments on the societal burden of schizophrenia in the People's Republic of China is needed.

Relationship of macrophage migration inhibitory factor levels in PBMCs, lesional skin and serum with disease severity and activity in vitiligo vulgaris.

Melanocyte loss in vitiligo vulgaris is believed to be an autoimmune process. Macrophage migration inhibitory factor (MIF) is involved in many autoimmune skin diseases. We determined the possible role of MIF in the pathogenesis of vitiligo vulgaris, and describe the relationship between MIF expressions and disease severity and activity. Serum MIF concentrations and mRNA levels in PBMCs were measured in 44 vitiligo vulgaris patients and 32 normal controls, using ELISA and real-time RT-PCR. Skin biopsies from 15 patients and 6 controls were analyzed by real-time RT-PCR. Values are reported as median (25th-75th percentile). Serum MIF concentrations were significantly increased in patients [35.81 (10.98-43.66) ng/mL] compared to controls [7.69 (6.01-9.03) ng/mL]. MIF mRNA levels were significantly higher in PBMCs from patients [7.17 (3.59-8.87)] than controls [1.67 (1.23-2.42)]. There was also a significant difference in MIF mRNA levels in PBMCs between progressive and stable patients [7.86 (5.85-9.13) vs 4.33 (2.23-8.39)] and in serum MIF concentrations [40.47 (27.71-46.79) vs 26.80 (10.55-36.07) ng/mL]. In addition, the vitiligo area severity index scores of patients correlated positively with changes of both serum MIF concentrations (r = 0.488) and MIF mRNA levels in PBMCs (r = 0.426). MIF mRNA levels were significantly higher in lesional than in normal skin [2.43 (2.13-7.59) vs 1.18 (0.94-1.83)] and in patients in the progressive stage than in the stable stage [7.52 (2.43-8.84) vs 2.13 (1.98-2.64)]. These correlations suggest that MIF participates in the pathogenesis of vitiligo vulgaris and may be useful as an index of disease severity and activity.

A double-blind, placebo-controlled study of traditional Chinese medicine sarsasapogenin added to risperidone in patients with negative symptoms dominated schizophrenia.

OBJECTIVE To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia. METHODS The trial was a double-blind, placebo-controlled, parallel-group design. The eligible patients were randomized into 2 treatment groups: sarsasapogenin group (sarsasapogenin plus risperidone for 8 weeks, n = 41) and placebo group (risperidone only for 8 weeks, n = 39). At the baseline, as well as at weeks 2, 4 and 8 of treatment, the therapeutic response was measured by using scales including Positive and Negative Symptoms Scale (PANSS), Wechsler Memory Scale (WMS), modified Chinese Wechsler Adult Intelligence Scale (mWAIS), Clinical Global Impression (CGI) and Brief Psychiatry Rating Scale (BPRS). The study period for each subject was 8 weeks and duration of overall trial was 2 years. RESULTS Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS, WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone. The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group. CONCLUSION Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia. Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2-4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.

Relationship of macrophage migration inhibitory factor levels in PBMCs, lesional skin and serum with disease severity and activity in vitiligo vulgaris

Melanocyte loss in vitiligo vulgaris is believed to be an autoimmune process. Macrophage migration inhibitory factor (MIF) is involved in many autoimmune skin diseases. We determined the possible role of MIF in the pathogenesis of vitiligo vulgaris, and describe the relationship between MIF expressions and disease severity and activity. Serum MIF concentrations and mRNA levels in PBMCs were measured in 44 vitiligo vulgaris patients and 32 normal controls, using ELISA and real-time RT-PCR. Skin biopsies from 15 patients and 6 controls were analyzed by real-time RT-PCR. Values are reported as median (25th-75th percentile). Serum MIF concentrations were significantly increased in patients [35.81 (10.98-43.66) ng/mL] compared to controls [7.69 (6.01-9.03) ng/mL]. MIF mRNA levels were significantly higher in PBMCs from patients [7.17 (3.59-8.87)] than controls [1.67 (1.23-2.42)]. There was also a significant difference in MIF mRNA levels in PBMCs between progressive and stable patients [7.86 (5.85-9.13) vs 4.33 (2.23-8.39)] and in serum MIF concentrations [40.47 (27.71-46.79) vs 26.80 (10.55-36.07) ng/mL]. In addition, the vitiligo area severity index scores of patients correlated positively with changes of both serum MIF concentrations (r = 0.488) and MIF mRNA levels in PBMCs (r = 0.426). MIF mRNA levels were significantly higher in lesional than in normal skin [2.43 (2.13-7.59) vs 1.18 (0.94-1.83)] and in patients in the progressive stage than in the stable stage [7.52 (2.43-8.84) vs 2.13 (1.98-2.64)]. These correlations suggest that MIF participates in the pathogenesis of vitiligo vulgaris and may be useful as an index of disease severity and activity.