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Objective:To explore predictive factors for the efficacy of omalizumab in the treatment of refractory chronic spontaneous urticaria (CSU) .Methods:Totally, 40 patients with refractory CSU treated with omalizumab were enrolled from Department of Dermatology, the Second Affiliated Hospital of Soochow University from 2019 to 2021. Before treatment, clinical data including the urticaria activity score over 7 days (UAS7) and dermatology life quality index (DLQI) were collected; venous blood samples were collected for the detection of total immunoglobulin E (IgE) antibodies, eosinophil counts and basophil counts, anti-thyroid peroxidase (TPO) IgG antibody levels, mean platelet volume, as well as C-reactive protein (CRP) , D-dimer, complements C3 and C4, interleukin (IL) -2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor (TNF) -α and interferon (IFN) -γ levels, and percentages of CD4 + T cells and CD8 + T cells; meanwhile, the autologous serum skin test (ASST) was performed. After 12-week treatment with omalizumab, 40 CSU patients were divided into well-responding group and poorly-responding group according to the UAS7 score, and the above laboratory indicators were compared between the two groups. For continuous variable indicators with significant differences, the accuracy of prediction and optimal cut-off values were determined by using the receiver operating characteristic (ROC) curve; for categorical variable indicators with significant differences, the sensitivity and specificity for the prediction of poor clinical response to omalizumab were calculated; correlations among the above indicators were analyzed by Pearson correlation analysis. Results:After 12-week treatment with omalizumab, 28 CSU patients responded well to omalizumab, and 12 responded poorly. Before treatment, the poorly-responding group showed significantly increased proportions of patients with eosinopenia (6/12) , basopenia (7/12) , decreased C3 (6/12) , decreased C4 (6/12) , positive anti-TPO IgG antibodies (5/12) and low total IgE levels (8/12) , increased proportion of CD4 + T cells (71.13% ± 3.26%) , and increased IL-17A levels (27.16 ± 9.75 pg/ml) compared with the well-responding group (14.3%, 10.7%, 14.3%, 7.1%, 10.7%, 14.3%, 60.33% ± 5.12%, 19.24 ± 10.84 pg/ml, respectively; all P < 0.05) , but decreased IL-6 levels compared with the well-responding group ( t = 5.75, P < 0.05) . According to the ROC analysis and calculation of sensitivity, specificity and accuracy, the above indicators showed high accuracy in predicting therapeutic effect of omalizumab, and the optimal cut-off values of IL-6, IL-17A, and CD4 + T cell proportion were 8.672 pg/ml, 23.415 pg/ml, and 67.95%, respectively. In addition, the IL-6 level was significantly positively correlated with the total IgE level in CSU patients at baseline ( r = 0.43, P = 0.006) . Conclusion:Before the selection of omalizumab for the treatment of refractory CSU, there is a need to detect the eosinophil and basophil counts, levels of complements C3, C4, anti-TPO IgG antibodies, total IgE, IL-17A and IL-6, and CD4 + T cell proportions to predict therapeutic effect of omalizumab, so as to determine whether omalizumab is suitable for the patients.
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Objective:To analyze clinical characteristics of neurosyphilis patients with abnormal mental behaviors as the initial symptom, and to provide a reference for clinical classification of, as well as outcome prediction and efficacy monitoring in neurosyphilis.Methods:Clinical data were collected from 67 HIV-negative neurosyphilis patients with abnormal mental behaviors as the initial symptom in the Second Affiliated Hospital of Soochow University from November 2012 to November 2019, and retrospectively analyzed. Statistical analysis was carried out by using t test. Results:Among the 67 patients, 52 (77.6%) were males, and 15 (22.4%) were females; there were 63 (94.0%) middle-aged and elderly patients and 4 (6.0%) adolescent patients; 38 (56.7%) patients were diagnosed with progressive general paresis, 21 (31.3%) with meningovascular neurosyphilis, 1 (1.5%) with meningeal neurosyphilis, 3 (4.5%) with tabes dorsalis, and 4 (6.0%) with mixed-type neurosyphilis. As laboratory examination showed, 67 patients all presented with positive serum rapid plasma reagin (RPR) test, serum Treponema pallidum particle agglutination (TPPA) test, and cerebrospinal fluid TPPA test, 55 (82.1%) had positive cerebrospinal fluid RPR test, 47 (70.1%) had elevated cerebrospinal fluid protein levels of > 0.45 g/L, 50 (74.6%) had increased white blood cell counts of > 8 ×10 6/L in cerebrospinal fluids, and 28 (41.8%) had elevated IgG levels in cerebrospinal fluids. Magnetic resonance imaging of the brain revealed multiple ischemic foci in 21 (31.3%) cases, multiple leukodystrophy in 17 (25.4%) , cerebral atrophy in 15 (22.4%) , infarction in 8 (11.9%) , and encephalitis-like changes in 2 (3.0%) . Of the 67 patients, 48 were treated with penicillin in aqueous solutions, 15 with ceftriaxone, and 4 with doxycycline. Six months later, the follow-up showed that 46 (68.7%) patients responded to the treatment, and the early course of disease was significantly shorter in the highly responsive group than in the poorly responsive group ( P < 0.05) . Conclusion:The middle-aged and elderly males were predominant in the neurosyphilis patients with abnormal mental behaviors as the initial symptom, magnetic resonance imaging is helpful for clinical classification and prognosis prediction of neurosyphilis, and early and standardized antisyphilitic treatment can markedly improve the prognosis of patients.
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Objective:To evaluate the efficacy and safety of recombinant human tumor necrosis factor-α receptorⅡ: IgG Fc fusion protein (rhTNFR:Fc) in the treatment of drug-induced toxic epidermal necrolysis (TEN) .Methods:From 2009 to 2018, 22 patients with TEN were enrolled from 8 centers such as the Second Affiliated Hospital of Soochow University, including 10 males and 12 females, whose age ranged from 22 to 75 years. These patients were subcutaneously injected with rhTNFR:Fc at a dose of 25 mg once every 3 days for 6 - 8 consecutive sessions, and the initial dose was doubled. The drug eruption area and severity index (DASI) score and DASI improvement indices (DASI50, DASI75 and DASI90) were assessed before treatment and on days 4, 7, 10, 13, 16, 19, 22 and 25 after treatment; cytometric bead array (CBA) technology was used to detect the level of tumor necrosis factor (TNF) -α in peripheral blood and blister fluid samples. During the treatment, body temperature, rash changes, liver and kidney function of patients were monitored, and adverse reactions were recorded. Statistical analysis was carried out by using repeated measures analysis of variance, paired t test and Pearson correlation analysis. Results:Of the 22 patients, the temperature stopped rising in 20 patients without infections 24 - 72 hours after the first treatment, and returned to normal after 48 - 120 hours. Among the 22 patients, new blisters stopped appearing 24 - 48 hours after the first treatment, the skin color changed from bright red to dark purple after 48 - 96 hours, and most skin lesions subsided after 2 weeks. After 2 - 4 weeks of treatment, levels of alanine aminotransferase and aspartate aminotransferase returned to normal in 19 patients with abnormal liver function. After 4 - 13 days of treatment, levels of creatinine and urea nitrogen stopped rising in 7 patients with abnormal renal function. During the treatment, the DASI score of the 22 patients gradually decreased ( F = 532.81, P < 0.01) , from 53.64 ± 8.67 before treatment to 2.05 ± 1.21 on day 25 after treatment ( t = 26.60, P < 0.001) . On day 10 after treatment, 22 patients (100%) achieved DASI50; on day 19, 22 (100%) achieved DASI75; on day 25, 20 (90.90%) achieved DASI90. The level of TNF-α in peripheral blood of the 22 patients gradually decreased along with the extension of treatment duration, from 33.95 ± 27.90 ng/L before treatment to 2.38 ± 0.79 ng/L on day 25. Before treatment, the level of TNF-α in blister fluid of 15 patients was 111.99 ± 99.41 ng/L, and the ratio of blister-fluid TNF-α level to peripheral blood TNF-α level was 1.83 - 28.21. Before treatment, no correlation was observed between the serum level of TNF-α and DASI score in the 22 patients ( P = 0.10) , while the blister-fluid TNF-α level was positively correlated with DASI score in the 15 patients ( r = 0.59, P = 0.02) . No acute adverse reactions were observed during the treatment. All the 22 patients completed the treatment and were discharged with complete recovery. During 6 months of follow-up after discharge, no recurrence or any complication was observed. Conclusion:rhTNFR:Fc is effective and safe for the treatment of drug-induced TEN.
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Objective To estimate the treatment effect of a tumor necrosis factor ? alpha antagonist (etanercept) on Stevens?Johnson syndrome induced by drugs. Methods After exclusion of tuberculosis, hepatitis, severe infections and tumors, 17 patients with drug?induced Stevens?Johnson syndrome were treated with subcutaneous injections of 25 mg(initial dose, 50 mg)etanercept once every 3 days for 6 times. Meanwhile, supportive therapies and compound glycyrrhizin injections were given to counteract inflammation and protect the liver. Results All of the patients were cured. Body temperature in 15 febrile patients gradually decreased within 24- 48 hours after the first injection of etanercept, and returned to normal in 72 hours. The number of vesicles stopped increasing, and lesion color turned from bright red to dull red within 24 hours. Skin condition was evidently controlled within 72 hours, and skin appearance almost returned to normal after 2 weeks of treatment, and was completely restored after 4- 5 weeks. The recovery of mucous membrane was slower than that of skin. Serum aminotransferase levels gradually declined after the first dose of etanercept and almost returned to normal in 2-4 weeks in 14 patients. Serum levels of urea nitrogen and creatinine began to decrease after 1- 2 weeks of treatment. The serum level of tumor necrosis factor?alpha nearly dropped into or was maintained in the normal range within 3 weeks after the start of treatment. Conclusion Early usage of tumor necrosis factor?alpha antagonists at an adequate dose is beneficial to the rapid control of Stevens?Johnson syndrome.
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Objective To explore the role of p16 gene methylation in fibroblasts in the occurrence and development of keloid.Methods Skin tissue specimens were resected from the lesions of patients with keloid and normal skin of healthy human controls.Fibroblasts were isolated from these tissue specimens and subjected a primary culture.An immunohistochemical analysis was performed to measure the expression of p16 protein in tissue specimens,real-time fluorescence-based quantitative PCR to determine the mRNA expression level (expressed as 2-△△Ct) of p 16 and DNA methyltransferases (DNMTs) in fibmblasts,and bisulfite sequencing PCR (BSP) to estimate the methylation status of p16 gene in the tissue specimens and primary fibroblasts.Results The keloid fibroblasts (KFbs) showed significandy lower mRNA expression of p16 gene (0.64 ± 0.18 vs.1.92 ± 0.23,t =10.54,P＜ 0.05),but significantly higher mRNA expressions of 3 DNMTs (DNMT1:2.58 ± 0.23 vs.1.13 ± 0.21,t =11.22,P ＜ 0.05; DNMT3A:4.87 ± 0.46 vs.2.38 ± 0.32,t =10.81,P＜ 0.05; DNMT3B:1.57 ± 0.12 vs.0.57 ± 0.16,t =12.45,P＜ 0.05) compared with the normal fibmblasts (NFbs).The DNA methylation rate in the p16 gene promoter region was significantly increased in keloid tissue (1.81％ ± 0.46％) and KFbs (3.15％ ± 0.94％) compared with normal skin tissue (0.90％ ± 0.35％,F =14.23,P＜ 0.01) and NFbs (0.17％ ± 0.29％,F=37.62,P＜ 0.01).Conclusions The methylation and low expression of p16 gene in KFbs may be associated with the uncontrolled growth of keloid,and DNMTs may play a role in the pathogenesis of keloid.
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Objective To study the proliferation,collagen production and related gene expression in keloids and normal skin fibroblast.Methods Isolated primary cells of keloid fibroblasts (KFb,n=12) and normal human dermal fibroblasts (NFb,n=12) were identified,the cell viability and proliferating potential and the cell cycle were detected,and the difference on the collagen synthesis between KFb and NFb were compared.The expression of cell cycle-associated genes such as p21,p16,and p27 was dectected by real-time fluorescent quantitative PCR.Results The phase contrast optical microscopy imaging showed that both KFb isolated from keloid tissues and NFb from normal skin tissues possessed classic and similar fibroblast morphology.But there was a significant difference between cell proliferation,Hyp [(2.30±0.10) μg/ml vs.(1.66±0.13) μg/ml,P＜0.05] and collagen levels [(17.19±0.75) μg/ml vs.(12.37±0.94) μg/ml,P＜0.05].Compared with NFb,KFb exhibited more percentage of G2/M phase cells [(5.90±0.62)％ vs.(16.94 ％±1.93)％,P＜0.05]and less percentage of G0/G1 phase cells [(90.24 ±2.27)％ vs.(75.65±1.92)％,P＜0.05].Cell cycle related genes p16,p21 and p27 were low expressed.Collagen type Ⅰ was highly expressed at mRNA levels in KFb than that in NFb [0.84±0.11,1.32±0.2,1.69±0.12,4.33±0.27 in KFb vs.1.43±0.13,2.56±0.26,2.89±0.37,1.40±0.12 in NFb,P＜0.05].Conclusions There are cell dysfunction and abnormal cellular dynamics in keloid fibroblasts.The formation of keloid likely involves aberrant interactions of some genes that affected its development at different extents.
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<p><b>OBJECTIVE</b>To injvestigate the cerebral blood flow of patients with early syphilis.</p><p><b>METHODS</b>(99)Tc(m)-ECD as brain perfusion imaging agent was used in single photon emission computed tomography (SPECT) for 32 patients with early syphilis and 15 controls. Visual analyses were made on every BSPECT image.</p><p><b>RESULTS</b>The 32 patients with early syphilis had general, patchy hypoperfusion of cerebral blood flow. Fourteen of the 32 patients had 48 episodes of marked patchy hypoperfusion of rCBF. The responsible areas of hypoperfusion in a patchy distribution involved the left frontal lobe (6 episodes), right frontal lobe (3), left parietal lobe (7), right parietal lobe (6), left temporal lobe (11), right temporal lobe (5), left occipital lobe (3), left basal ganglia (3), cerebellum (1), and nerve nuceus (1). No abnormality was found in the control group.</p><p><b>CONCLUSIONS</b>Cerebral blood flow abnormalities exist in patients with early syphilis. General patchy hypoperfusion on SPECT imaging is common.</p>
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Adult , Humans , Middle Aged , Brain , Diagnostic Imaging , Cerebrovascular Circulation , Physiology , Regional Blood Flow , Syphilis , Diagnostic Imaging , Tomography, Emission-Computed, Single-PhotonABSTRACT
Objective To explore the significance of RPR te st and Tp -IgM-Capture -ELISA in fol-lowing-up of early syphilis.Methods Sixty-one cases of primary syphilis with less than one-year course and 77cases of secondary syphilis were enr olled into the study.The patients we re followed up by RPR test and Tp -IgM-Capture -ELISAat intervals of three months for two years after treatment .Results By the end of 3,6,9,12,15,18,21and 24months,RPRtest became negative in 6.2%,31.5%,61.5%,83.8%,90.7%,92.3%,94.6%,and95.3%of patients,respectively.By the end of 3,6,9,12and 15months,Tp -IgM-Capture -ELISA became negative in 25.4%,56.5%,86.2%,97.1%and 100.0%of patients,respectiv ely.In primary syphilis the RPR test became nonreactive in 8.2%(3months after treatment ),31.1%(6months),57.4%(9months),75.4%(12months),83.6%(15months),85.2%(18months),and 100.0%(21months)of patients,and Tp -IgM-Cap-ture -ELISA in 45.9%(3months),85.2%(6months),98.4%(9months),100.0%(12months)of patients.In secondary syphilis RPRtest became n onreactive in 2.6%(3months after treatment ),28.6%(6months),58.4%(9months),81.8%(12months),84.4%(15months),88.3%(18months),90.9%(21months)and 92.2%(24months)of patients,and Tp -IgM-Capture -ELISAin 9.1%(3months),33.8%(6months),71.4%(9months),94.8%(12months)and 100.0%(15months)of patients.Tp -IgM-Capture -ELISA was found to be negative earlier than that of RPR test in all ca ses.No sero-resistant was shown in T p -IgM-Capture -ELISA.Conclusions Tp -IgM turns to negative in 12months after treatment for nearly all patie nts with early syphilis.Tp -IgM-Cap-ture -ELISA may be served as a useful t ool to follow up early syphilis patie nts after treatment.[