Treatment of Netherton Syndrome With Abrocitinib.

This case report describes a 28-year-old woman with Netherton syndrome who had large erythematous migratory patches with serpiginous double-edged scales on her face, neck, trunk, and extremities.

Effects of scale and contrast of spatial heterogeneity in plant-soil feedbacks on plant growth.

Spatial heterogeneity in plant-soil feedbacks (PSFs) has been evidenced to influence plant growth. However, it is unclear whether patch size and contrast of PSF heterogeneity influence plant growth. We first conditioned a background soil by seven species separately and then grew each of them in a homogeneous soil and three heterogeneous soils. The first heterogeneous soil (large patch and high contrast; LP-HC) consisted of two large patches, of which one was filled with the sterilized background soil and the other with the conditioned soil. The second heterogeneous soil (small patch and high contrast; SP-HC) consisted of four small patches, of which two were filled the sterilized background soil and the other two with the conditioned soil. The third heterogeneous soil (small patch and low contrast; SP-LC) also consisted of four patches, of which two were filled with a 1:3 (w:w) mixture and the other two with a 3:1 mixture of the sterilized background soil and the conditioned soil. In the homogeneous soil, all patches were filled with a 1:1 mixture of the two soils. Both shoot biomass and root biomass were equal in the homogeneous and heterogeneous soils. No significant growth difference was observed between the SP-HC and LP-HC heterogeneous soil. However, shoot biomass and root biomass of the legume Medicago sativa, and root biomass of the grass Lymus dahuricus were greater in the SP-HC heterogeneous soil than in the SP-LC heterogeneous soil, probably due to enhanced root growth in the conditioned soil. Moreover, plant growth in the heterogeneous soils was associated with plant growth but not soil nutrient availability at the end of the conditioning phase. Our results show for the first time that patch contrast of PSF heterogeneity can influence plant growth via changing root placement and highlight the importance of fundamentally different facets of PSF variability.

A novel model to assess disease activity in Takayasu arteritis based on 18F-FDG-PET/CT: a Chinese cohort study.

OBJECTIVE: To investigate the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in assessing disease activity in Takayasu arteritis (TA). METHODS: Ninety-one patients with TA were recruited from a Chinese cohort. Clinical data, acute-phase reactants and 18F-FDG-PET/CT findings were simultaneously recorded. The value of using 18F-FDG-PET/CT to identify active disease was evaluated, using ESR as a reference. Disease activity assessment models were constructed and concordance index (C-index), net reclassification index (NRI), and integrated discrimination index (IDI) were evaluated to compare the benefits of the new modes with ESR and the Kerr score. RESULTS: In total, 64 (70.3%) cases showed active disease. Higher levels of ESR and CRP, and lower IL-2 receptor (IL-2R) levels were observed in active cases. 18F-FDG-PET/CT parameters measured by determining the standard uptake value (SUV), including SUVmean, SUVratio1, SUVratio2, sum of SUVmean and sum of SUVmax, were significantly higher in active disease groups. The C-index threshold of ESR to indicate active disease was 0.78 (95% CI: 0.69, 0.88). The new activity assessment model combining ESR, sum of SUVmean and IL-2R showed significant improvement in C-index over the ESR method (0.96 vs 0.78, P < 0.01; NRI 1.63, P < 0.01; and IDI 0.48, P < 0.01). The new model also demonstrated modest superiority to the Kerr score assessment (0.96 vs 0.87, P = 0.03; NRI 1.19, P < 0.01; and IDI 0.33, P < 0.01). CONCLUSIONS: A novel 18F-FDG-PET/CT-based method that involves combining the sum of SUVmean with ESR score and IL-2R levels demonstrated superiority in identifying active TA compared with conventional methods.

The value of ultrasonography combined with clinical features for predicting carotid imaging progression of Takayasu's arteritis: a prospective cohort study.

OBJECTIVES: To identify valuable ultrasonography findings combined with clinical markers for predicting carotid progression of Takayasu's arteritis (TAK) on imaging during a 1-year follow-up period. METHODS: From May 2016 to June 2019, 77 Chinese TAK patients with carotid artery involvement were enrolled in the present study. The patients' clinical characteristics and serological test and carotid ultrasonography results were recorded at baseline and each visit. Carotid progression was evaluated by ultrasonography every 3 months during the 1-year follow-up. Baseline clinical characteristics and ultrasonography results for predicting progression on imaging were identified. RESULTS: Sixteen (20.8%) patients presented with carotid progression on imaging during the 1-year follow-up period. The patients in the progressive group were younger (23.4±3.7 vs. 32.3±9.8 years, p<0.01) than those in the non-progressive group. At baseline, the vessel wall was thicker in the progressive group than in the non-progressive group (2.4±0.8 vs. 1.9±0.5 mm, p=0.041). Furthermore, the proportion of patients with refractory disease (87.5% vs. 16.4%, p<0.01) was higher in the progressive group than in the non-progressive group. Patients with a thickened carotid wall (≥1.9 mm), refractory disease, and younger age (≤30 years) might be at a high risk of carotid progression on imaging (75%, AUC: 0.93, sensitivity: 75%, specificity: 93.4%). CONCLUSIONS: Younger patients with early vascular structural changes at baseline as well as refractory disease seemed more likely to show carotid progression on imaging.

A six-herb Chinese medicine composition ointment as a promising candidate for treatment of hypertrophic scars.

Objective: To study the anti-hypertrophic scar effect of the six-herb Chinese medicine composition (SCMC) ointment on the rabbit ear hypertrophic scar models. Methods: The optimal formulation of SCMC ointment matrix was screened by the orthogonal designs and a series of evaluation tests. The SCMC ointment was prepared through emulsifying method. The rabbit ear hypertrophic scar models were established and used to investigate the anti-hypertrophic scar effect of SCMC ointment. Results: Our results demonstrated that all the quality control indications of the SCMC ointment met the requirements. Anti-hypertrophic scar activity results showed that all the rabbit ear scar tissues appeared different degrees of shrink and fading, and took an unobvious but palpable shift from hard to soft texture with the low, middle and high concentration SCMC ointments treatments in vivo. Additionally, on 21st day the scar area and thickness in different concentrations of SCMC ointment groups were significantly reduced than control group, in a concentration-dependent manner. The immunohistochemical results also indicated that the SCMC ointment had good anti-hypertrophic scar properties and could inhibit hypertrophic scar formation. Conclusion: The SCMC ointment could improve the blood circulation condition of hypertrophic scar tissues. Our research has demonstrated the Chinese medicine composition ointment with good anti-hypertrophic scar properties that could be used to treat hypertrophic scars. Meanwhile, it provides a theoretical basis for further clinical application.

Potential risk of hyperuricemia: leading cardiomyocyte hypertrophy by inducing autophagy.

BACKGROUND: Clinical studies have shown that hyperuricemia is associated with many cardiovascular diseases; however, the mechanisms involved remain unclear. In this study, we investigated the effect of uric acid on cardiomyocytes and the underlying mechanism. METHODS AND RESULTS: H9c2 cardiomyocytes were treated with various concentrations of uric acid. 3-Methyladenine (3-MA) or Compound C was added before treatment with uric acid. The expression of myocardial hypertrophy-related genes was measured using polymerase chain reaction (PCR). The cell surface area was calculated using ImageJ Software. Western blotting was used to measure the protein levels. Uric acid increased the gene expression of Nppa, Nppb, and Myh5, which are involved in myocardial hypertrophy, and the relative cell surface area of cardiomyocytes in a dose-dependent manner. Consistently, the ratio of LC3II/I, which is a biomarker of autophagy, increased dose-dependently, whereas the protein level of p62, a protein that is degraded by autophagy, decreased. 3-MA, an autophagy inhibitor, rescued uric acid-induced myocardial hypertrophy. Treatment with uric acid increased the level of phosphorylated adenosine monophosphate kinase (AMPK), as well as its downstream effector unc-51-like kinase (ULK1). Pharmacological inhibition of AMPK by Compound C attenuated the uric acid-induced activation of autophagy and myocardial hypertrophy. CONCLUSIONS: Uric acid induces myocardial hypertrophy by activating autophagy via the AMPK-ULK1 signaling pathway. Decreasing the serum uric acid level may therefore be clinically beneficial in alleviating cardiac hypertrophy.

Complement C4 induces regulatory T cells differentiation through dendritic cell in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. Complement component 4 (C4) has be proved to play a role in pathogenesis of SLE. In the present study, we investigated the effect of C4 on T cells differentiation. METHODS: Thirty SLE patients were included in this study. CD4+ T cells were isolated from healthy subjects, and dendritic cells (DCs) were isolated from healthy subjects or SLE patients. C4 was supplemented to co-incubate with T cells and DCs. RESULTS: Serum C4 concentration was positively correlated with regulatory T cell (Treg) percentage (R(2) = 0.5907, p < 0.001) and TGFß concentration (R(2) = 0.5641, p < 0.001) in SLE patients. Different concentrations of C4 had no effect on T cells differentiation. Co-incubated T cells with DCs and C4 for 7 days, the Treg percentage and TGF-ß concentration were significantly elevated. In addition, pre-treated DCs (from healthy subjects or SLE patients) with C4 and then co-incubated with T cells, the increases of Treg percentage and TGF-ß concentration were also observed. CONCLUSION: C4 takes part in T cells differentiation to Treg cells via DCs.

Estradiol inhibits Th17 cell differentiation through inhibition of RORγT transcription by recruiting the ERα/REA complex to estrogen response elements of the RORγT promoter.

The symptoms of vaginal candidiasis exacerbate in the second half of the menstrual cycle in premenopausal women when the serum estradiol level is elevated. Estradiol has been shown to inhibit Th17 differentiation and production of antifungal IL-17 cytokines. However, little is known about the mechanisms. In the present study, we used mouse splenocytes and found that estradiol inhibited Th17 differentiation through downregulation of Rorγt mRNA and protein expression. Estradiol activated estrogen receptor (ER)α to recruit repressor of estrogen receptor activity (REA) and form the ERα/REA complex. This complex bound to three estrogen response element (ERE) half-sites on the Rorγt promoter region to suppress Rorγt expression. Estradiol induced Rea mRNA and protein expression in mouse splenocytes. Using Rea small interfering RNA to knock down Rea expression enhanced Rorγt expression and Th17 differentiation. Alternatively, histone deacetylase 1 and 2 bound to the three ERE half-sites, independent of estradiol. Histone deacetylase inhibitor MS-275 dose- and time-dependently increased Rorγt expression and subsequently enhanced Th17 differentiation. In 15 healthy premenopausal women, high serum estradiol levels are correlated with low RORγT mRNA levels and high REA mRNA levels in the vaginal lavage. These results demonstrate that estradiol upregulates REA expression and recruits REA via ERα to the EREs on the RORγT promoter region, thus inhibiting RORγT expression and Th17 differentiation. This study suggests that the estradiol/ERα/REA axis may be a feasible target in the management of recurrent vaginal candidiasis.

Symmetrical acrokeratoderma: A peculiar entity in China? Clinicopathologic and immunopathologic study of 34 new cases.

BACKGROUND: Symmetrical acrokeratoderma seems to be a new disorder in China, and 138 cases have been reported in the Chinese literature. OBJECTIVE: We sought to summarize the clinicopathologic features and immunophenotyping of inflammatory cells in 34 new cases. METHODS: Clinical data of 34 patients were prospectively collected over 4 years. Histopathology and immunostaining of infiltrated cells were performed in 27 and 9 patients, respectively. RESULTS: Brown to black hyperkeratotic patches were symmetrically distributed over the acral regions in 33 cases and on the scalp in 1 case, with a whitish change after water contact or sweating. The condition was aggravated in summer and alleviated in winter in 33 patients. History of ichthyosis vulgaris was seen in 23 cases. The typical histopathology included epidermal hyperkeratosis, acanthosis, and papillary dermal perivascular infiltrate of lymphohistiocytes. Number of CD3(+), CD4(+), and CD8(+) cells increased in lesional and perilesional skin compared with normal-appearing skin. The skin lesions developed slowly but were confined to the acral predilection sites after the mean follow-up of 25.4 ± 13.8 months. LIMITATIONS: The follow-up time was short. CONCLUSION: This disorder may represent a peculiar dermatosis that is frequently associated with ichthyosis vulgaris. No specific therapy is available for the disorder.

Feasibility of histological scoring and colony count for evaluating infective severity in mouse vaginal candidiasis.

Qualitative measurement of the infective level is relatively difficult in experimental vaginal candidiasis. Female BALB/c mice aged 8 to 10 weeks were randomly divided into E1, E2 and E0 groups, which received subcutaneous injection of 0.05 mg, 0.1 mg of estradiol benzoate or 0.1 ml soybean oil 3 days before vaginal inoculation, respectively, and hormone treatment continued every other day thereafter. Each group was further divided into infected and noninfected subgroups. The infected mice were inoculated intravaginally with 10 µl (5 × 10(4) conidia) of Candida albicans suspension, while the noninfected mice were inoculated with 10 µl phosphate-buffered saline. Direct microscopic examination, colony count and vaginal histopathology including infection degree and inflammation extent were performed at 3, 7 and 14 days post inoculation. Estrogen treatment increased the vaginal fungal burden and extent of infection and inflammation compared with the control group, and 0.3 mg/week estrogen generally induced more severe infection and inflammation than 0.15 mg/week estrogen did. Colony count peaked on day 3 and decreased remarkably after 7 days. Infection score increased gradually during the first 7 days and decreased on day 14, while inflammation extent exacerbated progressively over the course of 14 days. This study demonstrates that the modified histological scoring system might be more feasible than colony count for evaluation of infectivity and dynamic change in experimental vaginal candidiasis.

Immunosuppressive effect of cyclophosphamide on white blood cells and lymphocyte subpopulations from peripheral blood of Balb/c mice.

There has been lack of the uniform standard for establishment of animal immunodepressive models induced by cyclophosphamide (CTX), and the information about the immunosuppressive effect of CTX on peripheral blood lymphocyte subsets in rodents. Here we describe a CTX-induced mouse model and try to establish a feasible immunosuppressive model for studying the fungal pathogenicity. Balb/c mice received two intraperitoneal injections of different CTX doses (50-200 mg/kg) at 2-day intervals. Peripheral whole blood collected at different time-points before and after CTX injection was used to detect white blood cells (WBCs), lymphocytes and their subsets by automated hematology analyzer and flow cytometry, respectively. WBCs and lymphocytes in all groups except CTX50 (50 mg/kg CTX) group commenced to decrease in a dose-dependent manner on day 1, reached the nadir on day 4, rebounded on day 10, and declined again on day 17 after CTX treatment. Low dose (50 mg/kg) CTX produced no obvious change of percentage of CD3(+), CD4(+) and CD8(+) T cells and CD19(+) cells, but high doses (100 or 150 mg/kg) yielded a significant decrease of CD3(+) and CD4(+) cells on day 4 and CD19(+) cells on day 10, and increase of CD8(+) cells on day 4. The CD4(+)/CD8(+) ratio decreased on day 4, followed by a rebound thereafter when treated with 3 different doses of CTX. The results indicate that two intraperitoneal injections of CTX at 150 mg/kg at 2-day intervals may establish good immunosuppressive models of Balb/c mice for studying the fungal pathogenicity.

Intratumoral injection of pEGFC1-IGFBP7 inhibits malignant melanoma growth in C57BL/6J mice by inducing apoptosis and down-regulating VEGF expression.

Malignant melanoma (MM) is a type of aggressive skin cancer, and the effective therapy for MM is highly desired. Recently, genome-wide RNA interference screening study revealed that loss of expression of insulin-like growth factor binding protein 7 (IGFBP-7) is a critical step in development of MM, and this secreted protein plays a central role in apoptosis of MM. Furthermore, a prostatic carcinoma cell line stably transfected with IGFBP-7 cDNA showed poor tumorigenicity. Thus, we supposed it to be an efficacious agent for inhibiting melanomas. In this study, we constructed pEGFC1-IGFBP7 to try to obtain high expression of IGFPB7 and then we demonstrated that this plasmid inhibited proliferation of B16-F10 melanoma cells efficiently in vitro. Moreover, intratumoral injection of pEGFC1-IGFBP7 inhibited MM growth in C57BL/6J mice. The inhibition of MM growth is due to apoptosis and reduced expression of VEGF induced by pEGFC1-IGFBP7. These results suggest a potential new clinical strategy for MM treatment.

In-vivo transfection of pcDNA3.1-IGFBP7 inhibits melanoma growth in mice through apoptosis induction and VEGF downexpression.

BACKGROUND: Genome-wide RNA interference screening study revealed that loss of expression of insulin-like growth factor binding protein 7 (IGFBP7) is a critical step in development of a malignant melanoma (MM), and this secreted protein plays a central role in apoptosis of MM. In this study we constructed pcDNA3.1-IGFBP7 to obtain high expression of IGBPF7 and to inhibit the growth of MM in C57BL/6J mice. METHODS: pcDNA3.1-IGFBP7 was transfected into B16-F10 cell, the expression of IGFBP7 was detected by RT-PCR and western blot. The proliferations and apoptosis rates of transfected and control cells were measured by CCK8 and FCM, respectively. The tumorigenicity and tumor growth in both pcDNA3.1-IGFBP7 group and control groups were studied in C57BL/6J mice model. IGFBP7, caspase-3, and VEGF expressions in tumor tissue were measured by immunohistochemistry. Apoptosis of tumors were detected by TUNEL. RESULTS: We demonstrated this plasmid inhibited proliferation of B16-F10 melanoma cells efficiently in vivo, exploiting the high expression of IGFBP7. More importantly, in-vivo transfection of pcDNA3.1-IGFBP7 inhibited MM growth in C57BL/6J mice. The inhibition of MM growth was proved owing to apoptosis and reduced expression of VEGF induced by pcDNA3.1-IGFBP7. CONCLUSIONS: These results suggest a potential new clinical strategy for MM gene treatment.

Cutaneous phaeohyphomycosis of foot caused by Curvularia clavata.

A case of cutaneous lesions on the left foot caused by Curvularia clavata in a 64-year-old immunocompetent man is described. Fungal elements were found in the exudate and biopsy specimen. The isolate was identified as C. clavata based on its colonial and microscopic morphology in pure culture. The skin lesions healed after a 12-week regimen with oral fluconazole. This is the second case of cutaneous phaeohyphomycosis caused by C. clavata.

[Study on the classification of gonococcal island of different genotypes and effects of sac-4 gene on serum resistance of Neisseria gonorrhoeae].

OBJECTIVE: Using molecular methods to study the relationship between genotypes and serum resistance of Neisseria gonorrhoeae in Wuhan area. METHODS: NG-mast and serum bactericidal assays at the molecular level were used to differentiate the 46 strains which were isolated from the outpatients of sexually transmitted disease clinics and the relationship between different genotypes while phenotypes was also studied. RESULTS: 80.43% of the 46 strains contained the island and we were able to define three different combinations of genes in the isolates. Results from serum bactericidal assays showed that all 9 sac-4+ strains did not provide any serum resistance. CONCLUSION: Different isolates carried different gonococcal genetic islands (pathogenicity island) and certain phenotypes. There were no sobious relationship between sac-4 gene and serum resistance of Neisseria gonorrhoeae.

Granulomatous skin infection caused by Malassezia pachydermatis in a dog owner.

BACKGROUND: Malassezia pachydermatis is part of the normal cutaneous microflora of dogs and many other mammals. M pachydermatis has not yet been reported as an agent that causes skin infection in humans, although it has been found to cause fungemia and other nosocomial infections in preterm newborns and immunocompromised adults. OBSERVATIONS: Malassezia pachydermatis was isolated from the facial granuloma of a healthy woman and her dog's skin scrapings and cerumen. The yeast identity was established by standard methods and scanning electron microscopy. A skin biopsy specimen showed chronic inflammatory granuloma, numerous purple-red round or ovoid spores in the superficial necrotic tissue, and sparse red spores in the dermis. The skin lesions healed after oral fluconazole and cryotherapy. CONCLUSIONS: Definite diagnosis of M pachydermatis-induced skin infection principally depends on the results of fungal culture and histologic examination, and the combination of oral fluconazole and adjunctive cryotherapy seems to be an effective therapeutic regimen.