Injectable antimicrobial hydrogels with antimicrobial peptide and sanguinarine controlled release ability for preventing bacterial infections.

The emergence of antibiotic resistant bacteria represents a significant and common clinical problem worldwide as infections are becoming increasingly common. It is urgent to broaden the sources of biomaterials that can prevent both bacterial infection and antibiotic resistance. In this work, oxidized sodium alginate/aminated hyaluronic acid (OSA/AHA) hydrogel with various proportions was developed based on Schiff base reaction. Herein, polydopamine (PDA)-Bmkn2 nanoparticle and sanguinarine were incorporated into hydrogels to enhance antibacterial properties. The prepared PDA-Bmkn2 nanoparticles, with uniform particle size and good dispersion, could serve as a delivery system for Bmkn2. The prepared hydrogels showed appropriate swelling ratio, extremely good mechanical strengths and improved biodegradability. Meanwhile, the Bmkn2 and sanguinarine were released from the hydrogels in a sustainable manner. Furthermore, OSA/AHA/sanguinarine/PDA-Bmkn2 hydrogel (less than 10 µg/mL BmKn2 and 0.2 µg/mL sanguinarine) had excellent biocompatibility. Antibacterial experiments confirmed that OSA/AHA/sanguinarine/PDA-Bmkn2 hydrogel had effective antimicrobial activity on Escherichia coli and Staphylococcus aureus. Therefore, the prepared injectable hydrogels with good biocompatibility and excellent synergistic antibacterial activity promise great potential for preventing localized bacterial infections.

The clinical efficacy of treatment using the autologous non-cultured epidermal cell suspension technique for stable vitiligo in 41 patients.

Background: Vitiligo is an acquired depigmentation skin disorder mainly caused by the destruction of melanocytes. There are many therapeutic options available for vitiligo, but the options are not uniformly effective.Objectives: This study aimed to explore the clinical effect of the autologous non-cultured epidermal cell suspension (NCES) technique in the treatment of patients with stable vitiligo.Methods: A retrospective study of before-after comparisons was undertaken with 41 patients with stable vitiligo who received treatment with the NCES technique. The percentage of repigmentation area was evaluated using image analysis of the appearance before and 6-9 months after operation.Results: A total of 41 patients (18 males and 23 females) with a duration of clinical stability for ranging from 1 to 10 years (mean 1.6 ± 1.9) were included. The mean age was 20.2 years (range, 8-50) and 4 (9.8%) were children under the age of 14 years. After 6-9 months of follow-up, 80.5% (33/41) of the patients showed good response; among these patients, 17.1% (7/41) showed complete or almost complete repigmentation. Interestingly, all 4 children showed very good response (more than 76% repigmentation). There were no significant differences in the efficacy of treatment between the different transplantation areas of the facial neck, trunk, and distal limbs and there were no adverse effects such as infection or scar formation.Limitation: This study included only a single center with a small sample size.Conclusions: Our study shows that the NCES technique has a high therapeutic effect, is safe for patients with stable vitiligo, and may be a very promising potential option for treating children.

High expression of disabled homolog 2-interacting protein contributes to tumor development and proliferation in cutaneous squamous cell carcinoma.

BACKGROUND: Disabled homolog 2-interacting protein (DAB2IP), a Ras GTPase-activating protein, is downregulated in several cancers. Its depletion is involved in tumor cell proliferation, apoptosis, and metastasis, as well as epithelial-mesenchymal transition. The present study aimed to explore the potential role of DAB2IP in cutaneous squamous cell carcinoma (cSCC) and provide a theoretical basis for the diagnosis and targeted therapy of cSCC. METHODS: The clinicopathological features of DAB2IP expression in cSCC were analyzed by immunohistochemistry, and the effects of DAB2IP on SCL-1 cell behavior were determined via genetic interference in vitro. SCL-1 cell lines that exhibited reduced expression of DAB2IP and a scrambled shRNA control were constructed using a lentivirus vector-based shRNA technique. RNA extraction, reverse transcription-quantitative PCR (RT-qPCR), MTT assay, colony formation test, cell cycle analysis, apoptosis test, transwell assay, wound-healing assay, in vitro invasive assay were used in this study. RESULTS: The immunohistochemical results demonstrated that the expression of DAB2IP was higher in cSCC tissues than in soft fibroma. The level of DAB2IP expression was associated with the degree of malignancy and the depth of tumor infiltration; however, it had no association with patients' sex, tumor size, location, or phenotype. The results of the MTT, cell cycle, apoptosis, and invasion experiments demonstrated that knockdown of DAB2IP inhibited the viability and invasion of SCL-1 cells in vitro. CONCLUSIONS: High expression of DAB2IP may contribute to the development and proliferation of cSCC.

Secukinumab monotherapy successfully treated severe refractory type V (atypical juvenile) pityriasis rubra pilaris: A case report and literature review.

Pityriasis rubra pilaris (PRP) is a rare heterogeneous group of papulosquamous inflammatory disorders with unknown etiology. PRP is often resistant to many conventional therapies which has made more challenging on treatment. More recently, several studies have shown encouraging clinical results of secukinumab in the treatment of PRP in adult, but no studies have explored its effects in children. We herein report a 7-year-old boy with severe type V PRP responded rapidly to secukinumab monotherapy (150 mg once weekly) when conventional therapies have failed. The patient showed rapid and dramatic improvement of erythema, palmoplantar hyperkeratosis, scaling, and itching within only 5 weeks, with no adverse effects. Secukinumab could be considered as a treatment option for refractory PRP in children, as recently reported in adult.

Successful treatment of facial localized discoid lupus erythematosus with intralesional betamethasone: A report of three cases.

Discoid lupus erythematosus (DLE) is a chronic autoimmune skin disease that usually causes disfiguring scarring, dyspigmentation, and atrophy. Despite a range of available topical and systemic therapies, the treatment of DLE remains a therapeutic challenge, especially in some refractory cases. Here, we reported three male patients with long-term chronic lesions of unilateral facial localized DLE, who failed to have their disease controlled with many previous topical/systemic treatments, showed rapid and well response to intralesional injections of betamethasone (2 mg/mL, 0.2 mL/site) monotherapy once every 2 weeks for two, two, and four times of treatment, respectively. Intralesional betamethasone may provide a safe and effective alternative in the management of refractory localized DLE skin lesions.

Azithromycin-resistant Neisseria gonorrhoeae isolates in Guangzhou, China (2009-2013): coevolution with decreased susceptibilities to ceftriaxone and genetic characteristics.

BACKGROUND: The recent emergence of azithromycin-resistant (AZM-R) N. gonorrhoeae isolates that have coevolved decreased susceptibility to extended-spectrum cephalosporins has caused great concern. Here we investigated the prevalence of decreased susceptibility to ceftriaxone (CRO(D)) in AZM-R isolates and genetically characterized AZM-R isolates in Guangzhou, China from 2009 to 2013. METHODS: The minimum inhibitory concentration (MIC) of AZM and ceftriaxone was determined using an agar-dilution method. All AZM-R isolates were screened for mutations in 23S rRNA, mtrR and penA genes and genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST). RESULTS: Of the 485 identified N. gonorrhoeae isolates, 445 (91.8%) were isolated from male urethritis subjects, and 77 (15.9%) were AZM-R (MIC ≥ 1 mg/L), including 33 (6.8%) with AZM low-level resistant (AZM-LLR, MIC = 1 mg/L) and 44 (9.1%) with AZM middle-level resistant (AZM-MLR, MIC ≥ 2 mg/L). Significantly more CRO(D) (MIC ≥ 0.125 mg/L) showed in AZM-MLR isolates (43.2%, 19/44) as compared with that in AZM-LLR isolates (18.2%, 6/33) (p < 0.05). For the 23S rRNA, mtrR, penA or combined 23S rRNA/MtrR/penA mutations, no significant difference was found between AZM-LLR isolates and AZM-MLR isolates (P > 0.05); similar results were detected between combined AZM-LLR/CRO(D) isolates and combined AZM-MLR/CRO(D) isolates (P > 0.05). No mutation A2059G or AZM high-level resistant (AZM-HLR, MIC ≥ 256 mg/L) isolate was detected. Among 77 AZM-R isolates, 67 sequence types (STs) were identified by NG-MAST, of which 30 were novel. Most STs were represented by a single isolate. CONCLUSIONS: The AZM-R together CRO(D) isolates are now present in Guangzhou, China, which deserve continuous surveillance and the mechanism of concurrent resistance needs further study.

Identification and functional characterization of a novel transglutaminase 1 gene mutation associated with autosomal recessive congenital ichthyosis.

BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a group of genetically heterogeneous diseases. Mutations in transglutaminase (TGase) 1 gene (TGM1, OMIM 190195) have been implicated in ARCI. However, little is known about TGM1 mutations in the Chinese population, and no functional studies have investigated the biological effect of mutant TGM1 on human epidermal keratinocytes (HaCaT) cells. OBJECTIVES: To identify the pathogenic mutations of TGM1 gene in two Chinese siblings with ARCI and gain insight into functional consequences of these mutations. METHODS: Fifteen exons and flanking splice sites of TGM1 gene were amplified by polymerase chain reaction and then underwent bidirectional Sanger sequencing. The HaCaT cells were transfected with lentiviral vectors, which overexpressed either wild-type or mutant TGM1 cDNAs with deleted homeodomain. Cell proliferation and cell cycle progression were detected. The expression of cyclin D1, cyclin B1, CDK4, TGM1, K10, involucrin, and filaggrin proteins were investigated by Western blot analysis. RESULTS: We found two compound heterozygous missense mutations (c.515C>T, R143C in exon 3 and c.759C>T, S212F in exon 4) in both siblings. HaCaT cells transfected with mutant TGM1 cDNAs displayed a lower growth rate and delayed S phase while overexpression of wild-type TGM1 cDNAs led to accelerated growth. HaCaT cells transfected with mutant TGM1 cDNAs displayed lower expression of differentiation markers such as involucrin and filaggrin. Our findings suggest that the compound heterozygous missense (c.515C>T, R143C) mutations in exon 3 and missense (c.759C>T, S212F) mutations in exon 4 result in the phenotype of ARCI. TGM1 mutations can suppress keratinocyte growth and cornified cell envelope formation.

Trends in antimicrobial resistance in Neisseria gonorrhoeae isolated from Guangzhou, China, 2000 to 2005 and 2008 to 2013.

A total of 1224 Neisseria gonorrhoeae isolates from Guangzhou in 2 periods (2000-2005 and 2008-2013) were subjected to antimicrobial susceptibility testing. The percentage of penicillin- and ciprofloxacin-resistant isolates increased from 71.1% (473/665) to 90.9% (508/559) and 88.9% (591/665) to 98.0% (548/559), respectively. All isolates remain susceptible to spectinomycin and ceftriaxone, with increasing minimum inhibitory concentrations.

Ultrastructural study of symmetrical acral keratoderma.

BACKGROUND: Symmetrical acral keratoderma is characterized by symmetrical brown hyperkeratotic patches on the acral extremities. However, no studies about its electron microscopic examination have been documented. OBJECTIVE: Our study was performed to further characterize the histopathology of symmetrical acral keratoderma. METHODS: A biopsy was taken from brown hyperkeratotic patches on the wrists. Investigative studies included light and electron microscopy. RESULTS: Light microscopy showed epidermal basket-weave hyperkeratosis and acanthosis. Ultrastructurally, the epidermis was thickened by acanthosis and compact stratum corneum. The horny cell layers were remarkably thicker in clinical affected skin than in adjacent clinically unaffected and healthy skin. The keratin filaments were remarkably clumped or aggregated and irregularly distributed in the horny, spinous, granular and basal cell layers. The tonofilaments formed tight clumps or aggregated at the perinuclear cytoplasm. CONCLUSION: The main ultrastructural features of symmetrical acral keratoderma were epidermal hyperkeratosis and abnormalities of the keratin filaments and tonofilaments.

[Mutation analysis for GJB2 and LOR genes in two patients with Vohwinkel syndrome].

OBJECTIVE: To detect potential mutations of gap junction protein beta 2 (GJB2) and loricrin (LOR) genes in two patients with Vohwinkel syndrome. METHODS: Polymerase chain reaction and DNA sequencing were used for detecting potential mutations in the GJB2 and LOR genes. Parents of one patient and 50 healthy individuals were used as controls. RESULTS: A novel homozygous missense mutation (c.A796G) of LOR gene was detected in one patient. The same mutation was not found in the other patient, their relatives and the 50 healthy controls. CONCLUSION: A missence mutation of LOR gene was detected in a patient with Vohwinkel syndrome.

[Association of filaggrin gene polymorphism with atopic dermatitis in southern Chinese Han population].

OBJECTIVE: To investigate the association of filaggrin gene (FLG) polymorphism with atopic dermatitis (AD) in southern Chinese Han population. METHODS: The frequencies of the 13 known FLG gene single nucleotide polymorphism(SNPs), including 3321delA, 441delA, 1249insG, E1795X, S3296X, R501X, 2282del4, R2447X, S2889X, 7945delA, 3702delG, Q2417X, R4307X, were detected in a cohort of 50 AD patients and 100 control individuals using polymerase chain reaction (PCR) and DNA sequencing. RESULTS: FLG 3321delA and 441delA were detected in 14 (28%) and 6 (12%) AD patients, respectively. The other 11 SNPs were not detected in the patients. None of the 13 SNPs was detected in the controls. CONCLUSION: The results suggested that the FLG gene might be associated with atopic dermatitis susceptibility in southern Chinese Han population.

[Expression, clinical and pathological significance of KIAA1173 gene in skin squamous cell carcinoma].

OBJECTIVE: To clone, prepare probe for and explore the expression levels of KIAA1173 gene in skin squamous cell carcinoma (SSCC) and investigate its expression, clinical and pathological significance. METHODS: KIAA1173 gene fragment (354 bp) was cloned and its cDNA probe prepared. The expression of KIAA1173 gene in 133 SSCC tissue samples (including 52 specimens of I, 37 specimens of II, 31 specimens of III and 13 specimens of IV) and 47 normal controls were examined by in situ hybridization (ISH). And all specimens were embedded in paraffin. RESULTS: ISH showed brown positive granules in the cytoplasm of parenchymal cells. The positive rate of KIAA1173 mRNA was 38.3% (51/133) in SSCC and 93.6% (44/47) in normal controls. The rate was lower in cancer groups than that in normal tissues (chi(2) = 42.567, P < 0.01). The strongly positive rates were significantly lower in SSCC groups (6.0%, 8/133) than that in normal control (48.9%, 23/47, chi(2) = 44.876, P < 0.01). The negative rates of KIAA1173 mRNA were 53.8% (28/52) in SSCC I, 62.2% (23/37) in SSCC II, 67.7% (21/31) in SSCC III and 76.9% (10/13) in SSCC IV (chi(2) = 4.005, P > 0.05). The negative rates of KIAA1173 mRNA in the dys-good differentiation group (70.5%, 31/44) was higher than that in the good differentiation group (57.3%, 51/89), but there was not significant difference between the two groups (chi(2) = 2.154, P > 0.05). CONCLUSION: KIAA1173 gene is highly expressed in normal skin, but it becomes down-regulated in SSCC. It may play an important role in the development of SSCC.

Proteus syndrome: a case report and a case study review in China.

Proteus syndrome (PS) is a rare and sporadic disorder characterized by overgrowth of multiple tissues and a propensity to develop particular neoplasms. The clinical manifestations of PS include macrodactyly, vertebral abnormalities, asymmetric limb overgrowth and length discrepancy, hyperostosis, abnormal and asymmetric fat distribution, asymmetric muscle development, connective tissue nevi, and vascular malformations. We report a 16-year old female patient who manifested a number of these complications and review the Chinese literature about the diagnosis, natural history, and management of PS.

Acitretin systemic and retinoic acid 0.1% cream supression of basal cell carcinoma.

Retinoids have been used for years as monotherapy and/or in combination for treatment and suppression of cutaneous malignancies in patients with basal cell nevus syndrome, xeroderma pigmentosum, or cutaneous T-cell lymphoma (CTCL) basal cell carcinoma (BCC). We report 4 cases with BCC confirmed by histopathology who were treated by short-term systemic acitretin combined with retinoic acid 0.1% cream. The 4 cases with BCC showed good response to the treatment without severe adverse effects during treatment and follow-up. The finding suggests that acitretin may be an appropriate treatment option for elderly patients who require less invasive treatment for BCC.

Clinical investigation of acitretin in children with severe inherited keratinization disorders in China.

OBJECTIVE: Investigation into the clinical efficacy, side effects and safety of oral acitretin on severe inherited disorders of keratinization in children. METHODS: Acitretin was given as a treatment dose of 0.77-1.07 mg/kg x per day (mean 0.86+/-0.11) and maintenance dose of 0-0.94 mg/kg x per day (mean 0.33+/-0.26) to 28 children with severe inherited disorders of keratinization. Body height and weight were chosen as the monitoring indexes to evaluate the growth and development and other common side effects as the safety evaluation of the children for a follow-up of 2-36 months. RESULTS: After 2-4 months of treatment, the clinical cure rate was 82.1% and the effective rate was 17.9%. Most cases, such as bullous ichthyosiform erythroderma, lamellar ichthyosis, pityriasis rubra pilaris, and inflammatory linear verrucous epidermal nevus showed remarkable therapeutic response; non-bullous ichthyosiform erythroderma was also effective. Two cases with Darier's disease were previously shown to be resistant to acitretin therapy, but improved after 6 months of treatment. No previous investigation had been made on a negative effect on the growth and development of such children. CONCLUSION: Acitretin showed a satisfactory therapeutic effect on severe inherited disorders of keratinization in children.