Efficacy and safety profile of dupilumab for the treatment of atopic dermatitis in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Dupilumab is the first biologic approved for the treatment of moderate-to-severe atopic dermatitis (AD) in children and adolescents. Previous systematic reviews explored the effectiveness and safety of dupilumab in adults with AD. However, the underlying mechanisms of AD can vary among different age groups, emphasizing the need for separate investigation into the use of dupilumab in children and adolescents with AD. OBJECTIVE: To evaluate the efficacy and safety of dupilumab in children and adolescents with AD based on evidence from clinical trials and observational studies. METHODS: The process of meta-analysis was conducted according to preferred reporting items for systematic reviews and meta-analyses guidelines. RESULTS: Seven clinical trials and 11 observational studies involving 1275 children and adolescents with AD were eligible for quantitative analysis. Overall, the pooled percentages of eczema area and severity index (EASI) 50, EASI 75, EASI 90, EASI 100, and investigator's global assessment (IGA) 0/1 were 72.9% (95% CI: 61.6%-81.9%), 57.4% (48.1%-66.2%), 31.3% (24.0%-39.7%), 29.7% (23.3%-37.0%), and 35.2% (29.3%-41.5%). With prolonged treatment time, an increase was seen in the pooled rate of EASI response, indicating that dupilumab may provide sustained benefits for children and adolescents over the long term. The reported adverse events were primarily mild and manageable, with an overall incidence rate of 7.2% across clinical trials and 7.6% across observational studies. CONCLUSION: Dupilumab was an effective and safe treatment option for children and adolescents with AD, with positive results observed from long-term use and an acceptable safety profile. More long-term, high-quality, controlled studies in different regions are needed for further verification.

New era of medical education: asynchronous and synchronous online teaching during and after COVID-19.

COVID-19 struck the world suddenly and unexpectedly. Since traditional education requires face-to-face communication, to avoid further spreading of the virus a majority part of that education has moved online. Our study attempts to compare the differences between online medical education with a unique course design and traditional face-to-face education. We conducted a retrospective analysis of a total of 4,098 medical students between 2019 and 2020, including two groups of students who received online education and classroom education for the same subjects, respectively. Freshmen enrolled in September 2018 received traditional classroom physiology and pharmacology education in the spring semester of 2019. Because of the impact of the COVID-19 pandemic, freshmen who were enrolled in September 2019 received online physiology and pharmacology education in the spring semester of 2020. The final marks of the two groups of students were recorded and compared. Data on students participating in online discussions, learning, homework, and watching instructional videos were also recorded. There was no significant difference in the final academic performance between the two groups [average mark: 55.93 (online education) vs. 56.27 (classroom education), P = 0.488]. Further analysis showed that student participation rates in online discussions, online learning, and online viewing of instructional videos were closely correlated with final grades in online courses (P < 0.01). In conclusion, our results suggest that the pedagogical effects of online education during COVID-19 were promising, and we provide a well-designed medical online course to inspire further improvements in online education.NEW & NOTEWORTHY The COVID-19 pandemic has led to a massive temporary conversion of offline education to online education worldwide. Previous studies have noted that more students believed they had better learning experience in face-to-face learning. However, with our method of online teaching, we still showed a relatively similar performance result compared with offline education.

A meta-analysis of the effectiveness of antibacterial bone cement in the treatment of diabetic foot skin wound infections.

A meta-analysis research was implemented to appraise the effect of antibiotic bone cement (ABC) in treating infected diabetic foot wounds (IDFWs). Inclusive literature research till April 2023 was done and 1237 interconnected researches were revised. The 15 selected researches enclosed 895 IDFWs persons were in the utilized researchers' starting point, 449 of them were utilizing ABC, and 446 were in the control group. Odds ratio and 95% confidence intervals were utilized to appraise the consequence of ABC in treating IDFWs by the contentious approach and a fixed or random model. ABC had significantly lower wound healing time (MD, -9.83; 95% CI, -12.45--7.20, p < 0.001), and time to bacterial conversion of the wound (MD, -7.30; 95% CI, -10.38--4.32, p < 0.001) compared to control in IDFWs persons. However, caution needs to be taken when interacting with its values since there was a low sample size of most of the chosen research found for the comparisons in the meta-analysis.

Benefits and harms of NK1 R antagonists in pruritus: A systematic review and meta-analysis.

Accumulating evidence has showed the possibility of using NK1R antagonists for the treatment of chronic pruritus. However, the benefit and risk profile of NK1R antagonists-serlopitant and aprepitant for the treatment of pruritus remains unclear. To assess the efficacy and safety of NK1R antagonists-serlopitant and aprepitant in patients with pruritus based on analysis of clinical trials. The current systematic review and meta-analysis was performed according to PRISMA guidelines. A total of 10 randomized clinical trials including 631 patients were enrolled. Four randomized controlled trials investigated the comparative treatment effect of serlopitant on pruritus. Our results showed that serlopitant had reasonable anti-pruritic effectiveness in patients, with mild toxicities. The overall proportion of 4-point improvement of NRS and VAS in serlopitant-treatment group were both significantly higher relative to placebo group (OR 2.345, 95%CI 1.557 to 3.531, P < .001; OR 3.308, 95% CI 1.949 to 5.616, P < .001). Serlopitant treatment was also found to be associated with a significant reduction in NRS score as compared with placebo (SMD -0.381, 95%CI -0.599 to -0.164, P = .001). Six clinical trials reported the treatment effect of aprepitant on pruritus. The meta-analysis result of fixed-effect model showed that there was no significant difference between aprepitant and controlled treatment in terms of improved pruritus VAS score (SMD -0.088, 95%CI -0.384 to 0.207, P = .558). There is promising high-quality evidence regarding the efficacy of serlopitant on pruritus. More large-sample randomized controlled trials with appropriate treatment regimen are urgently needed to further evaluate the effectiveness of aprepitant in pruritus.

Emergency stress management among nurses: A lesson from the COVID-19 outbreak in China-a cross-sectional study.

AIMS AND OBJECTIVES: To assess the level of stress response, self-efficacy and perceived social support status of working nurses during the outbreak of the COVID-19 and investigate potential factors affecting their stress. BACKGROUND: The stress level of clinical nurses directly affects their physical and mental health and work efficiency. DESIGN: This study was a cross-sectional investigation, which was performed following the STROBE checklist. The current study was conducted in February 2020 by selecting clinical nurses from the Zigong First People's Hospital for investigation. METHODS: At the peak of the COVID-19 outbreak in China, we assessed clinical nurses with the Stanford Acute Stress Reaction Questionnaire, the General Self-Efficacy Scale and the Perceived Social Support Scale. Specifically, the nurses were divided into three groups: (a) nurses supporting Wuhan; (b) nurses in the department of treating the COVID-19 patients in our hospital (epidemic department); and (c) nurses in the general department without the COVID-19 patients in our hospital (non-epidemic department). RESULTS: A total of 1092 clinical nurses were surveyed with 94 nurses in Wuhan, 130 nurses treating COVID-19 patients in our hospital and 868 nurses working without direct contact with diagnosed COVID-19 patients. The mean stress score of all surveyed nurses was 33.15 (SD: 25.551). There was a statistically significant difference in stress response scores between different departments. Noticeably, the nurses who went to support in Wuhan showed a weaker stress response than the nurses who stayed in our hospital (mean: 19.98 (Wuhan) vs. 32.70 (epidemic department in our hospital) vs. 34.64 (non-epidemic department in our hospital)). In addition, stress was negatively correlated with general self-efficacy and perceived social support. CONCLUSION: The present study suggested that the stress status of second-line nurse without direct contact with diagnosed COVID-19 patients was more severe than that of first-line nurses who had direct contact with COVID-19 patients. RELEVANCE TO CLINICAL PRACTICE: Our study indicated the importance of psychological status of second-line medical staff during the global pandemic.

Current advances of Dendrobium officinale polysaccharides in dermatology: a literature review.

CONTEXT: Dendrobium officinale Kimura et Migo (Orchidaceae) is a naturally occurring precious traditional Chinese medicine (TCM) originally used in treating yin-deficiency diseases. The main active substances of Dendrobium officinale are polysaccharides (DOP). Recent findings highlighted the potential of DOP as a promising natural material for medical use with a diversity of pharmaceutical effects. OBJECTIVE: In this review, we provide a systematic discussion of the current development and potential pharmacological effects of Dendrobium officinale polysaccharides in dermatology. METHODS: English and Chinese literature from 1987 to 2019 indexed in databases including PubMed, PubMed Central, Web of Science, ISI, Scopus and CNKI (Chinese) was used. Dendrobium officinale, Dendrobium officinale polysaccharides, phytochemistry, chemical constituents, biological activities, and pharmacological activities were used as the key words. RESULTS: Dendrobium officinale polysaccharides have been found to possess hair growth promoting, skin moisturising and antioxidant effects, which are highly valued by doctors and cosmetic engineers. We highlighted advances in moisturising and antioxidant properties from in vivo and in vitro studies. Dendrobium officinale polysaccharides exhibited strong antioxidant effects by decreasing free radicals, enhancing antioxidant system, inhibiting nuclear factor-kappa B and down-regulating inflammatory response. CONCLUSIONS: Our review is a foundation to inspire further research to facilitate the application of Dendrobium officinale polysaccharides in dermatology and promote active research of the use of TCM in dermatology.

Impact of enhanced recovery program on patients with esophageal cancer in comparison with traditional care.

PURPOSE: Enhanced recovery program (ERP) was reported to be beneficial to patients undergoing esophageal surgery. However, evidence for ERP as a new standard perioperative pathway is insufficient. This meta-analysis aims to systematically investigate the differences between ERP and traditional care in terms of postoperative outcomes. METHODS: Studies comparing ERP with traditional care were searched in Pubmed and Ovid databases and subsequently analyzed. The primary outcome of interest was postoperative length of hospital stay (LOHS), and the secondary outcomes of interest were postoperative morbidity, mortality, and 30-day readmission rates. Statistical analysis was performed using weighted mean difference (WMD) and odds ratio (OR). Review Manager 5.3 was used to generate the eligible data. RESULTS: Thirteen studies with 2358 patients (1182 patients in the ERP group and 1176 patients in the control group) were included in this meta-analysis. The total LOHS (WMD -5.37; 95 % confidence interval (CI) -7.74 to -2.99; p < 0.00001) was significantly shorter in the ERP group than the control group. No statistically significant difference was found in morbidity (OR 0.78; 95 % confidence interval 0.58 to 1.05; p = 0.10), mortality (OR 0.76; 95 % CI 0.40 to 1.46; p = 0.41), and 30-day readmission rates (OR 1.01; 95 % CI 0.70 to 1.46; p = 0.97). CONCLUSIONS: This meta-analysis suggested that the implementation of ERP led to a reduction in LOHS, while morbidity, mortality, and 30-day readmission rates did not increase compared with traditional care in patients undergoing surgery for esophageal cancer.

Fabrication and in vitro characterization of gadolinium-based nanoclusters for simultaneous drug delivery and radiation enhancement.

We report the synthesis of a gadolinium hydroxide (Gd(OH)3) nanorod based doxorubicin (Dox) delivery system that can enhance both magnetic resonance imaging contrast and radiation sensitivity. A simple and cost effective wet-chemical method was utilized in the presence of manganese (Mn) ions and Dox to produce the Gd(OH)3:Mn·Dox nanocluster structure. The Gd(OH)3:Mn·Dox nanocluster was composed of Mn-doped Gd(OH)3 nanorods arranged in parallel with Dox as a linker molecule between the adjacent nanorods. No other studies have utilized Dox as both the linker and therapeutic molecule in a nanostructure to date. The Gd(OH)3 nanorod is reported to have no significant cellular or in vivo toxicity, which makes it an ideal base material for this biomedical application. The Gd(OH)3:Mn·Dox nanocluster exhibited paramagnetic behavior and was stable in a colloidal solution. The nanocluster also enabled high Dox loading capacity and specifically released Dox in a sustained and pH-dependent manner. The positively charged Gd(OH)3:Mn·Dox nanoclusters were readily internalized into MDA-MB-231 breast cancer cells via endocytosis, which resulted in intracellular release of Dox. The released Dox in cells was effective in conferring cytotoxicity and inhibiting proliferation of cancer cells. Furthermore, a synergistic anticancer effect could be observed with radiation treatment. Overall, the Gd(OH)3:Mn·Dox nanocluster drug delivery system described herein may have potential utility in clinics as a multifunctional theranostic nanoparticle with combined benefits in both diagnosis and therapy in the management of cancer.

Layered gadolinium-based nanoparticle as a novel delivery platform for microRNA therapeutics.

Specific expression patterns of microRNA (miRNA) molecules have been linked to cancer initiation, progression, and metastasis. The accumulating evidence for the role of oncogenic or tumor-suppressing miRNAs identified the need for nano-scaled platform that can help deliver nucleotides to modulate miRNAs. Here we report the synthesis of novel layered gadolinium hydroxychloride (LGdH) nanoparticles, a member of the layered double hydroxide (LDH) family, with physiochemical properties suitable for cell uptake and tracing via magnetic resonance (MR) imaging. As a proof of concept, we demonstrate the inhibition of mature miRNA-10b in metastatic breast cancer cell line using LGdH nanoparticle as a delivery platform. Through characterization analysis, we show that nanoparticles are easily and stably loaded with anti-miRNA oligonucleotides (AMO) and efficiently penetrate cell membranes. We demonstrate that AMOs delivered by LGdH nanoparticles remain functional by inducing changes in the expression of its downstream effector and by curbing the invasive properties. Furthermore, we demonstrate the traceability of LGdH nanoparticles via T1 weighted MR imaging. LGdH nanoparticles, which are biocompatible with cells in vitro, provide a promising multifunctional platform for microRNA therapeutics through their diagnostic, imaging, and therapeutic potentials.

2% Crisaborole Ointment for the Treatment of Chronic Cheilitis Caused by Lip Tattoos.

The increasing popularity of tattoo art, including facial cosmetic tattoos, has led to a growing societal acceptance of tattoos. However, complications such as lip inflammation following cosmetic lip tattoos remain a concern. This article presents the case of a 47-year-old Asian woman who experienced recurrent lip swelling, purulent discharge, and scarring after receiving lip tattoos. Despite previous treatment with corticosteroid injections yielding unsatisfactory results, the patient showed significant improvement with topical application of 2% Crisaborole, a phosphodiesterase-4 inhibitor. Crisaborole modulates intracellular cyclic adenosine monophosphate levels, thereby reducing tissue inflammation and swelling associated with chronic cheilitis. Additionally, pulse laser therapy was effective in addressing residual tattoo pigment and scar tissue. This case highlights the therapeutic challenges of managing chronic inflammatory diseases of the lips secondary to cosmetic tattoos and introduces Crisaborole as a promising treatment option, offering insights for managing similar conditions in the future.

Combinations of Energy-based Devices plus isotretinoin for management of acne and acne scars: A systematic review.

BACKGROUND AND OBJECTIVE: A 6-month interval between systemic isotretinoin (ISO) and the initiation of energy-based interventions has been recommended, due to concerns about keloid formation and delayed wound healing. While this postponement goes against the current trend of early intervention for acne scarring. This systematic review evaluates the efficacy, safety, and patient satisfaction of combinations of ISO with energy-based devices (EBD). STUDY DESIGN/METHODS AND MATERIALS: PubMed, Embase, Web of Science, Cochrane Library, and Cochrane Central Register of Controlled Trials were comprehensively searched up to April 2023 according to PRISMA guidelines. Two independent reviewers screened the titles and abstracts to select articles. The quality of the literature was assessed for each study design. RESULTS: A total of 16 studies addressing the efficacy and safety of energy-based modalities combined with ISO were identified, including six randomized controlled trials (RCTs), two case series, seven cohort studies, and one case report. ISO combinations with intense pulsed light (IPL), fractional ablative CO2 laser, pulsed dye laser (PDL), non-ablative fractional laser (NAFL) and fractional microneedle radiofrequency (FMRF) have been tested for improving acne severity, acne scarring and erythema. CONCLUSION: The current evidence does not justify delaying the use of EBDs for patients who have recently undergone or are currently receiving ISO treatment. Evidence-based treatments such as PDL, NAFL, and FMRF etc. are suggested relatively safe and effective in treating acne and acne scarring.

Recent Advances on Small-Molecule Inhibitors of Lipocalin-like Proteins.

Lipid transfer proteins (LTPs) are crucial players in nonvesicular lipid trafficking. LTPs sharing a lipocalin lipid transfer domain (lipocalin-like proteins) have a wide range of biological functions, such as regulating immune responses and cell proliferation, differentiation, and death as well as participating in the pathogenesis of inflammatory, metabolic, and neurological disorders and cancer. Therefore, the development of small-molecule inhibitors targeting these LTPs is important and has potential clinical applications. Herein, we summarize the structure and function of lipocalin-like proteins, mainly including retinol-binding proteins, lipocalins, and fatty acid-binding proteins and discuss the recent advances on small-molecule inhibitors for these protein families and their applications in disease treatment. The findings of our Perspective can provide guidance for the development of inhibitors of these LTPs and highlight the challenges that might be faced during the procedures.

Innovation and evaluation of vocational pharmaceutical education system under the 1 + X certificate system in China.

BACKGROUND AND OBJECTIVES: The 1 + X certificate system, introduced in China in 2019, integrates academic credentials with vocational skill certificates to meet the heightened demand for skilled talents in the growing economy. This study aims to innovate and evaluate the vocational pharmaceutical education system under the 1 + X certificate framework, specifically addressing the gap between theoretical education and workplace requirements. MATERIALS AND METHODS: A retrospective observational approach analyzed 490 pharmacy students over two academic years. The 2021 cohort underwent 1 + X integrated education, while the 2020 cohort followed conventional education. We collaborated closely with industry partners to identify and compile typical job competencies, formulating work projects aligned with industry demands. Combining the skill level standards and assessment content of "1+X Pharmaceutical Purchasing and Sales" and "1+X Pharmaceutical Preparation", we revised the course standards, incorporating typical work projects into the 2021 pharmacy professional teaching curriculum. This constituted the fundamental content of the 1 + X education reform. Statistical analysis compared course scores and 1 + X certificate examination performance. RESULTS: The 2021 cohort, under the 1 + X educational model, demonstrated higher average scores in pharmacy courses, with significant improvements in pharmacology (1 + X vs. Traditional education: 58.40 ± 14.20 vs. 53.44 ± 14.67), clinical pharmacotherapy (72.74 ± 10.28 vs. 63.15 ± 11.03), and pharmaceutical distribution and marketing (79.34 ± 10.96 vs. 67.50 ± 15.82). 1 + X certificate pass rates and satisfaction with the model were also higher than the 2020 cohort. CONCLUSION: The 1 + X certificate system is useful for developing talent in Chinese vocational education, effectively integrating assessments with industry standards. Future research should aim at evaluating long-term outcomes and improving quantitative skills assessments for enhanced effectiveness.

Polyphenolic Platform Ameliorated Sanshool for Skin Photoprotection.

Natural evolution has nurtured a series of active molecules that play vital roles in physiological systems, but their further applications have been severely limited by rapid deactivation, short cycle time, and potential toxicity after isolation. For instance, the instability of structures and properties has greatly descended when sanshool is derived from Zanthoxylum xanthoxylum. Herein, natural polyphenols are employed to boost the key properties of sanshool by fabricating a series of nanoparticles (NPs). The intracellular evaluation and in vivo animal model are conducted to demonstrate the decreased photodamage score and skin-fold thickness of prepared NPs, which can be attributed to the better biocompatibility, improved free radical scavenging, down-regulated apoptosis ratios, and reduced DNA double-strand breaks compared to naked sanshool. This work proposes a novel strategy to boost the key properties of naturally occurring active molecules with the assistance of natural polyphenol-based platforms.

Oral small-molecule tyrosine kinase 2 and phosphodiesterase 4 inhibitors in plaque psoriasis: a network meta-analysis.

Background: Orally administered small-molecule drugs including tyrosine kinase 2 (TYK2) inhibitors and phosphodiesterase 4 (PDE4) inhibitors are new candidates for systemic therapy in plaque psoriasis. However, no previous articles evaluated the benefit and risk profile of TYK2 and PDE4 inhibitors in psoriasis. Objectives: The objective of this study was to compare the efficacy and safety of oral small-molecule drugs, including TYK2 and PDE4 inhibitors, in treating moderate-to-severe plaque psoriasis. Methods: PubMed, Embase, and Cochrane library were searched for eligible randomized clinical trials (RCTs). Response rates for a 75% reduction from baseline in Psoriasis Area and Severity Index (PASI-75) and Physician's Global Assessment score of 0 or 1 (PGA 0/1) were used for efficacy assessment. Safety was evaluated with the incidence of adverse events (AEs). A Bayesian multiple treatment network meta-analysis (NMA) was performed. Results: In total, 13 RCTs (five for TYK2 inhibitors and eight for PDE4 inhibitors) involving 5274 patients were included. The study found that deucravacitinib at any dose (except for 3 mg QOD), ropsacitinib (200 and 400 mg QD), and apremilast (20 and 30 mg BID) had higher PASI and PGA response rates than placebo. In addition, deucravacitinib (3 mg BID, 6 mg QD, 6 mg BID, and 12 mg QD), and ropsacitinib (400 mg QD) showed superior efficacy than apremilast (30 mg BID). In terms of safety, deucravacitinib or ropsacitinib at any dose did not lead to a higher incidence of AEs than apremilast (30 mg BID). The ranking analysis of efficacy revealed that deucravacitinib 12 mg QD and deucravacitinib 3 mg BID had the highest chance of being the most effective oral treatment, followed by deucravacitinib 6 mg BID and ropsacitinib 400 mg QD. Conclusions: Oral TYK2 inhibitors demonstrated satisfactory performance in treating psoriasis, surpassing apremilast at certain doses. More large-scale, long-term studies focusing on novel TYK2 inhibitors are needed. Systematic review registration: PROSPERO (ID: CRD42022384859), available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022384859, identifier CRD42022384859.

Short-term risk and long-term incidence rate of infection and malignancy with IL-17 and IL-23 inhibitors in adult patients with psoriasis and psoriatic arthritis: a systematic review and meta-analysis.

The risk of infection and malignancy may be a concern for patients with psoriasis receiving interleukin (IL)-17 and IL-23 inhibitors, particularly with long-term treatments. We aimed to estimate the short-term risks and long-term incidence rates of infection and malignancy with IL-17 or IL-23 antagonists in adult patients with psoriasis and psoriatic arthritis through this comprehensive meta-analysis (PROSPERO registration number: CRD42022363127). We searched PubMed, MEDLINE, Web of Science and ClinicalTrials.gov until May 17, 2023 for randomized placebo-controlled trials and long-term (≥ 52 weeks) open-label extension studies. The estimates of short-term risk ratios (RRs) and long-term exposure-adjusted incidence rates (EAIRs) were pooled using R software 4.1.1 and STATA 16.0. This review included 45 randomized placebo-controlled studies and 27 open-label extension studies. Short-term RRs of serious infection, overall infection and malignancy were 1.45 (95% confidence intervals, 95% CI: 0.81-2.59), 1.20 (95% CI: 1.06-1.35), 0.83 (95% CI: 0.41-1.71) with IL-17 inhibitors; and 0.68 (95% CI: 0.38-1.22), 1.13 (95% CI: 1.00-1.28), 0.87 (95% CI: 0.37-2.04) with IL-23 inhibitors. Increased short-term risks of nasopharyngitis and Candida infection with IL-17 inhibitors were found. Long-term EAIRs of serious infection, overall infection, nonmelanoma skin cancer (NMSC), malignancies excluding NMSC, nasopharyngitis and upper respiratory tract infection were 1.11/100 patient-years (PYs), 57.78/100PYs, 0.47/100PYs, 0.24/100PYs, 15.07/100PYs, 8.52/100PYs, 3.41/100PYs with IL-17 inhibitors; and 1.09/100PYs, 48.50/100PYs, 0.40/100PYs, 0.43/100PYs, 10.75/100PYs, 5.84/100PYs with IL-23 inhibitors. Long-term EAIR of Candida infection was 3.41/100PYs with IL-17 inhibitors. No active or reactivated tuberculosis was ever reported in all the trials, and only a few cases of latent tuberculosis, hepatitis, and herpes zoster were reported during the long-term extension periods. No evidence of increased EAIRs of infection and malignancy with longer durations was found. Our study suggested that short-term risk and long-term incidence of infections and malignancies in psoriasis patients receiving IL-17 inhibitors and IL-23 inhibitors are generally low. However, close monitoring is required for nasopharyngitis and Candida infection with IL-17 inhibitors. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022363127.

5-azacytidine inhibits Sox2 promoter methylation during the induction of Thy-1+Lin- cells into hepatocytes.

OBJECTIVE: To investigate the changes and functions of Sox2 gene expression and promoter methylation during induced differentiation of bone marrow mesenchymal stem cells (BMSCs) into hepatocytes (HCs). METHODS: Rat bone marrow Thy-1+Lin- cells were prepared and divided into control group (directed induction of differentiation into HCs) and experimental group (5-azacytidine intervention induced differentiation). The mRNA expression levels of ALB and Sox2 were detected by fluorescence quantitative polymerase chain reaction (PCR), and the Sox2 gene promoter methylation level was determined by Bisulfite sequencing PCR (BSP). RESULTS: Sox mRNA expression level was significantly increased in experimental group compared to the control group at 0, 7, and 14 days, respectively (all P<0.05). The Sox2 promoter methylation level was gradually increased after 0, 7 and 14 days induction in both groups, accompanied by an increase in methylated loci (all P<0.05). Statistical significance was present in CpG methylated loci between groups (all P<0.05). CONCLUSIONS: The expression of Sox2 gene increased first and then decreased in the process of inducing rat BMSCs into stem cells, and the methylation level of CpG loci in the promoter region changed dynamically, with an increased overall methylation level. After 5-aza treatment, the Sox2 promoter was in a non-methylated state, and its mRNA expression increased, which hindered the cell differentiation.

Effect of maternal pregestational diabetes mellitus on congenital heart diseases.

BACKGROUND: The increasing population of diabetes mellitus in adolescent girls and women of childbearing age contributes to a large number of pregnancies with maternal pregestational diabetes mellitus. Congenital heart diseases are a common adverse outcome in mothers with pregestational diabetes mellitus. However, there is little systematic information between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring. DATA SOURCES: Literature selection was performed in PubMed. One hundred and seven papers were cited in our review, including 36 clinical studies, 26 experimental studies, 31 reviews, eight meta-analysis articles, and six of other types. RESULTS: Maternal pregestational diabetes mellitus poses a high risk of congenital heart diseases in the offspring and causes variety of phenotypes of congenital heart diseases. Factors such as persistent maternal hyperglycemia, oxidative stress, polymorphism of uncoupling protein 2, polymorphism of adiponectin gene, Notch 1 pathway, Nkx2.5 disorders, dysregulation of the hypoxia-inducible factor 1, and viral etiologies are associated with the occurrence of congenital heart diseases in the offspring of mothers with pregestational diabetes mellitus. Treatment options including blood sugar-reducing, anti-oxidative stress drug supplements and exercise can help to prevent maternal pregestational diabetes mellitus from inducing congenital heart diseases. CONCLUSIONS: Our review contributes to a better understanding of the association between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring and to a profound thought of the mechanism, preventive and therapeutic measurements of congenital heart diseases caused by maternal pregestational diabetes mellitus.

3D printing of microneedle arrays for hair regeneration in a controllable region.

Hair loss is a common skin disease that causes intense emotional suffering. Hair regeneration in a personalized area is highly desirable for patients with different balding conditions. However, the existing pharmaceutical treatments have difficulty precisely regenerating hair in a desired area. Here, we show a method to precisely control the hair regeneration using customized microneedle arrays (MNAs). The MNA with a customized shape is fast fabricated by a static optical projection lithography process in seconds, which is a 3D printing technology developed by our group. In the mouse model, MNA treatment could induce hair regrowth in a defined area corresponding to the customized shape of MNA. And the regenerated hair promoted by MNAs had improved quality. Cellular and molecular analysis indicated that MNA treatment could recruit macrophages in situ and then initiate the proliferation of hair follicle stem cells, thereby improving hair regeneration. Meanwhile, the activation of the Wnt/ß-catenin signaling pathway was observed in hair follicles. The expressions of Hgf, Igf 1 and Tnf-α were also upregulated in the treated skin, which may also be beneficial for the MNA-induced hair regeneration. This study provides a strategy to precisely control hair regeneration using customized microneedle arrays by recruiting macrophages in situ, which holds the promise for the personalized treatment of hair loss.