Hybrid Microneedle-Mediated Transdermal Delivery of Atorvastatin Calcium-Loaded Polymeric Micelles for Hyperlipidemia Therapy.

Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy. We first prepared various AC@PM formulations self-assembled from mPEG-PLA and mPEG-PLA-PEG block copolymers using a dialysis method and evaluated the physicochemical properties in combination with experiment skills and dissipative particle dynamics (DPD) simulations. Then, we encapsulated the AC@PMs into the PVA MN patch using a micromold filling method, followed by characterizing the performances, especially the structural stability, mechanical performance, and biosafety. After conducting in vivo experiments using a hyperlipidemic rat model, our findings revealed that the hybrid microneedle-mediated administration exhibited superior therapeutic efficacy when compared to oral delivery methods. In summary, we have successfully developed a hybrid microneedle (MN) patch system that holds promising potential for the efficient transdermal delivery of hydrophobic drugs.

Efficacy and safety of 1565-nm nonablative fractional laser combined with mucopolysaccharide polysulfate cream for erythematous acne scars.

PURPOSE: To evaluate the efficacy and safety of 1565-nm nonablative fractional laser (NAFL) combined with mucopolysaccharide polysulfate (MPS) cream in the treatment of erythematous acne scars. METHODS: A total of 28 subjects with erythematous acne scars from June 2021 to April 2022 were enrolled. One side of each subject's face was randomly assigned to be treated with 1565-nm NAFL (at 2 sessions with four-week intervals) combined with MPS cream (twice daily) for 8 weeks, and the other side with 1565-nm NAFL combined with placebo cream. CBS® images and parameters, dermoscopic images and the quantitative data processed by ImageJ software, and quantitative global scarring grading system (GSS) score were obtained at baseline and after treatment. Subjects' satisfaction assessment was performed after treatment. Adverse events were recorded during treatment. RESULTS: In CBS® parameters, the red area, red area concentration, and smoothness were improved more significantly on the 1565-nm NAFL combined with MPS cream side than on the 1565-nm NAFL combined with placebo cream side after treatment (p = 0.015, p = 0.013, and p = 0.021). For dermoscopy, both scar area and scar redness achieved a significantly greater percentage of improvement on the side of 1565-nm NAFL combined with MPS cream than the side of 1565-nm NAFL combined with placebo cream after treatment (p = 0.005 and p = 0.041). The reduction of quantitative GSS score and Subjects' satisfaction assessment were similarly superior on the 1565-nm NAFL combined with MPS cream side. Temporary erythema was experienced by all subjects after each 1565-nm NAFL treatment. No subject reported intolerance or allergy to the cream during follow-up. CONCLUSIONS: The combined application of 1565-nm NAFL and MPS cream could be an effective and safe treatment for erythematous acne scars. ImageJ software enables quantitative evaluation of dermoscopic images of acne scars.

Comparisons of Four Acne Grading Systems Recommended in China, Korea, and Japan.

Introduction: Acne vulgaris is one of the most prevalent skin disorders. The treatment regimen depends on how severe the AV is. The acne grading system is crucial for clinical and research work. The aim of this work was to evaluate intra-grader differences between 5 investigators using Acne Grading System (AGS), the International Improved Grading System (IIGS), the Korean Acne Grading System (KAGS), and the Japanese Acne Grading System (JAGS) to assess acne vulgaris (AV) severity. Patients and Methods: AV sufferers from dermatological clinics of five hospitals in China were the subject of a prospective cross-sectional study. AGS, IIGS, KAGS and JAGS were utilized by 5 investigators to verify the severity of AV. The correlation between AGS, IIGS, KAGS and JAGS was examined. Results: A complete of 1107 AV sufferers were enrolled in the study. There were indications that the AGS, IIGS, KAGS and JAGS had sufficient internal consistency. As for the reliability amongst raters, AGS, IIGS, KAGS and JAGS confirmed gorgeous reliability. There were strong correlations amongst AGS, IIGS, KAGS and JAGS (P≤0.01). The interior reliability of investigator 1 one year ago and later after usage of AGS and IIGS was excellent (P≤0.01). Conclusion: IIGS and AGS exhibited great correlation with KAGS and JAGS and were highly reliable.

Detection of skin thickness and density in healthy Chinese people by using high-frequency ultrasound.

OBJECTIVES: Due to a recent development of high-frequency ultrasound (HFUS) systems, it is easier to realize high-resolution in vivo imaging of the biological tissues. The object of this study was to map the thickness and echo density of skin layers in healthy Chinese people and assess the influence of gender, age, and region on it. METHODS: A total of 189 volunteers (85 male, 104 female) with age range of 22-75-year old (mean age of 41.2-year old) were enrolled. The thickness and density of the epidermis and dermis layer were detected by high-frequency (22 or 75 MHz) ultrasonography at 13 different anatomical sites, including the forehead, cheeks, flexor and extensor forearms, flexor and extensor upper arms, inner and outer legs, inner and outer thighs, back, and abdomen. RESULTS: The thickness and density of epidermis/dermis between different anatomical sites were statistically significant (p < 0.05). The epidermis thickness of the face and trunk were less than that of the limbs, whereas the thicknesses of the dermis were on the contrary. The density of the epidermis/dermis of the face and trunk were less than that of the limbs. The thickness of dermis in most of the sites were higher in male than in female, and the density of epidermis and dermis in most of the sites were less in men than in women. The thicknesses/densities of dermis were lower in older age group in almost all sites, whereas only several sites reached statistical. The difference between the north and south regions showed the environment also influenced the thickness and density of the skin. CONCLUSION: HFUS provides a simple noninvasive method for evaluating the skin thickness and echo-density, which, reflecting intradermal structure, exhibit systematic regional variation. With the establishment of Chinese phenotypic database of skin thickness and density, it will be helpful for the skin disease assessment, skin surgery, and cosmetology technology.

Diagnosis of Neisseria Gonorrhoeae by Loop-Mediated Isothermal Amplification: Systematic Review and Meta-Analysis.

Neisseria gonorrhoeae (gonococci) is the pathogen of gonorrhea. At present, there is no robust statistical analysis targeting the detection accuracy for N.gonorrhoeae of loop-mediated isothermal amplification (LAMP). We performed a full search of five databases for studies using the LAMP method to detect N.gonorrhoeae in this study. Nine datasets derived from eight studies satisfying the inclusion requirement were collected for this study. The pooled sensitivity rate and specificity were calculated as 98.53 and 99.49%. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were 66.0, 0.04 and 1863.8. After plotting the summary receiver operating characteristic (sROC), the area under the curve (AUC) and Q* index was calculated as 0.99 and 0.9774. Subgroup analyses based on the type of samples, location, and gold standard did not find sources of significant heterogeneity. In conclusion, the LAMP method could be an effective and convenient method with high accuracy for the clinical detection of N.gonorrhoeae. Moreover, the confirmation of this finding needs more high-quality studies with regional data and large samples.

Inter-rater variability and consistency within four acne grading systems recommended in China, USA, and Europe.

PURPOSE: To investigate the correlation among different investigators (intrarater variation) in the assessment of acne vulgaris severity using Acne Grading System (AGS), International Improvement Grading System (IIGS), Investigator Global Assessment of acne (IGA), and Global Evaluation Acne (GEA), and to compare AGS and IIGS with the IGA recommended in the United States, and GEA in Europe. METHODS: A prospective cross-sectional study was conducted among patients with acne vulgaris, attending the dermatology outpatient clinics at five hospitals in China. Four investigators were engaged using AGS, IIGS, IGA, and GEA to assess severity of acne vulgaris. Correlation among AGS, IIGS, GEA, and IGA were analyzed. RESULTS: A total of 1107 participants suffering from acne vulgaris were enrolled. There was evidence of adequate internal consistency among AGS, IIGS, IGA, and GEA. For the intrarater reliability, AGS, IIGS, GEA, and IGA demonstrated excellent reliability. Moreover, AGS, IIGS, IGA, and GEA were significantly correlated with each other (p ≤ 0.01). CONCLUSION: IIGS and AGS were reliable, and correlated well with IGA and GEA.

Infrared and visible image fusion algorithm based on a cross-layer densely connected convolutional network.

To preserve the saliency of targets in infrared images and the textures in visible images, a novel infrared and visible image fusion method, to the best of our knowledge, is proposed. First, we design a densely connected convolutional network that contains an encoder, fusion, and decoder to minimize the omission of source image effective information. Then, a loss function based on the variational model is designed to retain the thermal radiation information of the infrared image and the details of the visible image to the greatest extent. The experimental results show that the proposed method outperforms state-of-the-art methods in terms of six metrics and better preserves the clear target and textures of infrared and visible images.

Deficiency of two-pore segment channel 2 contributes to systemic lupus erythematosus via regulation of apoptosis and cell cycle.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq). RESULTS: TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown-TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation. CONCLUSION: TPCN2 might be a potential protective factor against SLE.

Skin diseases in the Da Qing Diabetes Study: a cross-sectional study.

BACKGROUND: The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM. METHODS: We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated. RESULTS: In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in "disturbances of pigmentation" and "neurological and psychogenic dermatoses". The duration of T2DM also significantly associated with the prevalence of "disturbances of pigmentation" and "neurological and psychogenic dermatoses". Subsequently, the prevalence of "disturbances of pigmentation" was higher in males than females in NGT (P < 0.01) and T2DM (P < 0.01) groups. In addition, the difference in the prevalence of "disturbances of pigmentation" was also significant in NGT and T2DM groups (P < 0.01). CONCLUSIONS: There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented.

Web-based study on Chinese dermatologists' attitudes towards artificial intelligence.

BACKGROUND: Artificial intelligence (AI) has become a powerful tool and is attracting more attention in the field of medicine. There are a number of AI studies focusing on skin diseases, and there are many AI products that have been applied in dermatology. However, the attitudes of dermatologists, specifically those from China, towards AI, is not clear as few, if any studies have focused on this issue. METHODS: A web-based questionnaire was designed by experts from the Chinese Skin Image Database (CSID) and published on the UMER Doctor platform (an online learning platform for dermatologists developed by the Shanghai Wheat Color Intelligent Technology Company, China). A total of 1,228 Chinese dermatologists were recruited and provided answers to the questionnaire online. The differences of dermatologists' attitudes towards AI among the different groups (stratified by age, gender, hospital level, education degree, professional title, and hospital ownership) were compared by using the Mann-Whitney U test and the Kruskal-Wallis H test. The correlations between stratified factors and dermatologists' attitudes towards AI were calculated by using the Spearman's rank correlation test. SPSS (version 22.0) was utilized for all analyses. A two-sided P value <0.05 was considered statistically significant in all analyses. RESULTS: A total of 1,228 Chinese dermatologists from 30 provinces, autonomous regions, municipalities, and other regions (including Hong Kong, Macau, and Taiwan) participated in this survey. The dermatologists who participated acquired AI-related information mainly through the Internet, meetings or forums, and 70.51% of participated dermatologists acquired AI-related information by two or more approaches. In total, 99.51% of participated dermatologists pay attention (general, passive-active, and active attention) to information pertaining to AI. Stratified analyses revealed statistically significant differences in their attention levels (unconcerned, general, passive-active, and active attention) to AI-related information by gender, hospital level, education degree, and professional title (P values ≤1.79E-02). In total, 95.36% of the participated dermatologists thought the role of AI to be in "assisting the daily diagnosis and treatment activities for dermatologists". Stratified analyses about the thought of AI roles (unconcerned, useless, assist, and replace) showed that there was no statistically significant difference except for the hospital level (P value =4.09E-03). The correlations between stratified factors with attention levels and the opinions of AI roles showed extremely weak correlations. Furthermore, 64.17% of participated dermatologists thought secondary hospitals in China are in most need of the application AI, and 91.78% of participated dermatologists thought the priority implementation of AI should be in skin tumors. CONCLUSIONS: The majority of Chinese dermatologists are interested in AI information and acquired information about AI through a variety of approaches. Nearly all dermatologists are attentive to information on AI and think the role of AI is in "assisting the daily diagnosis and treatment activities for dermatologists". Future AI implementation should be primarily focused on skin tumors and utilized in in secondary hospitals.

Dermoscopy in China: current status and future prospective.

OBJECTIVE: Dermoscopy is a useful technique for improving the diagnostic accuracy of various types of skin disorders. In China, dermoscopy has been widely accepted, and domestic researchers have made tremendous progress in the field of dermoscopy. The main purpose of this review is to summarize the current status of dermoscopy in China and identify its future directions. DATA SOURCES: Articles included in this review were obtained by searching the following databases: Wanfang, China National Knowledge Infrastructure, PubMed, and the Web of Science. We focused on research published before 2019 with keywords including dermoscopy, dermoscopic, dermoscope and trichoscopy. STUDY SELECTION: A total of 50 studies were selected. Of these studies, 20 studies were in Chinese and 30 in English, research samples of all the studies were collected from Chinese populations. RESULTS: Since 2000, more than 380 articles about dermoscopy have been published in domestic or foreign journals. Dermoscopy can improve the diagnostic accuracy of neoplastic diseases, evaluating the therapeutic effect of treatment, and determining the treatment endpoint, and it can also assist in the differential diagnosis of inflammatory diseases and in the assessment of the severity of the disease. In addition, researches about the applications of dermoscopy during surgical treatment have been published. Training courses aiming to improve the diagnostic ability of dermatologists, either face-to-face or online, have been offered. The Chinese Skin Image Database, launched in 2017 as a work platform for dermatologists, has promoted the development of dermoscopy in China. Computer-aided diagnostic systems based on the Chinese population are ready for use. In the future, cooperation, resource sharing, talent development, image management, and computer-aided diagnosis will be important directions for the development of dermoscopy in China. CONCLUSION: Dermoscopy has been widely used and developed in China, however, it still needs to address more challenges in the future.

Amelanotic acral melanoma misdiagnosed as verruca plantaris.

We report a case of amelanotic acral melanoma in a 42-year-old Chinese woman. Ten months previously the patient found a 2-cm asymmetric erythematous macular plaque on her left sole. The lesion was diagnosed as verruca plantaris by every physician the patient consulted. One month ago, an enlarged lymph node was detected in the left groin, which biopsy reported as metastatic melanoma. Dermoscopy suggested verruca plantaris, and positron emission tomography (PET) revealed increased glucose metabolism in the macular plaque. Finally, biopsy of the plaque revealed amelanotic melanoma. Misdiagnosis and diagnostic delay are usually associated with poorer patient outcomes. Awareness of atypical presentations of acral melanoma is thus important for decreasing misdiagnosis rates and improving patient outcomes.

Amelanotic acral melanoma misdiagnosed as verruca plantaris

Abstract: We report a case of amelanotic acral melanoma in a 42-year-old Chinese woman. Ten months previously the patient found a 2-cm asymmetric erythematous macular plaque on her left sole. The lesion was diagnosed as verruca plantaris by every physician the patient consulted. One month ago, an enlarged lymph node was detected in the left groin, which biopsy reported as metastatic melanoma. Dermoscopy suggested verruca plantaris, and positron emission tomography (PET) revealed increased glucose metabolism in the macular plaque. Finally, biopsy of the plaque revealed amelanotic melanoma. Misdiagnosis and diagnostic delay are usually associated with poorer patient outcomes. Awareness of atypical presentations of acral melanoma is thus important for decreasing misdiagnosis rates and improving patient outcomes.

Exome-wide association study identifies four novel loci for systemic lupus erythematosus in Han Chinese population.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of considerable genetic predisposition. Genome-wide association studies have identified tens of common variants for SLE. However, the majority of them reside in non-coding sequences. The contributions of coding variants have not yet been systematically evaluated. METHODS: We performed a large-scale exome-wide study in 5004 SLE cases and 8179 healthy controls in a Han Chinese population using a custom exome array, and then genotyped 32 variants with suggestive evidence in an independent cohort of 13 246 samples. We further explored the regulatory effect of one novel non-coding single nucleotide polymorphism (SNP) in ex vivo experiments. RESULTS: We discovered four novel SLE gene regions (LCT, TPCN2, AHNAK2 and TNFRSF13B) encompassing three novel missense variants (XP_016859577.1:p.Asn1639Ser, XP_016859577.1:p.Val219Phe and XP_005267356.1:p.Thr4664Ala) and two non-coding variants (rs10750836 and rs4792801) with genome-wide significance (pmeta <5.00×10-8). These variants are enriched in several chromatin states of primary B cells. The novel intergenic variant rs10750836 exhibited an expression quantitative trait locus effect on the TPCN2 gene in immune cells. Clones containing this novel SNP exhibited gene promoter activity for TPCN2 (P=1.38×10-3) whose expression level was reduced significantly in patients with SLE (P<2.53×10-2) and was suggested to be further modulated by rs10750836 in CD19+ B cells (P=7.57×10-5) in ex vivo experiments. CONCLUSIONS: This study identified three novel coding variants and four new susceptibility gene regions for SLE. The results provide insights into the biological mechanism of SLE.

Antimicrobial Susceptibility Evaluation and Multiple-Locus Variable Number Tandem Repeat Analysis of Neisseria gonorrhoeae Isolates in China in 2012.

OBJECTIVE: This study aimed to gain information on the antimicrobial susceptibility and molecular epidemiological typing of Neisseria gonorrhoeae (NG) isolates in China in 2012. METHODS: A total of 244 NG isolates were consecutively recovered from patients with uncomplicated gonorrhea attending sexually transmitted disease clinics in 3 Chinese cities-Guangzhou, Nanjing, and Tianjin-in 2012. Neisseria gonorrhoeae susceptibilities to penicillin and tetracycline were examined by detecting penicillinase-producing NG (PPNG) and high-level tetracycline-resistant NG, and NG susceptibilities to ciprofloxacin, spectinomycin, ceftriaxone, and cefixime were determined using an agar dilution method. Neisseria gonorrhoeae isolates were typed by multiple-locus variable number tandem repeat analysis. We conducted a χ analysis to compare clusters with Bonferroni correction and Kruskal-Wallis test. RESULTS: Neisseria gonorrhoeae isolates gathered from the 3 cities differed significantly in the prevalence of tetracycline-resistant NG (P < 0.001) and NG treated with ceftriaxone with a minimum inhibitory concentration of 0.125 mg/L or higher (P < 0.001). The analysis of the combination of the 7 variable number of tandem repeats loci for all of the 244 isolates yielded 110 multiple-locus variable number tandem repeat analysis types falling into 5 clusters. Cluster III was associated with PPNG, whereas cluster II was associated with non-PPNG (P < 0.05) and NG treated with ceftriaxone with a minimum inhibitory concentration of 0.125 mg/L or higher (P < 0.05). CONCLUSIONS: Antimicrobials that can be used with confidence to treat NG infection currently in China include ceftriaxone and spectinomycin, but not penicillin, tetracycline, ciprofloxacin, and cefixime. Moreover, some of the resulting clusters were associated with PPNG and NG with decreased ceftriaxone susceptibility.

Patchy alopecia areata sparing gray hairs: a case series.

Alopecia areata is an unpredictable, non-scarring hair loss condition. Patchy alopecia areata sparing gray hairs is rare. Here we present 4 cases with patchy non-scarring hair loss, which attacked pigmented hairs only and spared gray hairs. It should be differentiated from vitiligo, colocalization of vitiligo and alopecia areata, and depigmented hair regrowth after alopecia areata.