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Introduction: The role of bone marrow mesenchymal stem cells derived exosomes (BMSCs-exo) in skin photoaging was explored in human dermal fibroblasts (HDFs). The underlying mechanism was further explored. Methods: HDFs were exposed to UVB irradiation to establish the cell photodamage models. The cell viability, and levels of oxidative stress-related factors were tested. ELISA was done to detect TNF-α, IL-6 and IL-1β concentration. Western blot was applied for protein examination. Results: UVB treatment led to the inhibition of cell viability. But after BMSCs-exo addition, the inhibitory effect was returned in a dose manner. UVB exposure contributed to the increase of ROS and LDH, and the downregulation of SOD. In addition, excessive secretion of TNF-α, IL-6 and IL-1β was also detected in cells exposed to UVB. However, BMSCs-exo addition eliminated the effects of UVB on oxidative stress and inflammation in HDFs. BMSCs-exo inhibited MMP-1 and MMP-3 expression, but promoted collagen I expression. UVB radiation activated the MAPK/AP-1 signaling, manifested as the increase of p-p38, c-Jun and c-Fos protein levels, which was reversed by BMSCs-exo. As a p38 agonist, anisomycin (ANS) counteracted the effect of BMSCs-exo on HDFs viability, oxidative stress and inflammation. Conclusion: BMSCs-exo protected HDFs against UVB-induced inhibition of cell viability and the activation of cell oxidative stress and inflammation, which might be related to the inhibition of the MAPK/AP-1 signaling pathway.

Mesenchymal stem cells-derived exosome (MSCs-exo) was identified to reduce photoaging. The purpose of this study was to investigate the potential role of microRNA (miR)-29b-3p derived from bone marrow MSCs-exo (BMSCs-exo) in photoaging.Exosomes were isolated from BMSCs and verified by Western blot. A photoaging cell model was constructed by UVB irradiation of human dermal fibroblasts (HDFs). Quantitative real-time PCR (RT-qPCR) was performed to detect the mRNA levels of miR-29b-3p, collagen type I and matrix metalloproteinases (MMPs). CCK-8, Transwell and flow cytometry were applicated to examine cell viability, migration and apoptosis. Commercial kits are used to measure levels of oxidative stress indicators. Finally, a dual-luciferase reporter assay was applied to validate the target of miR-29b-3p.Extracted exosomes were positive for HSP70 and CD9. Survival of HDFs increased in an exosome concentration-dependent manner. UVB irradiation inhibited miR-29b-3p levels compared with controls, but BMSCs-exo treatment restored miR-29b-3p levels (p .05). Additionally, BMSCs-exo-miR-29b-3p reversed the inhibition of HDFs migration and oxidative stress by UVB irradiation, as well as the promotion of apoptosis. However, this reversal was attenuated by the suppression of miR-29b-3p (p .05). Furthermore, BMSCs-exo-miR-29b-3p also inhibited the degradation of collagen type I and the production of MMPs in photoaging, and they were also eliminated by the reduced miR-29b-3p. Finally, MMP-2 was the target gene of miR-29b-3p.Our study presented a novel role for BMSCs-exo-miR-29b-3p in improving skin photoaging function, and these findings may provide new insights into the targeted treatment of skin photoaging.

Background Immunotherapy is the first-line treatment for advanced hepatocellular carcinoma (HCC). However, immunotherapy benefits are limited in certain patients. Therefore, identifying effective biomarkers is important for the efficient use of immunotherapy. In the present study, acetyl-CoA acyltransferase 2 (ACAA2), which was decreased during HCC initiation, was identified as a gene of interest. Methods In this study, we aimed to explore the role of ACAA2 in the progression of HCC and the link between ACAA2 and tumor microenvironment. Bulk RNA data and single-cell RNA data were acquired from the Cancer Genome Atlas and Gene Expression Omnibus. Both in vitro and in vivo studies were used to determine the effect of ACAA2 on the progression of HCC, and RNA sequencing analysis was performed to explore the mechanism. Results The patient with low ACAA2 level had an immunosuppressive microenvironment in the HCC and could be poor response to immunotherapy. Decreased ACAA2 facilitated HCC proliferation and metastasis by activating the nuclear factor-κB (NFκB) signaling pathway. And increased CXCL1 induced by NFκB signaling pathway was responsible for low level of ACAA2 related immune suppression microenvironment. Furthermore, the expression of ACAA2 in immune cells, CD4+TCF7+T, CD4+FOXP3+T, CD8+GZMK+T, and CD8+KLRD1+T cells, was inversely correlated with the composition of CD8+PDCD1+T cells in HCC. This effect may be due to the CCL5-CCRs and HLA-E-KLRCs ligand-receptor networks. Conclusions ACAA2 was a favorable indicator for the prognosis of HCC and an ideal biomarker for immunotherapy.

To evaluate the efficacy and safety of 755 nm Q-Switched alexandrite laser for Hori’s nevus in a large cohort of Chinese women. We retrospectively analyzed the efficacy and safety of 755 nm Q-Switched alexandrite laser for Hori’s nevus. Reduction in pigment was evaluated using a 4-score method. A total of 482 patients, aged 16 to 52 years, were included in this analysis. Patients were treated with 755 nm Q-Switched alexandrite laser at fluence levels of 5–8 J/cm2 for 2–4 treatment sessions. Following the treatments, 53% of patients showed over 75% reductions in pigment while 50–75% reductions in pigment were observed in 28% of patients. The rest displayed less than 50% improvements. Efficacy was positively correlated with the number of treatment sessions (p

LncRNAs has been demonstrated to modulate neoplastic development by modulating downstream miRNAs and functional genes. In this study, we aimed to detect the interaction among lncRNA ZFAS1 miR‐296‐5p and USF1. We explored the proliferation, migration and invasion of cholangiocarcinoma. The differentially expressed ZFAS1 was discovered in both tissues and cell lines by qRT‐PCR. The targeting relationship between miR‐296‐5p and ZFAS1 or USF1 was validated by dual‐luciferase assay. The impact of ZFAS1 on CCA cell proliferation was observed by CCK‐8 assay. The protein expression of USF1 was determined by Western blot. The effects of ZFAS1, miR‐296‐5p and USF1 on tumour growth were further confirmed using xenograft model. LncRNA ZFAS1 expression was relatively up‐regulated in tumour tissues and cells while miR‐296‐5p was significantly down‐regulated. Knockdown of ZFAS1 significantly suppressed tumour proliferation, migration, invasion and USF1 expression. Overexpressed miR‐296‐5p suppressed cell proliferation and metastasis. Knockdown of USF1 inhibited cell proliferation and metastasis and xenograft tumour growth. In conclusion, ZFAS1 might promote cholangiocarcinoma proliferation and metastasis by modulating USF1 via miR‐296‐5p.

Cholangiocarcinoma (CCA) is one of the most fatal cancers in humans, with a gradually increasing incidence worldwide. The efficient diagnostic and therapeutic measures for CCA to reduce mortality are urgently needed. Long noncoding RNAs (lncRNAs) may provide the potential diagnostic and therapeutic option for suppressing the CCA development. LncRNAs are a type of non-protein-coding RNAs, which are larger than 200 nucleotides in length. Increasing evidence reveals that lncRNAs exhibit critical roles in the carcinogenesis and development of CCA. Deregulation of lncRNAs impacts the proliferation, migration, invasion, and antiapoptosis of CCA cells by multiple sophisticated mechanisms. Consequently, lncRNAs likely represent promising biomarkers or intervention targets of CCA. In this review, we summarize current studies regarding the biological functions and regulatory mechanisms of diverse lncRNAs in CCA.

BACKGROUND: Becker’s nevus is a common pigmented dermatosis, usually featured by ipsilateral pigmented patch with hypertrichosis. Becker’s nevus is often treated with various types of lasers although other regimens are available. However, clinical outcomes appear inconsistent among studies. OBJECTIVE: To summarize the clinical outcomes of Becker’s nevus treated with lasers via literature review. RESULTS: A variety of lasers had been used alone or in combination to treat Becker’s nevus. Laser wavelengths used for Becker’s nevus ranged from 504 nm to 10600 nm, while the number of treatment varied from 1 to 12 sessions. The clinical outcomes were mixed although combination of lasers with different wavelengths appeared to achieve a better efficacy. Adverse effects were usually mild to moderate erythema. CONCLUSION: While lasers are relatively safe, their efficacy for Becker’s nevus is moderate. It seems that combination therapy could improve the outcome. However, trials in larger group of patients are required to validate the efficacy of each type of lasers for Becker’s nevus.

Accumulation and spread of tau in Alzheimer’s disease and other tauopathies occur in a prion-like manner. However, the mechanisms and downstream consequences of tau trafficking remain largely unknown. We hypothesized that tau traffics from neurons to microglia via extracellular vesicles (EVs), leading to IL-6 generation and cognitive impairment. We assessed mice and neurons treated with anesthetics sevoflurane and desflurane, and applied nanobeam-sensor technology, an ultrasensitive method, to measure tau/p-tau amounts. Sevoflurane, but not desflurane, increased tau or p-tau amounts in blood, neuron culture medium, or EVs. Sevoflurane increased p-tau amounts in brain interstitial fluid. Microglia from tau knockout mice took up tau and p-tau when treated with sevoflurane-conditioned neuron culture medium, leading to IL-6 generation. Tau phosphorylation inhibitor lithium and EVs generation inhibitor GW4869 attenuated tau trafficking. GW4869 mitigated sevoflurane-induced cognitive impairment in mice. Thus, tau trafficking could occur from neurons to microglia to generate IL-6, leading to cognitive impairment., Using their previously developed nanobeam-sensor technology to detect tau protein in the blood, Yuanlin Dong et al. find that the anaesthetic sevoflurane induces trafficking of tau from neurons to microglia in mice. They further see that microglia can take up tau, leading to Il-6 production, overall bringing new insights into the mechanism of sevoflurane-mediated cognitive impairment.

Yiping Zhong,* Lining Huang,* Tingting Yan, Yongjun Chen, Bin Yang, Mao-Qiang Man Aesthetic Department, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong 510091, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao-Qiang Man; Bin YangDermatology Hospital, Southern Medical University, Guangzhou 510091, People’s Republic of ChinaTel+86-20-87257353Email mqman@hotmail.com; yangbin101@hotmail.comBackground: Hori’s nevus is a common pigmented disorder on the face, preferentially in females. The clinical features have not been well characterized.Aim: To characterize the clinical features of Hori’s nevus in Chinese adults.Subjects and Methods: Data were collected from files of patients who visited our hospital from 2015 to 2018. Age- and disease duration-related characteristics were analyzed.Results: A total of 497 patients, including 486 females and 11 males, were included in this analysis. One fifth of the patients had a family history of Hori’s nevus. Over 70% of patients were aged 21– 30 years. Age at onset was comparable between males and females (20.64 ± 1.01 vs 18.99 ± 0.24). Out of 497 subjects, 218 subjects (44%) displayed yellow-brown lesions while blue-brown lesions wwere observed in 103 subjects (21%). The rest (176 cases, 35%) showed slate-grey lesions. Involvement in the zygomatic area was observed in 496/497 subjects. Involvement in a single area accounted for 74% of patients, while two areas were involved in 19% of patients. The number of involved areas correlated positively with disease duration. However, the proportion of subjects with yellow-brown lesions correlated negatively with disease duration, while the proportion of subjects with slate-grey lesions correlated positively with disease duration. The proportion of subjects with lesions involving the lower eyelids, the root of the nose, the temple and the outer frontal area correlated positively with age.Conclusion: Hori’s nevus mainly involves the zygomatic area in subjects aged 21– 30 years. Lesion color is associated with age, age at onset, and disease duration.Keywords: Hori’s nevus, age, pigmentation

This paper reports a microfluidic lab-on-chip for dynamic particle sizing and real time individual cell membrane permeability measurements. To achieve this, the device measures the impedance change of individual cells or particles at up to ten time points after mixing with different media, e.g. dimethyl sulfoxide or DI water, from separate inlets. These measurements are enabled by ten gold electrode pairs spread across a 20 mm long microchannel. The device measures impedance values within 0.26 s after mixing with other media, has a detection throughput of 150 samples/second, measures impedance values at all ten electrodes at this rate, and allows tracking of individual cell volume changes caused by cell osmosis in anisosmotic fluids over a 1.3 s postmixing timespan, facilitating accurate individual cell estimates of water permeability. The design and testing were performed using yeast cells (Saccharomyces cerevisiae). The relationship between volume and impedance in both polystyrene calibration beads as well as the volume-osmolality relationship in yeast were demonstrated. Moreover, we present the first noninvasive and non-optically-based water permeability measurements in individual cells.

Long non-coding RNA (lncRNA) has been testified to influence the initiation and evolution of sundry carcinomas. Recently, lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) has been found to display vital regulating functions in various cancers. qRT-PCR was used to verify the dysregulation of FOXD2-AS1 expression in CCA cells and tissues, and the correlation of FOXD2-AS1 expression with clinicopathological characteristics was investigated. The viability, migration, and invasion of CCA cells were verified through CCK-8 assay, colony formation experiment, wound healing assay, and transwell assay. The regulatory networks of FOXD2-AS1 were analyzed by Bioinformatic prediction and dual-luciferase reporter assay. We discovered that FOXD2-AS1 was significantly upregulated in CCA and its up-regulation was closely correlated with terminal TNM stage, lymph node metastasis and poor survival in the current research. In addition, it was revealed that FOXD2-AS1 was an independent prognostic factor. Functional tests uncovered that the cell viability, migration, and invasion could be restrained through downregulating the expression of FOXD2-AS1, while FOXD2-AS1 overexpression could facilitate the cell viability, migration, and invasion. Mechanistically, FOXD2-AS1 was founded to interact directly with miR-760 and the oncogene E2F3 was the downstream target of miR-760 through bioinformatic prediction and dual-luciferase reporter assays. Finally, we testified that FOXD2-AS1 could competitively sponge miR-760 and further upregulated the E2F3 expression to play a vital part in cholangiocarcinoma. This research revealed that lncRNA FOXD2-AS1 could enhance CCA malignant progression through regulating the miR-760/E2F3 axis and was expected to be a prognostic biomarker and therapeutic target for cholangiocarcinoma.

Background and aims Circular RNAs (circRNAs) and extracellular vesicles (EVs) are involved in various malignancies. We aimed to clarify the functions and mechanisms of dysregulated circRNAs in the cells and EVs of cholangiocarcinoma (CCA). Approach and results CircRNA microarray was used to identify circRNA expression profiles in CCA tissues and bile-derived EVs (BEVs). CCA-associated circRNA 1 (circ-CCAC1) expression was measured by quantitative real-time PCR. The clinical importance of circ-CCAC1 was analyzed by receiver operating characteristic curves, Fisher's exact test, Kaplan-Meier plots, and Cox regression model. The functions of circ-CCAC1 and exosomal circ-CCAC1 were explored in CCA cells and human umbilical vein endothelial cells (HUVECs), respectively. Different animal models were used to verify the in vitro results. RNA sequencing, bioinformatics, RNA immunoprecipitation, RNA pulldown, chromatin immunoprecipitation followed by sequencing, and luciferase reporter assays were used to determine the regulatory networks of circ-CCAC1 in CCA cells and HUVECs. Circ-CCAC1 levels were increased in cancerous bile-resident EVs and tissues. The diagnostic and prognostic values of circ-CCAC1 were identified in patients with CCA. For CCA cells, circ-CCAC1 increased cell progression by sponging miR-514a-5p to up-regulate Yin Yang 1 (YY1). Meanwhile, YY1 directly bound to the promoter of calcium modulating ligand to activate its transcription. Moreover, circ-CCAC1 from CCA-derived EVs was transferred to endothelial monolayer cells, disrupting endothelial barrier integrity and inducing angiogenesis. Mechanistically, circ-CCAC1 increased cell leakiness by sequestering enhancer of zeste homolog 2 in the cytoplasm, thus elevating SH3 domain-containing GRB2-like protein 2 expression to reduce the levels of intercellular junction proteins. In vivo studies further showed that increased circ-CCAC1 levels in circulating EVs and cells accelerated both CCA tumorigenesis and metastasis. Conclusions Circ-CCAC1 plays a vital role in CCA tumorigenesis and metastasis and may be an important biomarker/therapeutic target for CCA.

The purpose of this article is to explore the function and mechanism of HOXD-AS1 in cholangiocarcinoma. TCGA, StarBase and JASPAR were applied to predict the differential expression and molecular mechanism. The qRT-PCR was conducted to detect molecular expression. The effect of HOXD-AS1 on tumor proliferation, metastasis and stemness was measured through corresponding experiments. ChIP, luciferase reporter and RIP assays were implemented to explore the regulatory mechanism of HOXD-AS1 in CCA. In this study, HOXD-AS1 expression was significantly upregulated in CCA tissues and cells compared with control groups, respectively. Increased HOXD-AS1 was markedly correlated with lymph node invasion, advanced TNM stage and poor survival of CCA patients. Moreover, HOXD-AS1 was confirmed to be an unfavorable independent prognostic factor for CCA patients. Functionally, gain- and loss-of-function experiments demonstrated that HOXD-AS1 facilitated tumor proliferation, migration, invasion, EMT, stemness and drug resistance in vitro and in vivo. For the mechanism, transcription factor SP1-induced HOXD-AS1 upregulated oncogene MYCN through competitively binding to miR-520c-3p. Furthermore, HOXD-AS1-induced malignant phenotypes were rescued by interfering miR-520c-3p and MYCN, respectively. SP1/HOXD-AS1/miR-520c-3p/MYCN plays a vital role in initiation and progression of CCA, and HOXD-AS1 is expected to be an efficient biomarker and therapeutic target.

Background Tracheal injury could cause intratracheal scar hyperplasia which in turn causes benign tracheal stenosis (TS). With the increasing use of mechanical ventilation and ventilator, the incidence of TS is increasing. However, the molecular mechanisms of TS have not been elucidated. It is significant to further explore the molecular mechanisms of TS. Methods The repeatability of public data was verified. Differently expressed genes (DEGs) and most significant genes were identified between TS and normal samples. Enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed. The comparative toxicogenomics database were analyzed. TS patients were recruited and RT‐qPCR were performed to verify the most significant genes. Results There exist strong correlations among samples of TS and normal group. There was a total of 194 DEGs, including 61 downregulated DEGs and 133 upregulated DEGs. GO were significantly enriched in mitotic nuclear division, cell cycle, and cell division. Analysis of KEGG indicated that the top pathways were cell cycle, and p53 pathway. MKI67(OMIM:176741), CCNB1(OMIM:123836), and CCNB2(OMIM:602755) were identified as the most significant genes of TS, and validated by the clinical samples. Conclusion Bioinformatics methods might be useful method to explore the mechanisms of TS. In addition, MKI67, CCNB1, and CCNB2 might be the most significant genes of TS., Bioinformatics methods could be useful tools to predict the progression of tracheal stenosis (TS) and to explore the mechanisms of the occurrence and development of TS. In addition, there are differently expressed genes (DEGs) between TS and normal tracheal tissues, especially MKI67, CCNB1, and CCNB2.

BACKGROUND: Adverse skin reactions to skin care products have been increasing in recent years. However, these reactions have not been characterized well to date. OBJECTIVE: To describe symptoms, clinical signs and frequency of adverse cutaneous reactions to skin care products on the face in males vs. females of various ages. PATIENTS AND METHODS: All outpatients diagnosed with adverse cutaneous reactions to skin care products on the face examined by dermatologists at Dermatology Hospital of Southern Medical University between November 1, 2016 and October 31, 2017, employing a questionnaire and interviewed by a dermatologist, were eligible. The association of adverse cutaneous reactions with age and gender was analyzed. RESULTS: A total of 433 outpatients, accounting for 0.12% of total outpatients, were assessed. Of these, 223 patients, including 204 females and 19 males, aged 4 to 75 years old, were eventually diagnosed with adverse reactions to skin care products on the face. Eighty-two per cent of patients experienced pruritus, while 80% showed erythema, and 48% visible swelling. The incidences of both xerosis and edema correlated positively with age, while acne-like lesions were negatively associated with age, but not with gender. CONCLUSIONS: Our results indicate that pruritus, xerosis and erythema are common adverse cutaneous reactions to facial skin care products. These reactions vary with age, but not gender. Vigorous safety testing should precede marketing of skin care products.

Objectives Long non-coding RNAs (lncRNAs), a group of transcripts with length greater than 200 nucleotides, have been involved in multiple pathophysiological processes of the human body, especially in tumorigenesis and progression of cancers. The aberrant expression of lncRNAs processes crucial functions involved in proliferation, apoptosis and metastatic capacity of cancers. Recent studies have revealed that small nucleolar RNA host gene 1 (SNHG1), a long non-coding RNA transcribed from UHG, was located in chromosome 11. Aberrant expression of SNHG1 has been demonstrated to be associated with various sites of cancers such as glioma, esophageal cancer, gastric cancer and many others, and its deregulation could be related to survival and prognosis of cancer patients. Pertinent to clinical practice, SNHG1 might act as a prognostic biomarker for tumors and might even serve as potential target for therapy. In this review, we summarized current researches concerning the role of SNHG1 in tumor progression and discussed its mechanisms involved. Materials and methods In this review, we summarized and figured out recent studies concerning the expression and biological mechanisms of SNHG1in tumor development. The related studies were obtained through a systematic search of PubMed, Embase and Cochrane Library. Results SNHG1 was a valuable cancer-related lncRNA that the expression level was up-regulation in a variety of malignancies, including glioma, esophageal cancer, lung cancer, gastric cancer, hepatocellular carcinoma, colorectal carcinoma, prostate cancer, cervical cancer, osteosarcoma, neuroblastoma, nasopharyngeal carcinoma. The aberrant expressions of SNHG1 have shown to contribute to proliferation, migration, and invasion of cancer cells. Conclusions SNHG1 represents promising novel biomarkers for various cancer types and have a great potential to be effectively used in clinical practice in the near future.

BACKGROUND. Adverse cutaneous reactions to skin care products (SCP) are becoming increasingly common, and may be indicative of defective permeability barrier function. AIM. To determine the differences in transepidermal water loss rates (TEWL) between skin patch positive versus negative to skin care products in normal Chinese females. METHODS. Skin patch test reactions to nine skin care products were assessed in 65 normal Chinese females. Correlations of cutaneous reactions to a panel of nine foreign and domestic SCP with permeability barrier function and stratum corneum (SC) hydration levels were analyzed. RESULTS. Out of 65 subjects, 24 (37%) displayed positive reactions to one or more SCP. However, the occurrence of positive reactions to patch tests did not correlate with either transepidermal water loss rates or SC hydration levels. CONCLUSIONS. Though a substantial proportion of normal females display adverse reactions to SCP, this problem cannot be attributed to differences in the qualities of their epidermal permeability barriers, and therefore, these reactions more likely reflect the potential adverse events of the SCP themselves. However, further studies in large cohort of both males and females would be helpful to ascertain whether TEWL levels can predict cutaneous reactions to SCP.

Objective To evaluate clinical efficacy and safety of microneedle-mediated intradermal injection with hyaluronic acid for the treatment of sensitive skin. Methods A total of 53 female patients aged 21-54 years and diagnosed with sensitive skin were enrolled from Department of Cosmetic Dermatology, Dermatology Hospital of Southern Medical University from January to June in 2018, and were divided into 3 groups by using a random number generator and a residue-based method: high-pressure jet injection group (n = 23) receiving high-pressure jet injection with hyaluronic acid on the right side of the face (treatment side) and high-pressure jet injection with 0.9% sodium chloride solution on the left side of the face (control side) once every 2 weeks, microneedle injection group (n = 15) receiving microneedle-mediated injection with hyaluronic acid on the right side of the face (treatment side) and microneedle-mediated injection with 0.9% sodium chloride solution on the left side of the face (control side) once every 4 weeks, combination group (n = 15) receiving microneedle-mediated injection with hyaluronic acid on the right side of the face (treatment side) and high-pressure jet injection with hyaluronic acid on the left side of the face (control side) once every 4 weeks. All the patients in the above 3 groups received 4 consecutive sessions of treatment. Before the initial treatment and 2 weeks after the final treatment, erythema and skin pore scores were determined on the right and left sides of the face by using VISIA facial imaging system, lactic acid stinging test was performed, and skin sensitivity including severity of itching, dryness, erythema and scaling was evaluated. Two weeks after the final treatment, the overall improvement was evaluated with the Global Aesthetic Improvement Scale (GAIS) by clinicians and patients. Adverse reactions were recorded during and after treatment. Statistical analysis was carried out by using paired t test, Wilcoxon sign rank sum test and chi-square test. Results Two weeks after the final treatment, the improvement of skin pore score in the treatment side was superior to that in the control side in the high-pressure jet injection group (t = 2.19, P = 0.03) , while no significant difference in the improvement of erythema score was observed between the treatment side and control side (t = 1.10, P = 0.27) ; in the microneedle injection group, the improvement of erythema and skin pore scores was greater in the treatment side than in the control side (t = 2.47, 3.02, both P = 0.01) ; in the combination group, the VISIA erythema score in the treatment and control sides was 0.59 ± 0.25 and 0.85 ± 0.31 respectively, the improvement of erythema score in the treatment side was superior to that in the control side (t = 5.02, P 0.05) . Two weeks after the final treatment, the severity of itching, dryness and scaling was significantly improved in both the treatment and control sides in the 3 groups compared with those before the initial treatment (P 0.05) . No severe adverse reactions were observed during or after the treatment. Conclusion Microneedle intradermal injection with hyaluronic acid can effectively and safely improve erythema, skin pore and sensitive symptoms in patients with sensitive skin. Key words: Injections, jet; Hyaluronic acid; Sensitive skin; Microneedle- mediated injection; High-pressure jet; Split-face study

Background Becker's nevus is a common skin disorder. Lasers and light instruments are the major modalities for the treatment of Becker's nevus, but the outcomes were mixed. Objective To evaluate the efficacy of the intense pulsed light for Becker's nevus in a large Chinese cohort. Methods We retrospectively analyzed the efficacy of the intense pulsed light for Becker's nevus in a single center. Results A total of 45 patients, including 26 males and 19 females (male to female ratio = 1.4), aged 5-42 years, were included in this analysis. Twenty-seven patients (60%) were with hypertrichosis. Treatments with intense pulsed light resulted in over 75% improvements in pigmentation and hair density in 1 and 2 cases, respectively. One patient displayed 51%-75% reductions in hair density. The rest displayed ≤50% improvements in pigmentation and hair density. Recurrence occurred in all cases within 6 months after the last treatment. Adverse reactions were temporary and mild hypopigmentation, hyperpigmentation, hypertrophic scar, pain, and erythema. Conclusion Intense pulsed light does not exhibit long-term benefits for Becker's nevus. Further studies in the large cohort are still required to validate the present results. Moreover, whether changes in the treatment parameters can improve the efficacy of intense pulsed light remains to be explored.

CD177 is considered to represent neutrophils. We analyzed mRNA expression level of CD177 and clinical follow-up survey of PDAC to estimate overall survival (OS) from Gene Expression Omnibus (GEO) dataset (GSE21501, containing samples from 102 PDAC patients) by R2 platform (http://r2.amc.nl). We also analyzed correlated genes of CD177 by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to predict the potential relationship between neutrophils and prognosis of PDAC. We then performed hematoxylin and eosin (HE) staining and immunohistochemical staining of surgical specimens to verify infiltration of neutrophils in PDAC tissues. After analyzing mRNA expression data and clinical follow-up survey provided in the GEO dataset (GSE21501, containing samples from 102 PDAC patients) and clinicopathological data of 23 PDAC patients, we demonstrated that CD177 was correlated with poor prognosis. The univariate Kaplan-Meier survival analysis revealed that OS was inversely associated with increased expression of CD177 (P = 0.012). Expression of phosphodiesterase (PDE)4D was positively related to CD177 in gene correlation analysis (R = 0.413, P 0.001) by R2 platform. HE staining and immunohistochemistry of CD177 in 23 PDAC surgical samples showed accumulation of neutrophils in the stroma and blood vessels around the cancer cells. In addition, immunohistochemical staining showed that CD177 was highly expressed in the stroma and blood vessels around tumor tissues of PDAC, which was similar to HE staining. Expression of CD177 can be used to represent infiltration of neutrophils, which may have potential prognostic value in PDAC.

Ketamine, a non-competitive N-methyl d-aspartate (NMDA) receptor antagonist, is widely used in pediatric clinical practice. However, prolonged exposure to ketamine results in widespread anesthetic neurotoxicity and long-term neurocognitive deficits. The molecular mechanisms that underlie this important event are poorly understood. We investigated effects of anesthetic ketamine on neuroapoptosis and further explored role of NMDA receptors in ketamine-induced neurotoxicity. Here we demonstrate that ketamine induces activation of cell cycle entry, resulting in cycle-related neuronal apoptosis. On the other hand, ketamine administration alters early and late apoptosis of cultured hippocampus neurons by inhibiting PKC/ERK pathway, whereas excitatory NMDA receptor activation reverses these effects. Ketamine-induced neurotoxicity blocked by NMDA is mediated through activation of PKC/ERK pathway in developing hippocampal neurons.

OBJECTIVE This study aimed to investigate the effects of dexmedetomidine on cerebral oxygen saturation [Sct(O2)] and postoperative cognitive function in elderly patients undergoing minimally invasive coronary artery bypass graft surgery. METHODS Sixty elderly patients who received minimally invasive coronary artery bypass graft surgery were randomly equally divided into dexmedetomidine group (group D) and control group (group N). The patients in group D were pumped with 1 μg/kg dexmedetomidine for 15 min before incision, followed by continuous pumping at 0.3-0.5 μg/(kg·h) till the end of the operation. The patients in group N received same dose of normal saline during the operation. Sct(O2) was monitored at pre-induction (T0), post-induction (T1), 30 min (T2) after single-lung ventilation, and after surgery (T3). Mini-mental state examination (MMSE) was used to assess the cognitive function at 1 day before, 72 hour and 7 days after surgery. RESULTS Sct(O2) level in group D was significantly higher than that in group N at T2 (P

LINC00261 plays a vital role in tumorigenesis and metastasis of digestive system cancer. However, an influence of LINC00261 on cholangiocarcinoma has a little research. There, we investigated clinical role and molecular mechanisms of LINC00261 in cholangiocarcinoma.The qRT-PCR was performed for the detection of LINC00261 level in 50 paired specimens from CCA patients and six cell lines. Cell proliferation were explored by CCK-8 and colony formation assays in QBC939 and RBE cells after transfected with si-LINC00261 or si-NC. Then, AO/EB double fluorescence staining and flow cytometric assays were performed to assess cell apoptosis. Transwell and wound healing assays were selected to evaluate migratory and invasive property of cells. Protein levels, such as PCNA, Bax, Bcl-2, and several epithelial-to-mesenchymal transition markers, including E-cadherin, N-cadherin and Vimentin, were detected by western blot assays. Furthermore, we use a R2 platform to evaluate the correlation between LINC00261 and EMT makers and predict the overall survival and relapse-free survival for CCA patients by the expression of LINC00261/ EMT makers.LINC00261 was overexpressed in cancerous tissues and CCA cell lines compared with adjacent tissues and HIBEC, respectively. Up-regulation of LINC00261 was related to larger tumor size (p = 0.009), positive lymph node metastasis (p = 0.021), advanced TNM stages (p = 0.017) and higher postoperative recurrence (p = 0.009) for CCA patients. Additionally, univariate and multivariate analysis displayed that LINC00261 an independent prognostic factor in CCA patients. Knockdown of LINC00261 expression in RBE and QBC939 cell lines inhibited cell proliferation, migration and invasion property and increased cell apoptosis and the EMT progression. Moreover, there was a strong correlation between LINC00261 and E-cadherin (CDH1) (p 0.05), and low expression of E-cadherin (CDH1) has a poor overall survival and relapse-free survival in CCA patients (p 0.05).Overall, high level of LINC00261 in CCA predicts a poor prognosis, and promotes a metastasis via EMT process. Thus, LINC00261 could be a promising biomarker and therapeutic target for CCA, and in the high level of LINC00261 in CCA, E-cadherin or CDH1 might be an effective factor for tumor metastasis or poor prognosis.

Objectives Hypoxia is a hallmark of the tumor microenvironment, and hypoxia regions are frequently found in gastrointestinal cancers, which are associated with worse patients’ survival and therapy resistance. However, the potential mechanisms of hypoxic tumor microenvironment still need to be further elucidated, especially about the roles of long non-coding RNAs (lncRNAs) in hypoxic tumor regions. In recent years, a great mount of independent research showed that many lncRNAs were modulated by hypoxia, and these lncRNAs were named as “hypoxia-regulated lncRNAs”. In this review, the recent developments in the expression, regulation and functions of hypoxia-regulated lncRNAs in gastrointestinal cancers were summarized. Materials and methods In this review, we summarized and figured out recent studies concerning the expression and biological mechanisms of hypoxia-regulated lncRNAs in gastrointestinal cancers. The related studies were obtained through a systematic search of PubMed, Embase and Cochrane Library. Results Hypoxia-regulated lncRNAs have various roles in the regulation of metabolism, autophagy, invasion and metastasis in the hypoxic microenvironment. More importantly, hypoxic-regulated lncRNAs have a variety of potential mechanisms in gastrointestinal tumors, including epigenetic, lncRNA-miRNA interaction, lncRNA-protein interactions. Conclusions Hypoxia-regulated lncRNAs will undoubtedly be developed as targets and promote the progress in ideal therapies for gastrointestinal cancer patients.